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.

Household Air Pollution and Child Lung Function: The Ghana Randomized Air Pollution and Health Study.

Rationale: The impact of a household air pollution (HAP) stove intervention on child lung function has been poorly described. Objectives: To assess the effect of a HAP stove intervention for infants prenatally to age 1 on, and exposure-response associations with, lung function at child age 4. Methods: The Ghana Randomized Air Pollution and Health Study randomized pregnant women to liquefied petroleum gas (LPG), improved biomass, or open-fire (control) stove conditions through child age 1. We quantified HAP exposure by repeated maternal and child personal carbon monoxide (CO) exposure measurements. Children performed oscillometry, an effort-independent lung function measurement, at age 4. We examined associations between Ghana Randomized Air Pollution and Health Study stove assignment and prenatal and infant CO measurements and oscillometry using generalized linear regression models. We used reverse distributed lag models to examine time-varying associations between prenatal CO and oscillometry. Measurements and Main Results: The primary oscillometry measure was reactance at 5 Hz, X5, a measure of elastic and inertial lung properties. Secondary measures included total, large airway, and small airway resistance at 5 Hz, 20 Hz, and the difference in resistance at 5 Hz and 20 Hz (R5, R20, and R5-20, respectively); area of reactance (AX); and resonant frequency. Of the 683 children who attended the lung function visit, 567 (83%) performed acceptable oscillometry. A total of 221, 106, and 240 children were from the LPG, improved biomass, and control arms, respectively. Compared with control, the improved biomass stove condition was associated with lower reactance at 5 Hz (X5 z-score: ß = -0.25; 95% confidence interval [CI] = -0.39, -0.11), higher large airway resistance (R20 z-score: ß = 0.34; 95% CI = 0.23, 0.44), and higher AX (AX z-score: ß = 0.16; 95% CI = 0.06, 0.26), which is suggestive of overall worse lung function. The LPG stove condition was associated with higher X5 (X5 score: ß = 0.16; 95% CI = 0.01, 0.31) and lower small airway resistance (R5-20 z-score: ß = -0.15; 95% CI = -0.30, 0.0), which is suggestive of better small airway function. Higher average prenatal CO exposure was associated with higher R5 and R20, and distributed lag models identified sensitive windows of exposure between CO and X5, R5, R20, and R5-20. Conclusions: These data support the importance of prenatal HAP exposure on child lung function. Clinical trial registered with www.clinicaltrials.gov (NCT01335490).

Prevalence and factors associated with malaria among children aged 6 months to 10 years in the Greater Accra Region of Ghana: a community-based cross-sectional survey.

BACKGROUND: Malaria remains a major public health problem, especially among children in sub-Saharan Africa. Knowledge of malaria parasite prevalence informs targeted interventions and helps to monitor the effectiveness of those interventions. This study aimed to determine prevalence and factors associated with malaria in children aged 6 months to 10 years in the Greater Accra Region of Ghana. METHODS: A community-based cross-sectional study was conducted among 8,741 children aged 6-59 months and 8,292 children aged 5-10 years in all 29 districts of the Greater Accra Region of Ghana in October 2020. Systematic random sampling was used to select communities, households and study participants. A structured questionnaire was used to collect data from caregivers. Rapid diagnostic test kits were used to determine the presence of malaria parasites in blood samples collected by fingerprick. Factors associated with malaria RDT-positivity were determined using multivariate logistic regression analysis. RESULTS: Of 8727 children aged 6-59 months and 8279 aged 5-10 years from whom blood samples were obtained, positive results were obtained for 289 (3.3%; 95% CI 3.0-3.7) and 406 (4.9%; 95% CI 4.5-5.4) respectively. Malaria parasite prevalence in the districts ranged from 0.9 to 10.7% and 1.4-15.0% in children aged 6-59 months and 5-10 years respectively. Factors associated with increased odds of malaria included higher age (AOR = 1.43; 95% CI 1.14-1.71), and living in households without nets on the windows (AOR 1.64; 95% CI 1.10-2.45). On the other hand, living in households located in urban communities was associated with a lower risk of malaria (AOR 0.56; 95% CI 0.40-0.78). CONCLUSION: The average prevalence of malaria in the Greater Accra Region is low compared with other regions. However, there are potential hotspots that need to be targeted with appropriate interventions to accelerate the drive towards malaria elimination.

Malaria prevention in children: an update.

PURPOSE OF REVIEW: Malaria cases and deaths decreased from 2000 to 2015 but remain increased since 2019. Several new developments and strategies could help reverse this trend. The purpose of this review is to discuss new World Health Organization (WHO) guidelines and recent research on malaria prevention in children. RECENT FINDINGS: Fifteen countries have now rolled out seasonal malaria chemoprophylaxis (SMC) in children at highest risk for severe malaria, and new WHO recommendations provide more flexibility for SMC implementation in terms of target age groups, geographic region, and number of cycles. Recent studies confirm that malaria burden in school aged children, and their contribution to transmission, is high. New guidelines permit expanded chemoprevention options for these children. Two vaccines have been approved for use in malaria endemic countries, RTS,S/AS01 E and R21/Matrix-M. Additionally, pyrethroid-chlorfenapyr bed nets are being deployed to combat resistant mosquitoes. SUMMARY: While challenges remain in malaria control towards elimination, new guidelines and recently approved vaccines offer hope. Monitoring for continued vaccine and chemoprevention effectiveness, and for possible epidemiologic shifts in severe malaria presentation and deaths as additional prevention efforts roll out will be paramount.

Beyond air pollution: a national assessment of cooking-related burns in Ghana.

INTRODUCTION: Household energy transitions have the potential to reduce the burden of several health outcomes but have narrowly focused on those mediated by reduced exposure to air pollution, despite concerns about the burden of injury outcomes. Here, we aimed to describe the country-level incidence of severe cooking-related burns in Ghana and identify household-level risk factors for adults and children. METHODS: We conducted a national household energy use survey including 7389 households across 370 enumeration areas in Ghana in 2020. In each household, a pretested version of the Clean Cooking Alliance Burns Surveillance Module was administered to the primary cook. We computed incidence rates of severe cooking-related burns and conducted bivariate logistic regression to identify potential risk factors. RESULTS: We documented 129 severe cooking-related burns that had occurred in the previous year. The incidence rate (95% CI) of cooking-related burns among working-age females was 17 (13 to 21) per 1000 person-years or 8.5 times higher than that of working-age males. Among adults, the odds of experiencing a cooking-related burn were 2.29 (95% CI 1.02 to 5.14) and 2.40 (95% CI 1.04 to 5.55) times higher among primary wood and charcoal users respectively compared with primary liquified petroleum gas users. No child burns were documented in households where liquified petroleum gas was primarily used. CONCLUSION: Using a nationally representative sample, we found that solid fuel use doubled the odds of cooking-related burns compared with liquified petroleum gas. Ghana's efforts to expand access to liquified petroleum gas should focus on safe use.

Association between malaria and household air pollution interventions in a predominantly rural area of Ghana.

BACKGROUND: Though anecdotal evidence suggests that smoke from HAP has a repellent effect on mosquitoes, very little work has been done to assess the effect of biomass smoke on malaria infection. The study, therefore, sought to investigate the hypothesis that interventions to reduce household biomass smoke may have an unintended consequence of increasing placental malaria or increase malaria infection in the first year of life. METHODS: This provides evidence from a randomized controlled trial among 1414 maternal-infant pairs in the Kintampo North and Kintampo South administrative areas of Ghana. Logistic regression was used to assess the association between study intervention assignment (LPG, Biolite or control) and placental malaria. Finally, an extended Cox model was used to assess the association between study interventions and all episodes of malaria parasitaemia in the first year of infant's life. RESULTS: The prevalence of placental malaria was 24.6%. Out of this, 20.8% were acute infections, 18.7% chronic infections and 60.5% past infections. The study found no statistical significant association between the study interventions and all types of placental malaria (OR = 0.88; 95% CI 0.59-1.30). Of the 1165 infants, 44.6% experienced at least one episode of malaria parasitaemia in the first year of life. The incidence of first and/or only episode of malaria parasitaemia was however found to be similar among the study arms. CONCLUSION: The findings suggest that cookstove interventions for pregnant women and infants, when combined with additional malaria prevention strategies, do not lead to an increased risk of malaria among pregnant women and infants.

Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria.

BACKGROUND: RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group. METHODS: To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria (to exclude the effect of naturally acquired immunity) using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009-2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and background malaria incidence. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01. RESULTS: We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by background incidence or parasitemia during the primary vaccination series. CONCLUSIONS: We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that control-group immunity is likely a major reason for lower efficacy in high transmission settings, not reduced immune responses to RTS,S/AS01. This may be reassuring for implementation in high transmission settings, though further studies are needed.

Prevalence and determinants of caesarean section deliveries in the Kintampo Districts of Ghana.

BACKGROUND: Globally, the increasing rate of caesarean section (CS) delivery has become a major public health concern due to its cost, maternal, neonatal, and perinatal risks. In Ghana, the Family Health Division of the Ghana Health Service in 2016 opted to initiate a program to prevent the abuse of CS and identify the factors contributing to its increase in the country. This study aimed to determine the prevalence and factors influencing CS deliveries in the Kintampo Districts of Ghana. METHODS: The current study used secondary data from the Every Newborn-International Network for the Demographic Evaluation of Populations and their Health (EN-INDEPTH) project in Kintampo, Ghana. The outcome variable for this study is CS delivery. The predictor variables were socio-demographic and obstetric factors. RESULTS: The prevalence of CS delivery in the study area was 14.6%. Women with secondary education were 2.6 times more likely to give birth by CS than those with primary education. Unmarried women were about 2.5 times more likely to deliver by CS compared to those who were married. There was an increasing order of CS delivery among women in the wealthy quintiles from poorer to richest. The likelihood of women with gestational ages from 37 to 40 weeks to give birth by CS was about 58% less compared to those with less than 37 gestational weeks. Women who had 4-7 and 8 or more antenatal care (ANC) visits were 1.95 and 3.5 times more likely to deliver by CS compared to those who had less than 4 ANC visits. The odds of women who have had pregnancy loss before to deliver by CS was 68% higher compared to women who have not lost pregnancy before. CONCLUSIONS: Caesarean section delivery prevalence in the study population was within the Ghana Health Service and World Health Organization ranges. In addition to known socio-demographic and obstetric factors, this study observed that a history of pregnancy loss increased the chances of a woman undergoing a CS. Policies should aim at addressing identified modifiable factors to stem the rise in CS deliveries.

A qualitative analysis of factors influencing the implementation of antiretroviral treatment adherence policy in Ghana: stakeholders perspective.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS launched the 90-90-90 initiative. Failure to meet the target reflects the difficulties in successfully implementing HIV treatment policy. There are research gaps in exploring personal and external factors influencing HIV treatment in Ghana. To fill this gap, we explored individual and environmental (interpersonal, community and structural) factors influencing stakeholders' HIV treatment policy implementation in Ghana. METHODS: Fifteen qualitative semi-structured in-depth interviews were conducted among representatives in different management positions at hospitals, health directorates, the Ghana AIDS Commission, the National AIDS and STI control program, and the National Association of People Living with HIV. RESULTS: Using thematic analysis, the findings suggest that individual and environmental factors such as attitude towards policy, awareness of HIV treatment policy, training received on policy implementation, difficulties related to patient factors, alternate sources of HIV care, inefficient policy decision-making, monitoring and evaluation of HIV treatment policy, lack of HIV treatment policy implementation training, poor availability of logistics, policy and guidelines, infrastructure, organization of training, and staff availability may hinder successful HIV treatment policy implementation. CONCLUSION: Several individual and environmental (interpersonal, community and structural) factors seem to influence HIV treatment policy implementation. To ensure successful policy implementation stakeholders need to receive training on new policies, availability of sufficient supplies of material resources, inclusive decision-making, receive supportive monitoring of policy implementation, and oversight.

Malaria Transmission Intensity Likely Modifies RTS, S/AS01 Efficacy Due to a Rebound Effect in Ghana, Malawi, and Gabon.

BACKGROUND: RTS,S/AS01 is the first malaria vaccine to be approved and recommended for widespread implementation by the World Health Organization (WHO). Trials reported lower vaccine efficacies in higher-incidence sites, potentially due to a "rebound" in malaria cases in vaccinated children. When naturally acquired protection in the control group rises and vaccine protection in the vaccinated wanes concurrently, malaria incidence can become greater in the vaccinated than in the control group, resulting in negative vaccine efficacies. METHODS: Using data from the 2009-2014 phase III trial (NCT00866619) in Lilongwe, Malawi; Kintampo, Ghana; and Lambaréné, Gabon, we evaluate this hypothesis by estimating malaria incidence in each vaccine group over time and in varying transmission settings. After estimating transmission intensities using ecological variables, we fit models with 3-way interactions between vaccination, time, and transmission intensity. RESULTS: Over time, incidence decreased in the control group and increased in the vaccine group. Three-dose efficacy in the lowest-transmission-intensity group (0.25 cases per person-year [CPPY]) decreased from 88.2% to 15.0% over 4.5 years, compared with 81.6% to -27.7% in the highest-transmission-intensity group (3 CPPY). CONCLUSIONS: These findings suggest that interventions, including the fourth RTS,S dose, that protect vaccinated individuals during the potential rebound period should be implemented for high-transmission settings.