Page 2569 - Hematology_ Basic Principles and Practice ( PDFDrive )

2292 Part XIII Consultative Hematology

especially in South Asia, by increasing drug resistance. There is who first demonstrated the parasite in the blood of cattle affected by
concern that drug resistance will develop to the alternative therapies, nagana. In humans, Aldo Castellani demonstrated trypanosomes in
and combination treatment aiming at short courses that also delay the cerebrospinal fluid (CSF) of patients with sleeping sickness. Bruce
the development of drug resistance are in progress. 53 was able to show the protozoa in blood and demonstrated that they
Amphotericin B is effective against Leishmania and is used in were transmitted from antelopes to cattle by the tsetse fly and blood
endemic areas where high levels of resistance to pentavalent antimoni- of patients with sleeping sickness.
als are present. It may be given as a slow intravenous infusion in 5%
dextrose over 4 to 6 hours, beginning at 250 µg/kg/day, increasing
to 1 mg/kg/day until a total dose of 20 mg/kg/day has been given. Epidemiology
Side effects include anaphylaxis, anemia, fever, bone chills, bone pain,
and thrombophlebitis. Hypokalemia and hypomagnesemia are sig- Trypanosomes are transmitted by some species of the large and dis-
nificant problems, and potassium loss and supplementation may be tinctive tsetse flies (Glossina spp.) in a sporadic distribution south of
reduced by the concurrent use of amiloride to prevent renal tubular the Sahara and north of the Zambezi River. Of the three subspecies,
potassium leakage. 176 Trypanosoma brucei brucei infects animals, whereas Trypanosoma
Reduced toxicity from amphotericin is achieved using a liposomal brucei gambiense causes infection and sleeping sickness in Central and
amphotericin preparation (AmBisome), which has been made more West Africa, and Trypanosoma brucei rhodesiense causes disease in East
widely available through preferential pricing in endemic areas. It and Central Africa. T. b. gambiense is transmitted mainly between
is an effective and safe treatment and is used when affordable. A humans by the Glossina palpalis group in foci along watercourses in
test dose of 1 mg should be given, and then the recommended West and Central Africa. T. b. rhodesiense is transmitted by the Glos-
dose is 1–3 mg/kg daily for 10–21 days to a cumulative dose of sina morsitans groups widely distributed in the East African savannah.
21–30 mg/kg, alternatively 3 mg/kg for 5 consecutive days, fol- Here the disease is clearly a zoonosis, with antelopes and domestic
lowed by 3 mg/kg after 6 days for 1 dose. In patients with HIV, cattle as reservoir hosts; it afflicts mainly hunters, guides, and game
a dose of liposomal amphotericin at 4 mg/kg/day on days 1 to 5 wardens and may occasionally occur in tourists on safari in the game
followed by 4 mg/kg/day on days 10, 17, 24, 31, and 38 is recom- parks of East Africa (Fig. 158.9).
mended. The relapse rate is high, and close monitoring of patients Historically the disease has caused major epidemics, causing
is required. hundreds of thousands of deaths, and has prevented human settle-
Miltefosine is a new drug and effective orally against VL in India ment in large areas of Africa. Over 50 million people are now at risk
and Africa. 177,178 The current regime is 2.5 mg/kg/day for adults and for trypanosomiasis, and it has been estimated that the disease causes
children older than 2 years for 4 weeks. Higher than 95% cure rates over 50,000 deaths each year. Most cases are reported in the Demo-
have been achieved. Gastrointestinal upset occurs frequently. Miltefo- cratic Republic of the Congo and northwestern Uganda, with a few
sine is teratogenic and may reduce fertility. It has a long half-life and hundred or fewer each year reported in neighboring East African
has a low therapeutic index, which may contribute to the develop- countries.
ment of resistance, and so combination chemotherapy is being Case-finding and control measures have substantially reduced the
investigated to combat development of resistance. risk for epidemics. Epidemics of disease have been associated with a
Intramuscular paromomycin has been used at a dose of 20 mg/ breakdown in health services, for example, in villages in the areas of
kg/day for 21 days. It has been shown to be equivalent to amphoteri- Lake Victoria in Uganda and more recently in the Democratic
179
cin B for the treatment of VL in India. Moreover, patients treated Republic of the Congo, Angola, and southern Sudan (for review of
for VL in Africa with sodium stibogluconate and paromomycin have current epidemiologic and clinical aspects of this disease, see Simarro
185
184
183
an improved outcome compared with therapy with sodium stiboglu- et al, Brun et al, and Franco et al ).
conate alone. 180
Post–kala-azar dermal leishmaniasis may occur in up to 10% of
patients after treatment for VL. It is seen mainly in India and is Parasitology
common in Africa. It occurs after treatment of VL and may appear
up to 10 years after treatment. It presents as a maculopapular rash The small, mobile trypomastigotes circulate and may be seen in
spreading around the mouth, trunk, and limbs. These nodules and peripheral blood. These flattened, fusiform organisms are pleomor-
papules contain amastigotes. Prolonged treatment may be required phic but are typically of a size similar to a red blood cell, approximately
to eliminate infection. 20 µm long, and have an undulating membrane, attached to the
protruding flagellum, extending from the anterior pole of the elon-
Leishmaniasis as a Transfusion- gated body (Fig. 158.10). Parasites multiply by binary fission and
may cause chronic parasitemia and evade humoral immune responses
Transmitted Infection by clonal antigenic variations of the major surface glycoprotein. 186
When trypomastigotes are taken up in a blood meal by the tsetse
Leishmaniasis poses problems as a potential transfusion-transmitted fly, they multiply in the midgut by simple fission. Later they penetrate
infection in endemic areas. The disease can be transmitted by blood the wall of the gut and migrate to the salivary glands. There, as
and platelet concentrates, although leukodepletion by filtration morphologically distinct epimastigotes, they become infective (or
reduces organisms by many orders of magnitude and so probably also metacyclic) trypomastigotes 15 to 30 days after first infecting the fly.
the risk for transmission. In Europe, given the low absolute risk for In endemic areas, up to 1% to 5% of flies may be infected. Flies
transmission, donor deferral is used to reduce the risk for donation remain infective until they die, several months later.
181
by anyone who is parasitemic. However, surveys of blood donors
in areas where the parasite is transmitted suggest parasite DNA can
be detected in 0.3% to 1.75% of blood donors. It has been noted Pathology
that service personnel returning from the Middle East represent
a group of potential donors who may have been exposed to The lymphatic, cardiac, and central nervous systems are involved by
infection. 182 the disease. Initially, proliferation of trypanosomes within lymph
nodes and the spleen is accompanied by expansion of the lympho-
cytes, macrophages, and erythrophagocytosis. Polyclonal activation
AFRICAN TRYPANOSOMIASIS of lymphocytes results in high production of IgM and rheumatoid
factor, and anti-DNA antibodies may appear. Later fibrosis and
African trypanosomiasis is caused by the flagellate protozoa Trypano- endarteritis supervenes with proliferation of endothelial cells and
soma brucei spp., named after David Bruce, a Scottish parasitologist perivascular infiltration of plasma cells and lymphocytes. The liver