Review

Wild and synanthropic reservoirs of Leishmania species in theAmericasAndreacute Luiz R Roque Ana Maria JansenLaboratory of Trypanosomatid Biology Oswaldo Cruz Institute FIOCRUZ Av Brasil 4365 21040-360 Rio de JaneiroRJ Brazil

A R T I C L E I N F O

Article historyReceived 3 June 2014Revised 19 August 2014Accepted 21 August 2014

KeywordsLeishmania sppReservoirWild mammalsLeishmaniasis

A B S T R A C T

The definition of a reservoir has changed significantly in the last century making it necessary to studyzoonosis from a broader perspective One important example is that of Leishmania zoonotic multi-hostparasites maintained by several mammal species in nature The magnitude of the health problem rep-resented by leishmaniasis combined with the complexity of its epidemiology make it necessary to clarifyall of the links in transmission net including non-human mammalian hosts to develop effective controlstrategies Although some studies have described dozens of species infected with these parasites onlya minority have related their findings to the ecological scenario to indicate a possible role of that hostin parasite maintenance and transmission Currently it is accepted that a reservoir may be one or a complexof species responsible for maintaining the parasite in nature A reservoir system should be consideredunique on a given spatiotemporal scale In fact the transmission of Leishmania species in the wild stillrepresents an complex enzootic ldquopuzzlerdquo as several links have not been identified This review presentsthe mammalian species known to be infected with Leishmania spp in the Americas highlighting thosethat are able to maintain and act as a source of the parasite in nature (and are thus considered potentialreservoirs) These hostreservoirs are presented separately in each of seven mammal orders ndash MarsupialiaCingulata Pilosa Rodentia Primata Carnivora and Chiroptera ndash responsible for maintaining Leishmaniaspecies in the wildcopy 2014 The Authors Published by Elsevier Ltd on behalf of Australian Society for Parasitology This is anopen access article under the CC BY-NC-ND license (httpcreativecommonsorglicensesby-nc-nd30)

Contents

1 Introduction 2522 What defines a reservoir host 2523 Understanding the pattern of Leishmania spp infection of mammalian hosts 2524 Leishmania hosts and putative reservoirs 253

41 Order Didelphimorphia 25342 Order Pilosa 25543 Order Cingulata 25644 Order Rodentia 25645 Order Carnivora 25746 Order Primata 25847 Order Chiroptera 258

5 Conclusions and perspectives 259Acknowledgements 259References 259

Corresponding author Oswaldo Cruz Institute Laboratory of Trypanosomatid Biology FIOCRUZ Av Brasil 4365 21040-360 Rio de JaneiroRJ Brazil Tel +55 21 25621416 fax +55 21 2562 1609

E-mail address roqueiocfiocruzbr (ALR Roque)

httpdxdoiorg101016jijppaw2014080042213-2244copy 2014 The Authors Published by Elsevier Ltd on behalf of Australian Society for Parasitology This is an open access article under the CC BY-NC-ND license(httpcreativecommonsorglicensesby-nc-nd30)

International Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

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1 Introduction

Upon their arrival in the Americas humans began be exposedto parasite species that circulate in the extant fauna (Arauacutejo et al2013) Even now though to a lesser extent we are still exposed tothe wild environment its wildlife and their parasites Habitat frag-mentation global warming non-sustainable exploratory activitiesexpansion of agriculture and eco-tourism are some factors that con-tribute to intensifying this contact (Aguirre and Tabor 2008Alexander et al 2012 Jones et al 2008) Human infection by para-sites that circulate in the wild is especially probable for multi-host parasites ie those capable of infecting a wide range ofmammalian and vector host species (Woolhouse et al 2001) Thisis the case for some Leishmania species including L infantum (=synL chagasi) L braziliensis L amazonensis and L mexicana the mostimportant etiological agents of human leishmaniasis in the Ameri-cas (Alvar et al 2012) These trypanosomatids are characterized byhigh genetic heterogeneity and biological eclecticism as evi-denced in varied orders of mammals that they are able to infectAs a result these protozoa species have complex transmission cycleswith region-specific epidemiological characteristics (Ashford 1996Rotureau 2006)

Cases of human leishmaniasis which may present distinct in-fection patterns are caused by more than 20 species of heteroxenicflagellates of the genus Leishmania These parasites circulate amongmammals belonging to seven orders and in the Americas are trans-mitted by sandflies of the genus Lutzomyia (Diptera Psychodidae)(Alvar et al 2012) The classification into visceral and cutaneousforms observed in human disease cannot be applied to the infec-tion in other mammals Dogs infected with L infantum presentviscero-dermic disease where parasite isolation is common evenfrom intact skin (Madeira et al 2009) Moreover Leishmania speciesassociated with human cutaneous infection have been observed inrodent viscera since the 1950s (Nery Guimaratildees 1951 Roque et al2010) We thus challenge the classical concept of tissue tropism ofLeishmania species This term comes from the Greek ldquotroposrdquo amovement in a particular direction in response to an external stim-ulus In Leishmania spp however the cells of the phagocyticmononuclear system represent the preferential niche In ecologi-cal terms the tissues where Leishmania species are found representmore favorable niches for permanent establishment (which may varyamong mammalian hosts) preferential infection is not the resultof a tropism for a given tissue

Although the concepts and methods employed for the investi-gation of parasite reservoirs have changed significantly over time(Ashford 1997 Haydon et al 2002 Lainson et al 1981a) most ofthe descriptions of Leishmania spp reservoirs are still based on find-ings of natural infection which do not provide information on theepidemiological importance of that host to parasite maintenancein the area Considering the new definition of reservoirs under-standing the role of each mammalian host species in Leishmaniatransmission from secondary data demands a critical analysis of fieldand laboratory studies Although knowledge of leishmaniasis hasimproved in recent decades (mainly concerning the cellular and mo-lecular biology of the parasite epidemiology and diagnosis of humaninfection) we still lack data on the transmission between their mam-malian hosts and vectors As a consequence this disease presentsan ongoing public-health problem and continues to expand its range(Alvar et al 2012)

2 What defines a reservoir host

As in any other hostndashparasite system patterns of Leishmania in-fection in any mammalian host species are determined by hostfactors (species concomitant infectionshealth sex age behavior-al patterns) parasite traits (generation time dispersion strategies

molecular and biochemical characteristics of its sub-populations)exposure (inoculum size) and local environmental conditions (in-fluenced eg by stress and availability of natural resources) wherethe hostndashparasite encounter takes place (Chaves et al 2007 DeTommasi et al 2013) The influence of these factors shows that agiven mammalian host species may not fill the same role in the trans-mission cycle in different localities and time periods (Desjeux 2004Mills and Childs 1998) Furthermore the competence to infectvectors (infectivity or transmissibility competence) is not homo-geneously distributed in host populations and transmission isassumed to be associated with only a minority of infected mammalsin an ecological pattern known as the 2080 rule (Miller and Huppert2013 Woolhouse et al 1997) Parasite transmission nets aredynamic thus it is likely that parasites are periodically extin-guished in a particular host population and are re-introduced sometime later (Mills and Childs 1998)

Assuming that an infected mammal is a host its importance inthe transmission cycle will depend both on the dispersion strate-gy of the parasite and the peculiarities of this hostndashparasiteinteraction The assemblage of these variables will determine theaccessibility of the parasite to the external environment or to theintermediate host for transmission and thus for maintenance Theseare the factors that determine the transmissibility competence ofthat host species defining thus its role as a reservoir host Mainlybased on studies by Ashford (1997) and Haydon et al (2002) weconsider a ldquoreservoirrdquo a system that includes one or more speciesof mammals that are responsible for maintaining the parasite innature and should be considered as unique within a certain spa-tiotemporal scale (Jansen and Roque 2010) Within this ldquoreservoirsystemrdquo each host species plays a distinct role in transmission ina certain time and space Transmissibility competence is thus a traitthat alters over the course of infection in given individual host suchthat one species or individual may assume different roles in the epi-demiology of a parasite during its lifespan Here we considerldquomaintenance hostsrdquo to be those mammals that can be infected andmaintain the infection and ldquoamplifier hostsrdquo to be those mammalsthat in addition to maintaining the infection display a character-istic that favors transmission (more parasites in the blood and skinfor longer periods) These conditions are interchangeable and main-tenance hosts may be converted into amplifier hosts according tothe hostrsquos health conditions for example immune suppression andconcomitant parasitic infections (Botero et al 2013) A schema ofthe reservoir system should include the ecologybiology of that host(life area and explored habitats) the local population structure andthe relative abundance and interaction of the host species with othermammals (Miller and Huppert 2013 Noireau et al 2009)

Finally a controversial point in the study of reservoirs is the as-sumption that a reservoir host must not show symptoms asasymptomatic infection is usually associated with ancient hostndashparasite relationships (WHO 1990) It is currently assumed howeverthat not all ancient hostndashparasite interactions necessarily evolve intoharmonic interactions because they may instead favor the trans-missibility of the parasite Transmission is crucial for parasite survivaland is dependent on their reproductive strategy (Giorgio 1995Woolhouse et al 2001) Indeed virulence and pathogenicity mayin some cases be considered fitness traits because both may improveparasite transmission and may therefore be positively selected

3 Understanding the pattern of Leishmania spp infection ofmammalian hosts

Although they are enzootic parasites there are few studies onthe roles of different mammalian host species in the transmissionof Leishmania spp and ldquohostsrdquo and ldquoreservoirsrdquo are usually treatedas synonymous terms (WHO 1990 Ashford 1996) Studies con-sidering long-lasting infection with these parasites in wild hosts are

252 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

scarce (Raymond et al 2003 Travi et al 2002) Understanding therole played by different mammalian species in the transmission ofLeishmania spp in nature requires an epidemiological investiga-tion that includes an infection follow-up and a representativesampling of the potential host species and mammalian popula-tions in the area Equally important is the adoption of a broadmethodological approach that should include the diagnosis of in-fection by direct and indirect parasitological tests to evaluatetransmissibility competence Additionally whenever possible ex-perimental studies on potential wild reservoirs must be performedto assist the interpretation of the data obtained in field investiga-tions (Roque et al 2010)

Direct examination and blood-culture techniques are less effec-tive for the detection of Leishmania spp in wild mammals Even indogs infected by L infantum its sensitivity varies among differentstudies and mostly depends on parasite load examined tissue andtechnical experience (Ikeda-Garcia and Feitosa 2006) On the otherhand specificity is always 100 The gold-standard methods are thecultures of punctures or fragments of hematopoietic tissues but thepositive result does not necessarily reflect the competence of thathost to transmit the parasite This competence is defined by the ac-cessibility of parasites to vectors which is correlated with the originof the cultured material Positive skin or blood cultures and xeno-diagnosis suggest transmissibility Direct visualization of parasitesin skin fragments has lower sensitivity but in combination with theconfirmation of the etiologic agent this technique also confirms vi-ability and thus therefore its transmissibility Positive cultures alwaysdemonstrate the presence of viable parasites but positive ob-tained from internal organs (liver spleen bone marrow and lymphnodes) do not necessarily indicate infectivity to the vector

Serological tests among which the most used are the immuno-fluorescence (IFAT) and immunoenzymatic (ELISA) assaysdemonstrate infection Sensitivity and specificity of these tests rangefrom 90 to 100 and 80 to 100 respectively for IFAT (Mettleret al 2005) and from 80 to 995 and 81 to 100 respectivelyfor ELISA (Mancianti et al 1995 Marcondes et al 2011) A hostthat is positive in serological but negative in parasitological testshas been exposed to Leishmania infection (expected to still be in-fected) but are not necessarily important for the maintenance ofthe parasite in nature ie are not necessarily reservoirs of the par-asite Molecular diagnosis by polymerase chain reaction (PCR) canbe considered a parasitological assay because it detects constitu-tive parts of the parasites (fragments of DNA) This technique mayreach sensitivity and specificity values near 100 but these valuesmay vary depending on the examined tissue (Ashford et al 1995Lachaud et al 2002 Troncarelli et al 2009) Despite certainly dem-onstrating the presence of the parasite it does not allow us toindicate the integrity of that parasite (Silva et al 2005) Concern-ing the parasite transmissibility only recently it was demonstratedthat the parasite load especially in the skin can be related to theinfectiousness during natural infection (Courtenay et al 2014) Al-though PCR is considered extremely sensitive its use as the goldstandard for diagnosis or therapeutic cure of human leishmani-asis remains a matter of debate (Mendonca et al 2004 Salam et al2010) In wild and synanthropic animals diagnosis by PCR is stilla challenge lacking standardization of techniques and speciesndashspecific molecular targets

4 Leishmania hosts and putative reservoirs

Studies of hostndashparasite interaction among wild mammals andLeishmania species are rare because of the complexity of perform-ing long-term field-work and the difficulties of maintaining captivitycolonies of wild species for experimental infection Moreover anessential aspect of this type of study is the accurate taxonomicidentification of the mammalian hosts Identification is not trivial

for taxa (eg rodents and bats) that comprise a great diversity ofspecies including several whose taxonomic position is still debat-able and can be identified only by karyotyping andor molecularanalysis Our aim in this review was to re-interpret the availabledata on Leishmania reservoirs using an ecological approach and toconsider the transmissibility potential from that species We alsoadded data on characterization of parasite in wild hosts fromthe Leishmania sp collection of the Oswaldo Cruz Institute(CLIOCFiocruz cliocfiocruzbr) Our main difficulties in thisreview involved (i) access to the full text of some articles espe-cially the older articles published in languages other than Englishand in journals that are not broadly distributed and (ii) in somecases identification of Leishmania species as the numerous taxo-nomic revisions have repeatedly changed the nomenclature of somespecies

In this context we discuss some of the wild and synanthropicspecies known to be infected with Leishmania spp distinguishingbetween ldquoparasite hostsrdquo and ldquopotential reservoirsrdquo with the latterdesignation used only when the authors demonstrated the reten-tion of infection or the potential to transmit the parasite to vectors(positive xenodiagnosis or cultures from skin or blood) As alreadynoted Leishmania reservoirs show regional and temporal varia-tion and only a local study including ecological and parasitologicalanalysis can determine whether these ldquopotential reservoirsrdquo mayserve as reservoir in a given environment

41 Order Didelphimorphia

The autochthonous American order Didelphimorphia is the onlymarsupial order recognized in the Americas Mammals from thisorder have a wide distribution mainly due to their remarkable adapt-ability to different ecological niches particularly to environmentswith a high degree of human activity The genus Didelphis is themost widely dispersed on the continent occurring from southeast-ern Canada to southern Argentina (Austad 1988) Didelphis sppare nomadic solitary (mainly males) and excellent climbers thatare mainly found in holes in trees and foliage These animals cancolonize ceilings of houses and other shelters in domestic and peri-domestic areas where they feed on human food garbage (Austad1988 Olifiers et al 2005) Most likely due to its synanthropic char-acter this species is one of most studied regarding infectionby Leishmania spp although only a few of these studies includedfollow up on the natural or experimental infection (Travi et al1994 1998b)

Didelphis marsupialis a species distributed from Mexico to theAmazon region has been found to be infected with at least four Leish-mania species (Arias et al 1981 Corredor et al 1989 Grimaldi et al1991) (Table 1) Its importance as a potential reservoir for L infantumwas demonstrated in a rural community from Colombia where theseanimals were abundant and displayed a high prevalence of posi-tive cultures and high parasite loads (as observed in slide imprints)in the spleen (Corredor et al 1989) Later studies also confirmedtheir importance elsewhere in Colombia and Venezuela (Quinnelland Courtenay 2009 Travi et al 1998a) Additionally its impor-tance as a reservoir was confirmed by the experimental infectionby L infantum of five specimens which resulted in clinical signs sug-gestive of visceral leishmaniasis in one young female that presentedamastigote parasites in the spleen liver and lymph nodes Para-sites were re-isolated from all of these specimens and three werealso infective for Lu longipalpis (Travi et al 1998b)

Didelphis albiventris is abundant in central South America fromColombia to northern Argentina and is quite abundant in north-eastern central and southern Brazil L infantum isolation from thismarsupial species was first described in Bahia Brazil (Sherlock et al1984) Later the same authors demonstrated its infectivity to vectorsby xenodiagnosis (Sherlock 1996) and others reported their natural

253ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

Table 1Mammal host species described infected by different Leishmania species in the Americas

Order Host species Leishmania species Infection pattern Country References

Didelphimorphia Didelphis marsupialis L infantum Potential reservoir CO VE Corredor et al 1989 apud Quinnell and Courtenay 2009L amazonensis Parasite host BR Grimaldi et al 1991L guyanensis Potential reservoir BR FG Arias et al 1981 Dedet et al 1989L forattinii Parasite host BR IOCL 0067

D albiventris L infantum Potential reservoir BR Sherlock et al 1984 Sherlock 1996L braziliensis Parasite host BR Quaresma et al 2011L peruviana Potential reservoir PE Llanos-Cuentas et al 1999

D aurita L infantum Parasite host BR Carreira et al 2012Philander opossum L amazonensis Parasite host BR Lainson et al 1981aMarmosa cinerea L amazonensis Parasite host BR Arias et al 1981Marmosa sp L (Viannia) sp Parasite host BR Brandatildeo-Filho et al 2003Micoreus paraguayanus L amazoensis Parasite host BR Quintal et al 2011

L braziliensis Parasite host BR Quintal et al 2011Gracilinanus agilis L braziliensis Parasite host BR Quaresma et al 2011Marmosops incanus L guyanensis Parasite host BR Quaresma et al 2011Metachirus nudicaudatus L amazonensis Parasite host BR Lainson et al 1981aMonodelphis domestica L (Viannia) sp Parasite host BR Lima et al 2013

Pilosa Choloepus didactylus L guyanensis Potential reservoir FG BR Gentile et al 1981 Lainson et al 1981aL shawi Parasite host BR Lainson et al 1989

C hoffmanni L colombiensis Parasite host PN Kreutzer et al 1991L equatoriensis Parasite host EC Grimaldi et al 1992L panamensis Parasite host PN apud Ashford 2000

Bradypus tridactylus L shawi Parasite host BR Lainson et al 1989Tamandua tetradactyla L guyanensis Parasite host BR Lainson et al 1981a

L amazonensis Parasite host EC Mimori et al 1989L infantum Parasite host BR Arauacutejo et al 2013

Cingulata Dasypus novemcinctus L naiffi Potential reservoir BR Lainson and Shaw 1989 Naiff et al 1991L guyanensis Parasite host BR Lainson et al 1979

Rodentia Proechimys species L amazonensis Potential reservoir BR FG Arias et al 1981 Dedet et al 1989L guyanensis Parasite host BR FG Dedet et al 1989 Lainson et al 1981b

P canicollis L infantum Parasite host CO Travi et al 1998aP semispinosus L panamensis Potential reservoir CO Travi et al 2002

L infantum Parasite host CO Travi et al 2002Thrichomys apereoides L braziliensis Parasite host BR Quaresma et al 2011

L guyanensis Parasite host BR Quaresma et al 2011L infantum Parasite host BR Oliveira et al 2005 Quaresma et al 2011L amazonensis Parasite host BR Oliveira et al 2005

T laurentius L infantum Potential reservoir BR Roque et al 2010L braziliensis Potential reservoir BR Roque et al 2010L naiffi Parasite host BR Caacutessia-Pires unpublished dataL shawi Parasite host BR Caacutessia-Pires unpublished data

T inermis L shawi Parasite host BR Caacutessia-Pires unpublished dataT pachyurus L naiffi Parasite host BR Caacutessia-Pires unpublished dataNectomys squamipes L infantum Parasite host BR Dantas-Torres and Brandao-Filho 2006

L braziliensis Parasite host BR Peterson et al 1988Rattus rattus L infantum Parasite host BR VE apud Quinnell and Courtenay 2009

L braziliensis Potential reservoir BR VE Vasconcelos et al 1994 De Lima et al 2002L mexicana Parasite host VE De Lima et al 2002

Clyomys laticeps L infantum Parasite host BR Caacutessia-Pires unpublished dataDasyprocta azarae L infantum Parasite host BR Caacutessia-Pires unpublished dataDasyprocta sp L amazonensis Parasite host BR Lainson et al 1981bRhipidomys mastacalis L infantum Parasite host BR Quaresma et al 2011Coendu sp L lainsoni Parasite host BR IOCL 1058

L hertigiL deanei Parasite host PN BR Herrer 1971 Silva et al 2013Coendu prehensilis L infantum Parasite host BO Le Pont et al 1989Akodon arviculoides L braziliensis Parasite host BR Forattini et al 1972 Rocha et al 1988Akodon sp L amazonensis Parasite host BO Telleria et al 1999Necromys lasiurus L braziliensis Potential reservoir BR Brandatildeo-Filho et al 2003 de Freitas et al 2012Sigmodon hispidus L braziliensis Potential reservoir VE De Lima et al 2002

L mexicana Potential reservoir MX VE Van Wynsberghe et al 2000 De Lima et al 2002Holochilus scieurus L infantum Parasite host BR Lima et al 2013H scieurus L (Viannia) sp Parasite host BR Brandatildeo-Filho et al 2003Cerradomys subflavus L (Viannia) sp Parasite host BR Lima et al 2013Mus musculus L braziliensis Parasite host BR de Freitas et al 2012Oryzomys species L amazonensis Parasite host BO Kerr et al 2006O melanotis L amazonensis Potential reservoir MX Van Wynsberghe et al 2000O nigripes L braziliensis Parasite host BR Forattini et al 1972Oligoryzomys sp L amazonensis Parasite host BO Telleria et al 1999Sciurus vulgaris L amazonensis Parasite host EC Mimori et al 1989S granatensis L equatorensis Parasite host EC Grimaldi et al 1992Neotoma species L mexicana Potential reservoir US Kerr et al 1995 Raymond et al 2003Ototylomys phyllotis L mexicana Potential reservoir BE MX Ashford 1996 Van Wynsberghe et al 2000Heteromys species L mexicana Parasite host BE MX Ashford 1996 Van Wynsberghe et al 2009H dermarestianus L panamensis Parasite host CR Zeledon et al 1977

(continued on next page)

254 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

infection detected by PCR (Humberg et al 2012 Santiago et al2007) The other Leishmania species found infecting D albiventrisare L braziliensis (Quaresma et al 2011) and L peruviana(Llanos-Cuentas et al 1999) (Table 1)

L infantum has also been detected in D aurita (Carreira et al2012) and another study also strongly suggests such infection inthe periphery of urban areas (Santiago et al 2007) Although itsrole as a reservoir has not yet been demonstrated it has strong po-tential to act as a reservoir due to the great phylogenetic proximityamong the Didelphis species (Jansa et al 2014) A unique study ona marsupial species able to explore distinct forest strata the opossumPhilander opossum described its infection by L amazonensis (Lainsonet al 1981a) The Leishmania species found infecting other mar-supial species are described in Table 1 (Quintal et al 2011)

Apart from the Didelphis species which are proven as potentialLeishmania reservoirs other marsupial species are poorly studiedThese ancient mammals are perhaps the very first Leishmania spphosts in the Americas although their role in transmission net remainsto be defined

42 Order Pilosa

This order is composed of anteaters and sloths which along witharmadillos (order Cingulata) compose the superorder Xenarthra (oddjoints) previously known as Edentata (Moller-Krull et al 2007) To-gether with the marsupials these ancient Leishmania hosts are alsonative American fauna and present a peculiar bloodndashvessel struc-ture that allows an extremely low metabolic rate sparing energy(Bugge 1979) Since the Tertiary Period many representatives ofthis taxon have become extinct and the extant genera constituteonly a small proportion of the order Mammals from this order havea long co-evolutionary history with trypanosomatids includingseveral Leishmania and Trypanosoma species as well as the poorlystudied genus Endotrypanum (Rotureau 2006)

Sloths are arboreal inhabitants of tropical regions of Central andSouth America and are represented by two genera Bradypus(Bradypodidae family) and Choloepus (Magalonichidae family) Slothshave reduced muscle mass and move slowly between trees by trav-eling directly through the arboreal strata descending only weekly

Table 1 (continued)

Order Host species Leishmania species Infection pattern Country References

Peromyscus yucatanicus L mexicana Potential reservoir MX Van Wynsberghe et al 2000Nyctomys sumichrasti L mexicana Parasite host HN Lainson and Strangways-Dixon 1964Reithrodontomys gracilis L mexicana Parasite host HN Disney 1968Agouti paca L lainsoni Potential reservoir BR Silveira et al 1991Phyllotis andinum L peruviana Parasite host PE Llanos-Cuentas et al 1999Cavia porcellus L enriettii Parasite host BR Machado et al 1994

Carnivora Cerdocyon thous L infantum Potential reservoir BR Deane and Deane 1955 Courtenay et al 1996L amazonesis Parasite host BR apud Rotureau 2006

Speothos venaticus L infantum Potential reservoir BR Figueiredo et al 2008 Lima et al 2009Pseudalopex vetulus L infantum Parasite host BR Curi et al 2006 Luppi et al 2008Chrysocyon brachyurus L infantum Parasite host BR Curi et al 2006 Luppi et al 2008Puma concolor L infantum Parasite host BR Dahroug et al 2010Panthera onca L infantum Parasite host BR Dahroug et al 2010Nasua nasua L shawi Parasite host BR Lainson et al 1989Potos flavus L guyanensis Parasite host FG Pajot et al 1982

L amazonensis Parasite host EC Kreutzer et al 1991Conepatus chinga L amazonensis Parasite host BO Telleria et al 1999

L braziliensis Parasite host BO Buitrago et al 2011Primata Cebus apella L shawi Potential reservoir BR Lainson et al 1989

Cebus xanthosternos L infantum Parasite host BR Malta et al 2010Chiropotes satanas L shawi Potential reservoir BR Lainson et al 1989Saguinus geoffroyi L amazonensis Potential reservoir PN Herrer et al 1973Aotus trivirgatus L braziliensis Potential reservoir PN Herrer and Christensen 1976Aotus azarai L (Viannia) sp Parasite host AR Acardi et al 2013Aotus nigriceps L infantum Parasite host BR Malta et al 2010Callicebus nigrifrons L infantum Parasite host BR Malta et al 2010Alouatta guariba L infantum Parasite host BR Malta et al 2010Leonthopitecus crysomelas L infantum Parasite host BR Malta et al 2010Pithecia irrorata L infantum Parasite host BR Malta et al 2010Saguinus imperator L infantum Parasite host BR Malta et al 2010Ateles paniscus L amazonensis Parasite host BR Lima et al 2012a

Chiroptera Carollia perspicillata L infantum Potential reservoir VE De Lima et al 2008Molossus molossus L infantum Parasite host BR Savani et al 2010

L amazonensis Parasite host BR Savani et al 2010L (Viannia) sp Parasite host BR Shapiro et al 2013

M rufus L amazonensis Parasite host BR Savani et al 2010Glossophaga soricina L infantum Parasite host BR Savani et al 2010

L amazonensis Parasite host BR Savani et al 2010L (Viannia) sp Parasite host BR Shapiro et al 2013

Nyctinomops laticaudatus L amazonensis Parasite host BR Savani et al 2010Eumops glaucinus L amazonensis Parasite host BR Savani et al 2010E auripendulus L amazonensis Parasite host BR Savani et al 2010Artibeus literatus L amazonensis Parasite host BR Savani et al 2010Sturnira lilium L amazonensis Parasite host BR Savani et al 2010Myotis nigricans L amazonensis Parasite host BR Savani et al 2010

Countries AR ndash Argentine BR ndash Brazil CL ndash Chile CO ndash Colombia VE ndash Venezuela FG ndash French Guiana PE ndash Peru PN ndash Panama EC ndash Ecuador BO ndash Bolivia US ndash UnitedStates of America BE ndash Belize MX ndash Mexico HN ndash Honduras CR ndash Costa RicaIOC L Characterized Strains deposited in the Leishmania sp Collection of the Oswaldo Cruz Institute (wwwcliocfiocruzbr) The number refers to the deposit number inCLIOC Catalogue

255ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

to defecate (Miranda and Costa 2006) The two-toed sloth (Choloepusdidactylus) is a potential reservoir of L guyanensis as demon-strated by the high rates of parasite isolation from intact skin (aswell as viscera) which vary from 35 to 47 in French Guiana (Dedetet al 1989 Gentile et al 1981) and reach up to 46 in Brazil(Lainson et al 1981a)

L shawi was described infecting the two-toed sloth and the pale-throated sloth (Bradypus tridactylus) both in Brazil (Lainson et al1989) In Panama L colombiensis was isolated from the viscera ofHoffmannrsquos two-toed sloth (Choloepus hoffmanni) (Kreutzer et al1991) while L equatorensis was found infecting the same speciesin Ecuador (Grimaldi et al 1992) Finally L panamensis a speciesclosely related to L guyanensis has been described in Choloepushoffmanni from Panama (Ashford 2000) (Table 1)

The anteaters constitute a single family (Myrmecophagidae) thatare mainly arboreal but that may also explore the terrestrial strataThe isolation of Leishmania was described in only one species thelesser anteater Tamandua tetradactyla L guyanensis (Lainson et al1981a) L amazonensis (Mimori et al 1989) and L infantum thislast in mixed infection with T cruzi and T rangeli (de Araujo et al2013) were found infecting the lesser anteater (Table 1)

The diversity of Leishmania species already known to infect slothsand anteaters suggests that these mammals may be important hostsfor parasite species that are transmitted in the arboreal strata Infact most of the Leishmania species found infecting these hosts aretransmitted by vectors associated with the arboreal strata such asLu umbratilis and Lu whitmani

43 Order Cingulata

Armadillos together with didelphid marsupials and Pilosa arealso among the oldest mammal groups from the Americas Theyare also the most primitive of the xenarthrans Members of thefamily Dasypodidae are the only surviving species in the order andare found from the southern United States to the Straits of Magel-lan (Miranda and Costa 2006) So far the nine-banded armadillo(Dasypus novemcinctus) is the only non-human host from which Lnaiffi has been isolated (from blood liver and spleen) (Lainsonand Shaw 1989 Naiff et al 1991) L guyanensis is anotherspecies already detected in D novemcinctus from Brazil (Lainsonet al 1979) In some rural areas armadillos are commonly ob-served invading chicken pens searching for eggs and frequentingperidomestic areas (personal observations) where it is possiblethat they can be a source of Leishmania infection for sandflies inthis environment

Armadillos sloths and anteaters are hunted and eaten in someareas of South America such as the Amazon People commonly carefor the young in their backyards after having killed the mothersduring a hunt The young are kept until they reach adulthood andwe cannot exclude the possibility of they become sources of infec-tion in the peridomestic environment

44 Order Rodentia

Rodents are the most diverse and widespread order of mammalsand include several cryptic species that can only be separated bykaryotyping (Bonvicino et al 2002) The first rodents (Hystricognathindash caviomorphs) arrived in the Americas (along with primates) fromAfrica approximately 45 million years ago The second wave of rodentmigration to the Americas (Sciurognathi ndash cricetids) was much morerecent and included an initial establishment in North America (Flynnand Wyss 1998) Since their arrival rodents have diversified widelyand may be found in desert adapted to aquatic media digging longand interconnected tunnels and in forest canopies (Wilson andReeder 2005) This taxon is most likely the most studied in termsof infection by Leishmania spp in both natural and experimental

conditions however excepting a few studies experimentalinfections have been conducted in laboratory mouse lineages whichare not representative of the wild Mus musculus

After the Pilosa Marsupialia and Cingulata caviomorphs (sub-order Hystricognathi) are most likely the most ancient hosts ofLeishmania spp Moreover their arrival in the Americas is relatedto the entry of some species from the sub-genus Leishmania intothe continent (Thomaz-Soccol et al 1993) Caviomorphs from thegenus Proechimys were already found to be infected by various Leish-mania species These rodents are characterized by their longevity(more than 3 years in captivity) and high abundance in most lo-calities where they are found in tropical forests of Central and SouthAmerica (Ashford 1996) Various Proechimys species have been iden-tified as potential reservoirs of L amazonensis in Brazil and FrenchGuiana as demonstrated by the frequent skin parasitism con-firmed by tissue culture (Arias et al 1981 Dedet et al 1989) InFrench Guiana for example this infection was observed in two sym-patric species P cuvieri and P guyanensis (Rotureau 2006) Otherreports of natural infection in the skin of these rodents include Linfantum in P canicollis from Colombia (Travi et al 1998a) and Lguyanensis in Proechimys sp from French Guiana (Dedet et al 1989)and Brazil (Lainson et al 1981a) (Table 1)

P semispinosus from Colombia experimentally infected with Lpanamensis developed self resolving non-ulcerated lesions (fromwhich parasites could be re-isolated and which were demon-strated to be highly infective to vectors in the initial phase of infection(Travi et al 2002) This hostndashparasite interaction exemplifies a tem-poral reservoir competence in one host species passing from anamplifier host (in the beginning of infection) to a maintenance hostin which transmissibility competence is lower In contrast the samerodent species experimentally infected with L infantum devel-oped only subclinical infection and was not infective to vectorsalthough the authors re-isolated the parasites from the spleen ofsome rodents during necropsy (Travi et al 2002) Other authors havedetected no infection in laboratory-bred specimens of anotherspecies P guyannensis after inoculation with promastigotes oramastigotes of L infantum (Lainson et al 2002) This difference maybe due to many variables related to the host and the parasite suchas the intra-specific heterogeneity of both taxa andor the size androute of the inoculum

Considered monospecific until 2002 caviomorphs from the genusThrichomys comprise at least five cryptic species distributed acrossdifferent biomes in Brazil (Bonvicino et al 2002) T apereoides werefound to be infected with L braziliensis L guyanensis L infantumand L amazonensis in leishmaniasis-endemic areas in Minas GeraisBrazil (Oliveira et al 2005 Quaresma et al 2011) Recently we alsodetected infection by various Leishmania species in these rodentsL infantum L naiffi L braziliensis and L shawi in T laurentius L shawiin T inermis and L naiffi in T pachyurus (Caacutessia-Pires et al unpub-lished data) Moreover T laurentius experimentally infected withL infantum and L braziliensis were able to maintain the infectionand parasite re-isolation was achieved up to 12 months after in-fection Leishmania DNA was detected in all experimental groupsand in all tissues sampled independent of the Leishmania speciesinoculated (Roque et al 2010)

In addition to Proechimys spp and Thrichomys spp L infantumhas been diagnosed in Clyomys laticeps Dasyprocta azarae Nectomyssquamipes Holochilus sciureus and Rhipidomys mastacalis from Brazil(Caacutessia-Pires et al unpublished data Dantas-Torres andBrandatildeo-Filho 2006 Quaresma et al 2011 Lima et al 2013 ) andRattus rattus from Brazil and Venezuela (Quinnell and Courtenay2009) Natural infection of Coendu prehensilis used as sentinels inBolivia has been parasitologically confirmed in the liver and spleen(Le Pont et al 1989)

Regarding L braziliensis if we consider only studies that con-firmed the identity of the etiological agent (not considering the

256 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

ancient L braziliensis sensu lato) the following rodent species havebeen described to be naturally infected Akodon arviculoides Musmusculus Nectomys squamipes Necromys (=Bolomys) lasiurusOryzomys nigripes Rattus rattus and Sigmodon hispidus (Brandatildeo-Filhoet al 2003 de Freitas et al 2012 De Lima et al 2002 Forattiniet al 1972 Peterson et al 1988 Rocha et al 1988 Vasconceloset al 1994) In other cases the authors confirmed infection by thesubgenus Leishmania (Viannia) sp (Holochilus scieurus and Cerradomyssubflavus) (Brandatildeo-Filho et al 2003 Lima et al 2013) or tenta-tively identified the etiological agent through the biological patternof in vitro growth (Rhipidomys leucodactylus and Proechimysguyannensis) (Lainson et al 1981b)

Rodents are also usually considered as the main reservoirs ofLeishmania from the L mexicana complex (L mexicana and Lamazonensis) L amazonensis was described in rodents from the fol-lowing genera Akodon Dasyprocta Oligoryzomys OryzomysProechimys Thrichomys and Sciurus (Arias et al 1981 Kerr et al2006 Lainson et al 1981b Mimori et al 1989 Oliveira et al 2005Telleria et al 1999) None of these studies however included follow-up of the infection or demonstrated competence to infect vectors

L mexicana has been isolated from various species of Neotomaincluding a specimen of N floridana with a large lesion in the earfrom which the parasite could be isolated (Kerr et al 1995 McHughet al 2003) This finding was informative suggesting that this rodentspecies may be infective for the vector and an important reservoirof L mexicana Ototylomys phyllotis from Belize should be consid-ered as a possible reservoir of L mexicana because of its relativeabundance prevalence of infection and attraction to Lu flaviscutellatathe most important vector in the region Curiously the same authorfailed to reproduce this infection under experimental conditions(Ashford 1996) possibly due to factors occurring only in naturesuch as stress and concomitant infections which may be impor-tant for the establishment of Leishmania infection This situationhighlights the importance of the studies of naturally infected speci-mens and the difficulties of adopting potential reservoir hosts asalternative models for leishmaniasis studies Moreover these find-ings attest to the hazards of applying conclusions based solely onexperimental models to natural systems

The persistence of L mexicana infection in wild rodents was dem-onstrated twice The first such finding occurred in Mexico where29 naturally infected rodents were maintained in captivity and testedmonthly for parasites for up to 2 years In that study the authorsdemonstrated persistent infection including symptomatic infec-tions in Sigmodon hispidus Oryzomys melanotis Ototylomys phyllotisand Peromyscus yucatanicus the latter two being the most impor-tant because of their high relative abundance in local fauna andlonger life spans (Van Wynsberghe et al 2000) Second in the UnitedStates during a 19-month markndashreleasendashrecapture study of Neotomamicropus the authors reported the persistence of L mexicana in-fection for up to 1 year (Raymond et al 2003) Heteromys Nyctomysand Reithrodontomys were also found infected with L mexicana(Ashford 1996 De Lima et al 2002 Disney 1968 Lainson andStrangways-Dixon 1964 Van Wynsberghe et al 2009)

Leishmania lainsoni was isolated from fragments of intact skinfrom pacas (Agouti paca) in the Brazilian state of Paraacute (Silveira et al1991) and from Coendu sp (Table 1) Leishmania panamensis was iso-lated from naturally infected Heteromys dermarestianus from CostaRica (Zeledon et al 1977) while a squirrel Scirus granatensis wasfound to be infected with L equatorensis in Ecuador (Grimaldi et al1992) Leishmania peruviana a species suggested to be a synonymof L braziliensis was isolated from the Peruvian Phyllotis andinum(Llanos-Cuentas et al 1999) Finally L hertigiL deanei and L enriettiispecies taxonomically more similar to Endotrypanum than to Leish-mania have been described respectively in porcupines Coendu spp(Herrer 1971 Silva et al 2013) and in the guinea pig Cavia porcellus(Machado et al 1994)

Taken together a broad diversity of Leishmania species natural-ly infect this mammal group most likely reflecting the diversity ofecological niches occupied by the hosts The differences observedamong the rodent species include the forest strata they occupy andtheir reproductive strategies (seasonality gestation time and numberof offspring) and these traits should be considered evaluations ofthe importance of a rodent species as a Leishmania reservoir More-over as expected for every hostndashparasite interaction thisheterogeneous mammalian taxon shows a spectrum of compe-tence to maintain and transmit Leishmania from high susceptibilitywith high transmissibility competence to quick control ofinfection

45 Order Carnivora

The mammals from this order also comprise a very heteroge-neous group including strict carnivores such as ocelots (Leoparduspardalis) and tayras (Eira barbara) and species that supplement theirdiet with insects and fruits such as coatis (Nasua nasua) and manedwolves (Chrysocyon brachyurus) Most have a large biomass and largerange important aspects of parasite dispersion (Rocha et al 2013)Moreover some species such as raccoons and tayras are found bothon the ground and in the canopy favoring the dispersion of para-sites among forest strata Unfortunately carnivores require largeranges and because of their potential to predate on livestock (mainlychickens and cattle) are heavily hunted placing some carnivorespecies at risk of extinction (Silva and Adania 2007)

Two carnivore species are closely linked to humans dogs andcats Dogs are the most important reservoirs of L infantum through-out South America although they can be infected with at least sixother Leishmania species (Dantas-Torres 2009) Recently the im-portance of cats in Leishmania epidemiology has also been suggested(Pennisi et al 2013) Among the wild carnivore hosts of L infantumthe first description of infection was in the crab-eating fox Cerdocyonthous although the authors inaccurately reported the host asLycalopex vetulus (Courtenay et al 1996 Deane and Deane 1955)Since then many studies have confirmed L infantum infection inC thous by parasitological serological andor molecular assaysNotably these animals sometimes develop serious symptoms of thedisease and present with amastigotes in intact skin as also de-scribed in domestic dogs Their prevalence of infection may rangefrom 42 (by parasitological tests) to 78 (by serology) (Lainson et al1990 Quinnell and Courtenay 2009 Silva et al 2000) The vectorinfectivity was proven by xenodiagnosis although the infection rateof vectors is reported to be lower than that observed for domesticdogs (Courtenay et al 2002 Quinnell and Courtenay 2009)

Apart from C thous another wild carnivore that is a potentialreservoir of L infantum is the bush dog Speothos venaticus An in-dividual kept in a zoo in Rio de Janeiro Brazil is the only wild canidexcept for C thous from which L infantum was isolated (Figueiredoet al 2008) Infection in bush dogs was also confirmed by directvisualization PCR and serology in two females with clinical signsof visceral leishmaniasis and maintained in other Brazilian zoos (Limaet al 2009 Souza et al 2010) Other wild canid species found tobe infected albeit only by PCR andor serology were the hoary foxPseudalopex vetulus and the maned wolf Chrysocyon brachyurus (Curiet al 2006 Luppi et al 2008) (Table 1)

Some authors have investigated Leishmania infection in captivewild carnivores Five of 15 wild canids belonging to the four nativespecies mentioned earlier were found to be infected in a zoo in BeloHorizonte Brazil Of these one bush dog and one hoary fox devel-oped clinical signs of visceral leishmaniasis (Luppi et al 2008)Among the wild felines five pumas (Puma concolor) and one jaguar(Panthera onca) in a zoo from Cuiabaacute Brazil were PCR-positive inlymph-node puncture biopsy L infantum was specifically identi-fied by the digestion of the amplified products with restriction

257ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

enzymes (Dahroug et al 2010) Later the same authors demon-strated L infantum infection in one lion a non-native felid specieskept in the same zoo (Dahroug et al 2011)

In addition to L infantum at least four other Leishmania specieswere found in wild carnivores L shawi in coatis Nasua nasua (Lainsonet al 1989) L guyanensis in the kinkajou Potos flavus (Pajot et al1982) L amazonensis in kinkajous crab-eating foxes and skunksConepatus chinga (Kreutzer et al 1991 Rotureau 2006 Telleria et al1999) and L braziliensis in one Bolivian skunk (Buitrago et al 2011)(Table 1)

Contrary to the numerous reports of infection in dogs and catsmuch remains to study in terms of the putative roles of wild car-nivores as Leishmania reservoirs As in all hostndashparasite interactionsthe infection patterns display regional and even individual pecu-liarities (Rocha et al 2013) If we consider that in some biomes(ldquoPantanal or Chacordquo ldquoCerradordquo and ldquoPampardquo) carnivore species areabundant and represent a huge biomass any study of Leishmaniareservoirs must include carnivores including their Leishmania in-fection pattern density and population structure in the area Despiteits inherent difficulties the study of wild carnivores especially inthe areas where their relative abundance is high is of fundamen-tal importance to improve understanding of Leishmania ecology

46 Order Primata

Nonhuman primates can be divided in two groups the catar-rhines (infraorder Catarrhini) from Africa Europe and Asia (OldWorld Primates) and the platyrrhines (Platyrrhini) from the Ameri-cas (New World or Neotropical Primates) The main differencebetween them is that the catarrhines have upside-down nostrils ona long snout while platyrrhines have laterally-faced nostrils on ashorter snout (Verona and Pissinatti 2007) The different speciesof neotropical primates are included in the families Cebidae (tama-rins) and Callitrichidae (marmosets) although some classificationsalso recognize three other families Aotidae Pithecidae and AtelidaeThe neotropical primates occupy distinct arboreal strata and consumediverse diets including species that feed on fruits invertebrates andeven small mammals (Verona and Pissinatti 2007)

To date few studies have described natural infection by Leish-mania parasites in neotropical primates Infection by L shawi wasdescribed in the tufted capuchin monkey Cebus apella and thebearded saki Chiropotes satanas (Lainson et al 1989) while infec-tion by Leishmania (Viannia) sp was recently demonstrated in fourArgentinean owl monkeys Aotus azarai (Acardi et al 2013) InPanamaacute Geoffroyrsquos tamarin Saguinus geoffroyi and the owl monkeyAotus trivirgatus were found to be infected with L amazonensis andL braziliensis respectively (Herrer and Christensen 1976 Herrer et al1973) In a Brazilian zoo one black-fronted titi Callicebus nigrifronsfrom Belo HorizonteMG presented with a fatal disease thatresembled visceral leishmaniasis Histological and immunohisto-chemical examinations as well as a PCR specific for parasites fromthe L donovani complex confirmed infection with L infantum (Maltaet al 2010) The other primate species that had PCR-positive bloodsamples in the same study were Alouatta guariba Cebus xanthosternosLeonthopitecus crysomelas Aotus nigriceps Pithecia irrorata andSaguinus imperator (Malta et al 2010) In the zoo in BauruSP Leish-mania amazonensis was detected by PCR-RFLP in a spider monkeyAteles paniscus from the endemic Amazon region (Lima et al 2012b)(Table 1)

Leishmania species that circulate in the Americas have been dem-onstrated to infect other neotropical primates but only underexperimental conditions Most of these studies focused on theimmune response to different drug treatments or on vaccine de-velopment For many years black-tufted marmosets Callithrixpenicillata were used in experimental studies with L braziliensis andL amazonensis (Cuba et al 1990 Cuba-Cuba and Marsden 1993)

Experimental infection of the common squirrel monkey Saimirisciureus resulted in non-ulcerated skin lesions from which Lbraziliensis andor L panamensis could be re-isolated (Pung et al1988) Owl monkeys Aotus trivirgatus developed localized cutane-ous lesions after experimental infection with L braziliensis Lmexicana and L panamensis (Christensen and de Vasquez 1981 Lujanet al 1986) Cebus apella developed skin lesions after experimen-tal infection with L lainsoni L amazonensis L braziliensis L mexicanaand L guyanensis (Garcez et al 2002 Grimaldi 2008) ConverselyCebus nigrivittatus developed fatal disease when experimentally in-fected with L infantum (Vouldoukis et al 1986)

All neotropical primates are included in the list of the ldquoConven-tion on International Trade in Endangered Species of Wild Faunaand Florardquo (CITES) indicating that all are vulnerable to some degree(Verona and Pissinatti 2007) For this reason many species suchas the golden lion tamarin Leonthopitecus rosalia are included in con-servation programs These programs often include exchangetranslocation and re-introduction of animals without consider-ation of their parasite fauna here including Leishmania and othertrypanosomatids Data from naturally infected primates demon-strate that these mammals may be involved in the maintenance ofLeishmania in the wild especially considering their ecology speciestransmitted in the canopy Taking into account the transmission cycleof these parasites a lack of knowledge regarding the health statusof the relocated primates may result in the introduction of in-fected mammals into a given area promoting the establishment ofnew transmission cycles (Lisboa et al 2006)

47 Order Chiroptera

Bats are nocturnal mammals and the only able to fly (some-times associated with seasonal migration) an important trait thatcan result in the dissemination of parasite species Their disper-sion capacity is due to the ability to do true flapping flight(apparently evolved differently among bat lineages) and the so-phisticated echolocation system that allows them to identify theenvironment (Jones and Teeling 2006) Despite their known diver-sity bats are still considered as a monophyletic group (Bishop 2008Bisson et al 2009)

Bats are commonly infected with several trypanosomatid speciesmainly from the Trypanosoma genus T cruzi T vespertilionis andT (Megatrypanum) sp among others (Lima et al 2012a) There isonly one report of the isolation of Leishmania parasites (L infantum)from the blood of a short-tailed fruit bat Carollia perspicillata in Ven-ezuela (De Lima et al 2008) (Table 1) Before that Lampo et al haddemonstrated that bats could be sources of blood for Lutzomyialongipalpis in Venezuelan caves (Lampo et al 2000)

In Brazil two Leishmania species were identified in maceratedfragments of spleen and liver from bats using a nested PCR fol-lowed by sequencing of the amplified products Molossus molossusand Glossophaga soricina were found to be infected with L infantumand L amazonensis and the latter was also found in Molossus rufusNyctinomops laticaudatus Eumops glaucinus E auripendulus Artibeusliteratus Sturnira lilium and Myotis nigricans (Savani et al 2010) Re-cently Leishmania (Viannia) sp was detected in a skin lesion fromGlossophaga soricina and blood from Molossus molossus (Shapiro et al2013) (Table 1) In this article although the authors have de-scribed infection with L braziliensis PCR-RFLP using primers b1 andb2 (Schonian et al 2003) does not allow for differentiation amongother species from the same subgenus such as L guyanensis

Bats should not be excluded as potential reservoirs of Leishma-nia sp because of the lack of studies involving Leishmania and batsChiroptera represents 39 of the 560 mammal species reported inSouth American rainforests it is the most common mammal groupin terms of diversity and biomass (Emmons and Feer 1997 Rotureau2006) These flying mammals are found in wild domestic and

258 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

synanthropic environments being able to colonize different habi-tats in different ecotypes Their refuges include hollow trees thecanopies of palm trees and ceilings of human houses and other ruralbuildings Their high abundance and adaptability to peri-domesticenvironment reinforce the importance of investigating bats alreadyrecognized as reservoirs of other trypanosomatids (Jansen and Roque2010) in the transmission cycles of Leishmania species

5 Conclusions and perspectives

Many decades have passed since the description of Leishmaniaparasites but their epidemiology is still not well understood in partbecause of the human-health focus of most studies Only recentlyinfluenced by the ldquoone healthrdquo approach has the epidemiology ofleishmaniasis started to be evaluated from a broader perspective(Palatnik-de-Sousa and Day 2011)

In the case of human visceral leishmaniasis caused by L infantumthe idea that dogs are the only reservoir of the parasite has led healthauthorities to direct the eradication of seropositive dogs on the basisthat this action was the only way to control this zoonosis In factseveral studies have demonstrated that dogs are epidemiologi-cally important as reservoirs in different localities (reviewed byLainson and Rangel 2005 Dantas-Torres 2009 Quinnell andCourtenay 2009) Nevertheless the participation of other in-fected mammals rather than dogs in the transmission cycle of Linfantum in urban areas was already proposed for cats and opos-sums for example (Pennisi et al 2013 Santiago et al 2007) Thelow effectiveness of dog culling program in Brazil is probably dueto an assemblage of factors most of them related to the lack of astructured surveillance system and include the high interval betweentests and between the positive result and dog elimination the rapidreplacement of susceptible dogs when an infected dog is euthan-ized and the resistance of owners to euthanize their infected dogs(Costa et al 2013 Grimaldi et al 2012 Nunes et al 2008) Someof these localities are very close to sylvatic areas and the possibil-ity that wild mammals may serve as a source of infection to vectorsin peridomiciliary areas has been ignored The putative participa-tion of these mammals is an important additional factor to beconsidered in the proposition of measures to control this zoono-sis This review highlights species from distinct orders that maymaintain and serve as a source of infection to phlebotomine sandfly vectors providing a constant source of re-infection to a peri-domestic transmission system

The reservoirs of the Leishmania species responsible for the cu-taneous forms of human leishmaniasis are still unknown most likelybecause research has focused on the search for a specific reservoirhost as observed for dogs and L infantum These species may bemaintained in the wild by a different strategy as by a few ldquohotspeciesrdquo with high transmissibility competence or most likelythrough a reservoir system an assemblage of mammals with dis-tinct and transient degrees of transmissibility competencethroughout infection This hypothesis agrees with the reservoir def-inition proposed by Ashford (1997) almost 20 years ago This systeminvolves a tradeoff that could explain the evolutionary success ofthese parasite species several individuals are infected but each iscompetent for transmission for only a limited time while retain-ing the infection for long periods of time The sum of multiple shortperiods of infectivity in numerous infected mammals guaranteesthe maintenance and transmission of these Leishmania species

All the links in the epidemiological chain must be clarified as a pre-requisite for effective control strategies (Abdussalan 1959Palatnik-de-Sousa and Day 2011 Shaw 2007) We are still far from un-derstanding the maintenance of different Leishmania species in natureIn this sense the follow-up of naturally infected animals and experi-mental studies using potential reservoirs are essential to improvingunderstanding of the mechanisms of maintenance of these parasites

in their natural hosts In the field the studies should not be restrictedto previously described infected hosts but should be carried out usingan integrated ecological approach to understand the role of each hostspecies in the maintenance and amplification of Leishmania para-sites Priorities include the identification of the factors that influencethe transmissibility competence of the individual mammalian hosts andunderstanding how environmental management could decrease in-fections in humans living close to sylvatic

Over the last century the scientific community has shown thatdifferent and several wild mammal species can become infected withLeishmania species The focus must change to identify species thatmay serve as sources of infection to vectors and amplify enzooticfoci constituting a risk for human transmission To this end a par-adigm shift in research and surveillance of wild reservoirs ofLeishmania is urgently needed This change will depend among otherfactors on understanding reservoir systems and acknowledging theimportance of understanding the role each mammal species playsin maintaining these parasites in nature The factors involved in theamplification of enzootic foci are temporally and regionally spe-cific and understanding some of these factors may support thedevelopment of effective and sustainable strategies for leishmani-asis surveillance

Acknowledgements

AMJ is a ldquoCientista do Nosso Estadordquo provided by FAPERJ andis financially supported by CNPq (ldquoBolsista de Produtividade niacutevel1rdquo CNPq) ALRR is a ldquoJovem Cientista do Nosso Estadordquo providedby FAPERJ The authors have declared that no competing interestsexist

References

Abdussalan M 1959 Significance of ecological studies of wild animal reservoir ofzoonoses Bull World Health Organ 21 179ndash186

Acardi SA Rago MV Liotta DJ Fernandez-Duque E Salomon OD 2013Leishmania (Viannia) DNA detection by PCR-RFLP and sequencing in free-rangingowl monkeys (Aotus azarai azarai) from Formosa Argentina Vet Parasitol 193256ndash259

Aguirre AA Tabor GM 2008 Global factors driving emerging infectious diseasesAnn N Y Acad Sci 1149 1ndash3

Alexander KA Lewis BL Marathe M Eubank S Blackburn JK 2012 Modelingof wildlife-associated zoonoses applications and caveats Vector Borne ZoonoticDis 12 1005ndash1018

Alvar J Velez ID Bern C Herrero M Desjeux P Cano J et al 2012 Leishmaniasisworldwide and global estimates of its incidence PLoS ONE 7 e35671

Arauacutejo A Reinhard K Ferreira LF Pucu E Chieffi PP 2013 Paleoparasitologythe origin of human parasites Arq Neuropsiquiatr 71 722ndash726

Arias JR Naif RD Miles MA de Souza AA 1981 The opossum Didelphismarsupialis (Marsupialia didelphidae) as a reservoir host of Leishmaniabraziliensis guyanensis in the Amazon Basin of Brazil Trans R Soc Trop MedHyg 75 537ndash541

Ashford DA Bozza M Freire M Miranda JC Sherlock I Eulalio C et al 1995Comparison of the polymerase chain reaction and serology for the detection ofcanine visceral leishmaniasis Am J Trop Med Hyg 53 251ndash255

Ashford RW 1996 Leishmaniasis reservoir and their significance in control ClinDermatol 14 523ndash532

Ashford RW 1997 What it takes to be a reservoir host Belg J Zool 127 85ndash90Ashford RW 2000 The leishmaniases as emerging and reemerging zoonoses Int

J Parasitol 30 1269ndash1281Austad SN 1988 The adaptable opossum Sci Am 258 54ndash59Bishop KL 2008 The evolution of flight in bats narrowing the field of plausible

hypotheses Q Rev Biol 83 153ndash169Bisson IA Safi K Holland RA 2009 Evidence for repeated independent evolution

of migration in the largest family of bats PLoS ONE 4 e7504Bonvicino CR Otazu IB DrsquoAndrea PS 2002 Karyologic evidence of diversification

of the genus Thrichomys (Rodentia Echimyidae) Cytogenet Genome Res 97200ndash204

Botero A Thompson CK Peacock CS Clode PL Nicholls PK Wayne AF et al2013 Trypanosomes genetic diversity polyparasitism and the population declineof the critically endangered Australian marsupial the brush tailed bettong orwoylie (Bettongia penicillata) Int J Parasitol Parasite Wildl 2 77ndash89

Brandatildeo-Filho SP Brito ME Carvalho FG Ishikawa EA Cupolillo EFloeter-Winter L et al 2003 Wild and synanthropic hosts of Leishmania(Viannia) braziliensis in the endemic cutaneous leishmaniasis locality of AmarajiPernambuco State Brazil Trans R Soc Trop Med Hyg 97 291ndash296

259ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

scarce (Raymond et al 2003 Travi et al 2002) Understanding therole played by different mammalian species in the transmission ofLeishmania spp in nature requires an epidemiological investiga-tion that includes an infection follow-up and a representativesampling of the potential host species and mammalian popula-tions in the area Equally important is the adoption of a broadmethodological approach that should include the diagnosis of in-fection by direct and indirect parasitological tests to evaluatetransmissibility competence Additionally whenever possible ex-perimental studies on potential wild reservoirs must be performedto assist the interpretation of the data obtained in field investiga-tions (Roque et al 2010)

Direct examination and blood-culture techniques are less effec-tive for the detection of Leishmania spp in wild mammals Even indogs infected by L infantum its sensitivity varies among differentstudies and mostly depends on parasite load examined tissue andtechnical experience (Ikeda-Garcia and Feitosa 2006) On the otherhand specificity is always 100 The gold-standard methods are thecultures of punctures or fragments of hematopoietic tissues but thepositive result does not necessarily reflect the competence of thathost to transmit the parasite This competence is defined by the ac-cessibility of parasites to vectors which is correlated with the originof the cultured material Positive skin or blood cultures and xeno-diagnosis suggest transmissibility Direct visualization of parasitesin skin fragments has lower sensitivity but in combination with theconfirmation of the etiologic agent this technique also confirms vi-ability and thus therefore its transmissibility Positive cultures alwaysdemonstrate the presence of viable parasites but positive ob-tained from internal organs (liver spleen bone marrow and lymphnodes) do not necessarily indicate infectivity to the vector

Serological tests among which the most used are the immuno-fluorescence (IFAT) and immunoenzymatic (ELISA) assaysdemonstrate infection Sensitivity and specificity of these tests rangefrom 90 to 100 and 80 to 100 respectively for IFAT (Mettleret al 2005) and from 80 to 995 and 81 to 100 respectivelyfor ELISA (Mancianti et al 1995 Marcondes et al 2011) A hostthat is positive in serological but negative in parasitological testshas been exposed to Leishmania infection (expected to still be in-fected) but are not necessarily important for the maintenance ofthe parasite in nature ie are not necessarily reservoirs of the par-asite Molecular diagnosis by polymerase chain reaction (PCR) canbe considered a parasitological assay because it detects constitu-tive parts of the parasites (fragments of DNA) This technique mayreach sensitivity and specificity values near 100 but these valuesmay vary depending on the examined tissue (Ashford et al 1995Lachaud et al 2002 Troncarelli et al 2009) Despite certainly dem-onstrating the presence of the parasite it does not allow us toindicate the integrity of that parasite (Silva et al 2005) Concern-ing the parasite transmissibility only recently it was demonstratedthat the parasite load especially in the skin can be related to theinfectiousness during natural infection (Courtenay et al 2014) Al-though PCR is considered extremely sensitive its use as the goldstandard for diagnosis or therapeutic cure of human leishmani-asis remains a matter of debate (Mendonca et al 2004 Salam et al2010) In wild and synanthropic animals diagnosis by PCR is stilla challenge lacking standardization of techniques and speciesndashspecific molecular targets

4 Leishmania hosts and putative reservoirs

Studies of hostndashparasite interaction among wild mammals andLeishmania species are rare because of the complexity of perform-ing long-term field-work and the difficulties of maintaining captivitycolonies of wild species for experimental infection Moreover anessential aspect of this type of study is the accurate taxonomicidentification of the mammalian hosts Identification is not trivial

for taxa (eg rodents and bats) that comprise a great diversity ofspecies including several whose taxonomic position is still debat-able and can be identified only by karyotyping andor molecularanalysis Our aim in this review was to re-interpret the availabledata on Leishmania reservoirs using an ecological approach and toconsider the transmissibility potential from that species We alsoadded data on characterization of parasite in wild hosts fromthe Leishmania sp collection of the Oswaldo Cruz Institute(CLIOCFiocruz cliocfiocruzbr) Our main difficulties in thisreview involved (i) access to the full text of some articles espe-cially the older articles published in languages other than Englishand in journals that are not broadly distributed and (ii) in somecases identification of Leishmania species as the numerous taxo-nomic revisions have repeatedly changed the nomenclature of somespecies

In this context we discuss some of the wild and synanthropicspecies known to be infected with Leishmania spp distinguishingbetween ldquoparasite hostsrdquo and ldquopotential reservoirsrdquo with the latterdesignation used only when the authors demonstrated the reten-tion of infection or the potential to transmit the parasite to vectors(positive xenodiagnosis or cultures from skin or blood) As alreadynoted Leishmania reservoirs show regional and temporal varia-tion and only a local study including ecological and parasitologicalanalysis can determine whether these ldquopotential reservoirsrdquo mayserve as reservoir in a given environment

41 Order Didelphimorphia

The autochthonous American order Didelphimorphia is the onlymarsupial order recognized in the Americas Mammals from thisorder have a wide distribution mainly due to their remarkable adapt-ability to different ecological niches particularly to environmentswith a high degree of human activity The genus Didelphis is themost widely dispersed on the continent occurring from southeast-ern Canada to southern Argentina (Austad 1988) Didelphis sppare nomadic solitary (mainly males) and excellent climbers thatare mainly found in holes in trees and foliage These animals cancolonize ceilings of houses and other shelters in domestic and peri-domestic areas where they feed on human food garbage (Austad1988 Olifiers et al 2005) Most likely due to its synanthropic char-acter this species is one of most studied regarding infectionby Leishmania spp although only a few of these studies includedfollow up on the natural or experimental infection (Travi et al1994 1998b)

Didelphis marsupialis a species distributed from Mexico to theAmazon region has been found to be infected with at least four Leish-mania species (Arias et al 1981 Corredor et al 1989 Grimaldi et al1991) (Table 1) Its importance as a potential reservoir for L infantumwas demonstrated in a rural community from Colombia where theseanimals were abundant and displayed a high prevalence of posi-tive cultures and high parasite loads (as observed in slide imprints)in the spleen (Corredor et al 1989) Later studies also confirmedtheir importance elsewhere in Colombia and Venezuela (Quinnelland Courtenay 2009 Travi et al 1998a) Additionally its impor-tance as a reservoir was confirmed by the experimental infectionby L infantum of five specimens which resulted in clinical signs sug-gestive of visceral leishmaniasis in one young female that presentedamastigote parasites in the spleen liver and lymph nodes Para-sites were re-isolated from all of these specimens and three werealso infective for Lu longipalpis (Travi et al 1998b)

Didelphis albiventris is abundant in central South America fromColombia to northern Argentina and is quite abundant in north-eastern central and southern Brazil L infantum isolation from thismarsupial species was first described in Bahia Brazil (Sherlock et al1984) Later the same authors demonstrated its infectivity to vectorsby xenodiagnosis (Sherlock 1996) and others reported their natural

253ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

Table 1Mammal host species described infected by different Leishmania species in the Americas

Order Host species Leishmania species Infection pattern Country References

Didelphimorphia Didelphis marsupialis L infantum Potential reservoir CO VE Corredor et al 1989 apud Quinnell and Courtenay 2009L amazonensis Parasite host BR Grimaldi et al 1991L guyanensis Potential reservoir BR FG Arias et al 1981 Dedet et al 1989L forattinii Parasite host BR IOCL 0067

D albiventris L infantum Potential reservoir BR Sherlock et al 1984 Sherlock 1996L braziliensis Parasite host BR Quaresma et al 2011L peruviana Potential reservoir PE Llanos-Cuentas et al 1999

D aurita L infantum Parasite host BR Carreira et al 2012Philander opossum L amazonensis Parasite host BR Lainson et al 1981aMarmosa cinerea L amazonensis Parasite host BR Arias et al 1981Marmosa sp L (Viannia) sp Parasite host BR Brandatildeo-Filho et al 2003Micoreus paraguayanus L amazoensis Parasite host BR Quintal et al 2011

L braziliensis Parasite host BR Quintal et al 2011Gracilinanus agilis L braziliensis Parasite host BR Quaresma et al 2011Marmosops incanus L guyanensis Parasite host BR Quaresma et al 2011Metachirus nudicaudatus L amazonensis Parasite host BR Lainson et al 1981aMonodelphis domestica L (Viannia) sp Parasite host BR Lima et al 2013

Pilosa Choloepus didactylus L guyanensis Potential reservoir FG BR Gentile et al 1981 Lainson et al 1981aL shawi Parasite host BR Lainson et al 1989

C hoffmanni L colombiensis Parasite host PN Kreutzer et al 1991L equatoriensis Parasite host EC Grimaldi et al 1992L panamensis Parasite host PN apud Ashford 2000

Bradypus tridactylus L shawi Parasite host BR Lainson et al 1989Tamandua tetradactyla L guyanensis Parasite host BR Lainson et al 1981a

L amazonensis Parasite host EC Mimori et al 1989L infantum Parasite host BR Arauacutejo et al 2013

Cingulata Dasypus novemcinctus L naiffi Potential reservoir BR Lainson and Shaw 1989 Naiff et al 1991L guyanensis Parasite host BR Lainson et al 1979

Rodentia Proechimys species L amazonensis Potential reservoir BR FG Arias et al 1981 Dedet et al 1989L guyanensis Parasite host BR FG Dedet et al 1989 Lainson et al 1981b

P canicollis L infantum Parasite host CO Travi et al 1998aP semispinosus L panamensis Potential reservoir CO Travi et al 2002

L infantum Parasite host CO Travi et al 2002Thrichomys apereoides L braziliensis Parasite host BR Quaresma et al 2011

L guyanensis Parasite host BR Quaresma et al 2011L infantum Parasite host BR Oliveira et al 2005 Quaresma et al 2011L amazonensis Parasite host BR Oliveira et al 2005

T laurentius L infantum Potential reservoir BR Roque et al 2010L braziliensis Potential reservoir BR Roque et al 2010L naiffi Parasite host BR Caacutessia-Pires unpublished dataL shawi Parasite host BR Caacutessia-Pires unpublished data

T inermis L shawi Parasite host BR Caacutessia-Pires unpublished dataT pachyurus L naiffi Parasite host BR Caacutessia-Pires unpublished dataNectomys squamipes L infantum Parasite host BR Dantas-Torres and Brandao-Filho 2006

L braziliensis Parasite host BR Peterson et al 1988Rattus rattus L infantum Parasite host BR VE apud Quinnell and Courtenay 2009

L braziliensis Potential reservoir BR VE Vasconcelos et al 1994 De Lima et al 2002L mexicana Parasite host VE De Lima et al 2002

Clyomys laticeps L infantum Parasite host BR Caacutessia-Pires unpublished dataDasyprocta azarae L infantum Parasite host BR Caacutessia-Pires unpublished dataDasyprocta sp L amazonensis Parasite host BR Lainson et al 1981bRhipidomys mastacalis L infantum Parasite host BR Quaresma et al 2011Coendu sp L lainsoni Parasite host BR IOCL 1058

L hertigiL deanei Parasite host PN BR Herrer 1971 Silva et al 2013Coendu prehensilis L infantum Parasite host BO Le Pont et al 1989Akodon arviculoides L braziliensis Parasite host BR Forattini et al 1972 Rocha et al 1988Akodon sp L amazonensis Parasite host BO Telleria et al 1999Necromys lasiurus L braziliensis Potential reservoir BR Brandatildeo-Filho et al 2003 de Freitas et al 2012Sigmodon hispidus L braziliensis Potential reservoir VE De Lima et al 2002

L mexicana Potential reservoir MX VE Van Wynsberghe et al 2000 De Lima et al 2002Holochilus scieurus L infantum Parasite host BR Lima et al 2013H scieurus L (Viannia) sp Parasite host BR Brandatildeo-Filho et al 2003Cerradomys subflavus L (Viannia) sp Parasite host BR Lima et al 2013Mus musculus L braziliensis Parasite host BR de Freitas et al 2012Oryzomys species L amazonensis Parasite host BO Kerr et al 2006O melanotis L amazonensis Potential reservoir MX Van Wynsberghe et al 2000O nigripes L braziliensis Parasite host BR Forattini et al 1972Oligoryzomys sp L amazonensis Parasite host BO Telleria et al 1999Sciurus vulgaris L amazonensis Parasite host EC Mimori et al 1989S granatensis L equatorensis Parasite host EC Grimaldi et al 1992Neotoma species L mexicana Potential reservoir US Kerr et al 1995 Raymond et al 2003Ototylomys phyllotis L mexicana Potential reservoir BE MX Ashford 1996 Van Wynsberghe et al 2000Heteromys species L mexicana Parasite host BE MX Ashford 1996 Van Wynsberghe et al 2009H dermarestianus L panamensis Parasite host CR Zeledon et al 1977

(continued on next page)

254 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

infection detected by PCR (Humberg et al 2012 Santiago et al2007) The other Leishmania species found infecting D albiventrisare L braziliensis (Quaresma et al 2011) and L peruviana(Llanos-Cuentas et al 1999) (Table 1)

L infantum has also been detected in D aurita (Carreira et al2012) and another study also strongly suggests such infection inthe periphery of urban areas (Santiago et al 2007) Although itsrole as a reservoir has not yet been demonstrated it has strong po-tential to act as a reservoir due to the great phylogenetic proximityamong the Didelphis species (Jansa et al 2014) A unique study ona marsupial species able to explore distinct forest strata the opossumPhilander opossum described its infection by L amazonensis (Lainsonet al 1981a) The Leishmania species found infecting other mar-supial species are described in Table 1 (Quintal et al 2011)

Apart from the Didelphis species which are proven as potentialLeishmania reservoirs other marsupial species are poorly studiedThese ancient mammals are perhaps the very first Leishmania spphosts in the Americas although their role in transmission net remainsto be defined

42 Order Pilosa

This order is composed of anteaters and sloths which along witharmadillos (order Cingulata) compose the superorder Xenarthra (oddjoints) previously known as Edentata (Moller-Krull et al 2007) To-gether with the marsupials these ancient Leishmania hosts are alsonative American fauna and present a peculiar bloodndashvessel struc-ture that allows an extremely low metabolic rate sparing energy(Bugge 1979) Since the Tertiary Period many representatives ofthis taxon have become extinct and the extant genera constituteonly a small proportion of the order Mammals from this order havea long co-evolutionary history with trypanosomatids includingseveral Leishmania and Trypanosoma species as well as the poorlystudied genus Endotrypanum (Rotureau 2006)

Sloths are arboreal inhabitants of tropical regions of Central andSouth America and are represented by two genera Bradypus(Bradypodidae family) and Choloepus (Magalonichidae family) Slothshave reduced muscle mass and move slowly between trees by trav-eling directly through the arboreal strata descending only weekly

Table 1 (continued)

Order Host species Leishmania species Infection pattern Country References

Peromyscus yucatanicus L mexicana Potential reservoir MX Van Wynsberghe et al 2000Nyctomys sumichrasti L mexicana Parasite host HN Lainson and Strangways-Dixon 1964Reithrodontomys gracilis L mexicana Parasite host HN Disney 1968Agouti paca L lainsoni Potential reservoir BR Silveira et al 1991Phyllotis andinum L peruviana Parasite host PE Llanos-Cuentas et al 1999Cavia porcellus L enriettii Parasite host BR Machado et al 1994

Carnivora Cerdocyon thous L infantum Potential reservoir BR Deane and Deane 1955 Courtenay et al 1996L amazonesis Parasite host BR apud Rotureau 2006

Speothos venaticus L infantum Potential reservoir BR Figueiredo et al 2008 Lima et al 2009Pseudalopex vetulus L infantum Parasite host BR Curi et al 2006 Luppi et al 2008Chrysocyon brachyurus L infantum Parasite host BR Curi et al 2006 Luppi et al 2008Puma concolor L infantum Parasite host BR Dahroug et al 2010Panthera onca L infantum Parasite host BR Dahroug et al 2010Nasua nasua L shawi Parasite host BR Lainson et al 1989Potos flavus L guyanensis Parasite host FG Pajot et al 1982

L amazonensis Parasite host EC Kreutzer et al 1991Conepatus chinga L amazonensis Parasite host BO Telleria et al 1999

L braziliensis Parasite host BO Buitrago et al 2011Primata Cebus apella L shawi Potential reservoir BR Lainson et al 1989

Cebus xanthosternos L infantum Parasite host BR Malta et al 2010Chiropotes satanas L shawi Potential reservoir BR Lainson et al 1989Saguinus geoffroyi L amazonensis Potential reservoir PN Herrer et al 1973Aotus trivirgatus L braziliensis Potential reservoir PN Herrer and Christensen 1976Aotus azarai L (Viannia) sp Parasite host AR Acardi et al 2013Aotus nigriceps L infantum Parasite host BR Malta et al 2010Callicebus nigrifrons L infantum Parasite host BR Malta et al 2010Alouatta guariba L infantum Parasite host BR Malta et al 2010Leonthopitecus crysomelas L infantum Parasite host BR Malta et al 2010Pithecia irrorata L infantum Parasite host BR Malta et al 2010Saguinus imperator L infantum Parasite host BR Malta et al 2010Ateles paniscus L amazonensis Parasite host BR Lima et al 2012a

Chiroptera Carollia perspicillata L infantum Potential reservoir VE De Lima et al 2008Molossus molossus L infantum Parasite host BR Savani et al 2010

L amazonensis Parasite host BR Savani et al 2010L (Viannia) sp Parasite host BR Shapiro et al 2013

M rufus L amazonensis Parasite host BR Savani et al 2010Glossophaga soricina L infantum Parasite host BR Savani et al 2010

L amazonensis Parasite host BR Savani et al 2010L (Viannia) sp Parasite host BR Shapiro et al 2013

Nyctinomops laticaudatus L amazonensis Parasite host BR Savani et al 2010Eumops glaucinus L amazonensis Parasite host BR Savani et al 2010E auripendulus L amazonensis Parasite host BR Savani et al 2010Artibeus literatus L amazonensis Parasite host BR Savani et al 2010Sturnira lilium L amazonensis Parasite host BR Savani et al 2010Myotis nigricans L amazonensis Parasite host BR Savani et al 2010

Countries AR ndash Argentine BR ndash Brazil CL ndash Chile CO ndash Colombia VE ndash Venezuela FG ndash French Guiana PE ndash Peru PN ndash Panama EC ndash Ecuador BO ndash Bolivia US ndash UnitedStates of America BE ndash Belize MX ndash Mexico HN ndash Honduras CR ndash Costa RicaIOC L Characterized Strains deposited in the Leishmania sp Collection of the Oswaldo Cruz Institute (wwwcliocfiocruzbr) The number refers to the deposit number inCLIOC Catalogue

255ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

to defecate (Miranda and Costa 2006) The two-toed sloth (Choloepusdidactylus) is a potential reservoir of L guyanensis as demon-strated by the high rates of parasite isolation from intact skin (aswell as viscera) which vary from 35 to 47 in French Guiana (Dedetet al 1989 Gentile et al 1981) and reach up to 46 in Brazil(Lainson et al 1981a)

L shawi was described infecting the two-toed sloth and the pale-throated sloth (Bradypus tridactylus) both in Brazil (Lainson et al1989) In Panama L colombiensis was isolated from the viscera ofHoffmannrsquos two-toed sloth (Choloepus hoffmanni) (Kreutzer et al1991) while L equatorensis was found infecting the same speciesin Ecuador (Grimaldi et al 1992) Finally L panamensis a speciesclosely related to L guyanensis has been described in Choloepushoffmanni from Panama (Ashford 2000) (Table 1)

The anteaters constitute a single family (Myrmecophagidae) thatare mainly arboreal but that may also explore the terrestrial strataThe isolation of Leishmania was described in only one species thelesser anteater Tamandua tetradactyla L guyanensis (Lainson et al1981a) L amazonensis (Mimori et al 1989) and L infantum thislast in mixed infection with T cruzi and T rangeli (de Araujo et al2013) were found infecting the lesser anteater (Table 1)

The diversity of Leishmania species already known to infect slothsand anteaters suggests that these mammals may be important hostsfor parasite species that are transmitted in the arboreal strata Infact most of the Leishmania species found infecting these hosts aretransmitted by vectors associated with the arboreal strata such asLu umbratilis and Lu whitmani

43 Order Cingulata

Armadillos together with didelphid marsupials and Pilosa arealso among the oldest mammal groups from the Americas Theyare also the most primitive of the xenarthrans Members of thefamily Dasypodidae are the only surviving species in the order andare found from the southern United States to the Straits of Magel-lan (Miranda and Costa 2006) So far the nine-banded armadillo(Dasypus novemcinctus) is the only non-human host from which Lnaiffi has been isolated (from blood liver and spleen) (Lainsonand Shaw 1989 Naiff et al 1991) L guyanensis is anotherspecies already detected in D novemcinctus from Brazil (Lainsonet al 1979) In some rural areas armadillos are commonly ob-served invading chicken pens searching for eggs and frequentingperidomestic areas (personal observations) where it is possiblethat they can be a source of Leishmania infection for sandflies inthis environment

Armadillos sloths and anteaters are hunted and eaten in someareas of South America such as the Amazon People commonly carefor the young in their backyards after having killed the mothersduring a hunt The young are kept until they reach adulthood andwe cannot exclude the possibility of they become sources of infec-tion in the peridomestic environment

44 Order Rodentia

Rodents are the most diverse and widespread order of mammalsand include several cryptic species that can only be separated bykaryotyping (Bonvicino et al 2002) The first rodents (Hystricognathindash caviomorphs) arrived in the Americas (along with primates) fromAfrica approximately 45 million years ago The second wave of rodentmigration to the Americas (Sciurognathi ndash cricetids) was much morerecent and included an initial establishment in North America (Flynnand Wyss 1998) Since their arrival rodents have diversified widelyand may be found in desert adapted to aquatic media digging longand interconnected tunnels and in forest canopies (Wilson andReeder 2005) This taxon is most likely the most studied in termsof infection by Leishmania spp in both natural and experimental

conditions however excepting a few studies experimentalinfections have been conducted in laboratory mouse lineages whichare not representative of the wild Mus musculus

After the Pilosa Marsupialia and Cingulata caviomorphs (sub-order Hystricognathi) are most likely the most ancient hosts ofLeishmania spp Moreover their arrival in the Americas is relatedto the entry of some species from the sub-genus Leishmania intothe continent (Thomaz-Soccol et al 1993) Caviomorphs from thegenus Proechimys were already found to be infected by various Leish-mania species These rodents are characterized by their longevity(more than 3 years in captivity) and high abundance in most lo-calities where they are found in tropical forests of Central and SouthAmerica (Ashford 1996) Various Proechimys species have been iden-tified as potential reservoirs of L amazonensis in Brazil and FrenchGuiana as demonstrated by the frequent skin parasitism con-firmed by tissue culture (Arias et al 1981 Dedet et al 1989) InFrench Guiana for example this infection was observed in two sym-patric species P cuvieri and P guyanensis (Rotureau 2006) Otherreports of natural infection in the skin of these rodents include Linfantum in P canicollis from Colombia (Travi et al 1998a) and Lguyanensis in Proechimys sp from French Guiana (Dedet et al 1989)and Brazil (Lainson et al 1981a) (Table 1)

P semispinosus from Colombia experimentally infected with Lpanamensis developed self resolving non-ulcerated lesions (fromwhich parasites could be re-isolated and which were demon-strated to be highly infective to vectors in the initial phase of infection(Travi et al 2002) This hostndashparasite interaction exemplifies a tem-poral reservoir competence in one host species passing from anamplifier host (in the beginning of infection) to a maintenance hostin which transmissibility competence is lower In contrast the samerodent species experimentally infected with L infantum devel-oped only subclinical infection and was not infective to vectorsalthough the authors re-isolated the parasites from the spleen ofsome rodents during necropsy (Travi et al 2002) Other authors havedetected no infection in laboratory-bred specimens of anotherspecies P guyannensis after inoculation with promastigotes oramastigotes of L infantum (Lainson et al 2002) This difference maybe due to many variables related to the host and the parasite suchas the intra-specific heterogeneity of both taxa andor the size androute of the inoculum

Considered monospecific until 2002 caviomorphs from the genusThrichomys comprise at least five cryptic species distributed acrossdifferent biomes in Brazil (Bonvicino et al 2002) T apereoides werefound to be infected with L braziliensis L guyanensis L infantumand L amazonensis in leishmaniasis-endemic areas in Minas GeraisBrazil (Oliveira et al 2005 Quaresma et al 2011) Recently we alsodetected infection by various Leishmania species in these rodentsL infantum L naiffi L braziliensis and L shawi in T laurentius L shawiin T inermis and L naiffi in T pachyurus (Caacutessia-Pires et al unpub-lished data) Moreover T laurentius experimentally infected withL infantum and L braziliensis were able to maintain the infectionand parasite re-isolation was achieved up to 12 months after in-fection Leishmania DNA was detected in all experimental groupsand in all tissues sampled independent of the Leishmania speciesinoculated (Roque et al 2010)

In addition to Proechimys spp and Thrichomys spp L infantumhas been diagnosed in Clyomys laticeps Dasyprocta azarae Nectomyssquamipes Holochilus sciureus and Rhipidomys mastacalis from Brazil(Caacutessia-Pires et al unpublished data Dantas-Torres andBrandatildeo-Filho 2006 Quaresma et al 2011 Lima et al 2013 ) andRattus rattus from Brazil and Venezuela (Quinnell and Courtenay2009) Natural infection of Coendu prehensilis used as sentinels inBolivia has been parasitologically confirmed in the liver and spleen(Le Pont et al 1989)

Regarding L braziliensis if we consider only studies that con-firmed the identity of the etiological agent (not considering the

256 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

ancient L braziliensis sensu lato) the following rodent species havebeen described to be naturally infected Akodon arviculoides Musmusculus Nectomys squamipes Necromys (=Bolomys) lasiurusOryzomys nigripes Rattus rattus and Sigmodon hispidus (Brandatildeo-Filhoet al 2003 de Freitas et al 2012 De Lima et al 2002 Forattiniet al 1972 Peterson et al 1988 Rocha et al 1988 Vasconceloset al 1994) In other cases the authors confirmed infection by thesubgenus Leishmania (Viannia) sp (Holochilus scieurus and Cerradomyssubflavus) (Brandatildeo-Filho et al 2003 Lima et al 2013) or tenta-tively identified the etiological agent through the biological patternof in vitro growth (Rhipidomys leucodactylus and Proechimysguyannensis) (Lainson et al 1981b)

Rodents are also usually considered as the main reservoirs ofLeishmania from the L mexicana complex (L mexicana and Lamazonensis) L amazonensis was described in rodents from the fol-lowing genera Akodon Dasyprocta Oligoryzomys OryzomysProechimys Thrichomys and Sciurus (Arias et al 1981 Kerr et al2006 Lainson et al 1981b Mimori et al 1989 Oliveira et al 2005Telleria et al 1999) None of these studies however included follow-up of the infection or demonstrated competence to infect vectors

L mexicana has been isolated from various species of Neotomaincluding a specimen of N floridana with a large lesion in the earfrom which the parasite could be isolated (Kerr et al 1995 McHughet al 2003) This finding was informative suggesting that this rodentspecies may be infective for the vector and an important reservoirof L mexicana Ototylomys phyllotis from Belize should be consid-ered as a possible reservoir of L mexicana because of its relativeabundance prevalence of infection and attraction to Lu flaviscutellatathe most important vector in the region Curiously the same authorfailed to reproduce this infection under experimental conditions(Ashford 1996) possibly due to factors occurring only in naturesuch as stress and concomitant infections which may be impor-tant for the establishment of Leishmania infection This situationhighlights the importance of the studies of naturally infected speci-mens and the difficulties of adopting potential reservoir hosts asalternative models for leishmaniasis studies Moreover these find-ings attest to the hazards of applying conclusions based solely onexperimental models to natural systems

The persistence of L mexicana infection in wild rodents was dem-onstrated twice The first such finding occurred in Mexico where29 naturally infected rodents were maintained in captivity and testedmonthly for parasites for up to 2 years In that study the authorsdemonstrated persistent infection including symptomatic infec-tions in Sigmodon hispidus Oryzomys melanotis Ototylomys phyllotisand Peromyscus yucatanicus the latter two being the most impor-tant because of their high relative abundance in local fauna andlonger life spans (Van Wynsberghe et al 2000) Second in the UnitedStates during a 19-month markndashreleasendashrecapture study of Neotomamicropus the authors reported the persistence of L mexicana in-fection for up to 1 year (Raymond et al 2003) Heteromys Nyctomysand Reithrodontomys were also found infected with L mexicana(Ashford 1996 De Lima et al 2002 Disney 1968 Lainson andStrangways-Dixon 1964 Van Wynsberghe et al 2009)

Leishmania lainsoni was isolated from fragments of intact skinfrom pacas (Agouti paca) in the Brazilian state of Paraacute (Silveira et al1991) and from Coendu sp (Table 1) Leishmania panamensis was iso-lated from naturally infected Heteromys dermarestianus from CostaRica (Zeledon et al 1977) while a squirrel Scirus granatensis wasfound to be infected with L equatorensis in Ecuador (Grimaldi et al1992) Leishmania peruviana a species suggested to be a synonymof L braziliensis was isolated from the Peruvian Phyllotis andinum(Llanos-Cuentas et al 1999) Finally L hertigiL deanei and L enriettiispecies taxonomically more similar to Endotrypanum than to Leish-mania have been described respectively in porcupines Coendu spp(Herrer 1971 Silva et al 2013) and in the guinea pig Cavia porcellus(Machado et al 1994)

Taken together a broad diversity of Leishmania species natural-ly infect this mammal group most likely reflecting the diversity ofecological niches occupied by the hosts The differences observedamong the rodent species include the forest strata they occupy andtheir reproductive strategies (seasonality gestation time and numberof offspring) and these traits should be considered evaluations ofthe importance of a rodent species as a Leishmania reservoir More-over as expected for every hostndashparasite interaction thisheterogeneous mammalian taxon shows a spectrum of compe-tence to maintain and transmit Leishmania from high susceptibilitywith high transmissibility competence to quick control ofinfection

45 Order Carnivora

The mammals from this order also comprise a very heteroge-neous group including strict carnivores such as ocelots (Leoparduspardalis) and tayras (Eira barbara) and species that supplement theirdiet with insects and fruits such as coatis (Nasua nasua) and manedwolves (Chrysocyon brachyurus) Most have a large biomass and largerange important aspects of parasite dispersion (Rocha et al 2013)Moreover some species such as raccoons and tayras are found bothon the ground and in the canopy favoring the dispersion of para-sites among forest strata Unfortunately carnivores require largeranges and because of their potential to predate on livestock (mainlychickens and cattle) are heavily hunted placing some carnivorespecies at risk of extinction (Silva and Adania 2007)

Two carnivore species are closely linked to humans dogs andcats Dogs are the most important reservoirs of L infantum through-out South America although they can be infected with at least sixother Leishmania species (Dantas-Torres 2009) Recently the im-portance of cats in Leishmania epidemiology has also been suggested(Pennisi et al 2013) Among the wild carnivore hosts of L infantumthe first description of infection was in the crab-eating fox Cerdocyonthous although the authors inaccurately reported the host asLycalopex vetulus (Courtenay et al 1996 Deane and Deane 1955)Since then many studies have confirmed L infantum infection inC thous by parasitological serological andor molecular assaysNotably these animals sometimes develop serious symptoms of thedisease and present with amastigotes in intact skin as also de-scribed in domestic dogs Their prevalence of infection may rangefrom 42 (by parasitological tests) to 78 (by serology) (Lainson et al1990 Quinnell and Courtenay 2009 Silva et al 2000) The vectorinfectivity was proven by xenodiagnosis although the infection rateof vectors is reported to be lower than that observed for domesticdogs (Courtenay et al 2002 Quinnell and Courtenay 2009)

Apart from C thous another wild carnivore that is a potentialreservoir of L infantum is the bush dog Speothos venaticus An in-dividual kept in a zoo in Rio de Janeiro Brazil is the only wild canidexcept for C thous from which L infantum was isolated (Figueiredoet al 2008) Infection in bush dogs was also confirmed by directvisualization PCR and serology in two females with clinical signsof visceral leishmaniasis and maintained in other Brazilian zoos (Limaet al 2009 Souza et al 2010) Other wild canid species found tobe infected albeit only by PCR andor serology were the hoary foxPseudalopex vetulus and the maned wolf Chrysocyon brachyurus (Curiet al 2006 Luppi et al 2008) (Table 1)

Some authors have investigated Leishmania infection in captivewild carnivores Five of 15 wild canids belonging to the four nativespecies mentioned earlier were found to be infected in a zoo in BeloHorizonte Brazil Of these one bush dog and one hoary fox devel-oped clinical signs of visceral leishmaniasis (Luppi et al 2008)Among the wild felines five pumas (Puma concolor) and one jaguar(Panthera onca) in a zoo from Cuiabaacute Brazil were PCR-positive inlymph-node puncture biopsy L infantum was specifically identi-fied by the digestion of the amplified products with restriction

257ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

enzymes (Dahroug et al 2010) Later the same authors demon-strated L infantum infection in one lion a non-native felid specieskept in the same zoo (Dahroug et al 2011)

In addition to L infantum at least four other Leishmania specieswere found in wild carnivores L shawi in coatis Nasua nasua (Lainsonet al 1989) L guyanensis in the kinkajou Potos flavus (Pajot et al1982) L amazonensis in kinkajous crab-eating foxes and skunksConepatus chinga (Kreutzer et al 1991 Rotureau 2006 Telleria et al1999) and L braziliensis in one Bolivian skunk (Buitrago et al 2011)(Table 1)

Contrary to the numerous reports of infection in dogs and catsmuch remains to study in terms of the putative roles of wild car-nivores as Leishmania reservoirs As in all hostndashparasite interactionsthe infection patterns display regional and even individual pecu-liarities (Rocha et al 2013) If we consider that in some biomes(ldquoPantanal or Chacordquo ldquoCerradordquo and ldquoPampardquo) carnivore species areabundant and represent a huge biomass any study of Leishmaniareservoirs must include carnivores including their Leishmania in-fection pattern density and population structure in the area Despiteits inherent difficulties the study of wild carnivores especially inthe areas where their relative abundance is high is of fundamen-tal importance to improve understanding of Leishmania ecology

46 Order Primata

Nonhuman primates can be divided in two groups the catar-rhines (infraorder Catarrhini) from Africa Europe and Asia (OldWorld Primates) and the platyrrhines (Platyrrhini) from the Ameri-cas (New World or Neotropical Primates) The main differencebetween them is that the catarrhines have upside-down nostrils ona long snout while platyrrhines have laterally-faced nostrils on ashorter snout (Verona and Pissinatti 2007) The different speciesof neotropical primates are included in the families Cebidae (tama-rins) and Callitrichidae (marmosets) although some classificationsalso recognize three other families Aotidae Pithecidae and AtelidaeThe neotropical primates occupy distinct arboreal strata and consumediverse diets including species that feed on fruits invertebrates andeven small mammals (Verona and Pissinatti 2007)

To date few studies have described natural infection by Leish-mania parasites in neotropical primates Infection by L shawi wasdescribed in the tufted capuchin monkey Cebus apella and thebearded saki Chiropotes satanas (Lainson et al 1989) while infec-tion by Leishmania (Viannia) sp was recently demonstrated in fourArgentinean owl monkeys Aotus azarai (Acardi et al 2013) InPanamaacute Geoffroyrsquos tamarin Saguinus geoffroyi and the owl monkeyAotus trivirgatus were found to be infected with L amazonensis andL braziliensis respectively (Herrer and Christensen 1976 Herrer et al1973) In a Brazilian zoo one black-fronted titi Callicebus nigrifronsfrom Belo HorizonteMG presented with a fatal disease thatresembled visceral leishmaniasis Histological and immunohisto-chemical examinations as well as a PCR specific for parasites fromthe L donovani complex confirmed infection with L infantum (Maltaet al 2010) The other primate species that had PCR-positive bloodsamples in the same study were Alouatta guariba Cebus xanthosternosLeonthopitecus crysomelas Aotus nigriceps Pithecia irrorata andSaguinus imperator (Malta et al 2010) In the zoo in BauruSP Leish-mania amazonensis was detected by PCR-RFLP in a spider monkeyAteles paniscus from the endemic Amazon region (Lima et al 2012b)(Table 1)

Leishmania species that circulate in the Americas have been dem-onstrated to infect other neotropical primates but only underexperimental conditions Most of these studies focused on theimmune response to different drug treatments or on vaccine de-velopment For many years black-tufted marmosets Callithrixpenicillata were used in experimental studies with L braziliensis andL amazonensis (Cuba et al 1990 Cuba-Cuba and Marsden 1993)

Experimental infection of the common squirrel monkey Saimirisciureus resulted in non-ulcerated skin lesions from which Lbraziliensis andor L panamensis could be re-isolated (Pung et al1988) Owl monkeys Aotus trivirgatus developed localized cutane-ous lesions after experimental infection with L braziliensis Lmexicana and L panamensis (Christensen and de Vasquez 1981 Lujanet al 1986) Cebus apella developed skin lesions after experimen-tal infection with L lainsoni L amazonensis L braziliensis L mexicanaand L guyanensis (Garcez et al 2002 Grimaldi 2008) ConverselyCebus nigrivittatus developed fatal disease when experimentally in-fected with L infantum (Vouldoukis et al 1986)

All neotropical primates are included in the list of the ldquoConven-tion on International Trade in Endangered Species of Wild Faunaand Florardquo (CITES) indicating that all are vulnerable to some degree(Verona and Pissinatti 2007) For this reason many species suchas the golden lion tamarin Leonthopitecus rosalia are included in con-servation programs These programs often include exchangetranslocation and re-introduction of animals without consider-ation of their parasite fauna here including Leishmania and othertrypanosomatids Data from naturally infected primates demon-strate that these mammals may be involved in the maintenance ofLeishmania in the wild especially considering their ecology speciestransmitted in the canopy Taking into account the transmission cycleof these parasites a lack of knowledge regarding the health statusof the relocated primates may result in the introduction of in-fected mammals into a given area promoting the establishment ofnew transmission cycles (Lisboa et al 2006)

47 Order Chiroptera

Bats are nocturnal mammals and the only able to fly (some-times associated with seasonal migration) an important trait thatcan result in the dissemination of parasite species Their disper-sion capacity is due to the ability to do true flapping flight(apparently evolved differently among bat lineages) and the so-phisticated echolocation system that allows them to identify theenvironment (Jones and Teeling 2006) Despite their known diver-sity bats are still considered as a monophyletic group (Bishop 2008Bisson et al 2009)

Bats are commonly infected with several trypanosomatid speciesmainly from the Trypanosoma genus T cruzi T vespertilionis andT (Megatrypanum) sp among others (Lima et al 2012a) There isonly one report of the isolation of Leishmania parasites (L infantum)from the blood of a short-tailed fruit bat Carollia perspicillata in Ven-ezuela (De Lima et al 2008) (Table 1) Before that Lampo et al haddemonstrated that bats could be sources of blood for Lutzomyialongipalpis in Venezuelan caves (Lampo et al 2000)

In Brazil two Leishmania species were identified in maceratedfragments of spleen and liver from bats using a nested PCR fol-lowed by sequencing of the amplified products Molossus molossusand Glossophaga soricina were found to be infected with L infantumand L amazonensis and the latter was also found in Molossus rufusNyctinomops laticaudatus Eumops glaucinus E auripendulus Artibeusliteratus Sturnira lilium and Myotis nigricans (Savani et al 2010) Re-cently Leishmania (Viannia) sp was detected in a skin lesion fromGlossophaga soricina and blood from Molossus molossus (Shapiro et al2013) (Table 1) In this article although the authors have de-scribed infection with L braziliensis PCR-RFLP using primers b1 andb2 (Schonian et al 2003) does not allow for differentiation amongother species from the same subgenus such as L guyanensis

Bats should not be excluded as potential reservoirs of Leishma-nia sp because of the lack of studies involving Leishmania and batsChiroptera represents 39 of the 560 mammal species reported inSouth American rainforests it is the most common mammal groupin terms of diversity and biomass (Emmons and Feer 1997 Rotureau2006) These flying mammals are found in wild domestic and

258 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

synanthropic environments being able to colonize different habi-tats in different ecotypes Their refuges include hollow trees thecanopies of palm trees and ceilings of human houses and other ruralbuildings Their high abundance and adaptability to peri-domesticenvironment reinforce the importance of investigating bats alreadyrecognized as reservoirs of other trypanosomatids (Jansen and Roque2010) in the transmission cycles of Leishmania species

5 Conclusions and perspectives

Many decades have passed since the description of Leishmaniaparasites but their epidemiology is still not well understood in partbecause of the human-health focus of most studies Only recentlyinfluenced by the ldquoone healthrdquo approach has the epidemiology ofleishmaniasis started to be evaluated from a broader perspective(Palatnik-de-Sousa and Day 2011)

In the case of human visceral leishmaniasis caused by L infantumthe idea that dogs are the only reservoir of the parasite has led healthauthorities to direct the eradication of seropositive dogs on the basisthat this action was the only way to control this zoonosis In factseveral studies have demonstrated that dogs are epidemiologi-cally important as reservoirs in different localities (reviewed byLainson and Rangel 2005 Dantas-Torres 2009 Quinnell andCourtenay 2009) Nevertheless the participation of other in-fected mammals rather than dogs in the transmission cycle of Linfantum in urban areas was already proposed for cats and opos-sums for example (Pennisi et al 2013 Santiago et al 2007) Thelow effectiveness of dog culling program in Brazil is probably dueto an assemblage of factors most of them related to the lack of astructured surveillance system and include the high interval betweentests and between the positive result and dog elimination the rapidreplacement of susceptible dogs when an infected dog is euthan-ized and the resistance of owners to euthanize their infected dogs(Costa et al 2013 Grimaldi et al 2012 Nunes et al 2008) Someof these localities are very close to sylvatic areas and the possibil-ity that wild mammals may serve as a source of infection to vectorsin peridomiciliary areas has been ignored The putative participa-tion of these mammals is an important additional factor to beconsidered in the proposition of measures to control this zoono-sis This review highlights species from distinct orders that maymaintain and serve as a source of infection to phlebotomine sandfly vectors providing a constant source of re-infection to a peri-domestic transmission system

The reservoirs of the Leishmania species responsible for the cu-taneous forms of human leishmaniasis are still unknown most likelybecause research has focused on the search for a specific reservoirhost as observed for dogs and L infantum These species may bemaintained in the wild by a different strategy as by a few ldquohotspeciesrdquo with high transmissibility competence or most likelythrough a reservoir system an assemblage of mammals with dis-tinct and transient degrees of transmissibility competencethroughout infection This hypothesis agrees with the reservoir def-inition proposed by Ashford (1997) almost 20 years ago This systeminvolves a tradeoff that could explain the evolutionary success ofthese parasite species several individuals are infected but each iscompetent for transmission for only a limited time while retain-ing the infection for long periods of time The sum of multiple shortperiods of infectivity in numerous infected mammals guaranteesthe maintenance and transmission of these Leishmania species

All the links in the epidemiological chain must be clarified as a pre-requisite for effective control strategies (Abdussalan 1959Palatnik-de-Sousa and Day 2011 Shaw 2007) We are still far from un-derstanding the maintenance of different Leishmania species in natureIn this sense the follow-up of naturally infected animals and experi-mental studies using potential reservoirs are essential to improvingunderstanding of the mechanisms of maintenance of these parasites

in their natural hosts In the field the studies should not be restrictedto previously described infected hosts but should be carried out usingan integrated ecological approach to understand the role of each hostspecies in the maintenance and amplification of Leishmania para-sites Priorities include the identification of the factors that influencethe transmissibility competence of the individual mammalian hosts andunderstanding how environmental management could decrease in-fections in humans living close to sylvatic

Over the last century the scientific community has shown thatdifferent and several wild mammal species can become infected withLeishmania species The focus must change to identify species thatmay serve as sources of infection to vectors and amplify enzooticfoci constituting a risk for human transmission To this end a par-adigm shift in research and surveillance of wild reservoirs ofLeishmania is urgently needed This change will depend among otherfactors on understanding reservoir systems and acknowledging theimportance of understanding the role each mammal species playsin maintaining these parasites in nature The factors involved in theamplification of enzootic foci are temporally and regionally spe-cific and understanding some of these factors may support thedevelopment of effective and sustainable strategies for leishmani-asis surveillance

Acknowledgements

AMJ is a ldquoCientista do Nosso Estadordquo provided by FAPERJ andis financially supported by CNPq (ldquoBolsista de Produtividade niacutevel1rdquo CNPq) ALRR is a ldquoJovem Cientista do Nosso Estadordquo providedby FAPERJ The authors have declared that no competing interestsexist

References

Abdussalan M 1959 Significance of ecological studies of wild animal reservoir ofzoonoses Bull World Health Organ 21 179ndash186

Acardi SA Rago MV Liotta DJ Fernandez-Duque E Salomon OD 2013Leishmania (Viannia) DNA detection by PCR-RFLP and sequencing in free-rangingowl monkeys (Aotus azarai azarai) from Formosa Argentina Vet Parasitol 193256ndash259

Aguirre AA Tabor GM 2008 Global factors driving emerging infectious diseasesAnn N Y Acad Sci 1149 1ndash3

Alexander KA Lewis BL Marathe M Eubank S Blackburn JK 2012 Modelingof wildlife-associated zoonoses applications and caveats Vector Borne ZoonoticDis 12 1005ndash1018

Alvar J Velez ID Bern C Herrero M Desjeux P Cano J et al 2012 Leishmaniasisworldwide and global estimates of its incidence PLoS ONE 7 e35671

Arauacutejo A Reinhard K Ferreira LF Pucu E Chieffi PP 2013 Paleoparasitologythe origin of human parasites Arq Neuropsiquiatr 71 722ndash726

Arias JR Naif RD Miles MA de Souza AA 1981 The opossum Didelphismarsupialis (Marsupialia didelphidae) as a reservoir host of Leishmaniabraziliensis guyanensis in the Amazon Basin of Brazil Trans R Soc Trop MedHyg 75 537ndash541

Ashford DA Bozza M Freire M Miranda JC Sherlock I Eulalio C et al 1995Comparison of the polymerase chain reaction and serology for the detection ofcanine visceral leishmaniasis Am J Trop Med Hyg 53 251ndash255

Ashford RW 1996 Leishmaniasis reservoir and their significance in control ClinDermatol 14 523ndash532

Ashford RW 1997 What it takes to be a reservoir host Belg J Zool 127 85ndash90Ashford RW 2000 The leishmaniases as emerging and reemerging zoonoses Int

J Parasitol 30 1269ndash1281Austad SN 1988 The adaptable opossum Sci Am 258 54ndash59Bishop KL 2008 The evolution of flight in bats narrowing the field of plausible

hypotheses Q Rev Biol 83 153ndash169Bisson IA Safi K Holland RA 2009 Evidence for repeated independent evolution

of migration in the largest family of bats PLoS ONE 4 e7504Bonvicino CR Otazu IB DrsquoAndrea PS 2002 Karyologic evidence of diversification

of the genus Thrichomys (Rodentia Echimyidae) Cytogenet Genome Res 97200ndash204

Botero A Thompson CK Peacock CS Clode PL Nicholls PK Wayne AF et al2013 Trypanosomes genetic diversity polyparasitism and the population declineof the critically endangered Australian marsupial the brush tailed bettong orwoylie (Bettongia penicillata) Int J Parasitol Parasite Wildl 2 77ndash89

Brandatildeo-Filho SP Brito ME Carvalho FG Ishikawa EA Cupolillo EFloeter-Winter L et al 2003 Wild and synanthropic hosts of Leishmania(Viannia) braziliensis in the endemic cutaneous leishmaniasis locality of AmarajiPernambuco State Brazil Trans R Soc Trop Med Hyg 97 291ndash296

259ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

Table 1Mammal host species described infected by different Leishmania species in the Americas

Order Host species Leishmania species Infection pattern Country References

Didelphimorphia Didelphis marsupialis L infantum Potential reservoir CO VE Corredor et al 1989 apud Quinnell and Courtenay 2009L amazonensis Parasite host BR Grimaldi et al 1991L guyanensis Potential reservoir BR FG Arias et al 1981 Dedet et al 1989L forattinii Parasite host BR IOCL 0067

D albiventris L infantum Potential reservoir BR Sherlock et al 1984 Sherlock 1996L braziliensis Parasite host BR Quaresma et al 2011L peruviana Potential reservoir PE Llanos-Cuentas et al 1999

D aurita L infantum Parasite host BR Carreira et al 2012Philander opossum L amazonensis Parasite host BR Lainson et al 1981aMarmosa cinerea L amazonensis Parasite host BR Arias et al 1981Marmosa sp L (Viannia) sp Parasite host BR Brandatildeo-Filho et al 2003Micoreus paraguayanus L amazoensis Parasite host BR Quintal et al 2011

L braziliensis Parasite host BR Quintal et al 2011Gracilinanus agilis L braziliensis Parasite host BR Quaresma et al 2011Marmosops incanus L guyanensis Parasite host BR Quaresma et al 2011Metachirus nudicaudatus L amazonensis Parasite host BR Lainson et al 1981aMonodelphis domestica L (Viannia) sp Parasite host BR Lima et al 2013

Pilosa Choloepus didactylus L guyanensis Potential reservoir FG BR Gentile et al 1981 Lainson et al 1981aL shawi Parasite host BR Lainson et al 1989

C hoffmanni L colombiensis Parasite host PN Kreutzer et al 1991L equatoriensis Parasite host EC Grimaldi et al 1992L panamensis Parasite host PN apud Ashford 2000

Bradypus tridactylus L shawi Parasite host BR Lainson et al 1989Tamandua tetradactyla L guyanensis Parasite host BR Lainson et al 1981a

L amazonensis Parasite host EC Mimori et al 1989L infantum Parasite host BR Arauacutejo et al 2013

Cingulata Dasypus novemcinctus L naiffi Potential reservoir BR Lainson and Shaw 1989 Naiff et al 1991L guyanensis Parasite host BR Lainson et al 1979

Rodentia Proechimys species L amazonensis Potential reservoir BR FG Arias et al 1981 Dedet et al 1989L guyanensis Parasite host BR FG Dedet et al 1989 Lainson et al 1981b

P canicollis L infantum Parasite host CO Travi et al 1998aP semispinosus L panamensis Potential reservoir CO Travi et al 2002

L infantum Parasite host CO Travi et al 2002Thrichomys apereoides L braziliensis Parasite host BR Quaresma et al 2011

L guyanensis Parasite host BR Quaresma et al 2011L infantum Parasite host BR Oliveira et al 2005 Quaresma et al 2011L amazonensis Parasite host BR Oliveira et al 2005

T laurentius L infantum Potential reservoir BR Roque et al 2010L braziliensis Potential reservoir BR Roque et al 2010L naiffi Parasite host BR Caacutessia-Pires unpublished dataL shawi Parasite host BR Caacutessia-Pires unpublished data

T inermis L shawi Parasite host BR Caacutessia-Pires unpublished dataT pachyurus L naiffi Parasite host BR Caacutessia-Pires unpublished dataNectomys squamipes L infantum Parasite host BR Dantas-Torres and Brandao-Filho 2006

L braziliensis Parasite host BR Peterson et al 1988Rattus rattus L infantum Parasite host BR VE apud Quinnell and Courtenay 2009

L braziliensis Potential reservoir BR VE Vasconcelos et al 1994 De Lima et al 2002L mexicana Parasite host VE De Lima et al 2002

Clyomys laticeps L infantum Parasite host BR Caacutessia-Pires unpublished dataDasyprocta azarae L infantum Parasite host BR Caacutessia-Pires unpublished dataDasyprocta sp L amazonensis Parasite host BR Lainson et al 1981bRhipidomys mastacalis L infantum Parasite host BR Quaresma et al 2011Coendu sp L lainsoni Parasite host BR IOCL 1058

L hertigiL deanei Parasite host PN BR Herrer 1971 Silva et al 2013Coendu prehensilis L infantum Parasite host BO Le Pont et al 1989Akodon arviculoides L braziliensis Parasite host BR Forattini et al 1972 Rocha et al 1988Akodon sp L amazonensis Parasite host BO Telleria et al 1999Necromys lasiurus L braziliensis Potential reservoir BR Brandatildeo-Filho et al 2003 de Freitas et al 2012Sigmodon hispidus L braziliensis Potential reservoir VE De Lima et al 2002

L mexicana Potential reservoir MX VE Van Wynsberghe et al 2000 De Lima et al 2002Holochilus scieurus L infantum Parasite host BR Lima et al 2013H scieurus L (Viannia) sp Parasite host BR Brandatildeo-Filho et al 2003Cerradomys subflavus L (Viannia) sp Parasite host BR Lima et al 2013Mus musculus L braziliensis Parasite host BR de Freitas et al 2012Oryzomys species L amazonensis Parasite host BO Kerr et al 2006O melanotis L amazonensis Potential reservoir MX Van Wynsberghe et al 2000O nigripes L braziliensis Parasite host BR Forattini et al 1972Oligoryzomys sp L amazonensis Parasite host BO Telleria et al 1999Sciurus vulgaris L amazonensis Parasite host EC Mimori et al 1989S granatensis L equatorensis Parasite host EC Grimaldi et al 1992Neotoma species L mexicana Potential reservoir US Kerr et al 1995 Raymond et al 2003Ototylomys phyllotis L mexicana Potential reservoir BE MX Ashford 1996 Van Wynsberghe et al 2000Heteromys species L mexicana Parasite host BE MX Ashford 1996 Van Wynsberghe et al 2009H dermarestianus L panamensis Parasite host CR Zeledon et al 1977

(continued on next page)

254 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

infection detected by PCR (Humberg et al 2012 Santiago et al2007) The other Leishmania species found infecting D albiventrisare L braziliensis (Quaresma et al 2011) and L peruviana(Llanos-Cuentas et al 1999) (Table 1)

L infantum has also been detected in D aurita (Carreira et al2012) and another study also strongly suggests such infection inthe periphery of urban areas (Santiago et al 2007) Although itsrole as a reservoir has not yet been demonstrated it has strong po-tential to act as a reservoir due to the great phylogenetic proximityamong the Didelphis species (Jansa et al 2014) A unique study ona marsupial species able to explore distinct forest strata the opossumPhilander opossum described its infection by L amazonensis (Lainsonet al 1981a) The Leishmania species found infecting other mar-supial species are described in Table 1 (Quintal et al 2011)

Apart from the Didelphis species which are proven as potentialLeishmania reservoirs other marsupial species are poorly studiedThese ancient mammals are perhaps the very first Leishmania spphosts in the Americas although their role in transmission net remainsto be defined

42 Order Pilosa

This order is composed of anteaters and sloths which along witharmadillos (order Cingulata) compose the superorder Xenarthra (oddjoints) previously known as Edentata (Moller-Krull et al 2007) To-gether with the marsupials these ancient Leishmania hosts are alsonative American fauna and present a peculiar bloodndashvessel struc-ture that allows an extremely low metabolic rate sparing energy(Bugge 1979) Since the Tertiary Period many representatives ofthis taxon have become extinct and the extant genera constituteonly a small proportion of the order Mammals from this order havea long co-evolutionary history with trypanosomatids includingseveral Leishmania and Trypanosoma species as well as the poorlystudied genus Endotrypanum (Rotureau 2006)

Sloths are arboreal inhabitants of tropical regions of Central andSouth America and are represented by two genera Bradypus(Bradypodidae family) and Choloepus (Magalonichidae family) Slothshave reduced muscle mass and move slowly between trees by trav-eling directly through the arboreal strata descending only weekly

Table 1 (continued)

Order Host species Leishmania species Infection pattern Country References

Peromyscus yucatanicus L mexicana Potential reservoir MX Van Wynsberghe et al 2000Nyctomys sumichrasti L mexicana Parasite host HN Lainson and Strangways-Dixon 1964Reithrodontomys gracilis L mexicana Parasite host HN Disney 1968Agouti paca L lainsoni Potential reservoir BR Silveira et al 1991Phyllotis andinum L peruviana Parasite host PE Llanos-Cuentas et al 1999Cavia porcellus L enriettii Parasite host BR Machado et al 1994

Carnivora Cerdocyon thous L infantum Potential reservoir BR Deane and Deane 1955 Courtenay et al 1996L amazonesis Parasite host BR apud Rotureau 2006

Speothos venaticus L infantum Potential reservoir BR Figueiredo et al 2008 Lima et al 2009Pseudalopex vetulus L infantum Parasite host BR Curi et al 2006 Luppi et al 2008Chrysocyon brachyurus L infantum Parasite host BR Curi et al 2006 Luppi et al 2008Puma concolor L infantum Parasite host BR Dahroug et al 2010Panthera onca L infantum Parasite host BR Dahroug et al 2010Nasua nasua L shawi Parasite host BR Lainson et al 1989Potos flavus L guyanensis Parasite host FG Pajot et al 1982

L amazonensis Parasite host EC Kreutzer et al 1991Conepatus chinga L amazonensis Parasite host BO Telleria et al 1999

L braziliensis Parasite host BO Buitrago et al 2011Primata Cebus apella L shawi Potential reservoir BR Lainson et al 1989

Cebus xanthosternos L infantum Parasite host BR Malta et al 2010Chiropotes satanas L shawi Potential reservoir BR Lainson et al 1989Saguinus geoffroyi L amazonensis Potential reservoir PN Herrer et al 1973Aotus trivirgatus L braziliensis Potential reservoir PN Herrer and Christensen 1976Aotus azarai L (Viannia) sp Parasite host AR Acardi et al 2013Aotus nigriceps L infantum Parasite host BR Malta et al 2010Callicebus nigrifrons L infantum Parasite host BR Malta et al 2010Alouatta guariba L infantum Parasite host BR Malta et al 2010Leonthopitecus crysomelas L infantum Parasite host BR Malta et al 2010Pithecia irrorata L infantum Parasite host BR Malta et al 2010Saguinus imperator L infantum Parasite host BR Malta et al 2010Ateles paniscus L amazonensis Parasite host BR Lima et al 2012a

Chiroptera Carollia perspicillata L infantum Potential reservoir VE De Lima et al 2008Molossus molossus L infantum Parasite host BR Savani et al 2010

L amazonensis Parasite host BR Savani et al 2010L (Viannia) sp Parasite host BR Shapiro et al 2013

M rufus L amazonensis Parasite host BR Savani et al 2010Glossophaga soricina L infantum Parasite host BR Savani et al 2010

L amazonensis Parasite host BR Savani et al 2010L (Viannia) sp Parasite host BR Shapiro et al 2013

Nyctinomops laticaudatus L amazonensis Parasite host BR Savani et al 2010Eumops glaucinus L amazonensis Parasite host BR Savani et al 2010E auripendulus L amazonensis Parasite host BR Savani et al 2010Artibeus literatus L amazonensis Parasite host BR Savani et al 2010Sturnira lilium L amazonensis Parasite host BR Savani et al 2010Myotis nigricans L amazonensis Parasite host BR Savani et al 2010

Countries AR ndash Argentine BR ndash Brazil CL ndash Chile CO ndash Colombia VE ndash Venezuela FG ndash French Guiana PE ndash Peru PN ndash Panama EC ndash Ecuador BO ndash Bolivia US ndash UnitedStates of America BE ndash Belize MX ndash Mexico HN ndash Honduras CR ndash Costa RicaIOC L Characterized Strains deposited in the Leishmania sp Collection of the Oswaldo Cruz Institute (wwwcliocfiocruzbr) The number refers to the deposit number inCLIOC Catalogue

255ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

to defecate (Miranda and Costa 2006) The two-toed sloth (Choloepusdidactylus) is a potential reservoir of L guyanensis as demon-strated by the high rates of parasite isolation from intact skin (aswell as viscera) which vary from 35 to 47 in French Guiana (Dedetet al 1989 Gentile et al 1981) and reach up to 46 in Brazil(Lainson et al 1981a)

L shawi was described infecting the two-toed sloth and the pale-throated sloth (Bradypus tridactylus) both in Brazil (Lainson et al1989) In Panama L colombiensis was isolated from the viscera ofHoffmannrsquos two-toed sloth (Choloepus hoffmanni) (Kreutzer et al1991) while L equatorensis was found infecting the same speciesin Ecuador (Grimaldi et al 1992) Finally L panamensis a speciesclosely related to L guyanensis has been described in Choloepushoffmanni from Panama (Ashford 2000) (Table 1)

The anteaters constitute a single family (Myrmecophagidae) thatare mainly arboreal but that may also explore the terrestrial strataThe isolation of Leishmania was described in only one species thelesser anteater Tamandua tetradactyla L guyanensis (Lainson et al1981a) L amazonensis (Mimori et al 1989) and L infantum thislast in mixed infection with T cruzi and T rangeli (de Araujo et al2013) were found infecting the lesser anteater (Table 1)

The diversity of Leishmania species already known to infect slothsand anteaters suggests that these mammals may be important hostsfor parasite species that are transmitted in the arboreal strata Infact most of the Leishmania species found infecting these hosts aretransmitted by vectors associated with the arboreal strata such asLu umbratilis and Lu whitmani

43 Order Cingulata

Armadillos together with didelphid marsupials and Pilosa arealso among the oldest mammal groups from the Americas Theyare also the most primitive of the xenarthrans Members of thefamily Dasypodidae are the only surviving species in the order andare found from the southern United States to the Straits of Magel-lan (Miranda and Costa 2006) So far the nine-banded armadillo(Dasypus novemcinctus) is the only non-human host from which Lnaiffi has been isolated (from blood liver and spleen) (Lainsonand Shaw 1989 Naiff et al 1991) L guyanensis is anotherspecies already detected in D novemcinctus from Brazil (Lainsonet al 1979) In some rural areas armadillos are commonly ob-served invading chicken pens searching for eggs and frequentingperidomestic areas (personal observations) where it is possiblethat they can be a source of Leishmania infection for sandflies inthis environment

Armadillos sloths and anteaters are hunted and eaten in someareas of South America such as the Amazon People commonly carefor the young in their backyards after having killed the mothersduring a hunt The young are kept until they reach adulthood andwe cannot exclude the possibility of they become sources of infec-tion in the peridomestic environment

44 Order Rodentia

Rodents are the most diverse and widespread order of mammalsand include several cryptic species that can only be separated bykaryotyping (Bonvicino et al 2002) The first rodents (Hystricognathindash caviomorphs) arrived in the Americas (along with primates) fromAfrica approximately 45 million years ago The second wave of rodentmigration to the Americas (Sciurognathi ndash cricetids) was much morerecent and included an initial establishment in North America (Flynnand Wyss 1998) Since their arrival rodents have diversified widelyand may be found in desert adapted to aquatic media digging longand interconnected tunnels and in forest canopies (Wilson andReeder 2005) This taxon is most likely the most studied in termsof infection by Leishmania spp in both natural and experimental

conditions however excepting a few studies experimentalinfections have been conducted in laboratory mouse lineages whichare not representative of the wild Mus musculus

After the Pilosa Marsupialia and Cingulata caviomorphs (sub-order Hystricognathi) are most likely the most ancient hosts ofLeishmania spp Moreover their arrival in the Americas is relatedto the entry of some species from the sub-genus Leishmania intothe continent (Thomaz-Soccol et al 1993) Caviomorphs from thegenus Proechimys were already found to be infected by various Leish-mania species These rodents are characterized by their longevity(more than 3 years in captivity) and high abundance in most lo-calities where they are found in tropical forests of Central and SouthAmerica (Ashford 1996) Various Proechimys species have been iden-tified as potential reservoirs of L amazonensis in Brazil and FrenchGuiana as demonstrated by the frequent skin parasitism con-firmed by tissue culture (Arias et al 1981 Dedet et al 1989) InFrench Guiana for example this infection was observed in two sym-patric species P cuvieri and P guyanensis (Rotureau 2006) Otherreports of natural infection in the skin of these rodents include Linfantum in P canicollis from Colombia (Travi et al 1998a) and Lguyanensis in Proechimys sp from French Guiana (Dedet et al 1989)and Brazil (Lainson et al 1981a) (Table 1)

P semispinosus from Colombia experimentally infected with Lpanamensis developed self resolving non-ulcerated lesions (fromwhich parasites could be re-isolated and which were demon-strated to be highly infective to vectors in the initial phase of infection(Travi et al 2002) This hostndashparasite interaction exemplifies a tem-poral reservoir competence in one host species passing from anamplifier host (in the beginning of infection) to a maintenance hostin which transmissibility competence is lower In contrast the samerodent species experimentally infected with L infantum devel-oped only subclinical infection and was not infective to vectorsalthough the authors re-isolated the parasites from the spleen ofsome rodents during necropsy (Travi et al 2002) Other authors havedetected no infection in laboratory-bred specimens of anotherspecies P guyannensis after inoculation with promastigotes oramastigotes of L infantum (Lainson et al 2002) This difference maybe due to many variables related to the host and the parasite suchas the intra-specific heterogeneity of both taxa andor the size androute of the inoculum

Considered monospecific until 2002 caviomorphs from the genusThrichomys comprise at least five cryptic species distributed acrossdifferent biomes in Brazil (Bonvicino et al 2002) T apereoides werefound to be infected with L braziliensis L guyanensis L infantumand L amazonensis in leishmaniasis-endemic areas in Minas GeraisBrazil (Oliveira et al 2005 Quaresma et al 2011) Recently we alsodetected infection by various Leishmania species in these rodentsL infantum L naiffi L braziliensis and L shawi in T laurentius L shawiin T inermis and L naiffi in T pachyurus (Caacutessia-Pires et al unpub-lished data) Moreover T laurentius experimentally infected withL infantum and L braziliensis were able to maintain the infectionand parasite re-isolation was achieved up to 12 months after in-fection Leishmania DNA was detected in all experimental groupsand in all tissues sampled independent of the Leishmania speciesinoculated (Roque et al 2010)

In addition to Proechimys spp and Thrichomys spp L infantumhas been diagnosed in Clyomys laticeps Dasyprocta azarae Nectomyssquamipes Holochilus sciureus and Rhipidomys mastacalis from Brazil(Caacutessia-Pires et al unpublished data Dantas-Torres andBrandatildeo-Filho 2006 Quaresma et al 2011 Lima et al 2013 ) andRattus rattus from Brazil and Venezuela (Quinnell and Courtenay2009) Natural infection of Coendu prehensilis used as sentinels inBolivia has been parasitologically confirmed in the liver and spleen(Le Pont et al 1989)

Regarding L braziliensis if we consider only studies that con-firmed the identity of the etiological agent (not considering the

256 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

ancient L braziliensis sensu lato) the following rodent species havebeen described to be naturally infected Akodon arviculoides Musmusculus Nectomys squamipes Necromys (=Bolomys) lasiurusOryzomys nigripes Rattus rattus and Sigmodon hispidus (Brandatildeo-Filhoet al 2003 de Freitas et al 2012 De Lima et al 2002 Forattiniet al 1972 Peterson et al 1988 Rocha et al 1988 Vasconceloset al 1994) In other cases the authors confirmed infection by thesubgenus Leishmania (Viannia) sp (Holochilus scieurus and Cerradomyssubflavus) (Brandatildeo-Filho et al 2003 Lima et al 2013) or tenta-tively identified the etiological agent through the biological patternof in vitro growth (Rhipidomys leucodactylus and Proechimysguyannensis) (Lainson et al 1981b)

Rodents are also usually considered as the main reservoirs ofLeishmania from the L mexicana complex (L mexicana and Lamazonensis) L amazonensis was described in rodents from the fol-lowing genera Akodon Dasyprocta Oligoryzomys OryzomysProechimys Thrichomys and Sciurus (Arias et al 1981 Kerr et al2006 Lainson et al 1981b Mimori et al 1989 Oliveira et al 2005Telleria et al 1999) None of these studies however included follow-up of the infection or demonstrated competence to infect vectors

L mexicana has been isolated from various species of Neotomaincluding a specimen of N floridana with a large lesion in the earfrom which the parasite could be isolated (Kerr et al 1995 McHughet al 2003) This finding was informative suggesting that this rodentspecies may be infective for the vector and an important reservoirof L mexicana Ototylomys phyllotis from Belize should be consid-ered as a possible reservoir of L mexicana because of its relativeabundance prevalence of infection and attraction to Lu flaviscutellatathe most important vector in the region Curiously the same authorfailed to reproduce this infection under experimental conditions(Ashford 1996) possibly due to factors occurring only in naturesuch as stress and concomitant infections which may be impor-tant for the establishment of Leishmania infection This situationhighlights the importance of the studies of naturally infected speci-mens and the difficulties of adopting potential reservoir hosts asalternative models for leishmaniasis studies Moreover these find-ings attest to the hazards of applying conclusions based solely onexperimental models to natural systems

The persistence of L mexicana infection in wild rodents was dem-onstrated twice The first such finding occurred in Mexico where29 naturally infected rodents were maintained in captivity and testedmonthly for parasites for up to 2 years In that study the authorsdemonstrated persistent infection including symptomatic infec-tions in Sigmodon hispidus Oryzomys melanotis Ototylomys phyllotisand Peromyscus yucatanicus the latter two being the most impor-tant because of their high relative abundance in local fauna andlonger life spans (Van Wynsberghe et al 2000) Second in the UnitedStates during a 19-month markndashreleasendashrecapture study of Neotomamicropus the authors reported the persistence of L mexicana in-fection for up to 1 year (Raymond et al 2003) Heteromys Nyctomysand Reithrodontomys were also found infected with L mexicana(Ashford 1996 De Lima et al 2002 Disney 1968 Lainson andStrangways-Dixon 1964 Van Wynsberghe et al 2009)

Leishmania lainsoni was isolated from fragments of intact skinfrom pacas (Agouti paca) in the Brazilian state of Paraacute (Silveira et al1991) and from Coendu sp (Table 1) Leishmania panamensis was iso-lated from naturally infected Heteromys dermarestianus from CostaRica (Zeledon et al 1977) while a squirrel Scirus granatensis wasfound to be infected with L equatorensis in Ecuador (Grimaldi et al1992) Leishmania peruviana a species suggested to be a synonymof L braziliensis was isolated from the Peruvian Phyllotis andinum(Llanos-Cuentas et al 1999) Finally L hertigiL deanei and L enriettiispecies taxonomically more similar to Endotrypanum than to Leish-mania have been described respectively in porcupines Coendu spp(Herrer 1971 Silva et al 2013) and in the guinea pig Cavia porcellus(Machado et al 1994)

Taken together a broad diversity of Leishmania species natural-ly infect this mammal group most likely reflecting the diversity ofecological niches occupied by the hosts The differences observedamong the rodent species include the forest strata they occupy andtheir reproductive strategies (seasonality gestation time and numberof offspring) and these traits should be considered evaluations ofthe importance of a rodent species as a Leishmania reservoir More-over as expected for every hostndashparasite interaction thisheterogeneous mammalian taxon shows a spectrum of compe-tence to maintain and transmit Leishmania from high susceptibilitywith high transmissibility competence to quick control ofinfection

45 Order Carnivora

The mammals from this order also comprise a very heteroge-neous group including strict carnivores such as ocelots (Leoparduspardalis) and tayras (Eira barbara) and species that supplement theirdiet with insects and fruits such as coatis (Nasua nasua) and manedwolves (Chrysocyon brachyurus) Most have a large biomass and largerange important aspects of parasite dispersion (Rocha et al 2013)Moreover some species such as raccoons and tayras are found bothon the ground and in the canopy favoring the dispersion of para-sites among forest strata Unfortunately carnivores require largeranges and because of their potential to predate on livestock (mainlychickens and cattle) are heavily hunted placing some carnivorespecies at risk of extinction (Silva and Adania 2007)

Two carnivore species are closely linked to humans dogs andcats Dogs are the most important reservoirs of L infantum through-out South America although they can be infected with at least sixother Leishmania species (Dantas-Torres 2009) Recently the im-portance of cats in Leishmania epidemiology has also been suggested(Pennisi et al 2013) Among the wild carnivore hosts of L infantumthe first description of infection was in the crab-eating fox Cerdocyonthous although the authors inaccurately reported the host asLycalopex vetulus (Courtenay et al 1996 Deane and Deane 1955)Since then many studies have confirmed L infantum infection inC thous by parasitological serological andor molecular assaysNotably these animals sometimes develop serious symptoms of thedisease and present with amastigotes in intact skin as also de-scribed in domestic dogs Their prevalence of infection may rangefrom 42 (by parasitological tests) to 78 (by serology) (Lainson et al1990 Quinnell and Courtenay 2009 Silva et al 2000) The vectorinfectivity was proven by xenodiagnosis although the infection rateof vectors is reported to be lower than that observed for domesticdogs (Courtenay et al 2002 Quinnell and Courtenay 2009)

Apart from C thous another wild carnivore that is a potentialreservoir of L infantum is the bush dog Speothos venaticus An in-dividual kept in a zoo in Rio de Janeiro Brazil is the only wild canidexcept for C thous from which L infantum was isolated (Figueiredoet al 2008) Infection in bush dogs was also confirmed by directvisualization PCR and serology in two females with clinical signsof visceral leishmaniasis and maintained in other Brazilian zoos (Limaet al 2009 Souza et al 2010) Other wild canid species found tobe infected albeit only by PCR andor serology were the hoary foxPseudalopex vetulus and the maned wolf Chrysocyon brachyurus (Curiet al 2006 Luppi et al 2008) (Table 1)

Some authors have investigated Leishmania infection in captivewild carnivores Five of 15 wild canids belonging to the four nativespecies mentioned earlier were found to be infected in a zoo in BeloHorizonte Brazil Of these one bush dog and one hoary fox devel-oped clinical signs of visceral leishmaniasis (Luppi et al 2008)Among the wild felines five pumas (Puma concolor) and one jaguar(Panthera onca) in a zoo from Cuiabaacute Brazil were PCR-positive inlymph-node puncture biopsy L infantum was specifically identi-fied by the digestion of the amplified products with restriction

257ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

enzymes (Dahroug et al 2010) Later the same authors demon-strated L infantum infection in one lion a non-native felid specieskept in the same zoo (Dahroug et al 2011)

In addition to L infantum at least four other Leishmania specieswere found in wild carnivores L shawi in coatis Nasua nasua (Lainsonet al 1989) L guyanensis in the kinkajou Potos flavus (Pajot et al1982) L amazonensis in kinkajous crab-eating foxes and skunksConepatus chinga (Kreutzer et al 1991 Rotureau 2006 Telleria et al1999) and L braziliensis in one Bolivian skunk (Buitrago et al 2011)(Table 1)

Contrary to the numerous reports of infection in dogs and catsmuch remains to study in terms of the putative roles of wild car-nivores as Leishmania reservoirs As in all hostndashparasite interactionsthe infection patterns display regional and even individual pecu-liarities (Rocha et al 2013) If we consider that in some biomes(ldquoPantanal or Chacordquo ldquoCerradordquo and ldquoPampardquo) carnivore species areabundant and represent a huge biomass any study of Leishmaniareservoirs must include carnivores including their Leishmania in-fection pattern density and population structure in the area Despiteits inherent difficulties the study of wild carnivores especially inthe areas where their relative abundance is high is of fundamen-tal importance to improve understanding of Leishmania ecology

46 Order Primata

Nonhuman primates can be divided in two groups the catar-rhines (infraorder Catarrhini) from Africa Europe and Asia (OldWorld Primates) and the platyrrhines (Platyrrhini) from the Ameri-cas (New World or Neotropical Primates) The main differencebetween them is that the catarrhines have upside-down nostrils ona long snout while platyrrhines have laterally-faced nostrils on ashorter snout (Verona and Pissinatti 2007) The different speciesof neotropical primates are included in the families Cebidae (tama-rins) and Callitrichidae (marmosets) although some classificationsalso recognize three other families Aotidae Pithecidae and AtelidaeThe neotropical primates occupy distinct arboreal strata and consumediverse diets including species that feed on fruits invertebrates andeven small mammals (Verona and Pissinatti 2007)

To date few studies have described natural infection by Leish-mania parasites in neotropical primates Infection by L shawi wasdescribed in the tufted capuchin monkey Cebus apella and thebearded saki Chiropotes satanas (Lainson et al 1989) while infec-tion by Leishmania (Viannia) sp was recently demonstrated in fourArgentinean owl monkeys Aotus azarai (Acardi et al 2013) InPanamaacute Geoffroyrsquos tamarin Saguinus geoffroyi and the owl monkeyAotus trivirgatus were found to be infected with L amazonensis andL braziliensis respectively (Herrer and Christensen 1976 Herrer et al1973) In a Brazilian zoo one black-fronted titi Callicebus nigrifronsfrom Belo HorizonteMG presented with a fatal disease thatresembled visceral leishmaniasis Histological and immunohisto-chemical examinations as well as a PCR specific for parasites fromthe L donovani complex confirmed infection with L infantum (Maltaet al 2010) The other primate species that had PCR-positive bloodsamples in the same study were Alouatta guariba Cebus xanthosternosLeonthopitecus crysomelas Aotus nigriceps Pithecia irrorata andSaguinus imperator (Malta et al 2010) In the zoo in BauruSP Leish-mania amazonensis was detected by PCR-RFLP in a spider monkeyAteles paniscus from the endemic Amazon region (Lima et al 2012b)(Table 1)

Leishmania species that circulate in the Americas have been dem-onstrated to infect other neotropical primates but only underexperimental conditions Most of these studies focused on theimmune response to different drug treatments or on vaccine de-velopment For many years black-tufted marmosets Callithrixpenicillata were used in experimental studies with L braziliensis andL amazonensis (Cuba et al 1990 Cuba-Cuba and Marsden 1993)

Experimental infection of the common squirrel monkey Saimirisciureus resulted in non-ulcerated skin lesions from which Lbraziliensis andor L panamensis could be re-isolated (Pung et al1988) Owl monkeys Aotus trivirgatus developed localized cutane-ous lesions after experimental infection with L braziliensis Lmexicana and L panamensis (Christensen and de Vasquez 1981 Lujanet al 1986) Cebus apella developed skin lesions after experimen-tal infection with L lainsoni L amazonensis L braziliensis L mexicanaand L guyanensis (Garcez et al 2002 Grimaldi 2008) ConverselyCebus nigrivittatus developed fatal disease when experimentally in-fected with L infantum (Vouldoukis et al 1986)

All neotropical primates are included in the list of the ldquoConven-tion on International Trade in Endangered Species of Wild Faunaand Florardquo (CITES) indicating that all are vulnerable to some degree(Verona and Pissinatti 2007) For this reason many species suchas the golden lion tamarin Leonthopitecus rosalia are included in con-servation programs These programs often include exchangetranslocation and re-introduction of animals without consider-ation of their parasite fauna here including Leishmania and othertrypanosomatids Data from naturally infected primates demon-strate that these mammals may be involved in the maintenance ofLeishmania in the wild especially considering their ecology speciestransmitted in the canopy Taking into account the transmission cycleof these parasites a lack of knowledge regarding the health statusof the relocated primates may result in the introduction of in-fected mammals into a given area promoting the establishment ofnew transmission cycles (Lisboa et al 2006)

47 Order Chiroptera

Bats are nocturnal mammals and the only able to fly (some-times associated with seasonal migration) an important trait thatcan result in the dissemination of parasite species Their disper-sion capacity is due to the ability to do true flapping flight(apparently evolved differently among bat lineages) and the so-phisticated echolocation system that allows them to identify theenvironment (Jones and Teeling 2006) Despite their known diver-sity bats are still considered as a monophyletic group (Bishop 2008Bisson et al 2009)

Bats are commonly infected with several trypanosomatid speciesmainly from the Trypanosoma genus T cruzi T vespertilionis andT (Megatrypanum) sp among others (Lima et al 2012a) There isonly one report of the isolation of Leishmania parasites (L infantum)from the blood of a short-tailed fruit bat Carollia perspicillata in Ven-ezuela (De Lima et al 2008) (Table 1) Before that Lampo et al haddemonstrated that bats could be sources of blood for Lutzomyialongipalpis in Venezuelan caves (Lampo et al 2000)

In Brazil two Leishmania species were identified in maceratedfragments of spleen and liver from bats using a nested PCR fol-lowed by sequencing of the amplified products Molossus molossusand Glossophaga soricina were found to be infected with L infantumand L amazonensis and the latter was also found in Molossus rufusNyctinomops laticaudatus Eumops glaucinus E auripendulus Artibeusliteratus Sturnira lilium and Myotis nigricans (Savani et al 2010) Re-cently Leishmania (Viannia) sp was detected in a skin lesion fromGlossophaga soricina and blood from Molossus molossus (Shapiro et al2013) (Table 1) In this article although the authors have de-scribed infection with L braziliensis PCR-RFLP using primers b1 andb2 (Schonian et al 2003) does not allow for differentiation amongother species from the same subgenus such as L guyanensis

Bats should not be excluded as potential reservoirs of Leishma-nia sp because of the lack of studies involving Leishmania and batsChiroptera represents 39 of the 560 mammal species reported inSouth American rainforests it is the most common mammal groupin terms of diversity and biomass (Emmons and Feer 1997 Rotureau2006) These flying mammals are found in wild domestic and

258 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

synanthropic environments being able to colonize different habi-tats in different ecotypes Their refuges include hollow trees thecanopies of palm trees and ceilings of human houses and other ruralbuildings Their high abundance and adaptability to peri-domesticenvironment reinforce the importance of investigating bats alreadyrecognized as reservoirs of other trypanosomatids (Jansen and Roque2010) in the transmission cycles of Leishmania species

5 Conclusions and perspectives

Many decades have passed since the description of Leishmaniaparasites but their epidemiology is still not well understood in partbecause of the human-health focus of most studies Only recentlyinfluenced by the ldquoone healthrdquo approach has the epidemiology ofleishmaniasis started to be evaluated from a broader perspective(Palatnik-de-Sousa and Day 2011)

In the case of human visceral leishmaniasis caused by L infantumthe idea that dogs are the only reservoir of the parasite has led healthauthorities to direct the eradication of seropositive dogs on the basisthat this action was the only way to control this zoonosis In factseveral studies have demonstrated that dogs are epidemiologi-cally important as reservoirs in different localities (reviewed byLainson and Rangel 2005 Dantas-Torres 2009 Quinnell andCourtenay 2009) Nevertheless the participation of other in-fected mammals rather than dogs in the transmission cycle of Linfantum in urban areas was already proposed for cats and opos-sums for example (Pennisi et al 2013 Santiago et al 2007) Thelow effectiveness of dog culling program in Brazil is probably dueto an assemblage of factors most of them related to the lack of astructured surveillance system and include the high interval betweentests and between the positive result and dog elimination the rapidreplacement of susceptible dogs when an infected dog is euthan-ized and the resistance of owners to euthanize their infected dogs(Costa et al 2013 Grimaldi et al 2012 Nunes et al 2008) Someof these localities are very close to sylvatic areas and the possibil-ity that wild mammals may serve as a source of infection to vectorsin peridomiciliary areas has been ignored The putative participa-tion of these mammals is an important additional factor to beconsidered in the proposition of measures to control this zoono-sis This review highlights species from distinct orders that maymaintain and serve as a source of infection to phlebotomine sandfly vectors providing a constant source of re-infection to a peri-domestic transmission system

The reservoirs of the Leishmania species responsible for the cu-taneous forms of human leishmaniasis are still unknown most likelybecause research has focused on the search for a specific reservoirhost as observed for dogs and L infantum These species may bemaintained in the wild by a different strategy as by a few ldquohotspeciesrdquo with high transmissibility competence or most likelythrough a reservoir system an assemblage of mammals with dis-tinct and transient degrees of transmissibility competencethroughout infection This hypothesis agrees with the reservoir def-inition proposed by Ashford (1997) almost 20 years ago This systeminvolves a tradeoff that could explain the evolutionary success ofthese parasite species several individuals are infected but each iscompetent for transmission for only a limited time while retain-ing the infection for long periods of time The sum of multiple shortperiods of infectivity in numerous infected mammals guaranteesthe maintenance and transmission of these Leishmania species

All the links in the epidemiological chain must be clarified as a pre-requisite for effective control strategies (Abdussalan 1959Palatnik-de-Sousa and Day 2011 Shaw 2007) We are still far from un-derstanding the maintenance of different Leishmania species in natureIn this sense the follow-up of naturally infected animals and experi-mental studies using potential reservoirs are essential to improvingunderstanding of the mechanisms of maintenance of these parasites

in their natural hosts In the field the studies should not be restrictedto previously described infected hosts but should be carried out usingan integrated ecological approach to understand the role of each hostspecies in the maintenance and amplification of Leishmania para-sites Priorities include the identification of the factors that influencethe transmissibility competence of the individual mammalian hosts andunderstanding how environmental management could decrease in-fections in humans living close to sylvatic

Over the last century the scientific community has shown thatdifferent and several wild mammal species can become infected withLeishmania species The focus must change to identify species thatmay serve as sources of infection to vectors and amplify enzooticfoci constituting a risk for human transmission To this end a par-adigm shift in research and surveillance of wild reservoirs ofLeishmania is urgently needed This change will depend among otherfactors on understanding reservoir systems and acknowledging theimportance of understanding the role each mammal species playsin maintaining these parasites in nature The factors involved in theamplification of enzootic foci are temporally and regionally spe-cific and understanding some of these factors may support thedevelopment of effective and sustainable strategies for leishmani-asis surveillance

Acknowledgements

AMJ is a ldquoCientista do Nosso Estadordquo provided by FAPERJ andis financially supported by CNPq (ldquoBolsista de Produtividade niacutevel1rdquo CNPq) ALRR is a ldquoJovem Cientista do Nosso Estadordquo providedby FAPERJ The authors have declared that no competing interestsexist

References

Abdussalan M 1959 Significance of ecological studies of wild animal reservoir ofzoonoses Bull World Health Organ 21 179ndash186

Acardi SA Rago MV Liotta DJ Fernandez-Duque E Salomon OD 2013Leishmania (Viannia) DNA detection by PCR-RFLP and sequencing in free-rangingowl monkeys (Aotus azarai azarai) from Formosa Argentina Vet Parasitol 193256ndash259

Aguirre AA Tabor GM 2008 Global factors driving emerging infectious diseasesAnn N Y Acad Sci 1149 1ndash3

Alexander KA Lewis BL Marathe M Eubank S Blackburn JK 2012 Modelingof wildlife-associated zoonoses applications and caveats Vector Borne ZoonoticDis 12 1005ndash1018

Alvar J Velez ID Bern C Herrero M Desjeux P Cano J et al 2012 Leishmaniasisworldwide and global estimates of its incidence PLoS ONE 7 e35671

Arauacutejo A Reinhard K Ferreira LF Pucu E Chieffi PP 2013 Paleoparasitologythe origin of human parasites Arq Neuropsiquiatr 71 722ndash726

Arias JR Naif RD Miles MA de Souza AA 1981 The opossum Didelphismarsupialis (Marsupialia didelphidae) as a reservoir host of Leishmaniabraziliensis guyanensis in the Amazon Basin of Brazil Trans R Soc Trop MedHyg 75 537ndash541

Ashford DA Bozza M Freire M Miranda JC Sherlock I Eulalio C et al 1995Comparison of the polymerase chain reaction and serology for the detection ofcanine visceral leishmaniasis Am J Trop Med Hyg 53 251ndash255

Ashford RW 1996 Leishmaniasis reservoir and their significance in control ClinDermatol 14 523ndash532

Ashford RW 1997 What it takes to be a reservoir host Belg J Zool 127 85ndash90Ashford RW 2000 The leishmaniases as emerging and reemerging zoonoses Int

J Parasitol 30 1269ndash1281Austad SN 1988 The adaptable opossum Sci Am 258 54ndash59Bishop KL 2008 The evolution of flight in bats narrowing the field of plausible

hypotheses Q Rev Biol 83 153ndash169Bisson IA Safi K Holland RA 2009 Evidence for repeated independent evolution

of migration in the largest family of bats PLoS ONE 4 e7504Bonvicino CR Otazu IB DrsquoAndrea PS 2002 Karyologic evidence of diversification

of the genus Thrichomys (Rodentia Echimyidae) Cytogenet Genome Res 97200ndash204

Botero A Thompson CK Peacock CS Clode PL Nicholls PK Wayne AF et al2013 Trypanosomes genetic diversity polyparasitism and the population declineof the critically endangered Australian marsupial the brush tailed bettong orwoylie (Bettongia penicillata) Int J Parasitol Parasite Wildl 2 77ndash89

Brandatildeo-Filho SP Brito ME Carvalho FG Ishikawa EA Cupolillo EFloeter-Winter L et al 2003 Wild and synanthropic hosts of Leishmania(Viannia) braziliensis in the endemic cutaneous leishmaniasis locality of AmarajiPernambuco State Brazil Trans R Soc Trop Med Hyg 97 291ndash296

259ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

infection detected by PCR (Humberg et al 2012 Santiago et al2007) The other Leishmania species found infecting D albiventrisare L braziliensis (Quaresma et al 2011) and L peruviana(Llanos-Cuentas et al 1999) (Table 1)

L infantum has also been detected in D aurita (Carreira et al2012) and another study also strongly suggests such infection inthe periphery of urban areas (Santiago et al 2007) Although itsrole as a reservoir has not yet been demonstrated it has strong po-tential to act as a reservoir due to the great phylogenetic proximityamong the Didelphis species (Jansa et al 2014) A unique study ona marsupial species able to explore distinct forest strata the opossumPhilander opossum described its infection by L amazonensis (Lainsonet al 1981a) The Leishmania species found infecting other mar-supial species are described in Table 1 (Quintal et al 2011)

Apart from the Didelphis species which are proven as potentialLeishmania reservoirs other marsupial species are poorly studiedThese ancient mammals are perhaps the very first Leishmania spphosts in the Americas although their role in transmission net remainsto be defined

42 Order Pilosa

This order is composed of anteaters and sloths which along witharmadillos (order Cingulata) compose the superorder Xenarthra (oddjoints) previously known as Edentata (Moller-Krull et al 2007) To-gether with the marsupials these ancient Leishmania hosts are alsonative American fauna and present a peculiar bloodndashvessel struc-ture that allows an extremely low metabolic rate sparing energy(Bugge 1979) Since the Tertiary Period many representatives ofthis taxon have become extinct and the extant genera constituteonly a small proportion of the order Mammals from this order havea long co-evolutionary history with trypanosomatids includingseveral Leishmania and Trypanosoma species as well as the poorlystudied genus Endotrypanum (Rotureau 2006)

Sloths are arboreal inhabitants of tropical regions of Central andSouth America and are represented by two genera Bradypus(Bradypodidae family) and Choloepus (Magalonichidae family) Slothshave reduced muscle mass and move slowly between trees by trav-eling directly through the arboreal strata descending only weekly

Table 1 (continued)

Order Host species Leishmania species Infection pattern Country References

Peromyscus yucatanicus L mexicana Potential reservoir MX Van Wynsberghe et al 2000Nyctomys sumichrasti L mexicana Parasite host HN Lainson and Strangways-Dixon 1964Reithrodontomys gracilis L mexicana Parasite host HN Disney 1968Agouti paca L lainsoni Potential reservoir BR Silveira et al 1991Phyllotis andinum L peruviana Parasite host PE Llanos-Cuentas et al 1999Cavia porcellus L enriettii Parasite host BR Machado et al 1994

Carnivora Cerdocyon thous L infantum Potential reservoir BR Deane and Deane 1955 Courtenay et al 1996L amazonesis Parasite host BR apud Rotureau 2006

Speothos venaticus L infantum Potential reservoir BR Figueiredo et al 2008 Lima et al 2009Pseudalopex vetulus L infantum Parasite host BR Curi et al 2006 Luppi et al 2008Chrysocyon brachyurus L infantum Parasite host BR Curi et al 2006 Luppi et al 2008Puma concolor L infantum Parasite host BR Dahroug et al 2010Panthera onca L infantum Parasite host BR Dahroug et al 2010Nasua nasua L shawi Parasite host BR Lainson et al 1989Potos flavus L guyanensis Parasite host FG Pajot et al 1982

L amazonensis Parasite host EC Kreutzer et al 1991Conepatus chinga L amazonensis Parasite host BO Telleria et al 1999

L braziliensis Parasite host BO Buitrago et al 2011Primata Cebus apella L shawi Potential reservoir BR Lainson et al 1989

Cebus xanthosternos L infantum Parasite host BR Malta et al 2010Chiropotes satanas L shawi Potential reservoir BR Lainson et al 1989Saguinus geoffroyi L amazonensis Potential reservoir PN Herrer et al 1973Aotus trivirgatus L braziliensis Potential reservoir PN Herrer and Christensen 1976Aotus azarai L (Viannia) sp Parasite host AR Acardi et al 2013Aotus nigriceps L infantum Parasite host BR Malta et al 2010Callicebus nigrifrons L infantum Parasite host BR Malta et al 2010Alouatta guariba L infantum Parasite host BR Malta et al 2010Leonthopitecus crysomelas L infantum Parasite host BR Malta et al 2010Pithecia irrorata L infantum Parasite host BR Malta et al 2010Saguinus imperator L infantum Parasite host BR Malta et al 2010Ateles paniscus L amazonensis Parasite host BR Lima et al 2012a

Chiroptera Carollia perspicillata L infantum Potential reservoir VE De Lima et al 2008Molossus molossus L infantum Parasite host BR Savani et al 2010

L amazonensis Parasite host BR Savani et al 2010L (Viannia) sp Parasite host BR Shapiro et al 2013

M rufus L amazonensis Parasite host BR Savani et al 2010Glossophaga soricina L infantum Parasite host BR Savani et al 2010

L amazonensis Parasite host BR Savani et al 2010L (Viannia) sp Parasite host BR Shapiro et al 2013

Nyctinomops laticaudatus L amazonensis Parasite host BR Savani et al 2010Eumops glaucinus L amazonensis Parasite host BR Savani et al 2010E auripendulus L amazonensis Parasite host BR Savani et al 2010Artibeus literatus L amazonensis Parasite host BR Savani et al 2010Sturnira lilium L amazonensis Parasite host BR Savani et al 2010Myotis nigricans L amazonensis Parasite host BR Savani et al 2010

Countries AR ndash Argentine BR ndash Brazil CL ndash Chile CO ndash Colombia VE ndash Venezuela FG ndash French Guiana PE ndash Peru PN ndash Panama EC ndash Ecuador BO ndash Bolivia US ndash UnitedStates of America BE ndash Belize MX ndash Mexico HN ndash Honduras CR ndash Costa RicaIOC L Characterized Strains deposited in the Leishmania sp Collection of the Oswaldo Cruz Institute (wwwcliocfiocruzbr) The number refers to the deposit number inCLIOC Catalogue

255ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

to defecate (Miranda and Costa 2006) The two-toed sloth (Choloepusdidactylus) is a potential reservoir of L guyanensis as demon-strated by the high rates of parasite isolation from intact skin (aswell as viscera) which vary from 35 to 47 in French Guiana (Dedetet al 1989 Gentile et al 1981) and reach up to 46 in Brazil(Lainson et al 1981a)

L shawi was described infecting the two-toed sloth and the pale-throated sloth (Bradypus tridactylus) both in Brazil (Lainson et al1989) In Panama L colombiensis was isolated from the viscera ofHoffmannrsquos two-toed sloth (Choloepus hoffmanni) (Kreutzer et al1991) while L equatorensis was found infecting the same speciesin Ecuador (Grimaldi et al 1992) Finally L panamensis a speciesclosely related to L guyanensis has been described in Choloepushoffmanni from Panama (Ashford 2000) (Table 1)

The anteaters constitute a single family (Myrmecophagidae) thatare mainly arboreal but that may also explore the terrestrial strataThe isolation of Leishmania was described in only one species thelesser anteater Tamandua tetradactyla L guyanensis (Lainson et al1981a) L amazonensis (Mimori et al 1989) and L infantum thislast in mixed infection with T cruzi and T rangeli (de Araujo et al2013) were found infecting the lesser anteater (Table 1)

The diversity of Leishmania species already known to infect slothsand anteaters suggests that these mammals may be important hostsfor parasite species that are transmitted in the arboreal strata Infact most of the Leishmania species found infecting these hosts aretransmitted by vectors associated with the arboreal strata such asLu umbratilis and Lu whitmani

43 Order Cingulata

Armadillos together with didelphid marsupials and Pilosa arealso among the oldest mammal groups from the Americas Theyare also the most primitive of the xenarthrans Members of thefamily Dasypodidae are the only surviving species in the order andare found from the southern United States to the Straits of Magel-lan (Miranda and Costa 2006) So far the nine-banded armadillo(Dasypus novemcinctus) is the only non-human host from which Lnaiffi has been isolated (from blood liver and spleen) (Lainsonand Shaw 1989 Naiff et al 1991) L guyanensis is anotherspecies already detected in D novemcinctus from Brazil (Lainsonet al 1979) In some rural areas armadillos are commonly ob-served invading chicken pens searching for eggs and frequentingperidomestic areas (personal observations) where it is possiblethat they can be a source of Leishmania infection for sandflies inthis environment

Armadillos sloths and anteaters are hunted and eaten in someareas of South America such as the Amazon People commonly carefor the young in their backyards after having killed the mothersduring a hunt The young are kept until they reach adulthood andwe cannot exclude the possibility of they become sources of infec-tion in the peridomestic environment

44 Order Rodentia

Rodents are the most diverse and widespread order of mammalsand include several cryptic species that can only be separated bykaryotyping (Bonvicino et al 2002) The first rodents (Hystricognathindash caviomorphs) arrived in the Americas (along with primates) fromAfrica approximately 45 million years ago The second wave of rodentmigration to the Americas (Sciurognathi ndash cricetids) was much morerecent and included an initial establishment in North America (Flynnand Wyss 1998) Since their arrival rodents have diversified widelyand may be found in desert adapted to aquatic media digging longand interconnected tunnels and in forest canopies (Wilson andReeder 2005) This taxon is most likely the most studied in termsof infection by Leishmania spp in both natural and experimental

conditions however excepting a few studies experimentalinfections have been conducted in laboratory mouse lineages whichare not representative of the wild Mus musculus

After the Pilosa Marsupialia and Cingulata caviomorphs (sub-order Hystricognathi) are most likely the most ancient hosts ofLeishmania spp Moreover their arrival in the Americas is relatedto the entry of some species from the sub-genus Leishmania intothe continent (Thomaz-Soccol et al 1993) Caviomorphs from thegenus Proechimys were already found to be infected by various Leish-mania species These rodents are characterized by their longevity(more than 3 years in captivity) and high abundance in most lo-calities where they are found in tropical forests of Central and SouthAmerica (Ashford 1996) Various Proechimys species have been iden-tified as potential reservoirs of L amazonensis in Brazil and FrenchGuiana as demonstrated by the frequent skin parasitism con-firmed by tissue culture (Arias et al 1981 Dedet et al 1989) InFrench Guiana for example this infection was observed in two sym-patric species P cuvieri and P guyanensis (Rotureau 2006) Otherreports of natural infection in the skin of these rodents include Linfantum in P canicollis from Colombia (Travi et al 1998a) and Lguyanensis in Proechimys sp from French Guiana (Dedet et al 1989)and Brazil (Lainson et al 1981a) (Table 1)

P semispinosus from Colombia experimentally infected with Lpanamensis developed self resolving non-ulcerated lesions (fromwhich parasites could be re-isolated and which were demon-strated to be highly infective to vectors in the initial phase of infection(Travi et al 2002) This hostndashparasite interaction exemplifies a tem-poral reservoir competence in one host species passing from anamplifier host (in the beginning of infection) to a maintenance hostin which transmissibility competence is lower In contrast the samerodent species experimentally infected with L infantum devel-oped only subclinical infection and was not infective to vectorsalthough the authors re-isolated the parasites from the spleen ofsome rodents during necropsy (Travi et al 2002) Other authors havedetected no infection in laboratory-bred specimens of anotherspecies P guyannensis after inoculation with promastigotes oramastigotes of L infantum (Lainson et al 2002) This difference maybe due to many variables related to the host and the parasite suchas the intra-specific heterogeneity of both taxa andor the size androute of the inoculum

Considered monospecific until 2002 caviomorphs from the genusThrichomys comprise at least five cryptic species distributed acrossdifferent biomes in Brazil (Bonvicino et al 2002) T apereoides werefound to be infected with L braziliensis L guyanensis L infantumand L amazonensis in leishmaniasis-endemic areas in Minas GeraisBrazil (Oliveira et al 2005 Quaresma et al 2011) Recently we alsodetected infection by various Leishmania species in these rodentsL infantum L naiffi L braziliensis and L shawi in T laurentius L shawiin T inermis and L naiffi in T pachyurus (Caacutessia-Pires et al unpub-lished data) Moreover T laurentius experimentally infected withL infantum and L braziliensis were able to maintain the infectionand parasite re-isolation was achieved up to 12 months after in-fection Leishmania DNA was detected in all experimental groupsand in all tissues sampled independent of the Leishmania speciesinoculated (Roque et al 2010)

In addition to Proechimys spp and Thrichomys spp L infantumhas been diagnosed in Clyomys laticeps Dasyprocta azarae Nectomyssquamipes Holochilus sciureus and Rhipidomys mastacalis from Brazil(Caacutessia-Pires et al unpublished data Dantas-Torres andBrandatildeo-Filho 2006 Quaresma et al 2011 Lima et al 2013 ) andRattus rattus from Brazil and Venezuela (Quinnell and Courtenay2009) Natural infection of Coendu prehensilis used as sentinels inBolivia has been parasitologically confirmed in the liver and spleen(Le Pont et al 1989)

Regarding L braziliensis if we consider only studies that con-firmed the identity of the etiological agent (not considering the

256 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

ancient L braziliensis sensu lato) the following rodent species havebeen described to be naturally infected Akodon arviculoides Musmusculus Nectomys squamipes Necromys (=Bolomys) lasiurusOryzomys nigripes Rattus rattus and Sigmodon hispidus (Brandatildeo-Filhoet al 2003 de Freitas et al 2012 De Lima et al 2002 Forattiniet al 1972 Peterson et al 1988 Rocha et al 1988 Vasconceloset al 1994) In other cases the authors confirmed infection by thesubgenus Leishmania (Viannia) sp (Holochilus scieurus and Cerradomyssubflavus) (Brandatildeo-Filho et al 2003 Lima et al 2013) or tenta-tively identified the etiological agent through the biological patternof in vitro growth (Rhipidomys leucodactylus and Proechimysguyannensis) (Lainson et al 1981b)

Rodents are also usually considered as the main reservoirs ofLeishmania from the L mexicana complex (L mexicana and Lamazonensis) L amazonensis was described in rodents from the fol-lowing genera Akodon Dasyprocta Oligoryzomys OryzomysProechimys Thrichomys and Sciurus (Arias et al 1981 Kerr et al2006 Lainson et al 1981b Mimori et al 1989 Oliveira et al 2005Telleria et al 1999) None of these studies however included follow-up of the infection or demonstrated competence to infect vectors

L mexicana has been isolated from various species of Neotomaincluding a specimen of N floridana with a large lesion in the earfrom which the parasite could be isolated (Kerr et al 1995 McHughet al 2003) This finding was informative suggesting that this rodentspecies may be infective for the vector and an important reservoirof L mexicana Ototylomys phyllotis from Belize should be consid-ered as a possible reservoir of L mexicana because of its relativeabundance prevalence of infection and attraction to Lu flaviscutellatathe most important vector in the region Curiously the same authorfailed to reproduce this infection under experimental conditions(Ashford 1996) possibly due to factors occurring only in naturesuch as stress and concomitant infections which may be impor-tant for the establishment of Leishmania infection This situationhighlights the importance of the studies of naturally infected speci-mens and the difficulties of adopting potential reservoir hosts asalternative models for leishmaniasis studies Moreover these find-ings attest to the hazards of applying conclusions based solely onexperimental models to natural systems

The persistence of L mexicana infection in wild rodents was dem-onstrated twice The first such finding occurred in Mexico where29 naturally infected rodents were maintained in captivity and testedmonthly for parasites for up to 2 years In that study the authorsdemonstrated persistent infection including symptomatic infec-tions in Sigmodon hispidus Oryzomys melanotis Ototylomys phyllotisand Peromyscus yucatanicus the latter two being the most impor-tant because of their high relative abundance in local fauna andlonger life spans (Van Wynsberghe et al 2000) Second in the UnitedStates during a 19-month markndashreleasendashrecapture study of Neotomamicropus the authors reported the persistence of L mexicana in-fection for up to 1 year (Raymond et al 2003) Heteromys Nyctomysand Reithrodontomys were also found infected with L mexicana(Ashford 1996 De Lima et al 2002 Disney 1968 Lainson andStrangways-Dixon 1964 Van Wynsberghe et al 2009)

Leishmania lainsoni was isolated from fragments of intact skinfrom pacas (Agouti paca) in the Brazilian state of Paraacute (Silveira et al1991) and from Coendu sp (Table 1) Leishmania panamensis was iso-lated from naturally infected Heteromys dermarestianus from CostaRica (Zeledon et al 1977) while a squirrel Scirus granatensis wasfound to be infected with L equatorensis in Ecuador (Grimaldi et al1992) Leishmania peruviana a species suggested to be a synonymof L braziliensis was isolated from the Peruvian Phyllotis andinum(Llanos-Cuentas et al 1999) Finally L hertigiL deanei and L enriettiispecies taxonomically more similar to Endotrypanum than to Leish-mania have been described respectively in porcupines Coendu spp(Herrer 1971 Silva et al 2013) and in the guinea pig Cavia porcellus(Machado et al 1994)

Taken together a broad diversity of Leishmania species natural-ly infect this mammal group most likely reflecting the diversity ofecological niches occupied by the hosts The differences observedamong the rodent species include the forest strata they occupy andtheir reproductive strategies (seasonality gestation time and numberof offspring) and these traits should be considered evaluations ofthe importance of a rodent species as a Leishmania reservoir More-over as expected for every hostndashparasite interaction thisheterogeneous mammalian taxon shows a spectrum of compe-tence to maintain and transmit Leishmania from high susceptibilitywith high transmissibility competence to quick control ofinfection

45 Order Carnivora

The mammals from this order also comprise a very heteroge-neous group including strict carnivores such as ocelots (Leoparduspardalis) and tayras (Eira barbara) and species that supplement theirdiet with insects and fruits such as coatis (Nasua nasua) and manedwolves (Chrysocyon brachyurus) Most have a large biomass and largerange important aspects of parasite dispersion (Rocha et al 2013)Moreover some species such as raccoons and tayras are found bothon the ground and in the canopy favoring the dispersion of para-sites among forest strata Unfortunately carnivores require largeranges and because of their potential to predate on livestock (mainlychickens and cattle) are heavily hunted placing some carnivorespecies at risk of extinction (Silva and Adania 2007)

Two carnivore species are closely linked to humans dogs andcats Dogs are the most important reservoirs of L infantum through-out South America although they can be infected with at least sixother Leishmania species (Dantas-Torres 2009) Recently the im-portance of cats in Leishmania epidemiology has also been suggested(Pennisi et al 2013) Among the wild carnivore hosts of L infantumthe first description of infection was in the crab-eating fox Cerdocyonthous although the authors inaccurately reported the host asLycalopex vetulus (Courtenay et al 1996 Deane and Deane 1955)Since then many studies have confirmed L infantum infection inC thous by parasitological serological andor molecular assaysNotably these animals sometimes develop serious symptoms of thedisease and present with amastigotes in intact skin as also de-scribed in domestic dogs Their prevalence of infection may rangefrom 42 (by parasitological tests) to 78 (by serology) (Lainson et al1990 Quinnell and Courtenay 2009 Silva et al 2000) The vectorinfectivity was proven by xenodiagnosis although the infection rateof vectors is reported to be lower than that observed for domesticdogs (Courtenay et al 2002 Quinnell and Courtenay 2009)

Apart from C thous another wild carnivore that is a potentialreservoir of L infantum is the bush dog Speothos venaticus An in-dividual kept in a zoo in Rio de Janeiro Brazil is the only wild canidexcept for C thous from which L infantum was isolated (Figueiredoet al 2008) Infection in bush dogs was also confirmed by directvisualization PCR and serology in two females with clinical signsof visceral leishmaniasis and maintained in other Brazilian zoos (Limaet al 2009 Souza et al 2010) Other wild canid species found tobe infected albeit only by PCR andor serology were the hoary foxPseudalopex vetulus and the maned wolf Chrysocyon brachyurus (Curiet al 2006 Luppi et al 2008) (Table 1)

Some authors have investigated Leishmania infection in captivewild carnivores Five of 15 wild canids belonging to the four nativespecies mentioned earlier were found to be infected in a zoo in BeloHorizonte Brazil Of these one bush dog and one hoary fox devel-oped clinical signs of visceral leishmaniasis (Luppi et al 2008)Among the wild felines five pumas (Puma concolor) and one jaguar(Panthera onca) in a zoo from Cuiabaacute Brazil were PCR-positive inlymph-node puncture biopsy L infantum was specifically identi-fied by the digestion of the amplified products with restriction

257ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

enzymes (Dahroug et al 2010) Later the same authors demon-strated L infantum infection in one lion a non-native felid specieskept in the same zoo (Dahroug et al 2011)

In addition to L infantum at least four other Leishmania specieswere found in wild carnivores L shawi in coatis Nasua nasua (Lainsonet al 1989) L guyanensis in the kinkajou Potos flavus (Pajot et al1982) L amazonensis in kinkajous crab-eating foxes and skunksConepatus chinga (Kreutzer et al 1991 Rotureau 2006 Telleria et al1999) and L braziliensis in one Bolivian skunk (Buitrago et al 2011)(Table 1)

Contrary to the numerous reports of infection in dogs and catsmuch remains to study in terms of the putative roles of wild car-nivores as Leishmania reservoirs As in all hostndashparasite interactionsthe infection patterns display regional and even individual pecu-liarities (Rocha et al 2013) If we consider that in some biomes(ldquoPantanal or Chacordquo ldquoCerradordquo and ldquoPampardquo) carnivore species areabundant and represent a huge biomass any study of Leishmaniareservoirs must include carnivores including their Leishmania in-fection pattern density and population structure in the area Despiteits inherent difficulties the study of wild carnivores especially inthe areas where their relative abundance is high is of fundamen-tal importance to improve understanding of Leishmania ecology

46 Order Primata

Nonhuman primates can be divided in two groups the catar-rhines (infraorder Catarrhini) from Africa Europe and Asia (OldWorld Primates) and the platyrrhines (Platyrrhini) from the Ameri-cas (New World or Neotropical Primates) The main differencebetween them is that the catarrhines have upside-down nostrils ona long snout while platyrrhines have laterally-faced nostrils on ashorter snout (Verona and Pissinatti 2007) The different speciesof neotropical primates are included in the families Cebidae (tama-rins) and Callitrichidae (marmosets) although some classificationsalso recognize three other families Aotidae Pithecidae and AtelidaeThe neotropical primates occupy distinct arboreal strata and consumediverse diets including species that feed on fruits invertebrates andeven small mammals (Verona and Pissinatti 2007)

To date few studies have described natural infection by Leish-mania parasites in neotropical primates Infection by L shawi wasdescribed in the tufted capuchin monkey Cebus apella and thebearded saki Chiropotes satanas (Lainson et al 1989) while infec-tion by Leishmania (Viannia) sp was recently demonstrated in fourArgentinean owl monkeys Aotus azarai (Acardi et al 2013) InPanamaacute Geoffroyrsquos tamarin Saguinus geoffroyi and the owl monkeyAotus trivirgatus were found to be infected with L amazonensis andL braziliensis respectively (Herrer and Christensen 1976 Herrer et al1973) In a Brazilian zoo one black-fronted titi Callicebus nigrifronsfrom Belo HorizonteMG presented with a fatal disease thatresembled visceral leishmaniasis Histological and immunohisto-chemical examinations as well as a PCR specific for parasites fromthe L donovani complex confirmed infection with L infantum (Maltaet al 2010) The other primate species that had PCR-positive bloodsamples in the same study were Alouatta guariba Cebus xanthosternosLeonthopitecus crysomelas Aotus nigriceps Pithecia irrorata andSaguinus imperator (Malta et al 2010) In the zoo in BauruSP Leish-mania amazonensis was detected by PCR-RFLP in a spider monkeyAteles paniscus from the endemic Amazon region (Lima et al 2012b)(Table 1)

Leishmania species that circulate in the Americas have been dem-onstrated to infect other neotropical primates but only underexperimental conditions Most of these studies focused on theimmune response to different drug treatments or on vaccine de-velopment For many years black-tufted marmosets Callithrixpenicillata were used in experimental studies with L braziliensis andL amazonensis (Cuba et al 1990 Cuba-Cuba and Marsden 1993)

Experimental infection of the common squirrel monkey Saimirisciureus resulted in non-ulcerated skin lesions from which Lbraziliensis andor L panamensis could be re-isolated (Pung et al1988) Owl monkeys Aotus trivirgatus developed localized cutane-ous lesions after experimental infection with L braziliensis Lmexicana and L panamensis (Christensen and de Vasquez 1981 Lujanet al 1986) Cebus apella developed skin lesions after experimen-tal infection with L lainsoni L amazonensis L braziliensis L mexicanaand L guyanensis (Garcez et al 2002 Grimaldi 2008) ConverselyCebus nigrivittatus developed fatal disease when experimentally in-fected with L infantum (Vouldoukis et al 1986)

All neotropical primates are included in the list of the ldquoConven-tion on International Trade in Endangered Species of Wild Faunaand Florardquo (CITES) indicating that all are vulnerable to some degree(Verona and Pissinatti 2007) For this reason many species suchas the golden lion tamarin Leonthopitecus rosalia are included in con-servation programs These programs often include exchangetranslocation and re-introduction of animals without consider-ation of their parasite fauna here including Leishmania and othertrypanosomatids Data from naturally infected primates demon-strate that these mammals may be involved in the maintenance ofLeishmania in the wild especially considering their ecology speciestransmitted in the canopy Taking into account the transmission cycleof these parasites a lack of knowledge regarding the health statusof the relocated primates may result in the introduction of in-fected mammals into a given area promoting the establishment ofnew transmission cycles (Lisboa et al 2006)

47 Order Chiroptera

Bats are nocturnal mammals and the only able to fly (some-times associated with seasonal migration) an important trait thatcan result in the dissemination of parasite species Their disper-sion capacity is due to the ability to do true flapping flight(apparently evolved differently among bat lineages) and the so-phisticated echolocation system that allows them to identify theenvironment (Jones and Teeling 2006) Despite their known diver-sity bats are still considered as a monophyletic group (Bishop 2008Bisson et al 2009)

Bats are commonly infected with several trypanosomatid speciesmainly from the Trypanosoma genus T cruzi T vespertilionis andT (Megatrypanum) sp among others (Lima et al 2012a) There isonly one report of the isolation of Leishmania parasites (L infantum)from the blood of a short-tailed fruit bat Carollia perspicillata in Ven-ezuela (De Lima et al 2008) (Table 1) Before that Lampo et al haddemonstrated that bats could be sources of blood for Lutzomyialongipalpis in Venezuelan caves (Lampo et al 2000)

In Brazil two Leishmania species were identified in maceratedfragments of spleen and liver from bats using a nested PCR fol-lowed by sequencing of the amplified products Molossus molossusand Glossophaga soricina were found to be infected with L infantumand L amazonensis and the latter was also found in Molossus rufusNyctinomops laticaudatus Eumops glaucinus E auripendulus Artibeusliteratus Sturnira lilium and Myotis nigricans (Savani et al 2010) Re-cently Leishmania (Viannia) sp was detected in a skin lesion fromGlossophaga soricina and blood from Molossus molossus (Shapiro et al2013) (Table 1) In this article although the authors have de-scribed infection with L braziliensis PCR-RFLP using primers b1 andb2 (Schonian et al 2003) does not allow for differentiation amongother species from the same subgenus such as L guyanensis

Bats should not be excluded as potential reservoirs of Leishma-nia sp because of the lack of studies involving Leishmania and batsChiroptera represents 39 of the 560 mammal species reported inSouth American rainforests it is the most common mammal groupin terms of diversity and biomass (Emmons and Feer 1997 Rotureau2006) These flying mammals are found in wild domestic and

258 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

synanthropic environments being able to colonize different habi-tats in different ecotypes Their refuges include hollow trees thecanopies of palm trees and ceilings of human houses and other ruralbuildings Their high abundance and adaptability to peri-domesticenvironment reinforce the importance of investigating bats alreadyrecognized as reservoirs of other trypanosomatids (Jansen and Roque2010) in the transmission cycles of Leishmania species

5 Conclusions and perspectives

Many decades have passed since the description of Leishmaniaparasites but their epidemiology is still not well understood in partbecause of the human-health focus of most studies Only recentlyinfluenced by the ldquoone healthrdquo approach has the epidemiology ofleishmaniasis started to be evaluated from a broader perspective(Palatnik-de-Sousa and Day 2011)

In the case of human visceral leishmaniasis caused by L infantumthe idea that dogs are the only reservoir of the parasite has led healthauthorities to direct the eradication of seropositive dogs on the basisthat this action was the only way to control this zoonosis In factseveral studies have demonstrated that dogs are epidemiologi-cally important as reservoirs in different localities (reviewed byLainson and Rangel 2005 Dantas-Torres 2009 Quinnell andCourtenay 2009) Nevertheless the participation of other in-fected mammals rather than dogs in the transmission cycle of Linfantum in urban areas was already proposed for cats and opos-sums for example (Pennisi et al 2013 Santiago et al 2007) Thelow effectiveness of dog culling program in Brazil is probably dueto an assemblage of factors most of them related to the lack of astructured surveillance system and include the high interval betweentests and between the positive result and dog elimination the rapidreplacement of susceptible dogs when an infected dog is euthan-ized and the resistance of owners to euthanize their infected dogs(Costa et al 2013 Grimaldi et al 2012 Nunes et al 2008) Someof these localities are very close to sylvatic areas and the possibil-ity that wild mammals may serve as a source of infection to vectorsin peridomiciliary areas has been ignored The putative participa-tion of these mammals is an important additional factor to beconsidered in the proposition of measures to control this zoono-sis This review highlights species from distinct orders that maymaintain and serve as a source of infection to phlebotomine sandfly vectors providing a constant source of re-infection to a peri-domestic transmission system

The reservoirs of the Leishmania species responsible for the cu-taneous forms of human leishmaniasis are still unknown most likelybecause research has focused on the search for a specific reservoirhost as observed for dogs and L infantum These species may bemaintained in the wild by a different strategy as by a few ldquohotspeciesrdquo with high transmissibility competence or most likelythrough a reservoir system an assemblage of mammals with dis-tinct and transient degrees of transmissibility competencethroughout infection This hypothesis agrees with the reservoir def-inition proposed by Ashford (1997) almost 20 years ago This systeminvolves a tradeoff that could explain the evolutionary success ofthese parasite species several individuals are infected but each iscompetent for transmission for only a limited time while retain-ing the infection for long periods of time The sum of multiple shortperiods of infectivity in numerous infected mammals guaranteesthe maintenance and transmission of these Leishmania species

All the links in the epidemiological chain must be clarified as a pre-requisite for effective control strategies (Abdussalan 1959Palatnik-de-Sousa and Day 2011 Shaw 2007) We are still far from un-derstanding the maintenance of different Leishmania species in natureIn this sense the follow-up of naturally infected animals and experi-mental studies using potential reservoirs are essential to improvingunderstanding of the mechanisms of maintenance of these parasites

in their natural hosts In the field the studies should not be restrictedto previously described infected hosts but should be carried out usingan integrated ecological approach to understand the role of each hostspecies in the maintenance and amplification of Leishmania para-sites Priorities include the identification of the factors that influencethe transmissibility competence of the individual mammalian hosts andunderstanding how environmental management could decrease in-fections in humans living close to sylvatic

Over the last century the scientific community has shown thatdifferent and several wild mammal species can become infected withLeishmania species The focus must change to identify species thatmay serve as sources of infection to vectors and amplify enzooticfoci constituting a risk for human transmission To this end a par-adigm shift in research and surveillance of wild reservoirs ofLeishmania is urgently needed This change will depend among otherfactors on understanding reservoir systems and acknowledging theimportance of understanding the role each mammal species playsin maintaining these parasites in nature The factors involved in theamplification of enzootic foci are temporally and regionally spe-cific and understanding some of these factors may support thedevelopment of effective and sustainable strategies for leishmani-asis surveillance

Acknowledgements

AMJ is a ldquoCientista do Nosso Estadordquo provided by FAPERJ andis financially supported by CNPq (ldquoBolsista de Produtividade niacutevel1rdquo CNPq) ALRR is a ldquoJovem Cientista do Nosso Estadordquo providedby FAPERJ The authors have declared that no competing interestsexist

References

Abdussalan M 1959 Significance of ecological studies of wild animal reservoir ofzoonoses Bull World Health Organ 21 179ndash186

Acardi SA Rago MV Liotta DJ Fernandez-Duque E Salomon OD 2013Leishmania (Viannia) DNA detection by PCR-RFLP and sequencing in free-rangingowl monkeys (Aotus azarai azarai) from Formosa Argentina Vet Parasitol 193256ndash259

Aguirre AA Tabor GM 2008 Global factors driving emerging infectious diseasesAnn N Y Acad Sci 1149 1ndash3

Alexander KA Lewis BL Marathe M Eubank S Blackburn JK 2012 Modelingof wildlife-associated zoonoses applications and caveats Vector Borne ZoonoticDis 12 1005ndash1018

Alvar J Velez ID Bern C Herrero M Desjeux P Cano J et al 2012 Leishmaniasisworldwide and global estimates of its incidence PLoS ONE 7 e35671

Arauacutejo A Reinhard K Ferreira LF Pucu E Chieffi PP 2013 Paleoparasitologythe origin of human parasites Arq Neuropsiquiatr 71 722ndash726

Arias JR Naif RD Miles MA de Souza AA 1981 The opossum Didelphismarsupialis (Marsupialia didelphidae) as a reservoir host of Leishmaniabraziliensis guyanensis in the Amazon Basin of Brazil Trans R Soc Trop MedHyg 75 537ndash541

Ashford DA Bozza M Freire M Miranda JC Sherlock I Eulalio C et al 1995Comparison of the polymerase chain reaction and serology for the detection ofcanine visceral leishmaniasis Am J Trop Med Hyg 53 251ndash255

Ashford RW 1996 Leishmaniasis reservoir and their significance in control ClinDermatol 14 523ndash532

Ashford RW 1997 What it takes to be a reservoir host Belg J Zool 127 85ndash90Ashford RW 2000 The leishmaniases as emerging and reemerging zoonoses Int

J Parasitol 30 1269ndash1281Austad SN 1988 The adaptable opossum Sci Am 258 54ndash59Bishop KL 2008 The evolution of flight in bats narrowing the field of plausible

hypotheses Q Rev Biol 83 153ndash169Bisson IA Safi K Holland RA 2009 Evidence for repeated independent evolution

of migration in the largest family of bats PLoS ONE 4 e7504Bonvicino CR Otazu IB DrsquoAndrea PS 2002 Karyologic evidence of diversification

of the genus Thrichomys (Rodentia Echimyidae) Cytogenet Genome Res 97200ndash204

Botero A Thompson CK Peacock CS Clode PL Nicholls PK Wayne AF et al2013 Trypanosomes genetic diversity polyparasitism and the population declineof the critically endangered Australian marsupial the brush tailed bettong orwoylie (Bettongia penicillata) Int J Parasitol Parasite Wildl 2 77ndash89

Brandatildeo-Filho SP Brito ME Carvalho FG Ishikawa EA Cupolillo EFloeter-Winter L et al 2003 Wild and synanthropic hosts of Leishmania(Viannia) braziliensis in the endemic cutaneous leishmaniasis locality of AmarajiPernambuco State Brazil Trans R Soc Trop Med Hyg 97 291ndash296

259ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

to defecate (Miranda and Costa 2006) The two-toed sloth (Choloepusdidactylus) is a potential reservoir of L guyanensis as demon-strated by the high rates of parasite isolation from intact skin (aswell as viscera) which vary from 35 to 47 in French Guiana (Dedetet al 1989 Gentile et al 1981) and reach up to 46 in Brazil(Lainson et al 1981a)

L shawi was described infecting the two-toed sloth and the pale-throated sloth (Bradypus tridactylus) both in Brazil (Lainson et al1989) In Panama L colombiensis was isolated from the viscera ofHoffmannrsquos two-toed sloth (Choloepus hoffmanni) (Kreutzer et al1991) while L equatorensis was found infecting the same speciesin Ecuador (Grimaldi et al 1992) Finally L panamensis a speciesclosely related to L guyanensis has been described in Choloepushoffmanni from Panama (Ashford 2000) (Table 1)

The anteaters constitute a single family (Myrmecophagidae) thatare mainly arboreal but that may also explore the terrestrial strataThe isolation of Leishmania was described in only one species thelesser anteater Tamandua tetradactyla L guyanensis (Lainson et al1981a) L amazonensis (Mimori et al 1989) and L infantum thislast in mixed infection with T cruzi and T rangeli (de Araujo et al2013) were found infecting the lesser anteater (Table 1)

The diversity of Leishmania species already known to infect slothsand anteaters suggests that these mammals may be important hostsfor parasite species that are transmitted in the arboreal strata Infact most of the Leishmania species found infecting these hosts aretransmitted by vectors associated with the arboreal strata such asLu umbratilis and Lu whitmani

43 Order Cingulata

Armadillos together with didelphid marsupials and Pilosa arealso among the oldest mammal groups from the Americas Theyare also the most primitive of the xenarthrans Members of thefamily Dasypodidae are the only surviving species in the order andare found from the southern United States to the Straits of Magel-lan (Miranda and Costa 2006) So far the nine-banded armadillo(Dasypus novemcinctus) is the only non-human host from which Lnaiffi has been isolated (from blood liver and spleen) (Lainsonand Shaw 1989 Naiff et al 1991) L guyanensis is anotherspecies already detected in D novemcinctus from Brazil (Lainsonet al 1979) In some rural areas armadillos are commonly ob-served invading chicken pens searching for eggs and frequentingperidomestic areas (personal observations) where it is possiblethat they can be a source of Leishmania infection for sandflies inthis environment

Armadillos sloths and anteaters are hunted and eaten in someareas of South America such as the Amazon People commonly carefor the young in their backyards after having killed the mothersduring a hunt The young are kept until they reach adulthood andwe cannot exclude the possibility of they become sources of infec-tion in the peridomestic environment

44 Order Rodentia

Rodents are the most diverse and widespread order of mammalsand include several cryptic species that can only be separated bykaryotyping (Bonvicino et al 2002) The first rodents (Hystricognathindash caviomorphs) arrived in the Americas (along with primates) fromAfrica approximately 45 million years ago The second wave of rodentmigration to the Americas (Sciurognathi ndash cricetids) was much morerecent and included an initial establishment in North America (Flynnand Wyss 1998) Since their arrival rodents have diversified widelyand may be found in desert adapted to aquatic media digging longand interconnected tunnels and in forest canopies (Wilson andReeder 2005) This taxon is most likely the most studied in termsof infection by Leishmania spp in both natural and experimental

conditions however excepting a few studies experimentalinfections have been conducted in laboratory mouse lineages whichare not representative of the wild Mus musculus

After the Pilosa Marsupialia and Cingulata caviomorphs (sub-order Hystricognathi) are most likely the most ancient hosts ofLeishmania spp Moreover their arrival in the Americas is relatedto the entry of some species from the sub-genus Leishmania intothe continent (Thomaz-Soccol et al 1993) Caviomorphs from thegenus Proechimys were already found to be infected by various Leish-mania species These rodents are characterized by their longevity(more than 3 years in captivity) and high abundance in most lo-calities where they are found in tropical forests of Central and SouthAmerica (Ashford 1996) Various Proechimys species have been iden-tified as potential reservoirs of L amazonensis in Brazil and FrenchGuiana as demonstrated by the frequent skin parasitism con-firmed by tissue culture (Arias et al 1981 Dedet et al 1989) InFrench Guiana for example this infection was observed in two sym-patric species P cuvieri and P guyanensis (Rotureau 2006) Otherreports of natural infection in the skin of these rodents include Linfantum in P canicollis from Colombia (Travi et al 1998a) and Lguyanensis in Proechimys sp from French Guiana (Dedet et al 1989)and Brazil (Lainson et al 1981a) (Table 1)

P semispinosus from Colombia experimentally infected with Lpanamensis developed self resolving non-ulcerated lesions (fromwhich parasites could be re-isolated and which were demon-strated to be highly infective to vectors in the initial phase of infection(Travi et al 2002) This hostndashparasite interaction exemplifies a tem-poral reservoir competence in one host species passing from anamplifier host (in the beginning of infection) to a maintenance hostin which transmissibility competence is lower In contrast the samerodent species experimentally infected with L infantum devel-oped only subclinical infection and was not infective to vectorsalthough the authors re-isolated the parasites from the spleen ofsome rodents during necropsy (Travi et al 2002) Other authors havedetected no infection in laboratory-bred specimens of anotherspecies P guyannensis after inoculation with promastigotes oramastigotes of L infantum (Lainson et al 2002) This difference maybe due to many variables related to the host and the parasite suchas the intra-specific heterogeneity of both taxa andor the size androute of the inoculum

Considered monospecific until 2002 caviomorphs from the genusThrichomys comprise at least five cryptic species distributed acrossdifferent biomes in Brazil (Bonvicino et al 2002) T apereoides werefound to be infected with L braziliensis L guyanensis L infantumand L amazonensis in leishmaniasis-endemic areas in Minas GeraisBrazil (Oliveira et al 2005 Quaresma et al 2011) Recently we alsodetected infection by various Leishmania species in these rodentsL infantum L naiffi L braziliensis and L shawi in T laurentius L shawiin T inermis and L naiffi in T pachyurus (Caacutessia-Pires et al unpub-lished data) Moreover T laurentius experimentally infected withL infantum and L braziliensis were able to maintain the infectionand parasite re-isolation was achieved up to 12 months after in-fection Leishmania DNA was detected in all experimental groupsand in all tissues sampled independent of the Leishmania speciesinoculated (Roque et al 2010)

In addition to Proechimys spp and Thrichomys spp L infantumhas been diagnosed in Clyomys laticeps Dasyprocta azarae Nectomyssquamipes Holochilus sciureus and Rhipidomys mastacalis from Brazil(Caacutessia-Pires et al unpublished data Dantas-Torres andBrandatildeo-Filho 2006 Quaresma et al 2011 Lima et al 2013 ) andRattus rattus from Brazil and Venezuela (Quinnell and Courtenay2009) Natural infection of Coendu prehensilis used as sentinels inBolivia has been parasitologically confirmed in the liver and spleen(Le Pont et al 1989)

Regarding L braziliensis if we consider only studies that con-firmed the identity of the etiological agent (not considering the

256 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

ancient L braziliensis sensu lato) the following rodent species havebeen described to be naturally infected Akodon arviculoides Musmusculus Nectomys squamipes Necromys (=Bolomys) lasiurusOryzomys nigripes Rattus rattus and Sigmodon hispidus (Brandatildeo-Filhoet al 2003 de Freitas et al 2012 De Lima et al 2002 Forattiniet al 1972 Peterson et al 1988 Rocha et al 1988 Vasconceloset al 1994) In other cases the authors confirmed infection by thesubgenus Leishmania (Viannia) sp (Holochilus scieurus and Cerradomyssubflavus) (Brandatildeo-Filho et al 2003 Lima et al 2013) or tenta-tively identified the etiological agent through the biological patternof in vitro growth (Rhipidomys leucodactylus and Proechimysguyannensis) (Lainson et al 1981b)

Rodents are also usually considered as the main reservoirs ofLeishmania from the L mexicana complex (L mexicana and Lamazonensis) L amazonensis was described in rodents from the fol-lowing genera Akodon Dasyprocta Oligoryzomys OryzomysProechimys Thrichomys and Sciurus (Arias et al 1981 Kerr et al2006 Lainson et al 1981b Mimori et al 1989 Oliveira et al 2005Telleria et al 1999) None of these studies however included follow-up of the infection or demonstrated competence to infect vectors

L mexicana has been isolated from various species of Neotomaincluding a specimen of N floridana with a large lesion in the earfrom which the parasite could be isolated (Kerr et al 1995 McHughet al 2003) This finding was informative suggesting that this rodentspecies may be infective for the vector and an important reservoirof L mexicana Ototylomys phyllotis from Belize should be consid-ered as a possible reservoir of L mexicana because of its relativeabundance prevalence of infection and attraction to Lu flaviscutellatathe most important vector in the region Curiously the same authorfailed to reproduce this infection under experimental conditions(Ashford 1996) possibly due to factors occurring only in naturesuch as stress and concomitant infections which may be impor-tant for the establishment of Leishmania infection This situationhighlights the importance of the studies of naturally infected speci-mens and the difficulties of adopting potential reservoir hosts asalternative models for leishmaniasis studies Moreover these find-ings attest to the hazards of applying conclusions based solely onexperimental models to natural systems

The persistence of L mexicana infection in wild rodents was dem-onstrated twice The first such finding occurred in Mexico where29 naturally infected rodents were maintained in captivity and testedmonthly for parasites for up to 2 years In that study the authorsdemonstrated persistent infection including symptomatic infec-tions in Sigmodon hispidus Oryzomys melanotis Ototylomys phyllotisand Peromyscus yucatanicus the latter two being the most impor-tant because of their high relative abundance in local fauna andlonger life spans (Van Wynsberghe et al 2000) Second in the UnitedStates during a 19-month markndashreleasendashrecapture study of Neotomamicropus the authors reported the persistence of L mexicana in-fection for up to 1 year (Raymond et al 2003) Heteromys Nyctomysand Reithrodontomys were also found infected with L mexicana(Ashford 1996 De Lima et al 2002 Disney 1968 Lainson andStrangways-Dixon 1964 Van Wynsberghe et al 2009)

Leishmania lainsoni was isolated from fragments of intact skinfrom pacas (Agouti paca) in the Brazilian state of Paraacute (Silveira et al1991) and from Coendu sp (Table 1) Leishmania panamensis was iso-lated from naturally infected Heteromys dermarestianus from CostaRica (Zeledon et al 1977) while a squirrel Scirus granatensis wasfound to be infected with L equatorensis in Ecuador (Grimaldi et al1992) Leishmania peruviana a species suggested to be a synonymof L braziliensis was isolated from the Peruvian Phyllotis andinum(Llanos-Cuentas et al 1999) Finally L hertigiL deanei and L enriettiispecies taxonomically more similar to Endotrypanum than to Leish-mania have been described respectively in porcupines Coendu spp(Herrer 1971 Silva et al 2013) and in the guinea pig Cavia porcellus(Machado et al 1994)

Taken together a broad diversity of Leishmania species natural-ly infect this mammal group most likely reflecting the diversity ofecological niches occupied by the hosts The differences observedamong the rodent species include the forest strata they occupy andtheir reproductive strategies (seasonality gestation time and numberof offspring) and these traits should be considered evaluations ofthe importance of a rodent species as a Leishmania reservoir More-over as expected for every hostndashparasite interaction thisheterogeneous mammalian taxon shows a spectrum of compe-tence to maintain and transmit Leishmania from high susceptibilitywith high transmissibility competence to quick control ofinfection

45 Order Carnivora

The mammals from this order also comprise a very heteroge-neous group including strict carnivores such as ocelots (Leoparduspardalis) and tayras (Eira barbara) and species that supplement theirdiet with insects and fruits such as coatis (Nasua nasua) and manedwolves (Chrysocyon brachyurus) Most have a large biomass and largerange important aspects of parasite dispersion (Rocha et al 2013)Moreover some species such as raccoons and tayras are found bothon the ground and in the canopy favoring the dispersion of para-sites among forest strata Unfortunately carnivores require largeranges and because of their potential to predate on livestock (mainlychickens and cattle) are heavily hunted placing some carnivorespecies at risk of extinction (Silva and Adania 2007)

Two carnivore species are closely linked to humans dogs andcats Dogs are the most important reservoirs of L infantum through-out South America although they can be infected with at least sixother Leishmania species (Dantas-Torres 2009) Recently the im-portance of cats in Leishmania epidemiology has also been suggested(Pennisi et al 2013) Among the wild carnivore hosts of L infantumthe first description of infection was in the crab-eating fox Cerdocyonthous although the authors inaccurately reported the host asLycalopex vetulus (Courtenay et al 1996 Deane and Deane 1955)Since then many studies have confirmed L infantum infection inC thous by parasitological serological andor molecular assaysNotably these animals sometimes develop serious symptoms of thedisease and present with amastigotes in intact skin as also de-scribed in domestic dogs Their prevalence of infection may rangefrom 42 (by parasitological tests) to 78 (by serology) (Lainson et al1990 Quinnell and Courtenay 2009 Silva et al 2000) The vectorinfectivity was proven by xenodiagnosis although the infection rateof vectors is reported to be lower than that observed for domesticdogs (Courtenay et al 2002 Quinnell and Courtenay 2009)

Apart from C thous another wild carnivore that is a potentialreservoir of L infantum is the bush dog Speothos venaticus An in-dividual kept in a zoo in Rio de Janeiro Brazil is the only wild canidexcept for C thous from which L infantum was isolated (Figueiredoet al 2008) Infection in bush dogs was also confirmed by directvisualization PCR and serology in two females with clinical signsof visceral leishmaniasis and maintained in other Brazilian zoos (Limaet al 2009 Souza et al 2010) Other wild canid species found tobe infected albeit only by PCR andor serology were the hoary foxPseudalopex vetulus and the maned wolf Chrysocyon brachyurus (Curiet al 2006 Luppi et al 2008) (Table 1)

Some authors have investigated Leishmania infection in captivewild carnivores Five of 15 wild canids belonging to the four nativespecies mentioned earlier were found to be infected in a zoo in BeloHorizonte Brazil Of these one bush dog and one hoary fox devel-oped clinical signs of visceral leishmaniasis (Luppi et al 2008)Among the wild felines five pumas (Puma concolor) and one jaguar(Panthera onca) in a zoo from Cuiabaacute Brazil were PCR-positive inlymph-node puncture biopsy L infantum was specifically identi-fied by the digestion of the amplified products with restriction

257ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

enzymes (Dahroug et al 2010) Later the same authors demon-strated L infantum infection in one lion a non-native felid specieskept in the same zoo (Dahroug et al 2011)

In addition to L infantum at least four other Leishmania specieswere found in wild carnivores L shawi in coatis Nasua nasua (Lainsonet al 1989) L guyanensis in the kinkajou Potos flavus (Pajot et al1982) L amazonensis in kinkajous crab-eating foxes and skunksConepatus chinga (Kreutzer et al 1991 Rotureau 2006 Telleria et al1999) and L braziliensis in one Bolivian skunk (Buitrago et al 2011)(Table 1)

Contrary to the numerous reports of infection in dogs and catsmuch remains to study in terms of the putative roles of wild car-nivores as Leishmania reservoirs As in all hostndashparasite interactionsthe infection patterns display regional and even individual pecu-liarities (Rocha et al 2013) If we consider that in some biomes(ldquoPantanal or Chacordquo ldquoCerradordquo and ldquoPampardquo) carnivore species areabundant and represent a huge biomass any study of Leishmaniareservoirs must include carnivores including their Leishmania in-fection pattern density and population structure in the area Despiteits inherent difficulties the study of wild carnivores especially inthe areas where their relative abundance is high is of fundamen-tal importance to improve understanding of Leishmania ecology

46 Order Primata

Nonhuman primates can be divided in two groups the catar-rhines (infraorder Catarrhini) from Africa Europe and Asia (OldWorld Primates) and the platyrrhines (Platyrrhini) from the Ameri-cas (New World or Neotropical Primates) The main differencebetween them is that the catarrhines have upside-down nostrils ona long snout while platyrrhines have laterally-faced nostrils on ashorter snout (Verona and Pissinatti 2007) The different speciesof neotropical primates are included in the families Cebidae (tama-rins) and Callitrichidae (marmosets) although some classificationsalso recognize three other families Aotidae Pithecidae and AtelidaeThe neotropical primates occupy distinct arboreal strata and consumediverse diets including species that feed on fruits invertebrates andeven small mammals (Verona and Pissinatti 2007)

To date few studies have described natural infection by Leish-mania parasites in neotropical primates Infection by L shawi wasdescribed in the tufted capuchin monkey Cebus apella and thebearded saki Chiropotes satanas (Lainson et al 1989) while infec-tion by Leishmania (Viannia) sp was recently demonstrated in fourArgentinean owl monkeys Aotus azarai (Acardi et al 2013) InPanamaacute Geoffroyrsquos tamarin Saguinus geoffroyi and the owl monkeyAotus trivirgatus were found to be infected with L amazonensis andL braziliensis respectively (Herrer and Christensen 1976 Herrer et al1973) In a Brazilian zoo one black-fronted titi Callicebus nigrifronsfrom Belo HorizonteMG presented with a fatal disease thatresembled visceral leishmaniasis Histological and immunohisto-chemical examinations as well as a PCR specific for parasites fromthe L donovani complex confirmed infection with L infantum (Maltaet al 2010) The other primate species that had PCR-positive bloodsamples in the same study were Alouatta guariba Cebus xanthosternosLeonthopitecus crysomelas Aotus nigriceps Pithecia irrorata andSaguinus imperator (Malta et al 2010) In the zoo in BauruSP Leish-mania amazonensis was detected by PCR-RFLP in a spider monkeyAteles paniscus from the endemic Amazon region (Lima et al 2012b)(Table 1)

Leishmania species that circulate in the Americas have been dem-onstrated to infect other neotropical primates but only underexperimental conditions Most of these studies focused on theimmune response to different drug treatments or on vaccine de-velopment For many years black-tufted marmosets Callithrixpenicillata were used in experimental studies with L braziliensis andL amazonensis (Cuba et al 1990 Cuba-Cuba and Marsden 1993)

Experimental infection of the common squirrel monkey Saimirisciureus resulted in non-ulcerated skin lesions from which Lbraziliensis andor L panamensis could be re-isolated (Pung et al1988) Owl monkeys Aotus trivirgatus developed localized cutane-ous lesions after experimental infection with L braziliensis Lmexicana and L panamensis (Christensen and de Vasquez 1981 Lujanet al 1986) Cebus apella developed skin lesions after experimen-tal infection with L lainsoni L amazonensis L braziliensis L mexicanaand L guyanensis (Garcez et al 2002 Grimaldi 2008) ConverselyCebus nigrivittatus developed fatal disease when experimentally in-fected with L infantum (Vouldoukis et al 1986)

All neotropical primates are included in the list of the ldquoConven-tion on International Trade in Endangered Species of Wild Faunaand Florardquo (CITES) indicating that all are vulnerable to some degree(Verona and Pissinatti 2007) For this reason many species suchas the golden lion tamarin Leonthopitecus rosalia are included in con-servation programs These programs often include exchangetranslocation and re-introduction of animals without consider-ation of their parasite fauna here including Leishmania and othertrypanosomatids Data from naturally infected primates demon-strate that these mammals may be involved in the maintenance ofLeishmania in the wild especially considering their ecology speciestransmitted in the canopy Taking into account the transmission cycleof these parasites a lack of knowledge regarding the health statusof the relocated primates may result in the introduction of in-fected mammals into a given area promoting the establishment ofnew transmission cycles (Lisboa et al 2006)

47 Order Chiroptera

Bats are nocturnal mammals and the only able to fly (some-times associated with seasonal migration) an important trait thatcan result in the dissemination of parasite species Their disper-sion capacity is due to the ability to do true flapping flight(apparently evolved differently among bat lineages) and the so-phisticated echolocation system that allows them to identify theenvironment (Jones and Teeling 2006) Despite their known diver-sity bats are still considered as a monophyletic group (Bishop 2008Bisson et al 2009)

Bats are commonly infected with several trypanosomatid speciesmainly from the Trypanosoma genus T cruzi T vespertilionis andT (Megatrypanum) sp among others (Lima et al 2012a) There isonly one report of the isolation of Leishmania parasites (L infantum)from the blood of a short-tailed fruit bat Carollia perspicillata in Ven-ezuela (De Lima et al 2008) (Table 1) Before that Lampo et al haddemonstrated that bats could be sources of blood for Lutzomyialongipalpis in Venezuelan caves (Lampo et al 2000)

In Brazil two Leishmania species were identified in maceratedfragments of spleen and liver from bats using a nested PCR fol-lowed by sequencing of the amplified products Molossus molossusand Glossophaga soricina were found to be infected with L infantumand L amazonensis and the latter was also found in Molossus rufusNyctinomops laticaudatus Eumops glaucinus E auripendulus Artibeusliteratus Sturnira lilium and Myotis nigricans (Savani et al 2010) Re-cently Leishmania (Viannia) sp was detected in a skin lesion fromGlossophaga soricina and blood from Molossus molossus (Shapiro et al2013) (Table 1) In this article although the authors have de-scribed infection with L braziliensis PCR-RFLP using primers b1 andb2 (Schonian et al 2003) does not allow for differentiation amongother species from the same subgenus such as L guyanensis

Bats should not be excluded as potential reservoirs of Leishma-nia sp because of the lack of studies involving Leishmania and batsChiroptera represents 39 of the 560 mammal species reported inSouth American rainforests it is the most common mammal groupin terms of diversity and biomass (Emmons and Feer 1997 Rotureau2006) These flying mammals are found in wild domestic and

258 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

synanthropic environments being able to colonize different habi-tats in different ecotypes Their refuges include hollow trees thecanopies of palm trees and ceilings of human houses and other ruralbuildings Their high abundance and adaptability to peri-domesticenvironment reinforce the importance of investigating bats alreadyrecognized as reservoirs of other trypanosomatids (Jansen and Roque2010) in the transmission cycles of Leishmania species

5 Conclusions and perspectives

Many decades have passed since the description of Leishmaniaparasites but their epidemiology is still not well understood in partbecause of the human-health focus of most studies Only recentlyinfluenced by the ldquoone healthrdquo approach has the epidemiology ofleishmaniasis started to be evaluated from a broader perspective(Palatnik-de-Sousa and Day 2011)

In the case of human visceral leishmaniasis caused by L infantumthe idea that dogs are the only reservoir of the parasite has led healthauthorities to direct the eradication of seropositive dogs on the basisthat this action was the only way to control this zoonosis In factseveral studies have demonstrated that dogs are epidemiologi-cally important as reservoirs in different localities (reviewed byLainson and Rangel 2005 Dantas-Torres 2009 Quinnell andCourtenay 2009) Nevertheless the participation of other in-fected mammals rather than dogs in the transmission cycle of Linfantum in urban areas was already proposed for cats and opos-sums for example (Pennisi et al 2013 Santiago et al 2007) Thelow effectiveness of dog culling program in Brazil is probably dueto an assemblage of factors most of them related to the lack of astructured surveillance system and include the high interval betweentests and between the positive result and dog elimination the rapidreplacement of susceptible dogs when an infected dog is euthan-ized and the resistance of owners to euthanize their infected dogs(Costa et al 2013 Grimaldi et al 2012 Nunes et al 2008) Someof these localities are very close to sylvatic areas and the possibil-ity that wild mammals may serve as a source of infection to vectorsin peridomiciliary areas has been ignored The putative participa-tion of these mammals is an important additional factor to beconsidered in the proposition of measures to control this zoono-sis This review highlights species from distinct orders that maymaintain and serve as a source of infection to phlebotomine sandfly vectors providing a constant source of re-infection to a peri-domestic transmission system

The reservoirs of the Leishmania species responsible for the cu-taneous forms of human leishmaniasis are still unknown most likelybecause research has focused on the search for a specific reservoirhost as observed for dogs and L infantum These species may bemaintained in the wild by a different strategy as by a few ldquohotspeciesrdquo with high transmissibility competence or most likelythrough a reservoir system an assemblage of mammals with dis-tinct and transient degrees of transmissibility competencethroughout infection This hypothesis agrees with the reservoir def-inition proposed by Ashford (1997) almost 20 years ago This systeminvolves a tradeoff that could explain the evolutionary success ofthese parasite species several individuals are infected but each iscompetent for transmission for only a limited time while retain-ing the infection for long periods of time The sum of multiple shortperiods of infectivity in numerous infected mammals guaranteesthe maintenance and transmission of these Leishmania species

All the links in the epidemiological chain must be clarified as a pre-requisite for effective control strategies (Abdussalan 1959Palatnik-de-Sousa and Day 2011 Shaw 2007) We are still far from un-derstanding the maintenance of different Leishmania species in natureIn this sense the follow-up of naturally infected animals and experi-mental studies using potential reservoirs are essential to improvingunderstanding of the mechanisms of maintenance of these parasites

in their natural hosts In the field the studies should not be restrictedto previously described infected hosts but should be carried out usingan integrated ecological approach to understand the role of each hostspecies in the maintenance and amplification of Leishmania para-sites Priorities include the identification of the factors that influencethe transmissibility competence of the individual mammalian hosts andunderstanding how environmental management could decrease in-fections in humans living close to sylvatic

Over the last century the scientific community has shown thatdifferent and several wild mammal species can become infected withLeishmania species The focus must change to identify species thatmay serve as sources of infection to vectors and amplify enzooticfoci constituting a risk for human transmission To this end a par-adigm shift in research and surveillance of wild reservoirs ofLeishmania is urgently needed This change will depend among otherfactors on understanding reservoir systems and acknowledging theimportance of understanding the role each mammal species playsin maintaining these parasites in nature The factors involved in theamplification of enzootic foci are temporally and regionally spe-cific and understanding some of these factors may support thedevelopment of effective and sustainable strategies for leishmani-asis surveillance

Acknowledgements

AMJ is a ldquoCientista do Nosso Estadordquo provided by FAPERJ andis financially supported by CNPq (ldquoBolsista de Produtividade niacutevel1rdquo CNPq) ALRR is a ldquoJovem Cientista do Nosso Estadordquo providedby FAPERJ The authors have declared that no competing interestsexist

References

Abdussalan M 1959 Significance of ecological studies of wild animal reservoir ofzoonoses Bull World Health Organ 21 179ndash186

Acardi SA Rago MV Liotta DJ Fernandez-Duque E Salomon OD 2013Leishmania (Viannia) DNA detection by PCR-RFLP and sequencing in free-rangingowl monkeys (Aotus azarai azarai) from Formosa Argentina Vet Parasitol 193256ndash259

Aguirre AA Tabor GM 2008 Global factors driving emerging infectious diseasesAnn N Y Acad Sci 1149 1ndash3

Alexander KA Lewis BL Marathe M Eubank S Blackburn JK 2012 Modelingof wildlife-associated zoonoses applications and caveats Vector Borne ZoonoticDis 12 1005ndash1018

Alvar J Velez ID Bern C Herrero M Desjeux P Cano J et al 2012 Leishmaniasisworldwide and global estimates of its incidence PLoS ONE 7 e35671

Arauacutejo A Reinhard K Ferreira LF Pucu E Chieffi PP 2013 Paleoparasitologythe origin of human parasites Arq Neuropsiquiatr 71 722ndash726

Arias JR Naif RD Miles MA de Souza AA 1981 The opossum Didelphismarsupialis (Marsupialia didelphidae) as a reservoir host of Leishmaniabraziliensis guyanensis in the Amazon Basin of Brazil Trans R Soc Trop MedHyg 75 537ndash541

Ashford DA Bozza M Freire M Miranda JC Sherlock I Eulalio C et al 1995Comparison of the polymerase chain reaction and serology for the detection ofcanine visceral leishmaniasis Am J Trop Med Hyg 53 251ndash255

Ashford RW 1996 Leishmaniasis reservoir and their significance in control ClinDermatol 14 523ndash532

Ashford RW 1997 What it takes to be a reservoir host Belg J Zool 127 85ndash90Ashford RW 2000 The leishmaniases as emerging and reemerging zoonoses Int

J Parasitol 30 1269ndash1281Austad SN 1988 The adaptable opossum Sci Am 258 54ndash59Bishop KL 2008 The evolution of flight in bats narrowing the field of plausible

hypotheses Q Rev Biol 83 153ndash169Bisson IA Safi K Holland RA 2009 Evidence for repeated independent evolution

of migration in the largest family of bats PLoS ONE 4 e7504Bonvicino CR Otazu IB DrsquoAndrea PS 2002 Karyologic evidence of diversification

of the genus Thrichomys (Rodentia Echimyidae) Cytogenet Genome Res 97200ndash204

Botero A Thompson CK Peacock CS Clode PL Nicholls PK Wayne AF et al2013 Trypanosomes genetic diversity polyparasitism and the population declineof the critically endangered Australian marsupial the brush tailed bettong orwoylie (Bettongia penicillata) Int J Parasitol Parasite Wildl 2 77ndash89

Brandatildeo-Filho SP Brito ME Carvalho FG Ishikawa EA Cupolillo EFloeter-Winter L et al 2003 Wild and synanthropic hosts of Leishmania(Viannia) braziliensis in the endemic cutaneous leishmaniasis locality of AmarajiPernambuco State Brazil Trans R Soc Trop Med Hyg 97 291ndash296

259ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

ancient L braziliensis sensu lato) the following rodent species havebeen described to be naturally infected Akodon arviculoides Musmusculus Nectomys squamipes Necromys (=Bolomys) lasiurusOryzomys nigripes Rattus rattus and Sigmodon hispidus (Brandatildeo-Filhoet al 2003 de Freitas et al 2012 De Lima et al 2002 Forattiniet al 1972 Peterson et al 1988 Rocha et al 1988 Vasconceloset al 1994) In other cases the authors confirmed infection by thesubgenus Leishmania (Viannia) sp (Holochilus scieurus and Cerradomyssubflavus) (Brandatildeo-Filho et al 2003 Lima et al 2013) or tenta-tively identified the etiological agent through the biological patternof in vitro growth (Rhipidomys leucodactylus and Proechimysguyannensis) (Lainson et al 1981b)

Rodents are also usually considered as the main reservoirs ofLeishmania from the L mexicana complex (L mexicana and Lamazonensis) L amazonensis was described in rodents from the fol-lowing genera Akodon Dasyprocta Oligoryzomys OryzomysProechimys Thrichomys and Sciurus (Arias et al 1981 Kerr et al2006 Lainson et al 1981b Mimori et al 1989 Oliveira et al 2005Telleria et al 1999) None of these studies however included follow-up of the infection or demonstrated competence to infect vectors

L mexicana has been isolated from various species of Neotomaincluding a specimen of N floridana with a large lesion in the earfrom which the parasite could be isolated (Kerr et al 1995 McHughet al 2003) This finding was informative suggesting that this rodentspecies may be infective for the vector and an important reservoirof L mexicana Ototylomys phyllotis from Belize should be consid-ered as a possible reservoir of L mexicana because of its relativeabundance prevalence of infection and attraction to Lu flaviscutellatathe most important vector in the region Curiously the same authorfailed to reproduce this infection under experimental conditions(Ashford 1996) possibly due to factors occurring only in naturesuch as stress and concomitant infections which may be impor-tant for the establishment of Leishmania infection This situationhighlights the importance of the studies of naturally infected speci-mens and the difficulties of adopting potential reservoir hosts asalternative models for leishmaniasis studies Moreover these find-ings attest to the hazards of applying conclusions based solely onexperimental models to natural systems

The persistence of L mexicana infection in wild rodents was dem-onstrated twice The first such finding occurred in Mexico where29 naturally infected rodents were maintained in captivity and testedmonthly for parasites for up to 2 years In that study the authorsdemonstrated persistent infection including symptomatic infec-tions in Sigmodon hispidus Oryzomys melanotis Ototylomys phyllotisand Peromyscus yucatanicus the latter two being the most impor-tant because of their high relative abundance in local fauna andlonger life spans (Van Wynsberghe et al 2000) Second in the UnitedStates during a 19-month markndashreleasendashrecapture study of Neotomamicropus the authors reported the persistence of L mexicana in-fection for up to 1 year (Raymond et al 2003) Heteromys Nyctomysand Reithrodontomys were also found infected with L mexicana(Ashford 1996 De Lima et al 2002 Disney 1968 Lainson andStrangways-Dixon 1964 Van Wynsberghe et al 2009)

Leishmania lainsoni was isolated from fragments of intact skinfrom pacas (Agouti paca) in the Brazilian state of Paraacute (Silveira et al1991) and from Coendu sp (Table 1) Leishmania panamensis was iso-lated from naturally infected Heteromys dermarestianus from CostaRica (Zeledon et al 1977) while a squirrel Scirus granatensis wasfound to be infected with L equatorensis in Ecuador (Grimaldi et al1992) Leishmania peruviana a species suggested to be a synonymof L braziliensis was isolated from the Peruvian Phyllotis andinum(Llanos-Cuentas et al 1999) Finally L hertigiL deanei and L enriettiispecies taxonomically more similar to Endotrypanum than to Leish-mania have been described respectively in porcupines Coendu spp(Herrer 1971 Silva et al 2013) and in the guinea pig Cavia porcellus(Machado et al 1994)

Taken together a broad diversity of Leishmania species natural-ly infect this mammal group most likely reflecting the diversity ofecological niches occupied by the hosts The differences observedamong the rodent species include the forest strata they occupy andtheir reproductive strategies (seasonality gestation time and numberof offspring) and these traits should be considered evaluations ofthe importance of a rodent species as a Leishmania reservoir More-over as expected for every hostndashparasite interaction thisheterogeneous mammalian taxon shows a spectrum of compe-tence to maintain and transmit Leishmania from high susceptibilitywith high transmissibility competence to quick control ofinfection

45 Order Carnivora

The mammals from this order also comprise a very heteroge-neous group including strict carnivores such as ocelots (Leoparduspardalis) and tayras (Eira barbara) and species that supplement theirdiet with insects and fruits such as coatis (Nasua nasua) and manedwolves (Chrysocyon brachyurus) Most have a large biomass and largerange important aspects of parasite dispersion (Rocha et al 2013)Moreover some species such as raccoons and tayras are found bothon the ground and in the canopy favoring the dispersion of para-sites among forest strata Unfortunately carnivores require largeranges and because of their potential to predate on livestock (mainlychickens and cattle) are heavily hunted placing some carnivorespecies at risk of extinction (Silva and Adania 2007)

Two carnivore species are closely linked to humans dogs andcats Dogs are the most important reservoirs of L infantum through-out South America although they can be infected with at least sixother Leishmania species (Dantas-Torres 2009) Recently the im-portance of cats in Leishmania epidemiology has also been suggested(Pennisi et al 2013) Among the wild carnivore hosts of L infantumthe first description of infection was in the crab-eating fox Cerdocyonthous although the authors inaccurately reported the host asLycalopex vetulus (Courtenay et al 1996 Deane and Deane 1955)Since then many studies have confirmed L infantum infection inC thous by parasitological serological andor molecular assaysNotably these animals sometimes develop serious symptoms of thedisease and present with amastigotes in intact skin as also de-scribed in domestic dogs Their prevalence of infection may rangefrom 42 (by parasitological tests) to 78 (by serology) (Lainson et al1990 Quinnell and Courtenay 2009 Silva et al 2000) The vectorinfectivity was proven by xenodiagnosis although the infection rateof vectors is reported to be lower than that observed for domesticdogs (Courtenay et al 2002 Quinnell and Courtenay 2009)

Apart from C thous another wild carnivore that is a potentialreservoir of L infantum is the bush dog Speothos venaticus An in-dividual kept in a zoo in Rio de Janeiro Brazil is the only wild canidexcept for C thous from which L infantum was isolated (Figueiredoet al 2008) Infection in bush dogs was also confirmed by directvisualization PCR and serology in two females with clinical signsof visceral leishmaniasis and maintained in other Brazilian zoos (Limaet al 2009 Souza et al 2010) Other wild canid species found tobe infected albeit only by PCR andor serology were the hoary foxPseudalopex vetulus and the maned wolf Chrysocyon brachyurus (Curiet al 2006 Luppi et al 2008) (Table 1)

Some authors have investigated Leishmania infection in captivewild carnivores Five of 15 wild canids belonging to the four nativespecies mentioned earlier were found to be infected in a zoo in BeloHorizonte Brazil Of these one bush dog and one hoary fox devel-oped clinical signs of visceral leishmaniasis (Luppi et al 2008)Among the wild felines five pumas (Puma concolor) and one jaguar(Panthera onca) in a zoo from Cuiabaacute Brazil were PCR-positive inlymph-node puncture biopsy L infantum was specifically identi-fied by the digestion of the amplified products with restriction

257ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

enzymes (Dahroug et al 2010) Later the same authors demon-strated L infantum infection in one lion a non-native felid specieskept in the same zoo (Dahroug et al 2011)

In addition to L infantum at least four other Leishmania specieswere found in wild carnivores L shawi in coatis Nasua nasua (Lainsonet al 1989) L guyanensis in the kinkajou Potos flavus (Pajot et al1982) L amazonensis in kinkajous crab-eating foxes and skunksConepatus chinga (Kreutzer et al 1991 Rotureau 2006 Telleria et al1999) and L braziliensis in one Bolivian skunk (Buitrago et al 2011)(Table 1)

Contrary to the numerous reports of infection in dogs and catsmuch remains to study in terms of the putative roles of wild car-nivores as Leishmania reservoirs As in all hostndashparasite interactionsthe infection patterns display regional and even individual pecu-liarities (Rocha et al 2013) If we consider that in some biomes(ldquoPantanal or Chacordquo ldquoCerradordquo and ldquoPampardquo) carnivore species areabundant and represent a huge biomass any study of Leishmaniareservoirs must include carnivores including their Leishmania in-fection pattern density and population structure in the area Despiteits inherent difficulties the study of wild carnivores especially inthe areas where their relative abundance is high is of fundamen-tal importance to improve understanding of Leishmania ecology

46 Order Primata

Nonhuman primates can be divided in two groups the catar-rhines (infraorder Catarrhini) from Africa Europe and Asia (OldWorld Primates) and the platyrrhines (Platyrrhini) from the Ameri-cas (New World or Neotropical Primates) The main differencebetween them is that the catarrhines have upside-down nostrils ona long snout while platyrrhines have laterally-faced nostrils on ashorter snout (Verona and Pissinatti 2007) The different speciesof neotropical primates are included in the families Cebidae (tama-rins) and Callitrichidae (marmosets) although some classificationsalso recognize three other families Aotidae Pithecidae and AtelidaeThe neotropical primates occupy distinct arboreal strata and consumediverse diets including species that feed on fruits invertebrates andeven small mammals (Verona and Pissinatti 2007)

To date few studies have described natural infection by Leish-mania parasites in neotropical primates Infection by L shawi wasdescribed in the tufted capuchin monkey Cebus apella and thebearded saki Chiropotes satanas (Lainson et al 1989) while infec-tion by Leishmania (Viannia) sp was recently demonstrated in fourArgentinean owl monkeys Aotus azarai (Acardi et al 2013) InPanamaacute Geoffroyrsquos tamarin Saguinus geoffroyi and the owl monkeyAotus trivirgatus were found to be infected with L amazonensis andL braziliensis respectively (Herrer and Christensen 1976 Herrer et al1973) In a Brazilian zoo one black-fronted titi Callicebus nigrifronsfrom Belo HorizonteMG presented with a fatal disease thatresembled visceral leishmaniasis Histological and immunohisto-chemical examinations as well as a PCR specific for parasites fromthe L donovani complex confirmed infection with L infantum (Maltaet al 2010) The other primate species that had PCR-positive bloodsamples in the same study were Alouatta guariba Cebus xanthosternosLeonthopitecus crysomelas Aotus nigriceps Pithecia irrorata andSaguinus imperator (Malta et al 2010) In the zoo in BauruSP Leish-mania amazonensis was detected by PCR-RFLP in a spider monkeyAteles paniscus from the endemic Amazon region (Lima et al 2012b)(Table 1)

Leishmania species that circulate in the Americas have been dem-onstrated to infect other neotropical primates but only underexperimental conditions Most of these studies focused on theimmune response to different drug treatments or on vaccine de-velopment For many years black-tufted marmosets Callithrixpenicillata were used in experimental studies with L braziliensis andL amazonensis (Cuba et al 1990 Cuba-Cuba and Marsden 1993)

Experimental infection of the common squirrel monkey Saimirisciureus resulted in non-ulcerated skin lesions from which Lbraziliensis andor L panamensis could be re-isolated (Pung et al1988) Owl monkeys Aotus trivirgatus developed localized cutane-ous lesions after experimental infection with L braziliensis Lmexicana and L panamensis (Christensen and de Vasquez 1981 Lujanet al 1986) Cebus apella developed skin lesions after experimen-tal infection with L lainsoni L amazonensis L braziliensis L mexicanaand L guyanensis (Garcez et al 2002 Grimaldi 2008) ConverselyCebus nigrivittatus developed fatal disease when experimentally in-fected with L infantum (Vouldoukis et al 1986)

All neotropical primates are included in the list of the ldquoConven-tion on International Trade in Endangered Species of Wild Faunaand Florardquo (CITES) indicating that all are vulnerable to some degree(Verona and Pissinatti 2007) For this reason many species suchas the golden lion tamarin Leonthopitecus rosalia are included in con-servation programs These programs often include exchangetranslocation and re-introduction of animals without consider-ation of their parasite fauna here including Leishmania and othertrypanosomatids Data from naturally infected primates demon-strate that these mammals may be involved in the maintenance ofLeishmania in the wild especially considering their ecology speciestransmitted in the canopy Taking into account the transmission cycleof these parasites a lack of knowledge regarding the health statusof the relocated primates may result in the introduction of in-fected mammals into a given area promoting the establishment ofnew transmission cycles (Lisboa et al 2006)

47 Order Chiroptera

Bats are nocturnal mammals and the only able to fly (some-times associated with seasonal migration) an important trait thatcan result in the dissemination of parasite species Their disper-sion capacity is due to the ability to do true flapping flight(apparently evolved differently among bat lineages) and the so-phisticated echolocation system that allows them to identify theenvironment (Jones and Teeling 2006) Despite their known diver-sity bats are still considered as a monophyletic group (Bishop 2008Bisson et al 2009)

Bats are commonly infected with several trypanosomatid speciesmainly from the Trypanosoma genus T cruzi T vespertilionis andT (Megatrypanum) sp among others (Lima et al 2012a) There isonly one report of the isolation of Leishmania parasites (L infantum)from the blood of a short-tailed fruit bat Carollia perspicillata in Ven-ezuela (De Lima et al 2008) (Table 1) Before that Lampo et al haddemonstrated that bats could be sources of blood for Lutzomyialongipalpis in Venezuelan caves (Lampo et al 2000)

In Brazil two Leishmania species were identified in maceratedfragments of spleen and liver from bats using a nested PCR fol-lowed by sequencing of the amplified products Molossus molossusand Glossophaga soricina were found to be infected with L infantumand L amazonensis and the latter was also found in Molossus rufusNyctinomops laticaudatus Eumops glaucinus E auripendulus Artibeusliteratus Sturnira lilium and Myotis nigricans (Savani et al 2010) Re-cently Leishmania (Viannia) sp was detected in a skin lesion fromGlossophaga soricina and blood from Molossus molossus (Shapiro et al2013) (Table 1) In this article although the authors have de-scribed infection with L braziliensis PCR-RFLP using primers b1 andb2 (Schonian et al 2003) does not allow for differentiation amongother species from the same subgenus such as L guyanensis

Bats should not be excluded as potential reservoirs of Leishma-nia sp because of the lack of studies involving Leishmania and batsChiroptera represents 39 of the 560 mammal species reported inSouth American rainforests it is the most common mammal groupin terms of diversity and biomass (Emmons and Feer 1997 Rotureau2006) These flying mammals are found in wild domestic and

258 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

synanthropic environments being able to colonize different habi-tats in different ecotypes Their refuges include hollow trees thecanopies of palm trees and ceilings of human houses and other ruralbuildings Their high abundance and adaptability to peri-domesticenvironment reinforce the importance of investigating bats alreadyrecognized as reservoirs of other trypanosomatids (Jansen and Roque2010) in the transmission cycles of Leishmania species

5 Conclusions and perspectives

Many decades have passed since the description of Leishmaniaparasites but their epidemiology is still not well understood in partbecause of the human-health focus of most studies Only recentlyinfluenced by the ldquoone healthrdquo approach has the epidemiology ofleishmaniasis started to be evaluated from a broader perspective(Palatnik-de-Sousa and Day 2011)

In the case of human visceral leishmaniasis caused by L infantumthe idea that dogs are the only reservoir of the parasite has led healthauthorities to direct the eradication of seropositive dogs on the basisthat this action was the only way to control this zoonosis In factseveral studies have demonstrated that dogs are epidemiologi-cally important as reservoirs in different localities (reviewed byLainson and Rangel 2005 Dantas-Torres 2009 Quinnell andCourtenay 2009) Nevertheless the participation of other in-fected mammals rather than dogs in the transmission cycle of Linfantum in urban areas was already proposed for cats and opos-sums for example (Pennisi et al 2013 Santiago et al 2007) Thelow effectiveness of dog culling program in Brazil is probably dueto an assemblage of factors most of them related to the lack of astructured surveillance system and include the high interval betweentests and between the positive result and dog elimination the rapidreplacement of susceptible dogs when an infected dog is euthan-ized and the resistance of owners to euthanize their infected dogs(Costa et al 2013 Grimaldi et al 2012 Nunes et al 2008) Someof these localities are very close to sylvatic areas and the possibil-ity that wild mammals may serve as a source of infection to vectorsin peridomiciliary areas has been ignored The putative participa-tion of these mammals is an important additional factor to beconsidered in the proposition of measures to control this zoono-sis This review highlights species from distinct orders that maymaintain and serve as a source of infection to phlebotomine sandfly vectors providing a constant source of re-infection to a peri-domestic transmission system

The reservoirs of the Leishmania species responsible for the cu-taneous forms of human leishmaniasis are still unknown most likelybecause research has focused on the search for a specific reservoirhost as observed for dogs and L infantum These species may bemaintained in the wild by a different strategy as by a few ldquohotspeciesrdquo with high transmissibility competence or most likelythrough a reservoir system an assemblage of mammals with dis-tinct and transient degrees of transmissibility competencethroughout infection This hypothesis agrees with the reservoir def-inition proposed by Ashford (1997) almost 20 years ago This systeminvolves a tradeoff that could explain the evolutionary success ofthese parasite species several individuals are infected but each iscompetent for transmission for only a limited time while retain-ing the infection for long periods of time The sum of multiple shortperiods of infectivity in numerous infected mammals guaranteesthe maintenance and transmission of these Leishmania species

All the links in the epidemiological chain must be clarified as a pre-requisite for effective control strategies (Abdussalan 1959Palatnik-de-Sousa and Day 2011 Shaw 2007) We are still far from un-derstanding the maintenance of different Leishmania species in natureIn this sense the follow-up of naturally infected animals and experi-mental studies using potential reservoirs are essential to improvingunderstanding of the mechanisms of maintenance of these parasites

in their natural hosts In the field the studies should not be restrictedto previously described infected hosts but should be carried out usingan integrated ecological approach to understand the role of each hostspecies in the maintenance and amplification of Leishmania para-sites Priorities include the identification of the factors that influencethe transmissibility competence of the individual mammalian hosts andunderstanding how environmental management could decrease in-fections in humans living close to sylvatic

Over the last century the scientific community has shown thatdifferent and several wild mammal species can become infected withLeishmania species The focus must change to identify species thatmay serve as sources of infection to vectors and amplify enzooticfoci constituting a risk for human transmission To this end a par-adigm shift in research and surveillance of wild reservoirs ofLeishmania is urgently needed This change will depend among otherfactors on understanding reservoir systems and acknowledging theimportance of understanding the role each mammal species playsin maintaining these parasites in nature The factors involved in theamplification of enzootic foci are temporally and regionally spe-cific and understanding some of these factors may support thedevelopment of effective and sustainable strategies for leishmani-asis surveillance

Acknowledgements

AMJ is a ldquoCientista do Nosso Estadordquo provided by FAPERJ andis financially supported by CNPq (ldquoBolsista de Produtividade niacutevel1rdquo CNPq) ALRR is a ldquoJovem Cientista do Nosso Estadordquo providedby FAPERJ The authors have declared that no competing interestsexist

References

Abdussalan M 1959 Significance of ecological studies of wild animal reservoir ofzoonoses Bull World Health Organ 21 179ndash186

Acardi SA Rago MV Liotta DJ Fernandez-Duque E Salomon OD 2013Leishmania (Viannia) DNA detection by PCR-RFLP and sequencing in free-rangingowl monkeys (Aotus azarai azarai) from Formosa Argentina Vet Parasitol 193256ndash259

Aguirre AA Tabor GM 2008 Global factors driving emerging infectious diseasesAnn N Y Acad Sci 1149 1ndash3

Alexander KA Lewis BL Marathe M Eubank S Blackburn JK 2012 Modelingof wildlife-associated zoonoses applications and caveats Vector Borne ZoonoticDis 12 1005ndash1018

Alvar J Velez ID Bern C Herrero M Desjeux P Cano J et al 2012 Leishmaniasisworldwide and global estimates of its incidence PLoS ONE 7 e35671

Arauacutejo A Reinhard K Ferreira LF Pucu E Chieffi PP 2013 Paleoparasitologythe origin of human parasites Arq Neuropsiquiatr 71 722ndash726

Arias JR Naif RD Miles MA de Souza AA 1981 The opossum Didelphismarsupialis (Marsupialia didelphidae) as a reservoir host of Leishmaniabraziliensis guyanensis in the Amazon Basin of Brazil Trans R Soc Trop MedHyg 75 537ndash541

Ashford DA Bozza M Freire M Miranda JC Sherlock I Eulalio C et al 1995Comparison of the polymerase chain reaction and serology for the detection ofcanine visceral leishmaniasis Am J Trop Med Hyg 53 251ndash255

Ashford RW 1996 Leishmaniasis reservoir and their significance in control ClinDermatol 14 523ndash532

Ashford RW 1997 What it takes to be a reservoir host Belg J Zool 127 85ndash90Ashford RW 2000 The leishmaniases as emerging and reemerging zoonoses Int

J Parasitol 30 1269ndash1281Austad SN 1988 The adaptable opossum Sci Am 258 54ndash59Bishop KL 2008 The evolution of flight in bats narrowing the field of plausible

hypotheses Q Rev Biol 83 153ndash169Bisson IA Safi K Holland RA 2009 Evidence for repeated independent evolution

of migration in the largest family of bats PLoS ONE 4 e7504Bonvicino CR Otazu IB DrsquoAndrea PS 2002 Karyologic evidence of diversification

of the genus Thrichomys (Rodentia Echimyidae) Cytogenet Genome Res 97200ndash204

Botero A Thompson CK Peacock CS Clode PL Nicholls PK Wayne AF et al2013 Trypanosomes genetic diversity polyparasitism and the population declineof the critically endangered Australian marsupial the brush tailed bettong orwoylie (Bettongia penicillata) Int J Parasitol Parasite Wildl 2 77ndash89

Brandatildeo-Filho SP Brito ME Carvalho FG Ishikawa EA Cupolillo EFloeter-Winter L et al 2003 Wild and synanthropic hosts of Leishmania(Viannia) braziliensis in the endemic cutaneous leishmaniasis locality of AmarajiPernambuco State Brazil Trans R Soc Trop Med Hyg 97 291ndash296

259ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

enzymes (Dahroug et al 2010) Later the same authors demon-strated L infantum infection in one lion a non-native felid specieskept in the same zoo (Dahroug et al 2011)

In addition to L infantum at least four other Leishmania specieswere found in wild carnivores L shawi in coatis Nasua nasua (Lainsonet al 1989) L guyanensis in the kinkajou Potos flavus (Pajot et al1982) L amazonensis in kinkajous crab-eating foxes and skunksConepatus chinga (Kreutzer et al 1991 Rotureau 2006 Telleria et al1999) and L braziliensis in one Bolivian skunk (Buitrago et al 2011)(Table 1)

Contrary to the numerous reports of infection in dogs and catsmuch remains to study in terms of the putative roles of wild car-nivores as Leishmania reservoirs As in all hostndashparasite interactionsthe infection patterns display regional and even individual pecu-liarities (Rocha et al 2013) If we consider that in some biomes(ldquoPantanal or Chacordquo ldquoCerradordquo and ldquoPampardquo) carnivore species areabundant and represent a huge biomass any study of Leishmaniareservoirs must include carnivores including their Leishmania in-fection pattern density and population structure in the area Despiteits inherent difficulties the study of wild carnivores especially inthe areas where their relative abundance is high is of fundamen-tal importance to improve understanding of Leishmania ecology

46 Order Primata

Nonhuman primates can be divided in two groups the catar-rhines (infraorder Catarrhini) from Africa Europe and Asia (OldWorld Primates) and the platyrrhines (Platyrrhini) from the Ameri-cas (New World or Neotropical Primates) The main differencebetween them is that the catarrhines have upside-down nostrils ona long snout while platyrrhines have laterally-faced nostrils on ashorter snout (Verona and Pissinatti 2007) The different speciesof neotropical primates are included in the families Cebidae (tama-rins) and Callitrichidae (marmosets) although some classificationsalso recognize three other families Aotidae Pithecidae and AtelidaeThe neotropical primates occupy distinct arboreal strata and consumediverse diets including species that feed on fruits invertebrates andeven small mammals (Verona and Pissinatti 2007)

To date few studies have described natural infection by Leish-mania parasites in neotropical primates Infection by L shawi wasdescribed in the tufted capuchin monkey Cebus apella and thebearded saki Chiropotes satanas (Lainson et al 1989) while infec-tion by Leishmania (Viannia) sp was recently demonstrated in fourArgentinean owl monkeys Aotus azarai (Acardi et al 2013) InPanamaacute Geoffroyrsquos tamarin Saguinus geoffroyi and the owl monkeyAotus trivirgatus were found to be infected with L amazonensis andL braziliensis respectively (Herrer and Christensen 1976 Herrer et al1973) In a Brazilian zoo one black-fronted titi Callicebus nigrifronsfrom Belo HorizonteMG presented with a fatal disease thatresembled visceral leishmaniasis Histological and immunohisto-chemical examinations as well as a PCR specific for parasites fromthe L donovani complex confirmed infection with L infantum (Maltaet al 2010) The other primate species that had PCR-positive bloodsamples in the same study were Alouatta guariba Cebus xanthosternosLeonthopitecus crysomelas Aotus nigriceps Pithecia irrorata andSaguinus imperator (Malta et al 2010) In the zoo in BauruSP Leish-mania amazonensis was detected by PCR-RFLP in a spider monkeyAteles paniscus from the endemic Amazon region (Lima et al 2012b)(Table 1)

Leishmania species that circulate in the Americas have been dem-onstrated to infect other neotropical primates but only underexperimental conditions Most of these studies focused on theimmune response to different drug treatments or on vaccine de-velopment For many years black-tufted marmosets Callithrixpenicillata were used in experimental studies with L braziliensis andL amazonensis (Cuba et al 1990 Cuba-Cuba and Marsden 1993)

Experimental infection of the common squirrel monkey Saimirisciureus resulted in non-ulcerated skin lesions from which Lbraziliensis andor L panamensis could be re-isolated (Pung et al1988) Owl monkeys Aotus trivirgatus developed localized cutane-ous lesions after experimental infection with L braziliensis Lmexicana and L panamensis (Christensen and de Vasquez 1981 Lujanet al 1986) Cebus apella developed skin lesions after experimen-tal infection with L lainsoni L amazonensis L braziliensis L mexicanaand L guyanensis (Garcez et al 2002 Grimaldi 2008) ConverselyCebus nigrivittatus developed fatal disease when experimentally in-fected with L infantum (Vouldoukis et al 1986)

All neotropical primates are included in the list of the ldquoConven-tion on International Trade in Endangered Species of Wild Faunaand Florardquo (CITES) indicating that all are vulnerable to some degree(Verona and Pissinatti 2007) For this reason many species suchas the golden lion tamarin Leonthopitecus rosalia are included in con-servation programs These programs often include exchangetranslocation and re-introduction of animals without consider-ation of their parasite fauna here including Leishmania and othertrypanosomatids Data from naturally infected primates demon-strate that these mammals may be involved in the maintenance ofLeishmania in the wild especially considering their ecology speciestransmitted in the canopy Taking into account the transmission cycleof these parasites a lack of knowledge regarding the health statusof the relocated primates may result in the introduction of in-fected mammals into a given area promoting the establishment ofnew transmission cycles (Lisboa et al 2006)

47 Order Chiroptera

Bats are nocturnal mammals and the only able to fly (some-times associated with seasonal migration) an important trait thatcan result in the dissemination of parasite species Their disper-sion capacity is due to the ability to do true flapping flight(apparently evolved differently among bat lineages) and the so-phisticated echolocation system that allows them to identify theenvironment (Jones and Teeling 2006) Despite their known diver-sity bats are still considered as a monophyletic group (Bishop 2008Bisson et al 2009)

Bats are commonly infected with several trypanosomatid speciesmainly from the Trypanosoma genus T cruzi T vespertilionis andT (Megatrypanum) sp among others (Lima et al 2012a) There isonly one report of the isolation of Leishmania parasites (L infantum)from the blood of a short-tailed fruit bat Carollia perspicillata in Ven-ezuela (De Lima et al 2008) (Table 1) Before that Lampo et al haddemonstrated that bats could be sources of blood for Lutzomyialongipalpis in Venezuelan caves (Lampo et al 2000)

In Brazil two Leishmania species were identified in maceratedfragments of spleen and liver from bats using a nested PCR fol-lowed by sequencing of the amplified products Molossus molossusand Glossophaga soricina were found to be infected with L infantumand L amazonensis and the latter was also found in Molossus rufusNyctinomops laticaudatus Eumops glaucinus E auripendulus Artibeusliteratus Sturnira lilium and Myotis nigricans (Savani et al 2010) Re-cently Leishmania (Viannia) sp was detected in a skin lesion fromGlossophaga soricina and blood from Molossus molossus (Shapiro et al2013) (Table 1) In this article although the authors have de-scribed infection with L braziliensis PCR-RFLP using primers b1 andb2 (Schonian et al 2003) does not allow for differentiation amongother species from the same subgenus such as L guyanensis

Bats should not be excluded as potential reservoirs of Leishma-nia sp because of the lack of studies involving Leishmania and batsChiroptera represents 39 of the 560 mammal species reported inSouth American rainforests it is the most common mammal groupin terms of diversity and biomass (Emmons and Feer 1997 Rotureau2006) These flying mammals are found in wild domestic and

258 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

synanthropic environments being able to colonize different habi-tats in different ecotypes Their refuges include hollow trees thecanopies of palm trees and ceilings of human houses and other ruralbuildings Their high abundance and adaptability to peri-domesticenvironment reinforce the importance of investigating bats alreadyrecognized as reservoirs of other trypanosomatids (Jansen and Roque2010) in the transmission cycles of Leishmania species

5 Conclusions and perspectives

Many decades have passed since the description of Leishmaniaparasites but their epidemiology is still not well understood in partbecause of the human-health focus of most studies Only recentlyinfluenced by the ldquoone healthrdquo approach has the epidemiology ofleishmaniasis started to be evaluated from a broader perspective(Palatnik-de-Sousa and Day 2011)

In the case of human visceral leishmaniasis caused by L infantumthe idea that dogs are the only reservoir of the parasite has led healthauthorities to direct the eradication of seropositive dogs on the basisthat this action was the only way to control this zoonosis In factseveral studies have demonstrated that dogs are epidemiologi-cally important as reservoirs in different localities (reviewed byLainson and Rangel 2005 Dantas-Torres 2009 Quinnell andCourtenay 2009) Nevertheless the participation of other in-fected mammals rather than dogs in the transmission cycle of Linfantum in urban areas was already proposed for cats and opos-sums for example (Pennisi et al 2013 Santiago et al 2007) Thelow effectiveness of dog culling program in Brazil is probably dueto an assemblage of factors most of them related to the lack of astructured surveillance system and include the high interval betweentests and between the positive result and dog elimination the rapidreplacement of susceptible dogs when an infected dog is euthan-ized and the resistance of owners to euthanize their infected dogs(Costa et al 2013 Grimaldi et al 2012 Nunes et al 2008) Someof these localities are very close to sylvatic areas and the possibil-ity that wild mammals may serve as a source of infection to vectorsin peridomiciliary areas has been ignored The putative participa-tion of these mammals is an important additional factor to beconsidered in the proposition of measures to control this zoono-sis This review highlights species from distinct orders that maymaintain and serve as a source of infection to phlebotomine sandfly vectors providing a constant source of re-infection to a peri-domestic transmission system

The reservoirs of the Leishmania species responsible for the cu-taneous forms of human leishmaniasis are still unknown most likelybecause research has focused on the search for a specific reservoirhost as observed for dogs and L infantum These species may bemaintained in the wild by a different strategy as by a few ldquohotspeciesrdquo with high transmissibility competence or most likelythrough a reservoir system an assemblage of mammals with dis-tinct and transient degrees of transmissibility competencethroughout infection This hypothesis agrees with the reservoir def-inition proposed by Ashford (1997) almost 20 years ago This systeminvolves a tradeoff that could explain the evolutionary success ofthese parasite species several individuals are infected but each iscompetent for transmission for only a limited time while retain-ing the infection for long periods of time The sum of multiple shortperiods of infectivity in numerous infected mammals guaranteesthe maintenance and transmission of these Leishmania species

All the links in the epidemiological chain must be clarified as a pre-requisite for effective control strategies (Abdussalan 1959Palatnik-de-Sousa and Day 2011 Shaw 2007) We are still far from un-derstanding the maintenance of different Leishmania species in natureIn this sense the follow-up of naturally infected animals and experi-mental studies using potential reservoirs are essential to improvingunderstanding of the mechanisms of maintenance of these parasites

in their natural hosts In the field the studies should not be restrictedto previously described infected hosts but should be carried out usingan integrated ecological approach to understand the role of each hostspecies in the maintenance and amplification of Leishmania para-sites Priorities include the identification of the factors that influencethe transmissibility competence of the individual mammalian hosts andunderstanding how environmental management could decrease in-fections in humans living close to sylvatic

Over the last century the scientific community has shown thatdifferent and several wild mammal species can become infected withLeishmania species The focus must change to identify species thatmay serve as sources of infection to vectors and amplify enzooticfoci constituting a risk for human transmission To this end a par-adigm shift in research and surveillance of wild reservoirs ofLeishmania is urgently needed This change will depend among otherfactors on understanding reservoir systems and acknowledging theimportance of understanding the role each mammal species playsin maintaining these parasites in nature The factors involved in theamplification of enzootic foci are temporally and regionally spe-cific and understanding some of these factors may support thedevelopment of effective and sustainable strategies for leishmani-asis surveillance

Acknowledgements

AMJ is a ldquoCientista do Nosso Estadordquo provided by FAPERJ andis financially supported by CNPq (ldquoBolsista de Produtividade niacutevel1rdquo CNPq) ALRR is a ldquoJovem Cientista do Nosso Estadordquo providedby FAPERJ The authors have declared that no competing interestsexist

References

Abdussalan M 1959 Significance of ecological studies of wild animal reservoir ofzoonoses Bull World Health Organ 21 179ndash186

Acardi SA Rago MV Liotta DJ Fernandez-Duque E Salomon OD 2013Leishmania (Viannia) DNA detection by PCR-RFLP and sequencing in free-rangingowl monkeys (Aotus azarai azarai) from Formosa Argentina Vet Parasitol 193256ndash259

Aguirre AA Tabor GM 2008 Global factors driving emerging infectious diseasesAnn N Y Acad Sci 1149 1ndash3

Alexander KA Lewis BL Marathe M Eubank S Blackburn JK 2012 Modelingof wildlife-associated zoonoses applications and caveats Vector Borne ZoonoticDis 12 1005ndash1018

Alvar J Velez ID Bern C Herrero M Desjeux P Cano J et al 2012 Leishmaniasisworldwide and global estimates of its incidence PLoS ONE 7 e35671

Arauacutejo A Reinhard K Ferreira LF Pucu E Chieffi PP 2013 Paleoparasitologythe origin of human parasites Arq Neuropsiquiatr 71 722ndash726

Arias JR Naif RD Miles MA de Souza AA 1981 The opossum Didelphismarsupialis (Marsupialia didelphidae) as a reservoir host of Leishmaniabraziliensis guyanensis in the Amazon Basin of Brazil Trans R Soc Trop MedHyg 75 537ndash541

Ashford DA Bozza M Freire M Miranda JC Sherlock I Eulalio C et al 1995Comparison of the polymerase chain reaction and serology for the detection ofcanine visceral leishmaniasis Am J Trop Med Hyg 53 251ndash255

Ashford RW 1996 Leishmaniasis reservoir and their significance in control ClinDermatol 14 523ndash532

Ashford RW 1997 What it takes to be a reservoir host Belg J Zool 127 85ndash90Ashford RW 2000 The leishmaniases as emerging and reemerging zoonoses Int

J Parasitol 30 1269ndash1281Austad SN 1988 The adaptable opossum Sci Am 258 54ndash59Bishop KL 2008 The evolution of flight in bats narrowing the field of plausible

hypotheses Q Rev Biol 83 153ndash169Bisson IA Safi K Holland RA 2009 Evidence for repeated independent evolution

of migration in the largest family of bats PLoS ONE 4 e7504Bonvicino CR Otazu IB DrsquoAndrea PS 2002 Karyologic evidence of diversification

of the genus Thrichomys (Rodentia Echimyidae) Cytogenet Genome Res 97200ndash204

Botero A Thompson CK Peacock CS Clode PL Nicholls PK Wayne AF et al2013 Trypanosomes genetic diversity polyparasitism and the population declineof the critically endangered Australian marsupial the brush tailed bettong orwoylie (Bettongia penicillata) Int J Parasitol Parasite Wildl 2 77ndash89

Brandatildeo-Filho SP Brito ME Carvalho FG Ishikawa EA Cupolillo EFloeter-Winter L et al 2003 Wild and synanthropic hosts of Leishmania(Viannia) braziliensis in the endemic cutaneous leishmaniasis locality of AmarajiPernambuco State Brazil Trans R Soc Trop Med Hyg 97 291ndash296

259ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

synanthropic environments being able to colonize different habi-tats in different ecotypes Their refuges include hollow trees thecanopies of palm trees and ceilings of human houses and other ruralbuildings Their high abundance and adaptability to peri-domesticenvironment reinforce the importance of investigating bats alreadyrecognized as reservoirs of other trypanosomatids (Jansen and Roque2010) in the transmission cycles of Leishmania species

5 Conclusions and perspectives

Many decades have passed since the description of Leishmaniaparasites but their epidemiology is still not well understood in partbecause of the human-health focus of most studies Only recentlyinfluenced by the ldquoone healthrdquo approach has the epidemiology ofleishmaniasis started to be evaluated from a broader perspective(Palatnik-de-Sousa and Day 2011)

In the case of human visceral leishmaniasis caused by L infantumthe idea that dogs are the only reservoir of the parasite has led healthauthorities to direct the eradication of seropositive dogs on the basisthat this action was the only way to control this zoonosis In factseveral studies have demonstrated that dogs are epidemiologi-cally important as reservoirs in different localities (reviewed byLainson and Rangel 2005 Dantas-Torres 2009 Quinnell andCourtenay 2009) Nevertheless the participation of other in-fected mammals rather than dogs in the transmission cycle of Linfantum in urban areas was already proposed for cats and opos-sums for example (Pennisi et al 2013 Santiago et al 2007) Thelow effectiveness of dog culling program in Brazil is probably dueto an assemblage of factors most of them related to the lack of astructured surveillance system and include the high interval betweentests and between the positive result and dog elimination the rapidreplacement of susceptible dogs when an infected dog is euthan-ized and the resistance of owners to euthanize their infected dogs(Costa et al 2013 Grimaldi et al 2012 Nunes et al 2008) Someof these localities are very close to sylvatic areas and the possibil-ity that wild mammals may serve as a source of infection to vectorsin peridomiciliary areas has been ignored The putative participa-tion of these mammals is an important additional factor to beconsidered in the proposition of measures to control this zoono-sis This review highlights species from distinct orders that maymaintain and serve as a source of infection to phlebotomine sandfly vectors providing a constant source of re-infection to a peri-domestic transmission system

The reservoirs of the Leishmania species responsible for the cu-taneous forms of human leishmaniasis are still unknown most likelybecause research has focused on the search for a specific reservoirhost as observed for dogs and L infantum These species may bemaintained in the wild by a different strategy as by a few ldquohotspeciesrdquo with high transmissibility competence or most likelythrough a reservoir system an assemblage of mammals with dis-tinct and transient degrees of transmissibility competencethroughout infection This hypothesis agrees with the reservoir def-inition proposed by Ashford (1997) almost 20 years ago This systeminvolves a tradeoff that could explain the evolutionary success ofthese parasite species several individuals are infected but each iscompetent for transmission for only a limited time while retain-ing the infection for long periods of time The sum of multiple shortperiods of infectivity in numerous infected mammals guaranteesthe maintenance and transmission of these Leishmania species

All the links in the epidemiological chain must be clarified as a pre-requisite for effective control strategies (Abdussalan 1959Palatnik-de-Sousa and Day 2011 Shaw 2007) We are still far from un-derstanding the maintenance of different Leishmania species in natureIn this sense the follow-up of naturally infected animals and experi-mental studies using potential reservoirs are essential to improvingunderstanding of the mechanisms of maintenance of these parasites

in their natural hosts In the field the studies should not be restrictedto previously described infected hosts but should be carried out usingan integrated ecological approach to understand the role of each hostspecies in the maintenance and amplification of Leishmania para-sites Priorities include the identification of the factors that influencethe transmissibility competence of the individual mammalian hosts andunderstanding how environmental management could decrease in-fections in humans living close to sylvatic

Over the last century the scientific community has shown thatdifferent and several wild mammal species can become infected withLeishmania species The focus must change to identify species thatmay serve as sources of infection to vectors and amplify enzooticfoci constituting a risk for human transmission To this end a par-adigm shift in research and surveillance of wild reservoirs ofLeishmania is urgently needed This change will depend among otherfactors on understanding reservoir systems and acknowledging theimportance of understanding the role each mammal species playsin maintaining these parasites in nature The factors involved in theamplification of enzootic foci are temporally and regionally spe-cific and understanding some of these factors may support thedevelopment of effective and sustainable strategies for leishmani-asis surveillance

Acknowledgements

AMJ is a ldquoCientista do Nosso Estadordquo provided by FAPERJ andis financially supported by CNPq (ldquoBolsista de Produtividade niacutevel1rdquo CNPq) ALRR is a ldquoJovem Cientista do Nosso Estadordquo providedby FAPERJ The authors have declared that no competing interestsexist

References

Abdussalan M 1959 Significance of ecological studies of wild animal reservoir ofzoonoses Bull World Health Organ 21 179ndash186

Acardi SA Rago MV Liotta DJ Fernandez-Duque E Salomon OD 2013Leishmania (Viannia) DNA detection by PCR-RFLP and sequencing in free-rangingowl monkeys (Aotus azarai azarai) from Formosa Argentina Vet Parasitol 193256ndash259

Aguirre AA Tabor GM 2008 Global factors driving emerging infectious diseasesAnn N Y Acad Sci 1149 1ndash3

Alexander KA Lewis BL Marathe M Eubank S Blackburn JK 2012 Modelingof wildlife-associated zoonoses applications and caveats Vector Borne ZoonoticDis 12 1005ndash1018

Alvar J Velez ID Bern C Herrero M Desjeux P Cano J et al 2012 Leishmaniasisworldwide and global estimates of its incidence PLoS ONE 7 e35671

Arauacutejo A Reinhard K Ferreira LF Pucu E Chieffi PP 2013 Paleoparasitologythe origin of human parasites Arq Neuropsiquiatr 71 722ndash726

Arias JR Naif RD Miles MA de Souza AA 1981 The opossum Didelphismarsupialis (Marsupialia didelphidae) as a reservoir host of Leishmaniabraziliensis guyanensis in the Amazon Basin of Brazil Trans R Soc Trop MedHyg 75 537ndash541

Ashford DA Bozza M Freire M Miranda JC Sherlock I Eulalio C et al 1995Comparison of the polymerase chain reaction and serology for the detection ofcanine visceral leishmaniasis Am J Trop Med Hyg 53 251ndash255

Ashford RW 1996 Leishmaniasis reservoir and their significance in control ClinDermatol 14 523ndash532

Ashford RW 1997 What it takes to be a reservoir host Belg J Zool 127 85ndash90Ashford RW 2000 The leishmaniases as emerging and reemerging zoonoses Int

J Parasitol 30 1269ndash1281Austad SN 1988 The adaptable opossum Sci Am 258 54ndash59Bishop KL 2008 The evolution of flight in bats narrowing the field of plausible

hypotheses Q Rev Biol 83 153ndash169Bisson IA Safi K Holland RA 2009 Evidence for repeated independent evolution

of migration in the largest family of bats PLoS ONE 4 e7504Bonvicino CR Otazu IB DrsquoAndrea PS 2002 Karyologic evidence of diversification

of the genus Thrichomys (Rodentia Echimyidae) Cytogenet Genome Res 97200ndash204

Botero A Thompson CK Peacock CS Clode PL Nicholls PK Wayne AF et al2013 Trypanosomes genetic diversity polyparasitism and the population declineof the critically endangered Australian marsupial the brush tailed bettong orwoylie (Bettongia penicillata) Int J Parasitol Parasite Wildl 2 77ndash89

Brandatildeo-Filho SP Brito ME Carvalho FG Ishikawa EA Cupolillo EFloeter-Winter L et al 2003 Wild and synanthropic hosts of Leishmania(Viannia) braziliensis in the endemic cutaneous leishmaniasis locality of AmarajiPernambuco State Brazil Trans R Soc Trop Med Hyg 97 291ndash296

259ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

Bugge J 1979 Cephalic arterial pattern in New World edentates and Old Worldpangolins with special reference to their phylogenetic relationships andtaxonomy Acta Anat (Basel) 105 37ndash46

Buitrago R Cupolillo E Bastrenta B Le Pont F Martinez E Barnabe C et al2011 PCR-RFLP of ribosomal internal transcribed spacers highlights inter andintra-species variation among Leishmania strains native to La Paz Bolivia InfectGenet Evol 11 557ndash563

Carreira JC da Silva AV de Pita PD Brazil RP 2012 Natural infection of Didelphisaurita (Mammalia marsupialia) with Leishmania infantum in Brazil ParasitVectors 5 111

Chaves LF Hernandez MJ Dobson AP Pascual M 2007 Sources and sinksrevisiting the criteria for identifying reservoirs for American cutaneousleishmaniasis Trends Parasitol 23 311ndash316

Christensen HA de Vasquez AM 1981 Susceptibility of Aotus trivirgatus toLeishmania braziliensis and L mexicana Am J Trop Med Hyg 30 54ndash56

Corredor A Gallego JF Tesh RB Morales A De Carrasquilla CF Young DGet al 1989 Epidemiology of visceral leishmaniasis in Colombia Am J Trop MedHyg 40 480ndash486

Costa DN Codeccedilo CT Silva MA Werneck GL 2013 Culling dogs in scenariosof imperfect control realistic impact on the prevalence of canine visceralleishmaniasis PLoS Negl Trop Dis 7 e2355

Courtenay O Santana EW Johnson PJ Vasconcelos IA Vasconcelos AW 1996Visceral leishmaniasis in the hoary zorro Dusicyon vetulus a case of mistakenidentity Trans R Soc Trop Med Hyg 90 498ndash502

Courtenay O Quinnell RJ Garcez LM Shaw JJ Dye C 2002 Infectiousness ina cohort of Brazilian dogs why culling fails to control visceral leishmaniasis inareas of high transmission J Infect Dis 186 1314ndash1320

Courtenay O Carson C Calvo-Bado L Garcez LM Quinnell RJ 2014Heterogeneities in Leishmania infantum infection using skin parasite burdensto identify highly infectious dogs PLoS Negl Trop Dis 9 e2583

Cuba CA Ferreira V Bampi M Magalhaes A Marsden PD Vexenat A et al1990 Experimental infection with Leishmania (Viannia) braziliensis and Leishmania(Leishmania) amazonensis in the marmoset Callithrix penicillata (PrimatesCallithricidae) Mem Inst Oswaldo Cruz 85 459ndash467

Cuba-Cuba CA Marsden PD 1993 Marmosets in New World leishmaniasisresearch Medicina (B Aires) 53 419ndash423

Curi NH Miranda I Talamoni SA 2006 Serologic evidence of Leishmania infectionin free-ranging wild and domestic canids around a Brazilian National Park MemInst Oswaldo Cruz 101 99ndash101

de Araujo VA Boite MC Cupolillo E Jansen AM Roque AL 2013 Mixedinfection in the anteater Tamandua tetradactyla (Mammalia pilosa) from ParaState Brazil Trypanosoma cruzi T rangeli and Leishmania infantum Parasitology140 455ndash460

de Freitas TP DrsquoAndrea PS de Paula DA Nakazato L Dutra V Bonvicino CRet al 2012 Natural infection of Leishmania (Viannia) braziliensis in Mus musculuscaptured in Mato Grosso Brazil Vector Borne Zoonotic Dis 12 81ndash83

Dahroug MA Almeida AB Sousa VR Dutra V Turbino NC Nakazato L et al2010 Leishmania (Leishmania) chagasi in captive wild felids in Brazil Trans RSoc Trop Med Hyg 104 73ndash74

Dahroug MA Almeida AB Sousa VR Dutra V Guimaraes LD Soares CE et al2011 The first case report of Leishmania (leishmania) chagasi in Panthera leoin Brazil Asian Pac J Trop Biomed 1 249ndash250

Dantas-Torres F 2009 Canine leishmaniosis in South America Parasit Vectors 2(Suppl 1) S1

Dantas-Torres F Brandatildeo-Filho SP 2006 Visceral leishmaniasis in Brazil revisitingparadigms of epidemiology and control Rev Inst Med Trop S Paulo 48 151ndash156

De Lima H De Guglielmo Z Rodriguez A Convit J Rodriguez N 2002 Cottonrats (Sigmodon hispidus) and black rats (Rattus rattus) as possible reservoirs ofLeishmania spp in Lara State Venezuela Mem Inst Oswaldo Cruz 97 169ndash174

De Lima H Rodriguez N Barrios MA Avila A Canizales I Gutierrez S 2008Isolation and molecular identification of Leishmania chagasi from a bat (Carolliaperspicillata) in northeastern Venezuela Mem Inst Oswaldo Cruz 103 412ndash414

De Tommasi AS Otranto D Dantas-Torres F Capelli G Breitschwerdt EBde Caprariis D 2013 Are vector-borne pathogen co-infections complicating theclinical presentation in dogs Parasit Vectors 6 97

Deane LM Deane MP 1955 Observaccedilotildees preliminares sobre a importacircnciacomparativa do homem do catildeo e da raposa (Lycalopex vetulus) como reservatoacuteriosda Leishmania donovani em aacutereas endecircmicas de Calazar no Cearaacute Hospital 4879ndash98

Dedet JP Gay F Chatenay G 1989 Isolation of Leishmania species from wildmammals in French Guiana Trans R Soc Trop Med Hyg 83 613ndash615

Desjeux P 2004 Leishmaniasis current situation and new perspectives CompImmunol Microbiol Infect Dis 27 305ndash318

Disney RHL 1968 Observations on a zoonosis leishmaniasis in British HondurasJ Appl Ecol 5 1ndash59

Emmons LH Feer F 1997 Neotropical Rainforest Mammals A Field GuideUniversity of Chicago Press Chicago

Figueiredo FB Gremiao ID Pereira SA Fedulo LP Menezes RC Balthazar DAet al 2008 First report of natural infection of a bush dog (Speothos venaticus)with Leishmania (Leishmania) chagasi in Brazil Trans R Soc Trop Med Hyg 102200ndash201

Flynn JJ Wyss AR 1998 Recent advances in South American mammalianpaleontology Trends Ecol Evol 13 449ndash455

Forattini OP Pattoli DBG Rabello EX Ferreira OA 1972 Infecccedilotildees naturais demamiacuteferos silvestres em aacuterea endecircmica de leishmaniose tegumentar do Estadode Satildeo Paulo Bras Rev Saude Publica 6 255ndash261

Garcez LM Goto H Ramos PK Brigido MC Gomes PA Souza RA et al 2002Leishmania (Leishmania) amazonensis-induced cutaneous leishmaniasis in theprimate Cebus apella a model for vaccine trials Int J Parasitol 32 1755ndash1764

Gentile B Le Pont F Pajot FX Besnard R 1981 Dermal leishmaniasis in FrenchGuiana the sloth (Choloepus didactylus) as a reservoir host Trans R Soc TropMed Hyg 75 612ndash613

Giorgio S 1995 Moderna visatildeo da evoluccedilatildeo da virulecircncia Rev Saude Publica 29398ndash402

Grimaldi G Jr 2008 The utility of rhesus monkey (Macaca mulatta) and othernon-human primate models for preclinical testing of Leishmania candidatevaccines Mem Inst Oswaldo Cruz 103 629ndash644

Grimaldi G Jr Momen H Naiff RD Mahon-Pratt D Barrett TV 1991Characterization and classification of leishmanial parasites from humans wildmammals and sand flies in the Amazon region of Brazil Am J Trop Med Hyg44 645ndash661

Grimaldi G Jr Kreutzer RD Hashiguchi Y Gomez EA Mimory T Tesh RB1992 Description of Leishmania equatorensis sp n (Kinetoplastidatrypanosomatidae) a new parasite infecting arboreal mammals in Ecuador MemInst Oswaldo Cruz 87 221ndash228

Grimaldi G Jr Teva A Santos CB Ferreira AL Falqueto A 2012 The effect ofremoving potentially infectious dogs on the numbers of canine Leishmaniainfantum infections in an endemic area with high transmission rates Am J TropMed Hyg 86 966ndash971

Haydon DT Cleaveland S Taylor LH Laurenson MK 2002 Identifying reservoirsof infection a conceptual and practical challenge Emerg Infect Dis 8 1468ndash1473

Herrer A 1971 Leishmania hertigi spn from the tropical porcupine Coendourothschildi Thomas J Parasitol 57 626ndash629

Herrer A Christensen HA 1976 Epidemiological patterns of cutaneousleishmaniasis in Panama III Endemic persistence of the disease Am J Trop MedHyg 25 54ndash58

Herrer A Christensen HA Beumer RJ 1973 Reservoir host of cutaneousleishmaniasis among Panamanian forest mammals Am J Trop Med Hyg 22585

Humberg RM Oshiro ET Cruz MS Ribolla PE Alonso DP Ferreira AM et al2012 Leishmania chagasi in opossums (Didelphis albiventris) in an urban areaendemic for visceral leishmaniasis Campo Grande Mato Grosso do Sul BrazilAm J Trop Med Hyg 87 470ndash472

Ikeda-Garcia FA Feitosa MM 2006 Meacutetodos de diagnoacutestico da leishmaniosevisceral canina Clin Vet 62 32ndash38

Jansa SA Barker FK Voss RS 2014 The early diversification history of didelphidmarsupials a window into South Americarsquos ldquosplendid isolationrdquo Evolution 68684ndash695

Jansen AM Roque ALR 2010 Domestic and Wild Mammalian Reservoirs InTelleria J Tibyarenc M (Eds) American Trypanosomiasis ndash Chagas DiseaseElsevier London pp 249ndash276

Jones G Teeling EC 2006 The evolution of echolocation in bats Trends Ecol Evol21 149ndash156

Jones KE Patel NG Levy MA Storeygard A Balk D Gittleman JL et al 2008Global trends in emerging infectious diseases Nature 451 990ndash993

Kerr SF McHugh CP Dronen NO Jr 1995 Leishmaniasis in Texas prevalenceand seasonal transmission of Leishmania mexicana in Neotoma micropus Am JTrop Med Hyg 53 73ndash77

Kerr SF Emmons LH Melby PC Liu C Perez LE Villegas M et al 2006Leishmania amazonensis infections in Oryzomys acritus and Oryzomys nitidus fromBolivia Am J Trop Med Hyg 75 1069ndash1073

Kreutzer RD Corredor A Grimaldi G Jr Grogl M Rowton ED Young DG et al1991 Characterization of Leishmania colombiensis sp n (Kinetoplastidatrypanosomatidae) a new parasite infecting humans animals and phlebotominesand flies in Colombia and Panama Am J Trop Med Hyg 44 662ndash675

Lachaud L Machergui-Hammami S Chabbert E Dereure J Dedet JP BastienP 2002 Comparison of six PCR methods using peripheral blood for detectionof canine visceral leishmaniasis J Clin Microbiol 40 210ndash215

Lainson R Rangel EF 2005 Lutzomyia longipalpis and the eco-epidemiology ofAmerican visceral leishmaniasis with particular reference to Brazil a reviewMem Inst Oswaldo Cruz 100 811ndash827

Lainson R Shaw JJ 1989 Leishmania (Viannia) naiffi sp n a parasite of thearmadillo Dasypus novemcinctus in Amazonian Brazil Ann Parasitol Hum Comp64 3ndash9

Lainson R Strangways-Dixon J 1964 The epidemiology of dermal Leishmaniasisin British Honduras Trans R Soc Trop Med Hyg 58 136ndash153

Lainson R Shaw JJ Ward RD Ready PD Naiff RD 1979 Leishmaniasis in BrazilXIII Isolation of Leishmania from armadillos (Dasypus novemcinctus) andobservations on the epidemiology of cutaneous leishmaniasis in north Para StateTrans R Soc Trop Med Hyg 73 239ndash242

Lainson R Shaw JJ Povoa M 1981a The importance of edentates (sloths andanteaters) as primary reservoirs of Leishmania braziliensis guyanensis causativeagent of ldquopianboisrdquo in north Brazil Trans R Soc Trop Med Hyg 75 611ndash612

Lainson R Shaw JJ Ready PD Miles MA Povoa M 1981b Leishmaniasis inBrazil XVI Isolation and identification of Leishmania species from sandflies wildmammals and man in north Para State with particular reference to L braziliensisguyanensis causative agent of ldquopian-bois Trans R Soc Trop Med Hyg 75530ndash536

Lainson R Braga RR de Souza AA Povoa MM Ishikawa EA Silveira FT 1989Leishmania (Viannia) shawi sp n a parasite of monkeys sloths and procyonidsin Amazonian Brazil Ann Parasitol Hum Comp 64 200ndash207

260 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262

Lainson R Dye C Shaw JJ Macdonald DW Courtenay O Souza AA et al 1990Amazonian visceral leishmaniasisndashdistribution of the vector Lutzomyia longipalpis(Lutz amp Neiva) in relation to the fox Cerdocyon thous (linn) and the efficiencyof this reservoir host as a source of infection Mem Inst Oswaldo Cruz 85135ndash137

Lainson R Ishikawa EA Silveira FT 2002 American visceral leishmaniasis wildanimal hosts Trans R Soc Trop Med Hyg 96 630ndash631

Lampo M Feliciangeli MD Marquez LM Bastidas C Lau P 2000 A possiblerole of bats as a blood source for the Leishmania vector Lutzomyia longipalpis(Diptera psychodidae) Am J Trop Med Hyg 62 718ndash719

Le Pont F Mouchet J Desjeux P 1989 Leishmaniasis in Bolivia VII Infection ofsentinel porcupines (Coendou prehensilis L) by Leishmania (Le) chagasi MemInst Oswaldo Cruz 84 575

Lima BS Dantas-Torres F de Carvalho MR Marinho-Junior JF de Almeida ELBrito ME et al 2013 Small mammals as hosts of Leishmania spp in a highlyendemic area for zoonotic leishmaniasis in North-Eastern Brazil Trans R SocTrop Med Hyg 107 592ndash597

Lima L Silva FM Neves L Attias M Takata CS Campaner M et al 2012aEvolutionary insights from bat trypanosomes morphological developmental andphylogenetic evidence of a new species Trypanosoma (Schizotrypanum) erneyisp nov in African bats closely related to Trypanosoma (Schizotrypanum) cruziand allied species Protist 163 856ndash872

Lima VM Fattori KR Michelin AF Nogueira FS Souza LO 2009 Evidence ofLeishmania spp antibodies and DNA in bush dogs (Speothos venaticus) in BrazilJ Zoo Wildl Med 40 91ndash94

Lima VM Santiago ME Sanches LC Lima BD 2012b Molecular diagnosis ofLeishmania amazonensis in a captive spider monkey in Bauru Sao Paulo BrazilJ Zoo Wildl Med 43 943ndash945

Lisboa CV Mangia RH Luz SL Kluczkovski A Jr Ferreira LF Ribeiro CT et al2006 Stable infection of primates with Trypanosoma cruzi I and II Parasitology133 603ndash611

Llanos-Cuentas EA Roncal N Villaseca P Paz L Ogusuku E Perez JE et al1999 Natural infections of Leishmania peruviana in animals in the Peruvian AndesTrans R Soc Trop Med Hyg 93 15ndash20

Lujan R Chapman WL Jr Hanson WL Dennis VA 1986 Leishmania braziliensisdevelopment of primary and satellite lesions in the experimentally infected owlmonkey Aotus trivirgatus Exp Parasitol 61 348ndash358

Luppi MM Malta MC Silva TM Silva FL Motta RO Miranda I et al2008 Visceral leishmaniasis in captive wild canids in Brazil Vet Parasitol 155146ndash151

Machado MI Milder RV Pacheco RS Silva M Braga RR Lainson R 1994Naturally acquired infections with Leishmania enriettii Muniz and Medina 1948in guinea-pigs from Satildeo Paulo Brazil Parasitology 109 (Pt 2) 135ndash138

Madeira MF Figueiredo FB Pinto AG Nascimento LD Furtado MMouta-Confort E et al 2009 Parasitological diagnosis of canine visceralleishmaniasis is intact skin a good target Res Vet Sci 87 260ndash262

Malta MC Tinoco HP Xavier MN Vieira AL Costa EA Santos RL 2010Naturally acquired visceral leishmaniasis in non-human primates in Brazil VetParasitol 169 193ndash197

Mancianti F Falcone ML Giannelli C Poli A 1995 Comparison between anenzyme-linked immunosorbent assay using a detergent-soluble Leishmaniainfantum antigen and indirect immunofluorescence for the diagnosis of canineleishmaniosis Vet Parasitol 59 13ndash21

Marcondes M Biondo AW Gomes AA Silva AR Vieira RF Camacho AA et al2011 Validation of a Leishmania infantum ELISA rapid test for serological diagnosisof Leishmania chagasi in dogs Vet Parasitol 175 15ndash19

McHugh CP Thies ML Melby PC Yantis LD Jr Raymond RW Villegas MDet al 2003 Short report a disseminated infection of Leishmania mexicana inan eastern woodrat Neotoma floridana collected in Texas Am J Trop Med Hyg69 470ndash472

Mendonca MG de Brito ME Rodrigues EH Bandeira V Jardim ML Abath FG2004 Persistence of leishmania parasites in scars after clinical cure of Americancutaneous leishmaniasis is there a sterile cure J Infect Dis 189 1018ndash1023

Mettler M Grimm F Capelli G Camp H Deplazes P 2005 Evaluation ofenzyme-linked immunosorbent assays an immunofluorescent-antibody test andtwo rapid tests (immunochromatographic-dipstick and gel tests) for serologicaldiagnosis of symptomatic and asymptomatic Leishmania infections in dogs J ClinMicrobiol 43 5515ndash5519

Miller E Huppert A 2013 The effects of host diversity on vector-borne diseasethe conditions under which diversity will amplify or dilute the disease risk PLoSONE 8 e80279

Mills JN Childs JE 1998 Ecologic studies of rodent reservoirs their relevancefor human health Emerg Infect Dis 4 529ndash537

Mimori T Grimaldi G Jr Kreutzer RD Gomez EA Mahon-Pratt D Tesh RBet al 1989 Identification using isoenzyme electrophoresis and monoclonalantibodies of Leishmania isolated from humans and wild animals of EcuadorAm J Trop Med Hyg 40 154ndash158

Miranda F Costa AM 2006 Xenarthra In Cubas ZS Silva JCR Catatildeo-Dias JL(Eds) Tratado de Animais Selvagens Roca Satildeo Paulo pp 402ndash414

Moller-Krull M Delsuc F Churakov G Marker C Superina M Brosius J et al2007 Retroposed elements and their flanking regions resolve the evolutionaryhistory of xenarthran mammals (armadillos anteaters and sloths) Mol Biol Evol24 2573ndash2582

Naiff RD Freitas RA Naiff MF Arias JR Barrett TV Momen H et al 1991Epidemiological and nosological aspects of Leishmania naiffi Lainson amp Shaw1989 Mem Inst Oswaldo Cruz 86 317ndash321

Nery Guimaratildees F 1951 Comportamento da Leishmania braziliensis Vianna 1911em hamsters (Cricetus [Mesocricetus] auratus) Hospital 40 25ndash46

Noireau F Diosque P Jansen AM 2009 Trypanosoma cruzi adaptation to itsvectors and its hosts Vet Res 40 26

Nunes CM Lima VM Paula HB Perri SH Andrade AM Dias FE et al 2008Dog culling and replacement in an area endemic for visceral leishmaniasis inBrazil Vet Parasitol 153 19ndash23

Olifiers N Gentile R Fiszon JT 2005 Relation between small-mammal speciescomposition and anthropic variables in the Brazilian Atlantic Forest Braz J Biol65 495ndash501

Oliveira FS Pirmez C Pires MQ Brazil RP Pacheco RS 2005 PCR-baseddiagnosis for detection of Leishmania in skin and blood of rodents from anendemic area of cutaneous and visceral leishmaniasis in Brazil Vet Parasitol129 219ndash227

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Palatnik-de-Sousa CB Day MJ 2011 One Health the global challenge of epidemicand endemic leishmaniasis Parasit Vectors 4 197

Pennisi MG Hartmann K Lloret A Addie D Belak S Boucraut-Baralon C et al2013 Leishmaniosis in cats ABCD guidelines on prevention and managementJ Feline Med Surg 15 638ndash642

Peterson NE Vexemat JA Rosa ACOC Lago PRL 1988 Isolation of Leishmania(Viannia) braziliensis from the rodent Nectomys squamipes captured in Bahia BrazilMem Inst Oswaldo Cruz 83 (S1) 28

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Quaresma PF Rego FD Botelho HA da Silva SR Moura Junior AJ Teixeira NetoRG et al 2011 Wild synanthropic and domestic hosts of Leishmania in anendemic area of cutaneous leishmaniasis in Minas Gerais State Brazil Trans RSoc Trop Med Hyg 105 579ndash585

Quinnell RJ Courtenay O 2009 Transmission reservoir hosts and control ofzoonotic visceral leishmaniasis Parasitology 136 1915ndash1934

Quintal AP Ribeiro ES Rodrigues FP Rocha FS Floeter-Winter LM Nunes CM2011 Leishmania spp in Didelphis albiventris and Micoureus paraguayanus(Didelphimorphia didelphidae) of Brazil Vet Parasitol 176 112ndash119

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Rocha FL Roque AL de Lima JS Cheida CC Lemos FG de Azevedo FC et al2013 Trypanosoma cruzi infection in neotropical wild carnivores (Mammaliacarnivora) at the top of the T cruzi transmission chain PLoS ONE 8 e67463

Rocha NM Melo MN Baba EH Dias M Michalick MS Da Costa CA et al1988 Leishmania braziliensis braziliensis isolated from Akodon arviculoides capturedin Caratinga Minas Gerais Brazil Trans R Soc Trop Med Hyg 82 68

Roque AL Cupolillo E Marchevsky RS Jansen AM 2010 Thrichomys laurentius(Rodentia Echimyidae) as a putative reservoir of Leishmania infantum and Lbraziliensis patterns of experimental infection PLoS Negl Trop Dis 4 e589

Rotureau B 2006 Ecology of the leishmania species in the Guianan ecoregioncomplex Am J Trop Med Hyg 74 81ndash96

Salam MA Mondal D Kabir M Ekram AR Haque R 2010 PCR for diagnosisand assessment of cure in kala-azar patients in Bangladesh Acta Trop 113 52ndash55

Santiago ME Vasconcelos RO Fattori KR Munari DP Michelin AF Lima VM2007 An investigation of Leishmania spp in Didelphis spp from urban andperi-urban areas in Bauru (Sao Paulo Brazil) Vet Parasitol 150 283ndash290

Savani ES de Almeida MF de Oliveira Camargo MC DrsquoAuria SR Silva MMde Oliveira ML et al 2010 Detection of Leishmania (Leishmania) amazonensisand Leishmania (Leishmania) infantum chagasi in Brazilian bats Vet Parasitol 1685ndash10

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Shapiro JT da Costa Lima Junior MS Dorval ME de Oliveira FA Cepa MatosMF Bordignon MO 2013 First record of Leishmania braziliensis presencedetected in bats Mato Grosso do Sul southwest Brazil Acta Trop 128 171ndash174

Shaw J 2007 The leishmaniasesndashsurvival and expansion in a changing world Amini-review Mem Inst Oswaldo Cruz 102 541ndash547

Sherlock IA 1996 Ecological interactions of visceral leishmaniasis in the state ofBahia Brazil Mem Inst Oswaldo Cruz 91 671ndash683

Sherlock IA Miranda JC Sadigursky M Grimaldi G Jr 1984 Natural infectionof the opossum Didelphis albiventris (Marsupialia Didelphidae) with Leishmaniadonovani in Brazil Mem Inst Oswaldo Cruz 79 511

Silva DA Madeira MF Barbosa Filho CJ Schubach EY Barros JH FigueiredoFB 2013 Leishmania (Leishmania) hertigi in a porcupine (Coendou sp) foundin Brasilia Federal District Brazil Rev Bras Parasitol Vet 22 297ndash299

Silva ES Pirmez C Gontijo CM Fernandes O Brazil RP 2000 Visceralleishmaniasis in the crab-eating fox (Cerdocyon thous) in south-east Brazil VetRec 147 421ndash422

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Silva JCR Adania CH 2007 Carnivora ndash felidae (Onccedila Succediluarana JaguatiricaGato-do-mato) In Cubas ZS Silva JCR Catatildeo-Dias JL (Eds) Tratado deAnimais Selvagens Roca Satildeo Paulo pp 505ndash546

Silveira FT Lainson R Shaw JJ Braga RR Ishikawa EE Souza AA 1991Cutaneous leishmaniasis in Amazonia isolation of Leishmania (Viannia) lainsoni

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from the rodent Agouti paca (Rodentia dasyproctidae) in the state of Para BrazilRev Inst Med Trop Sao Paulo 33 18ndash22

Souza NP Almeida AB Freitas TP Paz RC Dutra V Nakazato L et al 2010Leishmania (Leishmania) infantum chagasi in wild canids kept in captivity in theState of Mato Grosso Rev Soc Bras Med Trop 43 333ndash335

Telleria J Bosseno MF Tarifa T Buitrago R Martinez E Torrez M et al 1999Putative reservoirs of Leishmania amazonensis in a Sub-Andean focus of Boliviaidentified by kDNA-polymerase chain reaction Mem Inst Oswaldo Cruz 94 5ndash6

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Travi BL Osorio Y Becerra MT Adler GH 1998a Dynamics of Leishmania chagasiinfection in small mammals of the undisturbed and degraded tropical dry forestsof northern Colombia Trans R Soc Trop Med Hyg 92 275ndash278

Travi BL Osorio Y Guarin N Cadena H 1998b Leishmania (Leishmania) chagasiclinical and parasitological observations in experimentally infected Didelphismarsupialis reservoir of New World visceral leishmaniasis Exp Parasitol 8873ndash75

Travi BL Arteaga LT Leon AP Adler GH 2002 Susceptibility of spiny rats(Proechimys semispinosus) to Leishmania (Viannia) panamensis and Leishmania(Leishmania) chagasi Mem Inst Oswaldo Cruz 97 887ndash892

Troncarelli MZ Camargo JB Machado JG Lucheis SB Langoni H 2009Leishmania spp andor Trypanosoma cruzi diagnosis in dogs from endemic andnonendemic areas for canine visceral leishmaniasis Vet Parasitol 164 118ndash123

Van Wynsberghe NR Canto-Lara SB Mian-Centeno AG Itza-Ortiz MFAndrade-Narvaez FJ 2000 Retention of Leishmania (Leishmania) mexicana innaturally infected rodents from the State of Campeche Mexico Mem InstOswaldo Cruz 95 595ndash600

Van Wynsberghe NR Canto-Lara SB Sosa-Bibiano EI Rivero-Cardenas NAAndrade-Narvaez FJ 2009 Comparison of small mammal prevalence ofLeishmania (Leishmania) mexicana in five foci of cutaneous leishmaniasis in theState of Campeche Mexico Rev Inst Med Trop Sao Paulo 51 87ndash94

Vasconcelos IA Vasconcelos AW Fe Filho NM Queiroz RG Santana EW BozzaM et al 1994 The identity of Leishmania isolated from sand flies and vertebratehosts in a major focus of cutaneous leishmaniasis in Baturiteacute northeastern BrazilAm J Trop Med Hyg 50 158ndash164

Verona CES Pissinatti A 2007 Primatas do novo mundo (Sagui Macaco-pregoMacaco-aranha Bugio) In Cubas ZS Silva JCR Catatildeo-Dias JL (Eds) Tratadode Animais Selvagens Roca Satildeo Paulo pp 358ndash377

Vouldoukis I Ogunkolade W Strazielle L Ploton I Monjour L 1986 Susceptibilityof Cebus nigrivittatus to Leishmania infantum J Parasitol 72 472ndash473

WHO - World Health Organization 1990 Control of the leishmaniasis Technicalreport series 793

Wilson DE Reeder DM 2005 Mammal Species of the World A Taxonomic andGeographic Reference Johns Hopkins University Press Baltimore Maryland

Woolhouse ME Dye C Etard JF Smith T Charlwood JD Garnett GP et al1997 Heterogeneities in the transmission of infectious agents implications forthe design of control programs Proc Natl Acad Sci USA 94 338ndash342

Woolhouse ME Taylor LH Haydon DT 2001 Population biology of multihostpathogens Science 292 1109ndash1112

Zeledon R McPherson B Ponce C 1977 Isolation of Leishmania braziliensis froma wild rodent in Costa Rica Am J Trop Med Hyg 26 1044ndash1045

262 ALR Roque AM JansenInternational Journal for Parasitology Parasites and Wildlife 3 (2014) 251ndash262