Flow diagram.

<p>Flow diagram.</p

Coverage of SMC defined as the proportion of children who received all three days of SMC treatment according to the method of delivery (door to door versus fixed point) in 2014.

<p>Coverage of SMC defined as the proportion of children who received all three days of SMC treatment according to the method of delivery (door to door versus fixed point) in 2014.</p

Proportions of children who did not receive any round of SMC, who received at least one round, and who received at least two rounds, according to the method of delivery (door to door versus fixed point).

<p>Proportions of children who did not receive any round of SMC, who received at least one round, and who received at least two rounds, according to the method of delivery (door to door versus fixed point).</p

Coverage of SMC defined as the proportion of children who received all three days SMC treatments according to the method of observation of the treatment, directly observed treatment versus not directly observed treatment.

<p>Coverage of SMC defined as the proportion of children who received all three days SMC treatments according to the method of observation of the treatment, directly observed treatment versus not directly observed treatment.</p

Proportions of children who received none, at least one, or at least two rounds of SMC according to the method of observation of the treatment (directly observed treatment versus not directly observed treatment).

<p>Proportions of children who received none, at least one, or at least two rounds of SMC according to the method of observation of the treatment (directly observed treatment versus not directly observed treatment).</p

Mother's opinion on SMC according to the method of delivery (door to door versus fixed point) and the method of observation of the treatment (directly observed treatment versus not directly observed treatment).

<p>Mother's opinion on SMC according to the method of delivery (door to door versus fixed point) and the method of observation of the treatment (directly observed treatment versus not directly observed treatment).</p

Table_1_Pregnancy outcomes in a malaria-exposed Malian cohort of women of child-bearing age.pdf

In Sub-Saharan Africa, malaria continues to be associated with adverse pregnancy outcomes including stillbirth, early neonatal death, preterm delivery, and low birth weight. Current preventive measures are insufficient and new interventions are urgently needed. However, before such interventions can be tested in pregnant women, background information on pregnancy outcomes in this target population must be collected. We conducted an observational study in Ouélessébougou, Mali, a malaria-endemic area where first antenatal visit commonly occurs during the second trimester of pregnancy, hindering calculation of miscarriage rate in the population. To accurately determine the rate of miscarriage, 799 non-pregnant women of child-bearing age were enrolled and surveyed via monthly follow up visits that included pregnancy tests. Out of 505 women that completed the study, 364 became pregnant and 358 pregnancies were analyzed: 43 (12%) resulted in miscarriage, 28 (65.1%) occurred during the first trimester of pregnancy. We also determined rates of stillbirth, neonatal death, preterm delivery, and small for gestational age. The results showed high rate of miscarriage during the first trimester and established a basis to evaluate new interventions to prevent pregnancy malaria. This survey design enabled identification of first trimester miscarriages that are often missed by studies conducted in antenatal clinics.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT0297 4608].</p

Table_1_Acquisition of antibodies that block Plasmodium falciparum adhesion to placental receptor chondroitin sulfate A with increasing gravidity in Malian women.docx

In malaria-endemic areas, pregnant women are more susceptible to Plasmodium falciparum infection, especially primigravidae. During pregnancy, parasites sequester in the placenta and bind to the receptor chondroitin sulfate (CSA). This unique adhesion is mediated by the parasite protein VAR2CSA expressed on the surface of infected erythrocytes (IE). Placental malaria is associated with poor pregnancy outcomes including perinatal mortality, preterm delivery, small for gestational age (SGA) and low birthweight deliveries. Over successive pregnancies, women acquire functional antibodies that inhibit IE adhesion to CSA. Here, we examine the development of anti-adhesion activity and the breadth of anti-adhesion activity as a function of number of previous pregnancies, using samples collected from pregnant women living in an area with high seasonal malaria transmission. Women reached plateau levels of anti-adhesion activity and breadth of anti-adhesion activity after 5 pregnancies. We related the level of anti-adhesion activity and reactivity with surface IE to SGA 19/232 pregnancies resulted in SGA, and report that an increase of 10% in median anti-adhesion activity reduced the odds of SGA by 13% and this relationship approached significance. Further, at an anti-adhesion activity level of 43.7%, an increase of 10% in the breadth of activity significantly reduced the odds of SGA by 21.5%. Antibodies that recognize IE surface increased over successive pregnancies, but were not associated with a reduction in SGA. These results can serve as a guideline for assessing vaccine candidates aiming to reduce poor pregnancy outcomes associated with placental malaria.</p

Additional file 1 of The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01E vaccination and seasonal malaria chemoprevention versus either intervention given alone

Additional file 1: Table S1. Number of clinical malaria episodes by time since vaccination in each year of the study, using 90-day periods (as used in the Piecewise Cox regression models). Table S2. Number of clinical malaria episodes by time since vaccination in each year of the study, using 60-day periods (not used in the Piecewise Cox regression models, but provided to show the declining incidence of malaria further into the dry season). Table S3. Number and percentage of children who were scheduled to receive SMC, received SMC, and received all daily SMC doses (full SMC) over the course of the study. Figure S1. Observed hazard function and Cumulative hazard function, and the fitted cumulative hazard and estimated protective efficacy from flexible parametric survival models used to estimate vaccine efficacy in each year of the study. Figure S2. Protective Efficacy of SMC in the first 21 days and first 30 days after SMC received, by cycle. Figure S3. Protective Efficacy by time since the final SMC cycle in each year. Figure S4. Comparison of the SMC protective efficacy profile obtained in this study with the profile estimated for an earlier placebo-controlled trial of SMC