Abstract
In mice, experimental infection with Trypanosoma brucei causes decreased bone marrow B-cell development, abolished splenic B-cell maturation and loss of antibody mediated protection including vaccine induced memory responses. Nothing is known about this phenomenon in human African trypanosomiasis (HAT), but if occurring, it would imply the need of revaccination of HAT patients after therapy and abolish hope for a HAT vaccine. The effect of gambiense HAT on peripheral blood memory T- and B-cells and on innate and vaccine induced antibody levels was examined. The percentage of memory B- and T-cells was quantified in peripheral blood, prospectively collected in DR Congo from 117 Trypanosoma brucei gambiense infected HAT patients before and six months after treatment and 117 controls at the same time points. Antibodies against carbohydrate antigens on red blood cells and against measles were quantified. Before treatment, significantly higher percentages of memory B-cells, mainly T-independent memory B-cells, were observed in HAT patients compared to controls (CD20+CD27+IgM+, 13.0% versus 2.0%, p<0.001). The percentage of memory T-cells, mainly early effector/memory T-cells, was higher in HAT (CD3+CD45RO+CD27+, 19.4% versus 16.7%, p = 0.003). After treatment, the percentage of memory T-cells normalized, the percentage of memory B-cells did not. The median anti-red blood cell carbohydrate IgM level was one titer lower in HAT patients than in controls (p<0.004), and partially normalized after treatment. Anti-measles antibody concentrations were lower in HAT patients than in controls (medians of 1500 versus 2250 mIU/ml, p = 0.02), and remained so after treatment, but were above the cut-off level assumed to provide protection in 94.8% of HAT patients, before and after treatment (versus 98.3% of controls, p = 0.3). Although functionality of the B-cells was not verified, the results suggest that immunity was conserved in T.b. gambiense infected HAT patients and that B-cell dysfunction might not be that severe as in mouse models.
Highlights
Human African Trypanosomiasis (HAT) or sleeping sickness, is a vector-borne parasitic disease occurring in sub-Saharan Africa
We show that gambiense human sleeping sickness is associated with a relevant increase in memory T- and B- cells in peripheral blood, in particular Tindependent memory B-cells
Inclusion criteria for controls were absence of clinical evidence for HAT, absence of trypanosome specific antibodies in whole blood detected by card agglutination test for trypanosomiasis (CATT) [13]; no trypanosomes in blood detected by the mini anion exchange centrifugation technique [14] and being 12 years or older
Summary
Human African Trypanosomiasis (HAT) or sleeping sickness, is a vector-borne parasitic disease occurring in sub-Saharan Africa. About 70 million persons are at risk for infection and 30 000 persons are estimated to be infected [1]. The parasites concerned belong to the Trypanosoma genus and are transmitted through the bites of tsetse flies (Glossina genus). Two subspecies of Trypanosoma brucei (T.b.), T.b. gambiense and T.b. rhodesiense, are responsible for human infection, which is usually fatal if left untreated. Infection with T.b. gambiense is responsible for chronic HAT in West- and Central-Africa, and characterized by low parasite numbers. In East-Africa, infection with T.b. rhodesiense leads to acute disease with relatively high parasite loads. Control of HAT relies on a combination of accurate diagnosis of cases, treatment of detected cases, and on control of the tsetse fly vector.
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