The parasite migrates to the internal organs such as the liver, spleen (hence "visceral"), and bone marrow, and, if left untreated, will almost always result in the death of the host.

Signs and symptoms include fever, weight loss, fatigue, anemia, and substantial swelling of the liver and spleen.

[5][6] Upendranath Brahmachari synthesised urea stibamine (carbostibamide) in 1922 and determined that it was an effective substitute for the other antimony-containing compounds in the treatment of VL caused by Leishmania donovani.

This condition manifests first as small, measle-like skin lesions on the face, which gradually increase in size and spread over the body.

Eventually the lesions may coalesce to form disfiguring, swollen structures resembling leprosy, and occasionally causing blindness if they spread to the eyes.

[14] The larvae grow in warm, moist organic matter around human habitations (such as old trees, house walls, or waste) making them hard to eradicate.

So, it appears that a great majority of kala-azar patients in the Indian subcontinent are exposed to a RNA virus in LS, the co-infecting parasite with LD i.e. the "LD-LS-Lepsey NLV1 triple pathogen" phenomenon.

Inside the stomach of the sandfly, the amastigotes quickly transform into elongated and motile forms called the promastigotes.

The promastigotes live extracellularly in the alimentary canal, reproducing asexually, then migrate to the proximal end of the gut where they become poised for a regurgitational transmission.

The amastigotes replicate in the most hostile part of the macrophage cell, inside the phagolysosome, whose normal defensive response they are able to prevent.

[30][31] CD4+ T regs are present at increased frequency in the bone marrow of VL patients, are one source of IL-10, and proliferate in response to Leishmania antigen.

[46] There are a number of problems with serological testing: in highly endemic areas, not everyone who becomes infected will actually develop clinical disease or require treatment.

As with many diseases in developing nations, (including trypanosomiasis and malaria) effective and affordable chemotherapy is sorely lacking and parasites or insect vectors are becoming increasingly resistant to existing anti-parasite drugs.

[60][61] In East Africa, the WHO recommended treatment is SSG&PM (sodium stibogluconate and paromomycin) developed by Drugs for Neglected Diseases initiative (DNDi) in 2010.

The cure rate of miltefosine in Phase III clinical trials is 95%; Studies in Ethiopia show that is also effective in Africa.

[63] It is now registered in other countries such as Nepal, Argentina, Bangladesh, Bolivia, Colombia, Ecuador, Guatemala, Honduras, Mexico, Pakistan, Paraguay, Peru, and Israel.

[3] The nonprofit Institute for OneWorld Health has adopted the broad spectrum antibiotic paromomycin for use in treating VL; its antileishmanial properties were first identified in the 1980s.

[75][76][77][78][79] T cells isolated from both cured and asymptomatic PBMC activate autologous macrophages to kill intracellular amastigotes.

[37] IL-12 is important in the development and maintenance of Type 1 T helper cell responses and protective immunity so its role in VL has also been studied.

[90] In addition to skin test negativity, VL patient PBMC do not proliferate or secrete IL-2 or IFN-γ in response to Leishmania antigens.

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.

[103] Kala-azar first came to the attention of Western doctors in 1824 in Jessore, British Raj (now Bangladesh), where it was initially thought to be a form of malaria.

[104] Another common name, kala-azar (Hindustani: काला आज़ार (Devanagari) کالا آزار (Nastaleeq) kālā āzār), is derived from kala which means black in Sanskrit, as well as in the languages descended from it, including Assamese,[105] Hindi and Urdu;[106] the word azar is a Persian loanword in Hindustani that means "fever";[105][107] as such the disease is named for the darkening of the skin on the extremities and abdomen that is a symptom of the Indian form of the disease.

[108] The agent of the disease was also first isolated in India by Scottish doctor William Leishman (who observed the parasite in spleen smears of a soldier who died of the disease in Dumdum, Calcutta, India[109] - hence the name dumdum fever) and Irish physician Charles Donovan, working independently of each other.

[112][113] Contemporary life has made itself felt even here, however—not as "progress" but in the form of the many small wars of Africa's post-colonial era.

One village at the center of the epidemic, Duar, was left with four survivors out of a population of a thousand, and from the late 1980s to the mid-1990s a total of 100,000 died from the sickness in that region alone.

In the words of Jill Seaman, the doctor who led relief efforts in the Upper Nile for the French organization Médecins Sans Frontières, "Where else in the world could 50% of a population die without anyone knowing?

[119] This work continued under Ernest Struthers and Lionel Napier at the School of Tropical Medicine at Calcutta to discover that kala-azar was transmitted by sandflies.

Single-dosage administrations of liposomal amphotericin B have been shown to be effective, and oral formulations are currently under development to increase access and facilitate distribution of the efficacious drug in the field.

[127][128][129] A 2018 study published details of a new potential preclinical drug candidate for the treatment for visceral leishmaniasis with an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold.