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Human African Trypanosomiasis or sleeping sickness, is a disease
caused by Trypanosoma brucei gambiense or T. brucei rhodesiense.
Humans are the main reservoir of both forms.
Image
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These hemoflagellate protozoa are transmitted
by the bite of various species of Glossina,
the tsetse fly
(Image) . The
trypanosomes give rise to two distinct clinical entities, Gambian trypanosomiasis
(chronic infection) and Rhodesian trypanosomiasis (acute infection).
The uneven
distribution of African trypanosomiasis is related to the habitats of
tsetse flies.
African
trypanosomiasis is limited to a wide belt of territory in the African
continent between the latitudes of 10 degrees north and 25 degrees
south. Neither type is present at elevations over 7000 feet above sea
level.
Visit:
American Trypanosomiasis(Chagas'Disease)
In Gambian trypanosomiasis
, Trypanosoma brucei gambiense
is transmitted by tsetse flies of the riverine bush, mainly in focal
areas of West and Central Africa. Man is the only important reservoir
for T.b. gambiense, which cause a chronic lesion often lasting more
than a year.
In Rhodesian trypanosomiasis,
T.b rhodesiense is transmitted by tsetse flies of the woodland savanna
of East Africa. Antelope, other game animals and domestic cattle are
natural reservoirs of T.b rhodesiense. Incidental infection of man is
an occupational hazard of game wardens, fisherman and cattle herders.
T.b rhodesiense causes a disabling, acute, fulminant infection in man,
killing the patient in 3 to 6 months.
Life Cycle :
(Click on the image)
A tsetse fly bites an infected animal or human and ingests
trypomastigotes which multiply into infective, metacyclic
trypomastigotes.
During another
fly bite, these are injected into lymphatic and blood vessels of a new
host.
A primary
chancre develops at the site of the bite (Stage 1a).
Trymastigotes
replicate further in the blood and lymph, causing a systemic infection
(Stage 1b).
Another fly
ingests trypomastigotes to complete the cycle.
In Stage 2,
invasion of central nervous system by trypomastigotes leads to
meningoencephalomyelitis and associated symptoms.
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The clinical
manifestations of trypanosomiasis are divided into:
Stage 1-
Primary Chancre and systemic infection excluding the brain ;
Stage 2- Invasion of the brain .
A firm,
tender, reddened nodule may develop in a matter of a few days at the
site of the bite.
Trypanosomes
may be identified in Giemsa-stained smears of fluid aspirated from the
nodule.
The ulcerated
nodule, or "trypanosomal chancre", is accompanied by a regional
lymphadenitis that lasts 1or 2 weeks. The rapidity of the development
of the chancre is related to the number of trypanosomes transmitted.
The chancre precedes parasitemia. The hemoflagellates apparently reach
the bloodstream via lymphatics.
This is
followed within 1 to 5 weeks by the onset of fever, sweating, general
malaise and a generalized lymphadenitis often involving involving
primarily the posterior cervical glands. Frequently there are
transient skin eruptions characterized by erythema or edema. These
symptoms and signs may progress to the phase of central nervous
system.
Numerous
trypanosomes are found in the blood soon after infection, specially
after symptoms have developed.
Image1
; Image2
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Other
hematologic findings may include anemia , granulocytopenia and
thrombocytopenia. There is an increase in sedimentation rate and a
hypergammaglobulinemia specially of the IgM class. Patients have
high levels of circulating immune complexes, which are believed to
lead to immune complex-mediated vasculitis.
Lymph node
enlargement, particularly of the posterior cervical lymphnodes (Winterbottom's
sign), is a common clinical feature.
The lymph
nodes contain numerous parasites, and there is a generalized
hyperplasia of lymphoid and reticular elements. Fibrosis of the lymph
nodes develops later, with reduction in their size.
Trypanosomes
evade the immunologic response of the host by presenting to the
immune system progressively different surface glycoprotein
constituents. By the time the host mounts an immune response,
the trypanosome has new surface antigens to which the formed
antibodies are not specific. This phenomenon of antigenic variation is
accomplished by the trypanosome through a mechanism of gene conversion
and DNA rearrangement. Trypanosomes also are known to cause
immunosuppression by limiting specific antibody response, specially of
the IgG type. The host is left with nonspecfic IgM production to
combat the infection. This partially explains the rise in IgM levels
in this chronic infection.
Although there is
much overlap between the clinical manifestation of T. brucei gambiense
and T. brucei rhodesiense infections , the latter usually follows a
much more acute course. Untreated persons with T. brucei rhodesiense
infection frequently die within 3 to 6 months after onset of the
disease.
The systemic
stage is often characterized by serous effusions and evidence of
pancarditis.
The parasites
in the Rhodesian variety, after entering the lymph nodes, produce
toxic substances that cause hyperplasia of the endothelial lining of
the blood sinuses and perivascular infiltration of leukocytes.
Only rarely
does the victim survive long enough for the trypanosome to invade the
central nervous system and produce lesions characteristic of the third
stage of T. brucei gambiense infection.
The neurologic
symptoms and signs, when present are similar to those of gambian
trypanosomiasis. Gambian trypanosomiasis is characteristically a
chronic disease.
In the third
stage the patient becomes indifferent, apathetic and drowsy.
Focal neurologic signs are uncommon, though athetosis, chorea, and
sphincter disturbances may become apparent. The syndrome resulting
from invasion of the central nervous system is commonly referred to as
" sleeping sickness,"
but this
designation suggests only one of the more advanced neurologic
symptoms.
In the majority
of cases there are no major macroscopic alterations in the brain
substance other than edema and occasionally petechiae.
Image Link1;
Image link2;
Image Link3 (Acute
haemorrhagic leucoencephalopathy)
Microscopically, the picture is that of a diffuse meningoencephalitis.
There is
mononuclear infiltration of the superficial leptomeninges , sulci and
Virchow-Robin spaces. The cellular infiltrate composed of lymphocytes
and plasma cells in various proportions, may also infiltrate the white
matter and to a lesser extent the gray matter.
The morular cell
described by Mott is a plasma cell whose cytoplasm contains numerous
Russell bodies, which coalesce and partially or totally hide the
nucleus of the cell. Although these cells are not pathognomonic of
trypanosomiasis, their presence in large numbers is fairly
characteristic of the disease.
Diagnosis of
the disease:
The simplest
diagnostic test is the demonstration of the trypanosomes in the
circulating blood during febrile episode. Lymph node imprints may be
useful for the identification of the parasite.
Examination of
the cerebrospinal fluid reveals trypanosomes as the disease progresses
and may serve as an index of the course of the disease.
The greatest
elevation of IgM in both the serum and cerebrospinal fluid can be used
as a screening diagnostic test.
Serodiagnosis is
available by indirect immunofluorescence, complement fixation and
enzyme-linked immunosorbent assay (ELISA).
Treatment:
The key drugs
used for therapy of African trypanosomiasis are pentamidine, for
chemoprophylaxis; suramin, for the treatment of the early disease in
which trypanosomes are found in the blood, lymph, and lymph nodes ;
and melarsoprol, for the later disease in which trypanosomes are
located in the brain.
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