Leishmaniasis is a
diseaseA disease or medical condition isan abnormal condition of an organism that impairs bodily functions, associated with specific symptoms and signs...
caused by protozoan parasites that belong to the genus
LeishmaniaLeishmania is a genus of trypanosome protozoa, and is the parasite responsible for the disease leishmaniasis. It is spread through sandflies of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. Their primary hosts are vertebrates; Leishmania commonly infects...
and is transmitted by the bite of certain species of sand fly (subfamily
PhlebotominaeMembers of the subfamily Phlebotominae are known outside of the United States by the name sand fly. This subfamily includes numerous genera of blood-feeding flies, including the primary vectors of leishmaniasis, bartonellosis and pappataci fever...
). Two genera transmit
Leishmania to humans:
LutzomyiaLutzomyia is a genus of "sand flies" in the Phlebotominae subfamily of the order Diptera. In the New World, Lutzomyia sand flies are responsible for the transmission of leishmaniasis, an important parasitic disease and Carrion's disease. Leishmaniasis is generally transmitted in the Old World by...
in the New World and
PhlebotomusPhlebotomus is a genus of "sand fly" in the Dipteran 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-Epidemiology:...
in the Old World.
Most forms of the disease are transmissible only from animals (
zoonosisA zoonosis or zoonose is any infectious disease that can be transmitted from non-human animals, both wild and domestic, to humans or from humans to non-human animals...
), but some can be spread between humans. Human infection is caused by about 21 of 30 species that infect mammals. These include the
L. donovani complex with three species (
L. donovani, L. infantum, and
L. chagasi); the
L. mexicana complex with 3 main species (
L. mexicana, L. amazonensis, and
L. venezuelensis);
L. tropica; L. major; L. aethiopica; and the subgenus
Viannia with four main species (
L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis, and
L. (V.) peruviana). The different species are morphologically indistinguishable, but they can be differentiated by isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies.
Cutaneous leishmaniasisCutaneous leishmaniasis is the most common form of leishmaniasis. It is a skin infection caused by a single celled parasite that is transmitted by sandfly bites...
is the most common form of leishmaniasis.
Visceral leishmaniasisVisceral leishmaniasis , also known as kala-azar, black fever, and Dumdum fever, is the most severe form of leishmaniasis. Leishmaniasis is a disease caused by protozoan parasites of the Leishmania genus. It is the second-largest parasitic killer in the world , responsible for an estimated 500,000...
is a severe form in which the parasites have migrated to the vital organs.
Classification
Leishmaniasis may be divided into the following types:
- Cutaneous leishmaniasis
Cutaneous leishmaniasis is the most common form of leishmaniasis. It is a skin infection caused by a single celled parasite that is transmitted by sandfly bites...
- Mucocutaneous leishmaniasis
Mucocutaneous leishmaniasis is a cutaneous condition which occurs at the site of a fly bite, and is characterized by an ulceration of the skin....
- Visceral leishmaniasis
Visceral leishmaniasis , also known as kala-azar, black fever, and Dumdum fever, is the most severe form of leishmaniasis. Leishmaniasis is a disease caused by protozoan parasites of the Leishmania genus. It is the second-largest parasitic killer in the world , responsible for an estimated 500,000...
- Post-kala-azar dermal leishmaniasis
Post-kala-azar dermal leishmaniasis is a cutaneous condition that is characterized by a macular, depigmented eruption found mainly on the face, arms, and upper part of the trunk....
- Viscerotropic leishmaniasis
Viscerotropic leishmaniasis is a systemic infection reported in soldiers fighting in Operation Desert Storm in Saudi Arabia....
Geography and epidemiology
Leishmaniasis can be transmitted in many tropical and sub-tropical countries, and is found in parts of about 88 countries. Approximately 350 million people live in these areas. The settings in which leishmaniasis is found range from rainforests in Central and South America to deserts in West Asia and the Middle East. It affects as many as 12 million people worldwide, with 1.5–2 million new cases each year. The visceral form of leishmaniasis has an estimated incidence of 500,000 new
cases and 60,000 deaths each year. More than 90 percent of the world's cases of
visceral leishmaniasisVisceral leishmaniasis , also known as kala-azar, black fever, and Dumdum fever, is the most severe form of leishmaniasis. Leishmaniasis is a disease caused by protozoan parasites of the Leishmania genus. It is the second-largest parasitic killer in the world , responsible for an estimated 500,000...
are in India, Bangladesh, Nepal, Sudan, and Brazil.
Leishmaniasis is found through much of the
AmericasThe Americas, or America, are lands in the Western hemisphere or New World, comprising the continents of North America and South America with their associated islands and regions. America may be ambiguous in English, as it is more commonly used to refer to the United States of America...
from northern
ArgentinaArgentina, officially the Argentine Republic , is the second largest country in South America, constituted as a federation of 23 provinces and an autonomous city, Buenos Aires. It is the eighth largest country in the world by land area and the largest among Spanish-speaking nations, though Mexico,...
to southern
TexasTexas is the second-largest U.S. state in both area and population, and the largest state in the contiguous United States.The name had wide usage among native Americans, meaning "friends" or "allies"...
, though not in
UruguayUruguay , is a country located in the southeastern part of South America. It is home to 3.46 million people, of whom 1.1 million live in the capital Montevideo and its metropolitan area. An estimated 88–94% of the population are of mostly European and/or mixed descent.Uruguay's only land border is...
or
ChileChile, officially the Republic of Chile , is a country in South America occupying a long, narrow coastal strip between the Andes mountains to the east and the Pacific Ocean to the west. It borders Peru to the north, Bolivia to the northeast, Argentina to the east, and the Drake Passage in the far...
, and has recently been shown to be spreading to North Texas. During 2004, it is calculated that some 3,400 troops from the
ColombiaColombia , officially the Republic of Colombia , is a constitutional republic in northwestern South America. Colombia is bordered to the east by Venezuela and Brazil; to the south by Ecuador and Peru; to the north by the Caribbean Sea; to the northwest by Panama; and to the west by the Pacific Ocean...
n army, operating in the jungles near the south of the country (in particular around the Meta and Guaviare departments), were infected with Leishmaniasis. Apparently, a contributing factor was that many of the affected soldiers did not use the officially provided
insect repellentAn insect repellent is a substance applied to skin, clothing, or other surfaces which discourages insects from landing or climbing on that surface. There are also insect repellent products available based on sound production, particularly ultrasound...
, because of its allegedly disturbing odor. It is estimated that 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
AsiaAsia is the world's largest and most populous continent, located in the eastern and northern hemispheres. It covers 8.6% of the earth's total surface area and with approximately 4 billion people, it hosts 60% of the world's current human population.Asia is traditionally defined as part of the...
, though not
Southeast AsiaManila
Bangkok
Ho Chi Minh City
Kuala Lumpur
Singapore
Yangon
Bandung
Hanoi
Surabaya
Taichung
Kaohsiung
Medan|-|}...
, and in the Middle East. Within
AfghanistanThe Islamic Republic of Afghanistan is a landlocked country in south central Asia. It is variously described as being located within Central Asia, South Asia, or the Middle East...
, leishmaniasis occurs commonly in
KabulKabul , is the capital and largest city of Afghanistan, with a population of over 2.5 million, and is located in the province of Greater Kabul...
- 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 is estimated at at least 200,000, and in three other towns (
HeratHerāt , classically called the Aria, is a major city in western Afghanistan, in the province also known as Herāt. It is situated in the valley of the Hari River, which flows from the mountains of central Afghanistan to the Karakum Desert in Turkmenistan. It is the third largest city of Afghanistan,...
,
KandaharKandahār, also spelled Qandahār, Pashtoکندهار or قندهار is the second largest city in Afghanistan, with a population of 324,800 . It is the capital of Kandahar province, located in the south of the country at about 1,005 m above sea level...
and Mazar-i-Sharif) there may be about 70,000 more, according to WHO figures from 2002.
AfricaAfrica is the world's second-largest and second most-populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area. With a billion people in 61 territories, it accounts for about 14.8% of the...
, in
particularIn philosophy, particulars are concrete entities existing in space and time as opposed to abstractions. There are, however, theories of abstract particulars or tropes. For example, Socrates is a particular...
the
EastEast Africa or Eastern Africa is the easterly region of the African continent, variably defined by geography or geopolitics. In the UN scheme of geographic regions, 19 territories constitute Eastern Africa:...
and
NorthNorth Africa or Northern Africa is the northernmost region of the African continent, linked by the Sahara to Sub-Saharan Africa.Geopolitically, the UN definition of Northern Africa includes the following seven countries or territories; Algeria, Egypt, Libya, Morocco, Sudan, Tunisia,Mauritania, and...
, is home to cases of Leishamaniasis. The disease is spreading to
Southern EuropeThe term Southern Europe, at its most general definition, is used to mean "all countries in the south of Europe". However, the concept, at different times, has had different meanings, providing additional political, linguistic and cultural context to the definition in addition to the typical...
but is not found in
AustraliaAustralia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the continental mainland , the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans...
or
OceaniaOceania is a geographical, often geopolitical, region consisting of numerous lands—mostly islands in the Pacific Ocean and vicinity. The term "Oceania" was coined in 1831 by French explorer Dumont d'Urville...
.
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. troopsThe United States Army is the branch of the United States Military responsible for land-based military operations. It is the largest and oldest established branch of the U.S. military and is one of seven uniformed services...
stationed in
Saudi ArabiaSaudi Arabia , is an Arab country and the largest country of the Arabian Peninsula. It is bordered by Jordan on the northwest, Iraq on the north and northeast, Kuwait, Qatar, Bahrain, and the United Arab Emirates on the east, Oman on the southeast, and Yemen on the south...
and
IraqIraq , officially the Republic of Iraq , also known as Mesopotamia, is a country in Western Asia spanning most of the northwestern end of the Zagros mountain range, the eastern part of the Syrian Desert and the northern part of the Arabian Desert.Iraq shares borders with Jordan to the west, Syria...
since the
Gulf War of 1990The Persian Gulf War , known also as the Gulf War, the First Gulf War,or often as the Second Gulf War and by Iraqi leader Saddam Hussein as The Mother of all Battles, or commonly as Desert Storm, for the military response...
, including visceral leishmaniasis.
In September 2005 the disease was contracted by at least four Dutch
marinesThe Korps Mariniers is the marine corps and amphibious infantry component of the Royal Netherlands Navy. It is trained to operate anywhere in the world in all environments, under any condition and circumstance, as a rapid reaction force. The Korps Mariniers can be deployed to a given location...
who were stationed in Mazari Sharif,
AfghanistanThe Islamic Republic of Afghanistan is a landlocked country in south central Asia. It is variously described as being located within Central Asia, South Asia, or the Middle East...
, and subsequently repatriated for treatment.
Life cycle
Leishmaniasis is transmitted by the bite of female phlebotomine sandflies. The sandflies inject the infective stage, metacyclic promastigotes, during blood meals
(1). Metacyclic promastigotes that reach the puncture wound are phagocytized by macrophages
(2) and transform into amastigotes
(3). Amastigotes multiply in infected cells and affect different tissues, depending in part on which
Leishmania species is involved
(4). These differing tissue specificities cause the differing clinical manifestations of the various forms of leishmaniasis. Sandflies become infected during blood meals on an infected host when they ingest macrophages infected with amastigotes
(5,6). In the sandfly's midgut, the parasites differentiate into promastigotes
(7), which multiply, differentiate into metacyclic promastigotes and migrate to the proboscis (8)
Signs and symptoms
The symptoms of leishmaniasis are skin sores which erupt weeks to months after the person affected is bitten by sand flies. Other consequences, which can become manifest anywhere from a few months to years after infection, include fever, damage to the
spleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells, holds a reserve in case of hemorrhagic shock, especially in...
and
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, and anaemia.
In the medical field, leishmaniasis is one of the famous causes of a markedly enlarged spleen, which may become larger even than the liver. There are four main forms of leishmaniasis:
- Visceral leishmaniasis
Visceral leishmaniasis , also known as kala-azar, black fever, and Dumdum fever, is the most severe form of leishmaniasis. Leishmaniasis is a disease caused by protozoan parasites of the Leishmania genus. It is the second-largest parasitic killer in the world , responsible for an estimated 500,000...
– the most serious form and potentially fatal if untreated.
- Cutaneous leishmaniasis
Cutaneous leishmaniasis is the most common form of leishmaniasis. It is a skin infection caused by a single celled parasite that is transmitted by sandfly bites...
– the most common form which causes a sore at the bite site, which heal in a few months to a year, leaving an unpleasant looking scar. This form can progress to any of the other three forms.
- Diffuse cutaneous leishmaniasis – this form produces widespread skin lesions which resemble leprosy and is particularly difficult to treat.
- Mucocutaneous leishmaniasis
Mucocutaneous leishmaniasis is a cutaneous condition which occurs at the site of a fly bite, and is characterized by an ulceration of the skin....
– commences with skin ulcers which spread causing tissue damage to (particularly) nose and mouth
Diagnosis
Leishmaniasis is diagnosed in the haematology laboratory by direct visualization of the amastigotes (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's or Giemsa's stain (
pHpH is a measure of the acidity or basicity of a solution. It is defined as the cologarithm of the activity of dissolved hydrogen ions . Hydrogen ion activity coefficients cannot be measured experimentally, so they are based on theoretical calculations...
7.2) for 20 minutes. Amastigotes are seen with monocytes or, less commonly in neutrophil in peripheral blood and in macrophages in aspirates. They are small, round bodies 2-4μm in diameter with indistinct cytoplasm, a nucleus and a small rod-shaped
kinetoplastA Kinetoplast is a disk-shaped mass of circular DNAs inside a large mitochondrion that contains many copies of the mitochondrial genome. Kinetoplasts are only found in protozoa of the class kinetoplastea...
. Occasionally amastigotes may be seen lying free between cells.
Treatment
There are two common therapies containing
antimonyAntimony is a chemical element with the symbol Sb and atomic number 51. A metalloid, antimony has four allotropic forms. The stable form of antimony is a blue-white metalloid. Yellow and black antimony are unstable non-metals...
(known as pentavalent antimonials),
meglumine antimoniateMeglumine antimoniate is a medicine used for treating leishmaniasis. It is manufactured by Aventis and sold as Glucantime in France, and Glucantim in Italy. It belongs to a group of compounds known as the pentavalent antimonials. It is administered by intramuscular injection....
(
Glucantime) and
sodium stibogluconateSodium stibogluconate is a medicine used to treat leishmaniasis and is only available for administration by injection. It belongs to the class of medicines known as the pentavalent antimonials. Sodium stibogluconate is sold in the UK as Pentostam...
(
Pentostam). It is not completely understood how these drugs act against the parasite; they may disrupt its energy production or
trypanothioneTrypanothione is an unusual form of glutathione containing two molecules of glutathione joined by a spermidine linker. It is found in parasitic protozoa such as leishmania and trypanosomes. These protozoal parasites are the cause of leishmaniasis, sleeping sickness and Chagas' disease....
metabolism. Unfortunately, in many parts of the world, the parasite has become resistant to antimony and for visceral or mucocutaneous leishmaniasis, but the level of resistance varies according to species.
AmphotericinAmphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...
(AmBisome) is now the treatment of choice; its failure in some cases to treat visceral leishmaniasis (
Leishmania donovani) has been reported in Sudan, but this may be related to host factors such as co-infection with HIV or
tuberculosisTuberculosis is a common and often deadly infectious disease caused by mycobacteria...
rather than parasite resistance.
MiltefosineMiltefosine is an antiprotozoal drug. Originally developed as an antineoplastic, it is finding use as an antiprotozoal drug...
(Impavido), is a new drug for visceral and cutaneous leishmaniasis. The cure rate of miltefosine in phase III clinical trials is 95%; Studies in Ethiopia show that it is also effective in Africa. In HIV immunosuppressed people who are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment. Clinical trials in Colombia showed a high efficacy for cutaneous leishmaniasis. In mucocutaneous cases caused by L.brasiliensis it has shown to be more effective than other drugs.
Miltefosine received approval by the Indian regulatory authorities in 2002 and in Germany in 2004. In 2005 it received the first approval for cutaneous leishmaniasis in Colombia. Miltefosine is also currently being investigated as treatment for mucocutaneous leishmaniasis caused by
Leishmania braziliensisLeishmania braziliensis is a Leishmania species.It is associated with leishmaniasis....
in Colombia, and preliminary results are very promising. It is now registered in many countries and is the first orally administered breakthrough therapy for visceral and cutaneous leishmaniasis.(More,
et al., 2003). In October 2006 it received
orphan drugAn orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...
status from the US Food and Drug administration.
The drug is generally better tolerated than other drugs. Main side effects are gastrointestinal disturbance in the 1–2 days of treatment which does not affect the efficacy. Because it is available as an oral formulation, the expense and inconvenience of hospitalisation is avoided, which makes it an attractive alternative.
The Institute for OneWorld Health has reintroduced the drug paromomycin for treatment of leishmaniasis, results with which led to its approval as an
orphan drugAn orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...
. The
Drugs for Neglected Diseases InitiativeThe Drugs for Neglected Diseases Initiative 501 non-profit drug research and development organization that is developing new treatments for neglected diseases....
is also actively facilitating the search for novel therapeutics. A treatment with paromomycin will cost about $10. The drug had originally been identified in 1960s, but had been abandoned because it would not be profitable, as the disease mostly affects poor people. The Indian government approved paromomycin for sale in August 2006. A 21-day course of paromomycin produces a definitive cure in >90% of patients with visceral leishmaniasis.
Drug-resistant leishmaniasis may respond to
immunotherapyImmunotherapy is a medical term defined as "Treatment of disease by inducing, enhancing, or suppressing an immune response".Immunotherapies designed to elicit or amplify an immune response are classified as Activation Immunotherapies....
(inoculation with parasite antigens plus an
adjuvantAdjuvants are pharmacological or immunological agents that modify the effect of other agents while having few if any direct effects when given by themselves...
) which aims to stimulate the body's own immune system to kill the parasite.
Several potential vaccines are being developed, under pressure from the
World Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health...
, but none is available. The team at the Laboratory for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zürich are trying to design a carbohydrate-based vaccine
http://news.bbc.co.uk/1/hi/health/4930528.stm. The genome of the parasite
Leishmania major has been sequenced, possibly allowing for identification of proteins that are used by the pathogen but not by humans; these proteins are potential targets for drug treatments.
The compound vasicine (peganine), found in the plant
Peganum harmala, has been tested
in vitro against the promastigote stage of
Leishmania donovaniLeishmania donovani is a species of Leishmania.It is an important cause of Leishmaniasis.-External links:* http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=5661...
, the causative agent of visceral leishmaniasis. It was shown that this compound induces apoptosis in
Leishmania promastigotes. "Peganine hydrochloride dihydrate, besides being safe, was found to induce
apoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed cell death involves a series of biochemical events leading to a characteristic cell morphology and death; in more specific terms, a series of biochemical events that lead to a variety of...
in both the stages of L. donovani via loss of mitochondrial transmembrane potential."
Another alkaloid
harmineHarmine is a fluorescent harmala alkaloid belonging to the beta-carboline family of compounds. It occurs in a number of different plants, most notably the Middle Eastern plant harmal or Syrian rue and the South American vine Banisteriopsis caapi . Harmine is a reversible monoamine oxidase...
found in
Peganum harmala, ". . .because of its appreciable efficacy in destroying intracellular parasites as well as non-hepatotoxic and non-nephrotoxic nature, harmine, in the vesicular forms, may be considered for clinical application in humans."
HIV Protease inhibitors have been found to be active against Leishmania species in two
in vitro studies in
CanadaCanada is a country occupying most of northern North America, extending from the Atlantic Ocean in the east to the Pacific Ocean in the west and northward into the Arctic Ocean...
and India. The study reported that the intracellular growth of Leishmania parasites was controlled by
nelfinavirNelfinavir is an antiretroviral drug used in the treatment of the human immunodeficiency virus . Nelfinavir belongs to the class of drugs known as protease inhibitors and like other PIs is generally used in combination with other antiretroviral drugs...
and
ritonavirRitonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS....
in a human
monocyteMonocyte is a type of white blood cell, part of the human body's immune system. Monocytes have two main functions in the immune system: replenish resident macrophages and dendritic cells under normal states, and in response to inflammation signals, monocytes can move quickly Monocyte is a type of...
cell line and also in human primary monocyte-derived macrophages.
Biology
Leishmaniasis is caused by infection with the
pathogenA pathogen , infectious agent, or germ, is a biological agent that causes disease or illness to its host....
LeishmaniaLeishmania is a genus of trypanosome protozoa, and is the parasite responsible for the disease leishmaniasis. It is spread through sandflies of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. Their primary hosts are vertebrates; Leishmania commonly infects...
. The
genomeIn modern molecular biology the genome refers to all of its hereditary information encoded in DNA .The genome includes both the genes and the non-coding sequences of the DNA. The term was adapted in 1920 by Hans Winkler, Professor of Botany at the University of Hamburg, Germany...
s of three
Leishmania speciesIn biology, a species is:* a taxonomic rank or* a unit at that rank ....
(
L. major,
L. infantum and
L. braziliensis) have been sequenced and this has provided much information about the biology of the parasite. For example it is now understood that in
Leishmania protein-coding genes are organized as large polycistronic 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.
Vaccines
Currently there are no
vaccineA vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains a small amount of an agent that resembles a microorganism...
s in routine use. However, the genomic sequence of
Leishmania has provided a rich source of vaccine candidates.
GenomeIn modern molecular biology the genome refers to all of its hereditary information encoded in DNA .The genome includes both the genes and the non-coding sequences of the DNA. The term was adapted in 1920 by Hans Winkler, Professor of Botany at the University of Hamburg, Germany...
-based approaches have been used to screen for novel vaccine candidates. One study screened 100 randomly selected
geneA gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cells and pass genetic traits to offspring...
s as DNA vaccines against
L. major infection in mice. Fourteen reproducibly protective novel vaccine candidates were identified. A separate study used a two-step procedure to identify T cell antigens. Six unique clones were identified: glutamine synthetase, a transitional endoplasmic reticulum ATPase, elongation factor 1gamma, kinesin K-39, repetitive protein A2, and a hypothetical conserved protein. The 20 antigens identified in these two studies are being further evaluated for vaccine development.
History
Descriptions of conspicuous lesions similar to cutaneous leishmaniasis (CL) has been discovered on
tabletsIn ancient times, small tablets made out of clay were used as a writing medium.From the 4th millennium BCE in the Sumerian, Babylonian, Assyrian and Hittite civilisations of the Mesopotamia region, cuneiform characters were imprinted on a wet clay tablet with a stylus often made of reed. Once...
from King
AshurbanipalAshurbanipal , also spelled Assurbanipal or Ashshurbanipal, was the son of Esarhaddon and the last great king of the Neo-Assyrian Empire...
from the 7th century BC, some of which may have been derived from even earlier texts from 1500 to 2500 BC.
MuslimIslam Islam Islam ( al-’islām,
[There are ten pronunciations of Islam in English, differing in whether the first or second syllable has the stress, whether the s is or , and whether the a is pronounced as in father, as in cat, or (when the stress is on the i) as in the a of sofa...]
physicians including
Avicenna, known as Abū Alī Sīnā or Ibn Sīnā , and commonly known in English by his Latinized name Avicenna , was a Persian polymath and the foremost physician and philosopher of his time...
in the 10th century AD gave detailed descriptions of what was called
BalkhBalkh , known as Bactra to the Greeks and Baktri or Bagdhi to the Persians, was an ancient city and centre of Zoroastrianism in Northern Afghanistan...
sore. In 1756, Alexander Russell, after examining a
TurkishThe Turkish people , also known as the "Turks" are defined mainly as citizens of the Republic of Turkey. An early historic text provided the definition of being a Turk as "any individual within the Republic of Turkey; whatever his/her faith or racial/ethnic background; who speaks Turkish, grows up...
patient, gave one of the most detailed clinical descriptions of the disease. Physicians in the
Indian subcontinentThe Indian subcontinent, also Indian Subcontinent and other terms, is a region of the Asian continent on the Indian tectonic plate south of the Himalayas, forming a peninsula which extends southward into the Indian Ocean...
would describe it as Kala-azar (pronounced
kālā āzār, the
UrduUrdu is a Central Indo-Aryan language of the Indo-Iranian branch, belonging to the Indo-European family of languages. It is one of the two official languages of Pakistan. It is also one of the 22 scheduled languages of India and is an official language of five Indian states...
,
HindiStandard Hindi, also known as High Hindi, Nagari Hindi or Literary Hindi is a standardised register of Hindi. It is one of the 22 languages with official status in India, and is used, along with English, for administration of the central government.Standard Hindi is a sanskritised register derived...
and
HindustaniHindustani or Hindi-Urdu is an Indo-Aryan language that spans several closely related dialects in Pakistan and northern India. Although Hindustani is based largely on the Khariboli dialect, it also includes several nonstandard dialects of the Hindi languages...
phrase for
black fever,
kālā meaning black and
āzār meaning fever or disease). As for the
new worldThe New World is one of the names used for the non-Afro-Eurasian parts of the Earth, specifically the Americas and possibly Australia. When the term originated in the late 15th century, the Americas were new to the Europeans, who previously thought of the world as consisting only of Europe, Asia,...
, evidence of the cutaneous form of the disease was found in
EcuadorEcuador , officially the Republic of Ecuador , literally, "Republic of the equator") is a representative democratic republic in South America, bordered by Colombia on the north, Peru on the east and south, and by the Pacific Ocean to the west. It is one of only two countries in South America that...
and
PeruPeru , officially the Republic of Peru , is a country in western South America. It is bordered on the north by Ecuador and Colombia, on the east by Brazil, on the southeast by Bolivia, on the south by Chile, and on the west by the Pacific Ocean.Peruvian territory was home to the Norte Chico...
in pre-Inca potteries depicting skin lesions and deformed faces dating back to the first century AD. 15th and 16th century texts from the
IncaThe Inca civilization began as a tribe in the Cuzco area, where the legendary first Sapa Inca, Manco Capac founded the Kingdom of Cuzco around 1200. Under the leadership of the descendants of Manco Capac, the Inca state grew to absorb other Andean communities. In 1442, the Incas began a...
period and from
Spanish colonialsThe Spanish colonization of the Americas was the settlement and political rule over much of the western hemisphere which was initiated by the Spanish conquistadors and fought mostly by their native allies...
mention
"valley sickness",
"Andean sickness" or
"white leprosy" which are likely to be CL.
Who first discovered the organism is somewhat disputed. It is possible that Surgeon major Cunningham of the British Indian army saw it first in 1885 without being able to relate it to the disease.
Peter BorovskyPiotr Fokich Borovsky was Russian and Soviet surgeon and public health administrator who worked in Tashkent, professor of surgery in Tashkent Medical Institute....
, a Russian military surgeon working in
TashkentTashkent is the capital of Uzbekistan and also of the Tashkent Province. The officially registered population of the city in 2008 was 2.18 million. According to unofficial data, the population is more than 3 million.- History :...
, 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 Protozoa. However, because his results were published in Russian in a journal with low circulation, his priority was not internationally acknowledged during his lifetime. In 1901,
LeishmanLieutenant-General Sir William Boog Leishman was a Scottish pathologist and British Army medical officer. He was Director-General of Army Medical Services from 1923 to 1926....
identified certain organisms in smears taken from the spleen of a patient who had died from "dum-dum fever" (
Dum DumDumdum is a city and a municipality in North 24 Parganas district in the state of West Bengal, India. It is a neighbourhood in North-west Kolkata and the location of Netaji Subhash Chandra Bose International Airport, formerly Dum Dum Airport.Now Dum Dum is a well known place in greater Kolkata...
is an area close to Calcutta) and in 1903 Captain
Charles DonovanColonel Charles Donovan MD was born in Calcutta. At the age of thirteen he was sent to Cork City to live with his grandfather to advance his secondary and university education. He studied at Queen's College, Cork and Trinity College, Dublin Colonel Charles Donovan MD (1863-1951) was born in...
(1863–1951) described them as being new organisms. Eventually
Ronald RossSir Ronald Ross KCB was a British physician.-Early life:Ross was born in Almora, India. He was the eldest son of General Sir Campbell Claye Grant Ross of the Indian Army and Matilda Charlotte Elderton. His grandfather was Lieutenant Colonel Hugh Ross.At the age of eight, Ross was sent to England...
established the link with the disease and named the organism
Leishmania donovani. The disease was a major problem for
Allied troops fighting in SicilyThe Allied invasion of Sicily, codenamed Operation Husky, was a major World War II campaign, in which the Allies took Sicily from the Axis . It was a large scale amphibious and airborne operation, followed by six weeks of land combat. It launched the Italian Campaign.Husky began on the night of...
during the Second World War, and it was then that research by
Leonard GoodwinLeonard George Goodwin CMG FRS 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, and became interested in nature thanks to holidays spent with his grandfather, a...
showed that Pentostam was an effective treatment.
Leishmaniasis as part of the CVBDs
CVBDCVBD - Canine Vector-Borne Diseases - is a veterinarian term for diseases transferred to dogs by various parasitic vectors. This includes diseases caused by pathogens transmitted by ectoparasites such as ticks, fleas, sand flies, or mosquitoes, as well as those transmitted by endoparasites such as...
stands for Canine Vector-borne diseases, which are diseases transmitted through Ectoparasites.
See also
- Visceral leishmaniasis
Visceral leishmaniasis , also known as kala-azar, black fever, and Dumdum fever, is the most severe form of leishmaniasis. Leishmaniasis is a disease caused by protozoan parasites of the Leishmania genus. It is the second-largest parasitic killer in the world , responsible for an estimated 500,000...
(kala azar)
- Cutaneous leishmaniasis
Cutaneous leishmaniasis is the most common form of leishmaniasis. It is a skin infection caused by a single celled parasite that is transmitted by sandfly bites...
- Canine leishmaniasis
Canine leishmaniasis is a zoonotic disease caused by Leishmania parasties transmitted by the bite of an infected Phlebotomine sandfly. Canine leishmaniasis was first identified in Europe in 1903, and in 1940 it was determined that 40% of all dogs in Rome were positive for leishmaniasis...
- Leishmania
Leishmania is a genus of trypanosome protozoa, and is the parasite responsible for the disease leishmaniasis. It is spread through sandflies of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. Their primary hosts are vertebrates; Leishmania commonly infects...
- List of parasites (human)
- 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 forcing hibernation. Insects such as mosquitoes and...
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