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 Trends in the Prevalence of Female Genital Mutilation and its Effect on Delivery Outcomes in the Kassena-Nankana District of Northern Ghana(Ghana Medical Journal, 2006-09) Oduro, A.R.; Ansah, P.; Hodgson, A.; Afful, T.M.; Baiden, F.; Adongo, P.; Koram, K.A.Rational: Female genital mutilation (FGM) is prevalent in northern Ghana, as the practice is seen as a passage rite to women adulthood and thus undertaken just before marriage. Objectives: We determined the changes in trend of FGM in deliveries at the Navrongo War Memo-rial hospital, and compared the outcomes and FGM status. Design: Retrospective extraction and analysis of delivery data at the hospital from 1st January 1996 to 31st December 2003. Results: Of the 5071 deliveries, about 29% (1466/5071) were associated with FGM. The high-est prevalence (95% CI) of 61.5% (50.9, 71.2) was in women aged 40 years and above, and the lowest of 14.4% (11.7, 17.0) was in women below 20 years. The all-age prevalence of FGM showed a significant decline (p-value for linear trend < 0.01) from 35.2% in 1996 to 21.1% in 2003. About 6% (89/1466) of mothers with FGM had stillbirths compared with about 3% (123/3605) of mothers without FGM. Again FGM was associated with 8.2% (120/1466) caesarean section rate compared with 6.7% (241/3605) in mothers without FGM. Mean birth weight and frequency of low birth weights were not significantly associated with FGM status. Conclusion: Although there is a high rate of FGM among mothers in the district and is associated with a higher proportion of stillbirths and caesar-ean sections, practice has shown a significant de-cline in the district in recent years due to the pre-vailing campaigns and intervention studies. There is therefore the need to sustain the ongoing inter-vention efforts.Item Does apolipoprotein E polymorphism influence susceptibility to malaria?(2003) Wozniak, M.A.; Faragher, E.B.; Todd, J.A.; Koram, K.A.; Riley, E.M.; Itzhaki, R.F.Outcome of infection varies greatly among people, and in the case of three very different viruses, it is determined by apolipoprotein E (APOE) genotype. APOE might affect outcome of malaria infection also, since apoE protein and the protozoon (like the viruses) share cell entry mediators (heparan sulphate proteoglycans and/or specific apoE receptors). APOE polymorphisms give rise to protein variants that differ in binding strength to these mediators; thus, the extent of competition between apoE and protozoon for cell entry, and hence magnitude of protozoan damage, might depend on apoE isoform. Genotypes of infants infected with malaria were examined. It was found that APOE ε2 homozygotes became infected at an earlier age than those carrying the other genotypes, the difference being statistically significant. Parasite densities, all of which were low, did not differ significantly. This effect, although based on small numbers, suggests that APOE ε2 may be a risk factor for early infection.Item Clinical case definitions and malaria vaccine efficacy.(2006-02) Rogers, W.O.; Atuguba, F.; Oduro, A.R.; Hodgson, A.; Koram, K.A.Reported efficacies from vaccine trials may depend heavily on the clinical case definition used in the trial. The dependence may be particularly striking for diseases such as malaria, in which no single case definition is appropriate. We used logistic regression modeling of the relationship between parasitemia and fever in data sets from Ghanaian children to determine the fraction of fevers attributable to malaria and to model how the choice of a threshold parasitemia in the clinical case definition affects the measured efficacy of malaria vaccines. Calculated clinical attack rates varied 10-fold as a function of the threshold parasitemia. Strikingly, measured vaccine efficacies in reducing clinical malaria depended heavily on the threshold parasitemia, varying between 20% and 80% as the threshold varied between 1 and 5000 parasites/μL. We suggest that clinical case definitions of malaria that incorporate a threshold parasitemia are arbitrary and do not yield stable estimates of vaccine trial end points. © 2005 by the Infectious Diseases Society of America. All rights reserved.Item Do maternally acquired antibodies protect infants from malaria infection?(2001-02) Riley, E.M.; Wagner, G. E.; Akanmori, B.D.; Koram, K.A.Neonates and infants are relatively protected from clinical malaria, but the mechanism of this protection is not well understood. Maternally derived antibodies are commonly believed to provide protection against many infectious diseases, including malaria, for periods of up to 6–9 months but several recent epidemiological studies have produced conflicting results regarding a protective role of passively acquired antimalarial antibodies. In this article, we review the epidemiological evidence for resistance of young infants to malaria, summarize the data on antimalarial antibody levels and specificity and their association with protection from malaria infection or clinical disease, and explore alternative explanations for resistance to malaria in infants.Item The in-vitro susceptibilities of Ghanaian plasmodium falciparum to antimalarial drugs.(2007-07) Quashie, N.B.; Duah, N.O.; Abuaku, B.; Koram, K.A.In Ghana in 2004 (when choroquine was still the nationally recommended drug for the first-line treatment of malaria), the sensitivities, to chloroquine, amodiaquine, quinine, mefloquine, artesunate and halofantrine, of 60 Plasmodium falciparum isolates from two ecologically distinct areas of the country were assessed in vitro. The aim was to make available, to policy-makers, the field-based evidence needed to review the national strategy for malaria treatment. Drug susceptibilities were explored using the standardized protocol of the Antimalarial Drug Resistance Network. Although 32 of the P. falciparum isolates evaluated (56.1% of die 57 isolates successfully investigated for their susceptibility to choroquine) showed resistance to chloroquine and two showed slightly reduced sensitivity to amodiaquine, all the isolates were sensitive to mefloquine, artesunate, quinine and halofantrine. The median inhibitory concentrations (IC 50) of chloroquine were positively correlated with those of quinine (r=0.4528; P=0.0008) but not those of any of the other drugs investigated. The IC 50 of amodiaquine and artesunate were also positively correlated (r=0.3703; P=0.0067). These results provide evidence of the presence, in Ghana, of P. falciparum isolates that are highly resistant to chloroquine but generally sensitive to most of the other antimalarial drugs commonly used in the country. Partly in consequence of these observations, the recommended first-line treatment for malaria in Ghana was changed to an amodiaquine-artesunate combination in January 2005. © 2007 The Liverpool School of Tropical Medicine.Item HLA-DRB1*04 allele is associated with severe malaria in northern Ghana.(2008) Osafo-Addo, A.D.; Koram, K.A.; Oduro, A.R.; Wilson, M.; Hodgson, A.; Rogers, W.O.Several associations between specific HLA alleles and susceptibility or resistance to Plasmodium falciparum malaria have been previously reported, but no associations have been confirmed in multiple populations. We studied associations between HLA-A, -B, and DRB1 alleles and severe malaria in northern Ghana. We analyzed HLA-DRB1*04 in 4,032 subjects from a severe malaria case-control study, 790 severe malaria cases, 1,611 mild malaria controls, and 1631 asymptomatic controls. The presence of HLA-DRB1*04 was associated with severe malaria (OR = 2.42, 95% CI = 1.64, 3.58). The allele frequency of DRB1*04 was similar in the two major ethnic groups in the study population, Kassem (4.4%) and Nankam (4.7%), and the OR for the association between DRB1*04 and severe malaria was similar in both ethnic groups. These findings are consistent with results from Gabon suggesting that DRB1*04 is a risk factor for severe malaria.Item Severe falciparum malaria in young children of the Kassena-Nankana district of northern Ghana.(2007) Oduro, A.R.; Koram, K.A.; Rogers, W.; Atuguba, F.; Ansah, P.; Anyorigiya, T.; Ansah, A.; Anto, F.; Mensah, N.; Hodgson, A.; Nkrumah, F.Study design. Severe falciparum malaria in children was studied as part of the characterization of the Kassena-Nankana District Ghana for future malaria vaccine trials. Children aged 6-59 months with diagnosis suggestive of acute disease were characterized using the standard WHO definition for severe malaria. Results. Of the total children screened, 45.2% (868/1921) satisfied the criteria for severe malaria. Estimated incidence of severe malaria was 3.4% (range: 0.4-8.3%) cases per year. The disease incidence was seasonal: 560 cases per year, of which 70.4% occurred during the wet season (June-October). The main manifestations were severe anaemia (36.5%); prolonged or multiple convulsions (21.6%); respiratory distress (24.4%) and cerebral malaria (5.4%). Others were hyperpyrexia (11.1%); hyperparasitaemia (18.5%); hyperlactaemia (33.4%); and hypoglycaemia (3.2%). The frequency of severe anaemia was 39.8% in children of six to 24 months of age and 25.9% in children of 25-60 months of age. More children (8.7%) in the 25-60 months age group had cerebral malaria compared with 4.4% in the 6-24 months age group. The overall case fatality ratio was 3.5%. Cerebral malaria and hyperlactataemia were the significant risk factors associated with death. Severe anaemia, though a major presentation, was not significantly associated with risk of death. Conclusion. Severe malaria is a frequent and seasonal childhood disease in northern Ghana and maybe an adequate endpoint for future malaria vaccine trials. © 2007 Oduro et al; licensee BioMed Central Ltd.Item Understanding and retention of the informed consent process among parents in rural northern Ghana.(2008) Oduro, A.R.; Aborigo, R.A.; Amugsi, D.; Anto, F.; Anyorigiya, T.; Atuguba, F.; Hodgson, A.; Koram, K.A.Background. The individual informed consent model remains critical to the ethical conduct and regulation of research involving human beings. Parental informed consent process in a rural setting of northern Ghana was studied to describe comprehension and retention among parents as part of the evaluation of the existing informed consent process. Methods. The study involved 270 female parents who gave consent for their children to participate in a prospective cohort study that evaluated immune correlates of protection against childhood malaria in northern Ghana. A semi-structured interview with questions based on the informed consent themes was administered. Parents were interviewed on their comprehension and retention of the process and also on ways to improve upon the existing process. Results. The average parental age was 33.3 years (range 18-62), married women constituted a majority (91.9%), Christians (71.9%), farmers (62.2%) and those with no formal education (53.7%). Only 3% had ever taken part in a research and 54% had at least one relation ever participate in a research. About 90% of parents knew their children were involved in a research study that was not related to medical care, and 66% said the study procedures were thoroughly explained to them. Approximately, 70% recalled the study involved direct benefits compared with 20% for direct risks. The majority (95%) understood study participation was completely voluntary but only 21% recalled they could withdraw from the study without giving reasons. Younger parents had more consistent comprehension than older ones. Maternal reasons for allowing their children to take part in the research were free medical care (36.5%), better medical care (18.8%), general benefits (29.4%), contribution to research in the area (8.8%) and benefit to the community (1.8%). Parental suggestions for improving the consent process included devoting more time for explanations (46.9%), use of the local languages (15.9%) and obtaining consent at home (10.3%). Conclusion. Significant but varied comprehension of the informed consent process exists among parents who participate in research activities in northern Ghana and it appears the existing practices are fairly effective in informing research participants in the study area. © 2008 Oduro et al; licensee BioMed Central Ltd.Item Unusual selection on the KIR3DL1/S1 natural killer cell receptor in africans.(2007) Norman, P. J.; Abi-Rached, L.; Gendzekhadze, K.; Korbel, D.; Gleimer, M.; Rowley, D.; Bruno, D.; Carrington, C.V.F.; Chandanayingyong, D.; Chang, Y.-H.; Crespí, C.; Saruhan-Direskeneli, G.; Fraser, P.A.; Hameed, K.; Kamkamidze, G.; Koram, K.A.; Layrisse, Z.; Matamoros, N.; Milà, J.; Park, M.H.; Pitchappan, R.M.; Ramdath, D.D.; Shiau, M-Y; Stephens, H.A.F.; Struik, S.; Verity, D.H.; Vaughan, R.W.; Tyan, D.; Davis, R.W.; Riley, E.M.; Ronaghi, M.; Parham, P.Interactions of killer cell immunoglobulin-like receptors (KIRs) with major histocompatibility complex (MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of protein">HLA-A and HLA-B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA-B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/S1 evolution in modern sub-Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression.Item Comparative efficacy of antimalarial drugs including ACTs in the treatment of uncomplicated malaria among children under 5 years in Ghana.(2005-09) Koram, K.A.; Abuaku, B.; Duah, N.; Quashie, N.The emergence and spread of Plasmodium falciparum resistance to commonly used antimalarials such as chloroquine and sulphadoxine/pyrimethamine poses major challenges to malaria control in sub-Saharan Africa. We undertook a study on the efficacy of some antimalarial drugs in 2003 with the view of supporting the National Malaria Control Programme in the review of the antimalarial drug treatment policy in Ghana. Children aged 6-59 months with signs/symptoms of uncomplicated malaria including axillary temperature ≥37.5°C; mono infection with P. falciparum; and parent's willingness to give consent, were randomized into four treatment groups and followed up for a maximum of 28 days. The treatment groups were chloroquine (CHQ), sulphadoxine/pyrimethamine (SP), amodiaquine + artesunate (ADQ + ART) combination, and artemether + lumefantrine (Coartem ®) combination. Clinical evaluation of 168 children studied showed that cumulative pcr-corrected cure rates on day 28 were 100% for ADQ + ART; 97.5% for coartem, 60% for SP and 25% for CHQ. The artemisinin-based combinations effected rapid fever and parasite clearance. Prevalence of gametocytaemia was highest in the SP group whilst the CHQ group did not show any significant changes in haemoglobin levels during the follow-up period. The findings are in agreement with current recommendations for using artemisinin-based combinations for treating uncomplicated malaria in areas of high CHQ failure such as Ghana. © 2005 Elsevier B.V. All rights reserved.