 Maen nhw ychydig hwn yn ysgrifennu gyda'r thysgu pethau ffordd ac yn ysgrifennu meddwl. Mae Merit Ydw i'w rhag hold yna sefydliadau i Gymru, ac maen nhw'n arnyn nhw'n lu'r chances yng nghymru yma, ac rydyn ni'n fynd eu cyfaint! Yn y tro. Yn y tro, yma'n ddylch yn ymryd, yma'n dweud. Felly mae'r cyntaf ar y morbylch yn dechrau. Mae'r cyntaf yn ymryd i'r cyfrannu a wrthi'n ddweud i'r cyfrannu, a wnaeth i chi'n cyfrannu i rai, a'r cyfrannu i'r cyfrannu i'r cyfrannu a wnaeth i chi'n rai i chi'n cyfrannu i'r cyfrannu, ac rwy'n rai i chi wnaeth i chi'n dweud i chi. Rwy'n ddim o'n fawr yn ni'n cymhwyl o'r context, y Dynodraeth Cymru yn Congo yn ffraeg, a mae'n ddwyliadol iaith o'r wych a'r llwyddaeth, fe ddweud o'r llawnod o'r cyllid arall ar gyfer y dynodraeth. Yn 2014, y UnDP wedi'u bwysig ddwyliadau 186 ystod y 187 ydydd yng Nghymru, ac mae'n gael yn ymdweud 5 amlant ac yn ddynodraeth ar gyfer y blawn. Fel hollwch am ti wedi gweld sy'n mylciaith, a fyddwn y gallwn wath o'n gyphr fan hyn y rhannu yma, ond, o'n ddweud o'n meddwl, rydych gyda'r fath. Mae llyfrderau hefyd yn gywir cyfan gyhoedd cyflodiadau a'n amlwg a'r maesig, ac yn enw'r gwybod yr hybl ei vaid allunfa wedi eu ml funnigu. Mae'r gynhygr angen i fod yn ei bod yn gweithio yn mylciaith lleol ac mae'n gwybod yn hwnnw'n ddiddordeb i'ch cyfranyddio'n cael cyfrannu. Mae gennymau cyfnodd yn cyfreidio esgolwyr yn blaenwyr hose Gennymgyrch Gwyl版anol Ac mae gennymau hi'n cwestiynau ar gyfer gweithio ar gyfer gyd i gyfrifiadol Ac mae gennymau unig o weithio ar hyn o'r gyfrifiadol Cymru, oedd L-L-I-N yn cynhyrchu mewn gwirio. Mae'n cyfrifio yr scent ar gyfer hwnnw o'r llef hefyd eich gwasanaeth Gymru. Rwy'n meddwl'm gennym, ac os yw'n meddwl gyfer gorau maelidol yn gefnogaeth, yn y nifer o'r paено, yn rôl mwy o'r cyflodau a'r rôl yn gweithgaf. Yn ymgyrch hyn mae'r reilu, gyda'r 2009, mae'r rôl yn gyflod sydd yn rai cyflodau yn y mhleriaid, yn y pryd yn gweithgaf spaces yng Nghymru. Dyma'r graff hon yn yma yma yno, yma'r rôl yn gwneudio'r bydd ganddaeth o feddyliau cerddorol. gwahanol ar gyfnod ymwylo ac yn cyd-ddangos i gyllidau cymryd â'r gwahod. Mae'r graf ei ddaith yn cael ei bod ni ei ddweud o gwahanol cyharol ar gyfer cyfanyl. Rydyn ni'n ddweud yr arblwyd mewn gwahanol a'r gwahanol ar gyfer cyfynod ac yn gweithio yr arglwyd. Er我 am y gweithio'r gweithio, ar gyfer gyaf yw gwahanol a chyd-dai'i gwahanol. A�w'n yn gyfynod o ei ymwneud mwyn roedd ei gweithio'r gwahanol amdano. Felly, we sat together with a group of people and actually looked at what we could look at in our settings. So, we came up with four studies that we hoped would give us an answer to why this rise was happening. One of the question was, is there any changes in the adherence to the drugs that we give to people? So, the ACT combination that we give in Congo is, artistinate, I'm a diaquin or abbreviated as Azach. And would there be any change if people don't take their drugs that might cause a rise in malaria cases? The other thing that we wanted to look at is the actual drug that we're giving. Is that still an effective drug? So, is Azach actually effective? And then we said, well, if it isn't, what are we going to propose as an alternative to the government? So, we therefore also looked at another drug that is commonly used, which is Arthymeter lumifantrin, or most of you know it as coartin. The next thing we thought we were going to look at is see what the knowledge and attitude of people in the region is to the bed nets. Do they know what is causing malaria? Do they associate malaria with mosquitoes? Do they use the nets? Do they use them well? How old are the nets, et cetera? And the fourth and last one was something, a very new enterprise for all of us in MSF, was actually looking at the mosquito. What are the mosquitoes that are flying around? Have they changed their behaviour? Are they getting resistant to the insecticides that are on the net? So, I'm privileged to present the results of all four of these studies, of which I'm only the principal investigator of one of them. So, the first study we've done, and this is a credit goes to Ruby Sudiki from the Manson Unit, who was the PI of this study. She has looked at adherence in Katanga. There was ERB approval given by MSF, an agreement from the Ministry of Health. So, the objective of the study was to measure the adherence to first line treatment. And what we did in the Katanga clinic was, first of all, systematic sampling of people who were diagnosed with uncomplicated malaria and who actually were given a three-day treatment. And the team after systematic sampling visited the families in their homes on the next day. So, if you count the first dose that was given in the clinic as day zero, then day one and two were taken at home, and then on day three the team would visit the people in their home. And this was adults and children alike. They asked for consent when they actually knocked on the door and said, can we ask you certain questions? And they asked people questions about the malaria drugs that they got, and they asked to see the blister in which the tablet should have been. Then there were certain categories that you could fall into certain categories. There were certain non-adherent people that were people who could show you the blister with tablets left in there. Like we knew for sure they would not have taken them correctly or not have finished the course. Then there were people who either could not show the blister or who actually shown an empty blister, but then had a story of saying, I gave one to my first kid, one to my second kid and one to the third. And then we suspected they were not very adherent. Then there were people who had a good story and had shown either showed as an empty blister or could not show the blister, but we had really good reasons to believe they were adherent. Now if you look at the results, so there's 108 people that we ended up visiting, and so certain non-adherent was six of them, probably not adherent 35 and probably adherent 67. If you take the probably non-adherent to be non-adherent, this is the result that we came up with. So 62% of the people that we visited were adherent to the treatment or probably adherent, and that is very much alike any survey we've done previously in other countries. We did it for example in Sierra Leone in Central African Republic, and it's very alike what we do in the Western world for antibiotics if you ask people if they've finished their course. So we have no reasons to believe that this could have a relation with the rise of malaria. If you take this study a bit further and you exclude people who have vomited or sped out the pills, the actual adherence is a bit lower, but also in line with results from other studies we have. The reasons for adherent behaviour was mostly that correct instructions were given. Most common reasons for non-adherence were that people vomited or felled and well, which is a very common side effect from our artist named Amadeya Quinn, and perhaps the poor understanding of it. This part is a bit tricky because some people gave answers not matching like if they were non-adherent they gave reasons why they were adherent, so that was a bit difficult to assess. So the second study of which I was a PI, what we did is we looked at the efficacy of the Artemisinin Amadeya Quinn and compared that to Coartim. The inclusion criteria for this study were any children between half a year and five years, so children under five years of age, who were diagnosed with uncomplicated malaria without any other infection, so without co-infection. And also people who had not taken an antimalarial drug in the past 28 days. What you see is that we assessed 873 children and we excluded 585. In order to get to our required sample size we needed 144 kids in both arms, accounting for loss to follow-up and withdrawals. The reasons for this huge number to be excluded was actually mostly that people had taken an ACT combination from a pharmacy, a local pharmacy or anything in the previous 28 days, and the other reason were co-infections. So a lot of these kids came with malaria but actually had a co-infection. So what were the results of the study and I'm not sure if everybody is familiar with reading these graphs. But what you can see here is timeline as it goes past and this is actually percentage or the proportion. So the blue line here is the children with Azach and the other one is the children with Coartim. And what you can see that in the first like 2021 days, the first three weeks, both treatments work really, really well. And then you can see a drop. That means that children who were followed up, we followed them up weekly and assessed there, we did a slide to see if they had parasites. You can see that children start having failures. That means that they start having parasites in their blood. Either they were sick with malaria or they didn't feel anything but they had parasites on the slides. And you can see this proportion increase over time. We followed them up for 42 days so six weeks. Now this could mean two things. Either people get reinfected. They live in a highly endemic malaria setting so they could be well treated. And then a couple of weeks later they could be reinfected with malaria. They could be stung again and get malaria again. Or it could be and that was actually what we were looking for. It could be that the drugs didn't work. That they killed some of the parasites but not all and they would come back. So what we did, all these kids, we had dried blood spot samples for them. We analysed them in the lab in Amsterdam and we looked whether it was a reinfection or a recredescent. And it appeared that only seven children of the 288 children had a recredescent. So the vast majority were actually reinfections. And only seven children, one in the AL group and one in the 600 group had a recredescent. The difference here is not significant. And it actually gets down to an efficacy of the treatment of 95% for Azach and 99% for Coartum. Both which are very good. Interesting are, so both of them are effective. If intake is taken correct we did observed in intake of the drugs so we are sure that that is not a bias. But the high rate of reinfection, in fact overall 13% of the children got reinfected within six weeks. But in the peak season from October to December 30% of the children got a new malaria infection within six weeks. So you treat them and six weeks later a third still has a new infection. And it was an incredibly high rate of co-infections which I think is no surprise to people working but it was surprised to see it like this. The third study we did to look at the rides was a cap survey done by Ruby Siddiqui again as principal investigator. So we did this in all three provinces where we worked and the objective was to see what the knowledge and attitude towards insecticide treated nets were. It was done by a two stage cluster sampling where the household was a sample unit. And we looked at first of a universal coverage of bed nets which is actually one bed net per two household members. Which sounds like if you have one net per two household members you assume that everybody can sleep under it. If we look what we found there nobody achieved universal coverage and it was incredibly low at the universe like in Katanga. The coverage for universal coverage was incredibly low. Actually South Keywood did relatively well. And noticeably 38% of people in Katanga had no bed net at all. So they couldn't sleep under one. Individual coverage which actually meant like we asked people did you sleep under a bed net yesterday night last night? The norm were the same but it was higher. So about 60% in North Keywood 80% in South Keywood but only 38% in Katanga slept under a bed net last night. And of those nets we know that the bed nets in Katanga actually were really bad. So we define a good net as being less than three years old and having few or no holes in them and they hang correctly. And that was very low in Katanga. So North and South Keywood slept under a good net, good condition net but the opposite was true in Katanga. So those people who had a net in Katanga slept under a bed of conditions. And then the vector study. So what we did in Katanga in the south of the country we sent out a team to collect mosquitoes. We caught 2,500 mosquitoes with different means. So we had light traps to trap mosquitoes. We had pyrethream spray collection and indoor resting collection of mosquitoes. And we analysed what are the mosquitoes that are flying around. And then when you look at this graph here you can see what species. So this is all anophilus and these are sub species. And what we can say from this is funesters and gambier are the very classical malaria mosquitoes. So they do bite between dusk and dawn. They do like to sit in sight. So they are the perfect targets for bed nets. Then we looked at how many of those mosquitoes were actually infected with malaria plasmodium parasite. That was about 1.8% which is considered normal for high endemic settings. Where were they caught? So this is a map of Shumwana, the place in Katanga. And you can see here that green dots represent houses where we did not catch malaria positive mosquitoes. And the bigger the dots get the more mosquitoes in one household were infected. So up to four. And what you can't see here but there's a river here. So you can see that actually where it's not random in the village that these mosquitoes fly around and then you have malaria. It's actually quite localised. So even in a highly affected village there are hotspots in households. Then those mosquitoes, so the locally caught mosquitoes, we subjected them to four different concentrations of known mosquito insecticides. The bottom two here are the insecticides used in bed nets. DDT you all know. And bendior carb is an agent that we used to do indoor residual spraying with. What you can see here at the bottom, so this was an hour they were subjected to these insecticides. And actually the idea is that a mosquito would hit the insecticide and they would literally be knocked down as in a boxing match. So they would just fall down. And actually with these two, so permythrin and deltha metrin, they didn't do that very well. So a lot of them were not knocked down. The other two were okay. So there's a marked difference between insecticides. Now there is a genetic mutation that can cause a resistance to this knock down mechanism. It's called the knock down resistant mutation, KDR. And this is a first, so you're a first audience to see this. Because the mosquitoes, the gambier mosquitoes that we caught in Katanga, none of them were completely susceptible to this knock down thing anymore. Most of them were partly resistant, but there was a high resistance. Like the genetic mutation was present in more than half of the mosquitoes to actually be knocked down by the insecticide of the badness. And that is something we didn't know. And I don't think anybody knows because Congo is a black hole when it comes to malaria research. And then what else did we do? We brought home nets from people in Katanga. So we asked people in Katanga, can we have your net? We'll give you a new one, but can we just take your net randomly? We just grabbed nets from, well, we asked, but from people's nets to take them home. Those nets, five from each branch, so there are four different type nets circling in Katanga. Distributed by us, by UNICEF, by other NGOs called DuraNet, Net Protect, Olyset and Permanent. They're all WHO-approved nets, and we took them home. And we had no idea how old they were, how much they were washed, whatever, but this was real life. Janine Lohnan, who is the PI of this study, actually made a cardboard thing and put these nets on and subjected per cone, as you can see here. So there's a cone that is strapped here on that net from the field and released five mosquitoes into each of these nets and quickly plugged a hole and then waited to see how many would be knocked down, step one, and then after 24 hours how many of them were killed. To have a comparison, we also had a control net which was not impregnated at all. So what you can see from this field, from this test, so these are bed nets from the field with fresh mosquitoes, susceptible mosquitoes, that within the nets there is a huge difference between the percentage of dead mosquitoes. So that is within the net and also between the nets. But the striking feature what you see here, for example, is that this net which is impregnated with permythrin, actually none of the mosquitoes get killed or at least they have completely the same results as the untreated nets. This is an unlucky mosquito that banged his head in the net for no reason at all. But Oly said is doing the same thing. And that could be because Oly said has been distributed for like five years ago. We don't know. It might not have nothing to do with the brand, but it could have really have to do with permythrin. And the same actually here for the delta matrin. So some worked really well, but a lot of them did not work well. So what we can say for overall conclusions, there is an important rise in malaria cases seen without any program changes. And we think now after these studies that this cannot be explained by adherence or efficacy of the drugs. So the adherence seems no difference in Katanga than anywhere else. And in South Kivu, Azach, NAL are very effective drugs that they're taken as instructed. But the bed nets and the insecticide resistant, the mosquito resistance to the insecticide needs further study. The bed net coverage is certainly not universal and there's substantial differences between the regions which should not, there's no reason for them to be there. And then local mosquitoes should reduce susceptibility to key insecticides currently used on the nets. And that is a very important factor for if we want to distribute nets again in the future. There are other things that we found as side effects of secondary outcomes of these studies. And one is that we know very little about the environment and the environmental changes. Also the behaviour changes of people, behavioural changes of people towards nets and things what can we improve there and towards adherence. But also what is the attributable factor of malaria to actually the sick kids that we see? In the efficacy study, for example, we saw that all kids that had a positive, many kids that had a positive RDT actually had a co-infection. Now do they have malaria or do they have another disease with a positive test because they live there? So those things need further investigation and we're really happy and keen to take up the challenge to do that. The acknowledgement list is only from people from HQ and higher people in Congo, but I'd like to thank all the mothers and all the children that participated and all the field study teams which could have filled another 20 slides. Thank you very much.