Browsing by Author "Tornyigah, B."
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Item Association of Endothelial Protein C Receptor (EPCR) rs867186 Gene Polymorphism With Increased Levels of Soluble EPCR and High Risk of Severe Malaria and Fatality in Beninese Children(The Journal of Infectious Diseases, 2023) Blankson, S.O.; Dikroh, L.; Tettey, P.; Tornyigah, B.; Adamou, R.; Moussiliou, A.; et al.The endothelial protein C receptor (EPCR)–rs867186 G allele has been linked to high plasma levels of soluble EPCR (sEPCR) and controversially associated with either susceptibility or resistance to severe and cerebral malaria. In this study, quantitative enzyme-linked immunosorbent assay and sequencing were used to assess sEPCR levels and EPCR-rs867186 polymorphism in blood samples from Beninese children with different clinical presentations of malaria. Our findings show that sEPCR levels were higher at hospital admission than during convalescence and that EPCR-rs867186 G allele was associated with increased sEPCR plasma levels, malaria severity, and mortality rate (P< .001, P =.03, and P=.04, respectively), suggesting a role of sEPCR in the pathogenesis of severe malaria.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 Effect of Drug Pressure on Promoting the Emergence of Antimalarial-Resistant Parasites among Pregnant Women in Ghana(Antimicrobial Agents and Chemotherapy, 2020-05-21) Tornyigah, B.; Coppée, R.; Houze, P.; Kusi, K.A.; Adu, B.; Quakyi, I.; Coleman, N.; Mama, A.; Deloron, P.; Anang, A.K.; Clain, J.; Tahar, R.; Ofori, M.F.; Ndam, N.T.The continuous spread of antimalarial drug resistance is a threat to current chemotherapy efficacy. Therefore, characterizing the genetic diversity of drug resistance markers is needed to follow treatment effectiveness and further update control strategies. Here, we genotyped Plasmodium falciparum resistance gene markers associated with sulfadoxine-pyrimethamine (SP) and artemisinin-based combination therapy (ACT) in isolates from pregnant women in Ghana. The prevalence of the septuple IRNI-A/FGKGS/T pfdhfr/pfdhps haplotypes, including the pfdhps A581G and A613S/T mutations, was high at delivery among post-SP treatment isolates (18.2%) compared to those of first antenatal care (before initiation of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine [IPTp-SP]; 6.1%; P = 0.03). Regarding the pfk13 marker gene, two nonsynonymous mutations (N458D and A481C) were detected at positions previously related to artemisinin resistance in isolates from Southeast Asia. These mutations were predicted in silico to alter the stability of the pfk13 propeller-encoding domain. Overall, these findings highlight the need for intensified monitoring and surveillance of additional mutations associated with increased SP resistance as well as emergence of resistance against artemisinin derivatives.Item High uptake of Intermittent Preventive Treatment of malaria in pregnancy is associated with improved birth weight among pregnant women in Ghana(Scientific Reports, 2019-12-13) Quakyi, I.; Tornyigah, B.; Houze, P.; Kusi, K.A.; Coleman, N.; Escriou, G.; Laar, A.; Cot, M.; Fobil, J.; Asare, G.Q.; Deloron, P.; Anang, A.K.; Cottrell, G.; Ofori, M.F.; Ndam, N.T.Despite the clinically proven advantages of intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), utilisation has been low in many African countries. To increase uptake and achieve the desired effect, the World Health Organization revised the policy to a monthly administration. Assessing the coverage and impact of the revised policy on pregnancy and neonatal outcomes is, therefore, a necessity. A 2-parallel cross-sectional hospital-based study was carried out among pregnant women attending first antenatal care (ANC) and delivery. Maternal and cord blood samples were assayed for malaria parasites by quantitative PCR targeting both the 18S rDNA and the acidic terminal segment of Plasmodium falciparum var genes, and plasma SP levels were measured by liquid chromatography coupled to tandem mass spectrometry. Parasite prevalence was similar between the two study sites but decreased significantly between the first ANC (9% or 43%) and delivery (4% or 11%) based on the qPCR target. At delivery, 64.5% of women received ≥3 IPTp-SP dose, 15.5% received 2 doses and 6% had 1 dose. Taking ≥3 IPTp-SP doses was associated with an average birth weight increase of more than 0.165 kg. IPTp-SP uptake was associated with plasma SP level at delivery (OR = 32.3, p ≤ 0.005, 95% CI (13.3;78.4) for those that reported ≥3 IPTp-SP doses) while the same trend of improved birth weight was observed with high plasma SP levels. The new IPTp policy is well implemented and well utilised by women in the sites considered in this study and translates to the improved birth weight observed. This study confirms the interest and the clinical benefit expected from this policy change.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 transmissionItem Persistent Plasmodium falciparum Infection in Women With an Intent to Become Pregnant as a Risk Factor for Pregnancy-associated Malaria(Clinical Infectious Diseases, 2018-11) Ndam, N.T.; Tornyigah, B.; Dossou, A.Y.; Escriou, G.; Nielsen, M.A.; Salanti, A.; Issifou, S.; Massougbodji, A.; Chippaux, J.P.; Deloron, P.Background: Pregnant women are more susceptible to Plasmodium falciparum than before pregnancy, and infection has consequences for both mother and offspring. The World Health Organization recommends that pregnant woman in areas of transmission receive intermittent preventive treatment (IPTp) starting in the second trimester. Consequently, women are not protected during the first trimester, although P. falciparum infections are both frequent and harmful. Methods: A cohort of nulligravid women was followed up during subsequent pregnancy. Malaria was diagnosed by means of microscopy and polymerase chain reaction. Parasites were genotyped at polymorphic loci. Results: Among 275 nulligravidae enrolled, 68 women became pregnant and were followed up during pregnancy. Before pregnancy, P. falciparum prevalence rates were 15% by microscopy and 66% by polymerase chain reaction. Microscopic infection rates increased to 29% until IPTp administration, and their density increased by 20-fold. Conversely, submicroscopic infection rates decreased. After IPTp administration, all types of infections decreased, but they increased again late in pregnancy. The risk of infection during pregnancy was higher in women with a microscopic (odds ratio, 6.5; P = .047) or submicroscopic (3.06; P = .05) infection before pregnancy and was not related to the season of occurrence. Most infections during pregnancy were persistent infections acquired before pregnancy. Conclusions: Microscopic and submicroscopic malaria infections were frequent in nulligravid women from south Benin. During the first trimester of pregnancy, microscopic infections were more frequent, with a higher parasite density, and mainly derived from parasites infecting the woman before conception. Preventive strategies targeting nonpregnant women with a desire for conception need to be designed.Item Putative, Secreted Ookinete Protein (PSOP24) Peptides As A Marker Of Infectious Bites And Malaria Transmission Assessment(University of Ghana, 2015-07) Tornyigah, B.As reported malaria cases continue to decline, heterogeneity in transmission will become more pronounced and thus more sensitive tools would be required to identify micro-geographic areas of higher risk for targeted interventions. Sero-positivity against antigens expressed at different stages of the parasite life cycle and proteins in the mosquito saliva cocktail have gained relevance as transmission monitoring tool. However, the persistent nature of blood stage antigens and the possible use of Circumsporozoite protein (CSP) as a vaccine has necessitated the search for additional markers that can measure even subtle differences in malaria transmission. Seropositive against antibodies to synthetic peptides of a ookinete stage marker may be a better alternative since it may show contact to an infectious vector. Thus, the study sought to evaluate further and possibly validate PSOP24 as an infectious bite marker of malaria transmission. Synthetic peptides of PSOP24 were designed to cover the most immunogenic epitopes based on several bioinformatic models. Total IgG antibody response to three of the peptides (PSOP24- 374, PSOP24-375 and PSOP24-377), CSP and gSG6-P1 were then determined using an indirect ELISA protocol to antibody eluates from two communities 2 Km apart with low malaria transmission during the dry and wet seasons. Malaria parasites were detected in study participants by both microscopy and molecular techniques. In this study, a 2-fold decrease in IgG responses to peptides PSOP24-374 and PSOP24-375 was observed between the dry and wet season (p < 0.005), whereas a 2-fold increase in IgG response to PSOP24-377 and the vector-antigen gSG6-P1 was observed between the same sample collection periods (p < 0.0001). However, CSP showed no significant difference between the seasons when compared. Spatial variation between the study communities also show a 1 fold increase in IgG response to PSOP24-375 while a 2 fold and 1 fold decrease in IgG response to PSOP24-374 and PSOP24-377 from Ayeigbekorpe to Odumase was observed during the dry season. In the wet season, Odumase had high median IgG responses to PSOP24-374, PSOP24- 377 and CSP than Ayigbekorpe while median IgG response to gSG6-P1 was high in Ayigbekorpe than in Odumase. Also, the study found greater proportion (36.4%) of submicroscopic infections in individuals in Odumase compared to Ayeigbekorpe during the dry season (p=0.02) while this trend was reversed during the wet season. Generally, there were less multiple infections per individual, described as the multiplicity of infection between the study communities and also between the sample collection times with majority of participants harboring single alleles of the 3D7 strain. This data shows a high antibody response particularly to PSOP24-377 that was similar to gSG6- P1, corresponding to the different transmissions in the study communities, hence can be exploited as additional marker for assessing transmission in low transmission settings.Item Seroprevalence of antibodies against plasmodium falciparum sporozoite antigens as predictive disease transmission markers in an area of Ghana with seasonal malaria transmission(Public Library of Science, 2016) Kusi, K.A.; Bosomprah, S.; Kyei-Baafour, E.; Dickson, E.K.; Tornyigah, B.; Angov, E.; Dutta, S.; Dodoo, D.; Sedegah, M.; Koram, K.A.Introduction As an increasing number of malaria-endemic countries approach the disease elimination phase, sustenance of control efforts and effective monitoring are necessary to ensure success. Mathematical models that estimate anti-parasite antibody seroconversion rates are gaining relevance as more sensitive transmission intensity estimation tools. Models however estimate yearly seroconversion and seroreversion rates and usually predict long term changes in transmission, occurring years before the time of sampling. Another challenge is the identification of appropriate antigen targets since specific antibody levels must directly reflect changes in transmission patterns. We therefore investigated the potential of antibodies to sporozoite and blood stage antigens for detecting short term differences in malaria transmission in two communities in Northern Ghana with marked, seasonal transmission. Methods Cross-sectional surveys were conducted during the rainy and dry seasons in two communities, one in close proximity to an irrigation dam and the other at least 20 Km away from the dam. Antibodies against the sporozoite-specific antigens circumsporozoite protein (CSP) and Cell traversal for ookinetes and sporozoites (CelTOS) and the classical blood stage antigen apical membrane antigen 1 (AMA1) were measured by indirect ELISA. Antibody levels and seroprevalence were compared between surveys and between study communities. Antibody seroprevalence data were fitted to a modified reversible catalytic model to estimate the seroconversion and seroreversion rates. Results Changes in sporozoite-specific antibody levels and seroprevalence directly reflected differences in parasite prevalence between the rainy and dry seasons and hence the extent of malaria transmission. Seroconversion rate estimates from modelled seroprevalence data did not however support the above observation. Conclusions The data confirms the potential utility of sporozoite-specific antigens as useful markers for monitoring short term/seasonal changes in malaria transmission. It may however be essential to update models to allow for assessment of seasonal changes in malaria transmission, which usually occur within four to six months.