Visceral leishmaniasis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Medical Therapy

As with many diseases in developing nations, (including trypanosomiasis and malaria) effective and affordable chemotherapy is sorely lacking and parasites or insect vectors are becoming increasingly resistant to existing anti-parasite drugs. Presumably due to the lack of financial return, new drugs are slow to emerge and much of the basic research into potential drug targets takes place in universities, funded by charitable organisations. This may or may not change as a result of infection of members of the armed forces from the "developed" nations that currently occupy nations such as Afghanistan and Iraq, where Leishmania is commonplace.

The traditional treatment is with pentavalent antimonials such as sodium stibogluconate and meglumine antimoniate. Resistance is now common in India,[1][2] and the treatment of choice for visceral leishmaniasis acquired in India is now Amphotericin B[3] in its various preparations (Ambisome®,[4] Abelcet®, Amphocil®[5])

  • AmBisome dose: total dose 21mg/kg (Mediterranean/Brazilian VL); total dose 7.5mg/kg over 6 days (Indian VL)
  • Amphocil dose: total dose 7.5mg/kg over 6 days (Indian VL)

A low dose (0.5–1mg/kg) is given on the first day, increasing to 1–2mg/kg on the second day, followed by 1.5–3mg/kg on the third and subsequent days.

Miltefosine Impavido® is the first oral treatment for this disease. The cure rate of miltefosine in phase III clinical trials is 95%; Studies in Ethiopia show that is also effective in Africa. In HIV immunosuppressed people which are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment. Miltefosine has received approval by the Indian regulatory authorities in 2002 and in Germany in 2004.It is now registered in many countries. The drug is generally better tolerated than other drugs. Main side effects are gastrointetinal disturbance in the first or second day of treatment (a course of treatment is 28 days) which does not affect the efficiency. Because it is available as an oral formulation, the expense and inconvenience of hospitalisation is avoided, which makes it a drug of choice.

The nonprofit Institute for OneWorld Health has developed the drug paromomycin, which they claim is effective and cheap. A treatment with paromomycin will cost about $10. The drug had originally been identified in th 1960's, but had been abandoned because it would not be profitable, as the disease mostly affects poor people.[6] The Indian government approved paromomycin for sale in August 2006.[7]

References

  1. Sundar S; et al. (2000). "Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic". Clin Infect Dis. 31: 1104&ndash, 7.
  2. Thakur CP; et al. (2004). "Epidemiological, clinical & pharmacological study of antimony-resistant visceral leishmaniasis in Bihar, India". Clin Infect Dis. 120: 166&ndash, 72.
  3. Thakur CP, Singh RK, Hassan SM, Kumar R, Narain S, Kumar A. "Amphotericin B deoxycholate treatment of visceral leishmaniasis with never modes of administration and precautions: a study of 938 cases". Trans R Soc Trop Med Hyg. 93: 319&ndash, 23.
  4. Thakur CP, Pandey AK, Sinha GP, Roy S, Behbehani K, Olliaro P (1996). "Comparison of three treatment regimens with liposomal amphotericin B (AmBisome) for visceral leishmaniasis in India: a randomized dose-finding study". Trans R Soc Trop Med Hyg. 90: 319&ndash, 22.
  5. Sundar S; et al. (2006). "Amphotericin B Colloidal Dispersion for the Treatment of Indian Visceral Leishmaniasis". Clin Infect Dis. 42 (5): 608&ndash, 13.
  6. A Small Charity Takes the Reins in Fighting a Neglected Disease, New York Times, July 31, 2006.
  7. NEW CURE FOR DEADLY VISCERAL LEISHMANIASIS (KALA-AZAR) APPROVED BY GOVERNMENT OF INDIA, Institute for OneWorld Health Press Release, Sept 8, 2006.

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