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جامعة تكريت
/ كلية الطب / فرع طب االطفال / أ.د. احمد هاشم عبد الغفور
Kala-azar/ Leishmaniasis :
objectives : the objectives of this lecture are to know :
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Symptoms, Causes, Diagnosis, Management& Prevention of
kala-azar.
Visceral leishmaniasis (VL), also known as kala-azar
fever,
and Dumdum
fever,
the
most
severe
form
of leishmaniasis and, without proper diagnosis and treatment, is
associated with high fatality.
Leishmaniasis is a disease caused
by protozoan parasites of the genus Leishmania.
Post
Kala-Azar
Dermal
Leishmaniasis
(PKDL)
Post Kala-Azar Dermal Leishmaniasis is a condition in which
Leishmania donovani parasites invades in skin cells. The parasite
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resides
and
develops
there
and
manifests
as dermal
lesions. Recently it is believed that PKDL may appear without
passing through visceral stage. However, adequate data is yet to
be generated on course of PKDL manifestation.
Life cycle[edit]
The life cycle of Leishmania is completed in two hosts, humans
and sandflies. The adult female sandfly is a bloodsucker, usually
feeding at night on sleeping prey. When the fly bites an individual
infected with Leishmania, the pathogen is ingested along with the
prey's blood. The protozoan is in the smaller of its two forms,
called an amastigote, which is round, non-motile, and only 3
–7
micrometers in diameter. Inside the stomach of the sandfly, the
amastigotes quickly transform into elongated and motile forms
called the promastigotes. Promastigote is spindle-shaped, triple
the size of the amastigote, and has a single flagellum that allows
mobility. The promastigotes live extracellularly in the alimentary
canal, reproducing asexually, then migrate to the proximal end of
the gut where they become poised for a regurgitational
transmission. As the fly bites, the promastigotes are released from
the proboscis and introduced locally at the bite site.
Once inside the human host, promastigotes invade macrophages.
Inside the cells they transform back into the smaller amastigote
form. The amastigotes replicate in the most hostile part of the
macrophage cell, inside the phagolysosome, whose normal
defensive response they are able to prevent. After repeated
multiplication, they break down their host cell by sheer pressure of
mass, but there is some recent speculation that they are able to
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leave the cell by triggering the exocytosis response of the
macrophage. The daughter cells protozoans then migrate to fresh
cells or through the bloodstream to find new hosts. In this way the
infection is progressive, spreading to the host's mononuclear
phagocyte system, particularly the spleen and liver. The free
amastigotes in peripheral tissues are then ingested by sandfly to
enter another cycle.
Symptoms
Recurrent fever intermittent or remittent with often double rise of
temperature.
Loss of appetite, pallor and weight loss with progressive
emaciation
Weakness
Skin
– Dry, thin and scaly and hair may be lost. Light colored
person show grayish discoloration of the skin of hands, feet,
abdomen and face which gives the Indian name Kala-Azar
meaning “Black fever”.
Anemia
– develops rapidly
Splenomegaly
– spleen enlarges rapidly to massive
enlargement, usually soft and non-tender.
Liver
– enlargement not to the extent of spleen, soft, smooth
surface, sharp edge.
Diagnosis : A case of fever of more than two weeks duration not
responding to anti-malarials and antibiotics. Clinical laboratory
findings may include anemia, progressive leucopenia
thrombocytopenia and hypergammaglobulinemia.
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Laboratory:
Serology tests: A variety of tests are available for diagnosis
of Kala-azar. The most commonly used tests based on
relative sensitivity; specificity and operational feasibility
include Direct Agglutination Test (DAT), rk39 dipstick and
ELISA. However all these tests detect IgG antibodies that
are relatively long lasting. Aldehyde Test is commonly used
but it is a non-specific test. IgM detecting tests are under
development and not available for field use.
Parasite demonstration in bone marrow/spleen/lymph node
aspiration or in culture medium is the confirmatory diagnosis.
However, sensitivity varies with the organ selected for
aspiration. Though spleen aspiration has the highest
sensitivity and specificity (considered gold standard) but a
skilled professional with appropriate precautions can perform
it only at a good hospital facility.
Management
The traditional treatment is with pentavalent antimonials such
as sodium stibogluconate and meglumine antimoniate. the WHO
recommended treatment is SSG&PM (sodium stibogluconate and
paromomycin) developed by Drugs for Neglected
Diseases initiative (DNDi)in 2010.
Miltefosine is the first oral treatment for this disease. The cure rate
of miltefosine in Phase III clinical trials is 95%; Studies in Ethiopia
show that is also effective in Africa. In HIV immunosuppressed
people which are coinfected with leishmaniasis it has shown that
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even in resistant cases 2/3 of the people responded to this new
treatment. Miltefosine has received approval by the Indian
regulatory authorities in 2002, in Germany in 2004 and in U.S.A. in
It is now registered in many countries.
Prevention
.The most effective method to prevent infection is to protect from
sand fly bites. To decrease the risk of being bitten following
precautions are suggested:
Outdoors:
-Avoid outdoor activities, especially from dusk to dawn, when sand
flies generally are the most active. When outdoors (or in
unprotected quarters): Minimize the amount of exposed
(uncovered) skin. To the extent that is tolerable in the climate,
wear long-sleeved shirts, long pants, and socks; and tuck your
shirt into your pants.
-Apply insect repellent to exposed skin and under the ends of
sleeves and pant legs. Follow the instructions on the label of the
repellent. The most effective repellents generally are those that
contain the chemical DEET (N,N
–diethylmetatoluamide)
Indoors:
-Stay in well-screened or air-conditioned areas.
-Keep in mind that sand flies are much smaller than mosquitoes
and therefore can get through smaller holes.
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-Spray living/sleeping areas with an insecticide to kill insects. If you
are not sleeping in a well-screened or air-conditioned area, use a
bed net and tuck it under your mattress.
-If possible, use a bed net that has been soaked in or sprayed with
a pyrethroid-containing insecticide. The same treatment can be
applied to screens, curtains, sheets, and clothing (clothing should
be retreated after five washings).”
On February 2012, the nonprofit Infectious Disease Research Institute
launched the world’s first clinical trial of the visceral leishmaniasis
vaccine. The vaccine is a recombinant form of two fused Leishmania
parasite proteins with an adjuvant.