Symptoms, transmission, and current treatments for visceral leishmaniasis
What is visceral leishmaniasis?
Visceral leishmaniasis, the most severe form of leishmaniasis also known as kala-azar, is a life-threatening disease caused by Leishmania parasites which are transmitted by female sandflies. Visceral leishmaniasis causes fever, weight loss, spleen and liver enlargement, and, if not treated, death. People with both visceral leishmaniasis and HIV are particularly difficult to cure.
Visceral leishmaniasis affects the poorest of the poor, being associated with malnutrition, population displacement, poor housing, a weak immune system, and lack of financial resources. The disease is also linked to environmental changes such as deforestation, building of dams, irrigation schemes, and urbanization.
A skin condition known as post-kala-azar dermal leishmaniasis (PKDL) may appear months or years after successful treatment for visceral leishmaniasis. While it is not life-threatening, PKDL can be disfiguring and stigmatizing. People with PKDL can still transmit visceral leishmaniasis, complicating efforts to eliminate the disease.
What is the impact of visceral leishmaniasis?
- Over 600 million at risk worldwide
- 50,000-90,000 new cases per year
- 5,710 deaths in 2019
- More than 100x higher risk of developing active visceral leishmaniasis in people living with HIV
- 5-10% of people treated for visceral leishmaniasis develop PKDL
- In 2020, more than 90% of new cases reported to WHO occurred in 10 countries: Brazil, China, Ethiopia, Eritrea, India, Kenya, Somalia, South Sudan, Sudan, and Yemen.
Existing drugs have serious drawbacks in terms of safety, resistance, stability, and cost. They have low tolerability, long treatment duration when used individually, and are difficult to administer:
Pentavalent antimonials (sodium stibogluconate and meglumine antimoniate)
- 30-day treatment by infusion, if given on its own
- Resistance has been seen in areas where the disease is very common
- Toxic, with risk of serious cardiotoxicity leading to death
Liposomal amphotericin B
- Much safer and highly effective in some regions: a single 10mg/kg infusion has a cure rate of greater than 90% in Asia
- Expensive and needs to be stored in a fridge
- 28-day, twice-a-day oral drug
- Nausea and vomiting are common side effects that may affect adherence to the four-week treatment
- Cannot be used during pregnancy
- Not available in many countries
- Three weeks of painful intramuscular injections
- Low-cost formulation
- Associated with toxic effects on the kidneys and ears
- Limited efficacy when used on its own in East Africa
Treatment responses to visceral leishmaniasis vary by region, and therefore the recommended treatments also differ. Together with our partners, we have worked to improve existing treatments by developing improved combination treatments for Africa and new treatments for Asia. We have also worked to build evidence for safer treatment alternatives in Latin America.
What new treatments for visceral leishmaniasis are needed?
WHO has set the target date for the elimination of this disease from the Indian subcontinent to 2020. In order to achieve this goal and improve treatment in other regions, people with visceral leishmaniasis need treatments that are oral, safe, effective, low cost, and short course.
What visceral leishmaniasis treatments are we working on?
We aim to make treatments safer, shorter and more affordable and effective. In the short term, better treatment regimens are being developed using existing drugs. In the long term, the goal is to develop an entirely new generation of all-oral drugs.
Find out about our work developing treatments for visceral leishmaniasis
How do you get visceral leishmaniasis?
- Insect bites: Leishmania parasites are transmitted through the bites of infected female phlebotomine sandflies
- Poor housing and domestic sanitary conditions may increase sandfly breeding and resting sites
- Malnutrition increases the risk that an infection will progress to full-blown disease
What are the symptoms of visceral leishmaniasis?
Visceral leishmaniasis has symptoms that occur progressively over a period of weeks or even months:
- prolonged fever
- enlarged spleen and liver
- substantial weight loss
- progressive anaemia
- usually fatal if untreated
How is visceral leishmaniasis diagnosed?
Visceral leishmaniasis is diagnosed by combining observations from a physical exam by a health worker with parasitological or antibody-based diagnostics. The main signs are prolonged fever, weight loss, enlargement of the spleen, and anemia.
Other approaches for visceral leishmaniasis diagnosis involve antibody detection using the rK39 rapid diagnostic test (RDT) and the alternative Direct Agglutination Test (DAT) to confirm infection. People with VL symptoms but negative diagnostic results are referred to hospitals or clinics where microscopic examination of tissue aspirate (spleen, bone marrow, or lymph node) is available. Spleen aspiration, if performed incorrectly, can cause fatal bleeding.
Easy-to-use, non-invasive diagnostics that can be used in remote settings by health workers with limited training are critical to improving patient care and visceral leishmaniasis control. We are part of a consortium project, AfriKADIA, which hopes to improve visceral leishmaniasis testing in eastern Africa. One of the project partners, FIND, is evaluating less invasive tests in Ethiopia, Kenya, Sudan, and Uganda to determine the best approach to diagnosis.
Last updated: March 2022
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