Visceral Leishmaniasis (VL) is a disseminated protozoan infection caused by Leishmania donovani that affects almost half a million people annually. In Northern Ethiopia, VL is common in migrant agricultural laborers returning from the lowland sesame fields of Metema and Humera. Recent VL foci have emerged in resident rural populations near the town. In the current study, we evaluate multilevel entomological, epidemiological and ecological factors associated with infection and disease through fine-scale eco-epidemiological analyses in three villages. Satellite images showed that villages constructed in or close to vertisols, were likely to become endemic for VL. Vertisols or black-cotton soil, are characterized by high contents of smectitic clay minerals, which swell when hydrated and shrink upon desiccation, causing extensive deep cracking during the dry season. The population densities of Phlebotomus orientalis, the vector, were negatively correlated with distance from vertisols and persons living close to vertisols were more likely to be bitten by sand flies, as evidenced by sero-positivity to Ph. orientalis saliva. Apparent (albeit non-significant) clustering of VL cases and abundant asymptomatic infections close to vertisols, suggest anthroponotic transmission around houses located close to vertisols. Comparable rates of male and female volunteers, mostly under 15 years of age, were infected with L. donovani but a significantly higher proportion of males succumbed to VL indicating a physiological gender-linked male susceptibility. Our data suggest that the abundant infected persons with high parasitemias who remain asymptomatic, may serve as reservoir hosts for anthroponotic transmission inside villages. Only limited insights on the transmission dynamics of L. donovani were gained by the study of environmental factors such as presence of animals, house structure and vegetation cover.

Aklilu Lemma Institute of Pathobiology Addis Ababa University Addis Ababa Ethiopia Ethiopia

Department of Biostatistics School of Public Health Yale University 60 College street New Haven CT 06520 USA USA

Department of Geography and Environmental Studies Haifa University Haifa Israel Israel

Department of Microbiology and Molecular Genetics The Institute of Medical Research Israel Canada [IMRIC] The Kuvin Centre for the Study of Infectious and Tropical Diseases Faculty of Medicine The Hebrew University of Jerusalem Israel Israel

Department of Parasitology Faculty of Science Charles University Vinicna 7 128 44 Prague 2 Czech Republic Czech Republic

Dept of Microbiology Immunology and Parasitology Faculty of Medicine Addis Ababa University Addis Ababa Ethiopia Ethiopia

Zobrazit více v PubMed

Abbasi I., Cunio R., Warburg A. Identification of blood meals imbibed by phlebotomine sand flies using cytochrome b PCR and reverse line blotting. Vector Borne Zoonotic Dis. 2009;9:79–86. PubMed

Abbasi I., Aramin S., Hailu A., Shiferaw W., Kassahun A., Belay S., Jaffe C., Warburg A. Evaluation of PCR procedures for detecting and quantifying Leishmania donovani DNA in large numbers of dried human blood samples from a visceral leishmaniasis focus in Northern Ethiopia. BMC Infect. Dis. 2013;13:153. PubMed PMC

Ali A., Ashford R. Visceral leishmaniasis in Ethiopia. IV. Prevalence, incidence and relation of infection to disease in an endemic area. Ann. Trop. Med. Parasitol. 1994;88:289–293. PubMed

Alvar J., Velez I.D., Bern C., Herrero M., Desjeux P., Cano J., Jannin J., den Boer M., Team W.H.O.L.C. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012;7:e35671. PubMed PMC

Artemiev M. A revision of sandflies of the subgenus Adlerius (Díptera, Phlebotommae, Phlebotomus) Zoologicheskii Zhurnal. 1980;59:1177–1192.

Ashford R., Seaman J., Schorscher J., Pratlong F. Epidemic visceral leishmaniasis in southern Sudan: identity and systematic position of the parasites from patients and vectors. Trans. R. Soc. Trop. Med. Hyg. 1992;86:379–380. PubMed

Berhe N., Hailu A., Abraham Y., Tadesse Y., Breivik K., Abebe Y. Inter-current and nosocomial infections among visceral leishmaniasis patients in Ethiopia: an observational study. Acta Trop. 2001;80:87–95. PubMed

Bern C., Hightower A.W., Chowdhury R., Ali M., Amann J., Wagatsuma Y., Haque R., Kurkjian K., Vaz L.E., Begum M. Risk factors for kala-azar in Bangladesh. Emerg. Infect. Dis. 2005;11:655. PubMed PMC

Chappuis F., Sundar S., Hailu A., Ghalib H., Rijal S., Peeling R.W., Alvar J., Boelaert M. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat. Rev. Microbiol. 2007;5:873–882. PubMed

Debrabant A., Joshi M.B., Pimenta P.F., Dwyer D.M. Generation of Leishmania donovani axenic amastigotes: their growth and biological characteristics. Int. J. Parasitol. 2004;34:205–217. PubMed

El Tai N., Osman O., El Fari M., Presber W., Schönian G. Genetic heterogeneity of ribosomal internal transcribed spacer in clinical samples of Leishmania donovani spotted on filter paper as revealed by single-strand conformation polymorphisms and sequencing. Trans. R. Soc. Trop. Med. Hyg. 2000;94:575–579. PubMed

Elnaiem D., Connor S., Thomson M., Hassan M., Hassan H., Aboud M., Ashford R. Environmental determinants of the distribution of Phlebotomus orientalis in Sudan. Ann. Trop. Med. Parasitol. 1998;92:877–887. PubMed

Elnaiem D., Hassan H., Ward R. Associations of Phlebotomus orientalis and other sandflies with vegetation types in the eastern Sudan focus of kala-azar. Med. Vet. Entomol. 1999;13:198–203. PubMed

Elnaiem D.E.A. Ecology and control of the sand fly vectors of Leishmania donovani in East Africa, with special emphasis on Phlebotomus orientalis. J. Vector Ecol. 2011;36:S23–S31. PubMed

Emmanuel N.N., Loha N., Okolo M.O., Ikenna O.K. Landscape epidemiology: an emerging perspective in the mapping and modelling of disease and disease risk factors. Asian Pac. J. Trop. Dis. 2011;1:247–250.

Exelis Visual Information Solutions . 2014. ENVI Classic Tutorial: Classification Methods.

Gebre-Michael T., Lane R.P. The roles of Phlebotomus martini and P.celiae (Diptera: phlebotominae) as vectors of visceral leishmaniasis in the Aba Roba focus southern Ethiopia. Med. Vet. Entomol. 1996;10:53–62. PubMed

Gebre-Michael T., Malone J., Balkew M., Ali A., Berhe N., Hailu A., Herzi A. Mapping the potential distribution of Phlebotomus martini and P. orientalis (Diptera: psychodidae), vectors of kala-azar in East Africa by use of geographic information systems. Acta Trop. 2004;90:73–86. PubMed

Gebre-Michael T., Balkew M., Berhe N., Hailu A., Mekonnen Y. Further studies on the phlebotomine sandflies of the kala-azar endemic lowlands of Humera-Metema (north-west Ethiopia) with observations on their natural blood meal sources. Parasit Vectors. 2010;3:6. PubMed PMC

Gebresilassie A., Abbasi I., Aklilu E., Yared S., Kirstein O.D., Moncaz A., Tekie H., Balkew M., Warburg A., Hailu A., Gebre-Michael T. Host-feeding preference of Phlebotomus orientalis (Diptera: psychodidae) in an endemic focus of visceral leishmaniasis in northern Ethiopia. Parasites Vectors. 2015;8:270. PubMed PMC

Gebresilassie A., Kirstein O.D., Yared S., Aklilu E., Moncaz A., Tekie H., Balkew M., Warburg A., Hailu A., Gebre-Michael T. Nocturnal periodicity of Phlebotomus (Larroussius) orientalis (Diptera: psychodidae) in an endemic focus of visceral leishmaniasis in Northern Ethiopia. Parasites Vectors. 2015;8:186. PubMed PMC

Gebresilassie A., Kirstein O.D., Yared S., Aklilu E., Moncaz A., Tekie H., Balkew M., Warburg A., Hailu A., Gebre-Michael T. Species composition of phlebotomine sand flies and bionomics of Phlebotomus orientalis (Diptera: psychodidae) in an endemic focus of visceral leishmaniasis in Tahtay Adiyabo district, Northern Ethiopia. Parasites Vectors. 2015;8:248. PubMed PMC

Guerin P.J., Olliaro P., Sundar S., Boelaert M., Croft S.L., Desjeux P., Wasunna M.K., Bryceson A.D. Visceral leishmaniasis: current status of control, diagnosis, and treatment: and a proposed research and development agenda. Lancet Infect. Dis. 2002;2:494–501. PubMed

Guerra-Silveira F., Abad-Franch F. Sex bias in infectious disease epidemiology: patterns and processes. PLoS One. 2013;8:e62390. PubMed PMC

Hailu A., Balkew M., Berhe N., Meredith S.E., Gemetchu T. Is Phlebotomus (Larroussius) orientalis a vector of visceral leishmaniasis in south-west Ethiopia? Acta Trop. 1995;60:15–20. PubMed

Herrero M., Orfanos G., Argaw D., Mulugeta A., Aparicio P., Parreño F., Bernal O., Rubens D., Pedraza J., Lima M.A. Natural history of a visceral leishmaniasis outbreak in highland Ethiopia. Am. J. Trop. Med. Hyg. 2009;81:373–377. PubMed

Kirk R., Lewis D.J. Taxonomy of the Ethiopian Sand flies (Phlebotomus) II. Keys for the indentification of the Ethiopian species. Ann. Trop. Med. Parasitol. 1946;40:117–129. PubMed

Kitron U. Landscape ecology and epidemiology of vector-borne diseases: tools for spatial analysis. J. Med. Entomol. 1998;35:435–445. PubMed

Lemma W., Tekie H., Abassi I., Balkew M., Gebre-Michael T., Warburg A., Hailu A. Nocturnal activities and host preferences of Phlebotomus orientalis in extra-domestic habitats of Kafta-Humera lowlands, Kala-azar endemic, Northwest Ethiopia. Parasites Vectors. 2014;7:594. PubMed PMC

Leta S., Dao T.H.T., Mesele F., Alemayehu G. Visceral leishmaniasis in Ethiopia: an evolving disease. PLoS Negl. Trop. Dis. 2014;8:e3131. PubMed PMC

Lewis D.J. 1982. Taxonomic Review of the Genus Phlebotomus (Diptera, Psychodidae)

Lewis D.J. Phlebotomine sandflies (Diptera: psychodidae) from the oriental region. Syst. Entomol. 1987;12:163–180.

Madden T. 2013. The BLAST Sequence Analysis Tool.

Moncaz A., Gebresilassie A., Kirstein O., Faiman R., Gebre-Michael T., Hailu A., Warburg A. Attraction of phlebotomine sand flies to baited and non-baited horizontal surfaces. Acta Trop. 2013;126:205–210. PubMed

Moncaz A., Kirstein O., Gebresellassie A., Lemma W., Yared S., Gebre-Michael T., Hailu A., Shenker M., Warburg A. Characterization of breeding sites of Phlebotomus orientalis? The vector of visceral leishmaniasis in northwestern Ethiopia. Acta Trop. 2014;139:5–14. PubMed

Nackers F., Mueller Y.K., Salih N., Elhag M.S., Elbadawi M.E., Hammam O., Mumina A., Atia A.A., Etard J.-F., Ritmeijer K. Determinants of visceral leishmaniasis: a case-control study in Gedaref State Sudan. PLoS Negl. Trop. Dis. 2015;9:e0004187. PubMed PMC

Perfil'ev P.P., Strelkov A.A., Theodor O. 1968. Phlebotomidae (Sandflies). Israel Program for Scientific Translations Available from the Clearinghouse for Federal Scientific and Technical Information, Springfield Va.

Quate L.W. Phlebotomus sandflies of the paloich area in the Sudan (Diptera, psychodidae) J. Med. Entomol. 1964;1:213–268. PubMed

Reisen W.K. Landscape epidemiology of vector-borne diseases. Annu. Rev. Entomol. 2010;55:461–483. PubMed

Singh S., Hasker E., Picado A., Gidwani K., Malaviya P., Singh R., Boelaert M., Sundar S. Risk factors for visceral leishmaniasis in India: further evidence on the role of domestic animals. Trop. Med. Int. Health. 2010;15:29–35. PubMed PMC

Singh O.P., Hasker E., Sacks D., Boelaert M., Sundar S. Asymptomatic Leishmania infection: a new challenge for Leishmania control. Clin. Infect. Dis. 2014;58:1424–1429. PubMed PMC

Sithiprasasna R., Lee W.J., Ugsang D.M., Linthicum K.J. Identification and characterization of larval and adult anopheline mosquito habitats in the Republic of Korea: potential use of remotely sensed data to estimate mosquito distributions. Int. J. Health Geogr. 2005;4:17. PubMed PMC

ter Horst R., Collin S.M., Ritmeijer K., Bogale A., Davidson R.N. Concordant HIV infection and visceral leishmaniasis in Ethiopia: the influence of antiretroviral treatment and other factors on outcome. Clin. Infect. Dis. 2008;46:1702–1709. PubMed

Travi B.L., Osorio Y., Melby P.C., Chandrasekar B., Arteaga L., Saravia N.G. Gender is a major determinant of the clinical evolution and immune response in hamsters infected with Leishmania spp. Infect. Immun. 2002;70:2288–2296. PubMed PMC

Vlkova M., Rohousova I., Drahota J., Stanneck D., Kruedewagen E.M., Mencke N., Otranto D., Volf P. Canine antibody response to Phlebotomus perniciosus bites negatively correlates with the risk of Leishmania infantum transmission. PLoS Negl. Trop. Dis. 2011;5:e1344. PubMed PMC

Human antibody reaction against recombinant salivary proteins of Phlebotomus orientalis in Eastern Africa