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Trypanosoma Gambiense Life Cycle
— Trypanosoma gambiense and rhodesiense: Life Cycle -
Trypanosome Fission Longitudinale

Fig. 9.6 Human blood: 1 trypomastigote, slender form with variant specific surface antigen (VSSA); 2 binary fission form; 3, 4 slender forms with other VSSA type; 5 short ("stumpy") form.

Glossina intestine: 6-8 procyclic forms without VSSA (reproduction by longitudinal fission).

Salivary gland of Glossina: 9, 10 epimastigote forms on epithelium; 11 trypomastigote form without VSSA; 12 trypomastigote form with VSSA (metacyclic form). (According to Vickerman K, Barry JE, in Kreier JP, Baker JR, eds. Parasitic Protozoa, Vol. 2, San Diego: Academic Press; 1992: 94.)

Fig. 9.6 Human blood: 1 trypomastigote, slender form with variant specific surface antigen (VSSA); 2 binary fission form; 3, 4 slender forms with other VSSA type; 5 short ("stumpy") form.

Glossina intestine: 6-8 procyclic forms without VSSA (reproduction by longitudinal fission).

Salivary gland of Glossina: 9, 10 epimastigote forms on epithelium; 11 trypomastigote form without VSSA; 12 trypomastigote form with VSSA (metacyclic form). (According to Vickerman K, Barry JE, in Kreier JP, Baker JR, eds. Parasitic Protozoa, Vol. 2, San Diego: Academic Press; 1992: 94.)

Epidemiology. There are epidemiological differences between T. gambiense and T. rhodesiense (Table 9.2), the main one being that T. rhodesiense persists in a latent enzootic cycle in wild and domestic animals and is normally transmitted by Glossina from animal to animal, more rarely to humans. T. gambiense, on the other hand, is transmitted mainly from human to human by the tsetse flies, although various animal species have also been identified as reservoir hosts for T. gambiense strains.

Clinical manifestations. Sleeping sickness is, in the initial phase, a febrile, generalized disease with lymphadenopathy and is later characterized by meningoencephalitic symptoms. The infection runs a two-stage course: the febrile-glandular or hemolymphatic stage 1 and the meningoencephalitic stage 2. The difference is therapeutically significant. In stage 1, the trypano-somes multiply in the tissue fluid at the inoculation site. Within 2-4 days an inflammatory, edematous swelling can develop—the primary lesion or "trypanosome chancre," which then disappears within about three weeks. Within a period of approximately two weeks the trypanosomes enter the bloodstream and lymphatic system. Later, in the second stage, they also invade the central nervous system. Table 9.3 summarizes further details of the disease.

Table 9.2 Epidemiological Differences between Trypanosoma gambiense and T. rhodesiense

Parameter

T. gambiense

T. rhodesiense

Distribution:

Western and central Africa

Eastern and central Africa

Vector:

Glossina palpalis group:

G. morsitans group:

Moist biotopes

Savanna biotopes

Sites of transmission:

■ Frequently focal:

At rivers, lakes,

-

watering holes, etc.

■ Less localized:

In moist forest areas

Savannas

Dominant cycle:

Human ! human

Wild and domestic ruminants,

other wild animals ! humans

Reservoir hosts

Pigs, cattle, sheep, dogs,

Antelope species, cattle,

(for certain

a small number of antelope

sheep, goats, warthogs, lions,

Trypanosoma strains)

species

hyenas, dogs, etc.

Table 9.3 Infection Course and Clinical Manifestations of Sleeping Sickness

Stage, course and symptoms

T. gambiense

T. rhodesiense

1st stage: Febrile-glandular or hemolymphatic phase

■ Trypanosome chancre

■ Onset of parasitemia:

■ Type of parasitemia:

Parasitemia-associated symptoms:

Course:

In Africans: <5% In Europeans: approximately 20%

Low-level, intermittent

Approximately 50%

High-level, often persistent

Fever, chills, headache, joint and muscle pain, transitory edemas, weight loss, generalized lymphadenopa-thy (swelling of lymph nodes in neck = Winterbot-tom's sign); cardiac dysfunction (especially in T. rhodesiense infections), anemia, thrombocytopenia, raised serum IgM

Chronic (also acute in persons without immunity)

2nd stage: Meningoencephalitic phase

Penetration of trypano- 4-6 months p.i. or later Frequently after only a few somes into CNS: weeks

Symptoms: Signs of progressive meningoencephalitis, epilepti form convulsions, later somnolence, apathy, coma. Pleocytosis in cerebrospinal fluid, raised total protein and IgM levels.

Duration of disease, Months to >6 years Rarely >3-7 months both stages

Pathogenesis and immunology. The course of the infection is characterized by successive waves of parasitemia caused by antigenic variation in successive trypanosome populations (see above). Parallel to an increasing parasite-mia, IgM antibodies are produced that are directed against a certain variant specific surface antigen (VSSA) of the trypanosomes, whereupon they eliminate the segment of the parasite population bearing this VSSA. The parasi-temia then declines, but the trypanosomes with a different VSSA multiply, whereupon specific antibodies are once again produced. Antigen variation is one of a number of strategies to circumvent host defenses (immunoevasion). About the time when one VSSA variant of trypanosomes is being eliminated from the body, the concentrations of IgG antibodies rise and immune complexes form.

Many factors contribute to the pathogenesis of sleeping sickness, among them the activation of kallikrein, kinin, complement, and the coagulation system by circulating immune complexes (resulting in increased vascular permeability, edema, hemostasis, tissue hypoxia, tissue damage, disseminated intravasal coagulation), in addition anemia, deposition of immune complexes in the kidneys and other organs, immunosuppression, endocrinal disturbances, and CNS damage. The trypanosomes cause CD8+ T cells and macrophages to produce IFNy and TNF. IFNy stimulates trypanosomes to multiply. TNF contributes to immunosuppression and may initiate tissue damage.

Diagnosis. Important diagnostic tools include direct detection of the trypa-nosomes in the blood, lymph node aspirate and, in cerebral forms, in the ce-rebrospinal fluid (Fig. 9.5). Trypanosomes can be detected in native blood preparations, in Giemsa-stained thin smears or in thick blood films (p. 622). Since low-level parasitemias are often present, concentration methods may be required, e.g., microhematocrit centrifugation, anion exchange chromatography, or the QBC technique (p. 531). Other methods are cultivation and mouse inoculation tests (suitable for T. rhodesiense). Analysis of lymph node aspirate has a high diagnostic value in infections with T. gam-biense. To confirm or exclude CNS infections obtain a cerebrospinal fluid sample, centrifuge it, and examine the sediment for trypanosomes. Antibodies in the bloodstream can be detected using various techniques (p. 625). The card agglutination trypanosomosis test (CATT) has proved valuable in epidemiological surveys. Indicators of a stage 2 infection include presence of trypanosomes and/or raised leukocyte numbers and elevated concentrations of protein and IgM in cerebrospinal fluid.

Therapy. Medical treatment of sleeping sickness is highly problematical, since only a small number of effective drugs are available, serious side effects are fairly frequent and drug-resistant trypanosomes are to be expected. In stage 1, T. gambiense infections are mainly treated with pentamidine, whereas T. rhodesiense infections are treated with suramin. These drugs are not effective in the second stage (cerebrospinal fluid-positive cases), so that the arsenic compound melarsoprol, a relatively toxic substance, must be used in these cases. The worst side effect of this substance is a potentially lethal en-cephalopathy observed in 1-10% of patients treated with melarsoprol. Eflor-nithine is used for treating the late stage of the T. gamibiense infection. Treatment of sleeping sickness victims should be entrusted to specialists if possible.

Prevention and control. Use individual prophylactic measures to protect against the diurnally active (!) Glossina flies. It is very important that tourists wear clothing that covers the skin as much as possible and treat uncovered skin with repellents (see Malaria, p. 535). They should also inspect the inte rior of cars for tsetse flies and spray with insecticides. Glossina flies are targeted by insecticide sprayings in preventive programs. More recently, the flies are also being caught in insecticide-charged traps using attractant colors and odors.

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