Rickettsioses in Sub-Saharan Africa

PHILIPPE PAROLA

Unite des Rickettsies, CNRS UMR 6020 IFR 48, WHO Collaborative Center forRickettsial Reference and Research, Faculte de Medecine, 13385 MarseilleCedex 5, France

ABSTRACT: Although rickettsioses are among the oldest known vector-borne zoonoses, several species or subspecies of rickettsias have beenidentified in recent years as emerging pathogens throughout the worldincluding in sub-Saharan Africa. To date, six tick-borne spotted fevergroup pathogenic rickettsias are known to occur in sub-Saharan Africa,including Rickettsia conorii conorii, the agent of Mediterranean spottedfever; R. conorii caspia, the agent of Astrakhan fever; R. africae, the agentof African tick-bite fever; R. aeschlimannii; R. sibirica mongolitimonae;and R. massiliae. On the other hand, fleas have long been known as vectorsof the ubiquitous murine typhus, a typhus group rickettsiosis induced byR. typhi. However, a new spotted fever rickettsia, R. felis, has also beenfound to be associated with fleas, to be a human pathogen, and to bepresent in sub-Saharan Africa. Finally, R. prowazekii the agent of louse-borne epidemic typhus continues to strikes tens to hundreds of thousandsof persons who live in Sub-Saharan with civil war, famine and poorconditions. We present an overview of these rickettsioses occurring insub-Saharan Africa, focusing on the epidemiological aspects of emergingdiseases.

KEYWORDS: rickettsioses; ticks; fleas; lice; Rickettsia africae; Rickettsiaconorii; Rickettsia aeschlimannii; Rickettsia sibirica mongolitimonae;Rickettsia prowazekii; Rickettsia felis; Rickettsia massiliae

Rickettsial diseases are zoonoses caused by obligate intracellular bacteriagrouped in the order Rickettsiales. Although bacteria of this order were first de-scribed as short, gram-negative rods that retained basic fuchsin when stained bythe method of Gimenez, the taxonomy of rickettsias has undergone significantreorganization in the last decade. For example, Coxiella burnetii, the agent ofQ fever has been removed recently from the Rickettsiales.1 The classificationwithin the Rickettsiales, including at the species level, continues to be modi-fied as new data become available.2 To date, three groups of diseases are stillcommonly classified as rickettsial diseases. These include (a) rickettsioses on

This paper was presented as an oral communication at ICRRD in Logrono.Address for correspondence: P. Parola, Unite des Rickettsies, CNRS UMR 6020 IFR 48, WHO

Collaborative Center for Rickettsial Reference and Research, Faculte de Medecine, 27 Bd Jean Moulin,13385 Marseille Cedex 5, France. Voice: 33-4-91-32-43-75; fax: 33-4-91-83-03-90.

e-mail: philippe.parola@medecine.univ-mrs.fr

Ann. N.Y. Acad. Sci. 1078: 42–47 (2006). C© 2006 New York Academy of Sciences.doi: 10.1196/annals.1374.005

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account of bacteria of the genus Rickettsia, including the spotted fever groupand the typhus group rickettsiae, (b) ehrlichioses and anaplasmoses on accountof bacteria within the family Anaplasmataceae that has been reorganized, and(c) scrub typhus on account of Orientia tsutsugamushi. As scrub typhus isprevalent in the Asia–Pacific region, it will not been discussed in this articlefocusing on sub-Saharan Africa.

Six tick-borne spotted fever group rickettsioses are currently known to occurin sub-Saharan Africa. Indeed, it has now been almost 15 years since Rickettsiaafricae, the agent of African tick-bite fever (ATBF) was rediscovered in sub-Saharan Africa, and definitely distinguished from Mediterranean spotted fever(MSF) on account of R. conorii conorii.3 In southern Africa Amblyommahebraeum, a tick of large ruminants and wildlife species is a recognized vectorand reservoir of R. africae. R. africae has also been detected in A. variegatumthroughout west, central, and eastern sub-Saharan Africa, and in A. lepidumfrom the Sudan.4 Infection rates of the ticks are remarkably high. BecauseAmblyomma readily bite humans, cases of ATBF often occur in clusters andpatients often present with multiple inoculation eschars. However, despite highseroprevalence to R. africae among native Africans, nearly all acute cases ofATBF described in the literature (more than 250) have occurred in European orAmerican travelers.4 Recently, however, cases of ATBF were documented byserology and molecular techniques among indigenous patients in Cameroon.5

Although MSF is endemic in the Mediterranean area where it is transmittedby the brown dog tick Rhipicephalus sanguineus, R. conorii conorii has beenpoorly detected in sub-Saharan Africa (South Africa, Zimbabwe, and Kenya).However, a strain of the closely related R. conorii caspia, the agent of Astrakhanfever, was obtained recently from a patient from Chad.6

Three more tick-borne pathogenic rickettsiae are now known to occur in sub-Saharan Africa. R. aeschlimannii had been first characterized as a new spot-ted fever group rickettsia following its isolation from Hyalomma marginatummarginatum ticks in Morocco in 1997.7 Since that time, it has also been de-tected and/or isolated in H. m. rufipes in Zimbabwe, Niger, and Mali, as well asin Hyalomma m. marginatum in southern Europe. Preliminary data have sug-gested that transstadial and transovarial transmission of the rickettsia occursin these ticks, suggesting that the geographic distribution of R. aeschlimanniiwould be, at least that of H. m. marginatum (southern Europe and northernAfrica) and H. m. rufipes (Sahelian and southern Africa).8 Other tick speciesincluding Rh. appendiculatus have also been implicated in the transmissionof R. aeschlimannii.9,10 The pathogenic role of this rickettsia was achieved in2002, when the first human infection was reported in a patient returning fromMorocco to France.11 A second case was reported in a patient returning froma hunting and fishing trip in South Africa.10

R. sibirica mongolitimonae (formally named R. mongolotimonae) was re-ported in sub-Saharan Africa in 2001, when it was detected in Hyalommatruncatum in Niger.12 This rickettsia had been first isolated in Hyalomma

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asiaticum ticks collected in Inner Mongolia in China in 1991. In 1996 thefirst human cases were reported in Marseille, southern France, where thevector is still unknown.13 In 2004 the first proven human infection with R.sibirica mongolitimonae in sub-Saharan Africa was reported in a constructionworker, working in South Africa’s Northern Province.14 Although migratorybirds have been suggested to play a role in the epidemiology of this emerg-ing disease, detection of R. sibirica mongolitimonae in Hyalomma spp. inMongolia and Africa also suggests a possible association of this rickettsiawith ticks of this genus. On the basis of evaluation of a total of nine cases(France, Algeria, and South Africa), specific characteristics include the oc-casional findings, alone or in combination, of multiple eschars and draininglymph nodes, and a lymphangitis that extends from the inoculation eschar to thedraining node. These particular clinical features of this new rickettsiosis haveled to the moniker, “lymphangitis-associated rickettsiosis” (LAR).13 Finally, R.massiliae has recently been recognized as a human pathogen.15 This rickettsia,which was first isolated in Europe, has been also detected in Africa in Rh. mun-samae, Rh. lunulatus, and Rh. sulcatus in the central African Republic and inRh. muhsamae collected on Cattle in Mali.

On the other hand, Rickettsia prowazekii the agent of louse-borne epidemictyphus continues to strikes tens to hundreds of thousands of persons who livein sub-Saharan with civil war, famine, and poor conditions. The most recentoutbreak (and the largest since World War II) has been observed in Burundiin the 1990s during the civil war.16 The Unite des Rickettsies was involved inthe surveillance of the outbreak. Lice were collected on three occasions (1998,2000, and 2001) after the outbreak had been controlled.17 They were shippedto the laboratory and tested by polymerase chain reaction (PCR). Althoughthey were negative for R. prowazekii DNA in 1998 and 2000 as a result of theadministration of doxycycline to patients, the persistence of the vector enabledthe spread of R. prowazekii from human carriers back into the louse population.Indeed, in 2001, 21% of lice from refugee camps in the same areas of Burundias sampled earlier were shown to be positive by PCR for R. prowazekii. Furthersamples thereafter submitted to the Unite des Rickettsies indicated that a typhusoutbreak was developing in refugee camps in Burundi. Also, R. prowazekii wasdetected in 7% of body lice collected in 2001 from a jail in Rwanda.17 At thattime, the country was host to 300,000 refugees from the January 2002 eruptionof the Nyiragongo volcano.

Fleas are also known vectors of rickettsioses in sub-Saharan Africa. Theyhave been historically associated with the transmission of the ubiquitousmurine typhus, a typhus group rickettsiosis induced by Rickettsia typhi andtransmitted by the rat fleas Xenopsylla cheopis.18 In sub-Saharan Africa, theprevalence of antibodies against R. typhi in humans is higher in costal ar-eas where rats are prevalent. More recently, fleas have been involved in thecycle of Rickettsia felis, an emerging pathogen belonging to the spotted fevergroup of Rickettsia.19 Arguments on the pathogenicity of R. felis for humans

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were provided starting 2000.20 At that time, three patients with fever rash werediagnosed with R. felis infection by specific PCR of blood or skin and a sero-conversion to rickettsial antigens.21 Serological evidence of R. felis infectionhas also been shown in patients from France and Brazil. Moreover, molec-ular documentation was obtained in the serum of one Brazilian patient.22 In2002 two typical cases of rickettsial spotted fever including generalized macu-lopapular rash and a black eschar were reported in an adult couple in Germany.R. felis infections were documented by serology for both patients and by de-tection of R. felis DNA in the woman’s sera.23 Finally, the first case in Asia ofR. felis infection was recently documented by serology in Thailand.24 How-ever, to date, few confirmed cases of the so-called flea-borne spotted feverhave been described throughout the world. R. felis has been detected in fleasthroughout the world including sub-Saharan Africa (Ethiopia Gabon). Speciesof fleas that have been associated with R. felis include Ctenocephalides felis,C. canis, Pulex irritans, and more recently Archeopsylla erinacei.25 The roleof mammals, including cats, dogs, rodents, and hedgehogs, in the life cycleand circulation of R. felis is still unclear, in sub-Saharan Africa and elsewhere.

Finally, human ehrlichioses and anaplasmosis have been suspected to occurin sub-Saharan Africa. However, serological cross-reactivity has been foundbetween the agents of human ehrlichioses and members of Anaplasmataceaeof veterinary importance, which are widely distributed in Africa.26 To date,then, there is no definitive evidence for the presence of human ehrlichioses oranaplasmosis in Africa.

Still only little is known about rickettsial diseases in sub-Saharan Africa.Most of the sub-Saharan African countries lack specific laboratory facilitiesfor the diagnosis of rickettsial diseases. However, many emerging diseases havebeen reported in the recent years. Much of the information on the epidemiol-ogy of the diseases has been obtained in first-world laboratories that promoteinternational cooperation and have well-developed facilities. Similarly, dataon the clinical aspects of the diseases have often been derived from infectedvisitors to the continent returning to their homes in developed countries. Thedevelopment of the molecular methods has greatly facilitated collaborativeresearch between rickettsial reference laboratories and laboratories in coun-tries with less-developed facilities for research. It is hoped, however, that ashealth workers in Africa become increasingly aware of rickettsioses, betterdescriptions of rickettsial diseases on the continent will become available andin particular the disease situation in the local peoples.

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