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 Fever in Africa and WHO recommendation.(Lancet, 1997) Dunyo, S.K.; Koram, K.A.; Nkrumah, F.K.Item Lack of association between maternal antibody and protection of African infants from malaria infection.(Infection and Immunity, 2000) Riley, E.M.; Wagner, G.E.; Ofori, M.F.; Wheeler, J.G.; Akanmori, B.D.; Tetteh, K.; McGuinness, D.; Bennett, S.; Nkrumah, F.K.; Anders, R.F.; Koram, K.A.Maternally derived antibodies are believed to protect infants against infection, but there is little direct evidence for a protective role of passively acquired antibodies against malaria. A longitudinal study of malaria infection in 143 infants was conducted in a region of southern Ghana where Plasmodium falciparum is endemic. Infants born in the high-transmission season were less likely to become infected in the first 20 weeks of life than children born in the low-transmission season. Plasma, obtained at birth, was tested for immunoglobulin G (IgG) and IgG subclasses to P. falciparum schizonts and recombinant circumsporozoite antigen, MSP-1 19, MSP-2, AMA-1, and Pf155 (also called ring-infected erytrocyte surface antigen). Antibody levels at birth were not associated with resistance to malaria infection. On the contrary, antibodies at birth were positively associated with infection, indicating that high levels of maternally derived antibodies represent a marker for intensity of exposure to malaria infection in infants. However, all five children who experienced high-density infections (>100 parasites/?l of blood) were seronegative for MSP-1 19 at the time of infection.Item Incidence of symptomatic and asymptomatic plasmodium falciparum infection following curative therapy in adult residents of northern Ghana.(American Journal of Tropical Medicine and Hygiene, 2001) Owusu-Agyei, S.; Koram, K.A.; Baird, J.K.; Utz, G.C.; Binka, F.N.; Nkrumah, F.K.; Fryauff, D.J.; Hoffman, S.L.Adult residents of holoendemic malaria regions in Africa have a naturally acquired immunity (NAI) to malaria that renders them more resistant to new infections, limits parasitemia, and reduces the frequency and severity of illness. Given such attributes, it is not clear how one might evaluate drug or vaccine efficacy in adults without serious confounding. To determine symptomatic and asymptomatic malaria attack rates in adults of northern Ghana, 197 men and women underwent curative therapy for any pre-existing malaria infections at the start of the high transmission (wet) season. They were monitored for first parasitemia and first clinical episode of infection by Plasmodium falciparum over a 20-week period (May-October 1996). The cumulative incidence of primary infection by P. falciparum was 0.98 and incidence density of infection was calculated to be 7.0 cases/person-year. Symptoms were reported by 19.5% of the individuals at the time of first recurrent parasitemia. Incidence of infection, parasite density, and the frequency of symptoms were comparable in males and females. The results suggest that NAI did not provide these adults with significant defense against rapid re-infection and suggest that this population-infection design could serve to demonstrate the efficacy of a drug or vaccine in preventing parasitemia.Item Characteristics of severe anemia and its association with malaria in young children of the Kassena-Nankana district of northern Ghana.(American Journal of Tropical Medicine and Hygiene, 2002) Owusu-Agyei, S.; Fryauff, D.J.; Chandramohan, D.; Koram, K.A.; Binka, F.N.; Nkrumah, F.K.; Utz, G.C.; Hoffman, S.L.Severe anemia is thought to be the principal underlying cause of malaria death in areas of intense seasonal malaria transmission such as the Kassena-Nankana District of northern Ghana. Factors associated with severe anemia in young children, 6-24 months old, were elucidated by analyzing results of 2 malaria-associated anemia surveys (1996, 2000), separated by 4 years, but conducted in the same community and at the same seasonal time point. Age-adjusted comparison confirmed that the proportion of severely anemic children and overall mean hemoglobin (Hb) levels in the November 2000 sample were significantly improved over those of the 1996 sample (17.5 versus 26.4%, P = 0.03; Hb 7.5 versus 6.9 g/dL, P = 0.002). Weight-for-age Z-scores also indicated a significant improvement in the 2000 sample (-1.93 versus -2.20, P < 0.05). Independently, each survey identified statistically significant associations between severe anemia and age, parasite rate, fever, and sex. Relative to children with Hb > or = 6.0 g/dL, those with severe anemia (Hb < 6.0 g/dL) were older, more frequently parasitemic (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.08-2.35), more often febrile (OR, 2.44; 95% CI, 1.71-3.48), and predominantly male (OR, 1.50; 95% CI, 1.05-2.13). An association was identified in both surveys between severe anemia and residence in the northern part of the district, but no clear link was observed in relation to irrigation. Blood transfusions, a likely surrogate index of severe anemia in young children, followed a distinct seasonal pattern. Evidence suggests that dramatic peaks and troughs of severe anemia are regular and possibly predictable events that may be used to gauge the health and survival of young children in this area.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 Severe anemia in young children after high and low malaria transmission seasons in the Kassena-Nankana district of northern Ghana.(American Journal of Tropical Medicine and Hygiene, 2000) Koram, K.A.; Owusu-Agyei, S.; Utz, G.; Binka, F.N.; Baird, J.K.; Hoffman, S.L.; Nkrumah, F.K.Malaria and anemia accounted for 41% and 18% respectively of hospital deaths in the Kassena-Nankana district of northern Ghana during 1996. We measured hemoglobin (Hb), malaria prevalence, and anthropometric indices of 6—24-month-old infants and young children randomly selected from this community at the end of the high (May–October, n 347) and low (November–April, n 286) malaria transmission seasons. High transmission season is characterized by rainfall (the equivalent of 800–900 mm/yr.), while the remaining months receive less than 50 mm/yr. Severe anemia, defined as Hb 6.0 g/dL, was 22.1% at the end of the high transmission season compared to 1.4% at the end of the low transmission season (Odds Ratio [OR] 20.1; 95% CI: 7.1–55.3). Parasitemia was 71% and 54.3% at these time points (OR 2.1; 95% CI: 1.5–2.9). Nutritional anemia appeared to have little impact upon this seasonal difference since anthropometric indices were comparable. Although the relative contributions of other causes of severe anemia were not assessed, repeated malaria infections may be a primary determinant of severe anemia among infants and young children during the high transmission season.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 Naturally acquired antibodies to the glutamate-rich protein are associated with protection against plasmodium falciparum malaria.(Journal of Infectious Diseases, 2000) Dodoo, D.; Theisen, M.; Kurtzhals, J.A.L.; Akanmori, B.D.; Koram, K.A.; Jepsen, S.; Nkrumah, F.K.; Theander, T.G.; Hviid, L.The development of effective malaria vaccines depends on the identification of targets of well-defined protective immune responses. Data and samples from a longitudinal study of a cohort of children from coastal Ghana were used to investigate the role of antibody responses to 3 regions of the Plasmodium falciparum glutamate-rich protein (GLURP). The data show that levels of the GLURP-specific IgG that occurs in the nonrepeat region of the antigen are significantly correlated with clinical protection from P. falciparum malaria, after correction for the confounding effect of age. Furthermore, levels of cytophilic antibodies were found to be of particular importance for protection, lending support to the hypothesis that antibody-dependent cellular inhibition is the important element in GLURP-specific protective immunity.Item Anaemia caused by asymptomatic plasmodium falciparum infection in semi-immune african schoolchildren.(1999) Kurtzhals, J.A.L.; Addae, M.M.; Akanmori, B.D.; Dunyo, S.; Koram, K.A.; Appawu, M.A.; Nkrumah, F.K.; Hviid, L.A cohort of 250 Ghanaian schoolchildren aged 5-15 years was followed clinically and parasitologically for 4 months in 1997/98 in order to study the effect of asymptomatic Plasmodium falciparum infections on haematological indices and bone-marrow responses. Of the 250 children 65 met the predefined study criteria. Thus, 14 children were parasite-free throughout (group 1), 44 had P. falciparum in all blood samples collected but no symptoms of malaria (group 2), and 7 had 1 malaria attack during the study period (group 3). At the end of the study the mean haemoglobin (Hb) level in group 1 was 123 g/L, significantly higher than the value of 114 g/L in groups 2 and 3 (P < 0.02, adjusted for age and splenomegaly). The low Hb in group 2 was associated with subnormal plasma iron. Low Hb was associated with elevated erythropoietin (EPO) levels, and there was a positive correlation between EPO and reticulocyte counts. However, the reticulocyte response to EPO was more pronounced in uninfected than in infected children, suggesting a partial interference with erythropoiesis in asymptomatic infections. Children with asymptomatic infections had significantly higher plasma levels of tumour necrosis factor than uninfected children (geometric means 50 ng/L and 27 ng/L, respectively, P < 0.001) and this cytokine may contribute to bone-marrow suppression and disturbed iron metabolism. We suggest that asymptomatic malaria leads to a homeostatic imbalance in which erythrocyte loss due to parasite replication is only partially compensated for by increased erythropoiesis. The consequences of the reduced Hb levels on the development and cognitive abilities of children with asymptomatic infections, and the risk of precipitation of iron deficiency, deserve further study and should be considered in malaria control programmes that aim at reducing morbidity rather than transmission.