Visceral leishmaniasis and HIV co-infection: WHO publishes new guideline with region-specific treatment recommendations

“Optimal region-specific treatment regimens are needed because parasite virulence and drug susceptibility differ,said Dr Saurabh Jain, Medical Officer, Global Leishmaniasis Program, WHO Department of Control of Neglected Tropical Diseases. †Also, very few studies have been conducted in leishmaniasis endemic regions other than Europe in the past and this made it difficult to make recommendations appropriate to specific geographic situations.”

The new recommendations are based on the results of studies in India³ by Doctors Without Borders and partners, and in Ethiopia⁴ by the medicines for neglected diseases initiative and partner. They are expected to increase access to treatment and improve treatment outcomes, thereby benefiting national control programs for neglected tropical diseases, HIV, tuberculosis and vector-borne diseases. Up to 5-7% of visceral leishmaniasis patients in India are detected with HIV infection – the highest in South Asia; a significant proportion also suffer from another fatal comorbidity: tuberculosis.⁵

New evidence and better treatment

The new guideline updates the 2010 recommendations that were based on limited evidence, extrapolated mainly from experiences in Mediterranean countries where zoonotic diseases L. infantum is the main cause. The recommended treatment consisted of daily injections of liposomal amphotericin B (AmBisome) for a period of up to 38 days.

However, the studies in Ethiopia and India show that the new regimen that combines liposomal amphotericin B with oral miltefosine performs better. In India, the treatment outcome was superior, with a relapse-free survival of 96% versus 88% for standard treatment.

†We welcome the new recommendations and key indicators for monitoring outcomes in co-infected patients as it 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 of visceral leishmaniasis and HIV has increased by 20-30% since the early 1980s, with the highest co-infection rate in the world. Although the percentage has decreased somewhat, co-infection nevertheless remains a major public health challenge. The new combined regimen showed increased efficacy (88%) compared to the current standard treatment (55%).⁶

†We have a long experience in using various drugs and regimens to treat VL . to treat†HIV patients, who were less efficient and with high toxicity, relapse and mortality,” said Mr Tesfahun Bishaw Mengistie, Leishmaniasis Contact, Disease Prevention and Control Directorate, Federal Ministry of Health, Addis Ababa, Ethiopia. †We welcome the new recommendations as they allow for better management of this complex condition.”

Visceral leishmaniasis and HIV co-infection

Leishmania and HIV co-infections have challenged the control and elimination of visceral leishmaniasis, as HIV-infected people are particularly vulnerable to the disease. Leishmania and HIV are mutually reinforcing and cause significant clinical and public health problems.

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

First reported in the mid-1980s in southern Europe, the co-infection has now been documented in as many as 45 countries. High rates are reported from Brazil, Ethiopia and the state of Bihar in India.

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

The new WHO guideline offers hope to co-infected patients and fills an important gap in allowing countries where both diseases are present to adapt the guideline to treat complex clinical cases.

Leishmaniasis – the disease

Leishmaniasis is caused by a protozoan parasite above 20 Leishmania types. More than 90 species of sand flies are known to transmit them Leishmania parasites. There are 3 main forms of the disease:

Visceral leishmaniasis: Fatal if left untreated, it is characterized by infrequent attacks of fever, weight loss, enlargement of the spleen and liver, and anemia.

Cutaneous leishmaniasis: The most common form that causes skin lesions, primarily ulcers, on exposed areas of the body, with lifelong scarring and severe disability or stigma.

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

†

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

2. Infection or disease that can be transmitted from humans to animals under natural conditions.

3. AmBisome monotherapy and combination AmBisome miltefosine therapy for the treatment of visceral leishmaniasis in patients co-infected with human immunodeficiency virus (HIV) in India: a randomized, open-label, parallel-arm, phase 3 study
   https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac127/6527047

4. A randomized trial of AmBisome monotherapy and a 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 a public health problem in many countries. Leishmaniasis infection may alter protective immune response to BCG vaccine against tuberculosis https://parasitesandvectors.biomedcentral.com/articles/10.1186/1756-3305-6-79consulted on June 1, 2022.

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