 Thank you for giving me the opportunity to speak on a prospective case control study we conducted in Magaria, Niger to estimate the protective efficacy of SMC. First I would like to remind that SMC is a preventive measure against malaria targeting children aged 3 to 59 months with the highest risk of malaria. A three-day course of medicine is given once a month for up to four months during the high transmission rainy season. On the first day children receive a dose of sulfadoxin, pyrimetamin and amodiacin. And then subsequent dose of amodiacin on the next two days. Since 2012 the WHO recommended SMC as it was shown to reduce malaria incidence by 75% in a series of trial. SMC is recommended in the area in dark orange on this map where malaria transmission is highly seasonal with short rainy season compared to the blue zone where the transmission season is longer. In cooperation with the Ministry of Public Health of Niger MSF started implementing SMC in 2013 in Magaria that you can see in the red spot on the map. Between 2013 and 2016 on average more than 110,000 children aged 3 to 59 months received SMC each month between July and October that's the high transmission season. However in 2014 and 2015 despite a large-scale investment in the implementation program the result expected in terms of reduction of hospitalization and consultation have not been observed. The number of cases treated for malaria both in hospital and outpatient department has increased. Surveillance data suggested potential problem with the protective effectiveness and low protection beyond three weeks. What would explain this bad result? Many hypotheses were then suggested increase incoming patients from non-covered areas or poor adherence of patients to the SMC or a particular severe transmission of malaria. Another hypothesis was a potential reduction in the protective efficacy of SMC drugs due to parasites, resistance or tests related factors such as malnutrition. In terms of delivery strategy MSF used two strategies in 2016 in the dot zone that's the dot strategy the dose of SP that's sulfadoxine and first dose of amodeicine was directly observed the non-dot strategy were simpler that's just the caregiver received entire SPRQ that's sulfadoxine and amodeicine blister pack and the first day doses were not directly observed. During the 2016 season we initiated a case control study to estimate the protective effectiveness of SMC against developing clinical malaria in dots that's the direct observed treatment and the non-dot strategy zone. In each strategy zone we created case at one health center and two health posts in Magaria Health District. For each case we created there were three community controls matched by age, village of origin and date. We defined a case as any child age three to 59 months with fever and a history of fever in the previous 24 hours and a positive malaria rapid diagnosis test. The control with children with without fever or a history of fever in the 24 hours preceding the recruitment. All children with fever but with a negative malaria test. We asked caregivers about SMC received or collected and collected blood capillary blood sample for tick and ting, smear and some blood to estimate plasma level of desertile amodeicine which I will discuss the use later. We conducted univariate and multivariate comparison between case and controls by conditional logistic regression. We then estimate the relative risk of developing malaria from the odd ratio obtained. To gather objective information about adherence we had to describe the pharmacokinetics of amodeicine in this population in ideal condition. We conducted a sub-study on 165 children to whom we gave all three doses of amodeicine at home directly observed under ideal condition. Our goal was to construct a typical curve of the elimination of desertile amodeicine which is an active metabolite of amodeicine in the setting of SMC. To do that we collected blood samples in these children at specific time over six weeks following the administration of amodeicine. Once the pharmacokinetics curve was constructed we compare it with the sample taken in the main case control study. The SS and modeling were done by Joel Towning Group in Bangkok. Now let's look at the results. The graph on the left show the weekly recruitment rates of participants since the beginning of the study. The study period was between August 1st and December 2nd 2016. The map on the right show the village of origin of case and the area above is the dot zone and the area below is the non dots. The boundary line is the border with Nigeria. Here's the baseline description of the study participants. In the dot zone control were more likely to have received SMC both for children who had a program card and also those self-reporting received of SMC. Case were more likely to be enrolled in a nutritional program. Reported bed nets usage was high in both groups otherwise both cases and control were typical for the region and in the not dot zone control were also more likely to have received SMC but the difference was smaller than in the dot zone otherwise the children were largely similar to the children enrolled in the dot zone. Here are the main results of the study. In the whole study area if we only consider children who have a card proving that they received SMC regardless of the strategy the protective effectiveness was 85 percent which is really good but when we add in the children who didn't have a card but reported to have received SMC the effectiveness dropped to 50 percent. This raised concern as to whether children caregivers who self-reported received of SMC were actually telling the truth. Now comparing the dot zone to the non dot zone there were some highly significant differences when we look at card proving received of SMC. The effectiveness of SMC in the dot zone was 97 percent while in the non dot zone it was only 60 percent. Now when we add in the children who self-reported received of SMC in the dot zone the effectiveness remains very high 89 percent but in the non dot zone it drops to 21 percent with confidence interval that crosses the non value. Importantly there were no significant difference by age six and nutritional status. In general this result proved that SMC works at least when we directly observed the dose of sp that's suffodoxy and the first dose of amodiac in. At the same time they raise questions with adherence or subsequent days at home. So to know whether children that take SMC like to know whether children take SMC like they were supposed to here are the results of the pharmacokinetic sub study. We fitted a pharmacokinetic model for amodiac in on top and digital amodiac in on the bottom. You can see that if children receive SMC with all three doses observed they all have a detectable level of digital amodiac in in the blood even at six weeks after the first dose. But in the case control study in both the dot zone and the non dot zone alike over 80 percent of children who reported correct adherence at home had digital amodiac in level below the fifth percentile on the population pharmacokinetics curve for the given day since taking SMC. That means they are below the lowest gray shaded area on the bottom figure. This result clearly clearly indicate that many children were not taking their medicine as they should or as they reported. To conclude the protective effectiveness of SMC was acceptable and better when first dose is directly observed. Future campaign should therefore use a dot strategy for the first dose. But our result also suggested problem with correct correct adherence to a three day course of amodiac in at home. The obvious question is then whether the effectiveness of SMC that we observed is due to SP alone. That's the paradox in alone. Finally I would like to mention that medicine son frontier led the way with implementing SMC in Niger and now and has now largely handed off to other partners. But the fact that new implementers are in place means there may be there may well be new challenges and that MSF will continue to be on the front line for curative care if SMC does not work well. We wish to express our sincere appreciation to all partners in this study especially the staff of Magaria Health District and the MSF Operational Center of Geneva. Thank you very much for your attention.