Browsing by Author "Kyei-Baafour, E."

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Acute Phase Responses Vary Between Children of HbAS and HbAA Genotypes During Plasmodium falciparum Infection
(Dovepress, 2021) Tetteh, M.; Addai-Mensah, O.; Siedu, Z.; Kyei-Baafour, E.; Lamptey, H.; Williams, J.; Kupeh, E.; Egbi, G.; Kwayie, A.B.; Abbam, G.; Afrifah, D.A.; Debrah, A.Y.; Ofori, M.F.
Purpose: Haemoglobin genotype S is known to offer protection against Plasmodium falciparum infections but the mechanism underlying this protection is not completely under stood. Associated changes in acute phase proteins (APPs) during Plasmodium falciparum infections between Haemoglobin AA (HbAA) and Haemoglobin AS (HbAS) individuals also remain unclear. This study aimed to evaluate changes in three APPs and full blood count (FBC) indices of HbAA and HbAS children during Plasmodium falciparum infection. Methods: Venous blood was collected from three hundred and twenty children (6 months to 15 years) in Begoro in Fanteakwa District of Ghana during a cross-sectional study. Full blood count (FBC) indices were measured and levels of previously investigated APPs in malaria patients; C-reactive protein (CRP), ferritin and transferrin measured using Enzyme-Linked Immunosorbent Assays. Results: Among the HbAA and HbAS children, levels of CRP and ferritin were higher in malaria positive children as compared to those who did not have malaria. The mean CRP levels were significantly higher among HbAA children (p=0.2e-08) as compared to the HbAS children (p=0.43). Levels of transferrin reduced in both HbAA and HbAS children with malaria, but the difference was only significant among HbAA children (p=0.0038), as compared to the HbAS children. No significant differences were observed in ferritin levels between HbAA and HbAS children in both malaria negative (p=0.76) and positive (p=0.26) children. Of the full blood count indices measured, red blood cell count (p=0.044) and haemoglobin (Hb) levels (p=0.017) differed between HbAA and HbAS in those without malaria, with higher RBC counts and lower Hb levels found in HbAS children. In contrast, during malaria, lymphocyte and platelet counts were elevated, whilst granulocytes and Mean Cell Haematocrit counts were reduced among children of the HbAS genotypes. Conclusion: Significant changes in APPs were found in HbAA children during malaria as compared to HbAS children, possibly due to differences in malaria-induced inflammation levels. This suggests that the HbAS genotype is associated with better control of P. falciparum infection-induced inflammatory response than HbAA genotype.
Analysis of Plasmodium falciparum Rh2b deletion polymorphism across different transmission areas
(Scientific Reports, 2020-01-30) Aniweh, Y.; Suurbaar, J.; Morang’a, C.M.; Nyarko, P.B.; Wright, K.E.; Kusi, K.A.; Ansah, F.; Kyei-Baafour, E.; Quansah, E.; Asante, J.; Thiam, L.G.; Higgins, M.K.; Awandare, G.A.
Despite significant progress in controlling malaria, the disease remains a global health burden. The intricate interactions the parasite Plasmodium falciparum has with its host allows it to grow and multiply in human erythrocytes. The mechanism by which P. falciparum merozoites invade human erythrocytes is complex, involving merozoite proteins as well as erythrocyte surface proteins. Members of the P. falciparum reticulocyte binding-like protein homolog (PfRh) family of proteins play a pivotal role in merozoite invasion and hence are important targets of immune responses. Domains within the PfRh2b protein have been implicated in its ability to stimulate natural protective antibodies in patients. More specifically, a 0.58 kbp deletion, at the C-terminus has been reported in high frequencies in Senegalese and Southeast Asian parasite populations, suggesting a possible role in immune evasion. We analysed 1218 P. falciparum clinical isolates, and the results show that this deletion is present in Ghanaian parasite populations (48.5% of all isolates), with Kintampo (hyper-endemic, 53.2%), followed by Accra (Hypo-endemic, 50.3%), Cape Coast (meso-endemic, 47.9%) and Sogakope (meso-endemic, 43.15%). Further analysis of parasite genomes stored in the MalariaGEN database revealed that the deletion variant was common across transmission areas globally, with an overall frequency of about 27.1%. Interestingly, some parasite isolates possessed mixed PfRh2b deletion and full-length alleles. We further showed that levels of antibodies to the domain of PfRh2 protein were similar to antibody levels of PfRh5, indicating it is less recognized by the immune system.
Anti-sporozoite antibodies as alternative markers for malaria transmission intensity estimation
(2014-03-17) Kusi, K.A.; Bosomprah, S.; Dodoo, D.; Kyei-Baafour, E.; Dickson, K.; Mensah, D.; Angov, E.; Dutta, S.; Sedegah, M.; Koram, K.A.
Abstract Background 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.
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.
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).
Associations of IL13 gene polymorphisms and immune factors with Schistosoma haematobium infection in schoolchildren in four schistosomiasis-endemic communities in Ghana
(2021) Sarpong-Baidoo, M.; Ofori, M.F.; Asuming-Brempong, E.K.; Kyei-Baafour, E.; Idun, B.K.; Owusu-Frimpong, I.; Amonoo, N.A.; Quarshie, Q.D.; Tettevi, E.J.; Osei-Atweneboana, M.Y.
Schistosomiasis remains a major public health issue with over 90% of the prevalence rates recorded in Sub-Saharan Africa. In this study, the relationships between different interleukin gene polymorphisms (IL-13-591A/G, IL-13-1055C/T, IL-13-1258A/G) and Schistosoma haematobium infection levels were evaluated; as well as the host plasma antibodies and cytokine profiles associated with schistosomiasis infection. A total of 469 school children aged 6 to 19 years from four schistosomiasis-endemic communities in Ghana were involved. Single urine and stool samples were obtained from each pupil, processed via sedimentation and Kato-Katz, and examined via microscopy for Schistosoma and soil-transmitted helminth (STH) eggs. Next, venous blood samples were drawn from 350 healthy pupils, and used to measure antibody and plasma cytokine levels by ELISA. Single nucleotide polymorphisms in the IL-13 gene were genotyped on 71 selected blood samples using the Mass Array technique. Principal findings and conclusion The overall prevalence of urinary schistosomiasis was 21.11%. Community-level preva lences were 17.12%, 32.11%, 20.80%, and 15.32% for Asempaneye, Barikumah, Eyan Akotoguah, and Apewosika respectively. Generally, higher S. haematobium infection preva lence and intensity were recorded for participants with genotypes bearing the IL13-1055C allele, the IL13-591A, and the IL13-1258A alleles. Also, higher S. haematobium infection prevalence was observed among participants in the 12-14-year age group with the IL13- 1055C, IL13-591A, and IL13-1258A alleles. Interestingly, higher STH prevalence was also observed among participants with the IL13-1055C, IL13-591A, and IL13-1258A alleles. Fur thermore, the age-associated trends of measured antibodies and cytokines of S. haemato bium-infected school-children depicted a more pro-inflammatory immune profile for pupils aged up to 1l years, and an increasingly anti-inflammatory profile for pupils aged 12 years and above. This work provides insight into the influence of IL-13 gene polymorphisms on S. haematobium, and STH infections, in school-aged children (SAC).
Comparative analysis of the ex vivo IFNgamma responses to CD8+ T cell epitopes within allelic forms of PfAMA1 in subjects with natural exposure to malaria
(PLOS ONE, 2021) Nlinwe, O.N.; Ofori, E.A.; Akyea-Mensah, K.; Kyei-Baafour, E.; Ganeshan, H.; Belmonte, M.; Peters, B.; Villasante, E.; Sedegah, M.; Asamoah Kusi, K.
Antigen polymorphisms in essential malarial antigens are a key challenge to the design and development of broadly effective malaria vaccines. The effect of polymorphisms on antibody responses is fairly well studied while much fewer studies have assessed this for T cell responses. This study investigated the effect of allelic polymorphisms in the malarial antigen apical membrane antigen 1 (AMA1) on ex vivo T cell-specific IFN-γ responses in subjects with lifelong exposure to malaria. Human leukocyte antigen (HLA) class I-restricted peptides from the 3D7 clone AMA1 were bioinformatically predicted and those with variant amino acid positions used to select corresponding allelic sequences from the 7G8, FVO, FC27 and tm284 parasite strains. A total of 91 AMA1 9-10mer peptides from the five parasite strains were identified, synthesized, grouped into 42 allele sets and used to stimulate PBMCs from seven HLA class 1-typed subjects in IFN-γ ELISpot assays. PBMCs from four of the seven subjects (57%) made positive responses to 18 peptides within 12 allele sets. Fifty percent of the 18 positive peptides were from the 3D7 parasite variant. Amino acid substitutions that were associated with IFN-γ response abrogation were more frequently found at positions 1 and 6 of the tested peptides, but substitutions did not show a clear pattern of association with response abrogation. Thus, while we show some evidence of polymorphisms affecting T cell response induction, other factors including TCR recognition of HLA-peptide complexes may also be at play.
Effect of Parasite Diversity on the Levels and Quality of Antibody Responses to Plasmodium Falciparum in an Area of Seasonal Malaria Transmission
(University of Ghana, 2015-07) Kyei-Baafour, E.; Kusi, K.A.; University of Ghana, College of Basic and Applied Sciences School of Biological Sciences Department of Animal Biology and Conservation Science (DABCS)
The important role of antibody-mediated mechanisms in protection from clinical malaria has been demonstrated by passive transfer experiments but the targets of protective immunity are not clearly defined. A number of antigens are however in various stages of testing as possible vaccine candidates. Polymorphism in these antigens, which has been reported to be an immune evasion mechanism, has hampered the development of these antigens as vaccines since antibody responses against one allelic form of an antigen have been shown to be less effective against parasites that express a different allele of the same antigen. In animal studies, immunization with a mixture of allelic antigens induced cross-reactive antibodies that had greater and broader in vitro inhibition capacity compared to antibodies induced against the respective single antigens. This study therefore sought to determine the effect of parasite diversity on the levels and quality of antibody responses to P. falciparum in individuals living in an area of seasonal malaria transmission. Indirect ELISA was used to determine total IgG responses to AMA1-3D7, AMA1-FVO, MSP119, CSP, and CelTOS in stored plasma samples taken at two sites, one close to a dam and the other at least 20km away from the dam during the wet and dry season. Competition ELISA was used to determine the relative proportions of cross-reactive and stain-specific anti-AMA1 antibodies. Malaria parasites were detected in participant samples by both microscopy and molecular methods. The study found greater proportion of parasitaemic individuals at the dam site compared to those away from the dam during the dry season (p=0.0061), while proportions were similar in the rainy season. Generally, there were more multiple infections per individual, described as the multiplicity of infection (MOI) in the wet season (60% of participants) compared to the dry season (40.3%, p=0.001). A similar trend was observed when MOI was compared between seasons for the non-dam site (p=0.001), but MOI was similar between the wet and dry seasons at the dam site Antibody levels to sporozoites antigens (CSP and CelTOS) were higher at the dam site compared to the non-dam site, irrespective of the season. No differences between sites were however observed for the blood stage antigens (AMA1 and MSP119). Antibody specificities to multiple AMA1 alleles were observed at sites with MOI greater than 1 and specificity to only the 3D7 allele was observed at sites with single infections. This data generally shows high levels of clinical immunity that is observed in high transmission areas may be associated more with infection by multiple parasite strains (hence a wider breadth of antibody responses) rather than high parasite burden. Consequently low levels of clinical immunity in low transmission areas may be the result of infection with one or a few parasite strains that may induce responses that is not as broad as is seen in high transmission areas.
The Etiology of Placental Plasmodium Falciparum Malaria in African Women
(Journal of Infectious Diseases, 2018-03) Ofori, M.F.; Lamptey, H.; Dickson, E.K.; Kyei-Baafour, E.; Hviid, L.
Plasmodium falciparum parasites causing placental malaria (PM) express the VAR2CSA type of the clonally variant antigen family PfEMP1. This enables evasion of pre-existing immunity and results in placental accumulation of infected erythrocytes (IEs). We present data on seasonal variation in levels of VAR2CSA-specific IgG and IgG specific for a PM-unrelated PfEMP1 protein among Ghanaian women at first antenatal visit. Our results indicate that PM does not require recent exposure to infected mosquitoes, in contrast to malaria in general. This has implications for the impact of insecticide-treated bed nets on PM incidence, and for antenatal care in woman with pre-existing immunity.
Ex vivo Sensitivity Profile of Plasmodium falciparum Clinical Isolates to a Panel of Antimalarial Drugs in Ghana 13 Years After National Policy Change
(Dovepress, 2021) Ofori, M.F.; Kploanyi, E.E.; Mensah, B.A.; Dickson, E.K.; Kyei-Baafour, E.; Gyabaa, S.; Tetteh, M.; Koram, K.A.; Abuaku, B.K.; Ghansah, A.
Purpose: Malaria continues to be a major health issue globally with almost 85% of the global burden and deaths borne by sub-Saharan Africa and India. Although the current artemisinin derived combination therapies in Ghana are still efficacious against the Plasmodium falciparum (Pf) parasite, compounding evidence of artemisinin and amodiaquine resistance establish the need for a full, up-to-date understanding and monitoring of antimalarial resistance to provide evidence for planning control strategies. Materials and Methods: The study was cross-sectional and was conducted during the peak malaria transmission seasons of 2015, 2016, and 2017 in two ecological zones of Ghana. Study participants included children aged 6 months to 14 years. Using ex vivo 4,6-diamidino-2-phenylindole (DAPI) drug sensitivity assay, 330 Pf isolates were used to investigate susceptibility to five antimalarial drugs: chloroquine (CQ), amodiaquine (AMD) dihydroartemisinin (DHA), artesunate (ART) and mefloquine (MFQ). Results: The pooled geometric mean IC50S (GMIC50) of the five drugs against the parasites from Cape Coast and Begoro were 15.5, 42.4, 18.9, 4.6 and 27.3nM for CQ, AMD, DHA, ART, and MFQ, respectively. The GMIC50 values for CQ (p<0.001), ART (p<0.011) and DHA (p<0.018) were significantly higher for Cape Coast isolates as compared to Begoro isolates. However, GMIC50 estimates for MFQ (p<0.022) were significantly higher for Begoro isolates. Positive correlations were found between each pair of drugs with the weakest found between MFQ and DHA (r = 0.34;p<0.001), and the strongest between ART and DHA (r =0.66; p<0.001). Conclusion: The parasites showed reduced sensitivities to three (AMD, DHA and MFQ) out of the five drugs assessed. The study also demonstrated the continual return of chloroquine-sensitive parasites after 13 years of its withdrawal as the first-line drug for the treatment of uncomplicated malaria in Ghana. The ex vivo DAPI assay is a reliable method for assessing antimalarial drug sensitivities of Pf field isolates under field settings.
Fc gamma receptor 3B (FCGR3B-c.233C>A-rs5030738) polymorphism modifies the protective effect of malaria specific antibodies in ghanaian children
(Journal of Infectious Diseases, 2014) Adu, B.; Jepsen, M.P.G.; Gerds, T.A.; Kyei-Baafour, E.; Christiansen, M.; Dodoo, D.; Theisen, M.
Immunoglobulin G (IgG) cross-linking with Fc gamma receptor IIIB (FcγRIIIB) triggers neutrophil degranulation, releasing reactive oxygen species with high levels associated with protection against malaria. The FCGR3B-c.233C>A polymorphism thought to influence the interaction between IgG and FcγRIIIB was recently associated with malaria. We studied the statistical interaction between glutamate rich protein antibodies and FCGR3B-c.233C>A genotypes on risk of malaria in a cohort of Ghanaian children. The absolute risk of malaria decreased more rapidly with increasing antibody levels for 233AA/AC individuals compared with 233CC children. This genotype related effect modification may significantly influence malaria sero-epidemiological and vaccine trial studies. © The Author 2013.
High opsonic phagocytosis activity and growth inhibition of merozoites are associated with RON4 antibody levels and protect against febrile malaria in Ghanaian children
(Frontiers in Immunology, 2023) Kyei-Baafour, E.; Kusi, K.A.; Arthur, F.K.N.
Background: Naturally acquired immunity to malaria may involve different immune mechanisms working in concert, however, their respective contributions and potential antigenic targets have not been clearly established. Here, we assessed the roles of opsonic phagocytosis and antibody-mediated merozoite growth inhibition in Plasmodium falciparum (P. falciparum) infection outcomes in Ghanaian children. Methods: The levels of merozoite opsonic phagocytosis, growth inhibition activities and six P. falciparum antigen-specific IgG of plasma samples from children (n=238, aged 0.5 to 13 years) were measured at baseline prior to the malaria seasons in southern Ghana. The children were then actively and passively followed up for febrile malaria and asymptomatic P. falciparum infection detection in a 50-week longitudinal cohort. P. falciparum infection outcome was modelled as a function of the measured immune parameters while accounting for important demographic factors. Results: High plasma activity of opsonic phagocytosis [adjusted odds ratio (aOR)= 0.16; 95%CI= 0.05 - 0.50, p = 0.002], and growth inhibition (aOR=0.15; 95% CI = 0.04-0.47; p = 0.001) were individually associated with protection against febrile malaria. There was no evidence of correlation (b= 0.13; 95% CI= -0.04-0.30; p=0.14) between the two assays. IgG antibodies against MSPDBL1 correlated with opsonic phagocytosis (OP) while IgG against PfRh2a correlated with growth inhibition. Notably, IgG antibodies against RON4 correlated with both assays. Conclusion: Opsonic phagocytosis and growth inhibition are protective immune mechanisms against malaria that may be acting independently to confer overall protection. Vaccines incorporating RON4 may benefit from both immune mechanisms.
High opsonic phagocytosis activity and growth inhibition of merozoites are associated with RON4 antibody levels and protect against febrile malaria in Ghanaian children
(Frontiers in Immunology, 2023) Kyei-Baafour, E.; Kusi, K.A.; Owusu-Yeboa, E.; Dodoo, D.; Adu, B.; et al.
Background: Naturally acquired immunity to malaria may involve different immune mechanisms working in concert, however, their respective contributions and potential antigenic targets have not been clearly established. Here, we assessed the roles of opsonic phagocytosis and antibody-mediated merozoite growth inhibition in Plasmodium falciparum (P. falciparum) infection outcomes in Ghanaian children. Methods: The levels of merozoite opsonic phagocytosis, growth inhibition activities and six P. falciparum antigen-specific IgG of plasma samples from children (n=238, aged 0.5 to 13 years) were measured at baseline prior to the malaria seasons in southern Ghana. The children were then actively and passively followed up for febrile malaria and asymptomatic P. falciparum infection detection in a 50-week longitudinal cohort. P. falciparum infection outcome was modelled as a function of the measured immune parameters while accounting for important demographic factors. Results: High plasma activity of opsonic phagocytosis [adjusted odds ratio (aOR)= 0.16; 95%CI= 0.05 - 0.50, p = 0.002], and growth inhibition (aOR=0.15; 95% CI = 0.04-0.47; p = 0.001) were individually associated with protection against febrile malaria. There was no evidence of correlation (b= 0.13; 95% CI= -0.04-0.30; p=0.14) between the two assays. IgG antibodies against MSPDBL1 correlated with opsonic phagocytosis (OP) while IgG against PfRh2a correlated with growth inhibition. Notably, IgG antibodies against RON4 correlated with both assays. Conclusion: Opsonic phagocytosis and growth inhibition are protective immune mechanisms against malaria that may be acting independently to confer overall protection. Vaccines incorporating RON4 may benefit from both immune mechanisms.
Identification of Plasmodium falciparum circumsporozoite protein-specific CD8+ T cell epitopes in a malaria exposed population
(Plos One, 2020-02-10) Kusi, K.A.; Aggor, F.E.; Amoah, L.E.; Anum, D.; Nartey, Y.; Amoako-Sakyi, D.; Obiri-Yeboah, D.; Hollingdale, M.; Ganeshan, H.; Belmonte, M.; Peters, B.; Kim, Y.; Tetteh, J.; Kyei-Baafour, E.; Dodoo, D.; Villasante, E.; Sedegah, M.
Background Sterile protection against malaria, most likely mediated by parasite-specific CD8+ T cells, has been achieved by attenuated sporozoite vaccination of animals as well as malarianaïve and malaria-exposed subjects. The circumsporozoite protein (CSP)-based vaccine, RTS,S, shows low efficacy partly due to limited CD8+ T cell induction, and inclusion of such epitopes could improve RTS,S. This study assessed 8-10mer CSP peptide epitopes, present in predicted or previously positive P. falciparum 3D7 CSP 15mer overlapping peptide pools, for their ability to induce CD8+ T cell IFN-γ responses in natural malaria-exposed subjects. Methods Cryopreserved PBMCs from nine HLA-typed subjects were stimulated with 23 8-10mer CSP peptides from the 3D7 parasite in IFN-γ ELISpot assays. The CD8+ T cell specificity of IFN-γ responses was confirmed in ELISpot assays using CD8+ T cell-enriched PBMC fractions after CD4+ cell depletion. Results Ten of 23 peptide epitopes elicited responses in whole PBMCs from five of the nine subjects. Four peptides tested positive in CD8+ T cell-enriched PBMCs from two previously positive responders and one new subject. All four immunodominant peptides are restricted by globally common HLA supertypes (A02, A03, B07) and mapped to regions of the CSP antigen with limited or no reported polymorphism. Association of these peptide-specific responses with anti-malarial protection remains to be confirmed. Conclusions The relatively conserved nature of the four identified epitopes and their binding to globally common HLA supertypes makes them good candidates for inclusion in potential multi-epitope malaria vaccines
Immunodominant T cell peptides from four candidate malarial antigens as biomarkers of protective immunity against malaria
(Vaccine, 2023) Belmonte, M.; Ganeshan, H.; Huang, J.; Belmonte, A.; Inoue, S.; Velasco a, R.; Acheampong, N.; Ofori, E.A.; Akyea-Mensah, K.; Frimpong, A.; Ennuson, N.A.; Frempong, A.F.; Kyei-Baafour, E.; Amoah, L.E.; Edgel, K.; Peters, B.; Villasante, E.; Kusi, K.A.; Sedegah, N.
A malaria vaccine with high efficacy and capable of inducing sterile immunity against malaria within genetically diverse populations is urgently needed to complement ongoing disease control and elimination efforts. Parasite-specific IFN-c and granzyme B-secreting CD8 + T cells have been identified as key mediators of protection and the rapid identification of malaria antigen targets that elicit these responses will fast-track the development of simpler, cost-effective interventions. This study extends our previous work which used peripheral blood mononuclear cells (PBMCs) from adults with life-long exposure to malaria parasites to identify immunodominant antigen-specific peptide pools composed of overlapping 15mer sequences spanning full length proteins of four malarial antigens. Our current study aimed to identify CD8 + T cell epitopes within these previously identified positive peptide pools. Cryopreserved PBMCs from 109 HLA-typed subjects were stimulated with predicted 9-11mer CD8 + T cell epitopes from P. falciparum circumsporozoite protein (CSP), apical membrane antigen 1 (AMA1), thrombospondin related anonymous protein (TRAP) and cell traversal for ookinetes and sporozoites (CelTOS) in FluoroSpot assays. A total of 135 epitopes out of 297 tested peptides from the four antigens were experimentally identified as positive for IFN-c and/or granzyme B production in 65 of the 109 subjects. Forty three of 135 epitopes (32 %) were promiscuous for HLA binding, with 31 of these promiscuous epitopes (72 %) being presented by HLA alleles that fall within at least two different HLA supertypes. Furthermore, about 52 % of identified epitopes were conserved when the respective sequences were aligned with those from 16 highly diverse P. falciparum parasite strains. In summary, we have identified a number of conserved epitopes, immune responses to which could be effective against multiple P. falciparum parasite strains in genetically diverse populations.
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 transmission
Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates
(Journal of Infection, 2015-07) Jones, S.; Grignard, L.; Nebie, I.; Chilongola, J.; Dodoo, D.; Sauerwein, R.; Theisen, M.; Roeffen, W.; Singh, S.K.; Singh, R.K.; Singh, S.; Kyei-Baafour, E.; Tetteh, K.; Drakeley, C.; Bousema, T.
Objectives: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. Methods: We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined genetic polymorphisms in the P. falciparum gene pfs48/45. Results: Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p<0.001) and 230CMB (p=0.031). Membrane feeding assays on a separate dataset demonstrated an association between functional transmission reducing activity and antibody prevalence for both 10C (p=0.017) and 230CMB (p=0.049). 17 single nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non-synonymous SNPs in the Pfs48/45 10C region. Conclusions: We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity. © 2015 The British Infection Association.
The prevalence of submicroscopic Plasmodium falciparum gametocyte carriage and multiplicity of infection in children, pregnant women and adults in a low malaria transmission area in Southern Ghana
(Malaria Journal, 2018-09) Lamptey, H.; Ofori, M.F.; Kusi, K.A.; Adu, B.; Owusu-Yeboa, E.; Kyei-Baafour, E.; Arku, A.T.; Bosomprah, S.; Alifrangis, M.; Quakyi, I.A.
Background: The gametocyte stage of Plasmodium falciparum is considered an important target for disrupting malaria transmission. Indications are that various demographic groups, such as children and pregnant women may differ in risk of harbouring gametocytes, which may be crucial for targeted control. In this study, the relationship between the prevalence and multiplicity of P. falciparum, asexual parasite infections and gametocytaemia was assessed in three different demographic groups in an area of southern Ghana with low malaria endemicity. Levels of antibody responses to Pfs230 were also assessed as a proxy for the presence of gametocytes. Methods: The study involved multiple cross-sectional sampling of children (N = 184, aged 2-15 years), male and non-pregnant female adults (N = 154, aged 16-65 years) and pregnant women (N = 125, aged 18-45 years) from Asutsuare in the Shai Osudoku District of Greater Accra Region in Ghana. Asexual parasitaemia was detected by microscopy and PCR, and gametocytaemia was assessed by Pfs25-real time PCR. Multiclonal P. falciparum infections were estimated by msp2 genotyping and an indirect ELISA was used to measure plasma IgG antibodies to Pfs230 antigen. Results: Overall, children and pregnant women had higher prevalence of submicroscopic gametocytes (39.5% and 29.7%, respectively) compared to adults (17.4%). Multiplicity of infection observed amongst children (3.1) and pregnant women (3.9) were found to be significantly higher (P = 0.006) compared with adults (2.7). Risk of gametocyte carriage was higher in individuals infected with P. falciparum having both Pfmsp2 3D7 and FC27 parasite types (OR = 5.92, 95% CI 1.56-22.54, P = 0.009) compared with those infected with only 3D7 or FC27 parasite types. In agreement with the parasite prevalence data, anti-Pfs230 antibody levels were lower in gametocyte positive adults (β = - 0.57, 95% CI - 0.81, - 0.34, P < 0.001) compared to children. Conclusions: These findings suggest that children and pregnant women are particularly important as P. falciparum submicroscopic gametocyte reservoirs and represent important focus groups for control interventions. The number of clones increased in individuals carrying gametocytes compared to those who did not carry gametocytes. The higher anti-gametocyte antibody levels in children suggests recent exposure and may be a marker of gametocyte carriage.
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.
Suitability of IgG responses to multiple Plasmodium falciparum antigens as markers of transmission intensity and pattern
(PLoS ONE, 2021) Kyei-Baafour, E.; Oppong, M.; Kusi, K.A.; Frempong, A.F.; Aculley, B.; Arthur, F.K.N.; Tiendrebeogo, R.W.; Singh, S.K.; Theisen, M.; Kweku, M.; Adu, B.; Hviid, L.; OforiI, M.F.
Detection of antibody reactivity to appropriate, specific parasite antigens may constitute a sensitive and cost-effective alternative to current tools to monitor malaria transmission across different endemicity settings. This study aimed to determine the suitability of IgG responses to a number of P. falciparum antigens as markers of transmission intensity and pattern. Antibody responses to multiple malaria antigens were determined in 905 participants aged 1–12 years from three districts with low (Keta), medium (Hohoe) and high (Krachi) transmission intensity in the Volta region of Ghana. Blood film microscopy slides and dry blood spots (DBS) were obtained for parasitaemia detection and antibody measurement, respectively. Sera were eluted from DBS and levels of IgG specific for 10 malaria antigens determined by a multiplex assay. Results were compared within and among the districts. Total IgG responses to MSPDBL1, MSPDBLLeucine, MSP2-FC27, RAMA, and PfRh2a and PfRh2b were higher in Krachi than in Hohoe and Keta. Seroprevalence of IgG specific for MSPDBLLeucine, RON4, and PfRh2b were also highest in Krachi. Responses to RALP-1, PfRh2a and PfRh2b were associated with patent but asymptomatic parasitaemia in Keta, while responses to MSPDBL1, MSPDBLLeucine, MSP2-FC27, RAMA, Rh2-2030, and PfRh2b were associated with parasite carriage in Hohoe, but not in Krachi. Using ROC analysis, only PfRh2b was found to predict patent, but asymptomatic, parasitaemia in Keta and Hohoe. Antibody breadth correlated positively with age (r = 0.29, p<0.0001) and parasitaemia (β = 3.91; CI = 1.53 to 6.29), and medium to high transmission (p<0.0001). Our findings suggest differences in malaria-specific antibody responses across the three transmission zones and that PfRh2b has potential as a marker of malaria transmission intensity and pattern. This could have implications for malaria control programs and vaccine trials.