Selective activation of TCR-γδ+ cells in endemic Burkitt's lymphoma

<p>Abstract</p> <p>Background</p> <p>The overlap in geographical distribution of <it>Plasmodium falciparum </it>malaria and endemic Burkitt's lymphoma (eBL) – an aggressive Epstein-Barr virus (EBV)-associated B-cell tumour occurring almost exclusively in the tropics – strongly suggests a link between the two diseases. It is suspected that the polyclonal B-cell activation in <it>P. falciparum </it>malaria may precipitate a breakdown in homeostatic T-cell control of EBV-immortalized B-cell proliferation. Previous studies have suggested that a particular T-cell subset, characterized by expression of V<it>δ</it>1⁺<it>γδ </it>T-cell receptors, is important for maintaining B-cell homeostasis, both in <it>P. falciparum</it>- exposed populations and in individuals subject to polyclonal B-cell activation of other aetiology. The objective of the present study was, therefore, to characterize lymphocyte phenotypes and to investigate possible differences in T-cell subset composition and activation status in <it>P. falciparum</it>-exposed Ghanaian children with and without eBL.</p> <p>Methods</p> <p>Venous blood samples in heparin from 21 eBL patients (mean age: 7.0 years; range: 3–11 years), referred to the Burkitt's Tumour Centre at Korle-Bu Teaching Hospital, Accra and 15 healthy, age and sex matched children, were stained with fluorescein isothiocyanate (FITC)-, phycoerythrin (PE)-, R-phycoerythrin (RPE)- and RPE-Cy5-conjugated antibodies (CD3, CD4, CD8, CD25, CD69, CD95, HLA-DR, TCR-<it>γδ</it>, V<it>δ</it>1, V<it>δ</it>3, V<it>γ</it>9 and B-cells) and acquired on a flow cytometer.</p> <p>Results</p> <p>A reduction in the proportion of CD3⁺cells in eBL patients, due mainly to perturbations among TCR-<it>γδ</it>⁺cells was observed. In contrast, the proportions of CD4⁺or CD8⁺cells were relatively unaffected, as were the mean numbers of peripheral blood mononuclear cells.</p> <p>Conclusion</p> <p>Selective changes in numbers and activation status of TCR-<it>γδ</it>⁺cells occurs in Ghanaian children with eBL, a pattern which is similar to <it>P. falciparum</it>-induced changes. The data supports the hypothesis of a regulatory role for V<it>δ</it>1⁺TcR-<it>γδ </it>T-cells in maintaining B-cell homeostasis and provides insights into the pathogenesis of eBL.</p

Community-based Cluster Surveys on Treatment Preferences for Diarrhoea, Severe Diarrhoea, and Dysentery in Children Aged Less Than Five Years in Two Districts of Ghana

ABSTRACT Hospital-based surveillance for severe diarrhoea has been recommended to assess the burden of disease due to rotavirus. However, information on healthcare-seeking patterns of residents in the hospital catchment area is needed first to obtain the burden of disease in the community using the hospital data. A community-based cluster survey was conducted in two districts of Ghana, each served by a single district hospital, to determine the prevalence of severe diarrhoea among and treatment preferences for children aged less than five years. Caretakers of 619 children in Tema, an urban district, and caretakers of 611 children in Akwapim South, a rural district, were interviewed. During the month preceding the survey, the prevalence of severe diarrhoea in children aged less than five years was similar in the two districts (13.6% urban and 12.9% rural), as was the proportion of mothers who sought care outside the home (69.0% urban and 70.9% rural). 48.8% of urban mothers of children with severe diarrhoea visited public/private clinics, 9.5% pharmacies, and 3.6% the district hospital. Whereas, 22.8% of rural mothers visited public/private clinics, 19.0% pharmacies, and 13.9% the district hospital. Results of the study suggest that rotavirus surveillance should be guided by community studies on healthcare-use patterns. Where hospital use is low for severe diarrhoea, rotavirus surveillance should include other health facilities

Community-based Cluster Surveys on Treatment Preferences for Diarrhoea, Severe Diarrhoea, and Dysentery in Children Aged Less Than Five Years in Two Districts of Ghana

Hospital-based surveillance for severe diarrhoea has been recommended to assess the burden of disease due to rotavirus. However, information on healthcare-seeking patterns of residents in the hospital catchment area is needed first to obtain the burden of disease in the community using the hospital data. A community-based cluster survey was conducted in two districts of Ghana, each served by a single district hospital, to determine the prevalence of severe diarrhoea among and treatment preferences for children aged less than five years. Caretakers of 619 children in Tema, an urban district, and caretakers of 611 children in Akwapim South, a rural district, were interviewed. During the month preceding the survey, the prevalence of severe diarrhoea in children aged less than five years was similar in the two districts (13.6% urban and 12.9% rural), as was the proportion of mothers who sought care outside the home (69.0% urban and 70.9% rural). 48.8% of urban mothers of children with severe diarrhoea visited public/private clinics, 9.5% pharmacies, and 3.6% the district hospital. Whereas, 22.8% of rural mothers visited public/private clinics, 19.0% pharmacies, and 13.9% the district hospital. Results of the study suggest that rotavirus surveillance should be guided by community studies on healthcare-use patterns. Where hospital use is low for severe diarrhoea, rotavirus surveillance should include other health facilities

High Levels of IL-10 and CD4+CD25hi+ Treg Cells in Endemic Burkitt’s Lymphoma Patients

Background: The interplay between Epstein-Barr virus infection, malaria, and endemic Burkitt’s Lymphoma is not well understood. Reports show diminished EBV-specific Th1 responses in children living in malaria endemic areas and deficiency of EBNA1-specific IFN-γ T cell responses in children with endemic Burkitt’s Lymphoma (eBL). This study, therefore, examined some factors involved in the loss of EBNA-1-specific T cell responses in eBL. Methods: T-cell subset frequencies, activation, and IFN-γ- or IL-4-specific responses were analyzed by flow-cytometry. Plasma cytokine levels were measured by ELISA. Results: CD4+ and CD8+ cells in age- and sex-matched healthy controls (n = 3) expressed more IFN-γ in response to all immunostimulants than in pediatric endemic BL (eBL) patients (n = 4). In healthy controls, IFN-γ expression was higher than IL-4 expression, whereas in eBL patients the expression of IL-4 by CD4+ cells to EBNA-1 was slightly higher than IFN-γ. Moreover, the blood levels of TNF-α was significantly lower (p = 0.004) while IL-10 was significantly higher (p = 0.038), in eBL patients (n = 21) compared to controls (n = 16). Additionally, the frequency of CD4+CD25hi+ T cells was higher in both age-matched acute uncomplicated malaria (n = 26) and eBL (n = 14) patients compared to healthy controls (n = 19; p = 0.000 and p = 0.027, respectively). Conclusion: The data suggest that reduced Th1 response in eBL might be due to increased levels of IL-10 and T reg cells