The World Health Organization (WHO) has published new treatment recommendations for visceral leishmaniasis in patients who are coinfected with the human immunodeficiency virus (HIV). The guideline targets visceral leishmaniasis in East Africa and South-East Asia.
Visceral leishmaniasis, or kala azar, is caused by different Leishmania species in distinct geographical areas.1 In East Africa (Ethiopia, South Sudan and Sudan) and South-East Asia (Bangladesh, India and Nepal), it is caused by L. donovani and has an anthroponotic2 cycle with a human reservoir.
“Optimal region-specific treatment regimens are needed because parasite virulence and drug susceptibility differ,” said Dr Saurabh Jain, Medical Officer, Global leishmaniasis programme, WHO Department of Control of Neglected Tropical Diseases. “Also, very few studies have been conducted in the past in leishmaniasis-endemic regions other than Europe and this made it difficult to provide recommendations suitable to specific geographical settings.”
The new recommendations are based on the results of studies conducted in India3 by Médecins Sans Frontières and partners, and in Ethiopia4 by the Drugs for Neglected Diseases initiative and partners. They are expected to increase access to treatment and improve treatment outcomes, and thereby benefit national control programmes 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 which were based on limited evidence extrapolated mainly from experience in countries around the Mediterranean Basin where zoonotic L. infantum is the main causative species. The recommended treatment consisted of daily injections of liposomal amphotericin B (AmBisome) over a period of up to 38 days.
However, evidence from the studies in Ethiopia and India shows that the new regimen combining liposomal amphotericin B with oral miltefosine performs better. In India, the treatment outcome was superior, with relapse-free survival of 96% versus 88% for the standard treatment.
“We welcome the new recommendations as well as the key indicators for monitoring the outcomes of coinfected patients as this has the potential to accelerate efforts towards eliminating kala azar as a public health problem,” said Roderico H. Ofrin, WHO Representative to India.
In Ethiopia, visceral leishmaniasis-HIV coinfection has increased by 20-30% since the early 1980s, with the highest rate of coinfection rate in the world. Although the rate has somewhat declined, coinfection nevertheless remains a major public health challenge. The new combined regimen showed an increased efficacy (88%) compared with the current standard treatment (55%).6
“We have a long experience in using different medicines and regimens to treat VL-HIV patients, which were less efficient and with high toxicity, relapse and mortality,” said Mr. Tesfahun Bishaw Mengistie, Leishmaniasis focal person, Diseases Prevention and Control Directorate, Federal Ministry of Health, Addis Ababa, Ethiopia. “We welcome the new recommendations as they ensure better management of this complex condition.”
Visceral leishmaniasis and HIV coinfection
Leishmania and HIV coinfections have challenged the control and elimination of visceral leishmaniasis as HIV-infected people are particularly vulnerable to the disease. Leishmania and HIV reinforce each other, posing 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 medicines with increased toxicity and higher mortality rates.
First reported in the mid-1980s in southern Europe, the coinfection is now documented in as many as 45 countries. High rates are reported from Brazil, Ethiopia and Bihar state in India.
Coinfected patients are vulnerable not only to other comorbid conditions such as tuberculosis and cryptococcal meningitis but also to varying degrees of stigmatization and human rights issues.
The new WHO guideline offers hope to coinfected patients and fills an important gap in allowing countries where both diseases are prevalent to adapt the guideline for the treatment of complex clinical cases.
Leishmaniasis – the disease
Leishmaniasis is caused by a protozoa parasite from over 20 Leishmania species. Over 90 sandfly species are known to transmit Leishmania parasites. There are 3 main forms of the disease:
Visceral leishmaniasis: Fatal if left untreated, it is characterized by irregular bouts of fever, weight loss, enlargement of the spleen and liver, and anaemia.
Cutaneous leishmaniasis: The most common form that causes skin lesions, mainly ulcers, on exposed parts of the body, leaving life-long scars and serious disability or stigma.
Mucocutaneous leishmaniasis: Leads to partial or total destruction of mucous membranes of the nose, mouth and throat.
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Most cases of visceral leishmaniasis occur in Brazil, East Africa and in India, with an estimated 50 000-90 000 new cases worldwide annually; only 25-45% of cases are reported to WHO. Visceral leishmaniasis remains one of the leading parasitic diseases with outbreak and mortality potential. In 2020, more than 90% of new cases were reported to WHO from 10 countries: Brazil, China, Ethiopia, Eritrea, India, Kenya, Somalia, South Sudan, Sudan and Yemen.
Infection or disease that is transmissible from humans to animals under natural conditions.
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac127/6527047
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006988
Visceral leishmaniasis coinfection and pulmonary tuberculosis pose a public health problem in many countries. Leishmaniasis infection can change the protective immune response to BCG vaccine against tuberculosis https://parasitesandvectors.biomedcentral.com/articles/10.1186/1756-3305-6-79, accessed 1 June 2022.
Current standard treatment for HIV/visceral leishmaniasis coinfection comprises single injections of liposomal amphotericin B (LAmB). The new treatment course is a combination of the oral treatment miltefosine and LAmB.