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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    Fever in Africa and WHO recommendation.
    (Lancet, 1997) Dunyo, S.K.; Koram, K.A.; Nkrumah, F.K.
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    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.
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    High incidence of asymptomatic malara infections in a birth cohort of children less than one year of age in Ghana, detected by multicopy gene polymerase chain reaction.
    (1998) Wagner, G.; Koram, K.A.; McGuinness, D.; Bennett, S.; Nkrumah, F.; Riley, E.
    The incidence of Plasmodium falciparum infection has been followed in a birth cohort of 71 infants in southern Ghana, an area of perennial malaria transmission. Parasite DNA detection established the presence of a high rate of infection in newborns (13.6%), a low level of infection from two to 26 weeks (1.5-9.7%) and a steadily increasing parasite rate from 26 weeks of age. The median age to first infection was 42 weeks. Five cases of fever (temperature ≤ 37.5°C) and parasite density greater than 1,000 parasites/μl of blood, all in children more than 18 weeks of age, were considered possible cases of clinical malaria. The risk of infection was almost three times higher in the wet season than in the dry season and increased significantly from the age of 18 weeks. The level of malaria- specific IgG at birth was positively correlated with risk of infection in children 6-12 months of age, indicating that maternally derived anti-malarial IgG is correlated with exposure to malaria infection. There was no association between malaria-specific IgG at birth and risk of infection in children 0-6 months of age. However, infants do appear to possess mechanisms to limit parasite growth and a role for maternal antibody cannot be ruled out.
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    Clinical case definitions for malaria: Clinical malaria associated with very low parasite densities in african infants.
    (1998) McGuinness, D.; Koram, K.A.; Bennett, S.; Wagner, G.; Nkrumah, F.; Riley, E.
    In areas endemic for Plasmodium falciparum, clinical malaria is believed to be less common in infants than in older children, but specific case definitions have rarely been determined for this age group. As malaria case definitions are known to be both age- and site-specific, assessment of the risk of disease in infancy requires the development of appropriate diagnostic criteria. In southern Ghana, 154 children were recruited at birth and monitored for fever and malaria infection until 2 years of age. Logistic regression was used to model fever risk as a continuous function of parasite density to determine case definitions for the diagnosis of clinical malaria, and to determine age- and season-specific estimates of the fraction of fevers attributable to malaria (AF); 2360 observations were made on 154 children. For fevers defined by a measured temperature ≥ 37.5°C, the estimated population AF was 44% (95% confidence interval 34-53). Estimates of AF varied with age and season. For infants, AF was 51% during the wet season and 22% during the dry season; for children over one year of age, AF was 89% during the wet season and 36% during the dry season. The estimated parasite density threshold for initiation of a febrile episode was 100 parasites per μL of blood in infants, compared with 3500 parasites per μL for children over one year of age. Using these case definitions, the incidence of clinical malaria was estimated at 0.09 cases per child-year at risk for children less than 6 months of age, 0.40 for children aged 6-11 months, and 0.69 for children aged 12-23 months. Of 66 cases of clinical malaria, only 3 were observed in children under 5 months of age. We concluded that, although most fevers in infants are not due to malaria, infant clinical malaria may occur at extremely low parasite densities. This may be indicative of a lack of anti-disease immunity in this age group. In southern Ghana, an infant with axillary temperature ≥ 37.5°C and parasitaemia ≥ 100/μL should be considered to have clinical malaria. Nevertheless, the incidence of clinical malaria is very low in children under 6 months of age, confirming that they are significantly protected from clinical malaria compared to older children.
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    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.
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    Socio-economic risk factors for malaria in a peri-urban area of the Gambia.
    (1995) Koram, K.A.; Bennett, S.; Adiamah, J.H.; Greenwood, B.M.
    Successful control of malaria depends upon a detailed knowledge of its epidemiology, including knowledge of the social and economic factors that influence its prevalence. Little is known about the socio-economic factors that influence the prevalence of malaria in tropical Africa. Therefore, we undertook such a study in over 350 Gambian children with malaria resident in a peri-urban area with seasonal transmission, using the case-control approach. Malaria was associated with poor quality housing and crowding and with travel to rural areas, where the level of malaria transmission is higher than in urban centres. No association was found between the risk of malaria and the overall education level of parents or guardians of study children. However, the knowledge of malaria possessed by mothers of cases of malaria was less than that of controls, suggesting that further education of the study community on the causation of malaria and on ways of preventing it could be of value.
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    Socio-economic determinants are not major risk factors for severe malaria in Gambian children.
    (1995) Koram, K.A.; Bennett, S.; Adiamah, J.H.; Greenwood, B.M.
    Only a small proportion of subjects infected with Plasmodium falciparum develop severe disease. Why this should be is not fully understood. To investigate the possible importance of socio-economic variables on the severity of malaria in Gambian children we undertook a case-control study of 384 children with severe or mild malaria. Few differences were found between the 2 groups. Children with severe malaria had a longer duration of symptoms when recruited than mild cases but this difference was largely accounted for by the fact that most children with severe disease were recruited at a referral hospital, whilst mild cases were recruited at a primary health care facility nearer their home. There was no difference between groups in the time before mothers sought some form of health care. Mothers of children with severe disease were less ready to take their child to hospital than mothers of mild cases, suggesting that education on the importance of taking a child with features of malaria to a health centre as soon as possible might have some effect on the development of severe disease. However, overall, the results of this study suggested that socio-economic and behavioural factors are not the major determinants for severe malaria in African children.
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    Comparison of AIK-C measles vaccine in infants at 6 months with schwarz vaccine at 9 months: A randomized controlled trial in Ghana
    (1998) Nkrumah, F.K.; Osei-Kwasi, M.; Dunyo, S.K.; Koram, K.A.; Afari, E.A.
    In a randomized controlled trial in a measles endemic area, standard-dose (4.0 log10pfu) AIK-C measles vaccine administered at 6 months of age was compared to standard-dose Schwarz vaccine (3.7log10pfu) given at 9 months. Seroconversion rates at 3 and 6 months after immunization in the two groups were comparable and similar. The geometric mean titres achieved were, however, significantly higher in the Schwarz group (P < 0.05). No immediate serious side-effects were observed with either vaccine. We conclude that standard-dose AIK-C measles vaccine can be recommended for measles immunization in children below 9 months of age, especially in highly endemic and high-risk areas in developing countries. PIP: The seroresponse of standard-dose heat-stable AIK-C measles vaccine administered to infants at 6 months of age was compared to that of standard-dose Schwarz vaccine administered at 9 months of age in a measles-endemic area in West Africa. The study was conducted in Asamankese, the capital town of Ghana's East Akim District. Infants 24-27 weeks of age who had been attending the Asamankese maternal-child health clinic regularly and had received all the required immunizations were enrolled and randomly assigned to receive the AIK-C (n = 184) or the Schwarz (n = 193) vaccine. No severe adverse reactions were reported during the 10-day follow-up period in either vaccine group. In the AIK-C group, 96.9% of infants who were seronegative at preimmunization and 79.4% of those with preexisting antibodies had seroconverted by 3 months after immunization; at 6 months after immunization, these rates were 97.3% and 100%, respectively. In the Schwarz group, 98.2% of infants seronegative at immunization and 100% of those with preexisting antibodies seroconverted by 3 months after immunization; at 6 months, these rates were 99.1% and 80%, respectively. Although the geometric mean titres achieved were significantly higher in the Schwarz vaccine group, these titres were above the protective level of 200 mIU in the AIK-C group. Administration of measles vaccine at a younger age may be more easily incorporated into current Expanded Program on Immunization schedules.
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    Levels of antibody to conserved parts of plasmodium falciparum merozoite surface protein I in Ghanaian children are not associated with protection from clinical malaria.
    (Infection and Immunity, 1999) Dodoo, D.; Theander, T.G.; Kurtzhals, J.A.L.; Koram, K.A.; Riley, E.; Akanmori, B.D.; Nkrumah, F.K.; Hviid, L.
    The 19-kDa conserved C-terminal part of the Plasmodium falcifarum merozoite surface protein 1 (PfMSP1 19) is a malaria vaccine candidate antigen, and human antibody responses to PfMSP1 19 have been associated with protection against clinical malaria. In this longitudinal study carried out in an area of stable but seasonal malaria transmission with an estimated parasite inoculation of about 20 infective bites/year, we monitored 266 3-to 15-year-old Ghanaian children clinically and parasitologically over a period of 18 months. Blood samples were collected at the beginning of the study before the major malaria season in April and after the season in November. Using enzyme-linked immunosorbent assay, we measured antibody responses to recombinant gluthathione S-transferase-PfMSP1 19 fusion proteins corresponding to the Wellcome and MAD20 allelic variants in these samples. Prevalence of antibodies recognizing the Wellcome 19 construct containing both epidermal growth factor (EGF)-like motifs in Wellcome type PfMSP1 19 was about 30%. Prevalence of antibodies to constructs containing only the first EGF domain from either Wellcome or MAD20 type PfMSP1 19 was about 15%, whereas antibodies recognizing a construct containing only the second EGF domain of MAD20 type PfMSP1 19 was found in only about 4% of the donors. Neither the prevalence nor the levels of any of the antibody specificities varied significantly with season, age, or sex. Significantly, and in contrast to previous reports from other parts of West Africa, we found no evidence of an association between antibody responses to PfMSP1 19 and clinical protection against malaria.
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    Risk factors for severe malaria: Importance of careful study design [2].
    (Transactions of the Royal Society of Tropical Medicine and Hygiene,, 1999) Bennett, S.; Koram, K.A.; Greenwood, B.M.