 Okay, so next we have Issa Sigourneke, who is going to be, well, it's a bit of a link between this session and the session before, so she's going to be talking about malaria treatment, well, during the Ebola outbreak. Thank you. Thank you very much, and thank you very much for giving me opportunity to talk to you. I would like to share with you some interesting and unexpected findings from one of our Ebola centers that MSF managed in Liberia. So despite this being the largest ever Ebola outbreak and lasting now for more than 15 months, we still have absolutely no evidence that any of the therapeutic interventions we are using makes any difference on patients' mortality. The treatment we are using today is still symptomatic and partially presumptive, so part of this presumptive treatment is also systematic use of anti-malarial treatment that is either given systematically to all the patients at admission or based on the positive results of malaria rapid test. In MSF, we prefer the first option, so to give anti-malarial systematically to all the patients at admission, also with the intention to prevent malaria during the stay in the Ebola center. In MSF, the first choice, the preferred choice, is the combination of Artemitur and Rumofantrin. So the data I'm presenting is coming from Foya in Liberia. As you can see in the map up, the Foya is a town in northern Liberia bordering Guinea, and in fact it's just across the river from Gakedo where the outbreak first started. The outbreak in Foya started, the first cases were reported in March and April, and then after a little break, the epidemic really started in June 2014, and then the number of cases very rapidly increased in August. On the right side, you see the treatment center. Further, there was just an isolation unit in the big building in the middle that was a former refugee transit unit that was set up to manage 10 to 20 patients, and then when the number of cases inside the center increased to more than 100, the center kind of mushroomed in a chaotic way around this original center. So during this very busy time of very fast increase of new admitted cases, the team experienced a shortage of first-line anti-malarial treatment. So during this time, the first-line treatment Artemitur Rumofantrin was replaced by another commonly used combination, Artisan Atamodayakin, for a period of 12 days. Artisan Atamodayakin is also the first-line treatment in all three affected countries, including Liberia. It has been shown previously that Amodayakin has some in vitro activity against the Ebola virus. And on the left side, there's a picture that's a border crossing between Guinea and Liberia, and the team in Foya was, for most of the time, supplied from Gakedo through this way, and also the blood sample. There was a laboratory that was based in Gakedo, so the blood samples traveled every day across the river to them. So that's just another epidemiological curve showing you the confirmed and the number of new admitted patients per day. The confirmed cases are in red, and the patients that show not to be Ebola cases in green. And in the shaded area, you have the period of time where the only Artisan Atamodayakin combination was used due to the shortage. So we use this unfortunate opportunity of drug shortage to explore whether there is a difference in mortality between the patients that systematically received either Artemitur Lumifantrin or Artisan Atamodayakin. For this, we use the standardized line-listing, line-list data of the patients, very similar to what Francesco used to combine the analysis. But our data also included in this simple epidemiological line list, there was also the epidemiologist took time to also enter what type of treatment was prescribed. So that's just what the information we have, it's only about the treatment prescribed to the patients then. So if we look at the patient characteristics of the patients receiving either of anti-malaria combinations or those who were not prescribed any anti-malaria treatment were very similar in their baseline characteristics. However, the patients in the group of Artisan Atamodayakin and those that were not prescribed any anti-malaria treatment had a slightly lower CT value at admission, so that means higher viralated admission. And in particular patients in the Artisan Atamodayakin group, they were admitted during the particularly busy period, so there were an average 100 patients admitted in the center during that time compared to around 50 in the other two groups. And then we also, the last important differences in cases coming per unique home village in particular groups. So in fact, we tried to look, if there is a difference in mortality, because it could also be linked to the fact that a lot of patients would be coming from the same big families and there'd be genetically maybe a bit different and have different risk of dying. And we see that the patients in Artemata Lumafantrin group were more likely to come from the same village compared to the other two groups. The patients that were prescribed Artemata Lumafantrin had an overall mortality of 65%, very similar to those patients that were not prescribed any anti-malarial treatment. Our patients in the Artisan Atamodayakin group had 50% mortality. The risk ratio of dying for patients that prescribed Atamodayakin Artisan at compared to the Artemata Lumafantrin was 21% lower. In unadjusted analysis, and then 31% lower in adjusted analysis. So in adjusted analysis, we looked for different risk factors that were associated with mortality. So very similar to the previous analysis, those patients that were older had a higher risk of dying. And particularly the strongest predictor of that is the cycle threshold at admission. We also looked at the patients that were receiving or were prescribed IV fluids. And those had a higher risk of dying. That is probably just a proxy indicator for those patients that were more severely sick. That's why they were prescribed the treatment. And then the number of patients that were present at the day the person, the patient was admitted as a little bit of a proxy of quality of care that was provided. So patients that were admitted at the busiest time were also more likely to die. Then we did some sub-analysis. We thought maybe this effect that we are seeing of Artisan Atamodayakin on mortality, it might be just due to the patients having malaria and they have higher chances because we treat their malaria. However, when we look at the subgroup of patients that had RDT positive, so the rapid test confirmed malaria, this effect of there's no more difference between patients receiving either anti-malarial treatment. However, the effect is stronger in the patients that had no, that didn't have malaria at admission. We also looked at the patients that had a higher or lower viral load at admission because that's been a little bit directed in other treatment studies ongoing. So patients that had a lower viral load at admissions of higher CT values, the effect was of Amodiyakin Artisan Atamodayakin was much stronger compared to the patients that arrived with the high viral load at admission. So what we show in our analysis and what we observed in our group of patients, those patients that were prescribed Amodiyakin Artisan Atamodayakin had the higher chances of surviving. This study has many big limitations, first of all is observation and study. The only data we have is the data on what was prescribed, we have no idea which patients actually took treatment or not. So this is both anti-malarial treatment that were prescribed, our oral medications of the patients that are already sick and have nausea and vomiting might have difficulties taking the treatment and in the particular Amodiyakin is associated or is perceived to be associated with more side effects like nausea and vomiting. So it might be even more likely that patients prescribed Artisan Atamodiyakin didn't take it. The quality of data we have, it's limited by the conditions in the field so it was collected at a very busy times and we have a number of patients that were not prescribed any anti-malarial treatment and they were actually not really able to explain why this happened. For some patients probably because they had negative results and the team decided not to give treatment or because they were rationing Arthymeter lumifantrin doses when the shortage was foreseen. There might be other confounding factors that we did not think about and we could not control for and it's the sample size, the number of patients we had was rather small. There is alternative hypothesis to Amodiyakin having a positive effect on the survival is that the combination of Arthymeter lumifantrin might be harmful for the Ebola infected patients. There is some rationale on it because lumifantrin is a drug slightly similar to the Halofantrin that has been very much associated with the sudden deaths linked with the QT prolongation that might be more especially in patients that have hypokalemia or hypoknesemia which can be the case potentially in the Ebola affected patients so there might be a link to that as well. So what you do with this information so within the discussions we had within MSF and with the malaria working group is that it might be wise to change the first line anti-malarial treatment at least for our patients since the both drugs are similarly effective and it seems that there might be potential benefit of the combination of Arthymeter and Amodiyakin. We absolutely need more data to confirm this findings and to try to understand how the drug if at all works how this could be done so I think the first thing would be to look at any possible data that exists on the use of Arthymeter and Amodiyakin in those countries. Unfortunately it seems that majority of the centers not just MSF but also all the other centers prefer to use the combination of Arthymeter lumifantrin or just injectable Arthymeter and the other option might be to try to see something into this mass distribution of anti-malarias that were described earlier and then in parallel there should be pre-clinical studies both in vitro and animals to confirm the mechanism of action and to try to see if the drugs actually works and how would that happen and this is planned and we'll hopefully start seeing them. So I would like to thank everyone in the field for collecting the data the Ministry of Health to all the people to contribute it to discussions and brainstorming around this analysis and to all the patients and population in FOIA. Thank you very much. Thank you, Isis. So I think we have time for a couple of very quick questions. We don't really have time but we're going to have. At the back there. Or at the side. Thanks. Is that the alasri from MSF? Thank you for the presentation. Do you know if the drugs were given to the patients for them to take or if they were given on a daily basis? In some of the centres the bag was just given to the patient upon arrival. Yeah so they hear the for the it might have changed at the very end where the numbers went down but for the most of the time the treatment the presumptive systematic treatment was prescribed added mission and the treatment was pre-packaged for patients and it was up to them to take it so we have absolutely no idea if they actually took the treatment or not. Any others? If not we'll thank Isis again for a fascinating trip.