Transcript Leishmaniasis Paul R. Earl Facultad de Ciencias Biológicas

Leishmaniasis
Paul R. Earl
Facultad de Ciencias Biológicas
Universidad Autónoma de Nuevo León
San Nicolás, NL 66451, Mexico
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.
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?
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.
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.
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.
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.
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 (18631915) 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.
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.
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.
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.
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.
Amastigotes of L. infantum in dog blood
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.
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.
Promastogotes, Courtesy of Tsehay Atlaw
Rosette of promastigotes,
Courtesy of Duncan Kennedy
The sandfly vector,
Phlebotomus, Lutzomyia
or another similar one
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.
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.
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, hypergammaglobinemia, anemia
and darkening of the skin, tending towards a
chronic state.
Diagnosis.
Laboratory diagnosis by direct and indirect
methods can begin with the microscopy of
the ulcer, using Giemsa stain. Cultivation of
the parasite’s 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.
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%.
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.
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?
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.