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Structure and management

Endemic Foci of Kala Azar

GALLERY

Kala Azar in Ethiopia:  Drivers of transmission, human populations &  Parasite genetics

The Segen river and the adjoining Woitu river valleys are areas that exhibit a huge micro-focal variation in burden of VL and L. donovani infection. The local variations in the burden of VL in the valleys are associated with a unique human adaptation and settlement patterns of the affected communities and the very focal nature of sand fly habitats. An in-depth epidemiological study of VL in one of the villages at the escarpments of the Segen valley (Aba-Roba focus) showed that VL is preponderant in males, and affects mainly children and young adults (Ali and Ashford, 1994). 

The Metema and Humera plains are recognized as the most important foci of VL in Ethiopia. The first reported cases of VL in north western Ethiopia come from the works of Fuller et al. (1976a), Tekle et al. (1970), Ashford et al. (1973), Mengesha and Abuhoy (1978) and Maru (1979).  Presently, VL in the region has become a major public health problem affecting major settlements and seasonal migrant laborers seeking employment in the large cash crop farms. In these areas, the risk of HIV co-infection is high.

Previously, Ashford et al. (1973) reported a few cases of VL from the highlands of northwest Ethiopia in a place called Belessa. Clinical records from Gondar University Hospital in northwest Ethiopia, have revealed VL in a child of age 7 living in the town of Gondar located at altitude of 2130 m.  These observations were indications for the possibility that VL could intrude into the highlands - as witnessed by the recent outbreak in Lake Tana basin/Libo-Kemkem District (Alvar et al., 2007; Gebre-Michael et al., 2007).

The vast plains of Omo River and the lowlands of south and southeast Ethiopia are areas with significant burden of the disease. The lower Omo plains are among the areas where the first reports of VL in Ethiopia were made (Coles et al., 1942; Andersen, 1943); later confirmed by extensive surveys of Fuller et al. (1974, 1979), and Hailu et al. (1996). The areas represent sporadic endemicity characterized by widespread infection and low incidence of active VL affecting mainly children.

Other than the lowlands of the Segen, Woitu, and Lower Omo valleys, VL occurs in many other localities of the southern regions, e.g. in Moyale and Wadera (Ayele & Ali, 1984) and the Dawa Valley (Lindtjorn, 1987).  Cases have also been reported from Gelana on the north eastern shore of Lake Abaya (Hailu et al. 1996; Lindtjorn, 1980). These localities are known to be endemic for VL, albeit sporadically. Recent surveys (unpublished) have also confirmed the endemicity of VL in Negele Borena (Liben District) – an area close to a previously described VL focus in south east Ethiopia (Marlet et al, 2003).
In the vast lowlands of the north eastern Rift Valley of Ethiopia (Awash Valley), VL occurs only sporadically and in association with HIV co-infection (Hailu et al., unpublished). Active case finding surveys by Fuller et al. (1976b), Ali (1997), Ali et al. (2002) and Berhe et al. (unpublished) have not documented any confirmed cases of VL. Leishmanin skin test rates, on the other hand, remain high in the region. Fuller et al. (1976b) reported leishmanin rates of 59.5% among Afar pastoralists in the Awash Valley. More recent surveys in the Awash Valley have documented an average leishmanin skin test rate of 33% in the middle course of Awash river valley (Ali, 1997) and 39% in the upper sections (Ali et al., 2002). In addition, entomological studies have confirmed the existence of man biting sand fly species in the area, of which P. orientalis was found abundantly and widely distributed (Gemetchu and Fuller, 1976; Gebre-Michael et al., unpublished).
Other areas where VL can be expected to occur include the western regions e.g. Gambella Regional State and Benishangul-Gumz Regional State, which are adjacent to the Upper Nile Province in Eastern Sudan. On several occasions between 1989 and 1993, active case finding, leishmanin skin test and serological surveys have been carried out in these regions, and truly authochtonous cases of VL were not found during the active surveys or from hospital records (Hailu et al., 1996). 
Given the increasing mobility of people, there is an impending potential for VL to spread to the vast and highly populated areas of the country, since the distribution of sand fly vectors of VL is known to be more widespread that the disease itself.  It has thus become a necessary step to map areas endemic to VL and those likely to be affected. Concurrently, in-depth studies of VL transmission are direly needed to provide evidences needed for devising effective control tools. The Leishmaniasis Research Group (LRG) of Addis Ababa University is partnering with the Hebrew University of Jerusalem to undertake field ecological and epidemiological studies in selected endemic localities of VL - mainly in north Ethiopia.  The study localities are: - the Kefta-Humera (site 1) and Tahtay Adiabo (site 2) districts in Western Tigray; and the Metema (site 3) and Libo-Kemkem (site 4) districts in North Gondar of Amhara region. An additional site in southwestern Ethiopia (site 5, Aba Roba focus of VL) is also being considered.    

References:

Project personnel

Tamrat Abebe (tabebezeleke@gmail.com; tamicro2003@yahoo.com) is a full-time lecturer at Addis Ababa University Faculty of Medicine, Department of Microbiology, Immunology and Parasitology (DMIP). He obtained his B.Sc in Biology from Addis Ababa University Faculty of Science and M.Sc in Medical Microbiology from Addis Ababa University Faculty of Medicine. His research interest includes immunopathogenesis of leishmaniasis, HIV and tuberculosis. More recently, his research has focused on the impact of arginase-induced L-arginine depletion on T cell effector functions during leishmaniasis. Tamrat is a PhD student at University of Lausanne in Switzerland in the international Cancer and Immunology Program. Tamrat is involved in the diagnosis and treatment of leishmaniasis in Leishmania Research and Diagnostic Laboratory (LRDL) at Addis Ababa University Faculty of Medicine; and also in molecular typing of Leishmania.

Aysheshm Kassahun (e-mail: ayshek2000@yahoo.com) is Assistant Researcher at Department of Microbiology, Immunology and Parasitology (DMIP), Faculty of Medicine, Addis Ababa University (AAU). He completed his B.Sc in Biology from Faculty of Science and M.Sc in Medical Parasitology from Faculty of Medicine, Addis Ababa University. He is engaged in several activities of leishmaniasis diagnosis and treatment at Leishmania Research and Diagnostic Laboratory (LRDL) of Faculty of Medicine at AAU. He is currently setting up drug sensitivity assays for Leishmania.

 Manaye Mamo (amamo96@yahoo.com) is a research assistant in Department of Microbiology, Immunology, and Parasitology (DMIP), Faculty of medicine, Addis Ababa University. He completed his first degree in veterinary medicine (DVM) and master’s degree in medical parasitology from the above university. He did his masters research thesis on drug sensitivity of Ethiopian cutaneous leishmaniasispatient isolates. Currently, he is actively engaged in research on visceralleishmaniasisclinical isolates and their sensitivity to drugs.

Asrat Bezuneh (asrat_bezuneh@yahoo.com) is a research assistant in Addis Ababa University, Department of Microbiology, Immunology and Parasitology (DMIP). He completed his first degree in Biological Sciences from the same university and his M.Sc thesis work is in progress. His research experience includes intestinal parasites including schistosomiasis, onchocerciasis and HIV-Leishmaniasis co-infection. Currently, he is engaged in research study of animal reservoir hosts of visceral leishmaniasis, and also collaborating in testing Leishmania for drug sensitivity. He is also involved in molecular and sero-epidemiological studies of visceral leishmaniasis.

Welelta Shiferaw (weleltas@gmail.com) is a research assistant at the Department of Microbiology, Immunology and Parasitology (DMIP), Faculty of Medicine, Addis Ababa University. She received her first degree in Biological Science from the same university. Welelta is defending her master’s thesis work on “Serological and Leishmanin Skin Test Surveys of Visceral Leishmaniasis in Liben Wereda, Oromia Region and Hamer Wereda, SNNPR.  Currently, she is actively engaged in researches on Lymphatic Filariasis surveys in Ethiopia.

Selected publications of the research group at DMIP, Faculty of Medicine – AAU

Hailu A, Musa AM, Wasunna M, Balasegaram M, et al (submitted) Geographical variation in the response of visceral leishmaniasis to paromomycin sulphate in East Africa: a multi-centre, open-label, randomized, controlled trial. PLoS Negl Trop Dis. 

Hurissa Z, Gebre-Silassie S, Hailu W, Tefera T, Lalloo DG, Cuevas LE and Hailu A (accepted) Clinical characteristics and treatment outcome of patients with visceral leishmaniasis and HIV co-infection in north- west Ethiopia. Ann Trop Med Parasitol.

Cloke, T., Garvey L, Choi B.-S, Abebe T, Hailu A, Hancock M, Kadolsky U,  Bangham C.R.M, Munder M, M?ller I, Taylor G.P., Kropf P (accepted) Increased arginase activity correlates with disease severity in HIV seropositive patients.   JID.

Hailu A, Gramiccia M, Kager PA. (2009) Visceral leishmaniasis in Aba-Roba, south-western Ethiopia: prevalence and incidence of active and subclinical infections. Ann Trop Med Parasitol., 103(8):659-70.

Lemma W, Erenso G, Gadisa E, Balkew M, Gebre-Michael T, Hailu A. (2009) A zoonotic focus of cutaneous leishmaniasis in Addis Ababa, Ethiopia. Parasite & Vectors; 2(1):60.

Boelaert M., El-Safi S., Hailu A., M. Mukhtar, Rijal S., Sundar S., Wasunna M., Aseffa A., Mbui  J., Menten J., Desjeux P., and Peeling R. (2008) Diagnostic tests for kala-azar: a multi-centre study of the freeze-dried DAT, rK39 strip test and Katex in East Africa and the Indian subcontinent. Trans Roy Soc Trop Med & Hyg, 102, 32 – 40.

Hailu A., Musa A.M., Royce C. and Wasunna M. (2005) Visceral leishmaniasis: New health
tools are needed. PloS Medicine, 2, 590 - 4.

Hailu A., Pater P.M., Kager P.A. and van der Poll T. (2004) Increased expression of HIV       corecptor CXCR4 on CD4+ T  cells in patients with active visceral leishmaniasis.
Scand J  Infect Dis, 36, 56 – 58.

Hailu A., van der Poll T., Berhe N. and Kager P.A. (2004) Elevated plasma levels of
interferon (IFN)-g, IFN-g inducing cytokines and IFN-g inducible CXC chemokines in
visceral leishmaniasis.  American Journal of Tropical Medicine and Hygiene, 71, 561 – 567.

Negera E, Gadisa E, Yamuah L, Engers H, Hussein J, Kuru T, Hailu A, Gedamu L, Aseffa A. (2008) Outbreak of cutaneous leishmaniasis in Silti woreda, Ethiopia: risk factor assessment and causative agent identification. Trans R Soc Trop Med Hyg., 102(9):883-90.

Diro E., Techane Y., Tefera T., Assefa Y., Kebede T., Genetu A., Kebede Y., Tesfaye A., Ergicho B., Gebre-Yohannes A., Mengistu G., Engers H., Aseffa A., Desjeux P., Boelaert M. and Hailu A. (2007) Field evaluation of FD-DAT, rk-39 dipstick and KATEX (urine latex agglutination) for diagnosis of visceral leishmaniasis in northwest Ethiopia. Trans Roy Soc Trop Med & Hyg, 101, 908 – 914.

Modolell M, Choi BS, Ryan RO, Hancock M, Titus RG, Abebe T, Hailu A, M?ller I, Rogers ME, Bangham CR, Munder M, Kropf P. (2009) Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. PLoS Negl Trop Dis.  14;3(7):e480.

 Hailu A., Abebe T., Hunegnaw M., Di Muccio D., Lombardi D., Kager P.A. and Gramiccia M. (2006) Isolation of Leishmania  tropicafrom an Ethiopian cutaneous leishmaniasis patient. Trans Roy Soc Trop Med Hyg, 100, 53 – 58.
M?ller I, Hailu A, Choi BS, Abebe T, Fuentes JM, Munder M, Modolell M, Kropf P. (2008) Age-related alteration of arginase activity impacts on severity of leishmaniasis. PLoS Negl Trop Dis., 14;2(5):e235.

Bezuneh A, Birrie H and Debele K (1995). Colonization of irrigation canals by Bulinus abyssinicus and upsurge o urinary schistosomiasis in the Middle Awash Valley of Ethiopia. Ethiop. Med. J.33:259-263.

Birrie H., Balcha F., Bezuneh A. and Bero G. (1996). Susceptibility of Ethiopian Bulinid snails to Schistosoma haematobium from Somalia. East Afr. Med. J.,73: 79-80.

Birrie H., Balcha F., Erko B., Bezuneh A. and Gemeda N. (1998). Investigation into the miracidial and cercaricidal properties of Endod (Phytolocca dodecandra) berries (Type 44). East Afr. Med. J. 75:311-314.

Kim A., Tandon A., Hailu A., Birre H., Berhe N., Aga A., Mengistu G., Ali A., Balcha F., Gebre-Michael T., Bezuneh A., Gemechu T. (1997). Health and Labour Productivity: Economic impact of onchocercal skin disease Policy Research Working Paper. World Bank. 1836. 1-12.

Hailu A., Balcha F., Birrie H., Aga A., Mengistu G., Bezuneh A., Ali A., Gebre-Michael T., and Gemechu T. (2002) Prevalence of onchocercal skin disease and infection among workers of coffee plantation farms in Teppi , southwestern Ethiopia. Ethiop. Med. J. 40:259-269.

Volcani Center, Israel