Treatment of visceral leishmaniasis

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 today9s 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

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

Visceral Leishmaniasis: Recent Advances in Diagnostics and Treatment Regimens.

The goal of this review is to summarize the current knowledge of the epidemiology, clinical manifestations, diagnosis, and treatment of cutaneous, mucosal, and visceral leishmaniasis. We will describe the most recent findings and suggest areas of further research in the leishmaniasis field. This article reviews newer leishmaniasis tests (including rapid diagnostic tests using rK39 antibodies), vaccine candidates, and updated treatment recommendations. While leishmaniasis is a complex disease, learning the prominent clinical manifestations and major parasite species can guide the recommendations for diagnosis and treatment.

/pdf/a-review-of-leishmaniasis-current-knowledge-and-future-3pvz3lgwou.pdf

A Review of Leishmaniasis: Current Knowledge and Future Directions.

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

https://www.bmj.com/content/bmj/364/bmj.k5224.full.pdf

Eliminating visceral leishmaniasis in South Asia: the road ahead.

Visceral leishmaniasis (VL) can be fatal without timely diagnosis and treatment. Treatment efficacies vary due to drug resistance, drug toxicity and co-morbidities. It is important to monitor treatment responsiveness to confirm cure and curtail relapse. Currently, microscopy of spleen, bone marrow or lymph node biopsies is the only definitive method to evaluate cure. A less invasive test for treatment success is a high priority for VL management. In this study, we describe the development of a capture ELISA based on detecting Leishmania donovani antigens in urine samples and comparison with the Leishmania Antigen ELISA, also developed for the same purpose. Both were developed as prototype kits and tested on patient urine samples from Sudan, Ethiopia, Bangladesh and Brazil, along with appropriate control samples from endemic and non-endemic regions. Sensitivity and specificity were assessed based on accurate detection of patients compared to control samples. One- Way ANOVA was used to assess the discrimination capacity of the tests and Cohen’s kappa was used to assess their correlation. The Leishmania Antigen Detect™ ELISA demonstrated >90 % sensitivity on VL patient samples from Sudan, Bangladesh and Ethiopia and 88 % on samples from Brazil. The Leishmania Antigen ELISA was comparable in performance except for lower sensitivity on Sudanese samples. Both were highly specific. To confirm utility in monitoring treatment, urine samples were collected from VL patients at days 0, 30 and 180 post- treatment. For the Leishmania Antigen Detect™ ELISA, positivity was high at day 0 at 95 %, falling to 21 % at day 30. At day 180, all samples were negative, corresponding well with clinical cure. A similar trend was also seen for the Leishmania Antigen ELISA albeit; with lower positivity of 91 % at Day 0 and more patients, remaining positive at Days 30 and 180. The Leishmania Antigen Detect™ and the Leishmania Antigen ELISAs are standardized, user- friendly, quantitative and direct tests to detect Leishmania during acute VL as well as to monitor parasite clearance during treatment. They are a clear improvement over existing options. The ELISAs provide a non-invasive method to detect parasite antigens during acute infection and monitor its clearance upon cure, filling an unmet need in VL management. Further refinement of the tests with more samples from endemic regions will define their utility in monitoring treatment.

/pdf/development-and-comparative-evaluation-of-two-antigen-5f8iei3trb.pdf

Abdalla E. Ahmed

Papers

Development and Comparative Evaluation of Two Antigen Detection Tests for Visceral Leishmaniasis