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Visceral Leishmaniasis

  • Shyam Sundar
  • Jaya Chakravarty
Chapter

Abstract

Pentavalent antimonials (SbV) have been the sheet anchor of therapy for leishmaniasis for >75 years. In the early 1980s, it was realized that a significant subset of patients with visceral leishmaniasis were not responding to SbV in the state of Bihar, India. Revised recommendation using ten times more drug provided a transient reprieve; however, a large proportion of patients in India and to some extent in Nepal remained unresponsive to SbV. Diverse studies have suggested emergence of SbV refractory strains in India. Attempts to find a marker of unresponsiveness have failed so far. Alternative therapeutic options include conventional amphotericin-B or its lipid formulations, oral miltefosine, and paromomycin and short course multidrug therapy. In the Indian subcontinent, the only recommended monotherapy is a single dose of liposomal amphotericin-B (L-AMB, dose 10 mg/kg) which is efficacious, safe, and ensures complete compliance. Multidrug therapy has high efficacy, short course, less toxicity, and prevents development of resistance. If these scarce antileishmanial drugs are to be protected from going down the lane of SbV, multidrug, short course, affordable treatment of VL should be evolved with access to all.

Keywords

Visceral leishmaniasis Drug resistance Amphotericin-B Antimonials Miltefosine Paromomycin 

References

  1. 1.
    World Health Organization. Leishmaniasis: situation and trends. 2015. http://www.who.int/gho/neglected_diseases/leishmaniasis/en/
  2. 2.
    World Health Organization. Leishmaniasis. Kala azar elimination Program. Report of a WHO consultation of a partners. Geneva, Switzerland. 10–11 February 2015. http://apps.who.int/iris/bitstream/10665/185042/1/9789241509497_eng.pdf
  3. 3.
    Zijlstra EE, Musa AM, Khalil EA, el-Hassan IM, et al. Post-kala-azar dermal leishmaniasis. Lancet Infect Dis. 2003;3:87–98.CrossRefPubMedGoogle Scholar
  4. 4.
    Thakur CP, Kumar K. Post kala-azar dermal leishmaniasis: a neglected aspect of kala-azar control programmes. Ann Trop Med Parasitol. 1992;86:355–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Magill AJ. Epidemiology of the leishmaniases. Dermatol Clin. 1995;13:505–23.CrossRefPubMedGoogle Scholar
  6. 6.
    Pearson RD, Jeronimo SMB, de Queiroz SA. Leishmaniasis. In: Guerrant RL, Walker DH, Weller PF, editors. Tropical infectious diseases: principles, pathogens and practice. Philadelphia: Churchill Livingstone; 1999. p. 797–813.Google Scholar
  7. 7.
    Mary C, Faraut F, Drogoul MP, Xeridat B, et al. Reference values for Leishmania infantum parasitemia in different clinical presentations: quantitative polymerase chain reaction for therapeutic monitoring and patient follow-up. Am J Trop Med Hyg. 2006;75:858–63.PubMedCrossRefGoogle Scholar
  8. 8.
    Bhattarai NR, Van der Auwera G, Khanal B, De Doncker S, et al. PCR and direct agglutination as Leishmania infection markers among healthy Nepalese subjects living in areas endemic for kala-azar. Trop Med Int Health. 2009;14:404–11.CrossRefPubMedGoogle Scholar
  9. 9.
    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;25:862–71.CrossRefPubMedGoogle Scholar
  10. 10.
    Desjeux P. The increase in risk factors for leishmaniasis worldwide. Trans R Soc Trop Med Hyg. 2001;95:239–43.CrossRefPubMedGoogle Scholar
  11. 11.
    Alvar J, Cañavate C, Gutiérrez-Solar B, Jiménez M, et al. Leishmania and human immunodeficiency virus co-infection: the first 10 years. Clin Microbiol Rev. 1997;10:298–319.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Tremblay M, Olivier M, Bernier R. Leishmania and the pathogenesis of HIV infection. Parasitol Today. 1996;12:257–61.CrossRefPubMedGoogle Scholar
  13. 13.
    Olivier M, Badaro R, Medrano FJ, Moreno J. The pathogenesis of Leishmania/HIV co-infection: cellular and immunological mechanisms. Ann Trop Med Parasitol. 2003;97:79–98.CrossRefPubMedGoogle Scholar
  14. 14.
    Rosenthal E, Marty P, Poizot-Martin I, Reynes J, et al. Visceral leishmaniasis and HIV-1 co-infection in southern France. Trans R Soc Trop Med Hyg. 1995;89:159–62.CrossRefPubMedGoogle Scholar
  15. 15.
    Gradoni L, Scalone A, Gramiccia M, Troiani M. Epidemiological surveillance of leishmaniasis in HIV-1-infected individuals in Italy. AIDS. 1996;10:785–91.CrossRefPubMedGoogle Scholar
  16. 16.
    Lopez-Velez R, Perez-Molina JA, Guerrero A, Baquero F, et al. Clinicoepidemiologic characteristics, prognostic factors, and survival analysis of patients co-infected with human immunodeficiency virus and Leishmania in an area of Madrid, Spain. Am J Trop Med Hyg. 1998;58:436–43.CrossRefPubMedGoogle Scholar
  17. 17.
    Pintado V, Martín-Rabadán P, Rivera ML, Moreno S, et al. Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study. Medicine (Baltimore). 2001;80:54–73.CrossRefGoogle Scholar
  18. 18.
    Laguna F, Videla S, Jiménez-Mejías ME, Sirera G, et al. Amphotericin-B lipid complex versus meglumine antimoniate in the treatment of visceral leishmaniasis in patients infected with HIV: a randomized pilot study. J Antimicrob Chemother. 2003;52:464–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Alvar J, Gutiérrez-Solar B, Pachón I, Calbacho E, et al. AIDS and Leishmania infantum. New approaches for a new epidemiological problem. Clin Dermatol. 1996;14:541–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Molina R, Gradoni L, Alvar J. HIV and the transmission of Leishmania. Ann Trop Med Parasitol. 2003;97:29–45.CrossRefPubMedGoogle Scholar
  21. 21.
    Desjeux P, Alvar J. Leishmania HIV co-infections: epidemiology in Europe. Ann Trop Med Parasitol. 2003;97:3–15.CrossRefPubMedGoogle Scholar
  22. 22.
    Alvar J, Aparicio P, Aseffa A, Den Boer M, et al. The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev. 2008;21:334–59.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Burza S, Mahajan R, Sanz MG, Sunyoto T, et al. HIV and visceral leishmaniasis coinfection in Bihar, India: an underrecognized and underdiagnosed threat against elimination. Clin Infect Dis. 2014;59:552–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Burza S, Sinha PK, Mahajan R, Lima MA, et al. Five-year field results and long-term effectiveness of 20 mg/kg liposomal amphotericin B (Ambisome) for visceral leishmaniasis in Bihar, India. PLoS Negl Trop Dis. 2014;8:e2603.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Albuquerque LC, Mendonça IR, Cardoso PN, Baldaçara LR, et al. HIV/AIDS-related visceral leishmaniasis: a clinical and epidemiological description of visceral leishmaniasis in northern Brazil. Rev Soc Bras Med Trop. 2014;47:38–46.CrossRefPubMedGoogle Scholar
  26. 26.
    Mengesha B, Endris M, Takele Y, Mekonnen K, et al. Prevalence of malnutrition and associated risk factors among adult visceral leishmaniasis patients in Northwest Ethiopia: a cross sectional study. BMC Res Notes. 2014;7:75.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Mengistu G, Ayele B. Visceral Leishmaniasis and HIV co-infection in patients admitted to Gondar university hospital, northwest Ethiopia. Ethiop J Health Dev. 2007;21:53–60.Google Scholar
  28. 28.
    Zijlstra EE, el-Hassan AM, Ismael A, Ghalib HW. Endemic kala-azar in eastern Sudan: a longitudinal study on the incidence of clinical and subclinical infection and post-kala-azar dermal leishmaniasis. Am J Trop Med Hyg. 1994;51:826–36.CrossRefPubMedGoogle Scholar
  29. 29.
    Schaefer KU, Kurtzhals JA, Gachihi GS, Muller AS, et al. A prospective seroepidemiological study of visceral leishmaniasis in Baringo district, rift valley province, Kenya. Trans R Soc Trop Med Hyg. 1995;89:471–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Ali A, Ashford RW. Visceral leishmaniasis in Ethiopia. IV. Prevalence, incidence and relation of infection to disease in an endemic area. Ann Trop Med Parasitol. 1994;88:289–93.CrossRefPubMedGoogle Scholar
  31. 31.
    Bern C, Haque R, Chowdhury R, Ali M, et al. The epidemiology of visceral leishmaniasis and asymptomatic leishmanial infection in a highly endemic Bangladeshi village. Am J Trop Med Hyg. 2007;76:909–14.PubMedCrossRefGoogle Scholar
  32. 32.
    Ostyn B, Gidwani K, Khanal B, Picado A, et al. Incidence of symptomatic and asymptomatic Leishmania donovani infections in high-endemic foci in India and Nepal: a prospective study. PLoS Negl Trop Dis. 2011;5:e1284.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Topno RK, Das VN, Ranjan A, Pandey K, et al. Asymptomatic infection with visceral leishmaniasis in a disease-endemic area in Bihar, India. Am J Trop Med Hyg. 2010;83:502–6.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Evans TG, Teixeira MJ, McAuliffe IT, Vasconcelos I, et al. Epidemiology of visceral leishmaniasis in northeast Brazil. J Infect Dis. 1992;166:1124–32.CrossRefPubMedGoogle Scholar
  35. 35.
    Moral L, Rubio EM, Moya M. A leishmanin skin test survey in the human population of l’Alacantí region (Spain): implications for the epidemiology of Leishmania infantum infection in southern Europe. Trans R Soc Trop Med Hyg. 2002;96:129–32.CrossRefPubMedGoogle Scholar
  36. 36.
    Stauch A, Sarkar RR, Picado A, Ostyn B, et al. Visceral leishmaniasis in the Indian subcontinent: modelling epidemiology and control. PLoS Negl Trop Dis. 2011;5:e1405.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Rijal S, Boelaert M, Regmi S, Karki BMS, et al. Evaluation of a urinary antigen-based latex agglutination test in the diagnosis of kala-azar in eastern Nepal. Trop Med Int Health. 2004;9:724–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Sundar S, Agrawal S, Pai K, Chance M, et al. Detection of leishmanial antigen in the urine of patients with visceral leishmaniasis by a latex agglutination test. Am J Trop Med Hyg. 2005;73:269–71.PubMedCrossRefGoogle Scholar
  39. 39.
    Chappuis F, Rijal S, Singh R, Acharya P, et al. A meta-analysis of the diagnostic performance of the direct agglutination test and rK39 dipstick for visceral leishmaniasis. Br Med J. 2006;333:723.CrossRefGoogle Scholar
  40. 40.
    Sundar S, Jha TK, Thakur CP, Sinha PK, et al. Injectable paromomycin for visceral leishmaniasis in India. N Engl J Med. 2007;356:2571–81.CrossRefPubMedGoogle Scholar
  41. 41.
    Hailu A. Pre- and post-treatment antibody levels in visceral leishmaniasis. Trans R Soc Trop Med Hyg. 1990;84:673–5.CrossRefPubMedGoogle Scholar
  42. 42.
    De Almeida SL, Romero HD, Prata A, Costa RT, et al. Immunologic tests in patients after clinical cure of visceral leishmaniasis. Am J Trop Med Hyg. 2006;75:739–43.CrossRefGoogle Scholar
  43. 43.
    Koirala S, Karki P, Das ML, Parija SC, et al. Epidemiological study of kala-azar by direct agglutination test in two rural communities of eastern Nepal. Trop Med Int Health. 2004;9:533–7.CrossRefPubMedGoogle Scholar
  44. 44.
    Schenkel K, Rijal S, Koirala S, Koirala S, et al. Visceral leishmaniasis in southeastern Nepal: a cross-sectional survey on Leishmania donovani infection and its risk factors. Trop Med Int Health. 2006;11:1792–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Ibrahim ME, Lambson B, Yousif AO, Deifalla NS, et al. Kala-azar in a high transmission focus: an ethnic and geographic dimension. Am J Trop Med Hyg. 1999;61:941–4.CrossRefPubMedGoogle Scholar
  46. 46.
    Sundar S, Maurya R, Singh RK, Bharti K, et al. Rapid, noninvasive diagnosis of visceral leishmaniasis in India: comparison of two immunochromatographic strip tests for detection of anti-K39 antibody. J Clin Microbiol. 2006;44:251–3.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Sundar S, Singh RK, Maurya R, Kumar B, et al. Serological diagnosis of Indian visceral leishmaniasis: direct agglutination test versus rK39 strip test. Trans R Soc Trop Med Hyg. 2006;100:533–7.CrossRefPubMedGoogle Scholar
  48. 48.
    Burns JM Jr, Shreffler WG, Benson DR, Ghalib HW, et al. Molecular characterization of a kinesin-related antigen of Leishmania chagasi that detects specific antibody in African and American visceral leishmaniasis. Proc Natl Acad Sci USA. 1993;90:775–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Veeken H, Ritmeijer K, Seaman J, Davidson R. Comparison of an rK39 dipstick rapid test with direct agglutination test and splenic aspiration for the diagnosis of kala-azar in Sudan. Trop Med Int Health. 2003;8:164–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Diro E, Techane Y, Tefera T, Assefa Y, et al. Field evaluation of FD-DAT, rk-39 dipstick and KATEX (urine latex agglutination) for diagnosis of visceral leishmaniasis in northwest Ethiopia. Trans R Soc Trop Med Hyg. 2007;101:908–14.CrossRefPubMedGoogle Scholar
  51. 51.
    Boelaert M, El-Safi S, Hailu A, Mukhtar M, et al. 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 R Soc Trop Med Hyg. 2008;102:32–40.CrossRefPubMedGoogle Scholar
  52. 52.
    Ritmeijer K, Melaku Y, Mueller M, Kipngetich S, et al. Evaluation of a new recombinant K39 rapid diagnostic test for Sudanese visceral leishmaniasis. Am J Trop Med Hyg. 2006;74:76–80.PubMedCrossRefGoogle Scholar
  53. 53.
    Peters W. The treatment of kala-azar. New approach to an old problem. Indian J Med Res. 1981;73:1–18.PubMedGoogle Scholar
  54. 54.
    Anonymous. Proceedings of the meeting of an expert group on kala-azar held at Indian Council of Medical Research Headquarters. Indian Council of Medical Research, New Delhi, 9 Sept 1977.Google Scholar
  55. 55.
    Aikat BK, Sahaya S, Pathania AG, Bhattacharya PK, et al. Clinical profile of cases of kala-azar in Bihar. Indian J Med Res. 1979;70:563–70.PubMedGoogle Scholar
  56. 56.
    Thakur CP, Kumar M, Singh SK, Sharma D, et al. Comparison of regimens of treatment with sodium stibogluconate in kalaazar. Br Med J (Clin Res Ed). 1984;288:895–7.CrossRefGoogle Scholar
  57. 57.
    World Health Organization. The leishmaniases: report of a WHO expert committee. WHO Tech Rep Ser. 1984;701:99–108.Google Scholar
  58. 58.
    Thakur CP, Kumar M, Kumar P, Mishra BN, et al. Rationalisation of regimens of treatment of kala-azar with sodium stibogluconate in India: a randomised study. Br Med J (Clin Res Ed). 1988;296:1557–61.CrossRefGoogle Scholar
  59. 59.
    Thakur CP, Kumar M, Pandey AK. Evaluation of efficacy of longer duration of therapy of fresh cases of kala-azar with sodium stibogluconate. Indian J Med Res. 1991;93:103–10.PubMedGoogle Scholar
  60. 60.
    Jha TK, Singh NK, Jha SN. Therapeutic use of sodium stibogluconate in kala-azar from some hyperendemic districts of N. Bihar, India (Abstract). J Assoc Physicians India. 1992;40:868.Google Scholar
  61. 61.
    Sundar S, Agrawal NK, Sinha PR, Horwith GS, et al. Short-course, low dose Amphotericin-B lipid complex therapy for visceral leishmaniasis unresponsive to antimony. Ann Intern Med. 1997;127:133–7.CrossRefPubMedGoogle Scholar
  62. 62.
    Sundar S, More DK, Singh MK, Singh VP, et al. Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis. 2000;31:1104–7.CrossRefPubMedGoogle Scholar
  63. 63.
    Rijal S, Chappuis F, Singh R, Bovier PA, et al. Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline. Trans R Soc Trop Med Hyg. 2003;97:350–4.CrossRefPubMedGoogle Scholar
  64. 64.
    Lira R, Sundar S, Makharia A, Kenney R, et al. Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani. J Infect Dis. 1999;180:564–7.CrossRefPubMedGoogle Scholar
  65. 65.
    Sundar S, Thakur BB, Tandon AK, Agrawal NR, et al. Clinico-epidemiological study of drug resistance in Indian kala-azar. Br Med J. 1994;308:307.CrossRefGoogle Scholar
  66. 66.
    Sundar S, Sinha PR, Agrawal NK, Srivastava R, et al. A cluster of severe antimony cardiotoxicity in kala-azar due to high osmolality lot. Am J Trop Med Hyg. 1998;59:139–43.CrossRefPubMedGoogle Scholar
  67. 67.
    Jha TK. Evaluation of diamidine compounds (pentamidine isethionate) in the treatment of resistant cases of kala-azar occurring in North Bihar, India. Trans R Soc Trop Med Hyg. 1983;77:167–70.CrossRefPubMedGoogle Scholar
  68. 68.
    Jha SN, Singh NK, Jha TK. Changing response to diamidine compounds in cases of kalaazar unresponsive to antimonials. J Assoc Phys India. 1991;39:314–6.Google Scholar
  69. 69.
    Thakur CP, Kumar M, Pandey AK. Comparison of regimens of treatment of antimony resistant kala-azar patients: a randomized study. Am J Trop Med Hyg. 1991;45:435–41.CrossRefPubMedGoogle Scholar
  70. 70.
    Thakur CP, Singh RK, Hassan SM, Kumar R, et al. Amphotericin-B deoxycholate treatment of visceral leishmaniasis with newer modes of administration and precautions: a study of 938 cases. Trans R Soc Trop Med Hyg. 1999;93:9–23.CrossRefGoogle Scholar
  71. 71.
    Mishra M, Biswas UK, Jha DN, Khan AB. Amphotericin versus pentamidine in antimony-unresponsive kala-azar. Lancet. 1992;340:1256–7.CrossRefPubMedGoogle Scholar
  72. 72.
    National Vector Borne Disease Control Programme (NVBDCP). Guidelines for Vector Borne Disease http://nvbdcp.gov.in/kal8.html. Accessed 20 Sept 2010.
  73. 73.
    Sundar S, Singh VP, Sharma S, Makharia M, et al. Response to interferon-gamma plus pentavalent antimony in Indian visceral leishmaniasis. J Infect Dis. 1997;176:1117–9.CrossRefPubMedGoogle Scholar
  74. 74.
    Sundar S, Jha TK, Thakur CP, Mishra M, et al. Low-dose liposomal Amphotericin-B in refractory Indian visceral leishmaniasis: a multicenter study. Am J Trop Med Hyg. 2002;66:143–6.CrossRefPubMedGoogle Scholar
  75. 75.
    Berman JD. DS Food and Drug administration approval of AmBisome (liposomal Amphotericin-B) for treatment of visceral leishmaniasis. Clin Infect Dis. 1999;28:49–51.CrossRefPubMedGoogle Scholar
  76. 76.
    Sundar S, Jha TK, Thakur CP, Mishra M, et al. Single dose liposomal Amphotericin-B in the treatment of visceral leishmaniasis in India: a multicenter study. Clin Infect Dis. 2003;37:800–4.CrossRefPubMedGoogle Scholar
  77. 77.
    Olliaro P, Sundar S. Anthropometrically derived dosing and drug costing calculations for treating visceral leishmaniasis in Bihar, India. Trop Med Int Health. 2009;14:88–92.CrossRefPubMedGoogle Scholar
  78. 78.
    Sundar S, Jha TK, Thakur CP, Engel J, et al. Oral Miltefosine for Indian visceral leishmaniasis. N Engl J Med. 2002;347:1739–46.CrossRefPubMedGoogle Scholar
  79. 79.
    Sundar S, Murray HW. Availability of Miltefosine for the treatment of kala-azar in India. Bull World Health Organ. 2005;83:394–5.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Sundar S, Mondal D, Rijal S, Bhattacharya S, et al. Implementation research to support the initiative on the elimination of kala azar from Bangladesh, India and Nepal--the challenges for diagnosis and treatment. Trop Med Int Health. 2008;13:2–5.CrossRefPubMedGoogle Scholar
  81. 81.
    Sundar S, Singh A, Rai M, Prajapati VK, et al. Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use. Clin Infect Dis. 2012;55:543–50.CrossRefPubMedGoogle Scholar
  82. 82.
    Burza S, Nabi E, Mahajan R, Mitra G, et al. One-year follow-up of immunocompetent male patients treated with miltefosine for primary visceral leishmaniasis in Bihar. India Clin Infect Dis. 2013;57:1363–4.CrossRefPubMedGoogle Scholar
  83. 83.
    Rijal S, Ostyn B, Uranw S, Rai K, et al. Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance. Clin Infect Dis. 2013;56:1530–8.CrossRefPubMedGoogle Scholar
  84. 84.
    Rahman M, Ahmed BN, Faiz MA, Chowdhury MZ, et al. Phase IV trial of miltefosine in adults and children for treatment of visceral leishmaniasis (kala-azar) in Bangladesh. Am J Trop Med Hyg. 2011;85:66–9.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Ritmeijer K, Dejenie A, Assefa Y, Hundie TB, et al. A comparison of Miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection. Clin Infect Dis. 2006;43:357–64.CrossRefPubMedGoogle Scholar
  86. 86.
    Sundar S, Singh RK, Bimal SK, Gidwani K, et al. Comparative evaluation of parasitology and serological tests in the diagnosis of visceral leishmaniasis in India: a phase III diagnostic accuracy study. Trop Med Int Health. 2007;12:284–9.PubMedGoogle Scholar
  87. 87.
    Teklemariam S, Hiwot AG, Frommel D, Miko TL, et al. Aminosidine and its combination with sodium stibogluconate in the treatment of diffuse cutaneous leishmaniasis caused by Leishmania aethiopica. Trans R Soc Trop Med Hyg. 1994;88:334–9.CrossRefPubMedGoogle Scholar
  88. 88.
    Sundar S, Rai M. Treatment of visceral leishmaniasis. Expert Opin Pharmacother. 2005;6:2821–9.CrossRefPubMedGoogle Scholar
  89. 89.
    Hasker E, Singh SP, Malaviya P, Singh RP, et al. Management of visceral leishmaniasis in rural primary health care services in Bihar, India. Trop Med Int Health. 2010;15:55–62.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Sundar S, Rai M, Chakravarty J, Agarwal D, et al. New treatment approach in Indian visceral leishmaniasis: single-dose liposomal Amphotericin-B followed by short-course oral Miltefosine. Clin Infect Dis. 2008;47:1000–6.CrossRefPubMedGoogle Scholar
  91. 91.
    Sundar S, Sinha PK, Rai M, Verma DK, et al. Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial. Lancet. 2011;5:477–86.CrossRefGoogle Scholar
  92. 92.
    World Health Organization. Control of leishmaniasis: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22–26 March, 2010. http://www.whqlibdoc.WHO.int/trs/WHO_TRS_949_eng.pdf. Accessed 20 Mar 2011.
  93. 93.
    Sundar S, Chakravarty J, Agarwal D, Rai M, et al. Single-dose liposomal Amphotericin-B for visceral leishmaniasis in India. N Engl J Med. 2010;362:504–12.CrossRefPubMedGoogle Scholar
  94. 94.
    Mondal DAJ. Efficacy and safety of single-dose liposomal amphotericin B for visceral leishmaniasis in a rural public hospital in Bangladesh: A feasibility study. Lancet Glob Health. 2014;2:e51–e7.CrossRefPubMedGoogle Scholar
  95. 95.
    Khalil EA, Weldegebreal T, Younis BM, Omollo R, et al. Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. PLoS Negl Trop Dis. 2014;8:e2613.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Sundar S, Chakravarty J. An update on pharmacotherapy for leishmaniasis. Expert Opin Pharmacother. 2015;16:237–52.CrossRefPubMedGoogle Scholar
  97. 97.
    Kaul SM, Sharma RS, Dey KP, Rai RN, et al. Impact of DDT indoor residual spraying on Phlebotomus argentipes in a kala-azar endemic village in eastern Uttar Pradesh. Bull World Health Organ. 1994;72:79–81.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Hassan MM, Elraba’a FMA, Ward RD, Maingon R, et al. Detection of high rates of in-village transmission of Leishmania donovani in eastern Sudan. Acta Trop. 2004;92:77–82.CrossRefPubMedGoogle Scholar
  99. 99.
    Bern C, Joshi AB, Jha SN, Das ML, et al. Factors associated with visceral leishmaniasis in Nepal: bed-net use is strongly protective. Am J Trop Med Hyg. 2000;63:184–8.CrossRefPubMedGoogle Scholar
  100. 100.
    Bern C, Hightower AW, Chowdhury R, Ali M, et al. Risk factors for kala-azar in Bangladesh. Emerg Infect Dis. 2005;11:655–62.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Ritmeijer K, Davies C, van Zorge R, Wang SJ, et al. Evaluation of a mass distribution programme for fine-mesh impregnated bednets against visceral leishmaniasis in eastern Sudan. Trop Med Int Health. 2007;12:404–14.CrossRefPubMedGoogle Scholar
  102. 102.
    Singh SP, Hasker E, Picado A, Gidwani K, et al. Risk factors for visceral leishmaniasis in India: further evidence on the role of domestic animals. Trop Med Int Health. 2010;15:29–35.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Shyam Sundar
    • 1
  • Jaya Chakravarty
    • 1
  1. 1.Department of Medicine, Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia

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