Kala Azar in Ethiopia: Drivers of transmission, human populations & Parasite genetics
VL is distributed throughout the lowlands of Ethiopia with varying
degrees of endemicity (Hailu & Frommel, 1993; Ayele and Ali, 1984;
Hailu et al., 1996; Hailu et al., 2006). Important endemic foci
include the Humera and Metema plains in northwest (Fuller et al.,
1976b; Hailu & Frommel, 1993); and the Segen and Woitu river
valleys in southwest (Hailu & Frommel, 1993; Hailu et al., 1996;
Fuller et al., 1979).
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).
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
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.,
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.
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.,
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
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Ali A and RW Ashford (1994) Ann Trop Med & Parasitol, 88, 289 - 93.
Ali A., Berhe N., Mengistu G. and Gebre-Michael T. (2002) EJHD, 16, 157 - 63.
Alvar J, Bashaye S, Argaw D, et al. (2007) Am J Trop Med & Hyg, 77, 275 – 82.
Andersen T.F. (1943) East Afr Med J, 20, 172 - 5.
Ashford R. W., Hutchinson M. P. and Bray R. S. (1973) Ethiop Med J, 11, 259 - 65.
Ayele T. and Ali A. (1984) Am J Trop Med & Hyg, 33, 548 – 52
Cles A.C.E., Consgrove P.C. and Robinson G. (1942) Trans Roy Soc Trop Med & Hyg, 36, 25 - 34.
Fuller G.K., Lemma A., Haile T. and Atwood C.L. (1976a) Ann Trop Med & Parasitol, 70, 148 - 63.
Fuller G.K., Desole G. and Lemma A. (1976b) Ethiop Med J, 14, 87 - 94.
Fuller G.K., Lemma A., and Gemetchu T. (1974) Trans Roy Soc Trop Med & Hyg, 68, 166.
Fuller G.K., Lemma A., Haile T. and Gemeda N. (1979) Ann Trop Med & Parasitol, 73, 417 - 31.
Gebre-Michael T., Balkew M., Alamirew T. et al. (2007) Ann Trop Med & Parasitol, 101, 367 70.
Gemetchu T. and Fuller G. K. (1976) Ethiop Med J, 14, 81 - 5.
Hailu A., Gebre-Michael T., Berhe N and Balkew M. (2006) Leishmaniasis
in Ethiopia. In: The Ecology and Epidemiology of Health and Disease in
Ethiopia. New Edition; Eds, H. Kloos, Berhane Y and Hailemariam D. pp
615 - 34.
Hailu A. and Frommel D. Leishmaniasis in
Ethiopia. (1993) In: The Ecology of Health and Disease in
Ethiopia. Eds., H. Kloos & Z.A. Zein. Westview Press,
Boulder, Colorado, USA.; pp 375 - 88.
Hailu A., Berhe N., Sisay Z. et al. (1996) Ethiop Med J, 34, 11 - 24.
Lindtjorn B. (1980) Ethiop Med J, 18, 99 - 100.
Lindtjorn B. (1987) Ethiop Med J, 25, 211.
Marlet M.V.L., Sang D.K., Ritmeijer K., et al. (2003) Trans Roy Soc Trop Med & Hyg, 97, 515 - 18.
Maru M.. (1979) Am J Trop Med & Hyg, 28, 15 - 8.
Mengesha B. and Abuhoy M. (1979) Trop Geogr Med, 30, 199 - 206.Tekle
A., Neri P. and Debessai, A. (1970) Parassitologia, 12, 21 - 5.
Asrat Hailu (firstname.lastname@example.org; email@example.com)
is a professor of immunoparasitology at the Faculty of Medicine –
Addis Ababa University (AAU). The main research interests of Asrat are
leishmaniasis including HIV co-infection of visceral leishmaniasis and
lymphatic filariasis. Other research interests are onchocerciasis,
intestinal parasitosis and malaria. Asrat has established the
Leishmaniasis Research and Diagnostic Laboratory (LRDL) at the Faculty
of Medicine – AAU; and the two Leishmaniasis Research and
Treatment Centres in south and north Ethiopia. Asrat is a key member of
the Leishmaniasis East African Platform (LEAP), and coordinates the
currently ongoing clinical trials on visceral leishmaniasis treatments.
Asrat and his group at DMIP will be engaged in studies on
dynamics of transmission in humans, reservoir hosts, parasite genetics
and drug sensitivity patterns of clinical isolates of Leishmania, and clinical and immunological evolutions of VL patients in varying human ecological settings.
Tamrat Abebe (firstname.lastname@example.org; email@example.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: firstname.lastname@example.org)
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 (email@example.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 (firstname.lastname@example.org)
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 (email@example.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 W, Weldegebreal T, Hurissa Z, Tafes H, Omollo R, Yifru S,
Balasegaram M & Hailu A (submitted) Safety and effectiveness of
meglumine antimoniate in the treatment of Ethiopian visceral
leishmaniasis patients with and without HIV co-infection.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.