Research Articles
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A research article reports the results of original research, assesses its contribution to the body of knowledge in a given area, and is published in a peer-reviewed scholarly journal. The faculty publications through published and on-going articles/researches are captured in this community
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Item A Survey of Anaemia in Children in the Korle Bu Hospital, with Special Reference to Malaria(Ghana Medical Journal, 1964-09) Jilly, P.; Nkrumah, F.K.Item Reversible suppression of bone marrow response to erythropoietin in plasmodium falciparum malaria.(British Journal of Haematology, 1997) Kurtzhals, J.A.L.; Rodrigues, O.; Addae, M.; Commey, J.O.O.; Nkrumah, F.K.; Hviid, L.To study the importance of bone marrow inhibition in the pathogenesis of malarial anaemia, haematological and parasitological parameters were followed in patients with acute malaria. Three patient categories were studied, severe malarial anaemia (SA), cerebral malaria (CM) and uncomplicated malaria (UM). Red cell distribution width (RDW) was used as a surrogate marker of release of young erythrocytes and reticulocytes. Initially RDW was low in all patients in spite of markedly increased concentrations of erythropoietin (EPO). 3 d after institution of treatment and coinciding with parasite clearance RDW increased dramatically, reaching the highest levels 1–2 weeks later. Although severe anaemia was corrected by blood transfusion during the first 3 d of treatment, the peak RDW correlated significantly with the initial EPO levels. This suggests that Plasmodium falciparum infection causes a rapidly reversible suppression of the bone marrow response to EPO. Furthermore, the inhibition of bone marrow response was a general finding irrespective of initial haemoglobin levels suggesting that the severity of anaemia depends upon the degree of peripheral erythrocyte destruction in patients with suppressed bone marrow response to EPO.Item Increased eosinophil activity in acute plasmodium falciparum infection - association with cerebral malaria.(Clinical and Experimental Immunology, 1998) Kurtzhals, J.A.L.; Reimert, C.M.; Tette, E.; Dunyo, S.K.; Koram, K.A.; Akanmori, B.D.; Nkrumah, F.K.; Hviid, L.To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8–10.7 ng/ml)) than in SA (4.7 ng/ml (3.0–7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6–5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.Item Seasonal profiles of malaria infection, anaemia, and bednet use among age groups and communities in northern Ghana.(Tropical Medicine and International Health, 2003) Koram, K.A.; Owusu-Agyei, S.; Fryauff, D.J.; Anto, F.; Atuguba, F.; Hodgson, A.; Hoffman, S.L.; Nkrumah, F.K.We conducted all-age point prevalence surveys to profile the severity and seasonality of malaria and anaemia in Kassena-Nankana District of northern Ghana. Random cross-sectional surveys were timed to coincide with the end of low (May 2001) and high (November 2001) malaria transmission seasons and to yield information as to the potential value of haemoglobin (Hb) levels and parasitaemia as markers of malaria morbidity and/or malaria vaccine effect. Parasitaemia was found in 22% (515 of 2286) screened in May (dry-low transmission), and in 61% of the general population (1026 of 1676) screened in November (wet-high transmission). Malaria prevalence in May ranged from 4% (infants <6 months and adults 50–60 years) to 54% (children 5–10 years). Age-specific malaria prevalence in November ranged from 38% (adults 50–60 years) to 82% (children 5–10 years). Differences between low- and high-transmission periods in the prevalence of severe anaemia (SA) among young children (6–24 months) were unexpectedly comparable (low, 3.9%vs. high, 5.4%; P = 0.52) and greatly reduced from levels measured in this same community and age group in November 2000 (12.5%) and November 1996 (22.0%). Despite the lower frequency of anaemia/SA in young children surveyed in 2001, it was still clear that this condition was strongly associated with parasitaemia and that children under 5 years of age experienced a significant drop in their mean Hb levels by the end of the high transmission season. Prevalence of parasitaemia was significantly lower (P < 0.01) among infants and young children (<2 years) whose parents reported the use of bednets. There was a significantly lower risk of parasitaemia among infants [odds ratio (OR) 6–8] and young children (OR 3–4) living in the central, more urbanized sector of the study area.Item High frequency of circulating γδ T cells with dominance of the V(δ)1 subset in a healthy population.(International Immunology, 2000) Hviid, L.; Akanmori, B.D.; Loizon, S.; Kurtzhals, J.A.L.; Ricke, C.H.; Lim, A.; Koram, K.A.; Nkrumah, F.K.; Mercereau-Puijalon, O.; Behr, C.TCR γδ+ cells constitute <5% of all circulating T cells in healthy, adult Caucasians, and Vδ1+ cells constitute a minority of these cells. In contrast to TCR αβ+ cells, their repertoire is selected extrathymically by environmental antigens. Although increased frequencies of Vδ1+ cells are found in several diseases, their function remains obscure. Here we show that the frequency of peripheral blood γδ T cells in healthy West Africans is about twice that of Caucasians, mainly due to a 5-fold increase in Vδ1+ cells, which is consequently the dominant subset. No age dependency of Vδ1 frequencies was identified and the Vδ1+ cells in the African donors did not show preferential Vγ chain usage. Analysis of the CDR3 region size did not reveal any particular skewing of the Vδ1 repertoire, although oligoclonality was more pronounced in adults compared to children. The proportions of CD8+, CD38+ and CD45RAhiCD45RO– cells within the Vδ1+ subset were higher in the African than in the European donors, without obvious differences in expression of activation markers. No significant correlations between levels of Vδ1+ cells and environmental antigens or immunological parameters were identified. Taken together, the evidence argues against a CDR3-restricted, antigen-driven expansion of Vδ1+ cells in the African study population. Our study shows that high frequencies of TCR γδ+ cells with dominance of the Vδ1+ subset can occur at the population level in healthy people, raising questions about the physiological role of Vδ1+ T cells in the function and regulation of the immune system.Item Malaria vector studies in two ecological zones in southern Ghana.(African Entomology, 2001) Appawu, M.A.; Baffoe-Wilmot, A.; Afari, E.A.; Dunyo, S.; Koram, K.A.; Nkrumah, F.K.A two-year longitudinal malaria vector study was carried out in two communities, Dodowa and Prampram, located in the coastal forest and coastal savannah zones, respectively, of the Dangme West district of Ghana. Anopheles gambiae s.l. Giles was most prevalent in both study areas, followed by An. funestus Giles in Dodowa and An. pharoensis Theobald in Prampram. Anopheles gambiae s.s. occurred in sympatry with An. melas Theobald in Prampram. Small numbers of An. nili Theobald, An. hancocki Edwards, An. coustani Laveran, An. moucheti Evans and An. hargreavesi Evans were collected in Dodowa and their role in transmission was negligible. Anopheles gambiae s.l. and An. funestus were found to be the major human-biting species in Dodowa, while An. gambiae s.l. and An. pharoensis were the most common biting mosquitoes in Prampram. The overall biting rate of the anophelines at Dodowa was twice that at Prampram. Anopheles gambiae s.l. and An. funestus were identified as the main vectors of malaria by salivary gland dissections. Overall mean infectivity rate of both species was approximately 2.5 times higher at Dodowa than at Prampram. Anopheles pharoensis was not found to be infected with Plasmodium parasites. The intensity of malaria transmission at Dodowa, the coastal forest area, was about six times higher than Prampram, the coastal savanna area. Some aspects of control strategies are discussed.Item Distinct patterns of cytokine regulation in discrete clinical forms of plasmodium falciparum malaria.(European Cytokine Network, 2000) Akanmori, B.D.; Kurtzhals, J.A.L.; Goka, B.Q.; Adabayeri, V.; Ofori, M.F.; Nkrumah, F.K.; Behr, C.; Hviid, L.The pathogenesis of two of the most severe complications of Plasmodium falciparum malaria, cerebral malaria (CM) and severe malarial anaemia (SA) both appear to involve dysregulation of the immune system. We have measured plasma levels of TNF and its two receptors in Ghanaian children with strictly defined cerebral malaria (CM), severe malarial anaemia (SA), or uncomplicated malaria (UM) in two independent studies in an area of seasonal, hyperendemic transmission of P. falciparum. Levels of TNF, soluble TNF receptor 1 (sTNF-R1) and 2 (sTNF-R2) were found to be significantly higher in CM than in the other clinical categories of P. falciparum malaria patients. Levels of both receptors depended on clinical category, whereas only sTNF-R1 levels were significantly dependent on parasitemia. Detailed analysis of the interrelationship between these variables resolved this pattern further, and identified marked differences between the patient categories. While levels of TNF, sTNF-R1 and sTNF-R2 correlated with parasitemia in UM, this was not the case in CM and SA. Rather, there was a tendency towards high levels of TNF and its receptors in CM and low levels in SA without significant correlation to parasitemia in either category. This, and the fact that malaria-induced increases in plasma levels of IL-10 are much lower in SA compared to CM, suggest that distinct forms of dysregulation of the immune response to infection contribute to the pathogenesis of CM and SA.