Impact of seasonal malaria chemoprevention based on the number of medicines doses received on malaria burden among children aged 3-59 months in Nigeria: A propensity score-matched analysis.

BACKGROUND: Seasonal malaria chemoprevention using sulfadoxine-pyrimethamine plus amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine on Day 1 and amodiaquine on both Day 2 and Day 3) is delivered to children aged 3-59 months in areas of highly season malaria transmission. While the overall population-level impact of seasonal malaria chemoprevention on malaria control has been documented in various countries and time periods, there is no clear evidence regarding seasonal malaria chemoprevention impact based on the number of medicine doses children receive in one cycle in routine programmatic conditions. METHODS: Data were extracted from Nigeria's routinely collected seasonal malaria chemoprevention end-of-round coverage surveys (2021, 2022). We matched seasonal malaria chemoprevention-targeted children who received specific numbers of seasonal malaria chemoprevention medicines with those who did not receive any doses of seasonal malaria chemoprevention medicines (non-sulfadoxine-pyrimethamine plus amodiaquine) using multiple sets of propensity score matches. We performed multilevel logistic regression for each matched group to evaluate the association between the number of doses of seasonal malaria chemoprevention medicines and monthly confirmed malaria cases (caregiver-reported malaria infection diagnosed by rapid diagnostic test at a health facility following the penultimate cycle of seasonal malaria chemoprevention). RESULTS: Among 21,621 SMC-targeted children, 9.7% received non-sulfadoxine-pyrimethamine plus amodiaquine, 0.5% received only Day 1 sulfadoxine-pyrimethamine plus amodiaquine, 1.0% received Day 1 sulfadoxine-pyrimethamine plus amodiaquine and either Day 2 amodiaquine or Day 3 amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine), and 88.8% received Day 1 sulfadoxine-pyrimethamine plus amodiaquine and both Day 2 and Day 3 amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine + amodiaquine). Children receiving only Day 1 sulfadoxine-pyrimethamine plus amodiaquine did not have significant lower odds of rapid diagnostic tests-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.77, 0.42-1.42). However, children receiving sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine had significantly lower odds of rapid diagnostic tests-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.42, 95% CI 0.28-0.63). Similarly, children receiving sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine + amodiaquine also had significantly lower odds of rapid diagnostic test-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.54, 95% CI 0.47-0.62). CONCLUSION: Adherence to at least one daily dose of amodiaquine administration following receipt of Day 1 sulfadoxine-pyrimethamine plus amodiaquine by eligible children is crucial to ensure the effectiveness of seasonal malaria chemoprevention. This demonstrates the importance of enhancing caregiver awareness regarding the importance of amodiaquine and identifying barriers toward amodiaquine administration at the community level.

Update on numbers of tobacco-attributable deaths by country in the South-East Asia region: implications for policy.

BACKGROUND: The WHO South-East Asia Region is home to around 33% of adult tobacco users. To inform tobacco control policy and practice, we conducted a study using the latest available data to update mortality attributable to overall tobacco use, including smoked tobacco, smokeless tobacco (SLT) and secondhand smoke (SHS) exposure, in the 11 countries of the Region. METHODS: We estimated smoking, SLT use and SHS exposure using the latest available surveys for each country during 2016-2021, and then estimated all-cause and lung cancer-attributable annual deaths for each using the population-attributable fraction method. Finally, we estimated the annual total tobacco-attributable deaths including all three exposures using the multiplicative aggregation method. RESULTS: We estimated the occurrence of 4 087 920 all-cause deaths and 105 279 lung cancer deaths annually attributable to tobacco use among the 11 countries investigated. India accounted for 63.9% of all-cause tobacco-attributable deaths. CONCLUSIONS: The high annual number of tobacco-attributable deaths in the Region highlights the need for accelerating progress in reducing tobacco use. Implementation of the WHO Framework Convention on Tobacco Control (FCTC) and MPOWER policy package needs prioritisation at the country level. Tobacco cessation services, supply-side measures and policies to counter tobacco industry interference should be strengthened. Further work is needed to monitor progress towards FCTC implementation and analyse the impacts of policies on tobacco-related outcomes, including attributable mortality and disease burden, to inform advocacy efforts.

Predictors of accessing seasonal malaria chemoprevention medicines through non-door-to-door distribution in Nigeria.

BACKGROUND: In Nigeria, seasonal malaria chemoprevention (SMC) is typically administered door-to-door to children under five by community medicine distributors during high transmission seasons. While door-to-door distribution (DDD) is exclusively employed in Nigeria as part of standard operating procedures of SMC programmes, some households access SMC through non-DDD channels, such as fixed-point distributions, health facilities, and private purchase. However, analysis of access to SMC medicines through non-DDD has been limited, with little evidence of its outcomes on adherence to the three-day complete course of SMC medicines and caregiver actions in the event of adverse reactions to SMC medicines. METHODS: Data were obtained from SMC end-of-round coverage surveys conducted in Nigeria in 2021 and 2022, including 25,278 households for the analysis. The proportion of households accessing SMC medicine through non-DDD and the distribution of various non-DDD sources of SMC medicines were described. Multivariate random-effects logistic regression models were performed to identify predictors of accessing SMC medicines through non-DDD. The associations between non-DDD, and caregiver-reporting of adherence to complete administration of SMC medicines and caregiver actions in the event of adverse reactions to SMC medicines were also assessed. RESULTS: Less than 2% (314/24003) of households accessed SMC medicines through non-DDD in the states surveyed. Over 60% of non-DDD access was via health facility personnel and community medicine distributors from different locations. Variables associated with non-DDD access included heads of household being born in the local state (OR = 0.68, 95% CI 0.47 to 0.90), households residing in the study state since the first cycle of the SMC round (OR = 0.39, 95% CI 0.17 to 0.88), households with high wealth index (OR = 1.36, 95% CI 1.01 to 1.82), and caregivers hearing about date of SMC delivery in the previous cycle (OR = 0.18, 95%CI 0.14 to 0.24). Furthermore, non-DDD was associated with reduced SMC adherence and higher caregiver non-reporting of adverse reactions to SMC medicines in children compared with DDD. CONCLUSION: This study provides evidence on the characteristics of households accessing SMC medicines through non-DDD and its potential negative outcomes on adherence to SMC medicine and adverse reaction reporting, underscoring potential implementation issues that may arise if non-DDD delivery models are adopted in SMC, particularly in places where DDD had been firstly used.

From efficacy to effectiveness: a comprehensive framework for monitoring, evaluating and optimizing seasonal malaria chemoprevention programmes.

BACKGROUND: Seasonal Malaria Chemoprevention (SMC) is a highly effective intervention for preventing malaria, particularly in areas with highly seasonal transmission. Monitoring and evaluating (M&E) SMC programmes are complex due to the scale, time-sensitive delivery of the programme, and influence of external factors. This paper describes the process followed to develop a comprehensive M&E framework tailored specifically for the SMC context. METHODS: The Framework was developed through a literature and programme review, and stakeholder dialogues across three implementing countries-Burkina Faso, Chad, and Nigeria. Expert consultation further refined the Framework through an iterative approach drawing upon data collected through the three sources. The Framework was designed using the Logical Framework Approach incorporating external factors and intentionally aligned with global malaria M&E standards. RESULTS: An overall aim and seven programme objectives were developed measured by 70 indicators. The indicators also capture the causal links between the implementation and results of the programme. The Framework leverages the use of current data sources and existing mechanisms, ensuring efficient data use without requiring a significant increase in resources for overall programme optimization. It also promotes the use of data triangulation, and stratification for a more nuanced understanding of factors affecting programme performance and timely data informed decision-making. CONCLUSIONS: The SMC M&E Framework presented here provides a standardized approach for programme implementers to enhance decision-making for optimal programme performance. This is an essential tool as the scope of SMC programmes expands to new geographies and target age groups.

A quasi-experimental study to estimate effectiveness of seasonal malaria chemoprevention in Aweil South County in Northern Bahr El Ghazal, South Sudan.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is an effective intervention to prevent malaria in children in locations where the burden of malaria is high and transmission is seasonal. There is growing evidence suggesting that SMC with sulfadoxine-pyrimethamine and amodiaquine can retain its high level of effectiveness in East and Southern Africa despite resistance concerns. This study aims to generate evidence on the effectiveness of SMC when delivered under programmatic conditions in an area with an unknown anti-malarial drug resistance profile in the Northern Bahr el-Ghazal region of South Sudan. METHODS: A non-randomized quasi experimental study was conducted to compare an intervention county with a control county. Five monthly SMC cycles were delivered between July and November 2022, targeting about 19,000 children 3-59 months old. Data were obtained from repeated cross-sectional household surveys of caregivers of children aged 3-59 months using cluster sampling. Wave 1 survey took place in both counties before SMC implementation; Waves 2 and 3 took place after the second and fourth monthly SMC cycles. Difference-in-differences analyses were performed by fitting logistic regression models with interactions between county and wave. RESULTS: A total of 2760 children were sampled in the study across the three survey waves in both study counties. Children in the intervention arm had 70% lower odds of caregiver-reported fever relative to those in the control arm during the one-month period prior to Wave 2 (OR: 0.30, 95% CI 0.12-0.70, p = 0.003), and 37% lower odds in Wave 3 (OR: 0.63, 95% CI 0.22-1.59, p = 0.306) after controlling for baseline difference between counties in Wave 1. Odds of caregiver-reported RDT-confirmed malaria were 82% lower in the previous 1-month period prior to Wave 2 (OR: 0.18, 95% CI 0.07-0.49, p = 0.001) and Wave 3 (OR: 0.18, 95% CI 0.06-0.54, p = 0.003). CONCLUSION: These results show high effectiveness of SMC using SPAQ in terms of reducing malaria disease during the high transmission season in children 3-59 month. Despite the promising results, additional evidence and insights from chemoprevention efficacy cohort studies, and analyses of relevant resistance markers, are required to assess the suitability of SMC for this specific context.

How is nicotine vaping product (e-cigarette) use monitored in primary care electronic health records in the United Kingdom? An exploratory analysis of Clinical Practice Research Datalink (CPRD).

BACKGROUND: Electronic health records (EHRs) could identify long-term health effects of nicotine vaping. We characterised the extent to which vaping is recorded in primary care EHRs in the UK, on a population level. METHODS: We performed descriptive analysis of Clinical Practice Research Datalink (CPRD), primary care electronic health records of 25% of the UK population (~ 16 million patients). Patients aged ≥ 18 years whose vaping status was recorded using medical codes between 2006 and 2022 were identified. We reported the frequency of vaping codes; their distribution by patient age, gender, and ethnicity; trends in vaping recording over time (including interrupted time series analyses); and transitions in patient smoking status. RESULTS: Seven medical codes indicated current or former vaping, from 150,114 patients. When their vaping status was first recorded, mean patient age was 50.2 years (standard deviation: 15.0), 52.4% were female, and 82.1% were White. Of those recorded as currently vaping, almost all (98.9%) had records of their prior smoking status: 55.0% had been smoking, 38.3% had stopped smoking, 5.6% had never smoked. Of those who were smoking prior to being recorded as vaping, more than a year after the vaping record, over a third (34.2%) were still smoking, under a quarter (23.7%) quit smoking, 1.7% received a 'never smoked' status, and there was no smoking status for 40.4%. The 'e-cigarette or vaping product use-associated lung injury' (EVALI) outbreak was significantly associated with a declining trend in new records of current vaping between September 2019 and March 2020; and an immediate significant increase in new records of former vaping, followed by a declining trend. CONCLUSIONS: Few patients are being asked about vaping. Most who vape had smoked, and many quit smoking after starting vaping. To enable electronic health records to provide stronger evidence on health effects, we recommend improved completeness, accuracy and consistency.

Does armed conflict lead to lower prevalence of maternal health-seeking behaviours: theoretical and empirical research based on 55 683 women in armed conflict settings.

BACKGROUND: Women and children bear a substantial burden of morbidity and mortality due to armed conflict. Life-saving maternal and child health (MCH) services are low-quality in most conflict-affected regions. Previous studies on armed conflict and MCH services have been mostly cross-sectional, and a causal relationship between armed conflict and MCH services utilisation cannot be inferred. METHODS: First, we constructed a utility equation for maternal health-seeking behaviour. Next, we extracted MCH data from the Multiple Indicator Cluster Survey led by the UNICEF. Armed conflict data were obtained from the Uppsala Conflict Data Programme; 55 683 women aged 15-49 from Chad, the Central African Republic, the Democratic Republic of Congo (DRC) and the Republic of Iraq were selected as participants. We fitted a difference-in-differences (DID) model, taking before or after the conflict started as an exposure variable to estimate the effects of armed conflict on maternal health-seeking behaviours. RESULTS: According to the results of the DID model, in the regional sample, armed conflict had a positive effect on tetanus vaccination (ß=0.055, 95% CI 0.004 to 0.106, p<0.05), and had a negative effect on antenatal care at least eight visits (ANC8+) (ß=-0.046, 95% CI -0.078 to -0.015, p<0.01). And, the effects of armed conflict on ANC, ANC4+, institutional delivery and early initiation of breast feeding (EIB) were not statistically significant. As for the country sample, we found that armed conflict had a negative effect on EIB (ß=-0.085, 95% CI -0.184 to 0.015, p<0.1) in Chad. In Iraq, armed conflict had positive impacts on ANC (ß=0.038, 95% CI -0.001 to 0.078, p<0.1) and tetanus vaccination (ß=0.059, 95% CI 0.012 to 0.107, p<0.05), whereas it had a negative effect on ANC8+ (ß=-0.039, 95% CI -0.080 to 0.002, p<0.1). No statistically significant associations were discovered in DRC based on the DID model. CONCLUSIONS: There might be a mixed effect of armed conflict on maternal health-seeking behaviours. In the absence of humanitarian assistance, armed conflict reduces certain maternal health-seeking behaviours, such as ANC8+. When practical humanitarian health assistance is provided, the damage can be alleviated, and even the prevalence of maternal health-seeking behaviours can be improved, such as tetanus vaccination. Providing humanitarian assistance to conflict-affected regions improved the accessibility of MCH services for women living in those areas. However, the goals of saving lives and alleviating suffering still need to be achieved. In conflict-affected regions, humanitarian assistance on ANC, institutional delivery and breast feeding need strengthening.

Predictors of caregiver adherence to administration of amodiaquine during delivery of seasonal malaria chemoprevention in Nigeria, Burkina Faso, Chad, and Togo.

BACKGROUND: Malaria is the leading cause of morbidity and mortality among infants and children under-five in sub-Saharan Africa. In the Sahel, seasonal malaria chemoprevention (SMC) is delivered door-to-door in monthly cycles. In each cycle, children are administered sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) on Day 1 by community distributors, and AQ on Day 2 and Day 3 by caregivers. Non-adherence to AQ administration by caregivers has implications for emergence of antimalarial resistance. METHODS: Predictors of non-adherence to administration of AQ on Day 2 and Day 3 among caregivers of children aged 3-59 months who had received Day 1 SP and AQ during the last 2020 SMC cycle (n = 12,730) were analysed using data from SMC coverage surveys in Nigeria, Burkina Faso and Togo, and fitting multivariate random-effects logistic regression models. RESULTS: Previous adverse reaction to SMC medicines by eligible children (OR: 0.29, 95% CI 0.24-0.36, p < 0.001), awareness of the importance of administering Day 2 and Day 3 AQ (OR: 2.19, 95% CI 1.69-2.82, p < 0.001), caregiver age, and home visits to caregivers delivered by the Lead Mothers intervention in Nigeria (OR: 2.50, 95% CI 1.93-2.24, p < 0.001), were significantly associated with caregiver adherence to Day 2 and Day 3 AQ administration. CONCLUSIONS: Increasing caregivers' knowledge of SMC and interventions such as Lead Mothers have the potential to improve full adherence to AQ administration.

Viral respiratory infections in a rapidly changing climate: the need to prepare for the next pandemic.

Viral respiratory infections (VRIs) cause seasonal epidemics and pandemics, with their transmission influenced by climate conditions. Despite the risks posed by novel VRIs, the relationships between climate change and VRIs remain poorly understood. In this review, we synthesized existing literature to explore the connections between changes in meteorological conditions, extreme weather events, long-term climate warming, and seasonal outbreaks, epidemics, and pandemics of VRIs from an interdisciplinary perspective. We proposed a comprehensive conceptual framework highlighting the potential biological, socioeconomic, and ecological mechanisms underlying the impact of climate change on VRIs. Our findings suggested that climate change increases the risk of VRI emergence and transmission by affecting the biology of viruses, host susceptibility, human behavior, and environmental conditions of both society and ecosystems. Further interdisciplinary research is needed to address the dual challenge of climate change and pandemics.

A non-randomized controlled trial to assess the protective effect of SMC in the context of high parasite resistance in Uganda.

BACKGROUND: Until recently, due to widespread prevalence of molecular markers associated with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) resistance in east and southern Africa, seasonal malaria chemoprevention (SMC) has not been used at scale in this region. This study assessed the protective effectiveness of monthly administration of SP + AQ (SPAQ) to children aged 3-59 months in Karamoja sub-region, Uganda, where parasite resistance is assumed to be high and malaria transmission is seasonal. METHODS: A two-arm quasi-experimental, open-label prospective non-randomized control trial (nRCT) was conducted in three districts. In two intervention districts, 85,000 children aged 3-59 months were targeted to receive monthly courses of SMC using SPAQ during the peak transmission season (May to September) 2021. A third district served as a control, where SMC was not implemented. Communities with comparable malaria attack rates were selected from the three districts, and households with at least one SMC-eligible child were purposively selected. A total cohort of 600 children (200 children per district) were selected and followed using passive surveillance for breakthrough confirmed malaria episodes during the five-month peak transmission season. Malaria incidence rate per person-months and number of malaria episodes among children in the two arms were compared. Kaplan-Meier failure estimates were used to compare the probability of a positive malaria test. Other factors that may influence malaria transmission and infection among children in the two arms were also assessed using multivariable cox proportional hazards regression model. RESULTS: The malaria incidence rate was 3.0 and 38.8 per 100 person-months in the intervention and control groups, respectively. In the intervention areas 90.0% (361/400) of children did not experience any malaria episodes during the study period, compared to 15% (29/200) in the control area. The incidence rate ratio was 0.078 (95% CI 0.063-0.096), which corresponds to a protective effectiveness of 92% (95% CI 90.0-94.0) among children in the intervention area. CONCLUSION: SMC using SPAQ provided high protective effect against malaria during the peak transmission season in children aged 3-59 months in the Karamoja sub-region of Uganda.

Association Between Parental Education and Simultaneous Malnutrition Among Parents and Children in 45 Low- and Middle-Income Countries.

Importance: Parental education is known to be associated with the health status of parents and their offspring. However, the association between parental education and the simultaneous manifestation of multiple forms of malnutrition within households remains underinvestigated globally. Objective: To assess the association between parental education and the simultaneous manifestation of malnutrition of both parent and child (either overnutrition or undernutrition)-referred to as the double burden of malnutrition (DBM)-at the household level in mother-child and father-child pairs in low- and middle-income countries (LMICs). Design, Setting, and Participants: This cross-sectional study used data from the US Agency for International Development Demographic and Health Surveys (January 1, 2010, to December 31, 2021) to identify mother-child pairs and father-child pairs from LMICs. The eligibility criteria were as follows: (1) children aged 0 to 59 months; (2) nonpregnant mothers at the time of the survey in the sample of mother-child pairs; and (3) valid measures of the weight, height, and hemoglobin level for the child and at least 1 of their parents. Exposures: Highest level of parental education obtained and number of years of education completed. Main Outcomes and Measures: Four sets of multivariable logistic regression models were constructed to assess the association between parental education and DBM, and analysis was performed between March 10 and May 15, 2022. Results: This study included 423 340 mother-child pairs from 45 LMICs and 56 720 father-child pairs from 16 LMICs. The mean (SD) age of the mother-child pairs was 28.2 (6.1) and 1.9 (1.4) years, respectively; 48.8% of the children were female. We observed that 49.0% of mother-child pairs experienced DBM. Compared with mother-child pairs with no maternal education, higher maternal education was associated with a lower risk of DBM. For example, the odds ratio (OR) for tertiary maternal education was 0.71 (95% CI, 0.67-0.74). However, the association differed by DBM subtypes: higher maternal education was associated with a lower risk of both mothers and children being undernourished but with a higher risk of almost all DBM subtypes involving overnutrition. For example, compared with mother-child pairs with no maternal education, those with secondary education were less likely to develop simultaneous maternal and child undernutrition (OR, 0.83 [95% CI, 0.80-0.86]) but were more likely to experience simultaneous maternal and child overnutrition (OR, 2.20 [95% CI, 1.61-3.00]); similar results were observed for pairs with primary and tertiary education. The results in mother-child pairs remained consistent after controlling for paternal education. Among the father-child pairs, 26.5% had DBM, with fathers with tertiary education significantly more likely to experience simultaneous paternal overnutrition and child undernutrition (OR, 1.55 [95% CI, 1.23-1.95]) compared with pairs with no paternal education; they were also less likely to have both paternal and child undernutrition (OR, 0.70 [95% CI, 0.59-0.84]). Conclusions and Relevance: In this study, maternal education and paternal education were independently associated with DBM, and the associations differed by DBM subtypes. These findings suggest that the different risks of malnutrition faced by households with various levels of education should thus be considered in policy evaluation.

Trends in smokeless tobacco use and attributable mortality and morbidity in the South-East Asia Region: implications for policy.

OBJECTIVES: To describe the prevalence of smokeless tobacco (SLT) use and number of users by year, in addition to trends in mortality and attributable disease burden in countries of the WHO South-East Asia Region (SEAR), to inform policies for SLT control in the Region. METHODS: For each SEAR country, we obtained data from Global Adult Tobacco Surveys, WHO STEPwise Approach to NCD Risk Factor Surveillance surveys and Demographic and Health Surveys conducted since 2010 to estimate prevalence of SLT use by country, sex and year. Using data from the World Population Prospects database we estimated the number of users by country. Next, using the results of previous meta-analyses and prevalence results, we estimated the population attributable fractions and attributable mortality and morbidity in terms of annual deaths and disability-adjusted life years lost. We then characterised trends in attributable deaths and disease burden for countries with comparable data. RESULTS: There were wide differences in SLT use prevalence by country. We estimated that, during 2015-2019, there were 165 803 900 SLT users across SEAR, with 479 466 attributable deaths annually of which India accounted for 79.9% with 383 248. Attributable annual deaths increased in some countries during 2015-2019. CONCLUSIONS: Annual deaths and disease burden attributable to SLT remain high across SEAR and have only declined modestly in recent years. Effective implementation of all WHO Framework Convention on Tobacco Control measures, addressing both supply-side and demand-side issues, in relation to SLT and areca nut products must be prioritised to ensure reductions in mortality and disease burden are sustained and accelerated.

Adverse events over the life course and later-life wellbeing and depressive symptoms in older people.

OBJECTIVES: Exposures to adverse events are associated with impaired later-life psychological health. While these associations depend on the type of event, the manner in which associations for different event types depend on when they occur within the life course has received less attention. We investigated associations between counts of adverse events over the life course, and wellbeing and mental health outcomes in older people, according to their timing (age of occurrence), orientation (self or other) and, both their timing and orientation. DESIGN: Linear and logistic random-effects models for repeated observations. SETTING: England, 2002-2015. PARTICIPANTS: A total of 4,208 respondents aged >50 years with 22,146 observations across Waves 1-7 of the English Longitudinal Study of Ageing. MEASUREMENTS: Cumulative adversity was measured by counts of 16 types of events occurring within four age ranges over the life course using retrospective life history data. These were categorized into other- (experienced through harms to others) and self-oriented events. Outcomes included CASP-12 (control, autonomy, self-realization, and pleasure), the eight-item Centre of Epidemiological Studies Depression Scale, and self-appraised subjective life satisfaction. RESULTS: Additional adverse events were associated with lower CASP-12 and life satisfaction scores, and higher odds of probable depressive caseness. In childhood, other-oriented events had a larger negative association with later-life wellbeing than self-oriented events; the converse was found for events occurring in adulthood. CONCLUSIONS: Events occurring at all life course stages were independently associated with both later-life wellbeing and depression in a cumulative fashion. Certain age ranges may represent sensitive periods for specific event types.

A hybrid effectiveness-implementation study protocol to assess the effectiveness and chemoprevention efficacy of implementing seasonal malaria chemoprevention in five districts in Karamoja region, Uganda.

Background: The World Health Organization (WHO) recommends seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SPAQ) for children aged 3 to 59 months, living in areas where malaria transmission is highly seasonal. However, due to widespread prevalence of resistance markers, SMC has not been implemented at scale in East and Southern Africa. An initial study in Uganda showed that SMC with SPAQ was feasible, acceptable, and protective against malaria in eligible children in Karamoja region. Nonetheless, exploration of alternative regimens is warranted since parasite resistance threats persist. Objective: The study aims to test the effectiveness of SMC with Dihydroartemisinin-piperaquine (DP) or SPAQ (DP-SMC & SPAQ-SMC), chemoprevention efficacy as well as the safety and tolerability of DP compared to that of SPAQ among 3-59 months old children in Karamoja region, an area of Uganda where malaria transmission is highly seasonal. Methods: A Type II hybrid effectiveness-implementation study design consisting of four components: 1) a cluster randomized controlled trial (cRCT) using passive surveillance to establish confirmed malaria cases in children using both SPAQ and DP; 2a) a prospective cohort study to determine the chemoprevention efficacy of SPAQ and DP (if SPAQ or DP clears sub-patent infection and provides 28 days of protection from new infection) and whether drug concentrations and/or resistance influence the ability to clear and prevent infection; 2b) a sub study examining pharmacokinetics of DP in children between 3 to <6 months; 3) a resistance markers study in children 3-59 months in the research districts plus the standard intervention districts to measure changes in resistance marker prevalence over time and finally; 4) a process evaluation. Discussion: This study evaluates the effects of SPAQ-SMC versus DP-SMC on clinical malaria in vulnerable children in the context of high parasite SP resistance, whilst informing on the best implementation strategies. Conclusion: This study will inform malaria policy in high-burden countries, specifically on utility of SMC outside the sahel, and contribute to progress in malaria control.

To what extent do disparities in economic development and healthcare availability explain between-province health inequalities among older people in China?

Background: Uneven economic development has led to substantial health inequalities between Chinese provinces. The extent of, and factors underlying, between-province health inequalities have received little attention. Methods: Data from 15,278 respondents in Wave 2 (2013) of the China Health and Retirement Longitudinal Study (CHARLS) were used to investigate inequalities among people aged ≥50 years in five health outcomes between 27 Chinese province-level administrative units. After characterizing the between-province differences and the relevance of province effects, proportional change in variance between unadjusted and adjusted models was calculated to determine the percentage of between-province variance in health outcomes explained by province-level variables including measures of economic development and healthcare availability. Results: Although province effects explained <10% of overall variance in health outcomes, they underpinned large between-province inequalities among people aged ≥50 years. Gross Regional Product per capita was more important than doctor density in explaining between-province variance in health outcomes, particularly depression symptoms and instrumental activities of daily living impairment. Conclusion: Policy efforts, including more equal distribution of healthcare personnel, may be warranted to reduce between-province health inequalities.

Feasibility, Acceptability, and Protective Efficacy of Seasonal Malaria Chemoprevention Implementation in Nampula Province, Mozambique: Protocol for a Hybrid Effectiveness-Implementation Study.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a highly effective community-based intervention to prevent malaria infections in areas where the malaria burden is high and transmission occurs mainly during the rainy season. In Africa, so far, SMC has been implemented in the Sahel region. Mozambique contributes 4% of the global malaria cases, and malaria is responsible for one-quarter of all deaths in the country. Based on recommendations in the Malaria Strategic Plan, the Malaria Consortium, in partnership with the National Malaria Control Programme in Mozambique, initiated a phased SMC implementation study in the northern province of Nampula. The first phase of this 2-year implementation study was conducted in 2020-2021 and focused on the feasibility and acceptability of SMC. The second phase will focus on demonstrating impact. This paper describes phase 2 of the implementation study. OBJECTIVE: Specific objectives include the following: (1) to determine the effectiveness of SMC in terms of its reduction in incidence of malaria infection among children aged 3 to 59 months; (2) to determine the chemoprevention efficacy of sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) when used for SMC in Nampula Province, Mozambique, and the extent to which efficacy is impacted by drug resistance and drug concentrations; (3) to investigate the presence and change in SP+AQ- and piperaquine-resistance markers over time as a result of SMC implementation; and (4) to understand the impact of the SMC implementation model, determining the process and acceptability outcomes for the intervention. METHODS: This type 2, hybrid, effectiveness-implementation study uses a convergent mixed methods approach. SMC will be implemented in four monthly cycles between December 2021 and March 2022 in four districts of Nampula Province. Phase 2 will include four components: (1) a cluster randomized controlled trial to establish confirmed malaria cases, (2) a prospective cohort to determine the chemoprevention efficacy of the antimalarials used for SMC and whether drug concentrations or resistance influence the duration of protection, (3) a resistance marker study in children aged 3 to 59 months to describe changes in resistance marker prevalence over time, and (4) a process evaluation to determine feasibility and acceptability of SMC. RESULTS: Data collection began in mid-January 2022, and data analysis is expected to be completed by October 2022. CONCLUSIONS: This is the first effectiveness trial of SMC implemented in Mozambique. The findings from this trial will be crucial to policy change and program expansion to other suitable geographies outside of the Sahel. The chemoprevention efficacy cohort study is a unique opportunity to better understand SMC drug efficacy in this new SMC environment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05186363; https://clinicaltrials.gov/ct2/show/NCT05186363. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36403.

Impact of seasonal malaria chemoprevention on prevalence of malaria infection in malaria indicator surveys in Burkina Faso and Nigeria.

BACKGROUND: In 2012, the WHO issued a policy recommendation for the use of seasonal malaria chemoprevention (SMC) to children 3-59 months in areas of highly seasonal malaria transmission. Clinical trials have found SMC to prevent around 75% of clinical malaria. Impact under routine programmatic conditions has been assessed during research studies but there is a need to identify sustainable methods to monitor impact using routinely collected data. METHODS: Data from Demographic Health Surveys were merged with rainfall, geographical and programme data in Burkina Faso (2010, 2014, 2017) and Nigeria (2010, 2015, 2018) to assess impact of SMC. We conducted mixed-effects logistic regression to predict presence of malaria infection in children aged 6-59 months (rapid diagnostic test (RDT) and microscopy, separately). RESULTS: We found strong evidence that SMC administration decreases odds of malaria measured by RDT during SMC programmes, after controlling for seasonal factors, age, sex, net use and other variables (Burkina Faso OR 0.28, 95% CI 0.21 to 0.37, p<0.001; Nigeria OR 0.40, 95% CI 0.30 to 0.55, p<0.001). The odds of malaria were lower up to 2 months post-SMC in Burkina Faso (1-month post-SMC: OR 0.29, 95% CI 0.12 to 0.72, p=0.01; 2 months post-SMC: OR: 0.33, 95% CI 0.17 to 0.64, p<0.001). The odds of malaria were lower up to 1 month post-SMC in Nigeria but was not statistically significant (1-month post-SMC 0.49, 95% CI 0.23 to 1.05, p=0.07). A similar but weaker effect was seen for microscopy (Burkina Faso OR 0.38, 95% CI 0.29 to 0.52, p<0.001; Nigeria OR 0.53, 95% CI 0.38 to 0.76, p<0.001). CONCLUSIONS: Impact of SMC can be detected in reduced prevalence of malaria from data collected through household surveys if conducted during SMC administration or within 2 months afterwards. Such evidence could contribute to broader evaluation of impact of SMC programmes.

Knowledge and practices surrounding malaria and LLIN use among Arab, Dazagada and Fulani pastoral nomads in Chad.

BACKGROUND: Chadian pastoral nomads are highly exposed to malaria due to their lifestyle and their mobility between various endemic areas. To inform strategies to reduce nomads' risk of malaria and associated morbidity and mortality, it is important to understand the factors associated to their knowledge of malaria transmission and prevention practices. METHODS: A cross-sectional study among Arab, Dazagada and Fulani pastoral nomadic groups was conducted in February and October 2021. A validated structured electronic questionnaire was administered to assess knowledge of malaria. Attitudes and malaria prevention practices were assessed on the basis of perception of the causes of malaria and the use of a long-lasting insecticide-treated net (LLIN) the day before the survey. Data were analyzed using Chi-square tests and multivariate logistic regression with covariates adjustment. RESULTS: A total of 278 nomads aged 20 to 65 years were included in the study. Overall, 90.7% of participants surveyed had a good knowledge of malaria. Fulani respondents were more likely to have a good knowledge of malaria than Arab respondents (Adjusted Odd ratio (AOR): 5.00, 95% CI: 1.04-24.03) and households possessing a LLIN were more likely to have a good knowledge of malaria (AOR: 9.66, 95% CI: 1.24-75.36). Most nomad households surveyed reported sleeping under a mosquito net the night before the survey (87.1%) while 98.9% owned a LLIN. Daza respondents (AOR: 0.23, 95% CI: 0.09-0.56) were less likely to use LLINs than Arab respondents. The middle (AOR: 2.78, 95% CI: 1.17-6.62) and wealthier households (AOR: 6.68, 95% CI: 3.19-14.01) were more likely to use LLINs. Knowledge of malaria was associated with the use of LLIN (AOR: 12.77, 95% CI: 1.58-102.99). CONCLUSION: There remains a need to improve nomads' understanding of Plasmodium falciparum-carrying mosquitoes as the vector for malaria transmission and the quality of information provided. Knowledge of malaria and its prevention strategies in nomadic setting lead to the use of LLINs. Further reductions in malaria morbidity can be achieved by improving nomads' access to LLINs. This study can inform on the design policies to improve nomadic communities' knowledge of malaria prevention and promoting LLIN use as requested by the national policy against malaria.

Extending seasonal malaria chemoprevention to five cycles: a pilot study of feasibility and acceptability in Mangodara district, Burkina Faso.

BACKGROUND: Seasonal malaria chemoprevention (SMC) involves administering antimalarial drugs at monthly intervals during the high malaria transmission period to children aged 3 to 59 months as recommended by the World Health Organization. Typically, a full SMC course is administered over four monthly cycles from July to October, coinciding with the rainy season. However, an analysis of rainfall patterns suggest that the malaria transmission season is longer and starting as early as June in the south of Burkina Faso, leading to a rise in cases prior to the first cycle. This study assessed the acceptability and feasibility of extending SMC from four to five cycles to coincide with the earlier rainy season in Mangodara health district. METHODS: The mixed-methods study was conducted between July and November 2019. Quantitative data were collected through end-of-cycle and end-of-round household surveys to determine the effect of the additional cycle on the coverage of SMC in Mangodara. The data were then compared with 22 other districts where SMC was implemented by Malaria Consortium. Eight focus group discussions were conducted with caregivers and community distributors and 11 key informant interviews with community, programme and national-level stakeholders. These aimed to determine perceptions of the acceptability and feasibility of extending SMC to five cycles. RESULTS: The extension was perceived as acceptable by caregivers, community distributors and stakeholders due to the positive impact on the health of children under five. However, many community distributors expressed concern over the feasibility, mainly due to the clash with farming activities in June. Stakeholders highlighted the need for more evidence on the impact of the additional cycle on parasite resistance prior to scale-up. End-of-cycle survey data showed no difference in coverage between five SMC cycles in Mangodara and four cycles in the 22 comparison districts. CONCLUSIONS: The additional cycle should begin early in the day in order to not coincide with the agricultural activities of community distributors. Continuous sensitisation at community level is critical for the sustainability of SMC and acceptance of an additional cycle, which should actively engage male caregivers. Providing additional support in proportion to the increased workload from a fifth cycle, including timely remuneration, is critical to avoid the demotivation of community distributors. Further studies are required to understand the effectiveness, including cost-effectiveness, of tailoring SMC according to the rainy season. Understanding the impact of an additional cycle on parasite resistance to SPAQ is critical to address key informants' concerns around the deviation from the current four-cycle policy recommendation.

Paediatric pneumonia research priorities in the context of COVID-19: A eDelphi study.

Background: Pneumonia remains the leading cause of infectious deaths in children under-five globally. We update the research priorities for childhood pneumonia in the context of the COVID-19 pandemic and explore whether previous priorities have been addressed. Methods: We conducted an eDelphi study from November 2019 to June 2021. Experts were invited to take part, targeting balance by: gender, profession, and high (HIC) and low- and middle-income countries (LMIC). We followed a three-stage approach: 1. Collating questions, using a list published in 2011 and adding newly posed topics; 2. Narrowing down, through participant scoring on importance and whether they had been answered; 3. Ranking of retained topics. Topics were categorized into: prevent and protect, diagnosis, treatment and cross-cutting. Results: Overall 379 experts were identified, and 108 took part. We started with 83 topics, and 81 further general and 40 COVID-19 specific topics were proposed. In the final ranking 101 topics were retained, and the highest ranked was to "explore interventions to prevent neonatal pneumonia". Among the top 20 topics, epidemiological research and intervention evaluation was commonly prioritized, followed by the operational and implementation research. Two COVID-19 related questions were ranked within the top 20. There were clear differences in priorities between HIC and LMIC respondents, and academics vs non-academics. Conclusions: Operational research on health system capacities, and evaluating optimized delivery of existing treatments, diagnostics and case management approaches are needed. This list should act as a catalyst for collaborative research, especially to meet the top priority in preventing neonatal pneumonia, and encourage multi-disciplinary partnerships.