Page 2571 - Hematology_ Basic Principles and Practice ( PDFDrive )

2294 Part XIII Consultative Hematology

intermittent rashes (often circinate erythema), pruritus, or edema. levels may be elevated to four times normal and with raised IgG levels
Moderate splenomegaly occurs in 10% to 20% of patients. A few may cause an increased erythrocyte sedimentation rate.
infected patients are asymptomatic. The white blood cell count may be elevated with monocytosis,
This early stage of infection may last for up to 2 years or more lymphocytosis, and circulating plasma cells, but eosinophilia is
before CNS involvement, although rapidly progressive disease may absent. Plasma cells with eosinophilic inclusion or Mott morular cells
occur. The CNS phase of disease is marked by the progressive onset may occasionally be seen.
of headache; disinhibited behavior changes; and mood, thought, and Petechia and purpura may be secondary to vascular injury, throm-
sleep disturbances. Wasting is prominent. Signs of diffuse CNS bocytopenia, and a complex but poorly defined coagulopathy.
damage in the last phases of the disease include dementia, extrapyra- Abnormal liver function may cause prolonged clotting times. Func-
midal and cerebellar dysfunction, and hyperesthesia. Tendon reflexes tionally, both thrombosis and fibrinolysis are increased, and fibrin
are increased, and signs of upper motor neuron lesions are widespread. degradation products (D-dimers) are raised in acute disease; in T. b.
Death usually occurs by intercurrent infection. rhodesiense, a frank disseminated intravascular coagulation may
become evident. 195
Examination of the bone marrow shows hypercellularity. Gelati-
T. b. rhodesiense nous degeneration may be seen in patients with wasting.
Mononuclear cells are present late in the disease, and the cell
T. b. rhodesiense is more virulent, causing a more serious acute disease, count corresponds to the degree of neurologic involvement and may
with systemic features including serous effusions; hepatocellular reach more than 300/µL in severely ill patients. The CSF protein
jaundice; and a mild, normocytic, normochromic anemia. Hepato- levels are elevated (0.4 to 1.0 g/L).
splenomegaly and lymphadenopathy are common, but involvement As disease progresses, the circulating parasites become scarce.
of cervical lymph nodes is less typical. Myocarditis is rare but may However, anemia and endocrine dysfunction, including amenorrhea,
cause death before CNS involvement. Here CNS disease occurs reduced libido, and impotence becomes apparent.
sooner and is more rapidly progressive than T. b. gambiense infection
and is fatal within 1 to 3 months.
Infection with T. b. gambiense may resolve in the vast majority of Parasitologic Assays
cases. Where infection persists, there is typically a long asymptomatic
phase. Numerous lymph nodes are enlarged to 1 to 2 cm in diameter Direct detection of the parasite is particularly important in light of
and are soft, mobile, and painless. the toxicity of the treatment. Trypanosomes may be detected in
The differential diagnosis of trypanosomiasis includes malaria, lymph node aspirates and in wet and thick blood smears (Fig.
typhoid, fever, and viral hepatitis in the acute phase, whereas lymph- 158.11). An aspirate may be taken from enlarged nodes. Aspirated
adenopathy may suggest infectious mononucleosis or tuberculosis. In fluid can be examined under a coverslip, and motile trypanosomes
the cerebral phase of the disease, syphilis, tuberculosis, HIV-associated are typically seen at the edges of the coverslip.
cryptococcal meningitis, or chronic viral encephalitis must be Trypanosomes can be seen in wet smears, where a drop of blood is
considered. placed on a slide and examined under a coverslip. Alternatively, thick

Children

Those affected in utero may be born with CNS abnormalities. In
children the disease is more rapidly progressive, and epileptic seizures
and psychomotor retardation are the principal features of the disease.

HIV

The frequency of HIV seropositivity has been reported to show no
significant differences between those presenting with trypanosomiasis
and age-matched control subjects. 192,193 These results do not exclude
the possibility that coinfections may modulate the course of the
disease or the effectiveness of treatment.

Hematologic and Laboratory Features

The main hematologic features are a normocytic, normochromic
194
anemia and moderate thrombocytopenia. The anemia of trypano-
somiasis is multifactorial. Hemodilution, hemolysis, and dyserythro-
poiesis or ineffective erythropoiesis all contribute to the pathogenesis.
Hemolysis may be caused directly by lytic factors released by trypano-
somes or indirectly by deposition of immune complexes and subse-
quent clearance of coated erythrocytes. In vitro studies have suggested Fig. 158.11 TRYPANOSOMA BRUCEI RHODESIENSE IN HUMAN
that the variant surface glycoprotein from trypanosomes may be shed BLOOD. T. brucei brucei parasitizes wild and domestic animals but does not
and taken up onto the erythrocyte membrane, where antibody and infect humans. The different subspecies can be distinguished with certainty
complement deposition could contribute to hemolysis. Bone marrow only by biochemical techniques, such as electrophoretic typing of their iso-
response is inadequate, and although the nature of the defect is enzymes or by the use of DNA probes. T. brucei gambiense and T. b. rhodesiense
unclear, there is failure in incorporation of iron into erythroid precur- (and T. b. brucei of animals) are virtually indistinguishable in blood films.
sors, as is seen in many forms of the anemia of chronic disease. In Note the small kinetoplast and free flagellum. Both subspecies from humans
mice infected with human trypanosomiasis, TNF-α contributes to will infect guinea pigs, but only T. b. rhodesiense is infective to rats, in which
bone marrow suppression, but detailed studies of the pathogenesis of the parasites are polymorphic—that is, long, thin, intermediate, and short,
anemia in human infections have not been reported. Serum IgM stumpy forms of trypomastigotes may coincide.