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 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 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 Malaria causes long-term effects on markers of iron status in children: a critical assessment of existing clinical and epidemiological tools(Malaria Journal, 2018-12) Castberg, F.C.; Sarbah, E.W.; Koram, K.A.; Opoku, N.; Ofori, M.F.; Styrishave, B.; Hviid, L.; Kurtzhals, J.A.L.Background Most epidemiological studies on the interplay between iron deficiency and malaria risk classify individuals as iron-deficient or iron-replete based on inflammation-dependent iron markers and adjustment for inflammation by using C-reactive protein (CRP) or α-1-acid glycoprotein (AGP). The validity of this approach and the usefulness of fibroblast growth factor 23 (FGF23) as a proposed inflammation-independent iron marker were tested. Methods Conventional iron markers and FGF23 were measured in children with acute falciparum malaria and after 1, 2, 4, and 6 weeks. Children, who were transfused or received iron supplementation in the follow-up period, were excluded, and iron stores were considered to be stable throughout. Ferritin levels 6 weeks after admission were used as a reference for admission iron status and compared with iron markers at different time points. Results There were long-term perturbations in iron markers during convalescence from acute malaria. None of the tested iron parameters, including FGF23, were independent of inflammation. CRP and AGP normalized faster than ferritin after malaria episodes. Conclusion Malaria may bias epidemiological studies based on inflammation-dependent iron markers. Better markers of iron status during and after inflammation are needed in order to test strategies for iron supplementation in populations at risk of malaria.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 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 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 Measuring naturally acquired ex vivo IFN-γ responses to Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (CelTOS) in Ghanaian adults(Malaria Journal, 2015-01) Anum, D.; Kusi, K.A.; Ganeshan, H.; Hollingdale, M.R.; Ofori, M.F.; Koram, K.A.; Gyan, B.A.; Adu-Amankwah, S.; Badji, E.; Huang, J.; Belmonte, M.; Banania, G.J.; Kwofie, T.B.; Villasante, E.; Dodoo, D.; Sedegah, M.Background: A malaria vaccine that targets the sporozoite/liver stage parasites could potentially prevent blood stage infection and the associated clinical symptoms. Identification of sporozoite/liver stage antigens is, therefore, crucial for the development of effective vaccines. Cell-traversal protein for ookinetes and sporozoites (CelTOS) is a highly conserved antigen involved in sporozoite motility and hepatocyte invasion and has been shown to induce significant IFN-γ production in PBMCs from radiation-attenuated sporozoite-immunized malaria-na�ve individuals. The aim of this study was to ascertain whether such CelTOS-specific recall responses are also induced in individuals with natural exposure to Plasmodium falciparum. Methods: Ex vivo IFN-γ responses to 15mer overlapping peptide pools covering the entire sequence of CelTOS and five other candidate antigens, CSP, AMA1, MSP1, TRAP and LSA1, were characterized using PBMCs from 35 malaria exposed adults. Responses to four CelTOS peptide pools (CelTp1, CelTp2, CelTp3 and CelTp4), a pool containing peptides from the entire CelTOS antigen (CelTTp), and pools comprised of overlapping peptides from each of the other five malaria antigens were assessed by ex vivo ELISpot assay. A positive IFN-γ response for stimulants was defined by two criteria; a stimulation index of two or greater relative to the unstimulated control, and a difference of 10 or greater in spot forming cells between stimulant and the unstimulated control. Results: Of the 35 volunteers tested, five had positive IFN-γ recall responses against the four different CelTOS pools while four volunteers made responses against the CelTTp pool; six volunteers were, therefore, positive with CelTOS. By contrast, six volunteers responded to AMA1, seven to LSA1, 15 to MSP1 and two volunteers responded against CSP and TRAP. Conclusions: These results suggest natural malaria transmission induces CelTOS-specific ex vivo IFN-γ in Ghanaian adults and that the frequency of these responses was similar to those of other previously characterized malaria antigens. These findings support the further evaluation of CelTOS as a pre-erythrocytic candidate antigen for inclusion in a potential multi-antigen vaccine. � 2015 Anum et al.; licensee Biomed Central.Item A novel locus of resistance to severe malaria in a region of ancient balancing selection.(Nature Publishing Group, 2015-09) Band, G.; Rockett, K.A.; Spencer, C.C.A.; Johnson, K.J.; Koram, K.A.; Wilson, M.D.; Agbenyega, T.; Malaria Genomic Epidemiology NetworkAbstract The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-threatening Plasmodium falciparum infection (severe malaria) in over 11,000 African children, with replication data in a further 14,000 individuals. Here we report a novel malaria resistance locus close to a cluster of genes encoding glycophorins that are receptors for erythrocyte invasion by P. falciparum. We identify a haplotype at this locus that provides 33% protection against severe malaria (odds ratio = 0.67, 95% confidence interval = 0.60-0.76, P value = 9.5 × 10(-11)) and is linked to polymorphisms that have previously been shown to have features of ancient balancing selection, on the basis of haplotype sharing between humans and chimpanzees. Taken together with previous observations on the malaria-protective role of blood group O, these data reveal that two of the strongest GWAS signals for severe malaria lie in or close to genes encoding the glycosylated surface coat of the erythrocyte cell membrane, both within regions of the genome where it appears that evolution has maintained diversity for millions of years. These findings provide new insights into the host-parasite interactions that are critical in determining the outcome of malaria infection.