 Welcome back to our online audience. You'll notice that we're running on Phil Standard Time, which is about two minutes slower than Google, but what does Google know? Um... There's been a lot of debate, um, happening online. I just wanted to let you know that we actually trended briefly. I'm told in the Twitter sphere that actually means something important, but I guess yesterday and today in the UK has been a bit of a slow news day, nothing much happening. LAUGHTER It's my great pleasure today to introduce Ninka Vandenbroek, who is a specialist from the Liverpool School of Tropical Medicine and leads the Centre for Maternal and Newborn Health. And it's fantastic that we have a whole session looking at reproductive health and sexual violence, because it's an area that actually, while MSF has quite a lot of field programs around this, we've really neglected in terms of looking at the evidence and how we can add to that and improve our program. So, thank you, Ninka. Thank you very much. It's very nice of you to be here. I'm not entirely sure whether my microphone is working. Is it working? And I'm very pleased with the range of presentations we're about to hear. Good luck to our presenters, who will all be sticking to 10 minutes, and therefore there is loads of time for questions. And the first person speaking is Timothy Harrison. Timothy, would you care to come up? Timothy has joined MSF since 2009 and has worked in quite a large number of countries, including South Sudan, and he's presenting some work from that today. DRC, Zimbabwe, Ethiopia, and Myanmar. We look forward to your presentation. Thank you, and good morning. And thank you to the committee for the opportunity to present our project today. The conflict in South Sudan started in December of 2013. A civil war which largely has followed ethnic lines, Dinka versus New Air, and continues until today. This has led to large population displacements in key areas around the country and a general breakdown in health care services. IDPs, or internally displaced persons, fled through areas endemic for the parasitological disease, visceralishmeniasis, such as in Lankan, where we observed a large epidemic last year. MSF has treated VL in South Sudan and Sudan for 20 years, with over 50,000 cases treated. The last outbreak was in 2009-2012, with over 18,000 cases throughout the country. Lankan at its peak in this outbreak saw nearly 800 patients admitted in September of this year of 2014. As you can see, actually this outbreak started in late December of 2013, and has continued on to clearly the largest outbreak that this project has ever seen. In total, in 2014, MSF treated more than 6,700 cases of VL in Lankan, 6,000 of those cases, including its two outreach sites. This photograph was taken in January this year. This tent at its peak houses 50 patients and their caretakers, and it was at capacity from August through November. The man we see here being assisted by relatives is severely affected by VL. This is quite a clinical presentation, if you will, and I want to spend just a minute to give you a primer on the disease. Clinical suspicion and the case definition are used to make the case for testing. In an epidemic, it's actually easier, because your clinical suspicion is so high. The parasite of VL attacks the immune system, primarily affecting bone marrow, the lymph nodes, but it's a systemic disease, so all of the organ systems are affected. Fever, splenomegaly wasting, lymphadenopathy make the case for testing. Splenomegaly in particular is an important documentation finding. Your spleen, you normally can't feel. It lives protected up under your left rib cage. But in certain diseases, including VL, it enlarges or swells. And it's actually palpatable and measurable, which is an important part. It's measured in centimeters. And it's one of the findings that we make in the diagnosis of VL. In terms of evaluation of cure, cure is a bit of a misnomer. There's no sterility from the parasite. But what it is, is the body has recovered enough, such that your own immune system can fight off the disease. So subject of improvement, the patient feels well, he looks well. Improvement of anemia, a hallmark of VL, and spleen size reduction. So you measure spleen size on admission and discharge. And after admission, you also measure the hemoglobin. So improvement of these two key factors is involved in the evaluation of cure. If you can't clinically cure someone, which more than 2 thirds of the patients in VL can be established as a clinical improvement, you can do laboratory testing if needed. The primary laboratory test, the lymph node aspirate, however, the performance of the test is not optimal. A spleen aspirate is much better, but it's restricted in its use. And some vulnerable groups, you can't do it. In terms of VL and pregnancy, we had certain challenges for the pregnant population. They were more difficult to evaluate for VL. In advanced pregnancy, for example, the spleen size is harder to palpate and very difficult to measure. The gravity abdomen moves much of the organ systems around, preventing this important diagnostic sign. Pregnancy itself, especially in the first and second trimester, there's a physiological anemia. So your hemoglobin level naturally drops during pregnancy. Both of these together, plus the complications of the pregnant woman in general, make it difficult to evaluate for cure. And it's really important. These are not only one patient, but often two patients that we're trying to assure that improvement has been achieved. The VL team worked closely together with the midwives, and the midwives developed an additional database for us to monitor some of the different elements of VL and pregnancy. So we decided to analyze pregnancy and VL. Females with VL aged 15 to 49 were included. The inclusion period of time is the development of the maternity database. The non-maternity group was taken from the line listing for normal VL and numbered 230. And the maternity group was composed of pregnant women, postpartum, and post-abortion patients with a total of 69. As I said, anemia is an important hallmark of the disease, both in its severity and its signs of improvement. We divided admission hemoglobin and exit hemoglobin into four categories, mild, moderate, and severe, and normal, which we assigned greater than 11 grams per deciliter. At both admission and exit, maternity patients were significantly more likely to have severe anemias, especially in the moderate and severe group, over 73% versus 46 on admission. And again, on discharge, even higher in the maternity group, and some signs of improvement in the non-maternity group. This was significantly, highly significant for both admission and exit. We also conducted a paired analysis. The histogram on the left shows the difference between admission and exit hemoglobins per individual. The no group is the non-maternity, and the yes is the maternity group. The non-maternity histogram is weighted towards the right, showing clinical improvement, and the maternity group on the yes side is weighted towards the left, or showing less improvement. And this is shown also in the paired T test, where mean admission hemoglobins and exit hemoglobins and the mean difference were calculated, with a 95% confidence in limits and brackets. The non-maternity group showed improvement, although slightly, and this was statistically significant. The maternity group showed a mean difference of minus 0.41, and although this was not clinically significant as statistically significant as the confidence limits crossed zero, the parasite creates a large burden, and anemia, especially early in the treatment, often falls, rehydration in the continued disease process of hemolysis. But by exit, we expect patients to have some stabilization of their hemoglobin levels, and in most cases, improvement. Next, we looked at spinonomegaly. Both groups showed a spleen reduction, which is what we look for. However, the large number of zeros, indicating no measurement or no improvement, or perhaps in the case of pregnant women, the inability to measure, plays into the improvement that we see. Both groups showed a spleen reduction after admission and exit, and both were statistically significant. In terms of size of the spleen, though, I take note of this slide. Often you see spleen sizes that are six or eight centimeters in size. So the zero values here really play a role in terms of the mean spleen size, both in admission and exit, for both groups, actually. Finally, we looked at pregnancy outcomes. This slide should be taken very cautiously, as the count-sounding of the proportion of pregnancies and deliveries in the MSF clinic are difficult to analyze. For this, we took non-VO patients from the normal maternity program in Lankien, and compared the rate, the proportion of stillbirths in the VO group versus the non-VO group. Clearly, the proportion was higher, seven of 25, and this was highly significant as well. We also looked at prematurity, and again, the VO group was significantly more proportion of premature deliveries versus the non-VO group. Additionally, the women who present to maternity tend to do so with obstetrical problems. So this comparison and estimate for the VO group may actually be underestimated. We need to do an analysis on a larger dataset to further confirm these findings. In conclusion, pregnancy and VO are thought to be mutually exacerbating. For example, the anemia and your susceptibility to infection. Anemia does not appear to improve during treatment of pregnant VO women, but more aggressive treatment for anemia and an analysis of the anemia should be considered. Splendid evaluation appears to be a challenge. Innovative ideas regarding the diagnosis of VO in pregnancy is needed. VO appears to lead to a higher rate of stillbirths and premature deliveries. Further analysis of a larger dataset is to be carried out. This was a really well put together project and I want to thank the author group, in particular the midwives, Mama Jane and Habiba, who really generated the interest and their database really enabled the project to go forward. Court and Ruby Citiqui, Ruby who pushed this project. We started in late February and have been able to present what I think is a really interesting project today. Thank you. Thank you very much, Tim, and the floor is open for some questions. So if you have a question, would you care to raise your hand and make yourself known to one of the people as a gentleman in a gray T-shirt in the middle? Hi, Rafa Alamedek from MSF Belgium. Which treatment were your patients getting already all an embisome or is it the older treatment? Yeah, there is three treatment arms, essentially. Ambisome therapy and all the pregnant patients were on embisome and the non-pregnant patients were a mix of SSGPM and embisome, depending on where they were in the severity of their illness. Thank you for that. Given that anemia or hemoglobin level seems to be quite a difficult measure for cure or improvement in pregnancy, could you say anything about the other four or so measures of improvement, including perhaps fever, which you mentioned? So the perception of wellness, I think, is really important and of course that's the first thing you look at. The patient feels better, looks better. Weight gain, which we also look at in BL, or at least stabilization and return of appetite, weight gain is really confounded by pregnancy, so it's a little bit hard to sort that out. And hemoglobin levels, I think, are important, not just in the treatment, but also clinically in terms of what we saw, perhaps, in stillbirth and the like. So it's really a challenge and I'm not so sure we have the answers yet. In terms of spleen size, ultrasonography may play a role, at least for the identification of splenomegaly, but then you also need competent stenographers. Thank you. Yes, that's a question there. Hi, I guess it's a very predictable question coming from me, but did you look at HIV co-infection in those women as well? We do routinely test, and especially in this epidemic, we found an extremely low prevalence and none in the maternity group. OK, thank you very much for an exciting presentation. Thank you.