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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    Immune Signature Against Plasmodium falciparum Antigens Predicts Clinical Immunity in Distinct Malaria Endemic Communities
    (Molecular & Cellular Proteomics, 2019-10-28) Dodoo, D.; Proietti, C.; Krause, L.; Trieu, A.; Gyan, B.; Koram, K.A.; Rogers, W.O.; Richie, T.L.; Crompton, P.D.; Felgner, P.L.; Doolan, D.L.
    A large body of evidence supports the role of antibodies directed against the Plasmodium spp. parasite in the development of naturally acquired immunity to malaria, however an antigen signature capable of predicting protective immunity against Plasmodium remains to be identified. Key challenges for the identification of a predictive immune signature include the high dimensionality of data produced by high-throughput technologies and the limitation of standard statistical tests in accounting for synergetic interactions between immune responses to multiple targets. In this study, using samples collected from young children in Ghana at multiple time points during a longitudinal study, we adapted a predictive modeling framework which combines feature selection and machine learning techniques to identify an antigen signature of clinical immunity to malaria. Our results show that an individual's immune status can be accurately predicted by measuring antibody responses to a small defined set of 15 target antigens. We further demonstrate that the identified immune signature is highly versatile and capable of providing precise and accurate estimates of clinical protection from malaria in an independent geographic community. Our findings pave the way for the development of a robust point-of-care test to identify individuals at high risk of disease and which could be applied to monitor the impact of vaccinations and other interventions. This approach could be also translated to biomarker discovery for other infectious diseases
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    Probing the composition of Plasmodium species contained in malaria infections in the Eastern region of Ghana
    (BMC Public Health, 2019-12-02) Amoah, L.E.; Donu, D.; Abuaku, B.; Ahorlu, C.; Arhinful, D.; Afari, E.; Malm, K.; Koram, K.A.
    Background: Asymptomatic falciparum and non-falciparum malaria infections are major challenges to malaria control interventions, as they remain a source of continual infection in the community. This becomes even more important as the debate moves towards elimination and eradication. This study sought to quantify the burden of Plasmodium malaria infection in seven communities in the Eastern Region of Ghana. Methods: The cross-sectional study recruited 729 participants aged 85 years old and below from 7 closely linked communities. Finger pricked blood was used to prepare thick and thin blood smears as well as spot filter paper and an histidine rich protein 2 (HRP2) rapid diagnostic test kit (RDT). Genomic DNA was extracted from the filter paper dry blood spot (DBS) and used in PCR to amplify the Plasmodium 18S rRNA gene using species specific PCR. Results: 96.6% of the participants were identified as afebrile, with axillary temperatures below 37.5 °C. PCR identified 66% of the participants to harbor malaria parasites, with 9 P. malariae and 7 P. ovale mono-infections accounting for 2.2% and P. falciparum combined with either 36 P. malariae or 25 P. ovale infections, accounting for 13.3%. Parasite prevalence by microscopy (32%) was similar to the RDT positivity rate (33%). False positive RDT results ranged from 64.6% in children aged between 5 and 9 years to 10% in adults aged 20 years and above. No significant differences were observed in falciparum and non-falciparum parasite carriage at the community level, however young adults aged between 15 and 19 years had the highest prevalence (34.8% (16/46)) of P. falciparum and P. malariae parasite carriage whilst children aged between 5 and 9 years had the highest level (11.4% (14/123)) of P. ovale carriage. Conclusion: The high rate of misidentification of non-falciparum parasites and the total absence of detection of P. ovale by microscopy suggests that more sensitive malaria diagnostic tools including molecular assays are required to accurately determine the prevalence of carriers of non-falciparum parasites and low density P. falciparum infections, especially during national surveillance exercises. Additionally, malaria control interventions targeting the non-falciparum species P. malariae and P. ovale parasites are needed.
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    Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana
    (BMC Public Health, 2019-12-03) Ndong, I.C.; Okyere, D.; Enos, J.Y.; Mensah, B.A.; Nyarko, A.; Abuaku, B.; Amambua-Ngwa, A.; Merle, C.S.C.; Koram, K.A.; Ahorlu, C.S.
    Background: Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Indoor Residual Spraying, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly due to the fact that asymptomatic parasite carriage, not specifically targeted by most interventions, remains the bedrock that fuels transmission. This has led to mass testing, treatment and tracking (MTTT) as an alternative strategy to target asymptomatic individuals. We report the impact of MTTT on the prevalence of asymptomatic malaria parasitaemia over a one-year period in Ghana, hypothesizing that implementing MTTT could reduce the rate of asymptomatic parasitaemia. Methods: A population of about 5000 individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained communitybased health volunteers who conducted house-to-house testing using RDTs every 4 months and treated positive cases with Artemisinin–based Combination Therapy. Between interventions, community-based management of malaria was implemented for symptomatic cases. Results: MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 36.3% (1795/4941) in July 2017 to 32.9% (1303/3966) in July 2018 (p = 0.001). Prevalence of asymptomatic parasitaemia among children under 15 years declined from 52.6% (1043/1984) in July 2017 to 47.5% (820/1728) in July 2018 (p = 0.002). Implementing MTTT significantly reduced asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and axillary temperature (OR = 0.76, CI = 0.67, 0.85 p ≤ 0.001). Conclusion: This study has demonstrated that implementing MTTT is feasible and could reduce the prevalence of asymptomatic malaria parasitaemia in children under 15 years of age. Furthermore, the use of community-based health volunteers could ensure high coverage at lower cost of implementation.
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    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.
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    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.
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    Acquisition of IGG to ICAM-1-Binding DBLΒ Domains in the plasmodium falciparum erythrocyte membrane protein 1 antigen family varies between groups A, B, and C
    (Infection and Immunity, 2019-09-19) Ecklu-Mensah, G.; Olsen, R.W.; Bengtsson, A.; Ofori, M.F.; Kusi, K.A.; Koram, K.A.; Hviid, L.; Adams, Y.; Jensen, A.T.R.
    Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important malaria virulence factor. The protein family can be divided into clinically relevant subfamilies. ICAM-1-binding group A PfEMP1 proteins also bind endothelial protein C receptor and have been associated with cerebral malaria in children. IgG to these PfEMP1 proteins is acquired later in life than that to group A PfEMP1 not binding ICAM-1. The kinetics of acquisition of IgG to group B and C PfEMP1 proteins binding ICAM-1 is unclear and was studied here. Gene sequences encoding group B and C PfEMP1 with DBL domains known to bind ICAM-1 were used to identify additional binders. Levels of IgG specific for DBL domains from group A, B, and C PfEMP1 binding or not binding ICAM-1 were measured in plasma from Ghanaian children with or without malaria. Seven new ICAM-1-binding DBL domains from group B and C PfEMP1 were identified. Healthy children had higher levels of IgG specific for ICAM-1-binding DBL domains from group A than from groups B and C. However, the opposite pattern was found in children with malaria, particularly among young patients. Acquisition of IgG specific for DBL domains binding ICAM-1 differs between PfEMP1 groups.
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    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.
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    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.
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    Antigenicity and immune correlate assessment of seven Plasmodium falciparum antigens in a longitudinal infant cohort from northern Ghana
    (Scientific Reports, 2019) Kusi, K.A.; Aguiar, J.; Kumordjie, S.; Aggor, F.; Bolton, J.; Renner, A.; Kyei-Baafour, E.; Puplampu, N.; Belmonte, M.; Dodoo, D.; Gyan, B.A.; Ofori, M.F.; Oduro, R.A.; Atuguba, F.; Koram, K.A.; Adams, N.; Letizia, A.; Villasante, E.; Sedegah, M.
    The current global malaria control and elimination agenda requires development of additional effective disease intervention tools. Discovery and characterization of relevant parasite antigens is important for the development of new diagnostics and transmission monitoring tools and for subunit vaccine development. This study assessed the natural antibody response profile of seven novel Plasmodium falciparum pre-erythrocytic antigens and their potential association with protection against clinical malaria. Antigen-specific antibody levels in plasma collected at six time points from a longitudinal cohort of one-to-five year old children resident in a seasonal malaria transmission area of northern Ghana were assessed by ELISA. Antibody levels were compared between parasite-positive and parasite-negative individuals and the association of antibody levels with malaria risk assessed using a regression model. Plasma antibody levels against five of the seven antigens were significantly higher in parasite-positive children compared to parasite-negative children, especially during low transmission periods. None of the antigen-specific antibodies showed an association with protection against clinical malaria. The study identified five of the seven antigens as markers of exposure to malaria, and these will have relevance for the development of disease diagnostic and monitoring tools. The vaccine potential of these antigens requires further assessment. © 2019, The Author(s).
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    Information gaps in surveillance data and effects on the Ghanaian response to the Ebola outbreak in West Africa
    (Ghana medical journal, 2017-09) Awini, E.A.; Bonney, J.H.K.; Frimpong, J.A.; Ampofo, W.K.; Koram, K.A.
    Background: Complete and accurate information on disease occurrence is crucial for effective public health response to disease outbreaks. In response to the 2014 Ebola epidemic in West Africa, Ghana intensified surveillance for the disease across the country. However, the case definition provided by the Ministry of Health was not uniformly applied at all reporting health facilities.Objective: This paper analyses the accompanying Case Record Forms (CRFs) submitted to Noguchi Memorial Institute for Medical Research to determine its completeness and appropriateness for instituting an effective response to the epidemic.Methods: We determined the proportions of completeness in reporting for all criteria provided by the MOH for the clinical diagnosis of Ebola. New indicators were generated to measure the completeness of each variable. Tables and graphs of completeness of indicators were produced and presented.Results: Of the 156 samples, 69% were from males. Approximately 4.5% had no record for age. The date of specimen collection was filled for 96%; 34.6% (54) did not have date of onset of symptoms. In 37.8% (59) of cases, location was blank. In 12% of cases, no symptoms were recorded and about 30% had no record of fever. Travel history, especially to affected areas, was missing for 40.4%.Conclusions: Gaps on CRFs can significantly reduce the utility of results of laboratory analysis for outbreak control. Although all the samples analysed were negative for Ebola Virus, the high proportion of missing data on the forms should be a source of concern. We recommend that frontline health staff be trained on the importance of capturing all information required on the form.Source of funding: The funding for the analysis of suspected samples were provided partially by Ghana Health Servce and research funding from Noguchi Memorial Institute for Medical Research.