Potential impact of climatic factors on malaria in Rwanda between 2012 and 2021: a time-series analysis.

BACKGROUND: Malaria remains an important public health problem, particularly in sub-Saharan Africa. In Rwanda, where malaria ranks among the leading causes of mortality and morbidity, disease transmission is influenced by climatic factors. However, there is a paucity of studies investigating the link between climate change and malaria dynamics, which hinders the development of effective national malaria response strategies. Addressing this critical gap, this study analyses how climatic factors influence malaria transmission across Rwanda, thereby informing tailored interventions and enhancing disease management frameworks. METHODS: The study analysed the potential impact of temperature and cumulative rainfall on malaria incidence in Rwanda from 2012 to 2021 using meteorological data from the Rwanda Meteorological Agency and malaria case records from the Rwanda Health Management and Information System. The analysis was performed in two stages. First, district-specific generalized linear models with a quasi-Poisson distribution were applied, which were enhanced by distributed lag non-linear models to explore non-linear and lagged effects. Second, random effects multivariate meta-analysis was employed to pool the estimates and to refine them through best linear unbiased predictions. RESULTS: A 1-month lag with specific temperature and rainfall thresholds influenced malaria incidence across Rwanda. Average temperature of 18.5 °C was associated with higher malaria risk, while temperature above 23.9 °C reduced the risk. Rainfall demonstrated a dual effect on malaria risk: conditions of low (below 73 mm per month) and high (above 223 mm per month) precipitation correlated with lower risk, while moderate rainfall (87 to 223 mm per month) correlated with higher risk. Seasonal patterns showed increased malaria risk during the major rainy season, while the short dry season presented lower risk. CONCLUSION: The study underscores the influence of temperature and rainfall on malaria transmission in Rwanda and calls for tailored interventions that are specific to location and season. The findings are crucial for informing policy that enhance preparedness and contribute to malaria elimination efforts. Future research should explore additional ecological and socioeconomic factors and their differential contribution to malaria transmission.

Malaria positivity following a single oral dose of azithromycin among children in Burkina Faso: a randomized controlled trial.

BACKGROUND: Azithromycin is a broad-spectrum antibiotic that has moderate antimalarial activity and has been shown to reduce all-cause mortality when biannually administered to children under five in high mortality settings in sub-Saharan Africa. One potential mechanism for this observed reduction in mortality is via a reduction in malaria transmission. METHODS: We evaluated whether a single oral dose of azithromycin reduces malaria positivity by rapid diagnostic test (RDT). We conducted an individually randomized placebo-controlled trial in Burkina Faso during the high malaria transmission season in August 2020. Children aged 8 days to 59 months old were randomized to a single oral dose of azithromycin (20 mg/kg) or matching placebo. At baseline and 14 days following treatment, we administered a rapid diagnostic test (RDT) to detect Plasmodium falciparum and measured tympanic temperature for all children. Caregiver-reported adverse events and clinic visits were recorded at the day 14 visit. RESULTS: We enrolled 449 children with 221 randomized to azithromycin and 228 to placebo. The median age was 32 months and 48% were female. A total of 8% of children had a positive RDT for malaria at baseline and 11% had a fever (tympanic temperature ≥ 37.5 °C). In the azithromycin arm, 8% of children had a positive RDT for malaria at 14 days compared to 7% in the placebo arm (P = 0.65). Fifteen percent of children in the azithromycin arm had a fever ≥ 37.5 °C compared to 21% in the placebo arm (P = 0.12). Caregivers of children in the azithromycin group had lower odds of reporting fever as an adverse event compared to children in the placebo group (OR 0.41, 95% CI 0.18-0.96, P = 0.04). Caregiver-reported clinic visits were uncommon, and there were no observed differences between arms (P = 0.32). CONCLUSIONS: We did not find evidence that a single oral dose of azithromycin reduced malaria positivity during the high transmission season. Caregiver-reported fever occurred less often in children receiving azithromycin compared to placebo, indicating that azithromycin may have some effect on non-malarial infections. Trial registration Clinicaltrials.gov NCT04315272, registered 19/03/2020.

A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels.

Background: In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods: Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results: Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions: Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration: NCT01644721.

Ramadan Exposure In Utero and Child Mortality in Burkina Faso: Analysis of a Population-Based Cohort Including 41,025 Children.

Ramadan exposure in utero can be regarded as a natural experiment with which to study how nutritional conditions in utero influence susceptibility to disease later in life. We analyzed data from rural Burkina Faso on 41,025 children born between 1993 and 2012, of whom 25,093 were born to Muslim mothers. Ramadan exposure was assigned on the basis of overlap between Ramadan dates and gestation, creating 7 exclusive categories. We used proportional hazards regression with difference-in-differences analysis to estimate the association between Ramadan exposure at different gestational ages and mortality among children under 5 years of age. Under-5 mortality was 32 deaths per 1,000 child-years. Under-5 mortality among Muslims was 15% higher than that among non-Muslims (P < 0.001). In the difference-in-differences analysis, the occurrence of Ramadan during conception or the first or second trimester was associated with higher under-5 mortality rates among Muslims only. The mortality rates of children born to Muslim mothers were 33%, 29%, and 22% higher when Ramadan occurred during conception, the first trimester, and the second trimester, respectively, compared with children of non-Muslim mothers born at the same time (P = 0.01, P < 0.001, and P = 0.007). Having a Muslim mother was not associated with mortality when the child was not exposed to Ramadan, born during Ramadan, or exposed during the third trimester. Observance of Ramadan during early pregnancy can have detrimental consequences for the future health of the unborn child.

[Determinants of the choice of healthcare worker positions in rural areas in Burkina Faso.] / Déterminants du choix des postes en zone rurale par les professionnels de santé au Burkina Faso.

INTRODUCTION: In 2014, in Burkina Faso, more than 60% of healthcare workers were working in urban areas to the detriment of rural areas. The two largest cities concentrated the majority of healthcare workers, while these cities represent only 10% of the population. This study was designed to identify incentive strategies that could enable more equitable deployment of healthcare workers. METHODS: A cross-sectional survey was carried out in 2016 in six health regions in Burkina Faso. Key informant interviews were conducted to determine the factors influencing the choice of jobs. The results were used to construct job packages useful for the discrete choice experiment survey.Levels of preferences for 1,173 health workers for incentive packages linked to the job were explored by means of electronic questionnaire data collection.Sawtooth software was used to develop and randomize job pairing preferences proposed to healthcare workers. STATA14 software was used for mixed-logit analysis. RESULTS: The determinants to promote more equitable deployment and maintenance of health workers in their workplace include access to good accommodation, on-job training, responsibility, and improved salaries.In terms of acceptability of deployment, more than 75% (p-value < 0.001) of workers would agree to be redeployed in rural areas if the above conditions were met. CONCLUSION: Adequate and sustainable human resource development strategies should be set up by policymakers in order to improve the maintenance of healthcare workers in rural areas.

Efficacy and safety of triple combination therapy with artesunate-amodiaquine-methylene blue for falciparum malaria in children: a randomized controlled trial in Burkina Faso.

BACKGROUND: Methylene blue (MB) has been shown to be safe and effective against falciparum malaria in Africa and to have pronounced gametocytocidal properties. METHODS: Three days of treatment with artesunate (AS)-amodiaquine (AQ) combined with MB was compared with AS-AQ treatment in a randomized controlled phase IIb study; the study included 221 children aged 6-59 months with uncomplicated falciparum malaria in Burkina Faso. The primary end point was gametocyte prevalence during follow-up, as determined by microscopy and real-time quantitative nucleic acid sequence-based amplification (QT-NASBA). RESULTS: The gametocyte prevalence of Plasmodium falciparum at baseline was 3.6% (microscopy) and 97% (QT-NASBA). It was significantly lower in the AS-AQ-MB than in the AS-AQ group on day 7 of follow-up (microscopy, 1.2% vs 8.9% [P < .05]; QT-NASBA, 36.7% vs 63.3% [P < .001]). Hemoglobin values were significantly lower in the AS-AQ-MB group than in the AS-AQ group at days 2 and 7 of follow-up. Vomiting of the study medication occurred significantly more frequently in the AS-AQ-MB group. CONCLUSIONS: The combination of MB with an artemisinin-based combination therapy has been confirmed to be effective against the gametocytes of P. falciparum. MB-based combinations need to be compared with primaquine-based combinations, preferably using MB in an improved pediatric formulation. Clinical Trials Registration: NCT01407887.

Operational Differences between Product Development Partnership, Pharmaceutical Industry, and Investigator Initiated Clinical Trials.

Medicine development is a lengthy endeavour. Increasing regulatory stringency and trial complexity might lead to reduced efficiency, dwindled output, and elevated costs. However, alternative models are possible. We compared the operational differences between pharmaceutical industry sponsored trials, product development partnership trials, and investigator-initiated trials to identify key drivers of inefficiency in clinical research. We conducted an exploratory mixed-methods study with stakeholders, including clinical trial sponsors, contract research organisations, and investigators. The qualitative component included 40 semi-structured interviews, document reviews of 12 studies and observations through work shadowing in research institutions in Burkina Faso, Mali, and Switzerland. The findings were triangulated with an online survey polling clinical research professionals. The operational differences were grouped under five categories: (i) trial start-up differences including governance and management structure; (ii) study complexity; (iii) site structural and organisational differences; (iv) study conduct, quality approaches, and standard operating procedures; and (v) site capacity strengthening and collaboration. Early involvement of sites in the planning and tailored quality approaches were considered critical for clinical operations performance. Differences between the types of trials reviewed pertained to planning, operational complexities, quality approaches, and support to the sites. Integration of quality-by-design components has the potential to alleviate unnecessary process burden.

A description of a pre-emptive typhoid Vi capsular polysaccharide vaccination campaign after the 2015 earthquake in Nepal and vaccine effectiveness evaluation.

BACKGROUND: A 7.8 R scale earthquake hit Nepal in April 2015 and caused about 9000 deaths along with damage to infrastructure, including the water and sewage system. Bhaktapur was one of the highly affected districts. A typhoid vaccination campaign (pre-emptive) was carried out among children who were living in the temporary shelters in this district. The assessment of vaccine effectiveness after a pre-emptive typhoid vaccine campaign following an earthquake has previously not been attempted in Nepal. OBJECTIVE: To describe the pre-emptive typhoid Vi capsular polysaccharide vaccination campaign and an evaluation of the vaccine effectiveness. METHODS: We conducted a pre-emptive typhoid Vi capsular polysaccharide vaccination campaign among children between 2 and 15 years of age dwelling in 23 temporary shelters in Bhaktapur district after the earthquake. Surveillance of clinical typhoid was carried out from 2014 to 2017 in Siddhi Memorial Hospital, the only hospital for children in the district. We calculated vaccine effectiveness using a case-control study design (clinical typhoid as cases and chest x-ray confirmed pneumonia as controls). RESULTS: Three thousand nine hundred sixteen children of age 2-15 years residing in the 23 temporary shelters in Bhaktapur received the typhoid Vi capsular polysaccharide vaccine between July and December 2015. 2193 children of age 2-15 years were admitted to the hospital during the study period and 260 (11.9%) were diagnosed with clinical typhoid. The numbers of children admitted with clinical typhoid decreased over the study period (105 in 2014 and 47 in 2017; P = 0.001). Overall vaccine effectiveness was calculated at 52% (95% CI -46 to 85%), and it was 87% (95% CI -25 to 99) among children less than 5 years of age. CONCLUSIONS: We successfully conducted a pre-emptive vaccination campaign against typhoid after the 2015 Nepal earthquake. The pre-emptive vaccination campaign appeared to be more effective among children less than 5 years of age. Further studies are needed to assess the effectiveness of pre-emptive use of typhoid vaccines in the emergency situations. We highlight the challenges of calculating vaccine effectiveness of a typhoid vaccine in an emergency setting.

Contradictory mortality results in early 2-dose measles vaccine trials: interactions with oral polio vaccine may explain differences.

OBJECTIVES: Between 2003 and 2019, three trials (randomised controlled trials [RCTs]) in Guinea-Bissau randomised infants to an early 2-dose measles vaccine (MV) schedule at 4 and 9 months vs standard MV at 9 months. The RCTs produced contradictory mortality results; the effect being beneficial in the 2-dose group in the first but tending to have higher mortality in the last two RCTs. We hypothesised that increased frequency of campaigns with oral polio vaccine (C-OPV) explained the pattern. METHODS: We performed per-protocol analysis of individual-level survival data from the three RCTs in Cox proportional hazards models yielding hazard ratios (HR) for the 2-dose vs the 1-dose MV group. We examined whether timing of C-OPVs and early administration of OPV0 (birth to day 14) affected the HRs for 2-dose/1-dose MV. RESULTS: The combined HR(2-dose/1-dose) was 0.79 (95% confidence interval: 0.62-1.00) for children receiving no C-OPV-before-enrolment, but 1.39 (0.97-1.99) for those receiving C-OPV-before-enrolment (homogeneity, P = 0.01). C-OPV-before-enrolment had a beneficial effect in the 1-dose group but tended to have a negative effect in the 2-dose group, especially in females. These effects were amplified further by early administration of OPV0. CONCLUSION: In the absence of C-OPVs, an early 2-dose MV strategy had beneficial effects on mortality, but frequent C-OPVs may have benefitted the 1-dose group more than the 2-dose MV group, leading to varying results depending on the intensity of C-OPVs.

Gut Microbiome Diversity and Antimicrobial Resistance After a Single Dose of Oral Azithromycin in Children: A Randomized Placebo-Controlled Trial.

Mass antibiotic distribution to preschool children resulted in alterations of the gut microbiome months after distribution. This individually randomized, placebo-controlled trial evaluated changes in the gut microbiome and resistome in children aged 8 days to 59 months after one dose of oral azithromycin in Burkina Faso. A total of 450 children were randomized in a 1:1 ratio to either placebo or azithromycin. Rectal samples were collected at baseline, 2 weeks, and 6 months after randomization and subjected to DNA deep sequencing. Gut microbiome diversity and normalized antimicrobial resistance determinants for different antibiotic classes were evaluated. Azithromycin decreased gut bacterial diversity (Shannon P < 0.0001; inverse Simpson P < 0.001) 2 weeks after treatment relative to placebo. Concurrently, the normalized abundance of macrolide resistance genetic determinants was 243-fold higher (95% CI: 76-fold to 776-fold, P < 0.0001). These alterations did not persist at 6 months, suggesting that disruptions were transient. Furthermore, we were unable to detect resistance changes in other antibiotic classes, indicating that co-resistance with a single course of azithromycin when treated at the individual level was unlikely.

Opportunities and challenges for decentralised clinical trials in sub-Saharan Africa: a qualitative study.

INTRODUCTION: Digital health has gained traction in research and development, and clinical decision support systems. The COVID-19 pandemic accelerated the adoption of decentralised clinical trials (DCTs) as a mitigation and efficiency improvement strategy. We assessed the opportunities and challenges of a digital transformation in clinical research in sub-Saharan Africa from different stakeholders' perspectives. METHODS: A qualitative study, including 40 in-depth semi structured interviews, was conducted with investigators of three leading research institutions in sub-Saharan Africa and Switzerland, contract research organisations and sponsors managing clinical trials in sub-Saharan Africa. A thematic approach was used for the analysis. RESULTS: Interviewees perceived DCTs as an opportunity for trial efficiency improvement, quality improvement and reducing the burden of people participating in clinical trials. However, to gain and maintain an optimal quality of clinical trials, a transition period is necessary to tackle contextual challenges before DCTs are being implemented. The main challenges are categorised into four themes: (1) usability and practicability of the technology; (2) paradigm shift and trial data quality; (3) ethical and regulatory hurdles and (4) contextual factors (site-specific research environment and sociocultural aspects). CONCLUSION: The transformation from a site to a patient-centric model with an increased responsibility of participants should be context adapted. The transformation requires substantial investment, training of the various stakeholders and an efficient communication. Additionally, commitment of sponsors, investigators, ethics and regulatory authorities and the buy-in of the communities are essential for this change.

Examining African contributions to global health: Reflections on knowledge circulation and innovation.

This article unites different disciplinary debates on 'southern innovation', 'theory from the South', and 'decolonisation of knowledge' in order to discuss existing understandings around the role of Africa in the production of health-related knowledge, public health policy, and medical innovation. Arguing that high-income countries have much to learn from the global South when it comes to health-related knowledge and practices, we propose an interdisciplinary research approach to uncovering and examining African contributions to global health, drawing on an ongoing collaborative project funded by the Swiss National Science Foundation. We present four empirical case studies concerning drug development, healthcare systems, and urban planning to critically enquire into both historical and contemporary transcontinental knowledge circulation and learning potentials, as much as cases of forgetting and silencing. On this basis, we argue that 'learning from the South' must mean more than transplanting quick and cheap technological fixes to serve societies in the global North, but rather recognising the vast contributions that Africans have made to global epistemologies, without losing sight of the asymmetries inherent in South-North knowledge exchanges. Lessons learned might apply to fields other than those discussed here and go far beyond 'reverse innovation'.

Timely completion of childhood vaccination and its predictors in Burkina Faso.

BACKGROUND: Despite important progress in global vaccination coverage, many countries are still facing preventable disease outbreaks. Timely vaccination is important in getting adequate protection against disease. In light of the paucity of relevant literature, this study investigated the timely completion of childhood routine immunization and identified factors associated with timely vaccination in Burkina Faso. METHODS: We extracted data on child vaccination and other child characteristics from a household survey conducted across 24 districts in 2017. We extracted data on health system characteristics from a parallel facility survey. We applied a Kaplan-Meier time-to-event analysis to estimate timely vaccination coverage defined as the proportion of children that received a given vaccine in the period between three days before and 28 days after the recommended age. We used a Cox proportional hazard model with mixed effects to identify factors associated with timely vaccination. RESULTS: In total, 3,138 children aged between 16 and 36 months who could present an immunization booklet were included in the study.The main finding is the existence of an important gap showing that timely vaccination coverage was lower than vaccination coverage. More specifically,this gap ranged from 16% for BCG to 43% for Penta 3. In addition, region and distance between the household and the nearest health facility were the main factors associated with timely full vaccination coverage and specifically for Penta3, MCV1 and MCV2. CONCLUSIONS: This study highlights that timely vaccination coverage remains substantially lower than vaccination coverage. Timeliness of vaccination should therefore be considered as a metric to assess the status of immunization in a country. Geographical accessibility continues to represent a major barrier to timely vaccination, calling for specific interventions on both supply-side (e.g. outreach activities) and demand-side (e.g. vouchers or community-based interventions for vaccination) to counteract its negative effect.

Adverse Events and Clinic Visits following a Single Dose of Oral Azithromycin among Preschool Children: A Randomized Placebo-Controlled Trial.

Biannual mass azithromycin distribution reduces all-cause child mortality in some settings in sub-Saharan Africa; however, adverse events and short-term infectious outcomes following treatment have not been well characterized. Children aged 0-59 months were recruited in Nouna Town, Burkina Faso, and randomized 1:1 to a single directly observed oral 20 mg/kg dose of azithromycin or placebo. At 14 days after treatment, caregivers were interviewed about adverse event symptoms their child experienced since treatment and if they had sought health care for their child. All children had tympanic temperature measured at the 14-day visit. We compared adverse events and clinic visits using logistic regression models between azithromycin- and placebo-controlled children. Of 450 children enrolled, 230 were randomized to azithromycin and 220 to placebo. On average, children were aged 28 months, and 50.9% were female. Caregivers of 20% of children reported that their child experienced at least one adverse event, with no significant difference between study arms (19.9% azithromycin; 20.0% placebo, logistic regression P = 0.96). Vomiting was more often reported by caregivers of azithromycin-treated children than by those of placebo-treated children (7.2% azithromycin, 1.9% placebo, logistic regression P = 0.01). There were no significant differences in other adverse events or clinic visits. Adverse events following a single oral dose of azithromycin in preschool children were rare and mild. Azithromycin administration appears safe in this population.

Neonatal azithromycin administration to prevent infant mortality: study protocol for a randomised controlled trial.

INTRODUCTION: Biannual mass azithromycin distribution to children aged 1-59 months has been shown to reduce all-cause mortality. Children under 28 days of age were not treated in studies evaluating mass azithromycin distribution for child mortality due to concerns related to infantile hypertrophic pyloric stenosis (IHPS). Here, we report the design of a randomised controlled trial to evaluate the efficacy and safety of administration of a single dose of oral azithromycin during the neonatal period. METHODS AND ANALYSIS: The Nouveaux-nés et Azithromycine: une Innovation dans le Traitement des Enfants (NAITRE) study is a double-masked randomised placebo-controlled trial designed to evaluate the efficacy of a single dose of azithromycin (20 mg/kg) for the prevention of child mortality. Newborns (n=21 712) aged 8-27 days weighing at least 2500 g are 1:1 randomised to a single, directly observed, oral dose of azithromycin or matching placebo. Participants are followed weekly for 3 weeks after treatment to screen for adverse events, including IHPS. The primary outcome is all-cause mortality at the 6-month study visit. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Boards at the University of California, San Francisco in San Francisco, USA (Protocol #18-25027) and the Comité National d'Ethique pour la Recherche in Ouagadougou, Burkina Faso (Protocol #2018-10-123). The findings of this trial will be presented at local, regional and international meetings and published in open access peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03682653; Pre-results.

Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial.

Artemisinin resistance is threatening global efforts for malaria control and elimination. Primaquine (PQ) and methylene blue (MB) are gametocytocidal drugs that can be combined with artemisinin-based combination therapy (ACT) to reduce malaria transmission, including resistant strains. Children (6-59 months) with uncomplicated falciparum malaria in Burkina Faso were treated with artesunate-amodiaquine (AS-AQ) and randomized to MB (15 mg/kg/day for 3 days) or PQ (0.25 mg/kg at day 2) with the aim to show non-inferiority of the MB regimen with regard to haematological recovery at day 7 (primary endpoint). MB-AS-AQ could not be shown to be non-inferior to PQ-AS-AQ (mean Hb difference between treatment groups on day 7 was -0.352, 95% CI -0.832-0.128, p = 0.0767), however, haemoglobin recovery following treatment was alike in the two study arms (day 7: mean 0.2±1.4 g/dl vs. 0.5±0.9 g/dl, p = 0.446). Occurrence of adverse events was similar in both groups, except for vomiting, which was more frequent in the MB than in the PQ arm (20/50 vs 7/50, p = 0.003). Adequate clinical and parasitological response was above 95% in both groups, but significantly more asexual parasites were cleared in the MB arm compared to the PQ arm already on day 1 (48/50, 96%, vs 40/50, 80%, p = 0.014). Moreover, P. falciparum gametocyte prevalence and density were lower in the MB arm than in the PQ arm, which reached statistical significance on day 2 (prevalence: 2/50, 4%, vs 15/49, 31%, p<0.001; density: 9.6 vs 41.1/µl, p = 0.024). However, it should be considered that PQ was given only on day 2. MB-ACT appears to be an interesting alternative to PQ-ACT for the treatment of falciparum malaria. While there is a need to further improve MB formulations, MB-ACT may already be considered useful to reduce falciparum malaria transmission intensity, to increase treatment efficacy, and to reduce the risk for resistance development and spread. Trial registration: ClinicalTrials.gov NCT02851108.

No effect of an additional early dose of measles vaccine on hospitalization or mortality in children: A randomized controlled trial.

BACKGROUND: Non-specific effects (NSEs) of vaccines have increasingly gained attention in recent years. Recent studies suggest that live vaccines, such as measles vaccine (MV), have beneficial effects on health, while inactivated vaccines, such as the diphtheria-tetanus-pertussis (DTP) vaccine, may have harmful effects. If this is the case, it should improve child health to move MV closer to the last vaccination with DTP. The objective of this study was to investigate the NSEs of an additional early dose of MV on hospitalization or mortality. METHODS: Children were randomized to receive either the standard MV at 9 months (control) or an additional early dose of MV 4 weeks after the third dose of DTP-containing Pentavalent vaccine and the standard MV at 9 months (intervention). In this analysis of a secondary outcome in the trial, we investigated the effect of the intervention on a composite endpoint of over-night hospitalization with or without recovery, or death without previous hospitalization, in children between 4.5 and 36 months of age in the Nouna HDSS in Burkina Faso. We used Cox proportional hazards regression with repeated events and time since study enrolment as underlying time-scale. RESULTS: Among 2258 children in the intervention and 2238 children in the control group we observed a total of 464 episodes of hospitalization or mortality. There was no difference between intervention and control group (HR = 1.00, 95% Confidence Interval (CI) 0.83-1.20). Results from the per-protocol and intention-to-treat analysis were similar. Although no significant, results suggest a possible beneficial effect of early MV in children that had not been exposed to an OPV campaign after enrolment (HR = 0.83, 95% CI 0.55-1.29). CONCLUSIONS: We did not detect any effect of early MV on subsequent hospitalization or mortality. However, possible effects of early MV could have been obscured by NSEs of the frequent OPV campaigns. Registration: The trial was registered at ClinicalTrials.gov, NCT01644721.

Vaccination coverage and factors associated with adherence to the vaccination schedule in young children of a rural area in Burkina Faso.

BACKGROUND: Vaccination is an important tool for reducing infectious disease morbidity and mortality. In the past, less than 80% of children 12-23 months of age were fully immunized in Burkina Faso. OBJECTIVES: To describe coverage and assess factors associated with adherence to the vaccination schedule in rural area Burkina Faso. METHODS: The study population was extracted from the Nouna Health and Demographic surveillance system cohort. Data from four rounds of interviews conducted between November 2012 and June 2014 were considered. This study included 4016 children aged 12-23 months. We assessed the effects of several background factors, including sex, factors reflecting access to health care (residence, place of birth), and maternal factors (age, education, marital status), on being fully immunized defined as having received Bacillus Calmette-Guérin (BCG), three doses of diphtheria-tetanus-pertussis and oral polio vaccine, and measles vaccine by 12 months of age. The associations were studied using binomial regression to derive prevalence ratios (PRs) in univariate and multivariate regression models. RESULTS: The full vaccination coverage increased significantly over time (72% in 2012, 79% in 2013, and 81% in 2014, p = 0.003), and the coverage was significantly lower in urban than in rural areas (PR 0.84; 0.80-0.89). Vaccination coverage was neither influenced by sex nor influenced by place of birth or by maternal factors. CONCLUSION: The study documented a further improvement in full vaccination coverage in Burkina Faso in recent years and better vaccination coverage in rural than in urban areas. The organization of healthcare systems with systematic outreach activities in the rural areas may explain the difference between rural and urban areas.

Trends and risk factors for childhood diarrhea in sub-Saharan countries (1990-2013): assessing the neighborhood inequalities.

BACKGROUND: Diarrheal diseases are a major cause of child mortality and one of the main causes of medical consultation for children in sub-Saharan countries. This paper attempts to determine the risk factors and neighborhood inequalities of diarrheal morbidity among under-5 children in selected countries in sub-Saharan Africa over the period 1990-2013. DESIGN: Data used come from the Demographic and Health Survey (DHS) waves conducted in Burkina Faso (1992-93, 1998-99, 2003, and 2010), Mali (1995, 2001, 2016, and 2012), Nigeria (1990, 1999, 2003, 2008, and 2013), and Niger (1992, 1998, 2006, and 2012). Bivariate analysis was performed to assess the association between the dependent variable and each of the independent variables. Multilevel logistic regression modelling was used to determine the fixed and random effects of the risk factors associated with diarrheal morbidity. RESULTS: The findings showed that the proportion of diarrheal morbidity among under-5 children varied considerably across the cohorts of birth from 10 to 35%. There were large variations in the proportion of diarrheal morbidity across countries. The proportions of diarrheal morbidity were higher in Niger compared with Burkina Faso, Mali, and Nigeria. The risk factors of diarrheal morbidity varied from one country to another, but the main factors included the child's age, size of the child at birth, the quality of the main floor material, mother's education and her occupation, type of toilet, and place of residence. The analysis shows an increasing trend of diarrheal inequalities according to DHS rounds. In Burkina Faso, the value of the intraclass correlation coefficient (ICC) was 0.04 for 1993 DHS and 0.09 in 2010 DHS; in Mali, the ICC increased from 0.04 in 1995 to 0.16 in 2012; in Nigeria, the ICC increased from 0.13 in 1990 to 0.19 in 2013; and in Niger, the ICC increased from 0.07 in 1992 to 0.11 in 2012. CONCLUSIONS: This suggests the need to fight against diarrheal diseases on both the local and community levels across villages.

The non-specific effects of vaccines and other childhood interventions: the contribution of INDEPTH Health and Demographic Surveillance Systems.

Most childhood interventions (vaccines, micronutrients) in low-income countries are justified by their assumed effect on child survival. However, usually the interventions have only been studied with respect to their disease/deficiency-specific effects and not for their overall effects on morbidity and mortality. In many situations, the population-based effects have been very different from the anticipated effects; for example, the measles-preventive high-titre measles vaccine was associated with 2-fold increased female mortality; BCG reduces neonatal mortality although children do not die of tuberculosis in the neonatal period; vitamin A may be associated with increased or reduced child mortality in different situations; effects of interventions may differ for boys and girls. The reasons for these and other contrasts between expectations and observations are likely to be that the immune system learns more than specific prevention from an intervention; such training may enhance or reduce susceptibility to unrelated infections. INDEPTH member centres have been in an ideal position to document such additional non-specific effects of interventions because they follow the total population long term. It is proposed that more INDEPTH member centres extend their routine data collection platform to better measure the use and effects of childhood interventions. In a longer perspective, INDEPTH may come to play a stronger role in defining health research issues of relevance to low-income countries.