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 The cytokine balance in severe malarial anemia [5] (multiple letters).(Journal of Infectious Diseases, 1999) Kurtzhals, J.A.L.; Akanmori, B.D.; Quarm Goka, B.; Adabayeri, V.; Nkrumah, F.K.; Behr, C.; Hviid, L.; Othoro, C.; Udhayakumar, V.Item A longitudinal study of malaria infection, morbidity and antibody titres in infants of a rural community in Ghana.(Transactions of the Royal Society of Tropical Medicine and Hygiene, 1995) Akanmori, B.D.; Afari, E.A.; Sakatoku, H.; 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 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 Low plasma concentrations of interleukin-10 in severe malarial anaemia compared with cerebral and uncomplicated malaria.(Lancet, 1998) Kurtzhals, J.A.L.; Adabayeri, V.; Goka, B.Q.; Akanmori, B.D.; Oliver-Commey, J.O.; Nkrumah, F.K.; Behr, C.; Hviid, L.Background Severe anaemia is a major complication of malaria but little is known about its pathogenesis. Experimental models have implicated tumour necrosis factor (TNF) in induction of bone-marow suppression and eythrophagocytosis. Conversely, interleukin 10 (IL-10), which mediates feed-back regulation of TNF, stimulates bone-marrow function in vitro and counteracts anaemia in mice. We investigated the associations of these cytokines with malarial anaemia. Methods We enrolled 175 African children with malaria into two studies in 1995 and 1996. In the first study, children were classified as having severe anaemia (n=10), uncomplicated malaria (n=26), or cerebral anaemia (n=41). In the second study, patients were classified as having cerebral malaria (n=33) or being fully conscious (n=65), and the two groups were subdivided by measured haemoglobin as normal (>110 g/L), moderate anaemia (60–90 g/L), and severe anaemia (>50 g/L). IL-10 and TNF concentrations were measured by ELISA in plasma samples from all patients. Findings IL-10 concentrations were significantly lower in patients with severe anaemia than in all other groups. In 1995, geometric mean plasma IL-10 in patients with severe anaemia was 270 pg/mL (95% CI 152–482) compared with 725 pg/mL (465–1129) in uncomplicated malaria and 966 pg/mL (612–1526) in cerebral malaria (p<0·03). In 1996, fully conscious patients with severe anaemia also had significantly lower IL-10 concentrations than all other groups, including cerebral-malaria patients with severe anaemia and all patients with moderate anaemia (p<0·001). In both studies, TNF concentrations were significantly higher in cerebral malaria than in fully conscious patients (p<0·01). By contrast, the ratio of TNF to IL-10 was significantly higher in fully conscious patients with severe anaemia than in all other groups (p<0·001). Interpretation Our findings identify severe malarial anaemia as a distinct disorder in which insufficient IL-10 response to high TNF concentrations may have a central role.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.Item Pertussis immunization with acellular vaccines in Ghanaian children(1995-06) Hori, H.; Afari, E.A.; Akanmori, B.D.; Kamiya, Y.; Sakatoku, H.; Nkrumah, F.K.; Fukai, K.In the present study, the persistence of antibodies to pertussis antigens was assessed in 51 Ghanaian children immunized with one of two acellular vaccines and one whole cell vaccine in early infancy. The effect of a booster dose 1 year after primary immunization was also examined. Antibody titres to pertussis toxin (PT) and filamentous haemagglutinin (FHA) were measured 1 month and 1 year after primary immunization and 1 month after the booster dose. Although geometric titres (GMTs) to FHA were significantly higher in the two types of acellular vaccinees in the whole cell vaccinees 1 month after primary immunization, GMTs to FHA and PT after 1 year were not significantly different in the three groups. Geometric mean titres to PT and FHA following the booster dose were significantly higher in the acellular vaccinees than in the whole cell vaccinees. Seropositivity rates to PT and FHA in the acellular vaccinees, which were more than 93.3% 1 month after primary immunization, ranged from 50.0 to 77.8% after 1 year. In conclusion, the acellular vaccines did not produce higher antibody levels than the whole cell vaccine 1 year after primary immunization. The booster dose was essential to maintaining sufficient seropositivity to pertussis antigens.Item A randomized controlled trial of two acellular pertussis-diphtheria-tetanus vaccines in primary immunization in Ghana: Antibody responses and adverse reactions(1994) Hori, H.; Afari, E.A.; Akanmori, B.D.; Kamiya, Y.; Sakatoku, H.; Nkrumah, F.K.; Fukai, K.Two acellular pertussis vaccines combined with diphtheria and tetanus toxoids (APDT vaccines) were compared with a whole cell PDT (WCPDT) vaccine in primary immunization in Ghana. One is a liquid vaccine which is used for general immunization in Japan and the other is a freeze-dried vaccine newly developed as a heat-stable vaccine. Eighty-nine infants were recruited in the study. Sixty-eight who completed three doses of the immunization were assessed for immunological responses. Twenty-one dropped out because of sickness or moving from the study area. A total of 242 vaccinations in 89 infants were followed up for adverse reactions. Geometric mean titres (GMTs) to filamentous haemagglutinin in the two APDT vaccinees were significantly higher than in the WCPDT recipients. GMTs to pertussis toxin, diphtheria and tetanus toxoids were not significantly different among the three groups. Seropositive rates to pertussis antigens, tetanus and diphtheria toxoids were 94.4 to 100% in the two APDT vaccines. Systemic reactions within 7 days of inoculation were similarly low in the three groups, but significantly fewer infants had local reactions after either of the two APDT vaccines than after the WCPDT vaccine.