INTRODUCTION
Leishmaniasis is a vector borne-disease caused by obligate intracellular protozoan of the genus Leishmania.
It is endemic in 98 countries with >350 million people at risk1. An estimated 900,000–1.3 million new cases and 20,000 to 30,000 deaths occur annually. Among different forms of leishmaniasis, visceral leishmaniasis (VL) is most fatal, with around 200,000–400,000 new cases occurring annually around the world2. Over 90% of VL human cases occur in six countries, namely Bangladesh, Brazil, Ethio- pia, India, South Sudan, and Sudan2. The highest numbers of VL cases are recorded in Eastern Africa including Eritrea, Ethiopia, Kenya, Somalia, Sudan, South Sudan, and Uganda3. For instance, > 4,000 VL cases are recorded in the lowland and arid areas of Ethiopia per year4.
VL is the most severe forms of leishmaniasis which affects the reticuloendothelial systems2. Transmission is zoonotic and anthroponotic and conveyed through the bite of the female Phlebotomus in the Old World and Lutzomyia in the New World5–6.
The epidemiology of leishmaniasis is dynamic and the conditions of transmission are continually changing depending on changes in the environment, demography, human behaviour, socioeconomic status, and immuno- Review Articles
Challenges in visceral leishmaniasis control and elimination in the developing countries: A review
Tadesse Hailu, Mulat Yimer, Wondemagegn Mulu & Bayeh Abera
Department of Microbiology, Immunology and Parasitology, College of Medicine and Health Science, Bahir Dar University, Ethiopia
ABSTRACT
Leishmaniasis is a disease caused by an obligate intracellular protozoan that affects animals and human.
Transmission is zoonotic and/or anthroponotic through the bite of an infected female sandfly. Control and elimination of visceral leishmaniasis (VL) require proper case detection, identification of reservoir hosts, and launching of effective vector control strategies in endemic areas. The aim of this review was to highlight the challenges in VL control in developing countries. Literatures pertaining to VL burden, diagnosis, prevention and control from the year 1969 to 2014 were systematically reviewed from PubMed, Scopus, Medline and Google scholar sources during July 2015. Poor vector control strategies, limited diagnostic services, drugs, treatments and lack of community awareness are the most important challenges in VL control and elimination especially in endemic areas. Absence of highly sensitive and specific tests, lack of trained man power, and community awareness are the major challenges in VL control. Therefore, proper case diagnosis, community mobilization and launching of effective vector control strategies in endemic areas are vital.
Key words Migration; reservoir hosts; sandfly; visceral leishmaniasis
genic profile of affected human populations7–9. These factors might influence case identification, diagnosis, treatment, and preventive measures taken against leish- maniasis, especially in resource poor countries.
VL is not only a human disease; rather it affects do- mestic and wild animals. The disease can easily be trans- mitted from human to human, human to animal, animals to animals or animal to human through the vector10–13. This indicates that Leishmania infection has a complex life cycle. In order to tackle challenges in VL prevention, it is necessary to understand the complex life cycle of Leishmania infection.
Considering VL recent upsurge, we systematically reviewed the possible challenges that should be consid- ered for VL prevention and control in endemic countries.
Reservoir hosts
Humans, wild and domestic animals are believed to be reservoir hosts for VL. Still the reservoir hosts for VL are not well addressed in most endemic countries. For instance, no single animal reservoir host of VL is identi- fied in Ethiopia13. Wildlife is a potential source for emerg- ing infectious diseases in humans and domestic animals14. Some wild animals like foxes can serve as reservoir host for VL15–17. Currently, domestic dogs are the main reser-
voir for VL in Brazil18. The magnitude of VL combined with the complexity of its epidemiology and the links in transmission network should be clear to develop effec- tive control strategies19. Human beings might get infec- tion from wildlife source or domestic animals through sandfly bite. Unless the health of wild and domestic ani- mals is maintained, the human population will be at risk for VL infection. In this aspect the wildlife conservation specialists and veterinarians should be concerned about the health of the community20–21.
According to some reports, domestic dogs22, rodents and carnivores15–16 are reservoir hosts for VL in East Af- rica. The presence of unplastered house wall and previ- ous cases of canine are the major risk factors for domes- tic dogs23. The animal reservoir hosts vary from place to place. For instance domestic dogs24 and some wild ani- mals like grass rat, spinus mouse, serval, genet15 and jackal25 in Sudan15, 24–25; goats and cow in India26 and dogs in Brazil18 are reported as VL reservoir hosts. So far Leishmania donovani has not been found in animal res- ervoir hosts by parasitological investigations in Ethiopia13. The most important and possible reservoir hosts are the humans, and dogs13, 27. Measures to control VL in reser- voir hosts found in developing countries should be un- dertaken, as no disease control programmes are currently available. Therefore, unless reservoir hosts of VL are clearly identified, it is impossible to control and elimi- nate VL in endemic areas. The risk factors and reservoir hosts for VL in different countries is different (Table 1).
Poor vector control
Several factors have contributed to increased global interest in the epidemiology, control and prevention of
VL. Visceral leishmaniasis is an emerging infection adapt- ing environmental changes and spreading into new geo- graphical regions due to adaptation of the vector in dif- ferent geographical areas28.
Sandflies are very susceptible to dehydration. Most are nocturnal and seek shelter in animal burrows, tree buttresses or holes, caves, rocks and human habitations.
Generally, they are fragile and short flyers (about 300 m) and usually fly close to the ground in short hops29. The short flight range usually restricts the adult to the general vicinity around the larval development site. These sites are usually organically rich moist soils. In the old world for example, the sandflies are found near black cotton- clay soils, acacia forests, balantine trees, rodent burrows, domesticated animal shelters and termite hills which are possibly breeding sites in Eastern Africa30–31. On the other hand, sandflies are often found near tree buttresses and cave in the new world. For instance, Lutzomyia shannoni was found associated with hardwood forests in the United States32.
Different species need variable geographical settings to complete their life cycle. For instance in Ethiopia, Phle- botomus orientalis is found in association with black cot- ton-clay soils and acacia forests in northwestern foci30, and P. martini and P. celiae are believed to be associated with termite hills in southern foci31. High range of vector distribution in different geographical settings makes the vector control difficult. In addition, proper sandfly con- trol strategies are not launched in endemic areas. For ex- ample, there is no sandfly control strategy launched in Ethiopia.
Scientific elimination strategy of sandfly is not based on the epidemiological vulnerability, and effectiveness
Table 1. Reservoir hosts and way of transmission of Leishmania in high endemic countries
Countries Risk population/New Reservoir hosts Transmission References
cases per year
Bangladesh 20 million/40–45,000 Cattle and dogs Zonootic Bern and Chowdhury34;
Leta et al9 India 110 million/100,000 Dogs, sheep and goats Zoonotic and anthroponotic Singh et al12
Burki35; Bora36 Nepal 5.8 million/3000–5900 Human, buffaloes, goats, Zoonotic and anthroponotic Schenkel et al37
and cows Bhattarai et al38
Hotez et al39
Sudan 280,000/20,000 Grass rat, spinus mouse, Anthroponotic and zoonotic Hoogstraal and Heyneman15;
serval, gene and jackal Sixl et al25; Burki40
South Sudan 2.5 million/1756 Human and dogs Anthroponotic and zoonotic Abubakar et al33; Alvar et al41
Ethiopia 3.2 million/3700–7400 Human Anthroponotic Kenubih et al13
Brazil ---/3,500 Dogs and human Zoonotic and anthroponotic Dantas-Torres and
Brandão-Filho18; Costa et al42
and feasibility of intervention. Currently, an effective strat- egy for reducing human VL is to control sandfly vectors through chemicals, environmental management and per- sonal protection, but these are hard to apply in resource poor countries43.
Indoor residual spraying is a simple and cost- effective method of controlling endophilic sandflies; how- ever, resistance to insecticide is likely to become more widespread especially in those areas where insecticide has been used for years44. The spectrum of susceptibility of sandflies to insecticides is also not completely known in endemic countries43. These factors add to challenges in control and elimination of VL in resource poor coun- tries. Therefore, there is increasing consensus that all vec- tor control strategies should be reassessed and imple- mented in a framework of decision making and quality assurance that can be applied at the lowest health care system45.
Case detection, diagnosis and treatment
VL is a systemic disease caused by the L. donovani46 and L. infantum47. Leishmania donovani is causative agent of VL in the Indian subcontinent and in East African coun- tries48, namely Sudan, Ethiopia, Kenya and Somalia, which is prevalent mainly in the lowlands49, while in Europe, North Africa and Latin America L. infantum is the causal organism47. An estimated 3.2 million people are at risk of VL50 and 3700–7400 cases occur annually in Ethiopia51. The highest number of VL cases was re- ported in South Sudan33 and in the northern50, 52 and south- ern part of Ethiopia in Eastern Africa53. VL is also preva- lent in Northern Africa including Morocco, Algeria, Tunisia, Egypt and Libya. Relatively, low prevalence rates of VL is also recorded in West African countries, viz.
Cameroon, Ghana, Burkina Faso, Niger, Mali, Nigeria and Senegal54.
The clinical manifestation of VL patients includes:
fever (more than two weeks), fatigue, and weakness, loss of appetite, weight loss, enlarged lymph nodes, hepatosplenomegaly, pancytopenia and sometimes bleed- ing55. Leishmania donovani multiplies and survives in phagolysosomes through a complex parasite-host inter- action within the macrophages53. The parasites dissemi- nate through the lymphatic and vascular systems and in- fect other monocytes and macrophages in the reticul- oendothelial system, resulting in infiltration of the bone marrow, hepatosplenomegaly and lymphadenopathy55.
Post kala-azar dermal leishmaniasis (PKDL) is a se- quel of VL that appears as macular, papular or nodular rash usually on face, upper arms, trunks and other parts of the body. People with PKDL are considered to be a
potential source of kala-azar infection56. The prevalence of PKDL is higher in people co-infected with human im- munodeficiency virus (HIV) and VL57.
The L. donovani infected cases should be properly differentiated from other febrile cases, and should be di- agnosed using specific laboratory tests with high speci- ficity and sensitivity. The confirmatory diagnosis of leish- maniasis relies on either the microscopic demonstration of Leishmania amastigotes in tissues aspirates or biopsy smears58. However, both microscopic detection and cul- ture should be performed since smear negative lesion can be culture positive; and culture negative lesion can be smear positive59. The rK39 ICTs perform well for the primary diagnosis of VL, but further advancement in di- agnostic tests and their evaluation is required in develop- ing countries.
Although, parasitological detection of VL is a gold standard method, rK39 test has been used in peripheral health facilities of resource poor countries due to limita- tion of trained human resource, reagents, chemicals, and organized health facilities in VL endemic areas.
Treatment should be given based on the country drug line regimen. There are several drug treatments available including oral, parenteral, and topical medications60. Pen- tavalent antimonials such as stibogluconate and meglumine antimoniate, have been the main drugs, but they are limited by adverse side effects, development of resistance and cost. Liposomal amphotericin B is more favorable in regions where resistance is common46. For proper case management and prevention of drug resis- tance appropriate drugs for VL, trained man power, and sensitive, rapid, cost effective and easily applicable diag- nostic techniques should also be availed in peripheral health care systems.
Population movement and migration
Population movement is associated with the high prevalence of VL in endemic areas. For instance, marked increase in VL cases is particularly associated with mi- gration of non-immune labourers from the surrounding highlands to the extensive agricultural farm lands of the Humera and Metema lowlands in the northwestern parts of Ethiopia16, 61. There were also 904 VL confirmed cases among migrants coming from southern Somalia and southeast Ethiopia to Kenya62. The migration of people from high VL endemic countries to others might affect the prevalence of VL. For example, people migrate from Somalia and South Sudan to Kenya and Ethiopia for sev- eral reasons in East Africa, where high VL burden is found but screening of migratory people is limited. So, control of the disease burden in VL endemic neighbourhood coun-
tries need special attention concerning the migratory people within them.
HIV-VL co-infection
VL has emerged as an important opportunistic infec- tion associated with HIV. A concomitant HIV infection increases the risk of developing active VL by 100 to 2320 times. HIV-infected people are particularly vulnerable to VL, while VL accelerates HIV replication and progres- sion to AIDS63.
HIV-VL co-infected people have high chance of de- veloping the full blown clinical disease, high relapses and mortality rates56. Recent studies conducted in the north- western parts of Ethiopia indicated that the highest preva- lence of VL in Humera and Metema is associated with the high prevalence of HIV-VL co-infection64–65. Up to 30% of VL cases have been found co-infected with HIV in northwestern Ethiopia66. Co-infection cases have also been reported recently from institutions in, Brazil, Gedaref state in Sudan and India52.
People infected with HIV will develop VL more rap- idly than those who are not infected67. Co-infection of VL with HIV intensifies the burden of VL by causing severe forms and it become more difficult to manage due to drug resistance68. Therefore, treatment guidelines for HIV-VL co-infected cases should be regularly revised to overcome drug resistance challenges.
Community awareness
Visceral leishmaniasis is often found in areas that are remote with poor health facilities, where tools for screen- ing and identification of patients are inadequate, and with no or few trained man power. Factors such as family size, housing condition, cracked black soil near houses, prox- imity to animals and dumping animal dung near houses increases the risk of VL infection68. In addition, sleeping outside near animal shelters, under Balanites and Acacia trees and in the farm field overnight are also the major risk factors for VL in Ethiopia67. Due to lack of aware- ness and updated information, the most critical cases re- main untreated or unreported, and can act as a reservoir of infection for family members and neighbours69. There- fore, community mobilization should be done for the clini- cal manifestation, diagnosis, prevention and control mea- sures taken in VL endemic areas.
CONCLUSION
Complex transmission dynamics, lack of vector con- trol strategies, community awareness, limited trained health professionals and diagnostic approach for VL in
endemic areas are the major challenges of VL prevention and control. Identification of reservoir hosts for VL in different geographical areas is also another important as- pect. Therefore, proper case detection using sensitive di- agnostic techniques, community mobilization and launch- ing effective vector control strategies are the most important strategies to minimize the disease burden in endemic areas.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the Bahir Dar University, College of Medicine and Health Science’s ethical review committee which approved this review ar- ticle concerning the ethical issues.
Conflict of interest
The authors have no competing interest to declare in the publication of the manuscript.
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Correspondence to: Mr. Tadesse Hailu, Assistant Professor, Department of Microbiology, Immunology and Parasitology, College of Medicine and Health Science, Bahir Dar University, Ethiopia.
E-mail: [email protected]
Received: 28 December 2015 Accepted in revised form: 28 January 2016
