Browsing by Author "Awandare, G. A."
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Item Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia(2012-08-01) Boeuf, Philippe S.; Loizon, S.; Awandare, G. A.; Tetteh, John K.A.; Addae, M.M.; Adjei, G.O.; Goka, B.; Kurtzhals, J.; Puijalon, O.; Hviid, L.; Akanmori, B.D.; Behr, C.Abstract Background Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo, but little is known about the activation status of those cells in SMA patients. Methods The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR+ and/or CD69+ surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined. Results Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69+ and HLA-DR+ T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM (P = .003) and UM (P = .004). Although in SMA the IL-10 response to LPS-stimulation was larger in amplitude than in CM (P = .0082), the absolute levels of IL-10 reached were lower (P = .013). Both the amplitude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM (P = .019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM (P = .005) contrasting with TNF levels, which were higher (P = .001). Conclusions These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming/polarization pattern in response to infection.Item Investigation of Dengue Exposure and Infection in Ghanaian Children with Malaria(University of Ghana, 2014-07) Delimini, R. K.; Awandare, G. A.; Stoler, J.; University of Ghana, College of Basic and Applied Sciences, School of Biological Sciences, Department of Biochemistry, Cell and Molecular BiologyBackground: Dengue and malaria are two important mosquito-borne diseases. Together, both diseases are indistinguishable due to similarities in clinical and laboratory characteristics. These similarities have contributed immensely to the over-diagnosis of malaria and the under-recognition of dengue in many countries in sub-Saharan Africa. No baseline study has yet been conducted in Ghana to estimate the burden of dengue. This study therefore set out to estimate the prevalence of dengue infection in a population of Ghanaian children confirmed with malaria. Methods: Archived plasma samples, obtained from 216 study participants aged 2-14 years enrolled in a malaria study, were tested for the presence of dengue using Real-Time Reverse Transcriptase PCR, dengue Rapid Diagnostic Test (RDT) and dengue IgM/IgG capture ELISA. The study was conducted in three ecological zones of Ghana namely: Kintampo, Navrongo and Accra. Results: Dengue RDT and dengue IgM/IgG capture ELISAs estimated a prevalence of 54% and 24%, respectively. Dengue IgG capture ELISA showed that majority of seropositive study participants were positive for IgG (20%) and this was statistically significant between Kintampo and Navrongo. Estimated IgM/IgG ratio of 0.11 indicated that dengue infection was as a consequence of a previous exposure. Further analysis showed that 22% of the study populations were confirmed with exposure to dengue-malaria while exposure to malaria only, dengue only and absence of either diseases was confirmed in 70%, 2% and 6% of study population respectively. Molecular tests indicated negative for dengue in all study participants. Conclusion: Results in the study suggest an exposure to dengue virus in a subset of Ghanaian population. However, the inability to detect and identify circulating serotype calls for more research in this regard.