Zoonotic Causes of Non­Malarial Febrile IllnessPaul Holland, Sarah Cleaveland, Jo Halliday

Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, United Kingdom

University of Glasgow, charity number SC004401

Introduction

Methods

Results

References

Conclusions

Fig. 2 ­ Visual representation of the initial Fever and Zoonosessearch output showing the number of unique publications ineach year.

Zoonoses Publication Effort Over Timeof results from the initial Fever + Zoonoses search

Initial SearchWe constructed two search concepts (Fever

and Zoonoses) and queried each database forreferences containing both of these concepts.The resulting references were combined andde­duplicated using an R script to generate1915 unique references from which all subjectheadings were extracted. Each subject headingwas classified by two independent reviewers togenerate a list of distinct pathogens/diseases.Individual Pathogen/Disease Searches

To search for individual pathogens wecompiled a list of zoonoses that cause feverfrom the following sources:• WHO listed diseases (zoonoses and public health)3• OIE listed diseases known to be zoonotic4• subject headings from the initial search

The zoonotic status of each pathogen waschecked against an existing database5. Searchsyntax for a total of 62 pathogen/diseaseconcepts was formulated.

The results of the initial search revealed atrend of increasing publication effort onzoonoses in recent years (Fig. 2), consistentwith previous findings8.

There has been a considerable increase inthe publication effort on zoonotic causes offever. It is important that efforts are made toensure that this increasing academicawareness of the importance of zoonoses ascauses of significant human illness is translatedto inform clinical practice. We present somepoints of discussion regarding the groupsdefined in Fig 3:A: Apparently important zoonotic causes offever ­ may provide direction to prioritiseresearch into burden assessments anddiagnostic test development.B: Clearly important human pathogens ­ helpfulto develop techniques to understand theproportion of human cases attributable tozoonotic transmission.C: & D: Less frequently published inassociation with reports of human fever whichmay indicate less importance; however, manypathogens in these areas are consideredneglected ­ efforts to determine if these pose agreater zoonotic threat than is currentlyreported may be worthwhile.

The next step in this project will be toidentify retrieved articles that match a strictlydefined inclusion criteria. A detailed review willbe conducted to collate and present theavailable quantitative data. Gaps in knowledgemay suggest possible directions for futureresearch effort and funding.

1. Reyburn H, Mbatia R, Drakeley C, Carneiro I, Mwakasungula E, Mwerinde O, et al. Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study. BMJ. 2004 Nov 20;329(7476):1212.2. John K, Kazwala R, Mfinanga GS. Knowledge of causes, clinical features and diagnosis of common zoonoses among medical practitioners in Tanzania. BMC Infect Dis. 2008 Jan;8:162.3. WHO | Diseases [Internet]. [place unknown]: World Health Organization; 2010 Dec 1 [cited 2012 Aug 30]. Available from: http://www.who.int/zoonoses/diseases/en/4. OIE Listed diseases 2012: OIE ­ World Organisation for Animal Health [Internet]. [place unknown]: Office International des Epizooties; 2012 [cited 2012 Aug 30]. Available from: http://www.oie.int/animal­health­in­the­world/oie­listed­diseases­2012/5. Cleaveland S, Laurenson MK, Taylor LH. Diseases of humans and their domestic mammals: pathogen characteristics, host range and the risk of emergence. Philos Trans R Soc Lond B Biol Sci. 2001 Jul 29;356(1411):991–9.6. Murray CJL, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, et al. Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet. 2012 Feb 4;379(9814):413–31.7. WHO | World Malaria Report 2011 [Internet]. [place unknown]: World Health Organization; 2012 Feb 21 [cited 2012 Aug 30]. Available from: http://www.who.int/malaria/world_malaria_report_2011/en/8. Vrbova L, Stephen C, Kasman N, Boehnke R, Doyle­Waters M, Chablitt­Clark a, et al. Systematic review of surveillance systems for emerging zoonoses. Transbound Emerg Dis. 2010 Jun;57(3):154–61.

Recent studies have shown that malaria isconsiderably overdiagnosed as a cause offever1 and that zoonotic causes are often notconsidered by clinicians who may have limitedawareness of zoonoses and few appropriatediagnostic tests2. The aim of this project was toconduct a systematic review of newly publisheddata on zoonotic causes of fever. We examinethe recent publication history of a range ofzoonoses to examine the degree to whichdifferent pathogens are considered as a causeof human fever and which are most frequentlyidentified as zoonoses.

Search LimitsPathogen specific searches were limited to

retrieve references pertaining to humansubjects only and to retrieve only those articlespublished between 2004­2012, a documentedperiod of global malaria decline6. Searcheswere also limited geographically using a searchconcept constructed to capture all countries inwhich malaria is considered endemic (informedby the WHO World Malaria Report7 (Fig 1.), orthe broader term Africa, the principle area ofinterest.Zoonotic Proportions

To demonstrate the number and proportionof references for each pathogen that aredescribed/identified as zoonotic, pairs ofsearches (X & Y) were run for each individualpathogen and the number of referencesgenerated from each search were recorded:X: Pathogen + FeverY: Pathogen + Fever + Zoonoses

Fig. 3 shows the number of referencesretrieved from the X & Y searches for eachindividual zoonotic pathogen and indicates theproportion of references retrieved in search Xthat were also retrieved in search Y (includingthe additional Zoonoses search term). Severaldistinct pathogen groups can be observed:A: Pathogens with both large numbers ofreferences in search X and high proportions ofretrieved articles defined as zoonotic.B: For pathogens with the highest numbers ofreferences retrieved, the proportion cataloguedas zoonotic was often quite low.C: Pathogens with relatively few totalpublications and a high proportion tagged aszoonotic.

Fig. 1 ­ World map showing those countries defined by theWHO as malaria endemic filled in red.

WHO Defined Malaria Endemic Countries

BC

A

DWe queried two well known databases

(MEDLINE and EMBASE) with carefullyconstructed search concepts and tabulated thenumber of references resulting from eachsearch.

search Xsea

rchY

Fig. 3 ­ Scatterplot showing log number of references retrievedfrom the X & Y searches for each pathogen. The dotted linerepresents the upper limit of 100% of search X referencesbeing "tagged" as zoonotic (also retrieved in search Y). Thetext next to each point indicates the pathogen/disease name.

D: Pathogens with the fewest overallreferences and a low proportion of theseidentified as zoonotic.