Eliminating visceral leishmaniasis in South Asia: the road ahead

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Abstract

Suman Rijal and colleagues highlight lessons from a regional collaboration to eliminate visceral leishmaniasis and identify priorities for the post-elimination plan

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Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?

François Chappuis, Shyam Sundar, Asrat Hailu … (2007)

Visceral leishmaniasis (VL) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. Poor and neglected populations in East Africa and the Indian sub-continent are particularly affected. Early and accurate diagnosis and treatment remain key components of VL control. In addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. Miltefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphotericin B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies. New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients.

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Oral miltefosine for Indian visceral leishmaniasis.

Shyam Sundar, T Jha, C P Thakur … (2002)

There are 500,000 cases per year of visceral leishmaniasis, which occurs primarily in the Indian subcontinent. Almost all untreated patients die, and all the effective agents have been parenteral. Miltefosine is an oral agent that has been shown in small numbers of patients to have a favorable therapeutic index for Indian visceral leishmaniasis. We performed a clinical trial in India comparing miltefosine with the most effective standard treatment, amphotericin B. The study was a randomized, open-label comparison, in which 299 patients 12 years of age or older received orally administered miltefosine (50 or 100 mg [approximately 2.5 mg per kilogram of body weight] daily for 28 days) and 99 patients received intravenously administered amphotericin B (1 mg per kilogram every other day for a total of 15 injections). The groups were well matched in terms of age, weight, proportion with previous failure of treatment for leishmaniasis, parasitologic grade of splenic aspirate, and splenomegaly. At the end of treatment, splenic aspirates were obtained from 293 patients in the miltefosine group and 98 patients in the amphotericin B group. No parasites were identified, for an initial cure rate of 100 percent. By six months after the completion of treatment, 282 of the 299 patients in the miltefosine group (94 percent [95 percent confidence interval, 91 to 97]) and 96 of the 99 patients in the amphotericin B group (97 percent) had not had a relapse; these patients were classified as cured. Vomiting and diarrhea, generally lasting one to two days, occurred in 38 percent and 20 percent of the patients in the miltefosine group, respectively. Oral miltefosine is an effective and safe treatment for Indian visceral leishmaniasis. Miltefosine may be particularly advantageous because it can be administered orally. It may also be helpful in regions where parasites are resistant to current agents. Copyright 2002 Massachusetts Medical Society

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Recent Development of Visceral Leishmaniasis Treatments: Successes, Pitfalls, and Perspectives

Fabiana P. Alves, Graeme Bilbe, Severine Blesson … (2018)

SUMMARY Research in visceral leishmaniasis in the last decade has been focused on how better to use the existing medicines as monotherapy or in combination. Systematic research by geographical regions has shown that a universal treatment is far from today's reality. Substantial progress has been made in the elimination of kala-azar in South Asia, with a clear strategy on first- and second-line therapy options of single-dose liposomal amphotericin B and a combination of paromomycin and miltefosine, respectively, among other interventions. In Eastern Africa, sodium stibogluconate (SSG) and paromomycin in combination offer an advantage compared to the previous SSG monotherapy, although not exempted of limitations, as this therapy requires 17 days of painful double injections and bears the risk of SSG-related cardiotoxicity. In this region, attempts to improve the combination therapy have been unsuccessful. However, pharmacokinetic studies have led to a better understanding of underlying mechanisms, like the underexposure of children to miltefosine treatment, and an improved regimen using an allometric dosage. Given this global scenario of progress and pitfalls, we here review what steps need to be taken with existing medicines and highlight the urgent need for oral drugs. Furthermore, it should be noted that six candidates belonging to five new chemical classes are reaching phase I, ensuring an optimistic near future.

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Author and article information

Contributors

Suman Rijal: Role: director

Shyam Sundar: Role: professor

Dinesh Mondal: Role: senior scientist

Pradeep Das: Role: director

Jorge Alvar: Role: senior adviser

Marleen Boelaert: Role: professor

Journal

Journal ID (nlm-ta): BMJ

Journal ID (iso-abbrev): BMJ

Journal ID (publisher-id): BMJ-UK

Journal ID (hwp): bmj

Title: The BMJ

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1756-1833

Publication date Collection: 2019

Publication date (Electronic): 22 January 2019

Volume: 364

Electronic Location Identifier: k5224

Affiliations

[1 ]Drugs for Neglected Diseases Initiative, New Delhi, India

[2 ]Benaras Hindu University, Varanasi, India

[3 ]International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh

[4 ]Rajendra Memorial Research Institute of Medical Sciences, Patna, India

[5 ]Drugs for Neglected Diseases Initiative, Geneva, Switzerland

[6 ]Institute of Tropical Medicine, Antwerp, Belgium.

Author notes

Correspondence to: S Rijal srijal@ 123456dndi.org

Article

Publisher ID: rijs45502

DOI: 10.1136/bmj.k5224

PMC ID: 6340338

PubMed ID: 30670453

SO-VID: 3df476e1-2572-4edb-9946-4d7ba719f296

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This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Eliminating visceral leishmaniasis in South Asia: the road ahead

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Most cited references 30

Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?

Oral miltefosine for Indian visceral leishmaniasis.

Recent Development of Visceral Leishmaniasis Treatments: Successes, Pitfalls, and Perspectives

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