Characterising sources of PM2·5 exposure for school children with asthma: a personal exposure study across six cities in sub-Saharan Africa.

BACKGROUND: Air pollution is the second largest risk to health in Africa, and children with asthma are particularly susceptible to its effects. Yet, there is a scarcity of air pollution exposure data from cities in sub-Saharan Africa. We aimed to identify potential exposure reduction strategies for school children with asthma living in urban areas in sub-Saharan Africa. METHODS: This personal exposure study was part of the Achieving Control of Asthma in Children in Africa (ACACIA) project. Personal exposure to particulate matter (PM) was monitored in school children in six cities in sub-Saharan Africa (Blantyre, Malawi; Durban, South Africa; Harare, Zimbabwe; Kumasi, Ghana; Lagos, Nigeria; and Moshi, Tanzania). Participants were selected if they were aged 12-16 years and had symptoms of asthma. Monitoring was conducted between June 21, and Nov 26, 2021, from Monday morning (approximately 1000 h) to Friday morning (approximately 1000 h), by use of a bespoke backpack with a small air pollution monitoring unit with an inbuilt Global Positioning System (GPS) data logger. Children filled in a questionnaire detailing potential sources of air pollution during monitoring and exposures were tagged into three different microenvironments (school, commute, and home) with GPS coordinates. Mixed-effects models were used to identify the most important determinants of children's PM2·5 (PM <2·5 µm in diameter) exposure. FINDINGS: 330 children were recruited across 43 schools; of these, 297 had valid monitoring data, and 1109 days of valid data were analysed. Only 227 (20%) of 1109 days monitored were lower than the current WHO 24 h PM2·5 exposure health guideline of 15 µg/m3. Children in Blantyre had the highest PM2·5 exposure (median 41·8 µg/m3), whereas children in Durban (16·0 µg/m3) and Kumasi (17·9 µg/m3) recorded the lowest exposures. Children had significantly higher PM2·5 exposures at school than at home in Kumasi (median 19·6 µg/m3vs 14·2 µg/m3), Lagos (32·0 µg/m3vs 18·0 µg/m3), and Moshi (33·1 µg/m3vs 23·6 µg/m3), while children in the other three cities monitored had significantly higher PM2·5 exposures at home and while commuting than at school (median 48·0 µg/m3 and 43·2 µg/m3vs 32·3 µg/m3 in Blantyre, 20·9 µg/m3 and 16·3 µg/m3vs 11·9 µg/m3 in Durban, and 22·7 µg/m3 and 25·4 µg/m3vs 16·4 µg/m3 in Harare). The mixed-effects model highlighted the following determinants for higher PM2·5 exposure: presence of smokers at home (23·0% higher exposure, 95% CI 10·8-36·4), use of coal or wood for cooking (27·1%, 3·9-56·3), and kerosene lamps for lighting (30·2%, 9·1-55·2). By contrast, 37·2% (95% CI 22·9-48·2) lower PM2·5 exposures were found for children who went to schools with paved grounds compared with those whose school grounds were covered with loose dirt. INTERPRETATION: Our study suggests that the most effective changes to reduce PM2·5 exposures in these cities would be to provide paving in school grounds, increase the use of clean fuel for cooking and light in homes, and discourage smoking within homes. The most efficient way to improve air quality in these cities would require tailored interventions to prioritise different exposure-reduction policies in different cities. FUNDING: UK National Institute for Health and Care Research.

A cross-country qualitative analysis of teachers' perceptions of asthma care in sub-Saharan Africa.

Asthma is the most common chronic respiratory disease among school-going adolescents worldwide. However, the burden of severe asthma is highest in Sub-Saharan Africa. This study aimed to explore teachers' perceptions of asthma care across six African countries. We conducted focus group discussions (FGDs) using a semi-structured interview guide. Interviews were audio-recorded, transcribed verbatim and analysed thematically. FGDs were conducted in Kumasi(Ghana), Blantyre (Malawi), Lagos (Nigeria), Durban (South Africa), Kampala (Uganda), and Harare (Zimbabwe) between 01 November 2020 and 30 June 2021. We identified two key themes related to asthma care; barriers to asthma care and suggestions to improve the care of adolescents with asthma. Barriers reported by teachers included a lack of knowledge and skills among themselves, adolescents, and caregivers. In addition, some traditional beliefs of teachers on asthma exacerbated challenges with asthma care in schools. Regarding suggestions, most teachers identified a need for all-inclusive asthma training programmes for teachers, adolescents and caregivers, focusing on acute episodes and mitigating triggers. Utilising teachers with personal experiences with asthma to advocate and support these initiatives was suggested. Further suggestions included the need for annual screening to enable early identification of adolescents with asthma and clarify restrictions on teachers administering asthma medications. Teachers across African schools identify multiple barriers to asthma care. Structured school education programs and annual asthma screening are key to addressing some barriers to care.

Barriers to childhood asthma care in sub-Saharan Africa: a multicountry qualitative study with children and their caregivers.

OBJECTIVES: This study identifies barriers and provides recommendations to improve asthma care in children across sub-Saharan Africa, where qualitative data is lacking despite high rates. DESIGN: One of the aims of our National Institute for Health Research global health research group 'Achieving Control of Asthma in Children in Africa' was to use qualitative thematic analysis of transcribed audio recordings from focus group discussions (FGDs) to describe barriers to achieving good asthma control. SETTING: Schools in Blantyre (Malawi), Lagos (Nigeria), Durban (South Africa), Kampala (Uganda) and Harare (Zimbabwe). PARTICIPANTS: Children (n=136), 12-14 years with either asthma symptoms or a diagnosis and their caregivers participated in 39 FGDs. All were recruited using asthma control questions from the Global Asthma Network survey. RESULTS: There were four key themes identified: (1) Poor understanding, (2) difficulties experienced with being diagnosed, (3) challenges with caring for children experiencing an acute asthma episode and (4) suboptimal uptake and use of prescribed medicines. An inadequate understanding of environmental triggers, a hesitancy in using metred dose inhalers and a preference for oral and alternate medications were identified as barriers. In addition, limited access to healthcare with delays in diagnosis and an inability to cope with expected lifestyle changes was reported. Based on these findings, we recommend tailored education to promote access to and acceptance of metred dose inhalers, including advocating for access to a single therapeutic, preventative and treatment option. Furthermore, healthcare systems should have simpler diagnostic pathways and easier emergency access for asthma. CONCLUSIONS: In a continent with rapidly increasing levels of poorly controlled asthma, we identified multiple barriers to achieving good asthma control along the trajectory of care. Exploration of these barriers reveals several generalisable recommendations that should modify asthma care plans and potentially transform asthma care in Africa. TRIAL REGISTRATION NUMBER: 269211.

Effect of Gender on Clinical Presentation of Tuberculosis (TB) and Age-Specific Risk of TB, and TB-Human Immunodeficiency Virus Coinfection.

Background: Previous studies have shown gender differences in tuberculosis (TB) incidence; however, gender disparity has not been well documented across granular categorizations of anatomic sites affected by TB and in the presence of human immunodeficiency virus (HIV) coinfection, largely due to small sample size for less common TB clinical presentations and lack of detailed clinical data. Methods: The study population included TB cases aged ≥15 years (n = 41, 266) diagnosed in Harare, Zimbabwe. This cross-sectional study estimated male-to-female ratio (M/F ratio) for (1) age-specific TB incidence, (2) age-specific HIV prevalence among incident TB cases, and (3) 9 types of TB defined by affected anatomic site. Results: Males were at a 53% higher risk of TB compared to females (risk ratio [RR] = 1.53; 95% confidence interval [CI], 1.12-2.09). Based on adjusted odds ratios (aORs) from multinomial logistic regression model, the odds of abdominal TB (aOR = 0.51; 95% CI, .39-.68), TB bones/joints/spine (aOR = 0.63; 95% CI, .45-.90), and "other" extrapulmonary TB sites (aOR = 0.69; 95% CI = .59-.81) versus pulmonary TB were lower among males compared to females. The risk of TB-HIV coinfection among males was 17% (RR = .83; 95% CI, .74-.93) and 8% (RR = 0.92; 95% CI, .88-.95) lower in the 15- to 24-year and 25- to 44-year age groups, respectively. Conclusions: This study revealed a nuanced role of gender across finer categorizations of TB, indicating the need for future research to delineate underlying mechanisms driving gender disparities in TB. The finding that women had a greater likelihood of severe forms of TB and TB-HIV coinfection compared to men has important implications for women's health in TB-HIV high-burden settings.

Empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia: study protocol for a multicenter, open-label randomized controlled clinical trial.

BACKGROUND: Pneumonia is the primary cause of death among HIV-infected children in Africa, with mortality rates as high as 35-40% in infants hospitalized with severe pneumonia. Bacterial pathogens and Pneumocystis jirovecii are well known causes of pneumonia-related death, but other important causes such as cytomegalovirus (CMV) and tuberculosis (TB) remain under-recognized and undertreated. The immune response elicited by CMV may be associated with the risk of developing TB and TB disease progression, and CMV may accelerate disease caused both by HIV and TB. Minimally invasive autopsies confirm that CMV and TB are unrecognized causes of death in children with HIV. CMV and TB may also co-infect the same child. The aim of this study is to compare the impact on 15-day and 1-year mortality of empirical treatment against TB and CMV plus standard of care (SoC) versus SoC in HIV-infected infants with severe pneumonia. METHODS: This is a Phase II-III, open-label randomized factorial (2 × 2) clinical trial, conducted in six African countries. The trial has four arms. Infants from 28 to 365 days of age HIV-infected and hospitalized with severe pneumonia will be randomized (1:1:1:1) to (i) SoC, (ii) valganciclovir, (iii) TB-T, and (iv) TB-T plus valganciclovir. The primary endpoint of the study is all-cause mortality, focusing on the short-term (up to 15 days) and long-term (up to 1 year) mortality. Secondary endpoints include repeat hospitalization, duration of oxygen therapy during initial admission, severe and notable adverse events, adverse reactions, CMV and TB prevalence at enrolment, TB incidence, CMV viral load reduction, and evaluation of diagnostic tests such as GeneXpert Ultra on fecal and nasopharyngeal aspirate samples and urine TB-LAM. DISCUSSION: Given the challenges in diagnosing CMV and TB in children and results from previous autopsy studies that show high rates of poly-infection in HIV-infected infants with respiratory disease, this study aims to evaluate a new approach including empirical treatment of CMV and TB for this patient population. The potential downsides of empirical treatment of these conditions include toxicity and medication interactions, which will be evaluated with pharmacokinetics sub-studies. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03915366, Universal Trial Number U111-1231-4736, Pan African Clinical Trial Registry PACTR201994797961340.

Delays in presentation of intussusception and development of gangrene in Zimbabwe.

INTRODUCTION: prompt diagnosis and treatment are considered key to successful management of intussusception. We examined pre-treatment delay among intussusception cases in Zimbabwe and conducted an exploratory analysis of factors associated with intraoperative finding of gangrene. METHODS: data were prospectively collected as part of the African Intussusception Network using a questionnaire administered on consecutive patients with intussusception managed at Harare Children´s Hospital. Delays were classified using the Three-Delays-Model: care-seeking delay (time from onset of symptoms to first presentation for health care), health-system delay (referral time from presentation to first facility to treatment facility) and treatment delay (time from presentation at treatment facility to treatment). RESULTS: ninety-two patients were enrolled from August 2014 to December 2016. The mean care-seeking interval was 1.9 days, the mean health-system interval was 1.5 days, and the mean treatment interval was 1.1 days. Mean total time from symptom onset to treatment was 4.4 days. Being transferred from another institution added 1.4 days to the patient journey. Gangrene was found in 2 (25%) of children who received treatment within 1 day, 13 (41%) of children who received treatment 2-3 days, and 26 (50%) of children who received treatment more than 3 days after symptom onset (p = 0.34). CONCLUSION: significant care-seeking and health-system delays are encountered by intussusception patients in Zimbabwe. Our findings highlight the need to explore approaches to improve the early diagnosis of intussusception and prompt referral of patients for treatment.

Factors associated with unfavorable treatment outcomes among pediatric tuberculosis cases in Harare, Zimbabwe during 2013-2017.

BACKGROUND: Historical neglect of pediatric tuberculosis (TB), compounding the absence of a universally effective vaccine, highlights the importance of successful treatment in combating the global epidemic. Furthermore, compliance with international standards of pediatric TB treatment remains unknown in many high-burden, resource-limited settings. METHODS: In this cross-sectional study, using TB surveillance data, we assessed the treatment outcomes among 853 pediatric TB cases (<15 years old), a study sample that represented all the pediatric TB cases with treatment outcome records in Harare, Zimbabwe during 2013-2017. We also identified factors associated with treatment outcome by multivariate logistic regression. RESULTS: Of these 853 analyzed cases, 57% were either cured or had completed treatment. In a model accounting for confounding variables, hospital center and pretreatment sputum smear were associated with unfavorable treatment outcome. Cases from Beatrice Road Infectious Disease Hospital were four times as likely to have an unfavorable outcome compared with those from Wilkins Infectious Disease Hospital (adjusted odds ration [aOR]: 4.0; 95% CI 2.9-5.5). Children whose pretreatment sputum smear was positive were 2.4 times as likely to have an unfavorable outcome as those who were negative (aOR: 2.4; 95% CI 1.7-3.6). CONCLUSION: Pediatric TB case management needs to be improved, especially among those with a positive pretreatment sputum smear. Efforts to address TB treatment outcome disparities between clinical settings in high-burden settings, such as Harare, Zimbabwe, are essential in improving global TB control.

Achieving Control of Asthma in Children in Africa (ACACIA): protocol of an observational study of children's lung health in six sub-Saharan African countries.

INTRODUCTION: Little is known about asthma control in the rising number of African children who suffer from this condition. The Achieving Control of Asthma in Children in Africa (ACACIA) study is an observational study collecting evidence about paediatric asthma in urban areas of Ghana, Malawi, Nigeria, South Africa, Uganda and Zimbabwe. The primary objectives are: (1) to identify 3000 children aged between 12 years and 14 years with asthma symptoms; and (2) to assess their asthma control, current treatment, knowledge of and attitudes to asthma and barriers to achieving good control. Secondary objective is to develop interventions addressing identified barriers to good symptom control. METHODS AND ANALYSIS: Each centre will undertake screening to identify 500 school children with asthma symptoms using questions from the Global Asthma Network's questionnaire. Children identified to have asthma symptoms will fill in a digital survey, including: Asthma Control Test, questions on medication usage and adherence, medical care, the Brief-Illness Perception questionnaire and environmental factors. Exhaled nitric oxide testing and prebronchodilator and postbronchodilator spirometry will be performed. A subgroup of children will participate in focus group discussions. Results will be analysed using descriptive statistics and comparative analysis. Informed by these results, we will assess the feasibility of potential interventions, including the adaption of a UK-based theatre performance about asthma attitudes and digital solutions to improve asthma management. ETHICS AND DISSEMINATION: The ACACIA study has been reviewed by the Queen Mary University of London Ethics of Research Committee in the UK. All African centres have received local ethical approval for this study. Study results will be published in academic journals and at conferences. Study outputs will be communicated to the public via newsfeeds on the ACACIA website and Twitter, and through news media outlets and other local dissemination. TRIAL REGISTRATION NUMBER: 269211.

Metabolic gestational age assessment in low resource settings: a validation protocol.

Preterm birth is the leading global cause of neonatal morbidity and mortality. Reliable gestational age estimates are useful for quantifying population burdens of preterm birth and informing allocation of resources to address the problem. However, evaluating gestational age in low-resource settings can be challenging, particularly in places where access to ultrasound is limited. Our group has developed an algorithm using newborn screening analyte values derived from dried blood spots from newborns born in Ontario, Canada for estimating gestational age within one to two weeks. The primary objective of this study is to validate a program that derives gestational age estimates from dried blood spot samples (heel-prick or cord blood) collected from health and demographic surveillance sites and population representative health facilities in low-resource settings in Zambia, Kenya, Bangladesh and Zimbabwe. We will also pilot the use of an algorithm to identify birth percentiles based on gestational age estimates and weight to identify small for gestational age infants. Once collected from local sites, samples will be tested by the Newborn Screening Ontario laboratory at the Children's Hospital of Eastern Ontario (CHEO) in Ottawa, Canada. Analyte values will be obtained through laboratory analysis for estimation of gestational age as well as screening for other diseases routinely conducted at Ontario's newborn screening program. For select conditions, abnormal screening results will be reported back to the sites in real time to facilitate counseling and future clinical management. We will determine the accuracy of our existing algorithm for estimation of gestational age in these newborn samples. Results from this research hold the potential to create a feasible method to assess gestational age at birth in low- and middle-income countries where reliable estimation may be otherwise unavailable.

Timeliness of rotavirus vaccination at sentinel sites in four early-adopter African countries.

BACKGROUND: The majority of countries with the highest rotavirus-associated death rates are in sub-Saharan Africa. In 2009, the World Health Organization (WHO) recommended routine vaccination against rotavirus worldwide, with unique age recommendations to administer the first dose before 15 weeks of age and last dose by 32 weeks of age. These age restrictions were relaxed in January 2013, but they may still lead to lower rotavirus vaccine coverage. METHODS: Children age-eligible to have received rotavirus vaccine that were enrolled in Ghana, Zimbabwe, Rwanda or Burkina Faso's active rotavirus surveillance platforms from 2013 to 2017 and had a stool specimen that tested rotavirus-negative were included in the analysis. Proportion vaccinated and timeliness of rotavirus vaccine versus DTPw-HepB-Hib (pentavalent) first dose and last dose were compared at weeks 15 and 32, respectively, using Chi-square analyses. Odds ratios were calculated using logistic regression. RESULTS: Among children who received rotavirus vaccine dose 1, 96-99% received this dose by 15 weeks of age and among children who received the last dose, 98-99% received it by 32 weeks of age. In all four countries, there was no significant difference in the proportion of children who received first dose rotavirus versus pentavalent vaccine by week 15, or last dose rotavirus versus concordant pentavalent vaccine by week 32. Delayed administration of first dose pentavalent vaccine was significantly associated with missing first dose of rotavirus vaccine in 3 of the 4 countries studied, although delays in administration were rare (1-4%). CONCLUSIONS: Rotavirus vaccination was timely among sentinel sites in these four early rotavirus vaccine-introducing countries in Africa. Late presentation for vaccination may have resulted in some children with access to care missing first dose of rotavirus vaccine; however, vaccination delays were infrequent and therefore the potential impact of the age restrictions on overall proportion vaccinated was minimal.

Option A improved HIV-free infant survival and mother to child HIV transmission at 9-18 months in Zimbabwe.

OBJECTIVE: We evaluated the impact of Option A on HIV-free infant survival and mother-to-child transmission (MTCT) in Zimbabwe. DESIGN: Serial cross-sectional community-based serosurveys. METHODS: We analyzed serosurvey data collected in 2012 and 2014 among mother-infant pairs from catchment areas of 132 health facilities from five of 10 provinces in Zimbabwe. Eligible infants (alive or deceased) were born 9-18 months before each survey to mothers at least 16 years old. We randomly selected mother-infant pairs and conducted questionnaires, verbal autopsies, and collected blood samples. We estimated the HIV-free infant survival and MTCT rate within each catchment area and compared the 2012 and 2014 estimates using a paired t test and number of HIV infections averted because of the intervention. RESULTS: We analyzed 7249 mother-infant pairs with viable maternal specimens collected in 2012 and 8551 in 2014. The mean difference in the catchment area level MTCT between 2014 and 2012 was -5.2 percentage points (95% confidence interval = -8.1, -2.3, P < 0.001). The mean difference in the catchment area level HIV-free survival was 5.5 percentage points (95% confidence interval = 2.6, 8.5, P < 0.001). Between 2012 and 2014, 1779 infant infections were averted compared with the pre-Option A regimen. The association between HIV-free infant survival and duration of Option A implementation was NS at the multivariate level (P = 0.093). CONCLUSION: We found a substantial and statistically significant increase in HIV-free survival and decrease in MTCT among infants aged 9-18 months following Option A rollout in Zimbabwe. This is the only evaluation of Option A and shows the effectiveness of Option A and Zimbabwe's remarkable progress toward eMTCT.

Evaluating the Impact of Zimbabwe's Prevention of Mother-to-Child HIV Transmission Program: Population-Level Estimates of HIV-Free Infant Survival Pre-Option A.

OBJECTIVE: We estimated HIV-free infant survival and mother-to-child HIV transmission (MTCT) rates in Zimbabwe, some of the first community-based estimates from a UNAIDS priority country. METHODS: In 2012 we surveyed mother-infant pairs residing in the catchment areas of 157 health facilities randomly selected from 5 of 10 provinces in Zimbabwe. Enrolled infants were born 9-18 months before the survey. We collected questionnaires, blood samples for HIV testing, and verbal autopsies for deceased mothers/infants. Estimates were assessed among i) all HIV-exposed infants, as part of an impact evaluation of Option A of the 2010 WHO guidelines (rolled out in Zimbabwe in 2011), and ii) the subgroup of infants unexposed to Option A. We compared province-level MTCT rates measured among women in the community with MTCT rates measured using program monitoring data from facilities serving those communities. FINDINGS: Among 8568 women with known HIV serostatus, 1107 (12.9%) were HIV-infected. Among all HIV-exposed infants, HIV-free infant survival was 90.9% (95% confidence interval (CI): 88.7-92.7) and MTCT was 8.8% (95% CI: 6.9-11.1). Sixty-six percent of HIV-exposed infants were still breastfeeding. Among the 762 infants born before Option A was implemented, 90.5% (95% CI: 88.1-92.5) were alive and HIV-uninfected at 9-18 months of age, and 9.1% (95%CI: 7.1-11.7) were HIV-infected. In four provinces, the community-based MTCT rate was higher than the facility-based MTCT rate. In Harare, the community and facility-based rates were 6.0% and 9.1%, respectively. CONCLUSION: By 2012 Zimbabwe had made substantial progress towards the elimination of MTCT. Our HIV-free infant survival and MTCT estimates capture HIV transmissions during pregnancy, delivery and breastfeeding regardless of whether or not mothers accessed health services. These estimates also provide a baseline against which to measure the impact of Option A guidelines (and subsequently Option B+).