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Leishmaniasis is a wide array of clinical manifestations caused by
parasite Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson h ...
s of the trypanosome genus '' Leishmania''. It is generally spread through the bite of
phlebotomine The Phlebotominae are a subfamily of the family Psychodidae. In several countries, their common name is sandfly; but that name is also applied to other flies. The Phlebotominae include many genera of blood-feeding (hematophagous) flies, including ...
sandflies Sandfly (or sand fly) is a colloquial name for any species or genus of flying, biting, blood-sucking dipteran (fly) encountered in sandy areas. In the United States, ''sandfly'' may refer to certain horse flies that are also known as "green ...
, ''
Phlebotomus ''Phlebotomus'' is a genus of "sand flies" in the Diptera family Psychodidae. In the past, they have sometimes been considered to belong in a separate family, Phlebotomidae, but this alternative classification has not gained wide acceptance. ...
'' and ''
Lutzomyia ''Lutzomyia'' is a genus of phlebotomine sand flies consisting of nearly 400 species, at least 33 of which have medical importance as vectors of human disease. Species of the genus ''Lutzomyia'' are found only in the New World, distributed in ...
'', and occurs most frequently in the tropics and sub-tropics of Africa, Asia, the Americas, and southern Europe. The disease can present in three main ways: cutaneous, mucocutaneous, or
visceral In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a f ...
. The cutaneous form presents with skin ulcers, while the mucocutaneous form presents with ulcers of the skin, mouth, and nose. The visceral form starts with skin ulcers and later presents with fever, low red blood cell count, and enlarged spleen and liver. Infections in humans are caused by more than 20 species of ''Leishmania''. Risk factors include poverty,
malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
,
deforestation Deforestation or forest clearance is the removal of a forest or stand of trees from land that is then converted to non-forest use. Deforestation can involve conversion of forest land to farms, ranches, or urban use. The most concentrated ...
, and
urbanization Urbanization (or urbanisation) refers to the population shift from rural to urban areas, the corresponding decrease in the proportion of people living in rural areas, and the ways in which societies adapt to this change. It is predominantly th ...
. All three types can be diagnosed by seeing the parasites under microscopy. Additionally, visceral disease can be diagnosed by blood tests. Leishmaniasis can be partly prevented by sleeping under nets treated with insecticide. Other measures include spraying insecticides to kill sandflies and treating people with the disease early to prevent further spread. The treatment needed is determined by where the disease is acquired, the species of ''Leishmania'', and the type of infection. Some possible medications used for visceral disease include
liposomal amphotericin B Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcos ...
, a combination of pentavalent antimonials and
paromomycin Paromomycin is an antimicrobial used to treat a number of parasitic infections including amebiasis, giardiasis, leishmaniasis, and tapeworm infection. It is a first-line treatment for amebiasis or giardiasis during pregnancy. Otherwise it is gen ...
, and
miltefosine Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as ''Naegleria fowleri'' and ''Balamuthia mandrillaris''. This includes the three forms of le ...
. For cutaneous disease, paromomycin,
fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prev ...
, or pentamidine may be effective. About 4 to 12 million people are currently infected in some 98 countries. About 2 million new cases and between 20 and 50 thousand deaths occur each year. About 200 million people in Asia, Africa, South and Central America, and southern Europe live in areas where the disease is common. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
has obtained discounts on some medications to treat the disease. It is classified as a
neglected tropical disease Neglected tropical diseases (NTDs) are a diverse group of tropical infections that are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens, such as viruses, bac ...
. The disease may occur in a number of other animals, including
dogs The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. ...
and
rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...
s.


Signs and symptoms

The symptoms of leishmaniasis are skin sores which erupt weeks to months after the person is bitten by infected sand flies. Leishmaniasis may be divided into the following types: *
Cutaneous leishmaniasis Cutaneous leishmaniasis is the most common form of leishmaniasis affecting humans. It is a skin infection caused by a single-celled parasite that is transmitted by the bite of a phlebotomine sand fly. There are about thirty species of '' Leish ...
is the most common form, which causes an open sore at the bite sites, which heals in a few months to a year and half, leaving an unpleasant-looking
scar A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a ...
. Diffuse cutaneous leishmaniasis produces widespread skin lesions which resemble
leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria '' Mycobacterium leprae'' or '' Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve d ...
, and may not heal on its own. * Mucocutaneous leishmaniasis causes both skin and mucosal ulcers with damage primarily of the nose and mouth. *
Visceral leishmaniasis Visceral leishmaniasis (VL), also known as kala-azar ( Hindi: kālā āzār, "black sickness") or "black fever", is the most severe form of leishmaniasis and, without proper diagnosis and treatment, is associated with high fatality. Leishmanias ...
or ''kala-azar'' ('black fever') is the most serious form, and is generally fatal if untreated. Other consequences, which can occur a few months to years after infection, include
fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
, damage to the
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
and
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
, and
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
. Leishmaniasis is considered one of the classic causes of a markedly enlarged (and therefore palpable) spleen; the organ, which is not normally felt during examination of the abdomen, may even become larger than the liver in severe cases.


Cause

Leishmaniasis is transmitted by the bite of infected female
phlebotomine The Phlebotominae are a subfamily of the family Psychodidae. In several countries, their common name is sandfly; but that name is also applied to other flies. The Phlebotominae include many genera of blood-feeding (hematophagous) flies, including ...
sandflies which can transmit the protozoa '' Leishmania''. (1) The sandflies inject the infective stage, metacyclic promastigotes, during blood meals. (2) Metacyclic promastigotes in the puncture wound are phagocytized by
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
s, and (3) transform into
amastigote An amastigote is a protist cell that does not have visible external flagella or cilia. The term is used mainly to describe an intracellular phase in the life-cycle of trypanosomes that replicates. It is also called the leishmanial stage, since in ...
s. (4) Amastigotes multiply in infected cells and affect different tissues, depending in part on the host, and in part on which ''Leishmania'' species is involved. These differing tissue specificities cause the differing clinical manifestations of the various forms of leishmaniasis. (5,6) Sandflies become infected during blood meals on infected hosts when they ingest macrophages infected with amastigotes. (7) In the sandfly's midgut, the parasites differentiate into promastigotes, (8) which multiply, differentiate into metacyclic promastigotes, and migrate to the proboscis. The
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
s of three ''Leishmania''
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriat ...
(''L. major'', ''L. infantum'', and ''L. braziliensis'') have been sequenced, and this has provided much information about the biology of the
parasite Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson h ...
. For example, in ''Leishmania'', protein-coding genes are understood to be organized as large
polycistronic A cistron is an alternative term for " gene". The word cistron is used to emphasize that genes exhibit a specific behavior in a cis-trans test; distinct positions (or loci) within a genome are cistronic. History The words ''cistron'' and ''ge ...
units in a head-to-head or tail-to-tail manner; RNA polymerase II transcribes long polycistronic messages in the absence of defined RNA pol II promoters, and ''Leishmania'' has unique features with respect to the regulation of gene expression in response to changes in the environment. The new knowledge from these studies may help identify new targets for urgently needed drugs and aid the development of vaccines.


Vector

Although most of the literature mentions only one genus transmitting ''Leishmania'' to humans (''
Lutzomyia ''Lutzomyia'' is a genus of phlebotomine sand flies consisting of nearly 400 species, at least 33 of which have medical importance as vectors of human disease. Species of the genus ''Lutzomyia'' are found only in the New World, distributed in ...
'') in the New World, a 2003 study by Galati suggested a new classification for New World sand flies, elevating several subgenera to the genus level. Elsewhere in the world, the genus ''
Phlebotomus ''Phlebotomus'' is a genus of "sand flies" in the Diptera family Psychodidae. In the past, they have sometimes been considered to belong in a separate family, Phlebotomidae, but this alternative classification has not gained wide acceptance. ...
'' is considered the vector of leishmaniasis.


Possible non-human reservoirs

Some cases of infection of non-human animals of human-infecting species of Leishmania have been observed. In one study, ''L. major'' was identified in twelve out of ninety-one wild
western lowland gorilla The western lowland gorilla (''Gorilla gorilla gorilla'') is one of two Critically Endangered subspecies of the western gorilla (''Gorilla gorilla'') that lives in montane, primary and secondary forest and lowland swampland in central Af ...
fecal samples and in a study of fifty-two captive non-human primates under zoo captivity in a leishmaniasis endemic area, eight (all three chimpanzees, three golden lion tamarins, a tufted capuchin, and an
Angolan talapoin The Angolan talapoin (''Miopithecus talapoin''), also known as the southern talapoin, is a species of primate in the family Cercopithecidae. Talapoins are the smallest species of Old-World monkeys. Description The fur of the Angolan talapoin is ...
), were found to be infected with L. infantum and capable of infecting ''Lutzomyia longipalpis'' sand flies, although "parasite loads in infected sand flies observed in this study were considered low".


Organisms

Visceral disease is usually caused by '' Leishmania donovani'', ''L. infantum'', or ''L. chagasi'', but occasionally these species may cause other forms of disease. The cutaneous form of the disease is caused by more than 15 species of ''Leishmania''.


Risk factors

Risk factors include malnutrition, deforestation, lack of sanitation, suppressed immune system and urbanization.


Diagnosis

Leishmaniasis is diagnosed in the hematology laboratory by direct visualization of the
amastigotes An amastigote is a protist A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic ...
(Leishman–Donovan bodies). Buffy-coat preparations of peripheral blood or aspirates from marrow, spleen, lymph nodes, or skin lesions should be spread on a slide to make a thin smear and stained with Leishman stain or Giemsa stain ( pH 7.2) for 20 minutes. Amastigotes are seen within blood and spleen monocytes or, less commonly, in circulating neutrophils and in aspirated tissue macrophages. They are small, round bodies 2–4 μm in diameter with indistinct cytoplasm, a nucleus, and a small, rod-shaped
kinetoplast A kinetoplast is a network of circular DNA (called kDNA) inside a large mitochondrion that contains many copies of the mitochondrial genome. The most common kinetoplast structure is a disk, but they have been observed in other arrangements. Kineto ...
. Occasionally, amastigotes may be seen lying free between cells. However, the retrieval of tissue samples is often painful for the patient and identification of the infected cells can be difficult. So, other indirect immunological methods of diagnosis are developed, including enzyme-linked immunosorbent assay, antigen-coated dipsticks, and direct agglutination test. Although these tests are readily available, they are not the standard diagnostic tests due to their insufficient sensitivity and specificity. Several different
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
(PCR) tests are available for the detection of ''Leishmania'' DNA. With this assay, a specific and sensitive diagnostic procedure is finally possible. The most sensitive PCR tests use minicircle kinetoplast DNA found in the parasite. Kinetoplast DNA contains sequences for mitochondrial proteins in its maxicircles(~25-50 per parasite), and guide RNA in its minicircles(~10'000 per parasite) of the kinetoplast. With this specific method, one can still detect Leishmania even with a very low parasite load. When needing to diagnose a specific species of Leishmania, as opposed to only detection, other PCR methods have been superior. Most forms of the disease are transmitted only from nonhuman animals, but some can be spread between humans. Infections in humans are caused by about 21 of 30 species that infect mammals; the different species look the same, but they can be differentiated by isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies.


Prevention

* Using 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) * Leishmaniasis can be partly prevented by using nets treated with insecticide or insect repellent while sleeping. To provide good protection against sandflies, fine mesh sizes of 0.6 mm or less are required, but a mosquito net with 1.2mm mesh will provide a limited reduction in the number of sandfly bites. Finer mesh sizes have the downside of higher cost and reduced air circulation which can cause overheating. Many
Phlebotomine The Phlebotominae are a subfamily of the family Psychodidae. In several countries, their common name is sandfly; but that name is also applied to other flies. The Phlebotominae include many genera of blood-feeding (hematophagous) flies, including ...
sandfly attacks occur at sunset rather than at night, so it may also be useful to put nets over doors and windows or to use insect repellents. * Use of insecticide-impregnated dog collars and treatment or culling of infected dogs. * Spraying houses and animal shelters with insecticides.*


Treatment

The treatment is determined by where the disease is acquired, the species of ''Leishmania'', and the type of infection. For visceral leishmaniasis in India, South America, and the Mediterranean,
liposomal amphotericin B Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcos ...
is the recommended treatment and is often used as a single dose. Rates of cure with a single dose of
amphotericin Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis. F ...
have been reported as 95%. In India, almost all infections are resistant to pentavalent antimonials. In Africa, a combination of pentavalent antimonials and paromomycin is recommended. These, however, can have significant side effects.
Miltefosine Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as ''Naegleria fowleri'' and ''Balamuthia mandrillaris''. This includes the three forms of le ...
, an oral medication, is effective against both visceral and cutaneous leishmaniasis. Side effects are generally mild, though it can cause birth defects if taken within 3 months of getting pregnant. It does not appear to work for ''L. major'' or ''L. braziliensis''. The evidence around the treatment of cutaneous leishmaniasis is poor. A number of topical treatments may be used for cutaneous leishmaniasis. Which treatments are effective depends on the strain, with topical paromomycin effective for ''L. major'', ''L. tropica'', ''L. mexicana'', ''L. panamensis'', and ''L. braziliensis''. Pentamidine is effective for ''L. guyanensis''. Oral
fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prev ...
or itraconazole appears effective in ''L. major'' and ''L. tropica''. There is limited evidence to support the use of heat therapy in cutaneous leishmaniasis as of 2015. There are no studies determining the effect of oral nutritional supplements on visceral leishmaniasis being treated with anti-leishmanial drug therapy.


Epidemiology

Out of 200 countries and territories reporting to WHO, 97 countries and territories are endemic for leishmaniasis. The settings in which leishmaniasis is found range from rainforests in Central and South America to deserts in western Asia and the Middle East. It affects as many as 12 million people worldwide, with 1.5–2.0 million new cases each year. The visceral form of leishmaniasis has an estimated incidence of 500,000 new cases. In 2014, more than 90% of new cases reported to WHO occurred in six countries: Brazil, Ethiopia, India, Somalia, South Sudan and Sudan. As of 2010, it caused about 52,000 deaths, down from 87,000 in 1990. Different types of the disease occur in different regions of the world. Cutaneous disease is most common in Afghanistan, Algeria, Brazil, Colombia, and Iran, while mucocutaneous disease is most common in Bolivia, Brazil, and Peru, and visceral disease is most common in Bangladesh, Brazil, Ethiopia, India, and Sudan. Leishmaniasis is found through much of the
Americas The Americas, which are sometimes collectively called America, are a landmass comprising the totality of North America, North and South America. The Americas make up most of the land in Earth's Western Hemisphere and comprise the New World. ...
from northern
Argentina Argentina (), officially the Argentine Republic ( es, link=no, República Argentina), is a country in the southern half of South America. Argentina covers an area of , making it the List of South American countries by area, second-largest ...
to South Texas, though not in
Uruguay Uruguay (; ), officially the Oriental Republic of Uruguay ( es, República Oriental del Uruguay), is a country in South America. It shares borders with Argentina to its west and southwest and Brazil to its north and northeast; while bordering ...
or
Chile Chile, officially the Republic of Chile, is a country in the western part of South America. It is the southernmost country in the world, and the closest to Antarctica, occupying a long and narrow strip of land between the Andes to the eas ...
, and has recently been shown to be spreading to North Texas and Oklahoma, and further expansion to the north may be facilitated by climate change as more habitat becomes suitable for vector and reservoir species for leishmaniasis. Leishmaniasis is also known as ''papalomoyo'', ''papa lo moyo,'' ''úlcera de los chicleros'', and ''chiclera'' in Latin America. During 2004, an estimated 3,400 troops from the
Colombia Colombia (, ; ), officially the Republic of Colombia, is a country in South America with insular regions in North America—near Nicaragua's Caribbean coast—as well as in the Pacific Ocean. The Colombian mainland is bordered by the ...
n army, operating in the jungles near the south of the country (in particular around the Meta and Guaviare departments), were infected with leishmaniasis. Allegedly, a contributing factor was that many of the affected soldiers did not use the officially provided insect repellent because of its disturbing odor. Nearly 13,000 cases of the disease were recorded in all of Colombia throughout 2004, and about 360 new instances of the disease among soldiers had been reported in February 2005. The disease is found across much of Asia, and in the Middle East. Within Afghanistan, leishmaniasis occurs commonly in
Kabul Kabul (; ps, , ; , ) is the capital and largest city of Afghanistan. Located in the eastern half of the country, it is also a municipality, forming part of the Kabul Province; it is administratively divided into #Districts, 22 municipal dist ...
, partly due to bad sanitation and waste left uncollected in streets, allowing parasite-spreading sand flies an environment they find favorable. In Kabul, the number of people infected was estimated to be at least 200,000, and in three other towns (
Herat Herāt (; Persian: ) is an oasis city and the third-largest city of Afghanistan. In 2020, it had an estimated population of 574,276, and serves as the capital of Herat Province, situated south of the Paropamisus Mountains (''Selseleh-ye Safē ...
,
Kandahar Kandahar (; Kandahār, , Qandahār) is a city in Afghanistan, located in the south of the country on the Arghandab River, at an elevation of . It is Afghanistan's second largest city after Kabul, with a population of about 614,118. It is the c ...
, and
Mazar-i-Sharif , official_name = , settlement_type = City , image_skyline = , pushpin_map = Afghanistan#Bactria#West Asia , pushpin_label = Mazar-i-Sharif , pushpin ...
) about 70,000 more occurred, according to WHO figures from 2002. Kabul is estimated as the largest center of cutaneous leishmaniasis in the world, with around 67,500 cases as of 2004. Africa, in particular the East and
North North is one of the four compass points or cardinal directions. It is the opposite of south and is perpendicular to east and west. ''North'' is a noun, adjective, or adverb indicating direction or geography. Etymology The word ''north ...
, is also home to cases of leishmaniasis. Leishmaniasis is considered endemic also in some parts of southern parts of western Europe and spreading towards north in recent years. For example, an outbreak of cutaneous and visceral leishmaniasis was reported from Madrid, Spain, between 2010 and 2012. Leishmaniasis is mostly a disease of the developing world, and is rarely known in the developed world outside a small number of cases, mostly in instances where troops are stationed away from their home countries. Leishmaniasis has been reported by U.S. troops stationed in
Saudi Arabia Saudi Arabia, officially the Kingdom of Saudi Arabia (KSA), is a country in Western Asia. It covers the bulk of the Arabian Peninsula, and has a land area of about , making it the fifth-largest country in Asia, the second-largest in the Ara ...
and
Iraq Iraq,; ku, عێراق, translit=Êraq officially the Republic of Iraq, '; ku, کۆماری عێراق, translit=Komarî Êraq is a country in Western Asia. It is bordered by Turkey to Iraq–Turkey border, the north, Iran to Iran–Iraq ...
since the Gulf War of 1990, including visceral leishmaniasis. In September 2005, the disease was contracted by at least four Dutch
marines Marines, or naval infantry, are typically a military force trained to operate in littoral zones in support of naval operations. Historically, tasks undertaken by marines have included helping maintain discipline and order aboard the ship (refl ...
who were stationed in Mazar-i-Sharif, Afghanistan, and subsequently repatriated for treatment.


History

Descriptions of conspicuous lesions similar to cutaneous leishmaniasis appear on tablets from King
Ashurbanipal Ashurbanipal ( Neo-Assyrian cuneiform: , meaning " Ashur is the creator of the heir") was the king of the Neo-Assyrian Empire from 669 BCE to his death in 631. He is generally remembered as the last great king of Assyria. Inheriting the throne a ...
from the seventh century BCE, some of which may have derived from even earlier texts from 1500 to 2500 BCE.
Persia Iran, officially the Islamic Republic of Iran, and also called Persia, is a country located in Western Asia. It is bordered by Iraq and Turkey to the west, by Azerbaijan and Armenia to the northwest, by the Caspian Sea and Turkmeni ...
n physicians, including
Avicenna Ibn Sina ( fa, ابن سینا; 980 – June 1037 CE), commonly known in the West as Avicenna (), was a Persian polymath who is regarded as one of the most significant physicians, astronomers, philosophers, and writers of the Islamic ...
in the 10th century CE, gave detailed descriptions of what was called ''
balkh ), named for its green-tiled ''Gonbad'' ( prs, گُنبَد, dome), in July 2001 , pushpin_map=Afghanistan#Bactria#West Asia , pushpin_relief=yes , pushpin_label_position=bottom , pushpin_mapsize=300 , pushpin_map_caption=Location in Afghanistan ...
'' sore. In 1756, Alexander Russell, after examining a Turkish patient, gave one of the most detailed clinical descriptions of the disease. Physicians in the
Indian subcontinent The Indian subcontinent is a physiographical region in Southern Asia. It is situated on the Indian Plate, projecting southwards into the Indian Ocean from the Himalayas. Geopolitically, it includes the countries of Bangladesh, Bhutan, In ...
would describe it as ''kala-azar'' (pronounced ''kālā āzār'', the
Urdu Urdu (;"Urdu"
'' Hindi Hindi (Devanāgarī: or , ), or more precisely Modern Standard Hindi (Devanagari: ), is an Indo-Aryan language spoken chiefly in the Hindi Belt region encompassing parts of northern, central, eastern, and western India. Hindi has been ...
, and Hindustani phrase for "black fever", ''kālā'' meaning black and ''āzār'' meaning fever or disease). In the
Americas The Americas, which are sometimes collectively called America, are a landmass comprising the totality of North America, North and South America. The Americas make up most of the land in Earth's Western Hemisphere and comprise the New World. ...
, evidence of the cutaneous form of the disease in
Ecuador Ecuador ( ; ; Quechua: ''Ikwayur''; Shuar: ''Ecuador'' or ''Ekuatur''), officially the Republic of Ecuador ( es, República del Ecuador, which literally translates as "Republic of the Equator"; Quechua: ''Ikwadur Ripuwlika''; Shuar: ' ...
and Peru appears in pre-Inca pottery depicting skin lesions and deformed faces dating back to the first century CE. Some 15th- and 16th-century texts from the
Inca The Inca Empire (also known as the Incan Empire and the Inka Empire), called ''Tawantinsuyu'' by its subjects, ( Quechua for the "Realm of the Four Parts",  "four parts together" ) was the largest empire in pre-Columbian America. The adm ...
period and from Spanish colonials mention "valley sickness", "Andean sickness", or "white leprosy", which are likely to be the cutaneous form. It remains unclear who first discovered the organism.
David Douglas Cunningham David Douglas Cunningham (29 September 1843 – 31 December 1914) was a Scottish doctor and researcher who worked extensively in India on various aspects of public health and medicine. He studied the spread of bacteria and the spores of fungi th ...
, Surgeon Major of the
British Indian army The British Indian Army, commonly referred to as the Indian Army, was the main military of the British Raj before its dissolution in 1947. It was responsible for the defence of the British Indian Empire, including the princely states, which cou ...
, may have seen it in 1885 without being able to relate it to the disease. Peter Borovsky, a Russian military surgeon working in Tashkent, conducted research into the etiology of "oriental sore", locally known as ''sart'' sore, and in 1898 published the first accurate description of the causative agent, correctly described the parasite's relation to host tissues and correctly referred it to the protozoa. However, because his results were published in Russian in a journal with low circulation, his results were not internationally acknowledged during his lifetime. In 1901, William Boog Leishman identified certain organisms in smears taken from the
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
of a patient who had died from "dum-dum fever" ( Dum Dum is an area close to
Calcutta Kolkata (, or , ; also known as Calcutta , the official name until 2001) is the capital of the Indian state of West Bengal, on the eastern bank of the Hooghly River west of the border with Bangladesh. It is the primary business, commer ...
) and proposed them to be
trypanosomes Trypanosomatida is a group of kinetoplastid excavates distinguished by having only a single flagellum. The name is derived from the Greek ''trypano'' (borer) and ''soma'' (body) because of the corkscrew-like motion of some trypanosomatid species ...
, found for the first time in
India India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area, the List of countries and dependencies by population, second-most populous ...
. A few months later, Captain Charles Donovan (1863–1951) confirmed the finding of what became known as Leishman-Donovan bodies in smears taken from people in
Madras Chennai (, ), formerly known as Madras ( the official name until 1996), is the capital city of Tamil Nadu, the southernmost Indian state. The largest city of the state in area and population, Chennai is located on the Coromandel Coast of th ...
in southern India. But it was Ronald Ross who proposed that Leishman-Donovan bodies were the intracellular stages of a new parasite, which he named ''Leishmania donovani''. The link with the disease ''kala-azar'' was first suggested by Charles Donovan, and was conclusively demonstrated by Charles Bentley's discovery of ''L. donovani'' in patients with ''kala-azar''. Transmission by the sandfly was hypothesized by Lionel Napier and Ernest Struthers at the School of Tropical Medicine at Calcutta and later proven by his colleagues. The disease became a major problem for Allied troops fighting in Sicily during the
Second World War World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposi ...
; research by
Leonard Goodwin Leonard George Goodwin CMG FRS (11 July 1915 – 25 November 2008) was a British protozoologist noted for his work on testing the effectiveness of chemical compounds in treating tropical diseases. He was born in London to a shoe shop manager, an ...
then showed
pentostam Sodium stibogluconate, sold under the brand name Pentostam among others, is a medication used to treat leishmaniasis. This includes leishmaniasis of the cutaneous, visceral, and mucosal types. Some combination of miltefosine, paramycin and liposo ...
was an effective treatment.


Society and culture

The Institute for OneWorld Health has reintroduced the drug
paromomycin Paromomycin is an antimicrobial used to treat a number of parasitic infections including amebiasis, giardiasis, leishmaniasis, and tapeworm infection. It is a first-line treatment for amebiasis or giardiasis during pregnancy. Otherwise it is gen ...
for treatment of leishmaniasis, results with which led to its approval as an orphan drug. The
Drugs for Neglected Diseases Initiative The Drugs for Neglected Diseases ''initiative'' (DND''i'') is a collaborative, patients' needs-driven, non-profit drug research and development (R&D) organization that is developing new treatments for neglected diseases, notably leishmaniasis, ...
is also actively facilitating the search for novel therapeutics. A treatment with paromomycin will cost about US$10. The drug had originally been identified in the 1960s, but had been abandoned because it would not be profitable, as the disease mostly affects poor people. The
Indian government The Government of India (ISO: ; often abbreviated as GoI), known as the Union Government or Central Government but often simply as the Centre, is the national government of the Republic of India, a federal democracy located in South Asia, ...
approved paromomycin for sale in August 2006. By 2012 the World Health Organization had successfully negotiated with the manufacturers to achieve a reduced cost for
liposomal amphotericin B Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcos ...
, to US$18 a vial, but a number of vials are needed for treatment and it must be kept at a stable, cool temperature.


Research

As of 2017, no
leishmaniasis vaccine A Leishmaniasis vaccine is a vaccine which would prevent leishmaniasis. As of 2017, no vaccine for humans was available. Currently some effective leishmaniasis vaccines for dogs exist. The parasite which causes leishmaniasis is ''Leishmania'', whi ...
for humans was available. Research to produce a human vaccine is ongoing. Currently some effective leishmaniasis vaccines for dogs exist. There is also consideration that public health practices can control or eliminate leishmaniasis without a vaccine.


See also

* Canine vector-borne disease *
Tropical disease Tropical diseases are diseases that are prevalent in or unique to tropical and subtropical regions. The diseases are less prevalent in temperate climates, due in part to the occurrence of a cold season, which controls the insect population by f ...


References


External links

*
Doctors Without Borders' Leishmaniasis Information Page

CDC Leishmaniasis Page
{{Authority control Dog diseases Parasitic infestations, stings, and bites of the skin Tropical diseases Wikipedia medicine articles ready to translate Wikipedia infectious disease articles ready to translate Zoonoses