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 Therapeutic efficacy of dihydroartemisinin-piperaquine combination for the treatment of uncomplicated malaria in Ghana(Frontiers in Cellular and Infection Microbiology, 2023) Abuaku, B.; Boateng, P.; Peprah, N.Y.; Asamoah, A.; Duah-Quashie, N.O.; Matrevi, S.A.; Amoako, E.O.; Quashie, N.; Owusu-Antwi, F.; Malm, K.L.; Koram, K.A.In 2020, Dihydroartemisinin-Piperaquine (DHAP) was adopted as a second-line antimalarial for treatment of uncomplicated malaria in Ghana following a review of the country’s antimalarial medicines policy. Available data obtained in 2007 had shown PCR-uncorrected therapeutic efficacy of 93.3% using a 28- day follow-up schedule. In 2020, the standard 42-day follow-up schedule for DHAP was used to estimate efficacy levels among febrile children aged 6 months to 9 years in three malaria sentinel sites representing the three main ecological zones of the country- savannah, forest, and coastal. PCR genotyping distinguished between recrudescence and re-infection using merozoite surface protein 2 (MSP2)-specific primers for FC27 and 3D7 strains. Per protocol analyses showed day 28 efficacy of 100% in all three sentinel sites with day 42 PCR-corrected efficacy ranging between 90.3% (95% CI: 80.1 – 96.4%) in the savannah zone and 100% in the forest and coastal zones, yielding a national average of 97.0% (95% CI: 93.4 – 98.8). No day 3 parasitemia was observed in all three sites. Prevalence of measured fever (axillary temperature ≥ 37.5°C) declined from 50.0 - 98.8% on day 0 to 7.1-11.5% on day 1 whilst parasitemia declined from 100% on day 0 to 1.2 - 2.3% on day 1. Mean haemoglobin levels on days 28 and 42 were significantly higher than pretreatment levels in all three sites. We conclude that DHAP is highly efficacious in the treatment of uncomplicated malaria in Ghana. This data will serve as baseline for subsequent DHAP efficacy studies in the countryItem Ex vivo Sensitivity Profile of Plasmodium falciparum Clinical Isolates to a Panel of Antimalarial Drugs in Ghana 13 Years After National Policy Change(Dovepress, 2021) Ofori, M.F.; Kploanyi, E.E.; Mensah, B.A.; Dickson, E.K.; Kyei-Baafour, E.; Gyabaa, S.; Tetteh, M.; Koram, K.A.; Abuaku, B.K.; Ghansah, A.Purpose: Malaria continues to be a major health issue globally with almost 85% of the global burden and deaths borne by sub-Saharan Africa and India. Although the current artemisinin derived combination therapies in Ghana are still efficacious against the Plasmodium falciparum (Pf) parasite, compounding evidence of artemisinin and amodiaquine resistance establish the need for a full, up-to-date understanding and monitoring of antimalarial resistance to provide evidence for planning control strategies. Materials and Methods: The study was cross-sectional and was conducted during the peak malaria transmission seasons of 2015, 2016, and 2017 in two ecological zones of Ghana. Study participants included children aged 6 months to 14 years. Using ex vivo 4,6-diamidino-2-phenylindole (DAPI) drug sensitivity assay, 330 Pf isolates were used to investigate susceptibility to five antimalarial drugs: chloroquine (CQ), amodiaquine (AMD) dihydroartemisinin (DHA), artesunate (ART) and mefloquine (MFQ). Results: The pooled geometric mean IC50S (GMIC50) of the five drugs against the parasites from Cape Coast and Begoro were 15.5, 42.4, 18.9, 4.6 and 27.3nM for CQ, AMD, DHA, ART, and MFQ, respectively. The GMIC50 values for CQ (p<0.001), ART (p<0.011) and DHA (p<0.018) were significantly higher for Cape Coast isolates as compared to Begoro isolates. However, GMIC50 estimates for MFQ (p<0.022) were significantly higher for Begoro isolates. Positive correlations were found between each pair of drugs with the weakest found between MFQ and DHA (r = 0.34;p<0.001), and the strongest between ART and DHA (r =0.66; p<0.001). Conclusion: The parasites showed reduced sensitivities to three (AMD, DHA and MFQ) out of the five drugs assessed. The study also demonstrated the continual return of chloroquine-sensitive parasites after 13 years of its withdrawal as the first-line drug for the treatment of uncomplicated malaria in Ghana. The ex vivo DAPI assay is a reliable method for assessing antimalarial drug sensitivities of Pf field isolates under field settings.Item Utility of early diagnosis, contact tracing and stakeholder engagement in outbreak response in three COVID-19 outbreak settings in Ghana(Ghana Med J, 2021) Amoakoh-Coleman, M.; Bandoh, D.A.; Noora, C.L.; Alomatu, H.; Baidoo, A.; Quartey, S.; Kenu, E.; Koram, K.A.Objective: To describe how early case detection, testing and contact tracing measures were deployed by stakeholders in response to the COVID-19 outbreak in Ghana – using three outbreak scenarios. Design: A descriptive assessment of three case studies of COVID-19 outbreaks within three settings that occurred in Ghana from March 13 till the end of June 2020. Setting: A construction camp, a factory and a training institution in Ghana. Participants: Staff of a construction camp, a factory, workers and students of a training institution. Interventions: We described and compared the three COVID-19 outbreak scenarios in Ghana, highlighting identifi cation and diagnosis of cases, testing, contact tracing and stakeholder engagement for each scenario. We also outlined the challenges and lessons learnt in the management of these scenarios. Main outcome measures: Approach used for diagnosis, testing, contact tracing and stakeholder engagement. Results: Index cases of the training institution and construction camp were screened the same day of reporting symp toms, whiles the factory index case required a second visit before the screening. All index cases were tested with RT PCR. The training institution followed and tested all contacts, and an enhanced contact tracing approach was con ducted for staff of the other two sites. Multi-sectorial engagement and collaboration with stakeholders enabled effec tive handling of the outbreak response in all sites. Conclusion: Comparing all three settings, early diagnosis and prompt actions taken through multi-sectorial collabo rations played a major role in controlling the outbreak. Engaging stakeholders in the COVID-19 response is an effective way to mitigate the challenges in responding to the pandemicItem Data management during COVID-19 outbreak response in Ghana: a reference labor atory perspective on key issues and measures(Ghana Med J, 2021) Obodai, E.; Kyei, G.B.; Aboagye, J.; Bonney, E.Y.; Asante, I.A.; Bonney, J.K.H.; Adusei-Poku, M.; Lamptey, H.; Adu, B.; Kenu, E.; Koram, K.A.; Ampofo, W.K.; Odoom, J.K.The COVID-19 pandemic caused by SARS-CoV-2 is an important subject for global health. Ghana experienced low moderate transmission of the disease when the first case was detected in March 12, 2020 until the middle of July when the number of cases begun to drop. By August 24, 2020, the country's total number of confirmed cases stood at 43,622, with 263 deaths. By the same time, the Noguchi Memorial Institute for Medical Research (NMIMR) of the University of Ghana, the primary testing centre for COVID-19, had tested 285,501 with 28,878 confirmed cases. Due to database gaps, there were initial challenges with timely reporting and feedback to stakeholders during the peak surveillance period. The gaps resulted from mismatches between samples and their accompanying case investigation forms, sam ples without case investigation forms and vice versa, huge data entry requirements, and delayed test results. However, a revamp in data management procedures, and systems helped to improve the turnaround time for reporting results to all interested parties and partners. Additionally, inconsistencies such as multiple entries and discrepant patient-sample information were resolved by introducing a barcoding electronic capture system. Here, we describe the main chal lenges with COVID-19 data management and analysis in the laboratory and recommend measures for improvement.Item The impact of indoor residual spraying on Plasmodium falciparum microsatellite variation in an area of high seasonal malaria transmission in Ghana, West Africa(2021) Argyropoulos, D.C.; Ruybal-Pesántez, S.; Deed, S.L.; Oduro, A.R.; Dadzie, S.K.; Appawu, M.A.; Asoala, V.; Pascual, M.; Koram, K.A.; Day, K.P.; Tiedje, K.E.Here, we report the first population genetic study to examine the impact of indoor residual spraying (IRS) on Plasmodium falciparum in humans. This study was conducted in an area of high seasonal malaria transmission in Bongo District, Ghana. IRS was implemented during the dry season (November–May) in three consecutive years be tween 2013 and 2015 to reduce transmission and attempt to bottleneck the parasite population in humans towards lower diversity with greater linkage disequilibrium. The study was done against a background of widespread use of long-lasting insec ticidal nets, typical for contemporary malaria control in West Africa. Microsatellite genotyping with 10 loci was used to construct 392 P. falciparum multilocus infection haplotypes collected from two age-stratified cross-sectional surveys at the end of the wet seasons pre- and post-IRS. Three-rounds of IRS, under operational condi tions, led to a >90% reduction in transmission intensity and a 35.7% reduction in the P. falciparum prevalence (p < .001). Despite these declines, population genetic analysis of the infection haplotypes revealed no dramatic changes with only a slight, but significant increase in genetic diversity (He: pre-IRS = 0.79 vs. post-IRS = 0.81, p = .048). Reduced relatedness of the parasite population (p < .001) was observed post-IRS, probably due to decreased opportunities for outcrossing. Spatiotemporal genetic differentiation between the pre- and post-IRS surveys (D = 0.0329 [95% CI: 0.0209 – 0.0473], p = .034) was identified. These data provide a genetic explanation for the resilience of P. falciparum to short-term IRS programmes in high-transmission settings in sub-Saharan Africa.Item High frequency of the Dufy-negative genotype and absence of Plasmodium vivax infections in Ghana(Malaria Journal, 2021) Brown, C.A.; Pappoe‑Ashong, P.J.; Duah, N.; Ghansah, A.; Asmah, H.; Afari, E.; Koram, K.A.Background: Recent studies from diferent malaria-endemic regions including western Africa have now shown that Plasmodium vivax can infect red blood cells (RBCs) and cause clinical disease in Dufy-negative people, though the Dufy-negative phenotype was thought to confer complete refractoriness against blood invasion with P. vivax. The actual prevalence of P. vivax in local populations in Ghana is unknown and little information is available about the distribution of Dufy genotypes. The aim of this study was to assess the prevalence of P. vivax in both asymptomatic and symptomatic outpatients and the distribution of Dufy genotypes in Ghana. Methods: DNA was extracted from dried blood spots (DBS) collected from 952 subjects (845 malaria patients and 107 asymptomatic persons) from nine locations in Ghana. Plasmodium species identifcation was carried out by nested polymerase chain reaction (PCR) amplifcation of the small-subunit (SSU) rRNA genes. For P. vivax detection, a second PCR of the central region of the Pvcsp gene was carried out. Dufy blood group genotyping was performed by allele-specifc PCR to detect the presence of the FYES allele. Results: No cases of P. vivax were detected in any of the samples by both PCR methods used. Majority of infections (542, 94.8%) in the malaria patient samples were due to P. falciparum with only 1 infection (0.0017%) due to Plasmo dium malariae, and 2 infections (0.0034%) due to Plasmodium ovale. No case of mixed infection was identifed. Of the samples tested for the FYES allele from all the sites, 90.5% (862/952) had the FYES allele. All positive samples were genotyped as FY*B-33/FY*B-33 (Dufy-negative homozygous) and therefore classifed as Fy(a−b−). Conclusions: No cases of P. vivax were detected by both PCRs and majority of the subjects tested carried the FYES allele. The lack of P. vivax infections observed can be attributed to the high frequency of the FYES allele that silences erythroid expression of the Dufy. These results provide insights on the host susceptibility for P. vivax infections that had not been investigated in Ghana before.Item High frequency of the Duffy‑negative genotype and absence of Plasmodium vivax infections in Ghana(Malaria Journal, 2021) Brown, C.A.; Pappoe‑Ashong, P.J.; Duah, N.; Ghansah, A.; Asmah, H.; Afari, E.; Koram, K.A.Background: Recent studies from different malaria-endemic regions including western Africa have now shown that Plasmodium vivax can infect red blood cells (RBCs) and cause clinical disease in Duffy-negative people, though the Duffy-negative phenotype was thought to confer complete refractoriness against blood invasion with P. vivax. The actual prevalence of P. vivax in local populations in Ghana is unknown and little information is available about the distribution of Duffy genotypes. The aim of this study was to assess the prevalence of P. vivax in both asymptomatic and symptomatic outpatients and the distribution of Duffy genotypes in Ghana. Methods: DNA was extracted from dried blood spots (DBS) collected from 952 subjects (845 malaria patients and 107 asymptomatic persons) from nine locations in Ghana. Plasmodium species identification was carried out by nested polymerase chain reaction (PCR) amplification of the small-subunit (SSU) rRNA genes. For P. vivax detection, a second PCR of the central region of the Pvcsp gene was carried out. Duffy blood group genotyping was performed by allele-specific PCR to detect the presence of the FYES allele. Results: No cases of P. vivax were detected in any of the samples by both PCR methods used. Majority of infections (542, 94.8%) in the malaria patient samples were due to P. falciparum with only 1 infection (0.0017%) due to Plasmodium malariae, and 2 infections (0.0034%) due to Plasmodium ovale. No case of mixed infection was identified. Of the samples tested for the FYES allele from all the sites, 90.5% (862/952) had the FYES allele. All positive samples were genotyped as FY*B-33/FY*B-33 (Duffy-negative homozygous) and therefore classified as Fy(a−b−). Conclusions: No cases of P. vivax were detected by both PCRs and majority of the subjects tested carried the FYES allele. The lack of P. vivax infections observed can be attributed to the high frequency of the FYES allele that silences erythroid expression of the Duffy. These results provide insights on the host susceptibility for P. vivax infections that had not been investigated in Ghana before.Item Antibiotic prescription for febrile outpatients: a health facility-based secondary data analysis for the Greater Accra region of Ghana(University of Ghana, 2020-09) Opoku, M.M; Bonful, H.A.; Koram, K.A.Background: Misguided prescription of antibiotics is an important contributor towards the emergence and spread of antibiotic resistance. The absence of effective interventions to control antibiotic use leads to increased consumption beyond the needed requirements. Antibiotic stewardship interventions must be appropriately targeted and assessed to enhance the controlled use of antibiotics. The objective of this study was to determine the factors associated with antibiotic prescription to febrile outpatients who seek care in health facilities within the Greater Accra region of Ghana. Methods: Secondary data obtained from the medical records of 2519 febrile outpatients, consecutively sampled at the outpatient department of 6 health facilities in 3 municipalities during the baseline survey of a quasi-experiment in 2015 was used. The primary outcome was prescription of any antibiotic. Independent variables included patients’ demographics, symptoms, laboratory investigations (blood film microscopy, malaria rapid diagnostic test, full blood count, urine and stool routine examinations), diagnoses, and prescribers’ demographics. Crude and adjusted logistic regression analyses were used to determine the factors associated with antibiotic prescription. Results: The prevalence of antibiotic prescription was 70.1% (95% CI: 67.7–72.4). Prescribers with more years of practice (> 5 years) were more likely to prescribe antibiotics compared to those with less than 3 years of practice (p < 0.001). Integrated Management of Neonatal and Childhood Illnesses (IMNCI) training was associated with a 2.3 (95% CI: 1.54, 3.53, p < 0.001) fold odds of antibiotic prescribing. Patients aged 5 years or more were 60% less likely to receive antibiotics compared with those under 5 years (AOR = 0.40, 95% CI: 0.32, 0.51; p < 0.001). Patients referred for laboratory investigations were 29% less likely to be prescribed antibiotics than those not referred. The presence of cough as a presenting symptom was associated with a 3.5 (95% CI: 2.54, 4.92) fold odds of antibiotic prescription. Conclusion: Prescription of antibiotics to febrile outpatients was high. Promoting laboratory testing can potentially reduce irrational antibiotic prescription. Prescribing antibiotics for children under five and the prescribing practices of prescribers with longer years of practice should be targeted with interventions to reduce high use of antibioticsItem 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 Impact of an Irrigation Dam on the Transmission and Diversity of Plasmodium falciparum in a Seasonal Malaria Transmission Area of Northern Ghana(Journal of Tropical Medicine, 2020-03-19) Kyei-Baafour, E.; Tornyigah, B.; Buade, B.; Bimi, L.; Oduro, A.R.; Koram, K.A.; Gyan, B.A.; Kusi, K.A.Water bodies such as dams are known to alter the local transmission patterns of a number of infectious diseases, especially those transmitted by insects and other arthropod vectors. (e impact of an irrigation dam on submicroscopic asexual parasite carriage in individuals living in a seasonal malaria transmission area of northern Ghana was investigated. A total of 288 archived DNA samples from two cross-sectional surveys in two communities in the Bongo District of Northern Ghana were analysed. Parasite density was determined by light microscopy and PCR, and parasite diversity was assessed by genotyping of the polymorphic Plasmodium falciparum msp2 block-3 region. Submicroscopic parasitaemia was estimated as the proportional difference between positive samples identified by PCR and microscopy. Dry season submicroscopic parasite prevalence was significantly higher (71.0%, p = 0.013) at the dam site compared with the nondam site (49.2%). Similarly, wet season submicroscopic parasite prevalence was significantly higher at the dam site (54.5%, p = 0.008) compared with the nondam site (33.0%). (ere was no difference in parasite density between sites in the dry season (p = 0.90) and in the wet season (p < 0.85). Multiplicity of infection (MOI) based on PCR data was significantly higher at the dam site compared with the nondam site during the dry season (p < 0.0001) but similar between sites during the wet season. MOI at the nondam site was significantly higher in the wet season than in the dry season (2.49, 1.26, p < 0.0001) but similar between seasons at the dam site. Multivariate analysis showed higher odds of carrying submicroscopic parasites at the dam site in both dry season (OR = 7.46, 95% CI = 3.07–18.15) and in wet season (OR = 1.73, 95% CI = 1.04–2.86). (e study findings suggest that large water bodies impact year-round carriage of submicroscopic parasites and sustain Plasmodium transmission