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Leishmania
Classification: Taxonomic ranks under review (cf. Illustrated Guide to Protozoa, 2000. Allen Press)
Protista (unicellular eukaryotes)
Sarcomastigophora (with pseudopodia and/or flagella)
Mastigophora (flagellates)
Zoomastigophora (zooflagellates, without chloroplasts)
Kinetoplastida (presence of extranuclear DNA, kinetoplast
Family: Trypanosomatidae
All species are characterized by the possession of a kinetoplast, a unique structure formed by massed DNA (circles or
lattice) within the single large mitochondrion closely associated with the flagellar basal body. Four main developmental
stages are formed: trypomastigotes (with a posterior kinetoplast and an emergent flagellum forming a long undulating
membrane); epimastigotes (with an anterior kinetoplast and an emergent flagellum forming a short undulating
membrane); promastigotes (with an anterior kinetoplast and a short emergent flagellum, but no undulating membrane);
and amastigotes (with a kinetoplast but no emergent flagellum or undulating membrane). Many trypanosome species are
parasitic only in insects whereas others are transmitted by insect vectors to a wide range of vertebrate hosts. Three main
groups infect the blood and/or tissues of humans and animals causing severe clinical diseases:
> salivarian trypanosomes which undergo anterior station (foregut) development in the insect vector and are
transmitted via saliva to the blood of vertebrate hosts (e.g. tsetse flies transmit T. brucei which causes sleeping
sickness in humans and nagana in cattle)
> stercorarian trypanosomes which undergo posterior station (hindgut) development in vectors and are
transmitted via faecal contamination of bite site to infect blood and tissues of vertebrate hosts (e.g. reduviid
bugs transmit T. cruzi which causes Chagas’ disease in humans)
> leishmanias which develop in foregut of insect vectors and are transmitted via bite to the tissues of vertebrate
hosts (e.g. sandflies transmit Leishmania spp. causing 3 types of leishmaniasis in humans and animals)
Leishmania spp. [these species cause cutaneous, mucocutaneous or visceral leishmaniasis in humans]
Parasite morphology: Two developmental stages are formed: amastigotes and promastigotes. The amastigotes are
small spherical non-flagellated cells ranging from 2-4µm in diameter. The nucleus and kinetoplast are surrounded by
small ring of vacuolated cytoplasm and the cells are among the smallest nucleated cells known. Promastigotes are thin
elongate cells with an anterior kinetoplast and an emergent free flagellum. They are generally lance-like in shape and
range in size from 5-14µm in length by 1.5-3.5µm in width. Different parasite species are generally not differentiated by
morphological differences, but rather on the basis of geographical, biological and clinical features.
Host range: All Leishmania spp. infect mammals and are most commonly found in humans, dogs and rodents. Infections
are confined to tropical areas, different parasite species being found in the Old World (Middle-East and Africa) and the
New World (Central and South America).
Leishmania species Vertebrate hosts Disease Insect vector Distribution
CUTANEOUS LEISHMANIASIS
diffuse or dry
L. aethiopica humans, hyraxes Phlebotomus Ethiopia, Kenya
cutaneous
humans, dogs,
L. tropica minor dry cutaneous Phlebotomus Mediterranean
rodents
L. tropica major humans, dogs, wet cutaneous, oriental Phlebotomus Mediterranean
rodents sore
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L. peruviana humans, dogs uta, cutaneous Lutzomyia Peru
chicleros ulcer, Central America,
L. mexicana mexicana humans, rodents Lutzomyia
cutaneous Mexico
L. mexicana
humans, rodents diffuse, cutaneous Lutzomyia South America
amazonensis
cutaneous,
L. mexicana pifanoi humans, rodents Lutzomyia Venezuela
mucocutaneous
humans, rodents, espundia,
L. braziliensis Lutzomyia Mexico-Brazil
sloths mucocutaneous
VISCERAL LEISHMANIASIS
kala azar, dum-dum
Mediterranean,
L. donovani donovani humans, dogs, foxes fever, Old World Phlebotomus
South America
visceral
L. donovani infantum humans, dogs infantile, visceral Phlebotomus Mediterranean
L. donovani chagasi humans, foxes, cats New World visceral Lutzomyia South America
Site of infection: Amastigotes invade macrophage cells of the reticuloendothelial and lymphoid systems of the skin,
nasopharynx or viscera depending on the parasite species. The parasites survive within phagosomes but resist digestion
by lysosomal enzymes. They multiply and grow, ultimately rupturing the host cell and releasing stages to infect new
macrophages, including those which circulate in the blood (monocytes).
Pathogenesis: The parasites cause three distinct types of clinical disease, cutaneous, mucocutaneous and visceral
leishmaniasis. Old World cutaneous leishmaniasis is caused by L. tropica and L. aethiopica while New World cutaneous
leishmaniasis is caused by L. mexicana and L. braziliensis. Infections generally involve only one or a few lesions at the
bite site; they do not spread to other sites. Active lesions appear as open sores/ulcers with pronounced inflammation.
Most lesions heal spontaneously, leaving the host with solid protective immunity to re-infection. However, under certain
conditions (esp. immuno-compromised hosts), some L. aethiopica infections may spread giving rise to disseminated
cutaneous leishmaniasis (not unlike leprosy in appearance). Infections by L. braziliensis are also often confined to single
skin lesions, but sometimes they spread to the mucocutaneous junction in the pharynx and may cause severe destructive
nasopharyngeal lesions. Visceral leishmaniasis is caused by L. donovani whereby infected macrophages congregate in
the viscera, notably the liver and spleen, producing hepatosplenomegaly, oedema and anaemia. It is a slow but
progressive illness, with bouts of irregularly recurring fever, and is invariably fatal, unless treated.
Mode of transmission: All species are transmitted by small blood-sucking sandflies, notably Phlebotomus spp. in the
Old World and Lutzomyia spp. in the New World. Only the females feed on blood. Amastigotes ingested during feeding
transform in the midgut or hindgut into promastigotes which multiply by binary fission. The parasites migrate forward to
the foregut and proboscis where some become swept away by saliva into the bite site when the fly feeds.
Differential diagnosis: Amastigotes may be detected microscopically in biopsy tissues, smears or secretions before or
after culture. Parasites are best visualized using Giemsa’s or Leishman’s stains, and suitable culture media include
conventional nutrient agar-blood mixtures. Serological tests have been developed but there are difficulties in
distinguishing between recent and chronic infections and between infections by different parasite species, although a
delayed-type hypersensitivity (DTH) skin test has shown good promise as a marker of cured symptomatic or
asymptomatic visceral infection. Modern molecular characterization techniques have used the polymerase chain reaction
(PCR) to amplify parasite DNA from host tissues.
Treatment and control: Some cutaneous infections require no treatment as lesions may heal within several months.
Systemic therapy with pentavalent antimonials (sodium stibogluconate or meglumine antimonate) is the treatment of
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choice for disfiguring and visceral infections. The development of antimonial drug resistance, however, is a growing
problem in many endemic areas, including South America, India and the Middle-East. Pentamidine or amphotericin B can
be used if antimonials are ineffective, and miltefosine and aminosidine (paromomycin) have shown promise as treatment
options, especially when combined with immunotherapy using the tumour-necrosis factor-alpha (TNF-?) inhibitor
pentoxifylline. Preventive measures include protection from sandfly bites but this can be difficult as they are so small that
they can penetrate most mosquito nets. Reducing the size of reservoir host populations (especially dogs) has proven
beneficial in many endemic urban areas. Many cutaneous infections, however, are acquired in forests away from human
habitation, as the reservoir hosts are wild animals (esp. rodents). The prevention of sandfly bites in forest areas is almost
impossible but may be minimized by the use of protective clothing, insect repellants and insecticidal sprays in houses.
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