Early life ambient air pollution, household fuel use, and under-5 mortality in Ghana.

INTRODUCTION: Environmental exposures, such as ambient air pollution and household fuel use affect health and under-5 mortality (U5M) but there is a paucity of data in the Global South. This study examined early-life exposure to ambient particulate matter with a diameter of 2.5 µm or less (PM2.5), alongside household characteristics (including self-reported household fuel use), and their relationship with U5M in the Navrongo Health and Demographic Surveillance Site (HDSS) in northern Ghana. METHODS: We employed Satellite-based spatiotemporal models to estimate the annual average PM2.5 concentrations with the Navrongo HDSS area (1998 to 2016). Early-life exposure levels were determined by pollution estimates at birth year. Socio-demographic and household data, including cooking fuel, were gathered during routine surveillance. Cox proportional hazards models were applied to assess the link between early-life PM2.5 exposure and U5M, accounting for child, maternal, and household factors. FINDINGS: We retrospectively studied 48,352 children born between 2007 and 2017, with 1872 recorded deaths, primarily due to malaria, sepsis, and acute respiratory infection. Mean early-life PM2.5 was 39.3 µg/m3, and no significant association with U5M was observed. However, Children from households using "unclean" cooking fuels (wood, charcoal, dung, and agricultural waste) faced a 73 % higher risk of death compared to those using clean fuels (adjusted HR = 1.73; 95 % CI: 1.29, 2.33). Being born female or to mothers aged 20-34 years were linked to increased survival probabilities. INTERPRETATION: The use of "unclean" cooking fuel in the Navrongo HDSS was associated with under-5 mortality, highlighting the need to improve indoor air quality by introducing cleaner fuels.

Feasibility, safety, and impact of the RTS,S/AS01E malaria vaccine when implemented through national immunisation programmes: evaluation of cluster-randomised introduction of the vaccine in Ghana, Kenya, and Malawi.

BACKGROUND: The RTS,S/AS01E malaria vaccine (RTS,S) was introduced by national immunisation programmes in Ghana, Kenya, and Malawi in 2019 in large-scale pilot schemes. We aimed to address questions about feasibility and impact, and to assess safety signals that had been observed in the phase 3 trial that included an excess of meningitis and cerebral malaria cases in RTS,S recipients, and the possibility of an excess of deaths among girls who received RTS,S than in controls, to inform decisions about wider use. METHODS: In this prospective evaluation, 158 geographical clusters (66 districts in Ghana; 46 sub-counties in Kenya; and 46 groups of immunisation clinic catchment areas in Malawi) were randomly assigned to early or delayed introduction of RTS,S, with three doses to be administered between the ages of 5 months and 9 months and a fourth dose at the age of approximately 2 years. Primary outcomes of the evaluation, planned over 4 years, were mortality from all causes except injury (impact), hospital admission with severe malaria (impact), hospital admission with meningitis or cerebral malaria (safety), deaths in girls compared with boys (safety), and vaccination coverage (feasibility). Mortality was monitored in children aged 1-59 months throughout the pilot areas. Surveillance for meningitis and severe malaria was established in eight sentinel hospitals in Ghana, six in Kenya, and four in Malawi. Vaccine uptake was measured in surveys of children aged 12-23 months about 18 months after vaccine introduction. We estimated that sufficient data would have accrued after 24 months to evaluate each of the safety signals and the impact on severe malaria in a pooled analysis of the data from the three countries. We estimated incidence rate ratios (IRRs) by comparing the ratio of the number of events in children age-eligible to have received at least one dose of the vaccine (for safety outcomes), or age-eligible to have received three doses (for impact outcomes), to that in non-eligible age groups in implementation areas with the equivalent ratio in comparison areas. To establish whether there was evidence of a difference between girls and boys in the vaccine's impact on mortality, the female-to-male mortality ratio in age groups eligible to receive the vaccine (relative to the ratio in non-eligible children) was compared between implementation and comparison areas. Preliminary findings contributed to WHO's recommendation in 2021 for widespread use of RTS,S in areas of moderate-to-high malaria transmission. FINDINGS: By April 30, 2021, 652 673 children had received at least one dose of RTS,S and 494 745 children had received three doses. Coverage of the first dose was 76% in Ghana, 79% in Kenya, and 73% in Malawi, and coverage of the third dose was 66% in Ghana, 62% in Kenya, and 62% in Malawi. 26 285 children aged 1-59 months were admitted to sentinel hospitals and 13 198 deaths were reported through mortality surveillance. Among children eligible to have received at least one dose of RTS,S, there was no evidence of an excess of meningitis or cerebral malaria cases in implementation areas compared with comparison areas (hospital admission with meningitis: IRR 0·63 [95% CI 0·22-1·79]; hospital admission with cerebral malaria: IRR 1·03 [95% CI 0·61-1·74]). The impact of RTS,S introduction on mortality was similar for girls and boys (relative mortality ratio 1·03 [95% CI 0·88-1·21]). Among children eligible for three vaccine doses, RTS,S introduction was associated with a 32% reduction (95% CI 5-51%) in hospital admission with severe malaria, and a 9% reduction (95% CI 0-18%) in all-cause mortality (excluding injury). INTERPRETATION: In the first 2 years of implementation of RTS,S, the three primary doses were effectively deployed through national immunisation programmes. There was no evidence of the safety signals that had been observed in the phase 3 trial, and introduction of the vaccine was associated with substantial reductions in hospital admission with severe malaria. Evaluation continues to assess the impact of four doses of RTS,S. FUNDING: Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.

Exploring infant and young child-feeding practices among mothers of well-nourished children in northern Ghana: An INPreP substudy.

This study investigated infant and young child-feeding (IYCF) practices among mothers of well-nourished children in northern Ghana. This was a qualitative study where in-depth individual interviews were conducted with participants. The interviews were audio recorded, transcribed, and QSR Nvivo software version 11 was used to organize the data before thematic analysis. It was observed that mothers of well-nourished children were likely to adhere to breastfeeding guidelines and also practice appropriate complementary feeding. Furthermore, these mothers mostly had some form of support from their husbands and mother-in-laws in feeding their infants. While adoption and adherence to appropriate IYCF practices contribute to improved nutrition outcomes in children, social support systems are needed to sustain the practice.

Comparison of molecular surveillance methods to assess changes in the population genetics of Plasmodium falciparum in high transmission.

A major motivation for developing molecular methods for malaria surveillance is to measure the impact of control interventions on the population genetics of Plasmodium falciparum as a potential marker of progress towards elimination. Here we assess three established methods (i) single nucleotide polymorphism (SNP) barcoding (panel of 24-biallelic loci), (ii) microsatellite genotyping (panel of 12-multiallelic loci), and (iii) varcoding (fingerprinting var gene diversity, akin to microhaplotyping) to identify changes in parasite population genetics in response to a short-term indoor residual spraying (IRS) intervention. Typical of high seasonal transmission in Africa, multiclonal infections were found in 82.3% (median 3; range 1-18) and 57.8% (median 2; range 1-12) of asymptomatic individuals pre- and post-IRS, respectively, in Bongo District, Ghana. Since directly phasing multilocus haplotypes for population genetic analysis is not possible for biallelic SNPs and microsatellites, we chose ~200 low-complexity infections biased to single and double clone infections for analysis. Each genotyping method presented a different pattern of change in diversity and population structure as a consequence of variability in usable data and the relative polymorphism of the molecular markers (i.e., SNPs < microsatellites < var). Varcoding and microsatellite genotyping showed the overall failure of the IRS intervention to significantly change the population structure from pre-IRS characteristics (i.e., many diverse genomes of low genetic similarity). The 24-SNP barcode provided limited information for analysis, largely due to the biallelic nature of SNPs leading to a high proportion of double-allele calls and a view of more isolate relatedness compared to microsatellites and varcoding. Relative performance, suitability, and cost-effectiveness of the methods relevant to sample size and local malaria elimination in high-transmission endemic areas are discussed.

Birth preparedness and complications readiness among women in disadvantaged rural districts of Ghana.

INTRODUCTION: Essentially all women and babies irrespective of their economic and social status should reach their full potential for health and well-being. The study assessed the readiness of mothers and their preparedness for birth across three disadvantaged rural districts in Ghana. METHODS: A multi-centre quantitative survey from January to December 2018 using a multistage sampling approach was employed. Using a structured questionnaire data from mothers attending antenatal and postnatal clinics in three main ecological zones of Ghana were collected. Women who provided informed consent were consecutively recruited until the sample size was achieved. For categorical data, summary tables, proportions and percentage are presented. Multivariate logistic regression analysis determined the effect of selected characteristics on birth preparedness. Ethics approval was obtained from the Navrongo Health Research Centre. RESULTS: A total of 1058 mothers were enrolled: 33.6%, 33.4% and 33.0% respectively from the Ada west, Upper Denkyira west and Builsa south districts. About 94% of the women had prior knowledge of birth preparedness. Approximately 22.6% (95%CI 20.1, 25. 2) of the mothers were assessed to have poor birth preparedness: 8.0% in Builsa south, 27.8% in Ada west and 31.7% in Upper Denkyira west. Prenatal and postnatal data showed no statistically significant difference in poor preparedness (21.9% vs 23.3%; p-value > 0.05). Maternal age, employment status, religious affiliation and parity were not associated with birth preparedness (p-value > 0.05). Area of study (P < 0.001), educational level (P < 0.016), marital status (p < 0.001) and antenatal contacts (< 0.001) were significantly associated with birth preparedness. CONCLUSIONS: As an important safe motherhood strategy woman should plan their pregnancy and birth well to reduce maternal and neonatal mortality. Policy initiatives should take into consideration area of residence, education, marital status and antenatal contacts of women.

Genetic diversity of rotavirus infection among young children with diarrhoea in the Kassena-Nankana Districts of Northern Ghana: a seasonal cross-sectional survey.

Introduction: diarrhoea disease is a global health concern, persisting as one of the top five causes of morbidity and mortality in children. Viral aetiology of childhood diarrhoea is often associated with rotavirus infection of which preventable vaccines exist. Here we document circulating strains of rotavirus in the Kassena-Nankana Districts of Northern Ghana nearly a decade after the introduction of the rotavirus vaccine. Methods: a cross-sectional survey of children aged 0-60 months was conducted in six health facilities within the Kassena-Nankana Districts. Faecal samples obtained from the children were analysed and characterized for rotavirus detection and genotyping using Semi-Nested Polymerase Chain Reaction. Results: a total of 263 stool samples were analyzed. Out of which 14.8% and 18.6% of the diarrhoea cases were of rotavirus and parasitic etiologies respectively, with 17.4% being co-infections. Almost 27.5% of rotavirus diarrhoeal cases resulted in hospitalization. Household size (p=0.035), location (p=0.018), treatment outcome (p=0.007), vomiting (p=0.039), season (p=0.017) and month of sampling (p=0.000) were significantly associated with rotavirus infection. The rotavirus genotypes identified were G1P8, G3P6, G4P9, G10P6 and G12P8. Rotavirus vaccine-type, G1P8 was absent in Kassena-Nankana West District. Conclusion: the prevalence of rotavirus was low compared to the pre-vaccination era. Also, a new rotavirus strain, G4P9 was identified to be circulating in the study area which calls for surveillance measures and more studies to better understand the situation for appropriate public health intervention.

Measuring changes in Plasmodium falciparum census population size in response to sequential malaria control interventions.

Here we introduce a new endpoint "census population size" to evaluate the epidemiology and control of Plasmodium falciparum infections, where the parasite, rather than the infected human host, is the unit of measurement. To calculate census population size, we rely on a definition of parasite variation known as multiplicity of infection (MOIvar), based on the hyper-diversity of the var multigene family. We present a Bayesian approach to estimate MOIvar from sequencing and counting the number of unique DBLα tags (or DBLα types) of var genes, and derive from it census population size by summation of MOIvar in the human population. We track changes in this parasite population size and structure through sequential malaria interventions by indoor residual spraying (IRS) and seasonal malaria chemoprevention (SMC) from 2012 to 2017 in an area of high-seasonal malaria transmission in northern Ghana. Following IRS, which reduced transmission intensity by > 90% and decreased parasite prevalence by ~40-50%, significant reductions in var diversity, MOIvar, and population size were observed in ~2,000 humans across all ages. These changes, consistent with the loss of diverse parasite genomes, were short lived and 32-months after IRS was discontinued and SMC was introduced, var diversity and population size rebounded in all age groups except for the younger children (1-5 years) targeted by SMC. Despite major perturbations from IRS and SMC interventions, the parasite population remained very large and retained the var population genetic characteristics of a high-transmission system (high var diversity; low var repertoire similarity) demonstrating the resilience of P. falciparum to short-term interventions in high-burden countries of sub-Saharan Africa.

Impact of community health interventions on maternal and child health indicators in the upper east region of Ghana.

BACKGROUND: This paper reports on results of a health system strengthening implementation research initiative conducted the Upper East Region of northern Ghana. Transformative interventions to accelerate and strengthen the health delivery were implemented that included empowering community leaders and members to actively participate in health delivery, strengthening the referral systems through the provision of community transport systems, providing basic medical equipment to community clinics, and improving the skills of critical health staff through training. METHODS: A mixed method design was used to evaluate the impact of the interventions. A quantitative evaluation employed a flexible research design to test the effects of various component activities of the project. To assess impact, a pre-versus-post randomized cluster survey design was used. Qualitative research was conducted with focus group data and individual in depth interviews to gauge the views of various stakeholders associated with the implementation process. RESULTS: After intervention, significant improvements in key maternal and child health indicators such as antenatal and postnatal care coverage were observed and increases in the proportion of deliveries occurring in health facilities and assisted by skilled health personnel relative to pre-intervention conditions. There was also increased uptake of oral rehydration salts (ORS) for treatment of childhood diarrhoea, as well as marked reductions in the incidence of upper respiratory infections (URI). CONCLUSIONS: A pre-and post-evaluation of impact suggests that the programme had a strong positive impact on the functioning of primary health care. Findings are consistent with the proposition that the coverage and content of the Ghana Community-based Health Planning and Services programme was improved by program interventions and induced discernable changes in key indicators of health system performance.

Community perspectives on cardiovascular disease control in rural Ghana: A qualitative study.

BACKGROUND: Cardiovascular disease (CVD) prevalence is high in Ghana-but awareness, prevention, and treatment is sparse, particularly in rural regions. The nurse-led Community-based Health Planning and Services program offers general preventive and primary care in these areas, but overlooks CVD and its risk factors. METHODS: We conducted in-depth interviews with 30 community members (CM) in rural Navrongo, Ghana to understand their knowledge and beliefs regarding the causes and treatment of CVD and the potential role of community nurses in rendering CVD care. We transcribed audio records, coded these data for content, and qualitatively analyzed these codes for key themes. RESULTS: CMs described CVD as an acute, aggressive disease rather than a chronic asymptomatic condition, believing that CVD patients often die suddenly. Yet CMs identified causal risk factors for CVD: not only tobacco smoking and poor diet, but also emotional burdens and stressors, which cause and exacerbate CVD symptoms. Many CMs expressed interest in counseling on these risk factors, particularly diet. However, they felt that nurses could provide comprehensive CVD care only if key barriers (such as medication access and training) are addressed. In the interim, many saw nurses' main CVD care role as referring to the hospital. CONCLUSIONS: CMs would like CVD behavioral education from community nurses at local clinics, but feel the local health system is now too fragile to offer other CVD interventions. CMs believe that a more comprehensive CVD care model would require accessible medication, along with training for nurses to screen for hypertension and other cardiovascular risk factors-in addition to counseling on CVD prevention. Such counseling should build upon existing community beliefs and concerns regarding CVD-including its behavioral and mental health causes-in addition to usual measures to prevent CVD mortality such as diet changes and physical exercise.

Non-HDL-C and LDL-C/HDL-C are associated with self-reported cardiovascular disease in a rural West African population: Analysis of an array of lipid metrics in an AWI-Gen sub-study.

Few studies have compared the utility of serum levels of lipid fractions in cardiovascular disease (CVD) risk assessment in sub-Saharan Africa (SSA). The current study interrogated this question among men and women aged 40-60 years in rural northern Ghana. This was a cross-sectional study in which data was collected on socio-demography, behaviour, health history, anthropometry and lipid levels. Adjusted multivariable logistic regression models were used to assess the association of various lipid metrics with CVD. All tests were considered statistically significant at P<0.05. Data were available for 1839 participants. The prevalence of self-reported CVD was 1.6% (n = 29). Non-HDL-C (median (interquartile range): 2.4 (1.9-3.0) vs 2.0 (1.6-2.5) mmol/L; P = 0.009), LDL-C/HDL-C (1.8 (1.4-2.4) vs 1.5 (1.1-2.6); P = 0.019) and TC/HDL-C (3.3 (2.9-3.9) vs 2.9 (2.4-3.5); P = 0.003) were all significantly higher in participants with self-reported CVD compared to those without. However, after adjusting for socioeconomic status (SES) and meals from vendors in a logistic regression model, only non-HDL-C (odds ratio [95% CIs]): (1.58 [1.05, 2.39]), P = 0.029 and LDL-C/HDL-C levels (odds ratio [95% CIs]): (1.26 [1.00, 1.59]), P = 0.045 remained significantly associated with self-reported CVD. While our findings suggest non-HDL-C and LDL-C/HDL-C measures may be appropriate biomarkers for assessing CVD risk in this population, further studies using established clinical endpoints are required to validate these findings in sub-Saharan Africans.

Optimising reporting of adverse events following immunisation by healthcare workers in Ghana: A qualitative study in four regions.

INTRODUCTION: Despite the emphasis on reporting of Adverse Events Following Immunisation (AEFIs) during didactic training sessions, especially prior to new vaccine introductions, it remains low in Ghana. We explored the factors underlying the under-reporting of AEFI by healthcare workers (HCWs) to provide guidance on appropriate interventions to increase reporting. METHODS: We conducted an exploratory descriptive in-depth study of the factors contributing to low reporting of AEFI among HCWs in four regions in Ghana. Key informant interviews (KII) were held with purposively selected individuals that are relevant to the AEFI reporting process at the district, regional, and national levels. We used KII guides to conduct in-depth interviews and used NVivo 10 qualitative software to analyse the data. Themes on factors influencing AEFI reporting were derived inductively from the data, and illustrative quotes from respondents were used to support the narratives. RESULTS: We conducted 116 KIIs with the health managers, regulators and frontline HCWs and found that lack of information on reportable AEFIs and reporting structures, misunderstanding of reportable AEFIs, heavy workload, cost of reporting AEFIs, fear of blame by supervisors, lack of motivation, and inadequate feedback as factors responsible for underreporting of AEFIs. Respondents suggested that capacity building for frontline HCWs, effective supervision, the provision of motivation and feedback, simplification of reporting procedures, incentives for integrating AEFI reporting into routine monitoring and reporting, standardization of reporting procedures across regions, and developing appropriate interventions to address the fear of personal consequences would help improve AEFI reporting. CONCLUSION: From the perspectives of a broad range of key informants at all levels of the vaccine safety system, we found multiple factors (both structural and behavioural), that may impact HCW reporting of AEFI in Ghana. Improvements in line with the suggestions are necessary for increased AEFI reporting in Ghana.

Bio-efficacy, physical integrity, use and attrition of long-lasting insecticidal nets under operational conditions for malaria prevention in Ghana.

BACKGROUND: Malaria remains a public health challenge in endemic countries of the world. The use of Long-lasting Insecticidal Nets (LLINs) is one of the major ways of malaria vector control. Recent evidence however suggests some LLINs are unable to maintain their effectiveness over their useful life span. This study assessed the bio-efficacy, physical integrity, use and attrition at 6 and 12-months post-distribution of LLINs (LifeNet). METHODS: Following a mass distribution of LLINs in the West Mamprusi District of the North-East region of Ghana in 2018, a total of 147 LLINs were sampled for physical integrity and attrition assessment using hole size and the number of holes as a measure of the proportionate hole index (pHI). Bioassays were conducted on sixty randomly selected LLINs using the WHO guidelines for bio-efficacy testing (cone tests), (20 each at baseline, midline and endline) over a one-year study period. Bed net ownership and use as well as malaria vector resistance status were also assessed. RESULTS: Findings indicate high bio-efficacy of approximately 100% average mortalities of mosquitoes at baseline, 6-months and 12-months post-distribution. A small proportion of LLINs (0.8% and 5.6% at the 6 and 12-months surveys respectively) were damaged beyond maintenance while 62.4% and 62.7% of LLINs were used the night before the survey for 6 and 12-months post-distribution respectively. Households with electricity were less likely to use LLINs compared to those without electricity (P-value = 0.016, OR = 0.39). There were 20 fewer LLINs recovered at the 12-months relative to the 6-months resulting in 14.3% attrition rate. Susceptibility testing showed high pyrethroid and organochlorine resistance (18%, 67.5% and 3.8%) to local malaria vectors respectively), whereas organophosphates and carbamates recorded vector susceptibility of 100% for pirimiphos-methyl and 98.7% for bendiocarb. CONCLUSION: Biological efficacy, physical integrity and net attrition during the study period were in conformity with respect to the WHOPES one year net use. LLINs remained effective after one-year of usage. Net ownership was high in the study households. There should be continuous and regular distribution campaigns to maintain high coverage.

Compliance to HIV testing and counseling guidelines at antenatal care clinics in the Kassena-Nankana districts of northern Ghana: A qualitative study.

BACKGROUND: Utilization of antenatal care services in Ghana has substantially increased over the years, but the rates of mother-to-child transmission of HIV is still high. The high burden of HIV among pregnant women has serious implications for mother-to-child transmission. The main objective of this study was to assess the compliance of HIV testing and counseling provided at antenatal care clinics in two rural districts in northern Ghana by comparing reported practices to the national guidelines. METHODS: This study was a descriptive qualitative study conducted in the Kassena-Nankana Districts of northern Ghana. In-depth interviews were conducted with 10 midwives, 10 mothers, and 2 public health nurses who were recruited through purposive and snowball sampling. All interviews were audio recorded, transcribed into English, and imported into NVivo 12.0 software for open, axial, and selective coding. RESULTS: The findings indicate that not all pregnant women were informed prior to testing nor informed of their test results. Many mothers indicated that pre-test counseling is limited although the midwives claimed to provide it. Post-test counseling is primarily given to those who test positive, and several midwives agreed that there is no need to counsel HIV-negative women. Perceptions of the lack of confidentiality and privacy were pervasive among mothers despite the emphasis placed on its importance by the midwives. There were conflicting reports on whether HIV testing during antenatal care is voluntary or compulsory. The challenges with HIV testing and counseling that were mentioned by midwives include lack of adequate infrastructure, language barriers, and insufficient training. CONCLUSIONS: HIV testing and counseling provided at antenatal care is not uniform across all health facilities and does not strictly adhere to national guidelines. Future interventions that focus on standardization, monitoring, privacy, and capacity building are likely to prove valuable in ensuring quality services are provided.

Urogenital schistosomiasis transmission, malaria and anemia among school-age children in Northern Ghana.

Background: In sub-Saharan Africa, co-morbidity with malaria, schistosomiasis, and soil transmitted helminths (STH) is common among young children. The current study investigated malaria, urinary schistosomiasis and their co-infection and anemia among school-age children in an endemic community, Nakolo in the Kassena-Nankana East District of northern Ghana. Methods: A cross-sectional survey of 336 school-age children, 5-16 years was undertaken. Urine samples were examined for Schistosoma haematobium ova using microscopy. Finger prick blood samples were examined for Plasmodium parasites using microscopy and haemoglobin concentration measured with HemoCue Hb301 photometer. Results: The mean age was 10.52 (Standard deviation: ±2.27; range: 5-16 years), of which 50.6% (170/336) were males. The overall prevalence of urinary schistosomiasis and Plasmodium (P.) falciparum was 12.8% (43/336) and 37.8% (127/336), respectively with 6.0% (20/336) coinfection. Participants with only P. falciparum infection had 17.8% (19/107) of moderate anemia whilst 21.7% (5/23) of children infected with only S. haematobium had moderate anemia and 4.3% (1/23) had severe anemia. 5.0 % (1/20) of moderate anemia was observed in concurrent infections of P. falciparum and S. haematobium. Use of open water bodies was associated with increased risk of S. haematobium infection (OR = 1.21; 95% CI = [1.06-1.39]; p = 0.001), with females being at reduced risk (OR = 0.93; 95%CI = [0.87-0.99]; p = 0.005). Absence of self-reported haematuria had 0.81 times reduced odds of S. haematobium infection (OR = 0.81; 95%CI = [0.74-0.87]; p < 0.001). Conclusion: This study has revealed that urinary schistosomiasis remains prevalent in Kassena-Nankana East district and suggests that urinary schistosomiasis may contribute to moderate anemia among school-age children as compared to asymptomatic malaria infection. These findings call for an evaluation of the annual mass drug administration of Praziquantel among in-school children to ascertain its impact on urinary schistosomiasis prevalence across the district.

Racial and Ethnic Differences in the Association Between Classical Cardiovascular Risk Factors and Common Carotid Intima-Media Thickness: An Individual Participant Data Meta-Analysis.

Background The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid-intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. Methods and Results Cross-sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B-mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 2-stage individual participant data meta-analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coefficient, 0.39; 95% CI, 0.09-0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01-0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06-0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High-density lipoprotein-cholesterol had significant protective effects in African American (beta coefficient, -0.31; 95% CI, -0.42 to -0.21) and African (beta coefficient, -0.26; 95% CI, -0.31 to -0.19) populations only. Conclusions The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race- ethnicity-specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations.

Clinical evaluation of the BioFire Global Fever Panel for the identification of malaria, leptospirosis, chikungunya, and dengue from whole blood: a prospective, multicentre, cross-sectional diagnostic accuracy study.

BACKGROUND: Acute febrile illness is a common presentation for patients at hospitals globally. Assays that can diagnose a variety of common pathogens in blood could help to establish a diagnosis for targeted disease management. We aimed to evaluate the performance of the BioFire Global Fever Panel (GF Panel), a multiplex nucleic acid amplification test performed on whole blood specimens run on the BioFire FilmArray System, in the diagnosis of several pathogens that cause acute febrile illness. METHODS: We did a prospective, multicentre, cross-sectional diagnostic accuracy study to evaluate the GF Panel. Consenting adults and children older than 6 months presenting with fever in the previous 2 days were enrolled consecutively in sub-Saharan Africa (Ghana, Kenya, Tanzania, Uganda), southeast Asia (Cambodia, Thailand), central and South America (Honduras, Peru), and the USA (Washington, DC; St Louis, MO). We assessed the performance of six analytes (chikungunya virus, dengue virus [serotypes 1-4], Leptospira spp, Plasmodium spp, Plasmodium falciparum, and Plasmodium vivax or Plasmodium ovale) on the GF Panel. The performance of the GF Panel was assessed using comparator PCR assays with different primers followed by bidirectional sequencing on nucleic acid extracts from the same specimen. We calculated the positive percent agreement and negative percent agreement of the GF Panel with respect to the comparator assays. This study is registered with ClinicalTrials.gov, NCT02968355. FINDINGS: From March 26, 2018, to Sept 30, 2019, 1965 participants were enrolled at ten sites worldwide. Of the 1875 participants with analysable results, 980 (52·3%) were female and the median age was 22 years (range 0-100). At least one analyte was detected in 657 (35·0%) of 1875 specimens. The GF Panel had a positive percent agreement for the six analytes evaluated as follows: chikungunya virus 100% (95% CI 86·3-100), dengue virus 94·0% (90·6-96·5), Leptospira spp 93·8% (69·8-99·8), Plasmodium spp 98·3% (96·3-99·4), P falciparum 92·7% (88·8-95·6), and P vivax or P ovale 92·7% (86·7-96·6). The GF Panel had a negative percent agreement equal to or greater than 99·2% (98·6-99·6) for all analytes. INTERPRETATION: This 1 h sample-to-answer, molecular device can detect common causative agents of acute febrile illness with excellent positive percent agreement and negative percent agreement directly in whole blood. The targets of the assay are prevalent in tropical and subtropical regions globally, and the assay could help to provide both public health surveillance and individual diagnoses. FUNDING: BioFire Defense, Joint Project Manager for Medical Countermeasure Systems and US Army Medical Materiel Development Activity, and National Institute of Allergy and Infectious Diseases.

Indoor residual spraying with a non-pyrethroid insecticide reduces the reservoir of Plasmodium falciparum in a high-transmission area in northern Ghana.

High-malaria burden countries in sub-Saharan Africa are shifting from malaria control towards elimination. Hence, there is need to gain a contemporary understanding of how indoor residual spraying (IRS) with non-pyrethroid insecticides when combined with long-lasting insecticidal nets (LLINs) impregnated with pyrethroid insecticides, contribute to the efforts of National Malaria Control Programmes to interrupt transmission and reduce the reservoir of Plasmodium falciparum infections across all ages. Using an interrupted time-series study design, four age-stratified malariometric surveys, each of ~2,000 participants, were undertaken pre- and post-IRS in Bongo District, Ghana. Following the application of three-rounds of IRS, P. falciparum transmission intensity declined, as measured by a >90% reduction in the monthly entomological inoculation rate. This decline was accompanied by reductions in parasitological parameters, with participants of all ages being significantly less likely to harbor P. falciparum infections at the end of the wet season post-IRS (aOR = 0.22 [95% CI: 0.19-0.26], p-value < 0.001). In addition, multiplicity of infection (MOI var ) was measured using a parasite fingerprinting tool, designed to capture within-host genome diversity. At the end of the wet season post-IRS, the prevalence of multi-genome infections declined from 75.6% to 54.1%. This study demonstrates that in areas characterized by high seasonal malaria transmission, IRS in combination with LLINs can significantly reduce the reservoir of P. falciparum infection. Nonetheless despite this success, 41.6% of the population, especially older children and adolescents, still harboured multi-genome infections. Given the persistence of this diverse reservoir across all ages, these data highlight the importance of sustaining vector control in combination with targeted chemotherapy to move high-transmission settings towards pre-elimination. This study also points to the benefits of molecular surveillance to ensure that incremental achievements are not lost and that the goals advocated for in the WHO's High Burden to High Impact strategy are realized.

Assessing the safety, impact and effectiveness of RTS,S/AS01E malaria vaccine following its introduction in three sub-Saharan African countries: methodological approaches and study set-up.

BACKGROUND: Following a 30-year development process, RTS,S/AS01E (GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01E through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on Plasmodium falciparum variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01E through active participant follow-up in the context of its real-life implementation. METHODS: EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the P. falciparum genetic diversity in the periods before and after vaccine implementation. CONCLUSION: GSK's post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01E vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01E's benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa.

Carotid Atherosclerosis, Microalbuminuria, and Estimated 10-Year Atherosclerotic Cardiovascular Disease Risk in Sub-Saharan Africa.

Importance: Carotid atherosclerosis and microalbuminuria are associated with atherosclerotic cardiovascular disease (ASCVD) but are understudied in sub-Saharan Africa. Objective: To evaluate the association of carotid atherosclerosis and microalbuminuria with 10-year ASCVD risk in middle-aged sub-Saharan African individuals. Design, Setting, and Participants: This cross-sectional study conducted analyses of baseline data from the African-Wits-INDEPTH (International Network for the Demographic Evaluation of Populations and Their Health in Low- and Middle-Income Countries) genomic study (AWI-Gen). Women and men aged 40 to 60 years without baseline CVD and drawn from Burkina Faso, Ghana, Kenya, and South Africa were included. Main Outcomes and Measures: Hypotheses for the analyses were formulated after data collection. The main exposures were carotid atherosclerosis, assessed using carotid intima-media thickness (CIMT) using B-mode ultrasonography, and microalbuminuria, measured using spot urine albumin (SUA) and urine albumin-creatinine ratio (uACR). The main outcome was high ASCVD risk, defined as a 2018 Pooled Cohort Equations score of 7.5% or greater. Associations were estimated using adjusted multivariable logistic regression analyses. Findings: A total of 9010 participants with a mean (SD) age of 50 (6) years and 4533 (50.3%) women were included. High CIMT, SUA, and uACR were each associated with older age (eg, mean [SD] age of participants with high vs reference range CIMT: 55 [5] years vs 50 [6] years; P < .001) and high prevalence of both diabetes and hypertension (eg, hypertension among those with high vs reference range SUA: 213 of 1117 [19.1%] vs 356 of 2549 [14.0%]; P < .001). Smokers were likely to have higher vs reference range SUA (210 [18.8%] vs 407 [16.0%]) and uACR (138 of 707 [19.5%] vs 456 of 2797 [16.3%]). Carotid atherosclerosis was common in Burkina Faso (82 of 262 [31.3%]) and Ghana (91 [34.7%]), while microalbuminuria, measured by SUA, was common in Kenya (272 [24.4%]) and South Africa (519 [46.5%]). SUA was associated with higher odds of carotid atherosclerosis (odds ratio [OR], 1.77; 95% CI, 1.04-3.01) compared with uACR (OR, 0.51; 95% CI, 0.27-0.95). Common CIMT, SUA, and uACR were associated with 10-year ASCVD risk, with CIMT having a stronger association with 10-year ASCVD risk in both women (OR, 1.95; 95% CI, 1.78-2.14) and men (OR, 1.73; 95% CI, 1.55-1.93) than SUA (women: OR, 1.29; 95% CI, 1.12-1.43; men: OR, 1.46; 95% CI, 1.26-1.55) and uACR (women: OR, 1.32; 95% CI, 1.10-1.54; men: OR, 1.35; 95% CI, 1.15-1.46). Conclusions and Relevance: The presence of microalbuminuria measured by SUA may indicate risk of subclinical carotid atherosclerosis and high 10-year ASCVD risk in middle-aged residents of sub-Saharan Africa. These data should be confirmed in longitudinal studies of cardiovascular events.

Age-specific patterns of DBLα var diversity can explain why residents of high malaria transmission areas remain susceptible to Plasmodium falciparum blood stage infection throughout life.

Immunity to Plasmodium falciparum is non-sterilising, thus individuals residing in malaria-endemic areas are at risk of infection throughout their lifetime. Here we seek to find a genomic epidemiological explanation for why residents of all ages harbour blood stage infections despite lifelong exposure to P. falciparum in areas of high transmission. We do this by exploring, for the first known time, the age-specific patterns of diversity of variant antigen encoding (var) genes in the reservoir of infection. Microscopic and submicroscopic P. falciparum infections were analysed at the end of the wet and dry seasons in 2012-2013 for a cohort of 1541 residents aged from 1 to 91 years in an area characterised by high seasonal malaria transmission in Ghana. By sequencing the near ubiquitous Duffy-binding-like alpha domain (DBLα) that encodes immunogenic domains, we defined var gene diversity in an estimated 1096 genomes detected in sequential wet and dry season sampling of this cohort. Unprecedented var (DBLα) diversity was observed in all ages with 42,399 unique var types detected. There was a high degree of maintenance of types between seasons (>40% seen more than once), with many of the same types, especially upsA, appearing multiple times in isolates from different individuals. Children and adolescents were found to be significant reservoirs of var DBLα diversity compared with adults. Var repertoires within individuals were highly variable, with children having more related var repertoires compared to adolescents and adults. Individuals of all ages harboured multiple genomes with var repertoires unrelated to those infecting other hosts. High turnover of parasites with diverse isolate var repertoires was also observed in all ages. These age-specific patterns are best explained by variant-specific immune selection. The observed level of var diversity for the population was then used to simulate the development of variant-specific immunity to the diverse var types under conservative assumptions. Simulations showed that the extent of observed var diversity with limited repertoire relatedness was sufficient to explain why adolescents and adults in this community remain susceptible to blood stage infection, even with multiple genomes.