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Chapter 158 Hematologic Aspects of Parasitic Diseases 2293

Key
T. b. gambiense
T. b. rhodesiense

Fig. 158.9 DISTRIBUTION OF TRYPANOSOMA BRUCEI INFECTION IN HUMANS. African try-
panosomiasis is confined to equatorial Africa, with a patchy distribution depending on detailed topographic
conditions. It is caused by two subspecies of T. brucei: T. b. gambiense infection is widespread in West and
Central Africa, transmitted mainly by riverine species of tsetse fly (Glossina), but T. b. rhodesiense, transmitted
mostly by savannah species, is restricted to the eastern and east-central areas of Africa, with some overlap
between the two. Although domestic pigs form an important reservoir for T. b. gambiense infection, various
wild ruminants are the major sources for T. b. rhodesiense. The epidemic reemergence of African trypanoso-
miasis in recent years is exemplified by the death of at least 96 people in Angola in 2003, when 3115 cases
were confirmed among a suspected 270,000 new cases in that country. In the same year it was estimated that
some 500,000 people across Africa had trypanosomiasis, which was likely to have a mortality rate of approxi-
mately 80%. Recent reports indicate a spread of transmission from the northern toward the southern parts of
Angola. (Modified from World Health Organization Map No. 98005.)

shows infiltration of the portal tracts and fatty degeneration. In T. b.
rhodesiense, cardiac involvement may be extensive, with endocarditis,
myocarditis, and pericarditis leading to extensive damage and death.
In the second stage of the disease, trypanosomes multiply within
the central nervous system (CNS) and cause a chronic meningoen-
cephalitis. Edema, hemorrhages, granulomatous lesions, and throm-
bosis contribute to cerebral degeneration. Lymphocytosis and plasma
cells with large eosinophilic inclusions (Mott cells) may be found in
the CNS.
Intriguingly, nonpathogenic species of African trypanosomes may
be killed by the human high-density lipoprotein particles astonish-
ingly subverting a parasite pathway for heme uptake. The complex
of haptoglobin-related protein and apolipoprotein L1 (ApoL1) are
taken up into the parasite by a parasite glycoprotein receptor, which
binds the haptoglobin–hemoglobin complex. 187–190 T. b. rhodesiense is
resistant to killing by human sera because the ApoL1, which induces
parasite apoptosis, is neutralized in the lysosome by serum resistance–
associated protein, which binds to a specific ApoL1 domain. The
selection of trypanolytic ApoL1 variants have a cost. In African
Americans, focal segmental glomerulosclerosis and hypertension-
attributed end-stage kidney disease are associated with two indepen-
dent sequence variants in the APOL1 gene. 191

Clinical Features

T. brucei gambiense
Fig. 158.10 ORIGINAL MICRO-PHOTOGRAPH OF TRYPANOSOMA
(TRYPANOZOON) BRUCEI GAMBIENSE IN HUMAN BLOOD BY J. Local inflammation at the site of inoculation causes a distinctive
EVERETT DUTTON. Polymorphic trypanosomes were first discovered chancre or painful, indurated ulcer appearing 2 to 3 days after an
more than a century ago, in 1895, by David Bruce in the blood of domestic infective bite and lasting for up to 1 month. Trypanosomes multiply
cattle with the wasting disease nagana in South Africa. The first observation in the lymphatic system for 6 to 14 days before causing patent
of these protozoa in humans was made by R. M. Forde, who noted, in 1902, infection in the blood, characterized by waves of parasitemia and
“small worm-like, extremely active bodies” in the blood of a sick European fever. Later, invasion of the CNS may occur by transit of organisms
seaman in The Gambia. The parasites seen here in a Romanowsky-stained through the choroid plexus and/or endothelial cells.
thin blood film, which were described and named by Dutton in 1902, are In the blood stage of infection, fever, headache, and arthralgia are
responsible for sleeping sickness in West Africa. (Reproduced by kind permission prominent. Lymphadenopathy is common, particularly in the poste-
of the Director, Liverpool School of Tropical Medicine.) rior triangle of the neck (Winterbottom sign). There may be