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Options for Effective Treatment of Visceral Leishmaniasis

  • Neglected Tropical Diseases (A Sanchez, Section Editor)
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Opinion statement

Visceral Leishmaniasis (VL), also known as kala-azar, is caused by several species of Leishmania, a protozoan parasite (Leishmania donovani) transmitted to humans by the bite of infected phelobotomine argentipes sandflies. VL is a disease of poverty, affecting the poorest of the poor. It is a major cause of morbidity and mortality in some areas (localized). If the infection is left untreated, the patient dies in about 2 years. Several drugs are now available for the treatment of VL. However, some of them are very costly (miltefosine, lipid amphotericin B). Sodium stibogluconate is an effective drug and the backbone of VL treatment for about six decades. Unfortunately, parasites developed resistance against the drug. In some areas in India, for example in North Bihar, approximately 60% of isolates are resistant to this treatment. In addition, the compound exhibits high cardio-toxity, which is an important limiting factor for its use. Based on the new data, which became available, the WHO/SEARO Regional Technical Advisory Group (RTAG) especially constituted for the kala-azar elimination program undertaken by India, Nepal, and Bangladesh in 2005, recommended that miltefosine should be used as the first line drug. However, the RTAG at its meeting in Dhaka (Bangladesh) in 2009 modified the above recommendation and advised that miltefosine should be phased out and replaced by lipid amphotericin B. The decision to switch over to lipid amphotericin B could have been delayed, because the program had already made substantial progress using miltefosine. In view of drug resistance, low compliance, availability and cost, it is imperative that serious efforts should be made to develop new drugs, preferably oral, for the treatment of VL and PKDL.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Brahmachari U. Gleanings from my research. Vol. I. Kala azar, its chemotherapy. University of Calcutta Press; 1940.

  2. •• Thakur CP, Sinha GP, Pandey AK, Kumar N, Kumar P, Hassan SM, Narain S, Roy RK. Do the diminishing efficacy and increasing toxicity of sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar, India, justify its continued use as a first-line drug? An observational study of 80 cases. Ann Trop Med Parasitol. 1998;92(5):561–9. This article documents that the increasing resistance developed by the parasite against Stibogluconate led to make the decision for not continuing it as the first line treatment for Kala-azar.

  3. • Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK. Injectable paromomycin for visceral leishmaniasis in India. N Engl J Med. 2007;356(25):2571–81. This article gives information about an alternative treatment for VL.

  4. • Rosenblatt JE. Antiparasitic agents. Mayo Clin Proc. 1999;74(11):1161–75. This article provides information about various anti-parasitic drugs.

  5. • Narayan S, Gupta AK, Singh Subhankar K, Lal CS, Singh VP, Sinha PK, Das P, Thakur CP. Clinical and laboratory comparison of different brands of amphotericin B used for the treatment of kala-azar: an observational study. J Commune Dis. 2008;40(4):273–6. This article provides detailed information about Amphotericin B.

  6. •• Sundar S, Jha TK, Thakur CP, Mishra M, Singh VP, Buffels R. Single-dose liposomal amphotericin B in the treatment of visceral leishmaniasis in India: a multicenter study. Clin Infect Dis. 2003;37(6):800–4. That by a multi-centric study, effectiveness of Liposomal Amphotericin B was established and paved the pathway for it to be the first line of drug for treatment of VL.

  7. • Sundar S, Singh A, Rai M, Chakravarty J. Single-dose indigenous liposomal amphotericin B in the treatment of Indian visceral leishmaniasis: a phase 2 study. AmJTrop Med Hyg. 2015;92(3):513–517. This article describes a clinical trial of an indigenous liposomal amphotericin B.

  8. •• Bhattacharya SK, Dash AP. Treatment of visceral leishmaniasis: options and choice. Lancet Infect Dis. 2016;16(2):142–3. This article gives the options for VL treatment and the choice based argument.

  9. • Jha TK, Sundar S, Thakur CP, Felton JM, Sabin AJ, Horton J. A phase II dose-ranging study of sitamaquine for the treatment of visceral leishmaniasis in India. AmJTrop Med Hyg. 2005;73(6):1005–11. Drug trial of a new drug is described.

  10. •• Sundar S, Sinha P, Jha TK, Chakravarty J, Rai M, Kumar N, Pandey K, Narain MK, Verma N, Das VN, Das P, Berman J, Arana B. Oral miltefosine for Indian post-kala-azar dermal leishmaniasis: a randomised trial. Tropical Med Int Health. 2013;18(1):96–97. Efficacy of Miltefosine for PKDL is described.

  11. • Das VN, Pandey K, Kumar N, Hassan SM, Bimal S, Lal CS, Siddiqui NA, Bhattacharya SK. Visceral leishmaniasis and tuberculosis in patients with HIV co-infection. Southeast Asian J Trop Med Public Health. 2006;37(1):18–21. VL co-infection HIV is reported.

  12. •• Singh OP, Hasker E, Sacks D, Boelaert M, Sundar S. Asymptomatic Leishmania infection: a new challenge for Leishmania control. Clin Infect Dis. 2014;58(10):1424–9. Possibility of asymptomatic infection rapidly tuning into full-blown case when VL cases are infected with HIV.

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Authors and Affiliations

  1. Glocal Hospital, Krishnanagore, Nadia, West Bengal, India

    Sujit K. Bhattacharya MD, Jamal Khan DCH & Sabahat Azim MBBS, IAS

  2. Indira Gandhi Institute of Medical Sciences, Patna, India

    Prabhat K. Sinha MD

Authors
  1. Sujit K. Bhattacharya MD
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  2. Jamal Khan DCH
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  3. Prabhat K. Sinha MD
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  4. Sabahat Azim MBBS, IAS
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Correspondence to Sujit K. Bhattacharya MD.

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Conflict of Interest

Dr. Sujit Bhattacharya and Prabhat Sinha worked for development of miltefosine (zentris) and paromomycin (OneWorld Health Organization), and the funds were received by Rajendra Memorial Research Institute of Medical Sciences, Patna, India. Md Jamal Khan, and Sabahat Azim declare that they have no conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Neglected Tropical Diseases

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Bhattacharya, S.K., Khan, J., Sinha, P.K. et al. Options for Effective Treatment of Visceral Leishmaniasis. Curr Treat Options Infect Dis 9, 194–199 (2017). https://doi.org/10.1007/s40506-017-0119-7

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  • DOI: https://doi.org/10.1007/s40506-017-0119-7

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