Leishmaniasis (Kala azar)

• Leishmaniasis is a disease caused by parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sand fly, including flies in the genus Lutzomyia in the New World and Phlebotomus in the Old World.
• The disease was named in 1901 for the Scottish pathologist William Boog Leishman.
• This disease is also known as Leichmaniosis, Leishmaniose, leishmaniose, and formerly, Orient Boils, kala azar, black fever, sandfly disease, Dum-Dum fever or espundia.
• Most forms of the disease are transmissible only from animals (zoonosis), but some can be spread between humans. Human infection is caused by about 21 of 30 species that infect mammals.

Kala azar

• Largely unknown in the developed world,
• Threatens many poor countries,
• The disease principally affects poor communities in isolated regions,
• Often as devastating epidemics.
• In Sudan, where civil war had caused a flood of internal refugees,
  • an epidemic of visceral leishmaniasis lasted from 1984 to 1994 and
  • claimed more than 100,000 lives in the Western Upper Nile province,
  • a third of the population of the affected area. (Source: MSF)

Geography and Epidemiology

• Leishmaniasis can be transmitted in many tropical and sub-tropical countries, and is found in parts of about 88 countries. Approximately 350 million people live in these areas.
• The settings in which leishmaniasis is found range from rainforests in Central and South America to deserts in West Asia.
• More than 90 % of the world's cases of visceral leishmaniasis are in India, Bangladesh, Nepal, Sudan, and Brazil.

RESERVOIR

• Both animals and humans can act as the parasite's reservoir:
• the sandfly picks up the parasite by biting a host and then transmits it to another.
• Leishmaniasis is prone to epidemics, especially when previously unexposed populations are forced by war and famine to move into endemic areas.

Life cycle

• Transmitted by the bite of female phlebotomine sandflies.
  • The sandflies inject the infective stage, metacyclic promastigotes, during blood meals (1).
  • Metacyclic promastigotes that reach the puncture wound are phagocytized by macrophages (2)
  • and transform into amastigotes (3).
  • Amastigotes multiply in infected cells and affect different tissues, depending in part on which Leishmania species is involved (4).
• These differing tissue specificities cause the differing clinical manifestations of the various forms.
• Sandflies become infected during blood meals on an infected host when they ingest macrophages infected with amastigotes (5,6).
• In the sandfly's midgut, the parasites differentiate into promastigotes (7), which multiply, differentiate into metacyclic promastigotes and migrate to the proboscis (8)

Signs and symptoms

• Skin sores which erupt weeks to months after the person affected is bitten by sand flies.
• Other manifestations anywhere from a few months to years after infection, include fever, damage to the spleen and liver, and anaemia.
• In the medical field, leishmaniasis is one of the famous causes of a markedly enlarged spleen, which may become larger even than the liver.

Main forms of Leishmaniasis

• Visceral leishmaniasis - the most serious form and potentially fatal if untreated.
• Cutaneous leishmaniasis - the most common form which causes numerous sores on the body, which heal within a few months leaving unpleasant looking scars.
• Diffuse cutaneous leishmaniasis - this form produces widespread skin lesions which resemble leprosy and is particularly difficult to treat.
• Mucocutaneous leishmaniasis - commences with skin ulcers which spread causing tissue damage to (particularly) nose and mouth

Treatment

• There are two common therapies
  • Sodium stibogluconate SSG (Pentostam) first developed in the 1930s, using derivatives of antimony.
  • SSG is taken as an I.M over 30 or more days.
  • Another antimonial drug is meglumine antimoniate (brand name Glucantime).
    • It is not completely understood how these drugs act against the parasite; they may disrupt its energy production or trypanothione metabolism.
    • Unfortunately, in many parts of the world, the parasite has become resistant to antimony and for visceral or mucocutaneous leishmaniasis.
• Amphotericin is now the treatment of choice.
• Miltefosine (Impavido®), is a new drug for visceral and cutaneous leishmaniasis.
  • The cure rate of miltefosine in phase III clinical trials is 95%;
  • Studies in Ethiopia show that is also effective in Africa.
  • In HIV immunosuppressed people which are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment.
  • Clinical trials in Colombia showed a high efficacy for cutaneous leishmaniasis.
  • In mucocutaneous cases caused by L.brasiliensis it has shown to be much better effective than other drugs.

Prevention

• Control of vectors
• Spraying with effective insecticide should be carried out at regular intervals
• Attempt to decrease the reservoir of infection by destroying the animals and treating infected humans early.

Vaccine ??

• Several potential vaccines are being developed, under pressure from the WHO, but as of 2006 none is available.
• Drug-resistant leishmaniasis may respond to immunotherapy (inoculation with parasite antigens plus an adjuvant) which aims to stimulate the body's own immune system to kill the parasite.