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 Prevalence of malaria infection and the impact of mosquito bed net distribution among children aged 6–59 months in Ghana: Evidence from the Ghana demographic health and malarial indicator surveys(Parasite Epidemiology and Control, 2023) Tetteh, J.; Yorke, E.; Boima, V.; Yawson, A.E.Objective: To assess the prevalence of malaria infection and further quantify the impact of mosquito bed net distribution on malaria infection among children aged 6–59 months in Ghana. Methods: A cross-sectional study using Ghana Demographic Health (GDHS) and Malaria Indicator (GMIS) surveys (2014 GDHS, 2016 GMIS, and 2019 GMIS). The exposure and the main outcomes were mosquito bed net use (MBU) and malaria infection (MI). Relative percentage change (Δ) and prevalence ratio (PR) were estimated to assess the changes and the risk of MI by MBU respec tively. The Propensity-score matching treatment effect model was employed to estimate the average treatment effect (ATE) of MBU on MI. All analyses were performed using Stata 16.1 and p-value<0.05 was deemed significant. Results: The study involved 8781 children aged 6–59 months. MI ranged from 25.8%(22.3–29.7) in 2019 GMIS to 40.6%(37.0–44.2) in 2014 GDHS and the prevalence was significantly high among children who used mosquito bed net. The relative percentage change in MI prevalence showed a significant reduction rate and was high among non-MBU (p-value<0.05). In all, the adjusted PR of MI among children exposed to MBU was 1.21(1.08–1.35), 1.13(1.01–1.28), and 1.50(1.20–1.75) in 2014 GDHS, 2016 GMIS, and 2019 GMIS respectively. The average MI among participants who slept in mosquito bed net significantly increased by 8%(0.04 to 0.12), 4%(0.003 to 0.08), and 7%(0.03 to 0.11) in 2014 GDHS, 2016 GMIS, and 2019 GMIS respectively. Conclusion: Even though malaria infection prevalence among children aged 6–59 months is decreasing, the reduction rate seems not to be directly linked with mosquito bed nets distribution and/or use in Ghana. For a continued distribution of mosquito bed nets, and for Ghana to achieve her Malaria Strategic Plan (NMSP) 2021–2025, program managers should ensure effective use of the distributed nets in addition to other preventive measures and nuanced consideration of community behaviours in Ghana. The effective use and care of bed nets should be emphasized as part of the distribution.Item Extended follow-up of children in a phase2b trial of the GMZ2 malaria vaccine(Elsevier, 2021) Dassah, S.; Adu, B.; Sirima, S.B.; Mordmüller, B.; Ngoa, U.A.; Atuguba, F.; Arthur, F.K.N.; Mensah, B.A.; Kaddumukasa, M.; Bang, P.; Kremsner, P.G.; Mategula, D.; Flach, C.; Milligan, P.; Theisen, M.The GMZ2/alum candidate malaria vaccine had an efficacy of 14% (95% confidence interval [CI]: 3.6%, 23%) against clinical malaria over 6 months of follow-up in a phase2b multicentre trial in chil dren 1–5 years of age. Here we report the extended follow up of safety and efficacy over 2 years. Methods: A total of 1849 (GMZ2 = 926, rabies = 923) children aged 12–60 months were randomized to receive intramuscularly, either 3 doses of 100 lg GMZ2/alum or 3 doses of rabies vaccine as control 28 days apart. The children were followed-up for 24 months for clinical malaria episodes and adverse events. The primary endpoint was documented fever with parasitaemia of at least 5000/lL. Results: There were 2,062 malaria episodes in the GMZ2/alum group and 2,115 in the rabies vaccine group in the intention-to-treat analysis, vaccine efficacy (VE) of 6.5% (95%: CI 1.6%, 14.0%). In children aged 1–2 years at enrolment, VE was 3.6% (95 %CI: 9.1%, 14.8%) in the first year and 4.1% (95 %CI: 18.7%, 87%) in the second year. In children aged 3–5 years at enrolment VE was 19.9% (95 %CI: 7.7%, 30.4%) in the first year and 6.3% (95 %CI: 10.2%, 20.3%) in the second year (interaction by year, P = 0.025, and by age group, P = 0.085). A total of 187 (GMZ2 = 91, rabies = 96) serious adverse events were recorded in 167 individuals over the entire period of the study. There were no GMZ2 vaccine related serious adverse events. Conclusions: GMZ2/alum was well tolerated. Follow-up over 2 years confirmed a low level of vaccine efficacy with slightly higher efficacy in older children, which suggests GMZ2 may act in concert with naturally acquired immunity.Item Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection(Malaria Journal, 2018-07) Frimpong, A.; Kusi, K.A.; Tornyigah, B.; Ofori, M.F.; Ndifon, W.Background Asymptomatic Plasmodium infections are characterized by the absence of clinical disease and the ability to restrict parasite replication. Increasing levels of regulatory T cells (Tregs) in Plasmodium falciparum infections have been associated with the risk of developing clinical disease, suggesting that individuals with asymptomatic infections may have reduced Treg frequency. However, the relationship between Tregs, cellular activation and parasite control in asymptomatic malaria remains unclear. Methods In a cross-sectional study, the levels of Tregs and other T cell activation phenotypes were compared using flow cytometry in symptomatic, asymptomatic and uninfected children before and after stimulation with infected red blood cell lysates (iRBCs). In addition, the association between these T cell phenotypes and parasitaemia were investigated. Results In children with asymptomatic infections, levels of Tregs and activated T cells were comparable to those in healthy controls but significantly lower than those in symptomatic children. After iRBC stimulation, levels of Tregs remained lower for asymptomatic versus symptomatic children. In contrast, levels of activated T cells were higher for asymptomatic children. Strikingly, the pre-stimulation levels of two T cell activation phenotypes (CD8+CD69+ and CD8+CD25+CD69+) and the post-stimulation levels of two regulatory phenotypes (CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+) were significantly positively correlated with and explained 68% of the individual variation in parasitaemia. A machine-learning model based on levels of these four phenotypes accurately distinguished between asymptomatic and symptomatic children (sensitivity = 86%, specificity = 94%), suggesting that these phenotypes govern the observed variation in disease status. Conclusion Compared to symptomatic P. falciparum infections, in children asymptomatic infections are characterized by lower levels of Tregs and activated T cells, which are associated with lower parasitaemia. The results indicate that T cell regulatory and activation phenotypes govern both parasitaemia and disease status in paediatric malaria in the studied sub-Saharan African population.Item Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination(Frontiers in immunology, 2019-03) Dobaño, C.; Santano, R.; Vidal, M.; Jiménez, A.; Jairoce, C.; Ubillos, I.; Dosoo, D.; Aguilar, R.; Williams, N.A.; Díez-Padrisa, N.; Ayestaran, A.et.al.Naturally acquired immunity (NAI) to Plasmodium falciparum malaria is mainly mediated by IgG antibodies but the subclasses, epitope targets and effector functions have not been unequivocally defined. Dissecting the type and specificity of antibody responses mediating NAI is a key step toward developing more effective vaccines to control the disease. We investigated the role of IgG subclasses to malaria antigens in protection against disease and the factors that affect their levels, including vaccination with RTS,S/AS01E. We analyzed plasma and serum samples at baseline and 1 month after primary vaccination with RTS,S or comparator in African children and infants participating in a phase 3 trial in two sites of different malaria transmission intensity: Kintampo in Ghana and Manhiça in Mozambique. We used quantitative suspension array technology (qSAT) to measure IgG1-4 responses to 35 P. falciparum pre-erythrocytic and blood stage antigens. Our results show that the pattern of IgG response is predominantly IgG1 or IgG3, with lower levels of IgG2 and IgG4. Age, site and RTS,S vaccination significantly affected antibody subclass levels to different antigens and susceptibility to clinical malaria. Univariable and multivariable analysis showed associations with protection mainly for cytophilic IgG3 levels to selected antigens, followed by IgG1 levels and, unexpectedly, also with IgG4 levels, mainly to antigens that increased upon RTS,S vaccination such as MSP5 and MSP1 block 2, among others. In contrast, IgG2 was associated with malaria risk. Stratified analysis in RTS,S vaccinees pointed to novel associations of IgG4 responses with immunity mainly involving pre-erythrocytic antigens upon RTS,S vaccination. Multi-marker analysis revealed a significant contribution of IgG3 responses to malaria protection and IgG2 responses to malaria risk. We propose that the pattern of cytophilic and non-cytophilic IgG antibodies is antigen-dependent and more complex than initially thought, and that mechanisms of both types of subclasses could be involved in protection. Our data also suggests that RTS,S efficacy is significantly affected by NAI, and indicates that RTS,S vaccination significantly alters NAI.Item A Survey of Anaemia in Children in the Korle Bu Hospital, with Special Reference to Malaria(Ghana Medical Journal, 1964-09) Jilly, P.; Nkrumah, F.K.Item Complement binding to erythrocytes is associated with macrophage activation and reduced haemoglobin in Plasmodium falciparum malaria(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2001-09) Goka, B.Q.; Kwarko, H.; Kurtzhals, J.A.L.; Gyan, B.; Ofori-Adjei, E.; Ohene, S.A.; Hviid, L.; Akanmori, B.D.; Neequaye, J.We have examined IgG and complement factor C3d deposition on erythrocytes by means of the direct Coombs' test (DAT) and looked for an association with the anaemia seen in falciparum malaria in children living in an area of hyperendemic malaria transmission (in Ghana). In one study (in 1997), 53 out of 199 patients had a positive DAT. Of these, 45 samples reacted with anti-C3d antibodies, 2 with anti-IgG and 6 with both reagents. There were significantly lower haemoglobin (Hb)-levels and higher prevalence of spleen enlargement in DAT-positive than in DAT-negative patients. Hb-levels were independently associated with DAT and age. This initial study was designed to investigate the role of intravascular haemolysis (IVH), but we found no association between IVH and either DAT result or anaemia. Because of the risk of selection bias we repeated the study using consecutive enrolment of malaria patients and were able to confirm the results in a total of 49 DAT-positive and 183 DAT-negative patients. This second study (in 1998) was designed to look at the importance of erythrophagocytosis through measurement of plasma neopterin levels and total nitrite and nitrate as markers of NO-release. Both parameters were significantly higher in DAT-positive than in DAT-negative patients (P < 0.001), indicating that complement binding to erythrocytes was associated with macrophage activation. Plasma levels of haptoglobin, interleukin-10 and tumour necrosis factor-α did not vary between the groups. The studies support the role of complement activation and erythrophagocytosis in [-the pathogenesis of anaemia in falciparum malaria in African children.Item Electrocardiographic study in Ghanaian children with uncomplicated malaria, treated with artesunate-amodiaquine or artemether-lumefantrine(Malaria Journal, 2012-12) Adjei, G.O.; Oduro-Boatey, C.; Rodrigues, O.P.; Hoegberg, L.C.; Alifrangis, M.; Kurtzhals, J.A.; Goka, B.Q.Background: Several anti-malarial drugs are associated with adverse cardiovascular effects. These effects may be exacerbated when different anti-malarials are used in combination. There has been no report yet on the potential cardiac effects of the combination artesunate-amodiaquine. Methods. Electrocardiographic (ECG) intervals in Ghanaian children with uncomplicated malaria treated with artesunate-amodiaquine (n=47), were compared with that of children treated with artemether-lumefantrine (n=30). The ECG measurements were repeated one, two, three, seven and 28 days after treatment. The ECG intervals of artesunate-amodiaquine treated subjects were correlated with plasma concentrations of desethylamodiaquine (DEAQ), the main metabolite of amodiaquine. Results: The mean ECG intervals were similar in both groups before treatment. After treatment (day 3), ECG intervals changed significantly from baseline in all subjects, but there were no differences between the two treatment groups. A significantly higher proportion of children treated with artesunate-amodiaquine developed sinus bradycardia compared with artemether-lumefantrine treated subjects (7/47 vs 0/30; χ2 p=0.03). Subjects who developed bradycardia were significantly older, and had higher DEAQ concentrations than those who did not develop bradycardia. The proportion of subjects with QTc interval prolongations did not differ significantly between the groups, and no relationship between prolonged QTc intervals and DEAQ levels were observed. No clinically significant rhythm disturbances were observed in any of the subjects. Conclusion: Artesunate-amodiaquine treatment resulted in a higher incidence of sinus bradycardia than artemether-lumefantrine treatment in children with uncomplicated malaria, but no clinically significant rhythm disturbances were induced by combining artesunate with amodiaquine. These findings, although reassuring, may imply that non-amodiaquine based artemisinin combination therapy may be preferable for malaria treatment in patients who are otherwise at risk of cardiac effects. © 2012 Adjei et al.; licensee BioMed Central Ltd.Item Antibody-dependent cellular inhibition is associated with reduced risk against Febrile malaria in a longitudinal cohort study involving Ghanaian children(Open Forum Infectious Diseases, 2015-03) Tiendrebeogo, R.W.; Adu, B.; Singh, S.K.; Dziegiel, M.H.; Nébié, I.; Sirima, S.B.; Christiansen, M.; Dodoo, D.; Theisen, M.The antibody-dependent respiratory burst and opsonic phagocytosis assays have been associated with protection against malaria; however, other mechanisms may also be involved. The antibody-dependent cellular inhibition (ADCI) assay is yet to be correlated with protection in longitudinal cohort studies (LCS). We investigated the relationship between ADCI activity of immunoglobulin G before malaria season and risk of malaria in a LCS involving Ghanaian children. High ADCI activity was significantly associated with reduced risk against malaria. Findings here suggest a potential usefulness of the ADCI assay as a correlate of protection to guide malaria vaccine studies. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Societyof America.Item A randomized trial of artesunate-amodiaquine versus artemether-lumefantrine in Ghanaian paediatric sickle cell and non-sickle cell disease patients with acute uncomplicated malaria(Malaria Journal, 2014-09) Adjei, G.O.; Goka, B.Q.; Enweronu-Laryea, C.C.; Rodrigues, O.P.; Renner, L.; Sulley, A.M.; Alifrangis, M.; Khalil, I.; Kurtzhals, J.A.Background: Sickle cell disease (SCD) is a genetic disorder common in malaria endemic areas. In endemic areas, malaria is a major cause of morbidity and mortality among SCD patients. This suggests the need for prompt initiation of efficacious anti-malarial therapy in SCD patients with acute malaria. However, there is no information to date, on the efficacy or safety of artemisinin combination therapy when used for malaria treatment in SCD patients. Methods. Children with SCD and acute uncomplicated malaria (n = 60) were randomized to treatment with artesunate-amodiaquine (AA), or artemether-lumefantrine (AL). A comparison group of non-SCD children (HbAA genotype; n = 59) with uncomplicated malaria were also randomized to treatment with AA or AL. Recruited children were followed up and selected investigations were done on days 1, 2, 3, 7, 14, 28, 35, and 42. Selected clinical and laboratory parameters of the SCD patients were also compared with a group of malaria-negative SCD children (n = 82) in steady state. Results: The parasite densities on admission were significantly lower in the SCD group, compared with the non-SCD group (p = 0.0006). The parasite reduction ratio (PRR) was lower, clearance was slower (p < 0.0001), and time for initial parasitaemia to decline by 50 and 90% were longer for the SCD group. Adequate clinical and parasitological response (ACPR) on day 28 was 98.3% (58/59) in the SCD group and 100% (57/57) in the non-SCD group. Corresponding ACPR rates on day 42 were 96.5% (55/57) in the SCD group and 96.4% (53/55) in the non-SCD group. The fractional changes in haemoglobin, platelets and white blood cell counts between baseline (day 0) and endpoint (day 42) were 16.9, 40.6 and 92.3%, respectively, for the SCD group, and, 12.3, 48.8 and 7.5%, respectively, for the non-SCD group. There were no differences in these indices between AA- and AL-treated subjects. Conclusions: The parasite clearance of SCD children with uncomplicated malaria was slower compared with non-SCD children. AA and AL showed similar clinical and parasitological effects in the SCD and non-SCD groups. The alterations in WBC and platelet counts may have implications for SCD severity. Trial registration. Current controlled trials ISRCTN96891086. © 2014 Adjei et al.; licensee BioMed Central Ltd.Item Malaria, helminths and malnutrition: A cross-sectional survey of school children in the South-Tongu district of Ghana(BioMed Central Ltd., 2016) Ayeh-Kumi, P.F.; Addo-Osafo, K.; Attah, S.K.; Tetteh-Quarcoo, P.B.; Obeng-Nkrumah, N.; Awuah-Mensah, G.; Abbey, H.N.A.; Forson, A.; Cham, M.; Asare, L.; Duedu, K.O.; Asmah, R.H.Background: As part of malaria characterization study in the South-Tongu district of Ghana, the current study was conducted to explore relationships between malaria, schistosomiasis, soil transmitted helminths and malnutrition in riparian community settings that had hitherto encountered episodes of mass deworming exercises. Methods: School-age children were enrolled in a cross-sectional study from April through July 2012. Stool and urine samples were examined respectively for helminths and Schistosoma haematobium. Blood samples were analyzed for malaria parasites and haemoglobin (Hb) concentrations, respectively. Anthropometric indices were measured. Relationships were determined using generalized linear models. Results: The results show low numbers of asymptomatic Plasmodium falciparum (9.2 %, n = 37/404) and S. haematobium (2.5 %, n = 10/404) infections. The associations between significance terms in the multivariate analysis for P. falciparum infections were further assessed to test the significance of the product terms directly i.e., age in years [adjusted odds ratio (AOR), 3.1; 95 % confidence interval (CI) 1.1-5.6], Hb concentration (AOR = 0.71; 95 % CI 0.42-2.3), and stunted malnutrition (AOR, 8.72; 95 % CI 4.8-25.1). The P. falciparum-associated decrease in mean Hb concentration was 2.82 g/dl (95 % CI 1.63-4.1 g/dl; P = 0.001) in stunted children, and 0.75 g/dl (95 % CI 1.59-0.085 g/dl; P = 0.076) in the non-stunted cohort. The anaemia-associated decrease in mean parasitaemia in stunted children was 3500 parasites/μl of blood (95 % CI 262.46-6737.54 parasites/μl of blood; P = 0.036), and in non-stunted children 2127 parasites/μl of blood (95 % CI -0.27 to 4.53; P = 0.085). Stunted malnutrition was the strongest predictor of S. haematobium infection (AOR = 11; 95 % CI 3.1-33.6) but significant associations as described for P. falciparum infections were absent. The population attributable risk of anaemia due to P. falciparum was 6.3 % (95 % CI 2.5-9.3), 0.9 % (95 % CI 0.4-2.3) for S. haematobium, and 12.5 % (95 % CI 9.11-19.52) for stunted malnutrition. Conclusion: Plasmodium falciparum, S. haematobium, intestinal helminths and their co-infections were uncommon in our school-age children. Stunting exacerbated the extent to which malaria was associated with loss in Hb concentration.