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 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 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 transmissionItem Plasmodium falciparum Kelch Propeller Polymorphisms in Clinical Isolates from Ghana from 2007 to 2016(EPIDEMIOLOGY AND SURVEILLANCE, 2019-10-22) Matrevi, S.A.; Opoku-Agyeman, P.; Quashie, N.B.; Bruku, S.; Abuaku, B.; Koram, K.A.; Fox, A.; Letizia, A.; Duah-Quashie, N.O.The continuous surveillance of polymorphisms in the kelch propeller domain of Plasmodium falciparum from Africa is important for the discovery of the actual markers of artemisinin resistance in the region. The information on the markers is crucial for control strategies involving chemotherapy and chemoprophylaxis for residents and nonimmune travelers to the country. Polymorphisms in the kelch propeller domain of Ghanaian malaria parasites from three different ecological zones at several time periods were assessed. A total of 854 archived samples (2007 to 2016) collected from uncomplicated malaria patients aged 9 years old from 10 sentinel sites were used. Eighty-four percent had wild-type sequences (PF3D7_1343700), while many of the mutants had mostly nonsynonymous mutations clustered around codons 404 to 650. Variants with different amino acid changes of the codons associated with artemisinin (ART) resistance validated markers were observed in Ghanaian isolates: frequencies for I543I, I543S, I543V, R561P, R561R, and C580V were 0.12% each and 0.6% for R539I. Mutations reported from African parasites, A578S (0.23%) and Q613L (0.23%), were also observed. Three persisting nonsynonymous (NS) mutations, N599Y (0.005%), K607E (0.004%), and V637G (0.004%), were observed in 3 of the 5 time periods nationally. The presence of variants of the validated markers of artemisinin resistance as well as persisting polymorphisms after 14 years of artemisinin-based combination therapy use argues for continuous surveillance of the markers. The molecular markers of artemisinin resistance and the observed variants will be monitored subsequently as part of ongoing surveillance of antimalarial drug efficacy/resistance studies in the country.Item Extent of inappropriate prescription of artemisinin and anti‑malarial injections to febrile outpatients, a cross‑sectional analytic survey in the Greater Accra region, Ghana(BMC Malaria Journal, 2019-09-27) Adanu, R.M.K.; Bonful, H.A.; Awua, A.K.; Adjuik, M.; Tsekpetse, D.; Nortey, P.A.; Ankomah, A.; Koram, K.A.Background: Febrile children seen in malaria hypo-endemic settings, such as the Greater Accra region (GAR) of Ghana are more likely to be suffering from a non-malarial febrile illness compared to those seen in hyper-endemic settings. The need for prescribers to rely on malaria test results to guide treatment practices in the GAR is even greater. This study was designed to investigate the factors associated with inappropriate artemisinin-based combination therapy (ACT) prescription. Methods: A survey was conducted in six health facilities in the region in 2015. Treatment practices for febrile outpatient department (OPD) patients were obtained from their records. Prescribers were interviewed and availability of malaria commodities were assessed. The primary outcome was the proportion of patients prescribed ACT inappropriately. Independent variables included patient age and access to care, prescriber factors (professional category, work experience, access to guidelines, exposure to training). Data were analysed using Stata at 95% CI (α-value of 0.05). Frequencies and means were used to describe the characteristics of patients and prescribers. To identify the predictors of inappropriate ACT prescription, regression analyses were performed accounting for clustering. Results: Overall, 2519 febrile OPD records were analysed; 45.6% (n = 1149) were younger than 5 years. Only 40.0% of patients were tested. The proportion of patients who were prescribed ACT inappropriately was 76.4% (n = 791 of 1036). Of these 791 patients, 141 (17.8%) were prescribed anti-malarial injections. Patients seen in facilities with rapid diagnostic tests (RDT) in stock were less likely to be prescribed ACT inappropriately, (AOR: 0.04, 95% CI 0.01–0.14, p < 0.001) compared to those seen in facilities with RDT stock-outs. Prescribers who had been trained on malaria case management within the past year were 4 times more likely to prescribe ACT inappropriately compared to those who had not been trained (AOR: 4.1; 95% CI (1.5–11.6); p < 0.01). Patients seen by prescribers who had been supervised were 8 times more likely to be prescribed ACT inappropriately. Conclusion: Inappropriate ACT prescription to OPD febrile cases was high. Training and supervision of health workers appears not to be yielding the desired outcomes. Further research is needed to understand this observation.Item Malaria vaccine deployment in Africa: focus on Ghana(Ghana medical journal, 2019-06-02) Koram, K.A.; Asante, K.P.; Binka, F.N.The announcement by the Ghana Health Service /Ministry of Health at the beginning of May to begin the pilot implementation of the malaria vaccine – RTS,S/AS01 (Mosquirix®) – manufactured by GSK Biologicals was greeted with rumours about conspiracy theories of secret agenda to depopulate Africa through the use of vaccines and all the other stories that are often propagated by the anti vaxxers. This was not unlike the fear and panic spread throughout the country that prevented investigators from conducting clinical trials on new vaccines against the Ebola virus disease a few years ago.Item Challenges and perceptions of implementing mass testing, treatment and tracking in malaria control: a qualitative study in Pakro sub-district of Ghana(BMC Public Health, 2019-05-23) Enos, J.Y.; Ndong, I.C.; Okyere, D.; Amambua-Ngwa, A.; Merle, C.S.C.; Nyarko, A.; Koram, K.A.; Ahorlu, C.S.Background: Malaria remains endemic in Ghana despite several interventions. Studies have demonstrated very high levels of asymptomatic malaria parasitaemia in both under-five and school-age children. Mass testing, treatment and tracking (MTTT) of malaria in communities is being proposed for implementation with the argument that it can reduce parasite load, amplify gains from the other control interventions and consequently lead to elimination. However, challenges associated with implementing MTTT such as feasibility, levels of coverage to be achieved for effectiveness, community perceptions and cost implications need to be clearly understood. This qualitative study was therefore conducted in an area with on-going MTTT to assess community and health workers’ perceptions about feasibility of scale-up and effectiveness to guide scale-up decisions. Methods: This qualitative study employed purposive sampling to select the study participants. Ten focus group discussions (FGDs) were conducted in seven communities; eight with community members (n = 80) and two with health workers (n = 14). In addition, two in-depth interviews (IDI) were conducted, one with a Physician Assistant and another with a Laboratory Technician at the health facility. All interviews were recorded, transcribed, translated and analyzed using QSR NVivo 12. Results: Both health workers and community members expressed positive perceptions about the feasibility of implementation and effectiveness of MTTT as an intervention that could reduce the burden of malaria in the community. MTTT implementation was perceived to have increased sensitisation about malaria, reduced the incidence of malaria, reduced household expenditure on malaria and alleviated the need to travel long distances for healthcare. Key challenges to implementation were doubts about the expertise of trained Community-Based Health Volunteers (CBHVs) to diagnose and treat malaria appropriately, side effects of Artemisinin-based Combination Therapies (ACTs) and misconceptions that CBHVs could infect children with epilepsy. Conclusion: The study demonstrated that MTTT was perceived to be effective in reducing malaria incidence and related hospital visits in participating communities. MTTT was deemed useful in breaking financial and geographical barriers to accessing healthcare. The interventions were feasible and acceptable to community members, despite observed challenges to implementation such as concerns about CBHVs’ knowledge and skills and reduced revenue from internally generated funds (IGF) of the health facility.Item Prevalence of Plasmodium falciparum delayed clearance associated polymorphisms in adaptor protein complex 2 mu subunit (pfap2mu) and ubiquitin specific protease 1 (pfubp1) genes in Ghanaian isolates(Parasites and Vectors, 2018-12) Adams, T.; Ennuson, N.A.A.; Quashie, N.B.; Futagbi, G.; Matrevi, S.; Hagan, O.C.K.; Abuaku, B.; Koram, K.A.; Duah, N.O.Background Plasmodium falciparum delayed clearance with the use of artemisinin-based combination therapy (ACTs) has been reported in some African countries. Single nucleotide polymorphisms (SNPs) in two genes, P. falciparum adaptor protein complex 2 mu subunit (pfap2mu) and ubiquitin specific protease 1 (pfubp1), have been linked to delayed clearance with ACT use in Kenya and recurrent imported malaria in Britain. With over 12 years of ACT use in Ghana, this study investigated the prevalence of SNPs in the pfap2mu and pfubp1 in Ghanaian clinical P. falciparum isolates to provide baseline data for antimalarial drug resistance surveillance in the country. Methods Filter paper blood blots collected in 2015–2016 from children aged below 9 years presenting with uncomplicated malaria at hospitals in three sentinel sites Begoro, Cape Coast and Navrongo were used. Parasite DNA was extracted from 120 samples followed by nested polymerase chain reaction (nPCR). Sanger sequencing was performed to detect and identify SNPs in pfap2mu and pfubp1 genes. Results In all, 11.1% (9/81) of the isolates carried the wildtype genotypes for both genes. A total of 164 pfap2mu mutations were detected in 67 isolates whilst 271 pfubp1 mutations were observed in 72 isolates. The majority of the mutations were non-synonymous (NS): 78% (128/164) for pfap2mu and 92.3% (250/271) for pfubp1. Five unique samples had a total of 215 pfap2mu SNPs, ranging between 15 and 63 SNPs per sample. Genotypes reportedly associated with ART resistance detected in this study included pfap2mu S160N (7.4%, 6/81) and pfubp1 E1528D (7.4%, 6/81) as well as D1525E (4.9%, 4/81). There was no significant difference in the prevalence of the SNPs between the three ecologically distinct study sites (pfap2mu: χ2 = 6.905, df = 2, P = 0.546; pfubp1: χ2 = 4.883, df = 2, P = 0.769). Conclusions The detection of pfap2mu and pfubp1 genotypes associated with ACT delayed parasite clearance is evidence of gradual nascent emergence of resistance in Ghana. The results will serve as baseline data for surveillance and the selection of the genotypes with drug pressure over time. The pfap2mu S160N, pfubp1 E1528D and D1525E must be monitored in Ghanaian isolates in ACT susceptibility studies, especially when cure rates of ACTs, particularly AL, is less than 100%.