Leishmania donovani

Leishmania donovani is a species of intracellular parasites belonging to the genus Leishmania, a group of haemoflagellate kinetoplastids that cause the disease leishmaniasis. It is a human blood parasite responsible for visceral leishmaniasis or kala-azar, the most severe form of leishmaniasis. It infects the mononuclear phagocyte system including spleen, liver and bone marrow. Infection is transmitted by species of sandfly belonging to the genus Phlebotomus in Old World and Lutzomyia in New World. Therefore, the parasite is prevalent throughout tropical and temperate regions including Africa (mostly in Sudan), China, India, Nepal, southern Europe, Russia and South America. It is responsible for thousands of deaths every year and has spread to 88 countries, with 350 million people at constant risk of infection and 0.5 million new cases in a year. L. donovani was independently discovered by two British medical officers William Boog Leishman in Netley, England, and Charles Donovan in Madras, India, in 1903. However, the correct taxonomy was provided by Ronald Ross. The parasite requires two different hosts for a complete life cycle, humans as the definitive host and sandflies as the intermediate host. In some parts of the world other mammals, especially canines, act as reservoir hosts. In human cell they exist as small, spherical and unflagellated amastigote form; while they are elongated with flagellum as promastigote form in sandflies. Unlike other parasitic protists they are unable to directly penetrate the host cell, and are dependent upon phagocytosis. The whole genome sequence of L. donovani obtained from southeastern Nepal was published in 2011. One of the earliest known epidemics of L. donovani infection (kala-azar as it was called in Hindi) was known in India just after the Indian Rebellion of 1857. The first medical record was however only in 1870 by British medical officers from Assam. In 1900, an English soldier stationed at Dum Dum, West Bengal, died at the Army Medical School in Netley, England. The autopsy was performed by William Boog Leishman. He processed the tissue sample of the enlarged spleen using a staining technique (now known as Leishman's stain) which he had just developed, and discovered the protozoan parasites using microscopy. But he mistakenly considered the parasites to be degenerate trypanosomes, already known protozoan parasites in Africa and South America. In 1903, Leishman published his discovery of 'trypanosomes in India' in the British Medical Journal, which appeared on 11 May. Another British medical officer Charles Donovan, who was serving in the Indian Medical Service, had found the parasites in April of that year at the Government General Hospital in Madras. After reading Leishman paper, Donovan confirmed on 17 June that the parasites (by then known as 'Leishman bodies') were definitely the causative agents of kala-azar. He wrote a commentary of his discovery in relation to that of Leishman in the same journal, that appeared on 11 July 1903. Soon a controversy arose as to whom such a monumental discovery should be credited. Donovan sent some of his slides to Ronald Ross, who was at the time in Liverpool, and to Alphonse Laveran at the Pasteur Institute in Paris. Laveran and his colleague Félix Mesnil identified the protozoan (and yet wrongly) to be members of Piroplasmida, and gave the scientific name Piroplasma donovanii. It was Ross who resolved the conflict of priority in the discovery and correctly identified the species as member of the novel genus Leishmania. He gave the popular name 'Leishman-Donovan bodies', and subsequently the valid binomial Leishmania donovani, thereby equally crediting the two rivals. Leishmania donovani is a unicellular eukaryote having a well-defined nucleus and other cell organelles including a kinetoplast and a flagellum. Depending on its host it exists in two structural variants, as follows: Leishmania donovani is a digenetic parasite passing its life cycle in two different hosts. In humans the metacyclic promastigotes are injected by sandfly through the skin during its blood meal. When sandfly bites using its proboscis it ejects the parasites that are stored inside the hollow tube. Some promastigotes may enter the blood stream directly where some are destroyed by macrophagic cytolysis. But many are also taken up through phagocytosis by mononuclear phagocytes in liver, spleen and bone marrow. Inside the cells they undergo spontaneous transformation into oval-shaped amastigotes. Granulocytes selectively kill the promastigotes by oxidative mechanism, while amastigotes are resistant. Then the surviving amastigotes undergo cell division using simple binary fission. Multiplication continues until the host cell can no longer hold and ruptures. In a fully congested cell there can be as many as 50 to 200 amastigotes, which are released into tissue cavities. Each individual amastigote is then capable of invading fresh cells. As a result, the entire tissue is progressively infected and destroyed. A number of free amastigotes then enters the blood stream where many are phagocytosed by macrophages. These free and phagocytosed amastigotes in peripheral blood are then sucked up by blood-feeding sandfly. L. donovani undergo further development only in the digestive tract of the female sandfly. Hence only females are responsible for transmitting the infection. Once the amastigotes are ingested, they enter the midgut of the sandfly. Then they undergo structural modification into flagellated promastigotes, becoming larger and considerably elongated. They get attached to the gut epithelial lining where they multiply rapidly by binary fission. (They are also capable of sexual reproduction by genetic hybridisation in the sandfly gut.) They then migrate back towards the anterior part of the digestive system such as pharynx and buccal cavity. This process is known as anterior station development, which is unique in Leishmania. A heavy infection of pharynx can be observed within 6 to 9 days after initial blood meal. The promastigotes become infective only by this time, and the event is called the metacyclic stage. The metacyclic promastigotes then enter the hollow proboscis where they accumulate and completely block the food passage. Immediately upon biting a human, the parasites are released, which invariably results in infection. The stages of development in sandfly can be described as follows: Dogs are known to be susceptible to L. donovani infection. Especially in the New World, infection is a zoonotic disease, involving different canine species, including domestic dog and the two fox species, Lycalopex vetulus and Cerdocyon thous. In the Mediterranean region domestic dogs and the three fox species Vulpes vulpes, V. corsac and V. zerda are common reservoir hosts. In Africa and Brazil, some marsupials and rodents are also reported to harbour L. donovani.