Visceral leishmaniasis and HIV co-infection: WHO issues new guidelines with region-specific treatment recommendations

“Optimal region-specific treatment regimens are needed because parasite virulence and drug sensitivity vary,“Said Dr. Saurabh Jain, Physician, Global Leishmaniasis Program, WHO Department for the Control of Neglected Tropical Diseases. “There have also been very few studies in the past in areas with endemic leishmaniasis than in Europe, making it difficult to provide recommendations appropriate to specific geographical conditions.

The new recommendations are based on the results of studies conducted in India³ from Médecins Sans Frontières and partners and in Ethiopia⁴ from Drugs for neglected diseases initiative and partners. It is expected to improve access to treatment and treatment outcomes, benefiting national programs for the control of neglected tropical diseases, HIV, tuberculosis and vector-borne diseases. As many as 5-7% of patients with visceral leishmaniasis in India are detected with HIV infection – most in South Asia; a significant proportion also suffers from another fatal comorbidity: tuberculosis.⁵

New evidence and better treatment

The new guidelines update the 2010 recommendations, which were based on limited evidence extrapolated mainly from experience in Mediterranean countries where zoonotic L. infantum is the main cause. The recommended treatment consisted of daily injections of liposomal amphotericin B (AmBisome) for up to 38 days.

However, evidence from studies in Ethiopia and India shows that the new regimen combining liposomal amphotericin B with oral miltefosine works better. In India, treatment outcomes were better, with relapse-free survival of 96% compared to 88% for standard treatment.

“We welcome the new recommendations and key indicators for monitoring the outcomes of coinfected patients, as this has the potential to accelerate efforts to eliminate kala azar as a public health problem. ” said Roderico H. Ofrin, WHO representative in India.

In Ethiopia, co-infection with visceral leishmaniasis and HIV has increased by 20-30% since the early 1980s, with the highest rate of co-infection in the world. Although the rate has decreased somewhat, co-infection still remains a major public health problem. The new combination regimen showed increased efficacy (88%) compared to the current standard treatment (55%).⁶

“We have many years of experience in using various drugs and regimens to treat VL–HIV patients who were less effective and with high toxicity, relapse and mortality, “ said Mr. Tesfahun Bishaw Mengistie, Contact Person for Leishmaniasis, Directorate of Disease Prevention and Control, Federal Ministry of Health, Addis Ababa, Ethiopia. “We welcome the new recommendations because they provide better management of this difficult situation. ”

Visceral leishmaniasis and HIV co-infection

Leishmania and HIV co-infections have questioned the control and eradication of visceral leishmaniasis because HIV-infected people are particularly vulnerable to the disease. Leishmania and HIV are mutually reinforcing, which poses significant clinical and public health problems.

Both conditions suppress the immune system, resulting in more severe morbidity with limited therapeutic options and higher recurrence rates, exposure to drugs with increased toxicity, and higher mortality.

Co-infection was first reported in the mid-1980s in southern Europe and is now documented in up to 45 countries. High rates are reported from Brazil, Ethiopia and the state of Bihar in India.

Co-infected patients are vulnerable not only to other comorbid diseases, such as tuberculosis and cryptococcal meningitis, but also to varying degrees of stigma and human rights problems.

The new WHO directive offers hope to co-infected patients and fills an important gap in allowing countries where both diseases predominate to adapt guidelines for the treatment of complex clinical cases.

Leishmaniasis – a disease

Leishmaniasis is caused by a protozoan parasite older than 20 years Leishmania species. It is known to carry more than 90 species of sand flies Leishmania parasites. There are 3 main forms of the disease:

Visceral leishmaniasis: Fatal, if left untreated, is characterized by irregular fevers, weight loss, enlargement of the spleen and liver, and anemia.

Cutaneous leishmaniasis: The most common form that causes skin lesions, especially ulcers, on exposed parts of the body, leaving lifelong scars and severe disability or stigma.

Mucocutaneous leishmaniasis: Leads to partial or complete destruction of the mucous membranes of the nose, mouth and throat.

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1. Most cases of visceral leishmaniasis occur in Brazil, East Africa and India, with an estimated 50,000-90,000 new cases per year worldwide; only 25-45% of cases are reported to the WHO. Visceral leishmaniasis remains one of the leading parasitic diseases with the potential for outbreaks and mortality. In 2020, more than 90% of new cases from 10 countries were reported to the WHO: Brazil, China, Ethiopia, Eritrea, India, Kenya, Somalia, South Sudan, Sudan and Yemen.

2. An infection or disease that is naturally transmissible from humans to animals.

3. AmBisome Monotherapy and Combinations AmBisome – Miltefosine Therapy for the treatment of visceral leishmaniasis in patients co-infected with human immunodeficiency virus (HIV) in India: Randomized open-label, parallel, phase 3 study
   https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac127/6527047

4. Randomized study of AmBisome monotherapy and the combination of AmBisome and miltefosine for the treatment of visceral leishmaniasis in HIV co-infected patients in Ethiopia
   https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006988

5. Visceral leishmaniasis, co-infection and pulmonary tuberculosis are public health problems in many countries. Leishmaniasis infection may alter the protective immune response to BCG vaccine against tuberculosis https://parasitesandvectors.biomedcentral.com/articles/10.1186/1756-3305-6-79accessed June 1, 2022.

6. Current standard treatment for HIV / visceral leishmaniasis co-infection involves single injections of liposomal amphotericin B (LAmB). The new treatment cycle is a combination of oral miltefosine and LAmB.