Leishmaniasis

Leishmaniasis is a vector–borne disease caused by protozoan parasites of the genus Leishmania. This neglected tropical disease affects mainly the poorest people andit is associated with malnutrition, poor housing and domestic sanitary conditions, population movements, environmental changes. Approved drug treatments have several limitation including high costs, long term and complicated regimens, high toxicity, emergence of resistance. 

Cause

Leishmaniasis infection is caused by the Leishmania protozoan parasites. It transmitted to mammalian host by the bite of infected female phlebotomine sandflies. The female sandfly becomes infected by biting and sucking blood from a person or animal infected with the leishmania parasite. More than 20 Leishmania species are known to cause human infection.

Consequences

Infection with Leishmania manifests in various forms; visceral, cutaneous, mucocutaneous and post-kala-azar dermal leishmaniasis (PKDL). Visceral leishmaniasis (VL) also known as Kala-azar is the most severe form of the disease.

Cutaneous infection is the most common form with numerous ulcers developing on the exposed parts of the body (face, arms, and legs).  It usually heals spontaneously depending on the species but results in lifelong scars and serious disabilities. Mucocutaneous infection results in destruction of the mucous membranes of the nose, mouth and throat. Symptoms of visceral leishmaniasis (Kalar-Azar) include irregular bouts of fever, enlargement of the liver and spleen, marked weight loss and if left untreated can lead to death. Post-Kalar-azar dermal leishmaniasis is a sequel of visceral leishmaniasis. It is characterised by macular, papular or nodular rash usually on face, upper arms, and others parts of the body. The PKDL plays an important role in maintaining and contributing to transmission of the disease particularly in interepidemic periods of VL, acting as a reservoir for parasites.

In general, leishmaniasis is associated with pain, debilitating illnesses, permanent scarring, social rejection and death.

Global burden

Over 300 million people are at risk of the disease with 12 million people believed to be currently infected (WHO), with an additional 700,000 - 1,000,000 people becoming newly infected every year.  About 20,000 - 30,000 deaths in children and young adults occur annually.

An estimate of 50,000-90,000 new cases of VL occur each year. In 2015, more than 90% news cases of VL occurred in 7 countries including Brazil, Ethiopia, India, Kenya, Somalia, South Sudan and Sudan.

Worldwide, about 0.6 million-1 million new cases of CL occur each year and approximately 95% CL occur in the America, the Mediterranean basin, the Middle East and Central Asia. Over 90% of mucocutaneous cases occur in Bolivia, Brazil, Ethiopia and Peru.

Vaccines

There are currently no licensed vaccines for the treatment or prevention of human leishmaniasis. Several vaccines are at different stages of development. With the development of a marked resistance to available drugs, the development of a vaccine needs to be accelerated.  Efforts at developing an effective vaccine have recently being given prominence by the WHO.  However, difficulties arise in the induction of an effective immune response following the administration of vaccines.  The induction of strong Th1-type cytokine immune responses is required as it is known that Th2-type responses are induced in chronic leishmaniasis.

References

World Health Organisation. Global leishmaniasis update, 2006-2015: a turning point in leishmaniasis surveillance, Weekly epidemiological record 2017; 38(92), 557-572

Ghorbani M and Farhoudi R. Leishmaniasis in humans: drug or vaccine therapy. Drug design, Development and Therapy 2018, 12, 25-40

Gillespie PM, Beaumier CM, Strych U, Hayward T, Hotez PJ, Bottazzi ME. Status of vaccine research and development of vaccines for leishmaniasis. Vaccine. 2016 Jun 3;34(26):2992-2995

WHO. Leishmaniasis. Key facts. 14 March 2018. http://www.who.int/news-room/fact-sheets/detail/leishmaniasis. Accessed on 02 October 2018.