Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.

OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

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.

Did COVID-19 Change the Availability and Use of Clean Energy for Cooking? Evidence From Ghana.

A major part of Ghana's current household energy policy is focused on using a branded cylinder recirculation model (BCRM) to promote the safe use of Liquefied Petroleum Gas (LPG) for primary cooking. The implementation of the BCRM is expected to increase LPG adoption by households to the announced policy goal of 50% of the population by 2030. We investigated the impact of the COVID-19 pandemic on the implementation of the BCRM, availability, and household use of cleaner fuels. This was assessed using existing data on clean fuel use prior to the COVID-19 pandemic. Additional data was collected using questionnaire-based household surveys and qualitative interviews. It was found that the expansion of BCRM was significantly impacted by the COVID-19 pandemic. Planning activities such as baseline data collection and stakeholder engagement were delayed due to the COVID-19 restrictions. Changes in household incomes during the pandemic had the biggest percentage effect on household choice of cooking fuel, causing a regression in some cases, to polluting fuel use. This study provides insights that could be valuable in future understanding of the interactions between pandemic control measures and economic disruptions that may affect household energy choices for cooking.

Malaria Transmission Intensity 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 delayed malaria effect 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 malaria transmission intensity. 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 transmission intensity 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 delayed malaria is likely the main reason for lower efficacy in high transmission settings, not reduced immune responses. This may be reassuring for implementation in high transmission settings, though further studies are needed.

Neonatal mortality risk of vulnerable newborns: A descriptive analysis of subnational, population-based birth cohorts for 238 203 live births in low- and middle-income settings from 2000 to 2017.

OBJECTIVE: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). DESIGN: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. SETTING: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Live birth neonates. METHODS: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. RESULTS: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. CONCLUSIONS: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.

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.

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.

"I don't want to have anything to do with someone suspected of COVID-19": a genuine infection avoidance interest or inappropriate concerns related to stigma?

Background: Human existence is being challenged by an outbreak of coronavirus disease 2019 (COVID-19) caused by the virus SARS-CoV-2 that began in Wuhan, China in December 2019. Efforts to avoid the spread of COVID-19 are undermined by the appearance of disease-associated avoidance of infected persons due to reasons such as social stigma and discrimination. Objective: This study seeks to investigate avoidance and discrimination against persons suspected of COVID-19 to help fight the pandemic in a predominantly rural setting in Ghana. Materials and Methods: The study is a cross sectional survey. A random sample of 517 individuals drawn from a health and demographic surveillance system database was used for this study. Participants resided in six contiguous districts and municipalities of predominantly rural setting in the Bono East Region of Ghana. Results: The findings showed that majority (60%) of the respondents agreed that they won't have anything to do with someone suspected of COVID-19. However, 67% of them were willing to accommodate persons that recovered from the infection. The majority (91%) of respondents agreed that there is a need to adopt tolerant attitude towards persons who recovered from the infection, whilst another 98% also reported the need to show compassion towards persons who recovered from COVID-19. Conclusions: There is the need to pay special attention to avoidance of suspected infected persons due to stigma or any other reason since it is a threat to the fight against the pandemic.

Risk factors for COVID-19 virus infection among health workers: A case-control study in the Bono East Region of Ghana.

BACKGROUND: Disproportionately high rates of COVID-19 infection among health workers prompts the need to identify the risk factors to help guide the design and implementation of interventions. The aim of this study was to characterize the risk factors for COVID-19 infection among health workers. METHODS: A case-control study was designed to recruit 154 health workers who tested positive for the COVID-19 virus and 308 who tested negative from 8 hospitals and 11 health directorates in the Bono East Region of Ghana. Crude and adjusted logistic regression analysis was used to determine risk factors. RESULTS: Hand hygiene compliance for the recommended moments ranged from 55.3% to 77.4%. Personal protective equipments (PPE) use was 59.5% when patients' COVID-19 status was unknown and at least 90.7% when patient was positive. We identified years of practice experience (adjusted odds ratio (AOR) = 1.81; 95% CI: 1.07, 3.07; P = .028), adherence to infection prevention and control (IPC) when in contact with patients whose COVID-19 status is unspecified (AOR = 1.71; 95% CI: 1.09, 2.70; P = .020) and type of facility (AOR = 1.69, 95% CI: 1.09, 2.62; P = .019) as risk factors. CONCLUSION: The findings underscore the need for health workers to improve in COVID-19 risk perception.

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.

Head Injury Prevalence in a Population of Injured Patients Seeking Care in Ghana, West Africa.

Background/Significance: Much of the literature on head injury (HI) prevalence comes from high-income countries (HICs), despite the disproportionate burden of injuries in low to middle-income countries (LMICs). This study evaluated the HI prevalence in the Kintampo Injury Registry, a collaborative effort between Kintampo Health Research Centre (KHRC) in Ghana and the sidHARTe Program at Columbia University Mailman School of Public Health. In our first aim, we characterize the HI prevalence in the registry. In aim 2, we examine if there are any sex (male/female) differences in head injury outcomes in these populations for points of potential intervention. Methods: Secondary analysis of data from the Kintampo Injury Registry which had 7,148 registered patients collected during January 2013 to January 2015. The definition of a case was adopted to ensure consistency with the International Statistical Classification of Diseases and Related Health Problems, revision 10 (ICD-10). A 3-page questionnaire was used to collect data from injured patients to include in the registry. The questions were designed to be consistent with the World Health Organization (WHO) guidelines on injury surveillance and were adapted from the questionnaire used in a pilot, multi-country injury study undertaken in other parts of Africa. The questionnaire collected information on the anatomic site of injury (e.g., head), mechanism of injury (e.g., road traffic injuries, interpersonal injuries (including domestic violence), falls, drowning, etc.), severity and circumstances of the injury, as well as precipitating factors, such as alcohol and drug use. The questionnaire consisted mainly of close-ended questions and was designed for efficient data entry. For the secondary data analyses for this manuscript, we only included those with "1st visit following injury" and excluded all transfers and follow-up visits (n = 834). We then dichotomized the remaining 6,314 patients to head injured and non-head injured patients based on responses to the variable "Nature of injury =Head Injury". We used chi-square and Fisher's exact tests with p < 0.05 as cut-off for statistical significance. Logistic regression estimates were used for effect estimates. Results: Of the 6,314 patients, there were 208 (3.3%) head-injured patients and 6,106 (96.7%) patients without head injury. Head-injured patients tended to be older (Mean age: 28.9 +/-13.7; vs. 26.1 +/- 15.8; p = 0.004). Seven in 10 head injured patients sustained their injuries via transport/road traffic accidents, and head-injured patients had 13 times the odds of mortality compared with those without head injuries (OR: 13.3; 95% CI: 8.05, 22.0; p < 0.0001) even though over half of them had mild or moderate injury severity scores (p < 0.001). Evaluation of sex differences amongst the head-injured showed that in age-adjusted logistic regression models, males had 1.4 times greater odds of being head injured (OR: 1.4; 95% CI: 1.04, 2.00; p = 0.03) and over twice the risk of mortality (OR: 2.7; 95% CI: 0.74, 10.00; p = 0.13) compared to females. Conclusion: In these analyses, HI was associated with a higher risk of mortality, particularly amongst injured males; most of whom were injured in transport/road-traffic-related accidents. This study provides an impetus for shaping policy around head injury prevention in LMICs like Ghana.

Corrigendum to "Prenatal household air pollutant exposure is associated with reduced size and gestational age at birth among a cohort of Ghanaian infants" [Environ. Int. 155 (2021) 106659].

[This corrects the article PMC8628363.].

Prenatal and Postnatal Household Air Pollution Exposure and Infant Growth Trajectories: Evidence from a Rural Ghanaian Pregnancy Cohort.

BACKGROUND: The exposure-response association between prenatal and postnatal household air pollution (HAP) and infant growth trajectories is unknown. OBJECTIVES: To evaluate associations between prenatal and postnatal HAP exposure and stove interventions on growth trajectories over the first year of life. METHODS: The Ghana Randomized Air Pollution and Health Study enrolled n=1,414 pregnant women at ≤24wk gestation from Kintampo, Ghana, and randomized them to liquefied petroleum gas (LPG), improved biomass, or open fire (control) stoves. We quantified HAP exposure by repeated, personal prenatal and postnatal carbon monoxide (CO) and, in a subset, fine particulate matter [PM with an aerodynamic diameter of ≤2.5µm (PM2.5)] assessments. Length, weight, mid-upper arm circumference (MUAC) and head circumference (HC) were measured at birth, 3, 6, 9, and 12 months; weight-for-age, length-for-age (LAZ), and weight-for-length z (WLZ)-scores were calculated. For each anthropometric measure, we employed latent class growth analysis to generate growth trajectories over the first year of life and assigned each child to a trajectory group. We then employed ordinal logistic regression to determine associations between HAP exposures and growth trajectory assignments. Associations with stove intervention arm were also considered. RESULTS: Of the 1,306 live births, 1,144 had valid CO data and anthropometric variables measured at least once. Prenatal HAP exposure increased risk for lower length [CO odds ratio (OR)= 1.17, 95% CI: 1.01, 1.35 per 1-ppm increase; PM2.5 OR= 1.07, 95% CI: 1.02, 1.13 per 10-µg/m3 increase], lower LAZ z-score (CO OR= 1.15, 95% CI: 1.01, 1.32 per 1-ppm increase) and stunting (CO OR= 1.25, 95% CI: 1.08, 1.45) trajectories. Postnatal HAP exposure increased risk for smaller HC (CO OR= 1.09, 95% CI: 1.04, 1.13 per 1-ppm increase), smaller MUAC and lower WLZ-score (PM2.5 OR= 1.07, 95% CI: 1.00, 1.14 and OR= 1.09, 95% CI: 1.01, 1.19 per 10-µg/m3 increase, respectively) trajectories. Infants in the LPG arm had decreased odds of having smaller HC and MUAC trajectories as compared with those in the open fire stove arm (OR= 0.58, 95% CI: 0.37, 0.92 and OR= 0.45, 95% CI: 0.22, 0.90, respectively). DISCUSSION: Higher early life HAP exposure (during pregnancy and through the first year of life) was associated with poorer infant growth trajectories among children in rural Ghana. A cleaner-burning stove intervention may have improved some growth trajectories. https://doi.org/10.1289/EHP8109.

A cluster randomised trial of cookstove interventions to improve infant health in Ghana.

INTRODUCTION: Household air pollution from solid fuel combustion for cooking and heating is a leading cause of childhood morbidity and mortality worldwide. We hypothesised that clean cooking interventions delivered during pregnancy would improve child health. METHODS: We conducted a cluster randomised trial in rural Ghana to test whether providing pregnant women liquefied petroleum gas (LPG) cookstoves or improved biomass cookstoves would reduce personal carbon monoxide and fine particulate pollution exposure, increase birth weight and reduce physician-assessed severe pneumonia in the first 12 months of life, compared with control participants who continued to cook with traditional stoves. Primary analyses were intention-to-treat. The trial was registered with ClinicalTrials.gov and follow-up is complete. RESULTS: Enrolment began on 14 April 2014, and ended on 20 August 2015. We enrolled 1414 pregnant women; 361 in the LPG arm, 527 in the improved biomass cookstove arm and 526 controls. We saw no improvement in birth weight (the difference in mean birth weight for LPG arm births was 29 g lighter (95% CI -113 to 56, p=0.51) and for improved biomass arm births was 9 g heavier (95% CI -64 to 82, p=0.81), compared with control newborns) nor severe child pneumonia (the rate ratio for pneumonia in the LPG arm was 0.98 (95% CI 0.58 to 1.70; p=0.95) and for the improved biomass arm was 1.21 (95% CI 0.78 to 1.90; p=0.52), compared with the control arm). Air pollution exposures in the LPG arm remained above WHO health-based targets (LPG median particulate matter less than 2.5 microns in diameter (PM2.5) 45 µg/m³; IQR 32-65 vs control median PM2.5 67 µg/m³, IQR 46-97). CONCLUSIONS: Neither prenatally-introduced LPG nor improved biomass cookstoves improved birth weight or reduced severe pneumonia risk in the first 12 months of life. We hypothesise that this is due to lower-than-expected exposure reductions in the intervention arms. TRIAL REGISTRATION NUMBER: NCT01335490.

Prenatal and Postnatal Household Air Pollution Exposures and Pneumonia Risk: Evidence From the Ghana Randomized Air Pollution and Health Study.

BACKGROUND: Nearly 40% of the world's population is exposed daily to household air pollution. The relative impact of prenatal and postnatal household air pollution exposure on early childhood pneumonia, a leading cause of mortality, is unknown. RESEARCH QUESTION: Are prenatal or postnatal household air pollution, or both, associated with pneumonia risk in the first year of life? STUDY DESIGN AND METHODS: The Ghana Randomized Air Pollution and Health Study enrolled 1,414 nonsmoking, pregnant women before 24 weeks' gestation with prospective follow-up to the child's age of 1 year. We measured 72-h personal household air pollution exposures, indexed by carbon monoxide (CO), four times prenatally and three times postnatally. Weekly fieldworker surveillance identified ill-appearing children for physician pneumonia assessment. We used quasi-Poisson models to examine associations between prenatal and postnatal CO and physician-diagnosed pneumonia and severe pneumonia. Sex-specific effects were examined. RESULTS: Of the 1,306 live births, 1,141 infants were followed up with 55,605 child-weeks of fieldworker surveillance. The estimated risk for pneumonia and severe pneumonia in the first year of life increased by 10% (relative risk [RR], 1.10; 95% CI, 1.04-1.16) and 15% (RR, 1.15; 95% CI, 1.03-1.28), respectively, per 1-part per million (ppm) increase in average prenatal CO exposure and by 6% (RR, 1.06; 95% CI, 0.99-1.13) per 1-ppm increase in average postnatal CO exposure. Sex-stratified analyses suggest that in girls, higher prenatal CO exposure was associated with pneumonia risk, while no association was seen in boys. INTERPRETATION: Prenatal household air pollution exposure increased risk of pneumonia and severe pneumonia in the first year of life. Clean-burning interventions may be most effective when begun prenatally. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01335490; URL: www.clinicaltrials.gov.

Prenatal household air pollutant exposure is associated with reduced size and gestational age at birth among a cohort of Ghanaian infants.

BACKGROUND: Low birth weight and prematurity are important risk factors for death and disability, and may be affected by prenatal exposure to household air pollution (HAP). METHODS: We investigate associations between maternal exposure to carbon monoxide (CO) during pregnancy and birth outcomes (birth weight, birth length, head circumference, gestational age, low birth weight, small for gestational age, and preterm birth) among 1288 live-born infants in the Ghana Randomized Air Pollution and Health Study (GRAPHS). We evaluate whether evidence of malaria during pregnancy, as determined by placental histopathology, modifies these associations. RESULTS: We observed effects of CO on birth weight, birth length, and gestational age that were modified by placental malarial status. Among infants from pregnancies without evidence of placental malaria, each 1 ppm increase in CO was associated with reduced birth weight (-53.4 g [95% CI: -84.8, -21.9 g]), birth length (-0.3 cm [-0.6, -0.1 cm]), gestational age (-1.0 days [-1.8, -0.2 days]), and weight-for-age Z score (-0.08 standard deviations [-0.16, -0.01 standard deviations]). These associations were not observed in pregnancies with evidence of placental malaria. Each 1 ppm increase in maternal exposure to CO was associated with elevated odds of low birth weight (LBW, OR 1.14 [0.97, 1.33]) and small for gestational age (SGA, OR 1.14 [0.98, 1.32]) among all infants. CONCLUSIONS: Even modest reductions in exposure to HAP among pregnant women could yield substantial public health benefits, underscoring a need for interventions to effectively reduce exposure. Adverse associations with HAP were discernible only among those without evidence of placental malaria, a key driver of impaired fetal growth in this malaria-endemic area.

Determinants of the varied profiles of Plasmodium falciparum infections among infants living in Kintampo, Ghana.

BACKGROUND: Understanding why some infants tolerate infections, remaining asymptomatic while others succumb to repeated symptomatic malaria is beneficial for studies of naturally acquired immunity and can guide control interventions. This study compared demographic, host and maternal factors associated with being either parasite negative or having asymptomatic infections versus developing symptomatic malaria in the first year of life. METHODS: A birth cohort (n = 1264) was monitored longitudinally over two years for malaria infections in Kintampo, Ghana. Symptomatic and asymptomatic infections were detected actively through monthly home visits, complemented by passive case detection. Light microscopy was used to detect parasitaemia. Based on data from a minimum of eight monthly visits within the first year of life, infants were classified into one of four groups: "parasite negative", "only-asymptomatic", "only-symptomatic" or "alternating" i.e., sometimes symptomatic and other times asymptomatic. The host and maternal characteristics and demographic factors in relation to these four groups were compared. RESULTS: The parasite negative group formed 36% of the cohort, whilst the only-symptomatic were 35%. The alternating group were 22% and the only-asymptomatic were 7% of the cohort. There were significant associations between residence, socio-economic status (SES), parity, IPTp doses, delivery place of infant and having or not having malaria parasites. Maternal factors such as early commencement and frequency of ante-natal care (ANC) were significantly higher in the parasite negative group compared to all others. ITN use in pregnancy increased the odds of infant having only asymptomatic infections ("protected against disease"). Placental malaria was more common in the groups of infants with symptomatic malaria. Urban residence was significantly higher in the parasite negative group, while birth in the malaria transmission season were significantly more common in the alternating and parasite negative groups. Risk factors for infants with symptomatic malaria included low SES, birth in private maternity homes, sickle cell normal variant, lower MUAC, reported intake of anti-malarials and increased morbidity before the first microscopic infection was detected. CONCLUSION: Strengthening ANC by encouraging early and regular attendance, the use of IPTp, maternal bed nets and improving the nourishment of infants help reduce the frequency of symptomatic malaria over the first year of life.

Correction: Profiles of Plasmodium falciparum infections detected by microscopy through the first year of life in Kintampo a high transmission area of Ghana.

[This corrects the article DOI: 10.1371/journal.pone.0240814.].

Potential effect modification of RTS,S/AS01 malaria vaccine efficacy by household socio-economic status.

BACKGROUND: In the phase III RTS,S /AS01 trial, significant heterogeneity in efficacy of the vaccine across study sites was seen. Question on whether variations in socio - economic status (SES) of participant contributed to the heterogeinity of the vaccine efficacy (VE) remains unknown. METHODS: Data from the Phase III RTS,S /AS01 trial in children aged 5-17 months in Kintampo were re-analysed. SES of each child was derived from the Kintampo Health and Demographic Surveillance System, using principal component analysis of household assets. Extended Cox regression was used to estimate the interaction between RTS,S/AS01 VE and household SES. RESULTS: Protective efficacy of the RTS,S/AS0 vaccine significantly varied by participant's household SES, thus increase in household SES was associated with an increase in protective efficacy (P-value = 0.0041). Effect modification persisted after adjusting for age at first vaccination, gender, distance from community to the health facility, child's haemoglobin level, household size, place of residence and mothers' educational level. CONCLUSION: Household SES may be a proxy for malaria transmission intensity. The study showed a significant modification of the RTS,S/AS01 malaria vaccine efficacy by the different levels of child's household socio - economic status. TRIAL REGISTRATION: Efficacy of GSK Biologicals' candidate malaria vaccine (25049) against malaria disease in infants and children in Africa. NCT00866619 prospectively registered on 20 March 2009.

Profiles of Plasmodium falciparum infections detected by microscopy through the first year of life in Kintampo a high transmission area of Ghana.

Although malaria mortality among children under five years of age is high, the characteristics of their infection patterns are not well described. The aim of this study was to examine the longitudinal sequence pattern of Plasmodium falciparum infections in the first year of life within a birth cohort in Kintampo, Ghana (N = 1855). Infants were monitored at home with monthly sampling and also at the clinic for any febrile illness between 2008 and 2011. Light microscopy was performed on monthly scheduled visits and febrile ill visits over twelve months of follow-ups (n = 19231). Microscopy-positive visits accompanied with or without symptoms were rare during the first five months of life but were common from six to twelve months of age. Among 1264 infants with microscopy data over a minimum of eight monthly visits and also throughout in sick visits, some were microscopy negative (36%), and others positive: only-symptomatic (35%), alternating (22%) and only-asymptomatic (7%). The median age of microscopic infection was seven months for the alternating group and eight months for both the only-symptomatic and only-asymptomatic groups. The alternating group had the highest cumulative incidence of microscopic infections, the lowest age at first infection and 87 different infection patterns. Parasite densities detected by microscopy were significantly higher for symptomatic versus asymptomatic infection. We conclude that infants in malaria endemic areas experience diverse infection profiles throughout their first year of life. Further investigations should include submicroscopic reservoir and may shed more light on the factors that determine susceptibility to malaria during infancy.