Some clones secreted soluble factors that caused the death of CD8+ regulatory T cells but not CD4+ T cells from VL patients, which might explain the strong protective immunity of asymptomatic patients. Non-protective immunity
VL patients are unable to clear their infections because they lack CMI. This anergy may be limited to Leishmania antigens or extend to mitogens and other antigens as the disease progresses. In addition to skin test negativity, VL patient PBMC do not proliferate or secrete IL-2 or IFN-γ in response to Leishmania antigens. Memory T cells may be depleted in VL patient PBMC. Since IL-10 is known to suppress innate and acquired immunity and prevent IFN-γ from activating macrophages, its role in VL has been studied extensively and elevated IL-10 production is often used as a marker of non-protective immunity in VL. Elevated levels of IL-10 in the plasma, infected tissues, and PBMC of VL patients accompany the anergy of VL. PKDL patients also have elevated IL-10 levels. VL patients with the highest IL-10 levels are more likely to be unresponsive to treatment and progress to PKDL. PBMC secretion of IL-10 without the addition of Leishmania antigen (endogenous) is inversely correlated with antigen specific IFN-γ secretion but Leishmania antigen specific IL-10 and IFN-γ secretion are not correlated, suggesting that endogenous secretion is more important in pathology. Addition of anti-IL-10 increases proliferation and IFN-γ secretion by PBMC from some patients. Both CD4+ and CD8+ T cells have been shown to contribute to IL-10 secretion by VL PBMC.
The high level of immune complexes characteristic of VL have also been shown to increase IL-10 levels. Epidemiology
More than 90% of the global burden of visceral leishmaniasis (VL) was contributed by seven countries in 2015: Brazil, Ethiopia, India, Kenya, Somalia, South Sudan and Sudan. In India, more than 70% of VL cases are reported from the state of Bihar. North Bihar, India (including Araria, Purnea, and Kishanganj) is the endemic zone of this disease. The disease is endemic in more than 60 countries. In Iran this includes Ardabil, Fars, and North Khorasan.However, while the diseases geographical range is broad, it is not continuous. The disease clusters around areas of drought, famine, and high population density. In Africa, this has meant a knot of infection centers mostly in South Sudan, Sudan, Ethiopia, Kenya, and Somalia. Living conditions here have changed very little in the past century, and the people are not normally very mobile. Parts of South Sudan, in particular the Upper Nile region, are almost totally cut off from the rest of the country, and most people tend to remain at their place of birth although there have been huge population movements due to the civil war, leading to severe epidemics. History
Kala-azar first came to the attention of Western doctors in 1824 in Jessore, India (now Bangladesh), where it was initially thought to be a form of malaria. Assam gave kala-azar one of its common names, Assam fever.