Visceral leishmaniasis: Epidemiology and control
- Caryn Bern, MD, MPH
Caryn Bern, MD, MPH
- Professor, Global Health Sciences
- University of California, San Francisco
Leishmaniasis consists of a complex of vector-borne diseases caused by more than 20 species of the protozoan genus Leishmania and is transmitted by sand fly vectors (table 1) [1,2]. Clinical manifestations range from cutaneous ulcers to systemic multiorgan disease. Visceral leishmaniasis (VL) is caused primarily by the two related species Leishmania donovani and Leishmania infantum (synonym Leishmania chagasi).
An estimated 200,000 to 400,000 new VL cases and 20,000 to 40,000 deaths from VL occur each year [3,4]. Among tropical diseases, leishmaniasis ranks second in mortality and fourth in loss of disability-adjusted life years (DALYs) . Leishmaniasis is considered one of the "most neglected diseases" given its strong association with poverty and the limited resources invested in new tools for diagnosis, treatment, and control [6,7].
Issues related to epidemiology and control are discussed here. Issues related to clinical manifestations, diagnosis, and treatment are discussed separately. (See related topics.)
The epidemiology and ecology of visceral leishmaniasis (VL) in a particular region are determined by characteristics of the parasite species, sand fly species, and mammalian reservoir host(s) (figure 1). In all major endemic areas, asymptomatic infections (measured by seroconversion and/or leishmanin skin testing) outnumber clinically manifest disease [8-11]. Seroconversion reflects newly acquired infection but may precede onset of clinical VL by months [9,10].
The best measure of protective immunity is the leishmanin skin test (LST), which reflects durable but probably not permanent cell-mediated immunity. Individuals with positive LST have more than 95 percent reduced risk of VL compared to those with negative LST, and the age-related rise in positive LST prevalence in a community parallels the age-related decrease in disease risk [11-14]. A parallel fall in the average age of VL patients may be observed as an epidemic matures . Factors that increase the likelihood an individual will progress from leishmanial infection to clinical VL include poor nutritional status, age <5 years (for L. infantum infection), HIV coinfection, and host immunogenetic factors [13,16-20].
- Jeronimo SMB, de Queiroz Sousa A, Pearson RD. Leishmaniasis. In: Tropical Infectious Diseases: Principles, Pathogens and Practice, 3rd ed, Guerrant RL, Walker DH, Weller PF (Eds), Saunders Elsevier, Philadelphia 2011. p.696.
- World Health Organization. Control of the Leishmaniases: Report of the WHO Expert Committee Meeting, Geneva. March 22-26, 2010. WHO Technical Report Series 2010; 949:1.
- World Health Organization. The Global Burden of Disease: 2004 update. Geneva, Switzerland: World Health Organization, 2008.
- Alvar J, Vélez ID, Bern C, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One 2012; 7:e35671.
- Mathers CD, Ezzati M, Lopez AD. Measuring the burden of neglected tropical diseases: the global burden of disease framework. PLoS Negl Trop Dis 2007; 1:e114.
- Yamey G, Torreele E. The world's most neglected diseases. BMJ 2002; 325:176.
- Alvar J, Yactayo S, Bern C. Leishmaniasis and poverty. Trends Parasitol 2006; 22:552.
- Marty P, Lelievre A, Quaranta JF, et al. Use of the leishmanin skin test and western blot analysis for epidemiological studies in visceral leishmaniasis areas: experience in a highly endemic focus in Alpes-Maritimes (France). Trans R Soc Trop Med Hyg 1994; 88:658.
- Hasker E, Malaviya P, Gidwani K, et al. Strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in India and Nepal. PLoS Negl Trop Dis 2014; 8:e2657.
- Bern C, Haque R, Chowdhury R, et al. The epidemiology of visceral leishmaniasis and asymptomatic leishmanial infection in a highly endemic Bangladeshi village. Am J Trop Med Hyg 2007; 76:909.
- Lima ID, Queiroz JW, Lacerda HG, et al. Leishmania infantum chagasi in northeastern Brazil: asymptomatic infection at the urban perimeter. Am J Trop Med Hyg 2012; 86:99.
- Bern C, Amann J, Haque R, et al. Loss of leishmanin skin test antigen sensitivity and potency in a longitudinal study of visceral leishmaniasis in Bangladesh. Am J Trop Med Hyg 2006; 75:744.
- Davies CR, Mazloumi Gavgani AS. Age, acquired immunity and the risk of visceral leishmaniasis: a prospective study in Iran. Parasitology 1999; 119 ( Pt 3):247.
- Khalil EA, Zijlstra EE, Kager PA, El Hassan AM. Epidemiology and clinical manifestations of Leishmania donovani infection in two villages in an endemic area in eastern Sudan. Trop Med Int Health 2002; 7:35.
- Alvar J, Bashaye S, Argaw D, et al. Kala-azar outbreak in Libo Kemkem, Ethiopia: epidemiologic and parasitologic assessment. Am J Trop Med Hyg 2007; 77:275.
- Cerf BJ, Jones TC, Badaro R, et al. Malnutrition as a risk factor for severe visceral leishmaniasis. J Infect Dis 1987; 156:1030.
- Anstead GM, Chandrasekar B, Zhao W, et al. Malnutrition alters the innate immune response and increases early visceralization following Leishmania donovani infection. Infect Immun 2001; 69:4709.
- Soong L, Henard CA, Melby PC. Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis. Semin Immunopathol 2012; 34:735.
- Jeronimo SM, Duggal P, Ettinger NA, et al. Genetic predisposition to self-curing infection with the protozoan Leishmania chagasi: a genomewide scan. J Infect Dis 2007; 196:1261.
- van Griensven J, Carrillo E, López-Vélez R, et al. Leishmaniasis in immunosuppressed individuals. Clin Microbiol Infect 2014; 20:286.
- Bern C, Maguire JH, Alvar J. Complexities of assessing the disease burden attributable to leishmaniasis. PLoS Negl Trop Dis 2008; 2:e313.
- Singh N, Mishra J, Singh R, Singh S. Animal reservoirs of visceral leishmaniasis in India. J Parasitol 2013; 99:64.
- Elnaiem DA, Hassan HK, Ward RD. Phlebotomine sandflies in a focus of visceral leishmaniasis in a border area of eastern Sudan. Ann Trop Med Parasitol 1997; 91:307.
- Bucheton B, Kheir MM, El-Safi SH, et al. The interplay between environmental and host factors during an outbreak of visceral leishmaniasis in eastern Sudan. Microbes Infect 2002; 4:1449.
- Seaman J, Mercer AJ, Sondorp E. The epidemic of visceral leishmaniasis in western Upper Nile, southern Sudan: course and impact from 1984 to 1994. Int J Epidemiol 1996; 25:862.
- Elnaiem DA, Hassan MM, Maingon R, et al. The Egyptian mongoose, Herpestes ichneumon, is a possible reservoir host of visceral leishmaniasis in eastern Sudan. Parasitology 2001; 122:531.
- Dereure J, El-Safi SH, Bucheton B, et al. Visceral leishmaniasis in eastern Sudan: parasite identification in humans and dogs; host-parasite relationships. Microbes Infect 2003; 5:1103.
- Evans TG, Teixeira MJ, McAuliffe IT, et al. Epidemiology of visceral leishmaniasis in northeast Brazil. J Infect Dis 1992; 166:1124.
- Alvar J, Aparicio P, Aseffa A, et al. The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev 2008; 21:334.
- Gil-Prieto R, Walter S, Alvar J, de Miguel AG. Epidemiology of leishmaniasis in Spain based on hospitalization records (1997-2008). Am J Trop Med Hyg 2011; 85:820.
- Dye C, Williams BG. Malnutrition, age and the risk of parasitic disease: visceral leishmaniasis revisited. Proc Biol Sci 1993; 254:33.
- Seaman J, Ashford RW, Schorscher J, Dereure J. Visceral leishmaniasis in southern Sudan: status of healthy villagers in epidemic conditions. Ann Trop Med Parasitol 1992; 86:481.
- Gramiccia M, Bettini S, Gradoni L, et al. Leishmaniasis in Sardinia. 5. Leishmanin reaction in the human population of a focus of low endemicity of canine leishmaniasis. Trans R Soc Trop Med Hyg 1990; 84:371.
- Courtenay O, Quinnell RJ, Garcez LM, Dye C. Low infectiousness of a wildlife host of Leishmania infantum: the crab-eating fox is not important for transmission. Parasitology 2002; 125:407.
- Alexander B, Maroli M. Control of phlebotomine sandflies. Med Vet Entomol 2003; 17:1.
- Dey A, Singh S. Transfusion transmitted leishmaniasis: a case report and review of literature. Indian J Med Microbiol 2006; 24:165.
- Antinori S, Cascio A, Parravicini C, et al. Leishmaniasis among organ transplant recipients. Lancet Infect Dis 2008; 8:191.
- Herwaldt BL, Juranek DD. Laboratory-acquired malaria, leishmaniasis, trypanosomiasis, and toxoplasmosis. Am J Trop Med Hyg 1993; 48:313.
- Meinecke CK, Schottelius J, Oskam L, Fleischer B. Congenital transmission of visceral leishmaniasis (Kala Azar) from an asymptomatic mother to her child. Pediatrics 1999; 104:e65.
- Alvar J, Jiménez M. Could infected drug-users be potential Leishmania infantum reservoirs? AIDS 1994; 8:854.
- Cruz I, Morales MA, Noguer I, et al. Leishmania in discarded syringes from intravenous drug users. Lancet 2002; 359:1124.
- Bates PA, Depaquit J, Galati EA, et al. Recent advances in phlebotomine sand fly research related to leishmaniasis control. Parasit Vectors 2015; 8:131.
- Killick-Kendrick R, Rioux JA, Bailly M, et al. Ecology of leishmaniasis in the south of France. 20. Dispersal of Phlebotomus ariasi Tonnoir, 1921 as a factor in the spread of visceral leishmaniasis in the Cévennes. Ann Parasitol Hum Comp 1984; 59:555.
- Bora D. Epidemiology of visceral leishmaniasis in India. Natl Med J India 1999; 12:62.
- Sen Gupta PC. Return of kala-azar. J Indian Med Assoc 1975; 65:89.
- Reyburn H, Ashford R, Mohsen M, et al. A randomized controlled trial of insecticide-treated bednets and chaddars or top sheets, and residual spraying of interior rooms for the prevention of cutaneous leishmaniasis in Kabul, Afghanistan. Trans R Soc Trop Med Hyg 2000; 94:361.
- Courtenay O, Gillingwater K, Gomes PA, et al. Deltamethrin-impregnated bednets reduce human landing rates of sandfly vector Lutzomyia longipalpis in Amazon households. Med Vet Entomol 2007; 21:168.
- Mondal D, Huda MM, Karmoker MK, et al. Reducing visceral leishmaniasis by insecticide impregnation of bed-nets, Bangladesh. Emerg Infect Dis 2013; 19:1131.
- Picado A, Singh SP, Rijal S, et al. Longlasting insecticidal nets for prevention of Leishmania donovani infection in India and Nepal: paired cluster randomised trial. BMJ 2010; 341:c6760.
- Dinesh DS, Das P, Picado A, et al. Long-lasting insecticidal nets fail at household level to reduce abundance of sandfly vector Phlebotomus argentipes in treated houses in Bihar (India). Trop Med Int Health 2008; 13:953.
- Picado A, Singh SP, Vanlerberghe V, et al. Residual activity and integrity of PermaNet® 2.0 after 24 months of household use in a community randomised trial of long lasting insecticidal nets against visceral leishmaniasis in India and Nepal. Trans R Soc Trop Med Hyg 2012; 106:150.
- Gavgani AS, Hodjati MH, Mohite H, Davies CR. Effect of insecticide-impregnated dog collars on incidence of zoonotic visceral leishmaniasis in Iranian children: a matched-cluster randomised trial. Lancet 2002; 360:374.
- Schreck CE, Kline DL, Chaniotis BN, et al. Evaluation of personal protection methods against phlebotomine sand flies including vectors of leishmaniasis in Panama. Am J Trop Med Hyg 1982; 31:1046.
- Addy M, Nandy A. Ten years of kala-azar in west Bengal, Part I. Did post-kala-azar dermal leishmaniasis initiate the outbreak in 24-Parganas? Bull World Health Organ 1992; 70:341.
- Napier LE, Das Gupta CR. An epidemiological investigation of kala-azar in a rural area in Bengal. Indian J Med Res 1931; 19:295.
- Islam S, Kenah E, Bhuiyan MA, et al. Clinical and immunological aspects of post-kala-azar dermal leishmaniasis in Bangladesh. Am J Trop Med Hyg 2013; 89:345.
- Quinnell RJ, Courtenay O. Transmission, reservoir hosts and control of zoonotic visceral leishmaniasis. Parasitology 2009; 136:1915.
- Killick-Kendrick R. The race to discover the insect vector of kala-azar: a great saga of tropical medicine 1903-1942. Bull Soc Pathol Exot 2013; 106:131.
- Courtenay O, Quinnell RJ, Garcez LM, et al. Infectiousness in a cohort of brazilian dogs: why culling fails to control visceral leishmaniasis in areas of high transmission. J Infect Dis 2002; 186:1314.
- Courtenay O, Carson C, Calvo-Bado L, et al. Heterogeneities in Leishmania infantum infection: using skin parasite burdens to identify highly infectious dogs. PLoS Negl Trop Dis 2014; 8:e2583.
- Bern C, Courtenay O, Alvar J. Of cattle, sand flies and men: a systematic review of risk factor analyses for South Asian visceral leishmaniasis and implications for elimination. PLoS Negl Trop Dis 2010; 4:e599.