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Additional file 1. Interview guide for clinical trial experts

Additional file 1: Table S1. Determinants of the frequency of the K1 allelic family.

Additional file 2: Table S1. Hemoglobin g/dl measured among participants in therapeutic efficacy monitoring, 2017-2018, Burkina Faso

Additional file 1: Figure S1. The Nanoro health district is divided to four regions; north, east, south and west of lake. Figure S2. Hazard ratios associated with the probability of mortality of children under-­5. Risk factors reducing the probability of death have hazard ratios lower than 1 to the left of the vertical dashed line. Hazard ratios (yellow points), 95% confidence intervals (horizontal lines) and the p values are given. The variables with the yellow points on the vertical dashed line represent the reference groups. Figure S3. Mortality per 1000 live births per village for children under­-5. Each circle represents a village and the size of circle represents the number of live births. The lighter color indicates lower mortality rate and darker color indicates a higher mortality rate. Figure S4. Travel time of children under-­5, living in the Nanoro health district, from an inpatient health facility. Each circle represents an individual. Figure S5. Mortality per 1,000 live births for children under­-5 versus subgroups of distance, travel time and walking travel time to inpatient health facilities. Circle size represents the number of births within each subgroup. Figure S6. Mortality per 1,000 live births for children under­-5 versus subgroups of distance, travel time and walking travel time to outpatient health facilities.Circle size represents the number of births within each subgroup. Figure S7. Mortality per 1000 live births for each event month. Figure S8. Mortality count by age group. Figure S9. In-­ and out-­migration count by month. Table S1. Results of unadjusted Cox regression models for under­5 mortality. Hazard Ratios are presented with 95% confidence intervals in parentheses. Table S2. Results of unadjusted cox regression models for under­-5 mortality per 1000 live births. Each risk factor was fitted to the model as a continuous variable. Hazard Ratios are presented with 95% confidence intervals in parentheses.

Additional file 2: Table S2. Determinants of the frequency of the MAD20 allelic family.

Additional file 1: Supplemental Table 1. Agreement and reliability of fetal biometrics z scores using Intergrowth 21st and Salomon equations.

Standard operating procedures (PREGACT study) for obstetric ultrasound for the assessment of embryos and foetuses during pregnancy. (PDF 165 kb)

Standard operating procedures (PREGACT study) for obstetric ultrasound for the assessment of embryos and foetuses during pregnancy. (PDF 165 kb)

The RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection. We assessed the association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine effi cacy using data from a phase 3 trial done between 2009 and 2014. Using data from 8922 African children aged 5 1317 months and 6537 African infants aged 6 1312 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time. RTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5 1317 months than in those aged 6 1312 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6 1312 weeks and higher immunogenicity in those aged 5 1317 months. The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres wane according to a biphasic exponential distribution. In participants aged 5 1317 months, the half-life of the shortlived component of the antibody response was 45 days (95% credible interval 42 1348) and that of the long-lived component was 591 days (557 13632). After primary vaccination 12% (11 1313) of the response was estimated to be longlived, rising to 30% (28 1332%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98 13153) was estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of effi cacy against clinical malaria across diff erent age categories and transmission intensities, and effi cacy wanes more rapidly at higher transmission intensity Anti-circumsporozoite antibody titres are a surrogate of protection for the magnitude and duration of RTS,S/AS01 effi cacy, with or without a booster dose, providing a valuable surrogate of eff ectiveness for new RTS,S formulations in the age groups considered.

Figure S1. Scatter of the IC50 values with geometric mean and the resistance cutoff (where available) of each drug. In order to better visualize and understand the data, a figure showing the scatter of the IC50 values with geometric mean and the resistance cutoff (where available) of each drug is proposed.

Ultrasound Reference Manual for Pregnancy Dating. (PDF 3017 kb)

Newborn Examination. (PDF 1203 kb)

Additional file 1: Table S1. Risk factors for reinfection: multivariable analysis with pfcrt 76T. Data from AS-AQ and AL trial arms were analyzed separately using accelerated failure-time analysis. Regression coefficients are the ratio of time to reinfection, such that a coefficient > 1 indicates a longer time to reinfection. Covariates significantly associated with reinfection time after adjusting for EIR (Table 3, main text) were included in the final model. The prevalence of pfmdr1 86Y also had a significant effect in a multivariable model with the same covariates (Table 3, main text) but could not be included in the same model with pfcrt 76T due to strong correlation between the two variables. Models assume a log-normal time to reinfection and random site effects.