Jump to content

Visceral leishmaniasis

From Wikipedia, the free encyclopedia
(Redirected from Kala-azar)
This article is about visceral leishmaniasis in humans. For the disease in canids, see canine leishmaniasis.

Visceral leishmaniasis
kālā āzār
Other namesBlack fever, and Dumdum fever[1]
Amastigotes in a chorionic villus
Pronunciation
  • Kala-azar: (UK: /ˌkɑːlə əˈzɑːr/)
SpecialtyInfectious diseases Edit this on Wikidata

Visceral leishmaniasis (VL), also known as kala-azar (Hindi: kālā āzār, "black sickness")[2] or "black fever", is the most severe form of leishmaniasis and, without proper diagnosis and treatment, is associated with high fatality.[3] Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania.

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. Of particular concern, according to the World Health Organization (WHO), is the emerging problem of HIV/VL co-infection.[4]

VL is the second-largest parasitic killer in the world (after malaria), responsible for an estimated 20,000 to 30,000 deaths each year worldwide.[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.[7]

Signs and symptoms

[edit]

When people develop visceral leishmaniasis, the most typical symptoms are fever and the enlargement of the spleen, with enlargement of the liver sometimes being seen as well.[8] The blackening of the skin that gave the disease its common name in India does not appear in most strains of the disease, and the other symptoms are very easy to mistake for those of malaria. Misdiagnosis is dangerous, as without proper treatment the mortality rate for kala-azar is close to 100%.[9] L. donovani itself is not usually the direct cause of death in people with kala-azar, however. Pneumonia, tuberculosis, and dysentery are omnipresent in the immuno-depressed regions where leishmaniasis thrives, and, as with AIDS, it is these opportunistic infections that are more likely to kill, flaring up in a host whose immune system has been weakened by the L. donovani infection.[10] Progress of the disease is extremely variable, taking anywhere from one to twenty weeks, but a typical duration for the Sudanese strain of the disease is narrower, between twelve and sixteen weeks.[11]

Even with recovery, kala-azar does not always leave its hosts unmarked. Some time after successful treatment—generally a few months with African kala-azar, or as much as several years with the Indian strain—a secondary form of the disease may set in, called post kala-azar dermal leishmaniasis, or PKDL. 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. (This disease is not the same as cutaneous leishmaniasis, a milder disease caused by another protozoan of the Leishmania genus which also causes skin lesions.)[12]

Cause

[edit]

Two species of Leishmania are known to give rise to the visceral form of the disease. The species commonly found in East Africa and the Indian subcontinent is L. donovani and the species found in Europe, North Africa, and Latin America is L. infantum, also known as L. chagasi.[13]

The insect vectors are species of sandfly of the genus Phlebotomus in the Old World, and of Lutzomyia in the New World. Sandflies are tiny flies, measuring 3–6 mm long by 1.5–3 mm in diameter, and are found in tropical or temperate regions throughout the world. The sandfly species Lutzomyia longipalpis is the primary vector of this disease.[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.[15][16][17]

Visceral Leishmaniasis/kala-azar samples from India revealed the presence of not only the primary causative protozoan parasite, i.e. Leishmania donovani (LD) but also co-infection with another protozoan member called Leptomonas seymouri (LS). The latter parasite (LS) further contained a RNA virus known as Leptomonas seymouri narna-like virus 1 (Lepsey NLV1). 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.[18][19]

Life cycle

[edit]

The life cycle of Leishmania is completed in two hosts, humans and sandflies. The adult female sandfly is a bloodsucker, usually feeding at night on sleeping prey. When the fly bites an individual infected with Leishmania, the pathogen is ingested along with the prey's blood. The protozoan is in the smaller of its two forms, called an amastigote, which is round, non-motile, and only 3–7 micrometers in diameter. Inside the stomach of the sandfly, the amastigotes quickly transform into elongated and motile forms called the promastigotes. Promastigote is spindle-shaped, triple the size of the amastigote, and has a single flagellum that allows mobility. 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. As the fly bites, the promastigotes are released from the proboscis and introduced locally at the bite site.[20][21]

Once inside the human host, promastigotes invade macrophages. Inside the cells they transform back into the smaller amastigote form. The amastigotes replicate in the most hostile part of the macrophage cell, inside the phagolysosome, whose normal defensive response they are able to prevent. After repeated multiplication, they break down their host cell by sheer pressure of mass, but there is some recent speculation that they are able to leave the cell by triggering the exocytosis response of the macrophage.[22] The daughter cells protozoans then migrate to fresh cells or through the bloodstream to find new hosts. In this way the infection is progressive, spreading to the host's mononuclear phagocyte system, particularly the spleen and liver. The free amastigotes in peripheral tissues are then ingested by sandfly to enter another cycle.[23][24][25][26]

Regulatory T and B cells

[edit]

The cell-mediated immunity (CMI) that kills Leishmania also produces inflammation. If the inflammation is excessive, it can cause tissue damage. The role of regulatory T and regulatory B cells is to suppress CMI enough to prevent tissue damage.[27][28] However, an excessive regulatory response can prevent clearance of Leishmania and could explain the anergy of VL, poor response to drug treatment, development of PKDL, and relapses. A role for regulatory cells in VL has long been suspected.[29] A variety of regulatory T and B cells have been implicated in VL, including Type 1 T helper cells that secrete IL-10 in addition to IFN-γ, natural T reg, Tr1, CD8+ T reg, and B reg. All of these lymphocytes act, at least in part, by secreting IL-10 and other suppressive cytokines.[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.[32] Levels of FoxP3 mRNA were also up-regulated in lesional tissue from PKDL patients.[33] However, T regs are not elevated in spleen cells from VL patients nor does depletion of T regs increase Leishmania antigen specific IFN-γ secretion[34] The highest levels of IL-10 mRNA in spleen cells is in CD8+ and other non-FoxP3+ T cells.[35] White blood cell CD8+ T cells from VL patients have elevated IL-10 levels.[36] There is a 9.6 fold increase in IL-10 expressing CD8+ T cells among PBMC lymphocytes from PKDL patients.[33] In the one study of T cell clones from VL patients, the clones isolated from VL PBMC were 100% CD8+.[37] When mixed with self PBMC one or three years after successful treatment the CD8+ T cells decreased Leishmania antigen specific proliferation and IFN-γ secretion and increased IL-10 secretion. Depletion of CD8+ T cells from VL PBMC stopped endogenous IL-10 secretion but increased Leishmania antigen specific IL-10 secretion, suggesting that CD8+ regulatory T cells are responsible for endogenous IL-10 secretion.[38] CD4+ clones could only be isolated from VL PBMC after CD8+ T cell depletion. The CD4+ clones had little effect on IL-10 secretion but decreased IFN-γ secretion when mixed with self PBMC collected after successful treatment.[39]

Regulatory B cells are known to favor development of regulatory T cells and suppress development of Type 1 T helper cells by producing IL-10 and other down-regulatory cytokines.[28] IL-10 levels are elevated in B cells from VL PBMC.[36] A study of dogs with naturally acquired VL showed that the percentage of regulatory B cells increased three-fold during VL.[40] Depletion of B cells increased CD4+ T cell proliferation and IFN-γ secretion but decreased IL-10 secretion. Blocking IL-10 or programmed cell death receptors on B cells increased Leishmania antigen specific T cell proliferation and IFN-γ secretion. Co-culture of T cells with B cells decreased the percentage of CD4+ T cell proliferation and IFN-γ secretion four-fold.[41]

Diagnosis

[edit]

The gold standard for diagnosis is visualization of the amastigotes in splenic aspirate or bone marrow aspirate.[42] However, the technique is associated with discomfort, high risk of tissue damage, while being expensive and difficult.[43] The detection is also unreliable as it gives high false negative results, while the true positives are often having very low infection.[44]

Serological testing is much more frequently used in areas where leishmaniasis is endemic. A 2014 Cochrane review evaluated different rapid diagnostic tests. One of them (the rK39 immunochromatographic test) gave correct, positive results in 92% of the people with visceral leishmaniasis and it gave correct, negative results in 92% of the people who did not have the disease. A second rapid test (called latex agglutination test) gave correct, positive results in 64% of the people with the disease and it gave correct, negative results in 93% of the people without the disease. Other types of tests have not been studied thoroughly enough to ascertain their efficacy.[45]

The K39 dipstick test is easy to perform, and village health workers can be easily trained to use it. The kit may be stored at ambient temperature and no additional equipment needs to be carried to remote areas. The DAT anti-leishmania antigen test, standard within MSF, is much more cumbersome to use and appears not to have any advantages over the K39 test.[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. Indeed, up to 32% of the healthy population may test positive, but not require treatment.[47][48] Conversely, because serological tests look for an immune response and not for the organism itself, the test does not become negative after the patient is cured, it cannot be used as a check for cure, or to check for re-infection or relapse.[49] Likewise, patients with abnormal immune systems (e.g., HIV infection) will have false-negative tests.[50]

Other tests being developed include detects erythrosalicylic acid.[49]

Prevention

[edit]

As of 2018, there are no vaccines or preventive drugs for visceral leishmaniasis, but vaccines are in development.[51][52] The most effective method to prevent infection is to protect from sand fly bites. To decrease the risk of being bitten, these precautionary measures are suggested:[53][54][55]

  • Outdoors:

1. Avoid outdoor activities, especially from dusk to dawn, when sand flies generally are the most active.

2. When outdoors (or in unprotected quarters), minimize the amount of exposed (uncovered) skin to the extent that is tolerable in the climate. Wear long-sleeved shirts, long pants, and socks; and tuck your shirt into your pants.

3. Apply insect repellent to exposed skin and under the ends of sleeves and pant legs. Follow the instructions on the label of the repellent. The most effective repellents generally are those that contain the chemical DEET (N,N-diethylmetatoluamide).

  • Indoors:

1. Stay in well-screened or air-conditioned areas.

2. Keep in mind that sand flies are much smaller than mosquitoes and therefore can get through smaller holes.

3. Spray living/sleeping areas with an insecticide to kill insects.

4. If you are not sleeping in a well-screened or air-conditioned area, use a bed net and tuck it under your mattress. If possible, use a bed net that has been soaked in or sprayed with a pyrethroid-containing insecticide. The same treatment can be applied to screens, curtains, sheets, and clothing (clothing should be retreated after five washings).

Treatments

[edit]

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. Possibly due to the lack of financial return, new drugs are slow to emerge and much of the basic research into potential drug targets takes place in universities, funded by charitable organizations. Product Development Partnership, Drugs for Neglected Diseases initiative works on the development of new treatments (combination treatments and new chemical entities) for visceral leishmaniasis.[56]

The traditional treatment is with pentavalent antimonials such as sodium stibogluconate and meglumine antimoniate. Resistance is now common in India, and rates of resistance have been shown to be as high as 60% in parts of Bihar, India.[57][58]

The treatment of choice for visceral leishmaniasis acquired in India is now amphotericin B[59] in its various liposomal preparations.[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.[62]

Miltefosine is the first oral treatment for this disease. 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. Miltefosine has received approval by the Indian regulatory authorities in 2002, in Germany in 2004 and in U.S.A. in 2014.[63] It is now registered in other countries such as Nepal, Argentina, Bangladesh, Bolivia, Colombia, Ecuador, Guatemala, Honduras, Mexico, Pakistan, Paraguay, Peru, and Israel.[64]

The drug is generally better tolerated than other drugs. Main side effects are gastrointestinal disturbance in the first or second day of treatment (a course of treatment is 28 days) which does not affect the efficacy. Because it is available as an oral formulation, the expense and inconvenience of hospitalization is avoided, and outpatient distribution of the drug becomes an option, making miltefosine a drug of choice. However, there are some important disadvantages: 1) there is evidence of reduced efficacy after a decade of use[65] 2) it is potentially embryotoxic, fetotoxic and teratogenic, and thus cannot be used without anticonception in women of child-bearing age for three months (in some cases, five months[66][67]) after treatment.[68][69]

Incomplete treatment has been cited as a major reason of death from visceral leishmaniasis.[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. A treatment with paromomycin costs about US$15. The drug had originally been identified in the 1960s.[70] The Indian government approved paromomycin for sale and use in August 2006.[71]

Prognosis

[edit]

Protective immunity

[edit]

Immunity to Leishmania is determined by the interplay of white blood cells, cytokines, immune complexes, and genetic and environmental factors.[72] Protective immunity develops either after successful treatment of VL (cured) or after asymptomatic infections that resolve without development of VL (asymptomatic).[73][74] Both types of immunity are characterized by cell-mediated immunity (CMI), including skin test positivity, proliferation, and interleukin 2 (IL-2), interferon gamma (IFN-γ), and interleukin 12 (IL-12) secretion by peripheral blood mononuclear cells (PBMC) in response to Leishmania antigens.[75][76][77][78][79] T cells isolated from both cured and asymptomatic PBMC activate autologous macrophages to kill intracellular amastigotes.[80] IFN-γ activates macrophages to kill intracellular parasites so its role in VL has been studied extensively and IFN-γ production is often used as a marker of protective immunity. Cured PBMC generally secrete less IFN-γ and more interleukin 10 (IL-10) in response to Leishmania antigens than asymptomatic PBMC.[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. Addition of IL-12 to some VL PBMC increases proliferation and IFN-γ secretion in response to Leishmania antigens and anti-IL-12 inhibits proliferation and IFN-γ secretion by some cured PBMC.[79][81][82][83] Other cytokines also appear to be important in immunity to Leishmania but their roles are not as well characterized.[84][85]

Leishmania antigen stimulation of PBMC from cured patients show a mixed T helper cell and regulatory T cell response.[86] Both CD4+ and CD8+ T cells contributed to IFN-γ production.[35][87] Studies of Leishmania antigen specific T cell clones from cured patient PBMC confirm that cured patients have a mixed T cell response that involves both CD4+ helper T cells and CD4+ and CD8+ regulatory T cells.[38][88][89] Two studies of asymptomatic T cell clones show that most have Type 1 profiles and secrete more IFN-γ than T cell clones from cured patients. Neither study revealed the presence of Type 2 or regulatory T cells.[37][89] 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.[82]

Non-protective immunity

[edit]

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.[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.[75][76][91] Memory T cells may be depleted in VL patient PBMC.[92][93] 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.[37][92][94][95][96][97] PKDL patients also have elevated IL-10 levels.[33] VL patients with the highest IL-10 levels are more likely to be unresponsive to treatment and progress to PKDL.[32][98] 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.[38] Addition of anti-IL-10 increases proliferation and IFN-γ secretion by PBMC from some patients.[78][82] Both CD4+ and CD8+ T cells have been shown to contribute to IL-10 secretion by VL PBMC.[36][87] The high level of immune complexes characteristic of VL have also been shown to increase IL-10 levels.[99]

Epidemiology

[edit]
See also: Kala azar in India

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.[3] In India, more than 70% of VL cases are reported from the state of Bihar.[3] North Bihar, India (including Araria, Purnea, and Kishanganj) is the endemic zone of this disease. The disease is endemic in more than 70 countries.[100] In Iran this includes Ardabil, Fars, and North Khorasan.[101][102]

However, while the disease's 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.[103]

History

[edit]
See also: Leishmaniasis § History

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. Assam gave kala-azar one of its common names, Assam fever.[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. It is also pronounced kālāzar (कालाज़ार کالا زار).[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. As they published their discovery almost simultaneously, the species was named by Sir Ronald Ross for both of them—Leishmania donovani.[110][111]

The miracle of urea stibamine, drawn by Upendranath Brahmachari himself. The death rate is drastically declined from nearly 6300 to 750 within ten years in Assam.

Today, the name kala-azar is used interchangeably with the scientific name visceral leishmaniasis for the most acute form of the disease caused by L. donovani. The disease is endemic in West Bengal, where it was first discovered, but is seen at its most deadly in north and east Africa. It can also be found throughout the Arab world and southern Europe (where the causative organism is L. infantum), and a slightly different strain of the pathogen, L. chagasi, is responsible for leishmaniasis in the new world. Several species of canines serve as reservoir hosts of L. infantum (chagasi).[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. In the Sudan, where civil war has been continuous since 1983, the violence has been concentrated in the more populated south, and kala-azar was concentrated there too. But the wars have driven a steady stream of refugees out of the region, and these traveled either across the southern border or into the remoter western part of the country called the Upper Nile, where both war and the disease that went with it had not yet penetrated.[103]

These refugees, moving at foot-speed, carried the disease with them, and when it arrived it hit the Upper Nile with a force comparable to smallpox hitting the American Indians. The isolated people of the Upper Nile had no access to medicine or education about the new disease among them. Worse, their immune systems were defenseless against this new pathogen, foreign to them though it came only from another part of their own country. 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?"[114] Due to the South Sudanese Civil War, kala-azar has spread rapidly among the population.[115]

Upendranath Brahmachari

The Indian medical practitioner Upendranath Brahmachari was nominated for the Nobel Prize in Physiology or Medicine in 1929 for his discovery of ureastibamine (an antimonial compound for the treatment of kala-azar) and a new disease, post kala-azar dermal leishmaniasis.[116] Brahmachari's cure for visceral leishmaniasis was the urea salt of para-amino-phenyl stibnic acid which he called Urea Stibamine.[117]

During the nineteenth century, kala-azar was discovered near moving bodies of water in southeast Asia.[118] Dr. Jean Dow and Dr. William McClure, are credited with finding the cure for the disease in China. Largely uncredited for her contribution, Dow was one of the first to isolate the microorganism in China and conduct clinical studies on its origin.[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.[120][121]

On 31 October 2023, Bangladesh has been declared to be the first country to totally eradicate the disease.[122]

Research

[edit]

Combination drug therapies are currently under investigation, particularly by the Drugs for Neglected Diseases initiative (DNDi). Combination therapies allow for the use of existing drugs in combination, each in lower doses, which helps to decrease the incidence of severe side effects and drug toxicity, as well as the risk for development of resistance against the drugs; they have been shown to be cost-effective strategies.[123] Comparative homology modelling of the enzyme Hypoxanthine-guanine phosphoribosyl transferase (HGPRT; EC 2.4.2.8) in L. donovani suggest that among all of the computationally screened compounds, pentamidine, 1,3-dinitroadamantane, acyclovir and analogs of acyclovir had higher binding affinities than the real substrate (guanosine monophosphate).[124]

DNDi has a number of compounds in preclinical and phase 1 development,[125] but no novel drugs are expected in the next 5 years.[126] In the meantime, new combination therapies, and well as improvements to existing drugs targets, are under development. 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.[130]

There is no good vaccine candidate which prevents kala azar. A 2019 paper described designing an immunologic adjuvant which would make a VL vaccine more effective.[131]

References

[edit]
  1. ^ James, William D., Berger, Timothy G., et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. p. 426. ISBN 978-0-7216-2921-6.
  2. ^ "WHO | Visceral leishmaniasis". www.who.int. Archived from the original on July 15, 2013. Retrieved 2015-10-05.
  3. ^ a b c d Das A, Karthick M, Dwivedi S, Banerjee I, Mahapatra T, Srikantiah S, Chaudhuri I (2016-11-01). "Epidemiologic Correlates of Mortality among Symptomatic Visceral Leishmaniasis Cases: Findings from Situation Assessment in High Endemic Foci in India". PLOS Neglected Tropical Diseases. 10 (11): e0005150. doi:10.1371/journal.pntd.0005150. ISSN 1935-2735. PMC 5117587. PMID 27870870.
  4. ^ "Leishmaniasis and HIV co-infection". WHO. Archived from the original on February 19, 2007.
  5. ^ "Leishmaniasis". WHO Fact sheet N°375. World Health Organization. Retrieved 23 September 2014.
  6. ^ Desjeux P. (2001). "The increase of risk factors for leishmaniasis worldwide". Transactions of the Royal Society of Tropical Medicine and Hygiene. 95 (3): 239–43. doi:10.1016/S0035-9203(01)90223-8. PMID 11490989.
  7. ^ Hazra K (July 7, 2023). "Upendranath Brahmachari—forgotten Bengali scientist behind kala-azar cure got 2 Nobel nods". theprint.in. Retrieved July 8, 2023.
  8. ^ Poulaki A, Piperaki ET, Voulgarelis M (2021-04-05). "Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective". Microorganisms. 9 (4): 759. doi:10.3390/microorganisms9040759. ISSN 2076-2607. PMC 8066032. PMID 33916346.
  9. ^ Alemu C, Wudu H, Dessie G, Gashu C (2023-10-29). "Time to death and its determinant factors of visceral leishmaniasis with HIV co-infected patients during treatment period admitted at Metema hospital, Metema, Ethiopia: a hospital-based cross-sectional study design". Tropical Diseases, Travel Medicine and Vaccines. 9 (1): 18. doi:10.1186/s40794-023-00203-y. ISSN 2055-0936. PMC 10613359. PMID 37898767.
  10. ^ Mann S, Frasca K, Scherrer S, Henao-Martínez AF, Newman S, Ramanan P, Suarez JA (2021). "A Review of Leishmaniasis: Current Knowledge and Future Directions". Current Tropical Medicine Reports. 8 (2): 121–132. doi:10.1007/s40475-021-00232-7. ISSN 2196-3045. PMC 7966913. PMID 33747716.
  11. ^ Idris M, Farid J, Gul N, Anis-ur-Rehman n (2010). "Visceral leishmaniasis: adult population of Abbottabad at risk now". Journal of Ayub Medical College, Abbottabad: JAMC. 22 (2): 214–215. ISSN 1025-9589. PMID 21702307.
  12. ^ Burza S, Croft SL, Boelaert M (2018-09-15). "Leishmaniasis". The Lancet. 392 (10151): 951–970. doi:10.1016/S0140-6736(18)31204-2. ISSN 0140-6736. PMID 30126638. S2CID 208790410.
  13. ^ Chappuis F, et al. (2007). "Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?" (PDF). Nature Reviews Microbiology. 5 (11): 873–82. doi:10.1038/nrmicro1748. PMID 17938629. S2CID 6963295.
  14. ^ Alexander, Bruce; Lopes de Carvalho, Renata; McCallum, Hamish; Pereira, Marcos Horácio (December 2002). "Role of the Domestic Chicken (Gallus gallus)in the Epidemiology of Urban Visceral Leishmaniasis in Brazil". Emerging Infectious Diseases. 8 (12): 1480–1485. doi:10.3201/eid0812.010485. PMC 2738513. PMID 12498667.
  15. ^ Claborn DM (2010). "The biology and control of leishmaniasis vectors". Journal of Global Infectious Diseases. 2 (2): 127–134. doi:10.4103/0974-777X.62866. ISSN 0974-8245. PMC 2889652. PMID 20606968.
  16. ^ Feliciangeli MD (2004). "Natural breeding places of phlebotomine sandflies". Medical and Veterinary Entomology. 18 (1): 71–80. doi:10.1111/j.0269-283x.2004.0487.x. ISSN 0269-283X. PMID 15009450.
  17. ^ Alencar RB, de Queiroz RG, Barrett TV (2011-06-01). "Breeding sites of phlebotomine sand flies (Diptera: Psychodidae) and efficiency of extraction techniques for immature stages in terra-firme forest in Amazonas State, Brazil". Acta Tropica. 118 (3): 204–208. doi:10.1016/j.actatropica.2010.10.012. ISSN 0001-706X. PMID 21457701.
  18. ^ Sukla S, Roy, Syamal, Sundar, Shyam, Biswas, Subhajit (2017). "Leptomonas seymouri narna-like virus 1 and not leishmaniaviruses detected in kala-azar samples from India". Archives of Virology. 162 (12): 3827–35. doi:10.1007/s00705-017-3559-y. PMID 28939968. S2CID 31450182.
  19. ^ Sukla S, Nath, Himadri, Kamran, Mohd., Ejazi, Sarfaraz Ahmad, Ali, Nahid, Das, Pradeep, Ravichandiran, V, Roy, Syamal, Biswas, Subhajit (2022). "Detection of Leptomonas seymouri narna-like virus in serum samples of visceral leishmaniasis patients and its possible role in disease pathogenesis". Scientific Reports. 12 (1): 14436. Bibcode:2022NatSR..1214436S. doi:10.1038/s41598-022-18526-9. PMC 9402534. PMID 36002553.
  20. ^ Sacks DL (2001). "Leishmania-sand fly interactions controlling species-specific vector competence". Cellular Microbiology. 3 (4): 189–96. doi:10.1046/j.1462-5822.2001.00115.x. PMID 11298643. S2CID 39033146.
  21. ^ Ilg T, Stierhof, YD, Wiese, M, McConville, MJ, Overath, P (1994). "Characterization of phosphoglycan-containing secretory products of Leishmania". Parasitology. 108 (Suppl): S63-71. doi:10.1017/s0031182000075739. PMID 8084657. S2CID 22659332.
  22. ^ Lodge R, Descoteaux, A (2008). "Leishmania Invasion and Phagosome Biogenesis". Molecular Mechanisms of Parasite Invasion. Subcellular Biochemistry. Vol. 47. pp. 174–81. doi:10.1007/978-0-387-78267-6_14. ISBN 978-0-387-78266-9. PMID 18512351.
  23. ^ Chappuis F, Sundar, Shyam, Hailu, Asrat, Ghalib, Hashim, Rijal, Suman, Peeling, Rosanna W., Alvar, Jorge, Boelaert, Marleen (2007). "Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?". Nature Reviews Microbiology. 5 (11): S7 – S16. doi:10.1038/nrmicro1748. PMID 17938629. S2CID 6963295.
  24. ^ Pulvertaft RJ, Hoyle, GF (1960). "Stages in the life-cycle of Leishmania donovani". Transactions of the Royal Society of Tropical Medicine and Hygiene. 54 (2): 191–6. doi:10.1016/0035-9203(60)90057-2. PMID 14435316.
  25. ^ Chatterjee K (2009). Parasitology (protozoology and helminthology) in relation to clinical medicine (13th ed.). New Delhi: CBC Publishers. pp. 67–72. ISBN 9788123918105.
  26. ^ Pulvertaft R, Hoyle, G.F. (1960). "Stages in the life-cycle of Leishmania donovani". Transactions of the Royal Society of Tropical Medicine and Hygiene. 54 (2): 191–196. doi:10.1016/0035-9203(60)90057-2. PMID 14435316.
  27. ^ Belkaid Y (2007). "Regulatory T Cells and Infection: a Dangerous Necessity" (PDF). Nature Reviews Immunology. 7 (11): 875–88. doi:10.1038/nri2189. PMID 17948021. S2CID 28127648. Archived from the original (PDF) on 2018-10-18. Retrieved 2018-10-17.
  28. ^ a b Rosser E, Mauri C (2015). "Regulatory B Cells: Origin, Phenotype, and Function". Immunity. 42 (4): 607–12. doi:10.1016/j.immuni.2015.04.005. PMID 25902480.
  29. ^ Carvalho E, Bacellar O, Barral A, et al. (1989). "Antigen-specific Immunosuppression in Visceral Leishmaniasis Is Cell Mediated". J. Clin. Invest. 83 (3): 860–4. doi:10.1172/JCI113969. PMC 303759. PMID 2522103.
  30. ^ Rodrigues V, Cordeiro-da-Silva A, Laforge M, Silvestre R, Estaquier J (2016-03-01). "Regulation of immunity during visceral Leishmania infection". Parasites & Vectors. 9: 118. doi:10.1186/s13071-016-1412-x. ISSN 1756-3305. PMC 4774109. PMID 26932389.
  31. ^ Faleiro RJ, Kumar R, Hafner LM, Engwerda CR (2014). "Immune regulation during chronic visceral leishmaniasis". PLOS Neglected Tropical Diseases. 8 (7): e2914. doi:10.1371/journal.pntd.0002914. ISSN 1935-2735. PMC 4091888. PMID 25010815.
  32. ^ a b Rai A, Chandreshwar P, Singh A, et al. (2012). "Regulatory T Cells Suppress T Cell Activation at the Pathologic Site in Human Visceral Leishmaniasis". PLOS ONE. 7 (2): e31551. Bibcode:2012PLoSO...731551R. doi:10.1371/journal.pone.0031551. PMC 3275558. PMID 22347492.
  33. ^ a b c Ganguly S, Mukhopadhyay D, Das N, et al. (2010). "Enhanced Lesional FoxP3 Expression and Peripheral Anergic Lymphocytes Indicate a Role for Regulatory T Cells in Indian Post-Kala-azar Dermal Leishmaniasis". J. Invest. Dermatol. 130 (4): 1013–22. doi:10.1038/jid.2009.393. PMID 20032994.
  34. ^ Nylen S, Maurya R, Eidsmo L, et al. (2007). "Splenic Accumulation of IL-10 mRNA T Cells Distinct from CD4+ CD25+ (FoxP3+) Regulatory T Cells in Human Visceral Leishmaniasis". J Exp Med. 204 (4): 805–17. doi:10.1084/jem.20061141. PMC 2118563. PMID 17389235.
  35. ^ a b Gautam S, Kumar R, Singh N, et al. (2014). "CD8 T Cell Exhaustion in Human Visceral Leishmaniasis". J. Infect. Dis. 209 (2): 290–99. doi:10.1093/infdis/jit401. PMC 3873784. PMID 23922369.
  36. ^ a b c Peruhype-Magalhaes V, Martins-Filho O, Prata A, et al. (2006). "Mixed Inflammatory/Regulatory Cytokine Profile Marked by Simultaneous Raise of Interferon-g and Interleukin-10 and Low Frequency of Tumor Necrosis Factor-a Monocytes Are Hallmarks of Active Human Visceral Leishmaniasis Due to Leishmania chagasi Infection". Clin. Exp. Immunol. 146 (1): 124–32. doi:10.1111/j.1365-2249.2006.03171.x. PMC 1809731. PMID 16968407.
  37. ^ a b c d Holaday B, Pompeu M, Jeronimo S, et al. (1993). "Potential Role for Interleukin-10 in the Immunosuppression Associated with Kala-azar". J. Clin. Invest. 92 (6): 2626–32. doi:10.1172/JCI116878. PMC 288459. PMID 8254019.
  38. ^ a b c Holaday B (2000). "Role of CD8+ T Cells in Endogenous Interleukin-10 Secretion Associated with Visceral Leishmaniasis". Mem. Inst. Oswaldo Cruz. 95 (2): 217–20. doi:10.1590/s0074-02762000000200013. PMID 10733741.
  39. ^ Kumar R, Singh N, Gautam S, Singh OP, Gidwani K, Rai M, Sacks D, Sundar S, Nylén S (2014). "Leishmania specific CD4 T cells release IFNγ that limits parasite replication in patients with visceral leishmaniasis". PLOS Neglected Tropical Diseases. 8 (10): e3198. doi:10.1371/journal.pntd.0003198. ISSN 1935-2735. PMC 4183461. PMID 25275531.
  40. ^ Schaut R, Lamb I, Toepp A, et al. (2016). "Regulatory IgDhi B Cells Suppress T Cell Function Via IL-10 and PD-L1 during Progressive Visceral Leishmaniasis". J Immunol. 196 (10): 4100–9. doi:10.4049/jimmunol.1502678. PMC 4868652. PMID 27076677.
  41. ^ Schaut RG, Lamb IM, Toepp AJ, Scott B, Mendes-Aguiar CO, Coutinho JF, Jeronimo SM, Wilson ME, Harty JT, Waldschmidt TJ, Petersen CA (2016-05-15). "Regulatory IgDhi B Cells Suppress T Cell Function via IL-10 and PD-L1 during Progressive Visceral Leishmaniasis". Journal of Immunology. 196 (10): 4100–4109. doi:10.4049/jimmunol.1502678. ISSN 1550-6606. PMC 4868652. PMID 27076677.
  42. ^ "Leishmaniasis - Diagnosis". www.cdc.gov. 2022-03-16. Retrieved 2022-04-20.
  43. ^ Thakur S, Joshi J, Kaur S (2020). "Leishmaniasis diagnosis: an update on the use of parasitological, immunological and molecular methods". Journal of Parasitic Diseases. 44 (2): 253–272. doi:10.1007/s12639-020-01212-w. ISSN 0971-7196. PMC 7223249. PMID 32419743.
  44. ^ El-Amin LM, Khalid KE, El-Badry AA (2020). "Risk-free point-of-care visceral leishmaniasis diagnostics: combining buffy coat microscopy and immunoassay in tertiary rural hospitals in Sudan". Acta Tropica. 211: 105599. doi:10.1016/j.actatropica.2020.105599. ISSN 1873-6254. PMID 32592684.
  45. ^ Boelaert M, Verdonck K, Menten J, et al. (June 2014). "Rapid tests for the diagnosis of visceral leishmaniasis in patients with suspected disease". Cochrane Database Syst Rev. 2014 (6): CD009135. doi:10.1002/14651858.CD009135.pub2. PMC 4468926. PMID 24947503.
  46. ^ Chappuis F, Rijal S, Soto A, Menten J, Boelaert M (2006). "A meta-analysis of the diagnostic performance of the direct agglutination test and rK39 dipstick for visceral leishmaniasis". Br Med J. 333 (7571): 723–6. doi:10.1136/bmj.38917.503056.7C. PMC 1592383. PMID 16882683.
  47. ^ Sundar S, Singh RK, Maurya R, et al. (June 2006). "Serological diagnosis of Indian visceral leishmaniasis: direct agglutination test versus rK39 strip test". Trans. R. Soc. Trop. Med. Hyg. 100 (6): 533–7. doi:10.1016/j.trstmh.2005.08.018. PMID 16325874.
  48. ^ Sundar S, Maurya R, Singh RK, et al. (January 2006). "Rapid, noninvasive diagnosis of visceral leishmaniasis in India: comparison of two immunochromatographic strip tests for detection of anti-K39 antibody". J. Clin. Microbiol. 44 (1): 251–3. doi:10.1128/JCM.44.1.251-253.2006. PMC 1351954. PMID 16390983.
  49. ^ a b Lockwood DN, Sundar S (October 2006). "Serological tests for visceral leishmaniasis". BMJ. 333 (7571): 711–2. doi:10.1136/bmj.38989.567083.BE. PMC 1592372. PMID 17023436.
  50. ^ Pasquau F, Ena J, Sanchez R, et al. (June 2005). "Leishmaniasis as an opportunistic infection in HIV-infected patients: determinants of relapse and mortality in a collaborative study of 228 episodes in a Mediterranean region". Eur. J. Clin. Microbiol. Infect. Dis. 24 (6): 411–8. doi:10.1007/s10096-005-1342-6. PMID 15928908. S2CID 26991291.
  51. ^ "Parasites-Leishmaniasis Prevention and Control". January 10, 2013. Retrieved April 29, 2014.
  52. ^ Gillespie PM, Beaumier CM, Strych U, Hayward T, Hotez PJ, Bottazzi ME (2016-06-03). "Status of vaccine research and development of vaccines for leishmaniasis". Vaccine. 34 (26): 2992–2995. doi:10.1016/j.vaccine.2015.12.071. ISSN 1873-2518. PMID 26973063.
  53. ^ CDC (2024-03-11). "Preventing Leishmaniasis". Leishmaniasis. Retrieved 2024-06-06.
  54. ^ "Leishmaniasis: Types, symptoms, treatment, and prevention". www.medicalnewstoday.com. 2024-05-09. Retrieved 2024-06-06.
  55. ^ Davies CR, Kaye P, Croft SL, Sundar S (2003-02-15). "Leishmaniasis: new approaches to disease control". BMJ (Clinical Research Ed.). 326 (7385): 377–382. doi:10.1136/bmj.326.7385.377. ISSN 1756-1833. PMC 1125241. PMID 12586674.
  56. ^ "DNDi Annual Report 2015" (PDF). Drugs for Neglected Diseases initiatives. Retrieved 2016-09-19.
  57. ^ Sundar S, More DK, Singh MK, et al. (October 2000). "Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic". Clin. Infect. Dis. 31 (4): 1104–7. doi:10.1086/318121. PMID 11049798.
  58. ^ Thakur CP, Narayan S, Ranjan A (September 2004). "Epidemiological, clinical & pharmacological study of antimony-resistant visceral leishmaniasis in Bihar, India" (PDF). Indian J. Med. Res. 120 (3): 166–72. PMID 15489554.
  59. ^ Thakur CP, Singh RK, Hassan SM, Kumar R, Narain S, Kumar A (1999). "Amphotericin B deoxycholate treatment of visceral leishmaniasis with newer modes of administration and precautions: a study of 938 cases". Trans. R. Soc. Trop. Med. Hyg. 93 (3): 319–23. doi:10.1016/S0035-9203(99)90037-8. PMID 10492770.
  60. ^ Thakur CP, Pandey AK, Sinha GP, Roy S, Behbehani K, Olliaro P (1996). "Comparison of three treatment regimens with liposomal amphotericin B (AmBisome) for visceral leishmaniasis in India: a randomized dose-finding study". Trans. R. Soc. Trop. Med. Hyg. 90 (3): 319–22. doi:10.1016/S0035-9203(96)90271-0. PMID 8758093.
  61. ^ Sundar S, Mehta H, Chhabra A, et al. (March 2006). "Amphotericin B colloidal dispersion for the treatment of Indian visceral leishmaniasis". Clin. Infect. Dis. 42 (5): 608–13. doi:10.1086/500138. PMID 16447104.
  62. ^ New treatment for kala azar, the most deadly parasitic disease after malaria. ScienceDaily, 23 September 2011
  63. ^ FDA News Release (19 March 2014). "FDA approves Impavido to treat tropical disease leishmaniasis". FDA.
  64. ^ Sunyoto T, Potet J, Boelaert M (2018). "Why miltefosine-a life-saving drug for leishmaniasis-is unavailable to people who need it the most". BMJ Global Health. 3 (3): e000709. doi:10.1136/bmjgh-2018-000709. ISSN 2059-7908. PMC 5935166. PMID 29736277.
  65. ^ Rijal S, Ostyn B, Uranw S, Rai K, Bhattarai NR, Dorlo TP, Beijnen JH, Vanaerschot M, Decuypere S, Dhakal SS, Das ML (2013-06-01). "Increasing Failure of Miltefosine in the Treatment of Kala-azar in Nepal and the Potential Role of Parasite Drug Resistance, Reinfection, or Noncompliance". Clinical Infectious Diseases. 56 (11): 1530–1538. doi:10.1093/cid/cit102. ISSN 1058-4838. PMID 23425958.
  66. ^ Kämink S, Masih B, Ali N, Ullah A, Khan SJ, Ashraf S, Pylypenko T, Grobusch MP, Fernhout J, den Boer M, Ritmeijer K (January 2021). "Effectiveness of miltefosine in cutaneous leishmaniasis caused by Leishmania tropica in Pakistan after antimonial treatment failure or contraindications to first line therapy-A retrospective analysis". PLOS Neglected Tropical Diseases. 15 (1): e0008988. doi:10.1371/journal.pntd.0008988. ISSN 1935-2735. PMC 7872246. PMID 33507944.
  67. ^ Pijpers J, den Boer ML, Essink DR, Ritmeijer K (2019). "The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia - A review and meta-analysis". PLOS Neglected Tropical Diseases. 13 (2): e0007173. doi:10.1371/journal.pntd.0007173. ISSN 1935-2735. PMC 6386412. PMID 30742620.
  68. ^ Monge-Maillo B, López-Vélez R (2015-05-01). "Miltefosine for visceral and cutaneous leishmaniasis: drug characteristics and evidence-based treatment recommendations". Clinical Infectious Diseases. 60 (9): 1398–1404. doi:10.1093/cid/civ004. ISSN 1537-6591. PMID 25601455.
  69. ^ Sindermann H, Engel J (2006). "Development of miltefosine as an oral treatment for leishmaniasis". Transactions of the Royal Society of Tropical Medicine and Hygiene. 100 (Suppl 1): S17–20. doi:10.1016/j.trstmh.2006.02.010. ISSN 0035-9203. PMID 16730362.
  70. ^ A Small Charity Takes the Reins in Fighting a Neglected Disease, New York Times, July 31, 2006.
  71. ^ NEW CURE FOR DEADLY VISCERAL LEISHMANIASIS (KALA-AZAR) APPROVED BY GOVERNMENT OF INDIA Archived 2007-07-06 at the Wayback Machine, Institute for OneWorld Health Press Release, September 8, 2006.
  72. ^ Saha S, Mondal S, Banerjee, et al. (2006). "Immune Responses in Kala-azar". Indian J Med Res. 123 (3): 245–66. PMID 16778308.
  73. ^ Manson-Bahr P (1961). "Immunity in Kala-azar". Trans. R. Soc. Trop. Med. Hyg. 55 (6): 550–55. doi:10.1016/0035-9203(61)90078-5. PMID 14469435.
  74. ^ Manson-Bahr P (1967). "Cryptic Infections of Humans in an Endemic Kala-azar Area". E. African Med. J. 44 (4): 177–82. ISSN 0012-835X.
  75. ^ a b Carvalho E, Teixeira R, Johnson W Jr (1981). "Cell Mediated Immunity in American Visceral Leishmaniasis: Reversible Immunosuppression during Acute Infection". Infect. Immun. 33 (2): 498–502. doi:10.1128/IAI.33.2.498-500.1981. PMC 350726. PMID 7275314.
  76. ^ a b Carvalho E, Badaro R, Reed S, et al. (1985). "Absence of gamma interferon and interleukin 2 production during active visceral leishmaniasis". J. Clin. Invest. 76 (6): 2066–2069. doi:10.1172/JCI112209. PMC 424308. PMID 3935667.
  77. ^ Carvalho E, Barral A, Pedral-Sampaio D, et al. (1992). "Immunologic Markers of Clinical Evolution in Children Recently Infected with Leishmania donovani chagasi". J. Infect. Dis. 165 (3): 535–40. doi:10.1093/infdis/165.3.535. PMID 1347057.
  78. ^ a b Carvalho E, Bacellar O, Brownell C, et al. (1994). "Restoration of IFN-gamma Production and Lymphocyte Proliferation in Visceral Leishmaniasis". J. Immunol. 15 (12): 5949–56. doi:10.4049/jimmunol.152.12.5949. PMID 8207220. S2CID 31372945.
  79. ^ a b Ghalib H, Whittle J, Kubin M, et al. (1995). "IL-12 Enhances Th-1 Type Responses in Human Leishmania donovani Infections". J. Immunol. 154 (9): 4623–9. doi:10.4049/jimmunol.154.9.4623. PMID 7722314. S2CID 37383454.
  80. ^ Holaday B, Pompeu M, Evans T, et al. (1993). "Correlates of Leishmania-specific Immunity in the Clinical Spectrum of Infection with Leishmania chagasi". J. Infect. Dis. 167 (2): 411–17. doi:10.1093/infdis/167.2.411. PMID 8421174.
  81. ^ Bacellar O, Brodskyn C, Guerreiro J, et al. (1996). "Interleukin-12 Restores Interferon-γ Production and Cytotoxic Responses in Visceral Leishmaniasis" (PDF). J. Infect. Dis. 173 (6): 1515–8. doi:10.1093/infdis/173.6.1515. PMID 8648233.
  82. ^ a b c Holaday B (1999). "Immunotherapy for Visceral Leishmaniasis: Ability of Factors Produced during Anti-Leishmania Responses of Skin Test Positive Adults to Inhibit Peripheral Blood Mononuclear Cell Activities Associated with Visceral Leishmaniasis". Mem. Inst. Oswaldo Cruz. 94 (1): 55–66. doi:10.1590/S0074-02761999000100013. PMID 10029912.
  83. ^ Bacellar O, D'oliveira A Jr, Jerônimo S, et al. (2000). "IL-10 and IL-12 Are the Main Regulatory Cytokines in Visceral Leishmaniasis". Cytokine. 12 (8): 1228–31. doi:10.1006/cyto.2000.0694. PMID 10930301.
  84. ^ Almeida FS, Vanderley SE, Comberlang FC, Andrade AG, Cavalcante-Silva LH, Silva ED, Palmeira PH, Amaral IP, Keesen TS (2023-05-15). "Leishmaniasis: Immune Cells Crosstalk in Macrophage Polarization". Tropical Medicine and Infectious Disease. 8 (5): 276. doi:10.3390/tropicalmed8050276. ISSN 2414-6366. PMC 10222886. PMID 37235324.
  85. ^ Alimohmmadian MH, Ajdary S, Bahrami F (2022-03-01). "A Historic Review of the Role of CD4+ T-Cell Subsets in Development of the Immune Responses against Cutaneous and Visceral Leishmaniases". Iranian Biomedical Journal. 26 (2): 99–109. doi:10.52547/ibj.26.2.99 (inactive 1 November 2024). ISSN 2008-823X. PMC 8987415. PMID 35090305.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
  86. ^ Kemp K, Kemp M, Kharazmi A, et al. (1999). "Leishmania-specific T Cells Expressing Interferon-gamma (IFN-γ) and IL-10 upon Activation Are Expanded in Individuals Cured of Visceral Leishmaniasis". Clin. Exp. Immunol. 116 (3): 500–4. doi:10.1046/j.1365-2249.1999.00918.x. PMC 1905302. PMID 10361241.
  87. ^ a b Saha S, Mondal S, Ravindran R, et al. (2007). "IL-10- and TGF-B-Mediated Susceptibility in Kala-azar and Post-kala-azar Dermal Leishmaniasis: The Significance of Amphotericin B in the Control of Leishmania donovani Infection in India". J. Immunol. 179 (8): 5592–5603. doi:10.4049/jimmunol.179.8.5592. PMID 17911647.
  88. ^ Kemp M, Kurtzhals J, Bendtzen K, et al. (1993). "Leishmania donovani-reactive TH1-like T Cell Clones from Individuals Who Have Recovered from Visceral Leishmaniasis". Infect. Immun. 61 (3): 1069–73. doi:10.1128/IAI.61.3.1069-1073.1993. PMC 302840. PMID 8432588.
  89. ^ a b Mary C, Auriault V, Faugere B, et al. (1999). "Control of Leishmania infantum Infection Is Associated with CD8+ and Gamma-interferon and Interleukin-5 Producing CD4+ Antigen-specific T Cells". Infect. Immun. 67 (11): 5559–66. doi:10.1128/IAI.67.11.5559-5566.1999. PMC 96926. PMID 10531200.
  90. ^ Ho M, Koech D, Iha D, et al. (1983). "Immune Suppression in Kenyan Visceral Leishmaniasis". Clin. Exp. Immunol. 51 (2): 207–14. PMC 1536899. PMID 6839538.
  91. ^ Haldar J, Ghose S, Saha K, et al. (1983). "Cell-mediated Immune Response in Indian Kala-azar and Post-kala-azar Dermal Leishmaniasis". Infect. Immun. 42 (2): 702–7. doi:10.1128/IAI.42.2.702-707.1983. PMC 264486. PMID 6642649.
  92. ^ a b Cillari E, Vitale G, Arcoleo F, et al. (1995). "In Vivo and In Vitro Cytokine and Mononuclear Cell Subsets in Sicilian Patients with Visceral Leishmaniasis". Cytokine. 7 (7): 740–5. doi:10.1006/cyto.1995.0088. PMID 8580385.
  93. ^ Hailu A, van Baarle D, Knol G, et al. (2005). "T Cell and Cytokine Profiles in Human Visceral Leishmaniasis during Active and Asymptomatic or Sub-clinical Infection with Leishmania donovani". Clin. Immunol. 117 (2): 182–91. doi:10.1016/j.clim.2005.06.015. hdl:1874/380043. PMID 16125466. S2CID 3186886.
  94. ^ Karp C, el-Safi S, Wynn T, et al. (1993). "In vivo Cytokine Profiles in Patients with Kala-azar. Marked Elevation of Both Interleukin-10 and Interferon-gamma". J. Clin. Invest. 91 (4): 1664–8. doi:10.1172/JCI116372. PMC 288142. PMID 8097208.
  95. ^ Ghalib H, Piuvezam M, Skeiky Y, et al. (1993). "Interleukin-10 Production Correlates with Pathology in Human Leishmania donovani Infections". J Clin Invest. 92 (1): 324–9. doi:10.1172/JCI116570. PMC 293600. PMID 8326000.
  96. ^ Medeiros I, Castelo A, Salomão R (1998). "Presence of Circulating Levels of Interferon-gamma, Interleukin-10 and Tumor Necrosis Factor-alpha in Patients with Visceral Leishmaniasis". Rev Inst Med Trop Sao Paulo. 40 (1): 31–4. doi:10.1590/S0036-46651998000100007. PMID 9713135.
  97. ^ Peruhype-Magalhaes V, Martins-Filho O, Prata A, et al. (2005). "Immune Response in Human Visceral Leishmaniasis: Analysis of the Correlation between Innate Immunity Cytokine Profile and Disease Outcome". Scand. J. Immunol. 62 (5): 487–495. doi:10.1111/j.1365-3083.2005.01686.x. PMID 16305646. S2CID 25506998.
  98. ^ Gasim S, Elhassan A, Khalil E, et al. (1998). "High Levels of Plasma IL-10 and Expression of IL-10 by Keratinocytes during Visceral Leishmaniasis Predict Subsequent Development of Post-kala-azar Dermal Leishmanniasis". Clin. Exp. Immunol. 111 (1): 64–9. doi:10.1046/j.1365-2249.1998.00468.x. PMC 1904865. PMID 9472662.
  99. ^ Elshafie A, Ahlin E, Mathsson L, et al. (2007). "Circulating Immune Complexes (IC) and IC-induced Levels of GM-CSF Are Increased in Sudanese Patients with Acute Visceral Leishmania donovani Infection Undergoing Sodium Stibogluconate Treatment: Implications for Disease Pathogenesis". J. Immunol. 178 (8): 5383–89. doi:10.4049/jimmunol.178.8.5383. PMID 17404324.
  100. ^ Scarpini S, Dondi A, Totaro C, Biagi C, Melchionda F, Zama D, Pierantoni L, Gennari M, Campagna C, Prete A, Lanari M (2022-09-21). "Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics". Microorganisms. 10 (10): 1887. doi:10.3390/microorganisms10101887. ISSN 2076-2607. PMC 9609364. PMID 36296164.
  101. ^ Mohebali M (2013). "Visceral leishmaniasis in Iran: Review of the Epidemiological and Clinical Features". Iranian Journal of Parasitology. 8 (3): 348–358. ISSN 1735-7020. PMC 3887234. PMID 24454426.
  102. ^ Shamsian SA, Fata A, Alinezhad R, Mohebali M, Sadabadi F, Moghaddas E, Fakhar M (2020). "Clinical and Laboratory Findings of Visceral Leishmaniasis in Children Hospitalized in Mashhad, Northeastern Iran: A Twenty-Year Retrospective Study". Iranian Journal of Parasitology. 15 (4): 495–499. doi:10.18502/ijpa.v15i4.4854. ISSN 1735-7020. PMC 8039489. PMID 33884006.
  103. ^ a b Jean, Francois (1995). "Sudan: Speak no Evil, Do no Good". Life, Death and Aid: The Médecins Sans Frontières Report on World Crisis Intervention.
  104. ^ "Mosby's Medical Dictionary, 8th edition. © 2009, Elsevier.". "kala-azar". Retrieved 2010-01-21.{{cite web}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  105. ^ a b HarperCollins Publishers, 1991, 1994, 1998, 2000, 2003. "kala-azar". Retrieved 2010-01-21.{{cite web}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  106. ^ Merriam-Webster's online dictionary. "kala-azar". Retrieved 2010-01-21.
  107. ^ Taku TA (1999). Framework for Industrialization in Africa. Greenwood Publishing Group. p. 77. ISBN 9780275964986. Locally, the disease was called kala-azar or black fever, which is the meaning in the Hindustani language.
  108. ^ "kaalaa-zaar". Rekhta Dictionary. Retrieved 30 September 2024.
  109. ^ Paniker CJ (2013). Textbook of Medical Parasitology. Shorakhutte, Kathmandu, Nepal: Jaypee Brothers, Medical Publishers. p. 51. ISBN 978-93-5090-534-0.
  110. ^ Gibson ME (1983). "The identification of kala-azar and the discovery of Leishmania donovani". Medical History. 27 (2): 203–213. doi:10.1017/s0025727300042691. ISSN 0025-7273. PMC 1139308. PMID 6345968.
  111. ^ Steverding D (2017-02-15). "The history of leishmaniasis". Parasites & Vectors. 10 (1): 82. doi:10.1186/s13071-017-2028-5. ISSN 1756-3305. PMC 5312593. PMID 28202044.
  112. ^ Ribeiro RR, Michalick MS, da Silva ME, Dos Santos CC, Frézard FJ, da Silva SM (2018). "Canine Leishmaniasis: An Overview of the Current Status and Strategies for Control". BioMed Research International. 2018: 3296893. doi:10.1155/2018/3296893. ISSN 2314-6141. PMC 5896350. PMID 29789784.
  113. ^ Morales-Yuste M, Martín-Sánchez J, Corpas-Lopez V (2022-07-27). "Canine Leishmaniasis: Update on Epidemiology, Diagnosis, Treatment, and Prevention". Veterinary Sciences. 9 (8): 387. doi:10.3390/vetsci9080387. ISSN 2306-7381. PMC 9416075. PMID 36006301.
  114. ^ Dowell, William (1997). "Rescue in Sudan". Time.
  115. ^ "As South Sudan implodes, America reconsiders its support for the regime". The Economist. 12 October 2017.
  116. ^ Nobel Foundation (2008).The Nomination Database for the Nobel Prize in Physiology or Medicine, 1901-1951
  117. ^ Upendra Nath Brahmachari: A Pioneer of Modern Medicine in India Archived 2018-12-25 at the Wayback Machine. Vigyan Prasar: Government of India
  118. ^ Christensen E (2005). In War and Famine: Missionaries in China's Honan Province in the 1940s. MQUP. p. 195. ISBN 9780773572591.
  119. ^ Figuring it out : science, gender, and visual culture. Shteir, Ann B.; Lightman, Bernard V. (1st ed.). Hanover, N.H.: Dartmouth College Press. 2006. ISBN 1-58465-602-6. OCLC 70673140.{{cite book}}: CS1 maint: others (link)
  120. ^ "Dr. L. Everard Napier". Indian Medical Gazette. 78 (5): 252. May 1943. PMC 5158438. PMID 29012190.
  121. ^ Gewurtz MS (2017-01-01). "Transnationalism in Missionary Medicine: The Case of Kala-azar in China and India, 1909–1946". Social Sciences and Missions. 30 (1–2): 30–43. doi:10.1163/18748945-03001001. ISSN 1874-8945.
  122. ^ "Bangladesh world's first black-fever free country".
  123. ^ Olliaro, P., Darley, S., Laxminarayan, R., et al. (2009). "Cost-effectiveness projections of single and combination therapies for visceral leishmaniasis in Bihar, India". Trop Med Int Health. 14 (8): 918–925. doi:10.1111/j.1365-3156.2009.02306.x. PMID 19563434. S2CID 29278489.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  124. ^ Ansari MY, Dikhit MR, Sahoo GC, Das P (April 2012). "Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP". Int. J. Biol. Macromol. 50 (3): 637–49. doi:10.1016/j.ijbiomac.2012.01.010. PMID 22327112.
  125. ^ "Portfolio – DNDi". www.dndi.org. Retrieved 2020-02-13.
  126. ^ den Boer, M.L., Alvar, J., Davidson, R.N., et al. (2009). "Developments in the treatment of visceral leishmaniasis". Expert Opinion on Emerging Drugs. 14 (3): 395–410. doi:10.1517/14728210903153862. hdl:10144/127729. PMID 19708817. S2CID 32952275.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  127. ^ Sundar, S., Chakravarty, J., Agarwal, D., et al. (2010). "Single-dose liposomal amphotericin B for visceral leishmaniasis in India". N Engl J Med. 362 (6): 504–512. doi:10.1056/NEJMoa0903627. PMID 20147716. S2CID 7070133.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  128. ^ Wasan, K. M., Wasan, E. K., Gershkovich, P., et al. (2009). "Highly effective oral amphotericin B formulation against murine visceral leishmaniasis". J Infect Dis. 200 (3): 357–60. doi:10.1086/600105. PMID 19545212.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  129. ^ Arzamani K, Fazeli R, Shirzadi MR, Raeghi S, Arzamani M, Alavinia SM. Visceral Leishmaniasis in North Khorasan Province, Iran.
  130. ^ Wyllie S, Thomas M, Patterson S, Crouch S, De Rycker M, Lowe R, Gresham S, Urbaniak MD, Otto TD (2018-07-25). "Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis". Nature. 560 (7717): 192–197. Bibcode:2018Natur.560..192W. doi:10.1038/s41586-018-0356-z. ISSN 0028-0836. PMC 6402543. PMID 30046105.
  131. ^ Ratnapriya S, Keerti, Sahasrabuddhe AA, Dube A (12 June 2019). "Visceral leishmaniasis: An overview of vaccine adjuvants and their applications". Vaccine. 37 (27): 3505–3519. doi:10.1016/j.vaccine.2019.04.092. PMID 31103364. S2CID 159039859.

101.[1]

[2]

[edit]
  1. ^ Kumar P, Shivam P, Mandal S, Prasanna P, Kumar S, Prasad SR, Kumar A, Das P, Ali V, Singh SK, Mandal D (2019-08-20). "Synthesis, characterization, and mechanistic studies of a gold nanoparticle-amphotericin B covalent conjugate with enhanced antileishmanial efficacy and reduced cytotoxicity". International Journal of Nanomedicine. 14: 6073–6101. doi:10.2147/IJN.S196421. PMC 6709383. PMID 31686803.
  2. ^ Mookerjee Basu J, Mookerjee A, Banerjee R, Saha M, Singh S, Naskar K, Tripathy G, Sinha PK, Pandey K, Sundar S, Bimal S, Das PK, Choudhuri SK, Roy S (2008). "Inhibition of ABC Transporters Abolishes Antimony Resistance in Leishmania Infection". Antimicrobial Agents and Chemotherapy. 52 (3): 1080–1093. doi:10.1128/aac.01196-07. PMC 2258502. PMID 18056276.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Visceral_leishmaniasis&oldid=1254987806"