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Abstract Background To prepare field sites for malaria vaccine trials, it is important to determine baseline antibody and T cell responses to candidate malaria vaccine antigens. Assessing T cell responses is especially challenging, given genetic restriction, low responses observed in endemic areas, their variability over time, potential suppression by parasitaemia and the intrinsic variability of the assays. Methods In Part A of this study, antibody titres were measured in adults from urban and rural communities in Ghana to recombinant Plasmodium falciparum CSP, SSP2/TRAP, LSA1, EXP1, MSP1, MSP3 and EBA175 by ELISA, and to sporozoites and infected erythrocytes by IFA. Positive ELISA responses were determined using two methods. T cell responses to defined CD8 or CD4 T cell epitopes from CSP, SSP2/TRAP, LSA1 and EXP1 were measured by ex vivo IFN-γ ELISpot assays using HLA-matched Class I- and DR-restricted synthetic peptides. In Part B, the reproducibility of the ELISpot assay to CSP and AMA1 was measured by repeating assays of individual samples using peptide pools and low, medium or high stringency criteria for defining positive responses, and by comparing samples collected two weeks apart. Results In Part A, positive antibody responses varied widely from 17%-100%, according to the antigen and statistical method, with blood stage antigens showing more frequent and higher magnitude responses. ELISA titres were higher in rural subjects, while IFA titres and the frequencies and magnitudes of ex vivo ELISpot activities were similar in both communities. DR-restricted peptides showed stronger responses than Class I-restricted peptides. In Part B, the most stringent statistical criteria gave the fewest, and the least stringent the most positive responses, with reproducibility slightly higher using the least stringent method when assays were repeated. Results varied significantly between the two-week time-points for many participants. Conclusions All participants were positive for at least one malaria protein by ELISA, with results dependent on the criteria for positivity. Likewise, ELISpot responses varied among participants, but were relatively reproducible by the three methods tested, especially the least stringent, when assays were repeated. However, results often differed between samples taken two weeks apart, indicating significant biological variability over short intervals.

Hybrid organic-inorganic binders based on blast furnace slag were produced using sodium (NaAc) or potassium (KAc) acetate as the sole activator, and their properties were compared with those of sodium- or potassium hydroxide-activated slag pastes. The acetate-activated binders showed significantly lower cumulative heat release and extended setting time (∼230 h) than the hydroxide-activated binders. The main reaction products forming in all binders were calcium aluminosilicate hydrate-type gels and a hydrotalcite-like phase, independently of the activator type used. Compressive strengths of the acetate-activated pastes (∼40 MPa at 180 days) were lower than those of the hydroxide-activated binders (∼80 MPa at 180 days). However, the acetate-based binders exhibited superior impermeability and reduced wettability at 28 days, likely due to hydrophobic acetate groups. It is hypothesized that acetates dissociate in water, forming calcium acetate and alkali silicates via a reaction with species dissolving from the slag. This study demonstrates alkali acetates are effective activators for creating hybrid slag-based binders with reduced permeability., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Application of numerous malaria control interventions has led to reduction in clinical malaria cases and deaths but also the realisation that asymptomatic parasite carriers play a key role in sustaining transmission. This study assessed the effectiveness of using the Ultra-sensitive NxTek eliminate RDT (uRDT) and conventional SD Bioline HRP2 RDT (cRDT) in diagnosing asymptomatic parasitaemia while measuring the impact of mass testing, treatment and tracking (MTTT) on the prevalence of asymptomatic malaria over a 1-year period in Ghana., Methods: A total of 4000 targeted participants from two towns, Obom and Kofi Kwei, with their surrounding villages, were tested for asymptomatic malaria four times over the study period using uRDT (intervention) and the cRDT (control) respectively. Participants carrying malaria parasites were followed by home visit and phone calls for compliance to treatment, and filter paper blood blots collected from participants were used to determine true parasite carriage by PET-PCR. A mathematical model of the study site was developed and used to test the impact of test sensitivity and mass migration on the effect of MTTT., Results: The start and end point sensitivities of the cRDT were 48.8% and 41.7% and those for the uRDT were 52.9% and 59.9% respectively. After a year of MTTTs, asymptomatic parasite prevalence, as determined by PCR, did not differ statistically in the control site (40.6% to 40.1%, P = 0.730) but decreased at the intervention site (55.9% to 46.4%, P < 0.0001). Parasite prevalence by RDT, however, indicated statistical reduction in the control site (25.3% to 22.3%, P = 0.017) and no change in the intervention site (35.1% to 36.0%, P = 0.614). The model predicted a mild effect of both diagnostic sensitivity and human movement in diminishing the impact of MTTT in the study sites., Conclusions: Asymptomatic parasite prevalence at the molecular level reduced significantly in the site where the uRDT was used but not where the cRDT was used. Overall, the uRDT exhibited higher sensitivity relative to the cRDT. Highly sensitive molecular techniques such as PET-PCR should be included in parasite prevalence estimation during MTTT exercises., (© 2024. The Author(s).)

Background: The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by asymptomatic individuals has been reported since the early stages of the coronavirus disease 2019 (COVID-19) outbreak in various parts of the world. However, there are limited data regarding SARS-CoV-2 among asymptomatic individuals in Ghana. The aim of the study was to use test data of prospective travelers from Ghana as a proxy to estimate the contribution of asymptomatic cases to the spread of COVID-19., Methods: The study analyzed the SARS-CoV-2 PCR test data of clients whose purpose for testing was classified as "Travel" at the COVID-19 walk-in test center of the Noguchi Memorial Institute for Medical Research (NMIMR) from July 2020 to July 2021. These individuals requesting tests for travel generally had no clinical symptoms of COVID-19 at the time of testing. Data were processed and analyzed using Microsoft Excel office 16 and STATA version 16. Descriptive statistics were used to summarize data on test and demographic characteristics., Results: Out of 42,997 samples tested at the center within that period, 28,384 (66.0%) were classified as "Travel" tests. Of these, 1,900 (6.7%) tested positive for SARS-CoV-2. The majority (64.8%) of the "Travel" tests were requested by men. The men recorded a SARS-CoV-2 positivity of 6.9% compared to the 6.4% observed among women. Test requests for SARS-CoV-2 were received from all regions of Ghana, with a majority (83.3%) received from the Greater Accra Region. Although the Eastern region recorded the highest SARS-CoV-2 positivity rate of 8.35%, the Greater Accra region contributed 81% to the total number of SARS-CoV-2 positive cases detected within the period of study., Conclusion: Our study found substantial SARS-CoV-2 positivity among asymptomatic individuals who, without the requirement for a negative SARS-CoV-2 result for travel, would have no reason to test. These asymptomatic SARS-CoV-2-infected individuals could have traveled to other countries and unintentionally spread the virus. Our findings call for enhanced tracing and testing of asymptomatic contacts of individuals who tested positive for SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Akowuah, Akuffo, Boateng, Asigbee, Bonney, Lamptey, Adusei-Poku, Obodai, Asante, Adjei, Aboagye, Adu-Amankwah, Partey, Kyei, Ampofo, Odoom and Bonney.)

Ghana has been implementing mass drug administration (MDA) of ivermectin and albendazole for the elimination of lymphatic filariasis (LF) since the year 2000, as part of the Global Programme to Eliminate Lymphatic Filariasis (GPELF). It was estimated that 5⁻6 years of treatment would be sufficient to eliminate the disease. Tremendous progress has been made over the years, and treatment has stopped in many disease endemic districts. However, despite the successful implementation of MDA, there are districts with persistent transmission. In this study we assessed the epidemiology of LF in three adjoining districts that have received at least 16 years of MDA. The assessments were undertaken one year after the last MDA. 1234 adults and 182 children below the age of 10 years were assessed. The overall prevalence of circulating filarial antigen in the study participants was 8.3% (95% CI: 6.9⁻9.9), with an estimated microfilaria prevalence of 1.2%. The microfilarial intensity in positive individuals ranged from 1 to 57 microfilariae/mL of blood. Higher antigen prevalence was detected in males (13.0%; 95% CI: 10.3⁻16.2) compared to females (5.5%; 95% CI: 4.1⁻7.2). The presence of infection was also highest in individuals involved in outdoor commercial activities, with the risks of infection being four- to five-fold higher among farmers, fishermen, drivers and artisans, compared to all other occupations. Using bednets or participating in MDA did not significantly influence the risk of infection. No children below the age of 10 years were found with infection. Detection of Wb123 antibodies for current infections indicated a prevalence of 14.4% (95% CI: 8.1⁻23.0) in antigen-positive individuals above 10 years of age. No antibodies were detected in children 10 years or below. Assessment of infection within the An. gambiae vectors of LF indicated an infection rate of 0.9% (95% CI: 0.3⁻2.1) and infectivity rate of 0.5% (95% CI: 0.1⁻1.6). These results indicate low-level transmission within the districts, and suggest that it will require targeted interventions in order to eliminate the infection.

Background: The Global Program for the Elimination of Lymphatic Filariasis (GPELF) started operation in 2000 and aimed at eliminating the disease by the year 2020, following 5-6 rounds of effective annual Mass Drug Administration (MDA). The MDA programme took off in Ghana in 2001 and has interrupted transmission in many areas while it has persisted in some areas after 10 or more rounds of MDA. This study was to appreciate community members' perspectives on MDA after over 15 years of implementation. Findings will inform strategies to mobilise community members to participate fully in MDA to enhance the disease elimination process., Methods: This was a qualitative study, employing key-informant in-depth-interviews. Respondents were selected based on their recognition by community members as opinion leaders and persons who were knowledgeable about the topic of interest in the community. A snowball sampling technique was used to select respondents., Results: Respondents were well informed about the MDA with most of them saying, it has been implemented for over 12 years. They were aware that the MDA was for the treatment/control of LF (elephantiasis). It came to light that MDA compliance was affected by five related barriers. These are; Medication, Personal, Health system, Disease and Social structure related barriers. Adverse effects of the drugs and the fact that many people perceived that they were not susceptibility to the infection have grossly affected the ingestion of the drugs., Conclusion: There is a need for community mobilization and promotional activities to explain the expected adverse reactions associated with the drugs to the people. Also the importance of why every qualified person in the community must comply with MDA must be emphasized.

Background: The Global Programme for the Elimination of Lymphatic Filariasis (GPELF) has been in operation since the year 2000, with the aim of eliminating the disease by the year 2020, following five to six rounds of effective annual mass drug administration (MDA). The treatment regimen is ivermectin (IVM) in combination with diethylcarbamazine (DEC) or albendazole (ALB). In Ghana, MDA has been undertaken since 2001. While the disease has been eliminated in many areas, transmission has persisted in some implementation units that had experienced 15 or more rounds of MDA. Thus, new intervention strategies could eliminate residual infection in areas of persistent transmission and speed up the lymphatic filariasis (LF)-elimination process. This study, therefore, seeks to test the hypothesis that biannual treatment of LF-endemic communities will accelerate the interruption of LF in areas of persistent transmission., Methods: A cluster randomised trial will be implemented in LF-endemic communities in Ghana. The interventions will be yearly or twice-yearly MDA delivered to entire endemic communities. Allocation to study group will be by clusters identified using the prevalence of LF. Clusters will be randomised to one of two groups: receiving either (1) annual treatment with IVM + ALB or (2) annual MDA with IVM + ALB, followed by an additional MDA 6 months later. The primary outcome measure is the prevalence of LF infection, assessed by four cross-sectional surveys. Entomological assessments will also be undertaken to evaluate the transmission intensity of the disease in the study clusters. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, microfilaria prevalence will be assessed longitudinally. A nested process evaluation, using semi-structured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system., Discussion: It is expected that this study will add to the existing evidence on the need for alternative intervention strategies for the elimination of LF in Ghana and in other African countries that are facing similar challenges or are at the beginning of their LF-elimination programmes., Trial Registration: ClinicalTrials.gov, ID: NCT03036059 . Registered on 26 January 2017. Pan African Clinical Trials Registry, ID: PACTR201702002012425 . Registered on 23 February 2017.

The erythrocyte binding antigen region II (EBA-175 RII) is a Plasmodium falciparum ligand that mediates erythrocyte invasion and is considered an important malaria vaccine candidate. A phase Ia trial in malaria naïve adults living in the United States found the recombinant non-glycosylated vaccine antigen, EBA-175 RII-NG adjuvanted with aluminium phosphate to be safe, immunogenic and capable of inducing biologically active antibodies that can inhibit parasite growth in vitro. The aim of the current study was to assess the safety and immunogenicity of this vaccine in malaria exposed semi-immune healthy adults living in a malaria endemic country, Ghana. In this double-blinded, placebo controlled, dose escalation phase I trial, eighteen subjects per group received ascending dose concentrations (5 μg, 20 μg or 80 μg) of the vaccine intramuscularly at 0, 1 and 6 months, while 6 subjects received placebo (normal saline). The primary end point was the number of subjects experiencing Grade 3 systemic or local adverse events within 14 days post-vaccination. Serious adverse events were assessed throughout the study period. Blood samples for immunological analyses were collected at days 0, 14, 28, 42, 180 and 194. A total of 52 subjects received three doses of the vaccine in the respective groups. No serious adverse events were reported. The majority of all adverse events reported were mild to moderate in severity, with local pain and tenderness being the most common. All adverse events, irrespective of severity, resolved without any sequelae. Subjects who received any of the EBA-175 RII-NG doses had high immunoglobulin G levels which moderately inhibited P. falciparum growth in vitro, compared to those in the placebo group. In conclusion, the EBA-175 RII-NG vaccine was safe, well tolerated and immunogenic in malaria semi-immune Ghanaian adults. Its further development is recommended., Trial Registration: ClinicalTrials.gov. Identifier: NCT01026246., Competing Interests: The product developed in this study is owned by DMID /NIAID. Leidos was a contract manufacturer and has no commercial interests whatsoever after delivering the product to DMID/NIAID. Leidos had no part in the design, conduct, analysis or interpretation of data from the study. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

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-naïve 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.

Background: To prepare field sites for malaria vaccine trials, it is important to determine baseline antibody and T cell responses to candidate malaria vaccine antigens. Assessing T cell responses is especially challenging, given genetic restriction, low responses observed in endemic areas, their variability over time, potential suppression by parasitaemia and the intrinsic variability of the assays., Methods: In Part A of this study, antibody titres were measured in adults from urban and rural communities in Ghana to recombinant Plasmodium falciparum CSP, SSP2/TRAP, LSA1, EXP1, MSP1, MSP3 and EBA175 by ELISA, and to sporozoites and infected erythrocytes by IFA. Positive ELISA responses were determined using two methods. T cell responses to defined CD8 or CD4 T cell epitopes from CSP, SSP2/TRAP, LSA1 and EXP1 were measured by ex vivo IFN-γ ELISpot assays using HLA-matched Class I- and DR-restricted synthetic peptides. In Part B, the reproducibility of the ELISpot assay to CSP and AMA1 was measured by repeating assays of individual samples using peptide pools and low, medium or high stringency criteria for defining positive responses, and by comparing samples collected two weeks apart., Results: In Part A, positive antibody responses varied widely from 17%-100%, according to the antigen and statistical method, with blood stage antigens showing more frequent and higher magnitude responses. ELISA titres were higher in rural subjects, while IFA titres and the frequencies and magnitudes of ex vivo ELISpot activities were similar in both communities. DR-restricted peptides showed stronger responses than Class I-restricted peptides. In Part B, the most stringent statistical criteria gave the fewest, and the least stringent the most positive responses, with reproducibility slightly higher using the least stringent method when assays were repeated. Results varied significantly between the two-week time-points for many participants., Conclusions: All participants were positive for at least one malaria protein by ELISA, with results dependent on the criteria for positivity. Likewise, ELISpot responses varied among participants, but were relatively reproducible by the three methods tested, especially the least stringent, when assays were repeated. However, results often differed between samples taken two weeks apart, indicating significant biological variability over short intervals.

Summary Objectives: To estimate the reference intervals for commonly used blood haematology and biochemical parameters in an adult (18-55yrs) population of residents of Mampong Akuapem., Design: This was a population based cross sectional study of a randomly selected sample of the adult population of Mampong. The sample was selected from an updated census list of the Mampong area., Results: Median values (95% range) for measured parameters were established as follows: Haemoglobin, (males) 14.2 g/dl (females) 12.0 g/dl Alanine aminotransferase (ALT), (female) 19.6 U/L (males) 26.1 U/L and Creatinine, (males) 108 mmol/L (females) 93 mmol/L., Conclusion: In comparison to reference values that are commonly used in Ghana, the haemoglobulin levels from this study were lower, and liver function parameters higher. This could be a result of genetic or environmental differences and calls for the need to establish site specific reference values applicable to our population.