What is visceral leishmaniasis?

Vanessa Yardley: This section will clarify the definitions used when we talk about visceral leishmaniasis, and we will describe the life cycle of the parasite. We will also cover what the disease actually is. And we’ll briefly describe the other forms of leishmaniasis. Here are a few definitions of some of the words and terms that you will come across during the course of this MOOC. A pathogen is able to cause disease in humans. This includes viruses, bacteria, and parasites. The Leishmania parasite is the causative agent of leishmaniasis, of which there are three main forms. The first is cutaneous leishmaniasis, which is known to infect millions of people every year. As its name states, CL affects the skin.

Another manifestation of leishmaniasis is the mucocutaneous form. This affects the soft tissue areas of the face, such as the nasal passages, and the roof of the mouth, and usually follows a previous CL infection that has healed some time before. This form is mostly seen in Latin America. Visceral leishmaniasis, which we will cover in this MOOC, affects the liver, spleen, and bone marrow of the human host. Visceral leishmaniasis is commonly known as kala-azar. Interestingly, Leishmania is a member of the order Kinetoplastida and is related to the parasites that cause Chagas disease in Latin America, and Sleeping Sickness in Africa.

The disease kala-azar was first described in mid 18th century, in Africa and India. William Leishman, a British army doctor, identified ovoid bodies in a spleen sample from a British soldier who had been experiencing bouts of fever, anaemia, muscle wasting, and an enlarged spleen. He published his findings in 1903. Captain Charles Donovan recognised these symptoms in other patients, and also identified these same “bodies.” They were subsequently called Leishman-Donovan bodies after the two men. The liver and spleen enlargement is caused by large numbers of amastigotes multiplying within these organs, and by a massive cellular infiltration caused by the patient mounting an immune response to the presence of the parasite.

Visceral leishmaniasis is caused by two species of the Leishmania parasite, Leishmania donovani and Leishmania infantum. They are not usually found in the same areas. The geographical distribution of leishmaniasis will be covered in a later step. The parasite exists in two forms. The amastigote shown here is an obligate intracellular parasite of the mammalian host macrophage. This means that the parasite has to live within a host cell in order to survive. Amastigotes reside within a parasitophorous vacuole, also known as the phagolysosome. They’re able to thrive within this low pH environment, effectively hidden from the host’s immune response. In humans, the macrophages of the liver and spleen are most abundantly infected.

But infected cells are also present in the bone marrow and lymph nodes. In the sand fly vector, the morphology changes. The amastigotes transform into a promastigote inside the insect. They develop a flagellum at the front or anterior of the cell. About 50 species of sandfly have been implicated in Leishmania transmission. This slide shows the Leishmania life cycle. Number one, promastigotes are injected into a human when the female sandfly feeds on blood. Step two, macrophages phagocytose the promastigote, which in step three transforms into an amastigote within the host cell. At step 4, the intracellular amastigotes are multiplying in the macrophages of the liver, and spleen, and bone marrow in visceral leishmaniasis, or in the skin for cutaneous leishmaniasis.

At step 5, the female sand fly takes a blood meal, and ingests some infected cells. The blood meal is digested in the sand fly and amastigotes are released, as shown in step six. These then transform into promastigotes in step seven, in the gut of the sand fly, and attached to the midgut and begin to divide, as shown in step 8. After further maturation, the prime promastigotes will migrate to the sandfly proboscis in readiness for transmission to the next host. Post kala-azar dermal leishmaniasis (PKDL) is a manifestation of Leishmania donovani infection, which involves the skin, and is seen after a visceral infection has been resolved, although there are anecdotal reports of PKDL occurring without any previous history of the VL.

PKDL typically occurs months after clinical cure, with the initial appearance of plaques, nodules, and papules on the skin, each full of infected macrophages. Amastigotes are not usually detected in the liver, spleen, and bone marrow if tested. The occurrence of PKDL varies between endemic settings. In Sudan, for example, the rates of developing PKDL after VL is higher than in South Asia. And the interval between VL cure and the onset of PKDL is much shorter in East Africa. This cutaneous manifestation can last for weeks, months, and years, and is considered to be an important reservoir of infection due to the high number of amastigotes that can be found in the skin.

Leishmaniasis also exists in other forms, which will not be covered in detail by this MOOC. Briefly, cutaneous leishmaniasis is caused by the parasite residing in the macrophages of the skin, more precisely the dermis, and a lesion develops over time. Different species exist in the Old World and the New World and they cause different presentations, as can be seen from the images labelled (A). Usually, these infections will self-heal, but this can take a long time, and cause much scarring and distress. Mucocutaneous leishmaniasis usually occurs after a cutaneous lesion has healed. Leishmania braziliensis parasites, found only in the New World, can re-emerge months or years after the original lesion has been successfully resolved.

The Pan American Health Organisation has produced a MOOC and other material which explores leishmaniasis in Latin America more fully. In summary, we have learned how the causative agent of visceral leishmaniasis was identified and visualised by Leishman and Donovan. And that this has enabled the differential diagnosis from other fever-associated infections, such as malaria. This number is likely to rise as new species emerge from areas where sandflies are not the vector, and Leishmania has not been actively looked for. We also know that, at a microscopical level, the parasite has to live in a very specific environment in order to survive within the human host.