Research Articles
Permanent URI for this communityhttp://197.255.125.131:4000/handle/123456789/22010
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
Browse
68 results
Search Results
Item Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in children in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial(Lancet Infectious Diseases, 2020-03-19) Koram, K.A.; Tapia, M.D.; Sow, S.O.; Mbaye, K.D.; Thiongane, A.; Ndiaye, B.P.; Ndour, C.T.; Mboup, S.; Keshinro, B.; Kinge, T.N.; Vernet, G.; Bigna, J.J.; Oguche, S.; Asante, K.P.; Gobert, P.; Hogrefe, W.R.; De Ryck, I.; Debois, M.; Bourguignon, P.; Jongert, E.; Ballou, W.R.; Koutsoukos, M.; Roman, F.; Zaire EBola Research Alliance groupBackground: During the large 2013-16 Ebola virus outbreak caused by the Zaire Ebola virus, about 20% of cases were reported in children. This study is the first, to our knowledge, to evaluate an Ebola vaccine in children younger than 6 years. We aimed to evaluate the safety, reactogenicity, and immunogenicity of a monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in a paediatric population. Methods: This phase 2, randomised, observer-blind, controlled trial was done in a vaccine centre in Mali and a university hospital centre in Senegal. Healthy children were randomly assigned through a web-based system (1:1; stratified by age group, gender, and centre) to receive ChAd3-EBO-Z (day 0) and meningococcal serogroups A,C,W-135,Y tetanus toxoid conjugate vaccine (MenACWY-TT; month 6), or MenACWY-TT (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind from study start until interim day 30 analysis and became single-blind as of interim analysis. Primary outcomes assessed were serious adverse events (up to study end, month 12), solicited local or general adverse events (7 days post-vaccination), unsolicited adverse events (30 days post-vaccination), haematological or biochemical abnormalities, and clinical symptoms of thrombocytopenia (day 0-6). As secondary endpoints, we evaluated anti-glycoprotein Zaire Ebola virus antibody titres (ELISA) pre-vaccination and 30 days post-vaccination. This study is registered with ClinicalTrials.gov, NCT02548078. Findings: From Nov 11, 2015, to May 9, 2016, of 776 children screened for eligibility, 600 were randomly assigned (200 [33%] in each age strata: 1-5, 6-12, 13-17 years), 300 (50%) to the ChAd3-EBO-Z/MenACWY-TT group and 300 (50%) to the MenACWY-TT/ChAd3-EBO-Z group; all were included in the total vaccinated cohort. Post-day 0 vaccination, the most common solicited injection site symptom was pain (127 [42%] of 300 in the ChAd3-EBO-Z/MenACWY-TT group vs 60 [20%] of 300 in the MenACWY-TT/ChAd3-EBO-Z group); the most common solicited general adverse event was fever (95 [32%] of 300 in the ChAd3-EBO-Z/MenACWY-TT group vs 28 [9%] of 300 in the MenACWY-TT/ChAd3-EBO-Z group). Unsolicited adverse events post-day 0 vaccination were reported by 41 (14%) of 300 participants in the ChAd3-EBO-Z/MenACWY-TT group and 24 (8%) of 300 MenACWY-TT/ChAd3-EBO-Z recipients. Serious adverse events were reported for two (1%) of 300 children in each group; none were considered vaccination related. No clinical symptoms of thrombocytopenia were reported. At day 30, anti-glycoprotein Ebola virus antibody geometric mean concentrations (GMC) in the ChAd3-EBO-Z/MenACWY-TT group were 1564 (95% CI 1340-1826) for those aged 13-17 years, 1395 (1175-1655) for 6-12 years, and 2406 (1942-2979) for 1-5 years. Anti-glycoprotein Ebola virus IgG antibody responses persisted up to 12 months post-vaccination, with a GMC of 716 (95% CI 619-828) for those aged 13-17 years, 752 (645-876) for 6-12 years, and 1424 (1119-1814) for 1-5 years. Interpretation: ChAd3-EBO-Z was immunogenic and well tolerated in children aged 1-17 years. This study provides the first ChAd3-EBO-Z data in a paediatric population. Further development should focus on multivalent approaches including Sudan and Marburg strains, and heterologous prime-boost strategies, for instance using modified vaccinia Ankara-based vaccine to boost the immune response.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 Measuring regional and district variations in the incidence of pregnancy-induced hypertension in Ghana: Challenges, opportunities and implications for maternal and newborn health policy and programmes(Blackwell Publishing Ltd, 2016) Antwi, E.; Klipstein-Grobusch, K.; Quansah Asare, G.; Koram, K.A.; Grobbee, D.; Agyepong, I.A.Objectives: The objectives were to assess the quality of health management information system (HMIS) data needed for assessment of local area variation in pregnancy-induced hypertension (PIH) incidence and to describe district and regional variations in PIH incidence. Methods: A retrospective review of antenatal and delivery records of 2682 pregnant women in 10 district hospitals in the Greater Accra and Upper West regions of Ghana was conducted in 2013. Quality of HMIS data was assessed by completeness of reporting. The incidence of PIH was estimated for each district. Results: Key variables for routine assessment of PIH such as blood pressure (BP) at antenatal visits, weight and height were 95-100% complete. Fundal height, gestational age and BP at delivery were not consistently reported. The incidence of PIH differed significantly between Greater Accra region (6.1%) and Upper West region (3.2%). Prevalence of obesity among pregnant women in Greater Accra region (13.9%) was significantly higher than that of women in Upper West region (2.2%). Conclusions: More attention needs to be given to understanding local area variations in PIH and possible relationships with urbanisation and lifestyle changes that promote obesity, to inform maternal and newborn health policy. This can be done with good quality routine HMIS data. © 2016 John Wiley & Sons Ltd.Item Reduced transmission of Mycobacterium africanum compared to Mycobacterium tuberculosis in urban West Africa(International Journal of Infectious Diseases, 2018-08) Asare, P.; Asante-Poku, A.; Prah, D.A.; Borrell, S.; Osei-Wusu, S.; Otchere, I.D.; Forson, A.; Adjapong, G.; Koram, K.A.; Gagneux, S.; Yeboah-Manu, D.Objective: Understanding transmission dynamics is useful for tuberculosis (TB) control. A population-based molecular epidemiological study was conducted to determine TB transmission in Ghana. Methods: Mycobacterium tuberculosis complex (MTBC) isolates obtained from prospectively sampled pulmonary TB patients between July 2012 and December 2015 were characterized using spoligotyping and standard 15-locus mycobacterial interspersed repetitive unit variable number tandem repeat (MIRU-VNTR) typing for transmission studies. Results: Out of 2309 MTBC isolates, 1082 (46.9%) unique cases were identified, with 1227 (53.1%) isolates belonging to one of 276 clusters. The recent TB transmission rate was estimated to be 41.2%. Whereas TB strains of lineage 4 belonging to M. tuberculosis showed a high recent transmission rate (44.9%), reduced recent transmission rates were found for lineages of Mycobacterium africanum (lineage 5, 31.8%; lineage 6, 24.7%). Conclusions: The study findings indicate high recent TB transmission, suggesting the occurrence of unsuspected outbreaks in Ghana. The observed reduced transmission rate of M. africanum suggests other factor(s) (host/environmental) may be responsible for its continuous presence in West Africa. © 2018 The Author(s)Item Dynamics of the antibody response to Plasmodium falciparum infection in African children(Journal of Infectious Diseases, 2014-04) White, M.T.; Griffin, J.T.; Akpogheneta, O.; Conway, D.J.; Koram, K.A.; Riley, E.M.; Ghani, A.C.Background. Acquired immune responses to malaria have widely been perceived sto be short-lived, with previously immune individuals losing immunity when they move from malaria-endemic areas. However longlived Plasmodium falciparum-specific antibody responses lasting for an individual's lifetime are frequently observed. Methods. We fit mathematical models of the dynamics of antibody titers to P. falciparum antigens from longitudinal cohort studies of African children to estimate the half-lives of circulating immunoglobulin G (IgG) antibodies and IgG antibody-secreting cells (ASCs). Results. Comparison of antibody responses in the younger Ghanaian cohort and the older Gambian cohort suggests that young children are less able to generate the long-lived ASCs necessary to maintain the circulating antibodies that may provide protection against reinfection. Antibody responses in African children can be described by a model 15 including both short-lived ASCs (half-life range, 2-10 days), which are responsible for boosting antibody titers following infection, and long-lived ASCs (half-life range, 3-9 years), which are responsible for maintaining sustained humoral responses. Conclusions. The rapid decay of antibodies following exposure to malaria and the maintenance of sustained antibody responses can be explained in terms of populations of short-lived and long-lived ASCs. © The Author 2014.Item Reappraisal of known malaria resistance loci in a large multicenter study(Nature Genetics, 2014-11) Rockett, K.A.; Clarke, G.M.; Fitzpatrick, K.; Hubbart, C.; Ghansah, A.; Koram, K.A.; Wilson, M.Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10 '4 with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed. © 2014 Nature America, Inc. All rights reserved.Item Anti-sporozoite antibodies as alternative markers for malaria transmission intensity estimation(Malaria Journal, 2014) Kusi, K.A.; Bosomprah, S.; Dodoo, D.; Kyei-Baafour, E.; Dickson, E.K.; Mensah, D.; Angov, E.; Dutta, S.; Sedegah, M.; Koram, K.A.Reported malaria cases continue to decline globally, and this has been attributed to strategic implementation of multiple malaria control tools. Gains made would however need to be sustained through continuous monitoring to ensure malaria elimination and eradication. Entomological inoculation rate (EIR) is currently the standard tool for transmission monitoring but this is not sensitive enough, especially in areas of very low transmission. Transmission estimation models based on seroconversion rates (λ) of antibodies to Plasmodium falciparum blood stage antigens are gaining relevance. Estimates of λ, which is the measure of transmission intensity, correlate with EIR but are limited by long-term persistence of antibodies to blood stage antigens. Seroprevalence of antibodies to sporozoite antigens may be better alternatives since these antigens usually have shorter immune exposure times. The aim of this study was to develop transmission estimation models based on the seroprevalence of antibodies to two P. falciparum sporozoite antigens (CSP, CelTOS) and compare with models based on the classical blood stage antigen AMA1. Methods. Antibody levels in archived plasma from three cross-sectional surveys conducted in 2009 in a low transmission area of Southern Ghana were assessed by indirect ELISA. Seroprevalence of antibodies against CSP, CelTOS and AMA1 were fitted to reversible catalytic models to estimate λ and corresponding seroreversion rates (ρ) for each antibody. Results: Of the three models developed, the anti-CSP model predicted a 13-fold decrease in λ four years prior to the time of sampling (2009). Anti-AMA1 antibodies formed at a four-fold greater rate compared to that of anti-CelTOS antibodies, and anti-CSP antibodies during the period of decreased λ. In contrast, anti-AMA1 antibodies decayed at a five-fold slower rate relative to that of anti-CSP antibodies while anti-AMA1 and anti-CelTOS antibody decay rates were not significantly different. Anti-CSP antibodies were relatively short-lived as they formed at an 11.6-fold slower rate relative to their decay during the period of decreased λ. Conclusions: These features of anti-CSP antibodies can be exploited for the development of models for predicting seasonal, short-term changes in transmission intensity in malaria-endemic areas, especially as the elimination phase of malaria control is approached. © 2014 Kusi et al.; licensee BioMed Central Ltd.Item Anti-trypanosomal activity of diarylheptanoids isolated from the bark of alnus japonica(American Journal of Chinese Medicine, 2014) Tung, N.H.; Suzuki, M.; Uto, T.; Morinaga, O.; Kwofie, K.D.; Ammah, N.; Koram, K.A.; Aboagye, F.; Edoh, D.; Yamashita, T.; Yamaguchi, Y.; Setsu, T.; Yamaoka, S.; Ohta, N.; Shoyama, Y.The crude extract of Alnus japonica bark exhibited a strong effect on the growth of Trypanosoma brucei. Subsequent chromatographic separation resulted in the isolation of two novel diarylheptanoids, known as alnuside C (2) and alnuside D (3), and three known compounds, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3(R)-O-β-D-glucopyranoside (1), oregonin (4) and hirsutanone (5). The structures of the isolates were elucidated based on the use of extensive spectroscopic and chemical methods. Among the isolated diarylheptanoids, oregonin (4) (a major component of plant bark) and hirsutanone (5) exhibited potent in vitro inhibitory activity against T. brucei growth in the bloodstream with IC50 values of 1.14 and 1.78 μM, respectively. We confirmed that oregonin (4) and hirsutanone (5) were not toxic to human normal skin fibroblast cells (NB1RGB) and colon cancer cells (HCT-15) at a concentration of 50 μM; however, lower levels of toxicity were observed for leukemia cells. To determine the structure activity relationships of the isolated components, we performed Conformation Search and found that the 3-oxo function of the heptane chain in the diarylheptanoid molecule is required for their trypanocidal activity. © 2014 World Scientific Publishing Company and Institute for Advanced Research in Asian Science and Medicine.Item Development and validation of a prediction model for gestational hypertension in a Ghanaian cohort(BioMed Central Ltd., 2017) Antwi, E.; Groenwold, R.H.H.; Browne, J.L.; Franx, A.; Agyepong, I.A.; Koram, K.A.; Klipstein-Grobusch, K.; Grobbee, D.E.Objective To develop and validate a prediction model for identifying women at increased risk of developing gestational hypertension (GH) in Ghana. Design A prospective study. We used frequencies for descriptive analysis, Ï ‡ 2 test for associations and logistic regression to derive the prediction model. Discrimination was estimated by the c-statistic. Calibration was assessed by calibration plot of actual versus predicted probability. Setting Primary care antenatal clinics in Ghana. Participants 2529 pregnant women in the development cohort and 647 pregnant women in the validation cohort. Inclusion criterion was women without chronic hypertension. Primary outcome Gestational hypertension. Results Predictors of GH were diastolic blood pressure, family history of hypertension in parents, history of GH in a previous pregnancy, parity, height and weight. The c-statistic of the original model was 0.70 (95% CI 0.67-0.74) and 0.68 (0.60 to 0.77) in the validation cohort. Calibration was good in both cohorts. The negative predictive value of women in the development cohort at high risk of GH was 92.0% compared to 94.0% in the validation cohort. Conclusions The prediction model showed adequate performance after validation in an independent cohort and can be used to classify women into high, moderate or low risk of developing GH. It contributes to efforts to provide clinical decision-making support to improve maternal health and birth outcomes.Item Molecular epidemiology of Mycobacterium africanum in Ghana(BioMed Central Ltd., 2016) Asante-Poku, A.; Otchere, I.D.; Osei-Wusu, S.; Sarpong, E.; Baddoo, A.; Forson, A.; Laryea, C.; Borrell, S.; Bonsu, F.; Hattendorf, J.; Ahorlu, C.; Koram, K.A.; Gagneux, S.; Yeboah-Manu, D.Background: Mycobacterium africanum comprises two phylogenetic lineages within the M. tuberculosis complex (MTBC) and is an important cause of human tuberculosis (TB) in West Africa. The reasons for this geographic restriction of M. africanum remain unclear. Here, we performed a prospective study to explore associations between the characteristics of TB patients and the MTBC lineages circulating in Ghana. Method: We genotyped 1,211 MTBC isolates recovered from pulmonary TB patients recruited between 2012 and 2014 using single nucleotide polymorphism typing and spoligotyping. Associations between patient and pathogen variables were assessed using univariate and multivariate logistic regression. Results: Of the 1,211 MTBC isolates analysed, 71.9 % (871) belonged to Lineage 4; 12.6 % (152) to Lineage 5 (also known as M. africanum West-Africa 1), 9.2 % (112) to Lineage 6 (also known as M. africanum West-Africa 2) and 0. 6 % (7) to Mycobacterium bovis. Univariate analysis revealed that Lineage 6 strains were less likely to be isoniazid resistant compared to other strains (odds ratio = 0.25, 95 % confidence interval (CI): 0.05-0.77, P < 0.01). Multivariate analysis showed that Lineage 5 was significantly more common in patients from the Ewe ethnic group (adjusted odds ratio (adjOR): 2.79; 95 % CI: 1.47-5.29, P < 0.001) and Lineage 6 more likely to be found among HIV-co-infected TB patients (adjOR = 2.2; 95 % confidence interval (CI: 1.32-3.7, P < 0.001). Conclusion: Our findings confirm the importance of M. africanum in Ghana and highlight the need to differentiate between Lineage 5 and Lineage 6, as these lineages differ in associated patient variables.