By Levi Clancy for Student Reader on
Kala Azar (aka Black Fever) has existed in India and China for centuries. Kala Azar was considered to be a communicable malaria-like disease that showed relapses, emaciation, as well as enlargement of the liver and spleen, and spread slowly acrossthe continents along the trade routes.
In 1900, Scottish Army doctor William Leishman found Leishmania donovani in stained splenic smears from a soldier suffering from a fever contracted at Dum-Dumin, India. Leishman's observations were published in 1903. At the same time, a Professor of Physiology at Madras University named Charles Donovan described a similar parasite in splenic biopsy smears. The causative agent of Kala Azar was thus found.
In 1924 the Kala-Azar Commission noted that the distribution of a sandfly (Phlebotomus argentipes) in India tightly overlapped that of Kala Azar.
In 1939, Smith, Haldar and Ahmed discovered that if flies were given a blood meal and then disallowed to take additional bloodmeals (though kept alive on raisins), then flagellates grew so numerous that they blocked the pharynx as happens with plague bacilli in fleas. These workers then subjected hamsters to the bite of blocked sandflies and each hamster became infected.
In 1941, human transmission of leishmaniasis was demonstrated when Adler and Ber successfully infected volunteers with Leishmania major by the bite of Phlebotomus papatasi. In 1942, Swaminath, Shortt and Andersen allowed 6 human volunteers to be bitten by infected Phlebotomus argentipes and all developed Kala Azar.
Sandflies are pool feeders -- they prick their victim and suck up the resulting pool of blood. They are infected upon ingesting infected macrophages.
|Macrophage||Amastigotes are within the macrophages.|
|Ingestion||Upon ingestion by the sandfly, amastigotes transform into promastigotes.|
|Gut||The promastigotes in the gut of the female sandfly attach to the midgut-hindgut epithelium where they divide by binary fission for 8-20 days after initial ingestion of blood.|
|Pharynx||A decline in tetrahydrobiopterin triggers metacyclogenesis, whereby the promastigotes move forward to the pharynx.|
|Blockage||Metacyclic promastigotes secrete the promastigote secretory gel (aka PSG) to block the pharynx. The PSG plug forces the stomodeal valve open and extends into the pharynx region. Metacyclic promastigotes are concentrated at the anterior pole of the plug but are found along the foregut in both the cibarium and proboscis.|
|Feeding||When such a sandfly attempts to feed, it must egest the plug by regurgitating a bolus of metacyclic promastigotes -- "clearing its throat". This bolus is injected into the bite wound. There is no infection of the sandfly’s salivary glands.|
Microscopic detection of amastigotes (LD bodies) is made with stained smears made from the edges of the ulcer. Culturing parasites from the lesion can also be used in diagnosis.
|Old localized cutaneous||L. major (moist)|
L. tropica (dry)
|Human||Dog, rodent||Phlebotomus spp (Sandfly)|
|New cutaneous||L. mexicana||Human||Dog, rodent||Phlebotomus spp (Sandfly)|
|Diffuse cutaneous||L. aethiopica||Human||Hyrax||Phlebotomus spp (Sandfly)|
|New dry cutaneous||L. amazonensis||Human||Dog, rodent.||Lutzomyia|
|Human||Dog, rodent.||Phlebotomus spp (Sandfly)|
|Visceral||L. donovani||Human||Human||Phlebotomus spp (Sandfly)|
|Visceral||L. infantum||None, zoonosis||Dogs||Phlebotomus spp (Sandfly)|
|L. tropica||Urban areas of Mediterranean, Middle East, Pakistan and parts of India.|
|L. major||Rural (esp desert) areas of Central Asia, South Russia, Middle East and Africa.|
|Central and South America.|
|L. infantum||Africa, Asia and South Europe.|
|L. chagasi||South America|
Leishmania and HIV
Co-infection is an emerging disease, particularly in southern Europe where 25-70% of adult Visceral Leishmaniasis are related to HIV infection, and 1.5-9.5% of AIDS cases suffer from from newly acquired or reactivated Visceral Leishmaniasis.
Old world cutaneous leishmaniasis
Starts as a papule that runs an acute course (1-3 weeks) with early ulceration and a surrounding zone of inflammation, that usually heals in two months to a year leaving a depressed unpigmented scar, and lasting immunity.
|Leishmania major||Phlebotomus spp|
|Causes a moist, cutaneous, ulcerlike lesion at the site of the bite -- aka old world moist cutaneous leishmaniasis.|
|Leishmania tropica||Dogs||Causes dry cutaneous lesion that persists for months before ulcerating. Aka old world dry cutaneous leishmaniasis, Oriental Sore, Delhi Boil, Aleppo Button and Jericho Boil. Characteristically found in more densely populated urban areas.|
Diffuse cutaneous leishmaniasis
New world cutaneous leishmaniasis
The ulcer usually heals spontaneously in a few months. However, when the bite occurs on the ear it results in chronic lesions known as chiclero's ulcer. Because the cartilage of the ear pinna is poorly vascularized the immune response is weak, and in 40% of cases the result is mutilation of the pinna. Found principally in Central America where it occurs in the forest dwelling people who harvest latex from the chicle trees to be used in the manufacture of chewing gum. In Belize it is also known as bay sore.
|Leishmania mexicana||Tropical rodents|
Inoculation of promastigotes by the bite of a sandfly results in a small, red skin papule that is itchy and ulcerates in 1-4 weeks as in the case of cutaneous leishmaniasis; this ulcer usually heals spontaneously within 6-15 months. However, there is metastatic spread of the promastigotes from the site of the bite via the lymphatics. Disease is called espundia; the metastatic lesion involves the nasal and buccal mucosa causing destruction and malformations of the cartilage and soft tissues.
The ulcerations can involve the nose, pharynx, palate and lips resulting in camel nose or parrot beak. Invasino of the larynx may result in a loss of speech. In Brazil 1/3 of the espundia cases are in children. May take many years for it to spread form the initial site of bite. Death may occur from secondary infections or respiratory complications.
|Leishmania guyanensis||In Uruguay and Venezuela, the disease is called pian bois and the lesions are flattened ulcerated plaques that remain open and oozing all over the body. Similar to wet lesions of L. major.|
Diffuse cutaneous leishmaniasis
In some patients, particularly in Venezuela, a diffuse cutaneous form develops which is characterized by a macrophage granuloma and thickening of the skin. This condition looks like lepromatous leprosy and sometimes like fungal disease, and is often misdiagnosed.
Infection likely is due to a failure of the immune response.
|Leishmania mexicana||Leishmania mexicana may be a causative agent.|
|Leishmania panamensis||Lutzomyia spp||Dogs|
This is a metastatic disease. Parasites are only occasionally seen in blood, but are present in the spleen and lymph nodes. THe incubation period is 1-4 months.
Disease is characterized by fever, anemia, splenomegaly, wasting, imbalance of serum proteins (A/G ratio is reversed) and hyperpigmentation of the skin. The death rate is very high if left untreated.
|Leishmania donovani||Causes the form in India.|
|Causes the Mediterranean form of Kala Azar. Humans are accidental hosts.|