Leishmaniasis Paul R. Earl Facultad de Ciencias Biol

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Leishmaniasis Paul R. EarlFacultad de
Ciencias BiológicasUniversidad Autónoma de Nuevo
LeónSan Nicolás, NL 66451, Mexico
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Policies and generalities. The complete
management of diseases such as leishmaniasis,
trypanosomiasis and malaria throughout the
subtropical and tropical world awaits the much
improved management of poverty which is the lack
of resources, knowledge and industrial skills,
and should include birth control. Diseases like
the ones noted keep populations down, or they
used to before the antibiotics arose in the
1940s.
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A country like landcleared treefree Haiti without
decent water sewage facilities punctuated by
electricity failures is an example of Malthusian
misery. That is what can happen if rural
ignorance prevails. Will many tropical diseases
be soon eradicated, and will their demise be
accompanied by higher standards of living in much
of the world? What will the planet be like after
eradication?
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Cutaneous leishmaniasis usually divided into Old
World leishmaniasis caused primarily by L.
donovani, L. tropica, L. infantum, L. major, L.
aethiopica and New World leishmaniasis caused
primarily by L. mexicana and L. braziliensis.
Diffuse cutaneous leishmaniasis is caused
primarily by L. aethiopica or L. mexicana.
Mucocutaneous leishmaniasis (espundia) is caused
primarily by L. braziliensis.
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The trypanosomatids of the genus Leishmania are
the etiological agents of a variety of diseases,
collectively known as leishmaniasis. It is
prevalent throughout the tropical and subtropical
regions of Africa, Asia, the Mediterranean,
Southern Europe (Old World) and South and Central
America (New World). The impact of the
leishmaniasis on public health is modest, since
many cases go unreported or misdiagnosed. About
12 million people are currently infected, and a
further 367 million are at risk of acquiring
leishmaniasis in 88 nations, 72 of which are
developing countries.
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A little geography. The geographic distribution
of leishmaniasis is cosmopolitan. Thus L. tropica
and L. major, causing Oriental sore are found in
Russia, Indonesia, equitorial Africa, in the west
and east of the Mediterranean (Italy, Spain,
Greece, Bulgaria and Romania). For instance, L.
mexicana is found in the southeast of México in
Tabasco, Campeche and other states, Central
America and some countries of South America like
Venezuela.
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Leishmania brasiliensis and its subspecies cause
mucocutaneous leishmaniasis or espundia localized
in South and Central American countries and the
southeast of Mexico, principally Tabasco and
Quintana Roo. L. peruviana causes Uta found in
the Peruvian slopes of the Andes and Argentine
highlands. L. donovani with its subspecies and
closely related ones like L. infantum are found
in the Mediterranean basin, Africa, regions of
Asia and in America as L. donovani chagasi
localized mainly in Brasil, Venezuela, Colombia,
El Salvador, Guatemala and in Mexico in the
Balsas valley.
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History. In 1900, Major William B. Leishman
(1865-1926) performed a postmortem on an English
soldier returning from Bengal who had died of
"fever." He described finding enormous numbers of
oval bodies 2-3 ?m in diameter in the splenic
smears of this patient. In 1903, Captain James
Donovan (1863-1915) in Madras, described similar
findings in the splenic smears taken from the
enlarged spleens of Indian patients who had died,
presumably from malaria. It was Ronald Ross who
named the new protozoa the Leishman Donovan body.
Ninety percent of cases are found in Bangladesh,
India, Nepal, Sudan and Brazil.
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There are 3 distinct species L. infantum found
in the Mediterranean basin, Central Asia and
China, L. donovani in India and Eastern Africa,
and L. chagasi in South and Central America.
Leishmania ssp. are members of the family
Trypanosomatidae, order Kinetoplastida. L.
donovani and L. infantum are often
geographically associated, and dogs worldwide are
reservoirs for L. infantum. It is not especially
important if other good names like L. mexicana
are applied, because DNA sequencing has not yet
proceeded far enough to differentiate species as
in an efficient routine taxonomy.
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Leishmania needs a complete molecular revision.
It was greatly helped by isozyme plus cluster
analysis, but this is not enough. The list of 18
species now given requires scrutiny.
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PCR amplification of kinetoplast DNA minicircles
using general kinetoplastid primers, for all
Leishmania species and other kinetoplastids (k)
was followed by the identification of the L.
species complexes by hybridisation of the PCR
products with specific kDNA probes. The
polymorphic PCR-products were analysed by
electrophoresis and the banding patterns compared
with multilocus enzyme electrophoresis data.
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Life cycle. The reservoir of infection is the
amastigote form of the parasite, present in
animal reservoir hosts such as rodents, dogs,
foxes, jackals and humans. Dogs are especially
common reservoirs in the Mediterranean basin.
They are infected worldwide and particularly in
the Mediterranean basin as in Italy with L.
infantum which is like L. donovani.
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Amastigotes of L. infantum in dog blood
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In a very simple way, some amastogotes remain in
the skin causing cutaneous leishmaniasis, whereas
others are carried by macrophages into internal
organs thereby causing visceral leishmantiasis.
Many different strains of leishmania can cause
disease in humans with each strain differing in
its reservoir, vector, geographic location and in
the pathological lesions that it gives rise to.
This makes creating a passable taxonomy
difficult.
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The reservoir of infection is the amastigote form
of the parasite, present in animal reservoir
hosts such as rodents, dogs, foxes, jackals and
humans. Dogs are especially common reservoirs in
the Mediterranean basin such as in southern
Italy. The infection is usually transmitted by
the bite (blood feed) of the female sandfly,
although human infection has been reported from
blood transfusion, congenital transmission, and
by sexual intercourse. In the sandfly vectors and
on culture, the parasite takes up the
promastigote form.
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Promastogotes, Courtesy of Tsehay Atlaw
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Rosette of promastigotes,
Courtesy of Duncan Kennedy
The sandfly vector, Phlebotomus, Lutzomyia or
another similar one
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Visceral leishmaniasis. Nicolle in 1908 reported
that mammals including dogs could act as
reservoir hosts for the leishmania parasite.
Using human volunteers, Swaminath and coworkers
in 1942 proved that the leishmania parasite was
transmitted by the phlebotomus sandflies. The
only proven vector of the leishmania parasite is
the blood-sucking female of the genus Phlebotomus
in the Old World and Lutzomyia a copy in the New
World. These genera are extremely similar.
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Visceral leishmaniasis is also known as Kala-azar
(Hindi kala black, azar sickness). The
etiological agents belong to the Leishmania
donovani complex like L. d. donovani, L. d.
infantum and L. d. archibaldi in the Old World
and L. d. chagasi in the New World. The Old World
species are transmitted by the sandfly vector
Phlebotomus sp. and Lutzomyia sp. in the New
World. The acceptibility of this taxonomy depends
on the reader.
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Mucocutaneous leishmaniasis has a clinical
picture dominated by great destruction of the
nasal mucosa, sometimes with respiratory
complications. In visceral leishmaniasis or
kala-azar, the parasites multiply abundantly in
the medula of the spleen and bone marrow. The
infection causes fever, headache, anorexia, loss
of weight, splenomegly, hepatomegly,
lymphadenopathy, pancytopenia, hypergammaglobinemi
a, anemia and darkening of the skin, tending
towards a chronic state.
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Diagnosis. Laboratory diagnosis by direct and
indirect methods can begin with the microscopy of
the ulcer, using Giemsa stain. Cultivation of the
parasites cells is an indirect method, true also
for the infection of rodents that develop typical
lessions. The antibody titers are low in
cutaneus, high in mucocutaneous and very high in
disseminated cutaneous or visceral leishmaniasis.

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Treatment. The great stumbling block is cost of
both medication and hospitalization. The
traditional pentavalent antimony compounds like
pentamidine were the chosen medicaments over many
decades, but they are no longer recommended,
because of resistence. Amphotericin B especially
with lysosomes and miltefosin give excellent
curative results. Oral miltefosine for 28 days,
daily injections of aminosidine for 21 days,
infusions of conventional amphotericin B given
daily for 20 days or on alternate days for 30
days, and short courses of infusions of a
liposome formulation of amphotericin B have cure
rates of over 90.
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Treatments are not really affordable. US average
wholesale prices for the various lipid
formulations of amphotericin B are 188 per 50 mg
vial for AmBisome (liposomal), 93 per 50 mg for
Amphotec (cholesterol dispersion), and 194 per
100 mg for Abelcet (lipid complex). The regimen
for liposomal amphotericin B consists of 3 mg/kg
given on days 1-5, 14 21 (total dose 21
mg/kg). AmBisome currently costs about 173 per
50 mg. This amounts to roughly 500-2000 per
patient.
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Eradication. The eradication of various tropical
and other infectious diseases will be almost
commonplace in the first half of this century,
yet leishmaniasis may not be one of these.
Sandfly vector control in the Old and New Worlds
is never mentioned just as research is simply not
done with these creatures. Will DDT eradication
of malaria vectors also eliminate sandflies? Will
Brazil eradicate its leishmaniasis?
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Many infectious diseases from malaria on have the
same geography, which is to say that certain
diseases are wellknown in certain countries like
India. The tropical parasitoses have to be
eradicated in their strongholds like subSahara
Africa and India. All of these planned
eradications are exceedingly difficult, because
disease endemicity correlates to poverty much of
which is rural. On a lesser scale, the same thing
occurs in South America. However, the poverty is
not as severe, and how poverty correlates to
disease is not as clear. Are given diseases
causing poverty? Chronic leishmaniasis is one of
these.