Browsing by Author "Tetteh, J.K."

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Cerebral malaria is associated with low levels of circulating endothelial progenitor cells in African children
(American Journal of Tropical Medicine and Hygiene, 2009) Gyan, B.; Goka, B.Q.; Adjei, G.O.; Tetteh, J.K.; Kusi, K.A.; Aikins, A.; Dodoo, D.; Lesser, M.L.; Sison, C.P.; Das, S.; Howard, M.E.; Milbank, E.; Fischer, K.; Rafii, S.; Jin, D.; Golightly, L.M.
Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells and plasma levels of the chemokine stromal cell-derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebral malaria.
Cerebral malaria is associated with low levels of circulating endothelial progenitor cells in African children
(American Journal Trop. Med. Hyg. 80(4): 541-6, 2009) Adjei, G.O.; Gyan, B.; Goka, B.Q.; Tetteh, J.K.; Kusi, K.A.; Aikins, A.; Dodoo, D.; Lesser, M.L.; Sison, C.P.; Das, S.; Howard, M.E.; Milbank, E.; Fischer, K.; Rafii, S.; Jin, D.; Golightly, L.M.
Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells and plasma levels of the chemokine stromal cell-derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebral malaria.
Complement activation in Ghanaian children with severe Plasmodium falciparum malaria
(Malaria Journal, 2007) Helegbe, G.K.; Goka, B.Q.; Kurtzhals, J.A.; Addae, M.M.; Ollaga, E.; Tetteh, J.K.; Dodoo, D.; Ofori, M.F.; Obeng-Adjei, G.; Hirayama, K.; Awandare, G.A.; Akanmori, B.D.
Severe anaemia (SA), intravascular haemolysis (IVH) and respiratory distress (RD) are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. METHODS: The direct Coombs test (DCT) and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3balphabeta) and the regulatory proteins [complement receptor 1 (CD35) and decay accelerating factor (CD55)] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb) levels and RD were investigated. RESULTS: Of the 484 samples tested, 131(27%) were positive in DCT, out of which 115/131 (87.8%) were positive for C3d alone while 16/131 (12.2%) were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2-6.7, p < 0.001). DCT correlated significantly with RD (beta = -304, p = 0.006), but multiple regression analysis revealed that, Hb (beta = -0.341, p = 0.012) and coma (beta = -0.256, p = 0.034) were stronger predictors of RD than DCT (beta = 0.228, p = 0.061). DCT was also not associated with IVH, p = 0.19, while spleen size was inversely correlated with Hb (r = -402, p = 0.001). Flow cytometry showed similar mean fluorescent intensity (MFI) values of CD35, CD55 and C3balphabeta levels on the surfaces of RBC in patients and asymptomatic controls (AC). However, binding of C3balphabeta correlated significantly with CD35 or CD55 (p < 0.001). CONCLUSION: These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding
Complement activation in Ghanaian children with severe Plasmodium falciparum malaria
(Malaria Journal, 2007) Helegbe, G.K.; Goka, B.Q.; Kurtzhals, J.A.; Addae, M.M.; Ollaga, E.; Tetteh, J.K.; Dodoo, D.; Ofori, M.F; Obeng-Adjei, G.; Hirayama, K.; Awandare, G.A.; Akanmori, B.D.
Severe anaemia (SA), intravascular haemolysis (IVH) and respiratory distress (RD) are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. METHODS: The direct Coombs test (DCT) and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3balphabeta) and the regulatory proteins [complement receptor 1 (CD35) and decay accelerating factor (CD55)] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb) levels and RD were investigated. RESULTS: Of the 484 samples tested, 131(27%) were positive in DCT, out of which 115/131 (87.8%) were positive for C3d alone while 16/131 (12.2%) were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2-6.7, p < 0.001). DCT correlated significantly with RD (beta = -304, p = 0.006), but multiple regression analysis revealed that, Hb (beta = -0.341, p = 0.012) and coma (beta = -0.256, p = 0.034) were stronger predictors of RD than DCT (beta = 0.228, p = 0.061). DCT was also not associated with IVH, p = 0.19, while spleen size was inversely correlated with Hb (r = -402, p = 0.001). Flow cytometry showed similar mean fluorescent intensity (MFI) values of CD35, CD55 and C3balphabeta levels on the surfaces of RBC in patients and asymptomatic controls (AC). However, binding of C3balphabeta correlated significantly with CD35 or CD55 (p < 0.001). CONCLUSION: These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding.
Insights into deregulated TNF and IL-10 production in malaria: Implications for understanding severe malarial anaemia
(Malaria Journal, 2012) Boeuf, P.S.; Loizon, S.; Awandare, G.A.; Tetteh, J.K.; Addae, M.M.; Adjei, G.O.; 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.
Multiple Sexual Partnerships in Ghana Evidence from 2003 Ghana Demograhic and Health Survey (GDHS, 2003)
(University Of Ghana, 2009-07) Tetteh, J.K.
The objective of the study was to examine the magnitude and determinants of multiple sexual partnerships with regard to men's sexual behaviour in Ghana and the implication for public policy. The study employed data from the 2003 Ghana Demographic and Health Survey (GDHS, 2003) to examine the relationships between some selected socio-economic and demographic factors and sexual partnerships in Ghana. Nine independent variables formed the socio-economic characteristics of respondents. These were: age, marital status, occupation, religion, place of residence, region, wealth, age at first sex and education. The levels of sexual partnerships by background characteristics wee shown in the study. Both bivariate and multivariate analyses were employed to identify the most important factors determining sexual partnerships in Ghana. For the multivariate analysis, the logistic regression model was used. The study revealed that multiple sexual partnerships exists, and that about 15% of men aged 15 to 59 years are engaging in multiple sexual partnerships in Ghana. This sexual behaviour varies with socio-economic status of respondents. The study further shows that the most influencing factors of this behaviour are: occupational and educational status of respondents, place of residence and age at first sex. For example, bivariate analysis indicated that age at first sex has an inverse relationship with multiple sexual partnerships. It was also found that men in urban communities and those with high level of education are more likely to have more than one sexual partner than men in rural localities and those without any formal education ~espectively. These results were also substantiated by the multivariate or logistic analysis. The study made several recommendations including the importance of making sex education as part of the school curricular from basic to Junior High School level and the setting up of recreational and communities centers across the country. At these centers, indoor and outdoor games as well as counseling sections on issues about sex and the importance of family planning should form part of the programs for the youth. Older men in our communities were also called upon to show excellent examples for the youth to follow, especially married men who must realize the importance of faithfulness and respect for their wives, the people they love.
Multiple Sexual Partnerships in Ghana Evidence from 2003 Ghana Demograhic and Health Survey (GDHS, 2003)
(University of Ghana, 2009-07) Tetteh, J.K.
The objective of the study was to examine the magnitude and determinants of multiple sexual partnerships with regard to men's sexual behaviour in Ghana and the implication for public policy. The study employed data from the 2003 Ghana Demographic and Health Survey (GDHS, 2003) to examine the relationships between some selected socio-economic and demographic factors and sexual partnerships in Ghana. Nine independent variables formed the socio-economic characteristics of respondents. These were: age, marital status, occupation, religion, place of residence, region, wealth, age at first sex and education. The levels of sexual partnerships by background characteristics wee shown in the study. Both bivariate and multivariate analyses were employed to identify the most important factors determining sexual partnerships in Ghana. For the multivariate analysis, the logistic regression model was used. The study revealed that multiple sexual partnerships exists, and that about 15% of men aged 15 to 59 years are engaging in multiple sexual partnerships in Ghana. This sexual behaviour varies with socio-economic status of respondents. The study further shows that the most influencing factors of this behaviour are: occupational and educational status of respondents, place of residence and age at first sex. For example, bivariate analysis indicated that age at first sex has an inverse relationship with multiple sexual partnerships. It was also found that men in urban communities and those with high level of education are more likely to have more than one sexual partner than men in rural localities and those without any formal education ~espectively. These results were also substantiated by the multivariate or logistic analysis. The study made several recommendations including the importance of making sex education as part of the school curricular from basic to Junior High School level and the setting up of recreational and communities centers across the country. At these centers, indoor and outdoor games as well as counseling sections on issues about sex and the importance of family planning should form part of the programs for the youth. Older men in our communities were also called upon to show excellent examples for the youth to follow, especially married men who must realize the importance of faithfulness and respect for their wives, the people they love.
Selective activation of TCR-gammadelta+ cells in endemic Burkitt's lymphoma
(Malaria Journal (6): 69, 2007) Futagbi, G.; Welbeck, J.E.; Tetteh, J.K.; Hviid, L.; Akanmori, B.D.
The overlap in geographical distribution of Plasmodium falciparum 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 P. falciparum 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 Vdelta1+ gammadelta T-cell receptors, is important for maintaining B-cell homeostasis, both in P. falciparum- 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 P. falciparum-exposed Ghanaian children with and without eBL. METHODS: 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-gammadelta, Vdelta1, Vdelta3, Vgamma9 and B-cells) and acquired on a flow cytometer. RESULTS: A reduction in the proportion of CD3+ cells in eBL patients, due mainly to perturbations among TCR-gammadelta+ 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. CONCLUSION: Selective changes in numbers and activation status of TCR-gammadelta+ cells occurs in Ghanaian children with eBL, a pattern which is similar to P. falciparum-induced changes. The data supports the hypothesis of a regulatory role for Vdelta1+ TcR-gammadelta T-cells in maintaining B-cell homeostasis and provides insights into the pathogenesis of eBL.
Selective activation of TCR-γδ+ cells in endemic burkitt's lymphoma.
(PubMed, 2007-05-23) Futagbi, G.; Welbeck, J.E.; Tetteh, J.K.; Hviid, L.; Akanmori, B.D.
BACKGROUND: The overlap in geographical distribution of Plasmodium falciparum 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 P. falciparum 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 Vdelta1+ gammadelta T-cell receptors, is important for maintaining B-cell homeostasis, both in P. falciparum- 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 P. falciparum-exposed Ghanaian children with and without eBL. METHODS: 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-gammadelta, Vdelta1, Vdelta3, Vgamma9 and B-cells) and acquired on a flow cytometer. RESULTS: A reduction in the proportion of CD3+ cells in eBL patients, due mainly to perturbations among TCR-gammadelta+ 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. CONCLUSION: Selective changes in numbers and activation status of TCR-gammadelta+ cells occurs in Ghanaian children with eBL, a pattern which is similar to P. falciparum-induced changes. The data supports the hypothesis of a regulatory role for Vdelta1+ TcR-gammadelta T-cells in maintaining B-cell homeostasis and provides insights into the pathogenesis of eBL.
V beta profiles in African children with acute cerebral or uncomplicated malaria: very focused changes among a remarkable global stability
(Microbes and Infection 9(11): 1252-9, 2007) Loizon, S.; Boeuf, P.; Tetteh, J.K.; Goka, B.; Obeng-Adjei, G.; Kurtzhals, J.A.; Rogier, C.; Akanmori, B.D.; Mercereau-Puijalon, O.; Hviid, L.; Behr, C.
T cells are thought to play a critical role in cerebral malaria pathogenesis. However, available evidences are restricted to rodent models in which V beta specific T cell expansion has been associated with neurological syndrome suggesting involvement of superantigens or dominant antigens. Using flow cytometry, we studied the peripheral V beta T cell repertoire of Ghanaian children with cerebral malaria, uncomplicated malaria and asymptomatic control children, to look for either expansion or deletion of specific V beta associated with cerebral malaria. At admission, the general pattern of the repertoire of the patients was very similar, with no major distortion compared to the control group a part a significant increase of the frequency of the V beta 21.3 subset correlating with disease severity and attributed to the CD4 subset. During convalescence very limited fluctuations were observed including a significant decrease of the V beta 21.3 subset and increase of the V beta 20 subset, a subset not detected at admission. The remarkable stability of the V beta repertoire observed in acute malaria either cerebral or uncomplicated argues against the idea that cerebral malaria would result from a T cell-mediated inflammatory shock syndrome driven by some dominant super-antigenic activity(ies). The significance of the reproducible increase of the CD4+V beta 21.3T cell subset deserves further investigations.