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 randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum(Clinical Infectious Diseases, 2003-03) Hale, B.R.; Owusu-Agyei, S.; Fryauff, D.J.; Koram, K.A.; Adjuik, M.; Oduro, A.R.; Prescott, W.R.; Baird, J.K.; Nkrumah, F.; Ritchie, T.L.; Franke, E.D.; Binka, F.N.; Horton, J.; Hoffman, S.L.Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in non-pregnant persons with normal glucose-6-phosphate dehydrogenase (G6PD) function. A randomized, double-blind, placebo-controlled chemoprophylaxis trial was conducted with adult residents of northern Ghana to determine the minimum effective weekly dose of tafenoquine for the prevention of infection by Plasmodium falciparum. The primary end point was a positive malaria blood smear result during the 13 weeks of study drug coverage. Relative to the placebo, all 4 tafenoquine dosages demonstrated significant protection against P. falciparum infection: for 25 mg/week, protective efficacy was 32% (95% confidence interval [CI], 20%-43%); for 50 mg/week, 84% (95% CI, 75%-91%); for 100 mg/week, 87% (95% CI, 78%-93%); and for 200 mg/week, 86% (95% CI, 76%-92%). The mefloquine dosage of 250 mg/week also demonstrated significant protection against P. falciparum infection (protective efficacy, 86%; 95% CI, 72%-93%). There was little difference between study groups in the adverse events reported, and there was no evidence of a relationship between tafenoquine dosage and reports of physical complaints or the occurrence of abnormal laboratory parameters. Tafenoquine dosages of 50, 100, and 200 mg/week were safe, well tolerated, and effective against P. falciparum infection in this study population.Item Understanding and Retention of informed consent process among Parents in a Rural Northern Ghana(2008-06-19) Oduro, A.R.; Aborigo, R.A.; Amugsi, D.; Anto, F.; Anyorigiya, T.; Atuguba, F.; Hodgson, A.; Koram, K.A.Abstract 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.Item Community concepts of malaria-related illness with and without convulsions in southern Ghana(2005-09-27) Ahorlu, C.K.; Koram, K.A.; Ahorlu, C.; De Savigny, D.; Weiss, M.GAbstract Background Malaria, both with or without convulsions, is a serious hardship for people living in endemic areas, especially in sub-Saharan Africa. Community references to malaria, however, may encompass other conditions, which was collectively designated malaria-related illness (MRI). Inasmuch as the presence or absence of convulsions reportedly affects timely help-seeking for malaria, a local comparison of these conditions is needed to inform malaria control. Methods Vignette-based EMIC interviews (insider-perspective interviews) for MRI with convulsions (convulsion positive, MRI-CP) and without convulsions (convulsion negative, MRI-CN) were developed to study relevant features of MRI-related experience, meaning and behaviour in two rural communities in Ghana. These semi-structured interviews elicited both qualitative narrative and categorical codes for quantitative analysis. Interviews with 201 respondents were conducted. Results The conditions depicted in the vignettes were well recognized by respondents and named with various local terms. Both presentations were considered serious, but MRI-CP was more frequently regarded potentially fatal than MRI-CN. More than 90.0% of respondents in both groups acknowledged the need to seek outside help. However, significantly more respondents advised appropriate help-seeking within 24 (p = 0.01) and 48 (p = 0.01) hours for MRI-CP. Over 50.0% of respondents responding to questions about MRI-CP identified MRI-CN as a cause of convulsions. Conclusion Local comparison of MRI-CP and MRI-CN based on vignettes found a similar profile of reported categories of perceived causes, patterns of distress, help-seeking and preventive measures for both presentations. This differs from previous findings in sub-Saharan Africa, which assert communities regard the two conditions to be unrelated. The perceived relationships should be acknowledged in formulating strategies to control malaria through timely help-seeking and treatment to reduce childhood mortality.Item Effectiveness of combined intermittent preventive treatment for children and timely home treatment for malaria control(2009-12-11) Ahorlu, C.K.; Koram, K.A.; Seakey, A.K.; Weiss, M.G.Abstract Background Whiles awaiting for the arrival of an effective and affordable malaria vaccine, there is a need to make use of the available control tools to reduce malaria risk, especially in children under five years and pregnant women. Intermittent preventive treatment (IPT) has recently been accepted as an important component of the malaria control strategy. This study explored the potential of a strategy of intermittent preventive treatment for children (IPTC) and timely treatment of malaria-related febrile illness in the home in reducing the parasite prevalence and malaria morbidity in young children in a coastal village in Ghana. Methods The study combined home-based delivery of IPTC among six to 60 months old and home treatment of suspected febrile malaria illness within 24 hours. All children between six and 60 months of age received intermittent preventive treatment using amodiaquine and artesunate, delivered by community assistants every four months (three times in 12 months). Malaria parasite prevalence surveys were conducted before the first and after the third dose of IPTC. Results Parasite prevalence was reduced from 25% to 3% (p < 0.00, Mann-Whitney) one year after the inception of the two interventions. At baseline, 13.8% of the children were febrile (axillary temperature greater than or equal to 37.5 degree Celsius) compared to 2.2% at evaluation (post IPTC3 combined with timely home management of fever) (p < 0.00, Mann-Whitney). Conclusion The evaluation result indicates that IPTC given three times in a year combined with timely treatment of febrile malaria illness, impacts significantly on the parasite prevalence. The marked reduction in the parasite prevalence with this strategy points to the potential for reducing malaria-related childhood morbidity and mortality, and this should be explored by control programme managers.Item Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes.(2009-05) Norman, P. J.; Abi-Rached, L.; Gendzekhadze, K.; Hammond, J.A.; Moesta, A.K.; Sharma, D.; Graef, T.; McQueen, K.L.; Guethlein, L.A.; Carrington, C.V.F.; Chandanayingyong, D.; Chang, Y.-H.; Crespí, C.; Saruhan-Direskeneli, G.; Hameed, K.; Kamkamidze, G.; Koram, K.A.; Layrisse, Z.; Matamoros, N.; Milà, J.; Myoung, H.P.; Pitchappan, R.M.; Dan Ramdath, D.; Shiau, M.-Y.; Stephens, H.A.F.; Struik, S.; Tyan, D.; Verity, D.H.; Vaughan, R.W.; Davis, R.W.; Fraser, P.A.; Riley, E.M.; Ronaghi, M.; Parham, P.Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors. Studied here is KIR3DL1/S1, which encodes receptors for highly polymorphic human HLA-A and -B and comprises three ancient allelic lineages that have been preserved by balancing selection throughout human evolution. While the 3DS1 lineage of activating receptors has been conserved, the two 3DL1 lineages of inhibitory receptors were diversified through inter-lineage recombination with each other and with 3DS1. Prominent targets for recombination were D0-domain polymorphisms, which modulate enhancer function, and dimorphism at position 283 in the D2 domain, which influences inhibitory function. In African populations, unequal crossing over between the 3DL1 and 3DL2 genes produced a deleted KIR haplotype in which the telomeric "half" was reduced to a single fusion gene with functional properties distinct from its 3DL1 and 3DL2 parents. Conversely, in Eurasian populations, duplication of the KIR3DL1/S1 locus by unequal crossing over has enabled individuals to carry and express alleles of all three KIR3DL1/S1 lineages. These results demonstrate how meiotic recombination combines with an ancient, preserved diversity to create new KIR phenotypes upon which natural selection acts. A consequence of such recombination is to blur the distinction between alleles and loci in the rapidly evolving human KIR gene family. © 2009 by Cold Spring Harbor Laboratory Pres.Item When is "malaria" malaria? The different burdens of malaria infection, malaria disease, and malaria-like illnesses.(2007-12) Koram, K.A.; Molyneux, M.E.In this review we discuss the different meanings of the term 'malaria' and urge writers and readers to distinguish accurately between them. The distinction is important in clinical practice, clinical trials, epidemiology, and the evaluation of control programs. Both over- and under-diagnosis of malaria as the cause of a disease episode are inevitable; over-diagnosis is common in high-transmission areas and underdiagnosis is common in areas with little or no transmission. Parasite density thresholds, attributable fractions, and clinical algorithms have played important but only partial roles in strengthening diagnosis. Methods by which malaria infection could be confidently identified as the cause, rather than an irrelevant accompaniment, of an illness, are important targets for research. One such 'signature' is a distinctive retinopathy that occurs in severe malaria and not in clinically similar diseases. Other indicators of a malarial etiology of clinical disease are needed to strengthen clinical and scientific approaches to the control of malaria. Copyright © 2007 by The American Society of Tropical Medicine and Hygiene.Item Mefloquine treatment for uncomplicated falciparum malaria in young children 6-24 months of age in northern Ghana.(2007-02) Fryauff, D. J.,; Owusu-Agyei, S.; Utz, G.; Baird, J. K; Koram, K.A.; Binka, F.; Nkrumah, F.; Hoffman, S. L.Mefloquine (MQ) single dose 20 mg/kg treatment of falciparum malaria was evaluated in 186 children of 6-24 months of age in northern Ghana. There were 15 RII/RIII-type parasitologic failures, all with Day 2 MQ blood levels significantly lower than children whose parasitemias cleared before Day 7 and remained clear through 28 days. Predictors of RII/RIII parasitologic response were vomiting after MQ dosing, Day 2 MQ levels < 500 ng/mL, and undetectable Day 2 levels of the carboxymefloquine metabolite. There were 50 cases of delayed RI parasitologic failure, but 71% of these cases had undetectable Day 28 blood levels of MQ and drug levels in the remaining 29% ranged below the 620 ng/mL level that suppresses MQ sensitive strains of P. falciparum. Drug levels among infants that tolerated MQ well were not associated with age, weight, hemoglobin, parasitemia, and pre-existing symptoms of vomiting or diarrhea. An observed recurrent parasitemia of 34,400 trophozoites/μL against a MQ blood concentration of 550 ng/mL was taken as indication of tolerance to suppressive levels of the drug at this location. Copyright © 2007 by The American Society of Tropical Medicine and Hygiene.Item Genetic diversity and antigenic polymorphism in plasmodium falciparum: Extensive serological cross-reactivity between allelic variants of merozoite surface protein 2.(2003-06) Franks, S.; Baton, L.; Tetteh, K.; Tongren, E.; Dewin, D.; Akanmori, B.D.; Koram, K.A.; Ranford-Cartwright, L.; Riley, E.M.Diversity in the surface antigens of malaria parasites is generally assumed to be a mechanism for immune evasion, but there is little direct evidence that this leads to evasion of protective immunity. Here we show that alleles of the highly polymorphic merozoite surface protein 2 (MSP-2) can be grouped (within the known dimorphic families) into distinct serogroups; variants within a serogroup show extensive serological cross-reactivity. Cross-reactive epitopes are immunodominant, and responses to them may be boosted at the expense of responses to novel epitopes (original antigenic sin). The data imply that immune selection explains only some of the diversity in the msp-2 gene and that MSP-2 vaccines may need to include only a subset of the known variants in order to induce pan-reactive antibodies.Item Effect of removing direct payment for health care on utilisation and health outcomes in Ghanaian children:(2009) Ansah, E.K.; Narh-Bana, S.; Asiamah, S.; Dzordzordzi, V.; Biantey, K.; Dickson, K.; Gyapong, J.O.; Koram, K.A.; Greenwood, B.M.; Mills, A.; Whitty, C.J.M.Background: Delays in accessing care for malaria and other diseases can lead to disease progression, and user fees are a known barrier to accessing health care. Governments are introducing free health care to improve health outcomes. Free health care affects treatment seeking, and it is therefore assumed to lead to improved health outcomes, but there is no direct trial evidence of the impact of removing out-of-pocket payments on health outcomes in developing countries. This trial was designed to test the impact of free health care on health outcomes directly. Methods and Findings: 2,194 households containing 2,592 Ghanaian children under 5 y old were randomised into a prepayment scheme allowing free primary care including drugs, or to a control group whose families paid user fees for health care (normal practice); 165 children whose families had previously paid to enrol in the prepayment scheme formed an observational arm. The primary outcome was moderate anaemia (haemoglobin [Hb] < 8 g/dl); major secondary outcomes were health care utilisation, severe anaemia, and mortality. At baseline the randomised groups were similar. Introducing free primary health care altered the health care seeking behaviour of households; those randomised to the intervention arm used formal health care more and nonformal care less than the control group. Introducing free primary health care did not lead to any measurable difference in any health outcome. The primary outcome of moderate anaemia was detected in 37 (3.1%) children in the control and 36 children (3.2%) in the intervention arm (adjusted odds ratio 1.05, 95% confidence interval 0.66-1.67). There were four deaths in the control and five in the intervention group. Mean Hb concentration, severe anaemia, parasite prevalence, and anthropometric measurements were similar in each group. Families who previously self-enrolled in the prepayment scheme were significantly less poor, had better health measures, and used services more frequently than those in the randomised group. Conclusions: In the study setting, removing out-of-pocket payments for health care had an impact on health care-seeking behaviour but not on the health outcomes measured. Trial registration: ClinicalTrials.gov (#NCT00146692). © 2009 Ansah et al.Item Effectiveness of combined intermittent preventive treatment for children and timely home treatment for malaria control.(2009) Ahorlu, C.K.; Koram, K.A.; Seakey, A.K.; Weiss, M.G.Background. Whiles awaiting for the arrival of an effective and affordable malaria vaccine, there is a need to make use of the available control tools to reduce malaria risk, especially in children under five years and pregnant women. Intermittent preventive treatment (IPT) has recently been accepted as an important component of the malaria control strategy. This study explored the potential of a strategy of intermittent preventive treatment for children (IPTC) and timely treatment of malaria-related febrile illness in the home in reducing the parasite prevalence and malaria morbidity in young children in a coastal village in Ghana. Methods. The study combined home-based delivery of IPTC among six to 60 months old and home treatment of suspected febrile malaria illness within 24 hours. All children between six and 60 months of age received intermittent preventive treatment using amodiaquine and artesunate, delivered by community assistants every four months (three times in 12 months). Malaria parasite prevalence surveys were conducted before the first and after the third dose of IPTC. Results. Parasite prevalence was reduced from 25% to 3% (p < 0.00, Mann-Whitney) one year after the inception of the two interventions. At baseline, 13.8% of the children were febrile (axillary temperature greater than or equal to 37.5 degree Celsius) compared to 2.2% at evaluation (post IPTC3 combined with timely home management of fever) (p < 0.00, Mann-Whitney). Conclusion. The evaluation result indicates that IPTC given three times in a year combined with timely treatment of febrile malaria illness, impacts significantly on the parasite prevalence. The marked reduction in the parasite prevalence with this strategy points to the potential for reducing malaria-related childhood morbidity and mortality, and this should be explored by control programme managers. © 2009 Ahorlu et al; licensee BioMed Central Ltd.
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