 So today I'm going to present work that was done by a large group as well and I'll be talking about oral cholera vaccination. So we often think about cholera being an old disease we know we can prevent it with clean water with basic hygiene but first I wanted to start with a map of cholera today so you can see that cholera continues to cause a great burden of disease globally and if we look at the places where we're still seeing cholera we have the most of it in Central Africa also in Asia and India and some in Central America and these are the countries where diseases caused by poverty continue to claim lives and where cholera remains an acute threat. So I'm going to talk about Saisudan. We heard a little bit this morning from one of the presentations but Saisudan is the youngest country in the world so it became independent from Sudan in 2011 and civil war broke out in 2013 and now we have a dire situation where nearly two million of the 12 million people who live in Saisudan have been forced to leave their homes and are living in internal displaced camps in the country often with very poor access to to basic hygiene and water. So in the last two years we've had over 7,000 cases of medically attended cholera in Saisudan. So I mentioned clean water and hygiene but there's also a vaccine available which can help protect against cholera. There are three vaccines pre-qualified by WHO and the picture here shows Shankal which is an oral vaccine all of them are oral vaccines. It's fairly cheap at just under two dollars a vial and two doses of this vaccine given two weeks apart has been shown successful at preventing cholera and can be used in a reactive manner. So after an epidemic has been declared in mass vaccination campaigns helping protect the individuals at risk but the major obstacle here is is vaccine shortage. It's made by one company in India and supply of this vaccine is completely outstripped by demand. I showed you the countries where we still have cholera. The population at risk there simply isn't enough vaccine for all the places that are suffering cholera today. So cholera in 2015 we had an outbreak in in Juba so the capital of Saisudan. This is a graph showing the epidemic curve the original the first case was traced back to May in the camp for IDPs in Juba and decision to use the vaccination was here so we could see the number of cases was increasing exponentially and MSF and the Ministry of Health chose to include OCV as part of the the multi-dimensional response and then there was discussion on how to use it request for the vaccines and we actually started a campaign here so quite a lot after a lot of the the cases had already come but this is a country where long epidemics often occur for eight months and they just seem to go on and on and on. So why Juba? This was the nation's capital and it's a place where there's lots of population movement so the risk for cholera going to elsewhere in the country especially places in active conflict was there and we wanted to stop this happening because we was seen in 2014 and I mentioned there's limited doses available so here what's novel about what we did was the dosing strategy this was a one dose campaign and I mentioned the recommendation to use OCV as a reactive tool is to give two doses of the vaccine. We chose together with the Ministry of Health and the National Cholera Task Force to give one dose of the vaccine because there were limited number of vaccines available even to cover the whole of the city with two doses but also there was immunological studies showing that one dose of the vaccine could also elicit an immune response and mathematical modelling studies showing that being able to give one dose to double the number of people could essentially save lives and there were preliminary trial information available about using a single dose the idea being when we can reach a lot of people in the population the indirect benefit of the vaccine we can also see protection in people who are unvaccinated so herd immunity could could occur so the campaign started at the end of July as I mentioned we offered a single dose of shankle to to individuals aged over one year you can see a map of juba here we we had to identify and target the at-risk parts of juba because we still didn't have enough vaccines to cover the whole city there were three basic areas and we also targeted high-risk groups such as healthcare workers prisoners and we used large fixed sites and we also used limited social mobilization because we were only offering the vaccine in these areas there was some concern from ourselves and also other stakeholders that the population from these neighbouring areas that we weren't offering the vaccine might come into the the area and we didn't want there to spark civil unrest in a country that can be quite problematic to work in sometimes so limited social mobilization and then just after the campaign we did a vaccine coverage survey using geospatial spatially random sample of population in these three areas so the aim of what I'm going to present today was is the feasibility the coverage we achieved doing this targeted campaign and the vaccine effectiveness so we gave one dose and we want to estimate how effective was it at protecting color and protecting the population against color so for the the methods these methods I'm referring to the the effectiveness study so we used a case control study and this was done in the realms of research and the protocol was approved by the National Ethical Review Board and also an international ERB in the summer months so we recruited cases of cholera just after the campaign at all of the different sites cholera treatment sites in in juba and we also recruited a randomly selected cohort of juba's population both in the the vaccinated target areas and outside the vaccinated target area so all over the city of juba we wanted to ascertain vaccine status so we asked the both the cases and the cohort if they were vaccinated and we asked to look at their their vaccine cards to to check and to estimate vaccine effectiveness we used proportional hazard regression so first if I give you some results on feasibility we vaccinated 143 000 people more or less in the main campaign in the space of a week so this was in the three main areas in juba and the high-risk population and then following the main campaign there were a further 22 000 people vaccinated as part of a comprehensive targeted intervention so new cases that are right in the treatment centers we then went to their immediate neighborhood and offered the vaccine together with water and sanitation measures and health promotion so the vaccine coverage we estimated in the three main areas was nearly 70 so 68.8 percent with these confidence intervals and this was considering the whole population so anybody over one year old write up to all their people so for vaccine effectiveness there were 87 suspected cases in the period after the campaign and 34 of them were classified as cholera positive using multiple diagnostic techniques so we used culture in country and also internationally and we used PCR as the gold standard internationally and we were also using rapid tests enriched and direct rapid tests and there is a poster looking at a validation of the enriched testing method which I would invite you all to have a look at because the findings are interesting and then so then we also had almost 900 cohort members none of the cohort developed cholera during the the follow-up period and here you have our vaccine effectiveness estimation so we were looking at 80 percent unadjusted so this is just considering the data as it is we also adjusted for risk factors like having access to water living in a house with people who had had cholera and after adjusting for these confounders our vaccine effective estimate was 89.6 so you might be wondering those of you who know cholera vaccine why it's so high by using this case control methodology sorry case cohort methodology we're actually considering not only the the direct protection at an individual level but also the indirect protection that can be caused by hard immunity so we're able to gather these together and it's therefore linked in with how many people in the population received the vaccine and were had additional protection so limitations and this is an observational study and in quite challenging field conditions ideally to estimate vaccine effectiveness we'd want to do a trial but this is not was not really feasible the the study size is small I think we have to acknowledge that with 34 cases after confirmed cases and after the vaccination campaign took place we really had no more cases of cholera in in juba so this can cause a limitation to the study but it puts us in this position almost irony when we see that the success of our campaign can therefore limit our ability to to share the the findings on effectiveness but despite this limitation we did lots of different sensitivity analysis and and are confident that our our findings are what are true nearly 50% of the participants didn't have their vaccination cards on them so this could be a limitation we used their self-reported vaccination status and we also used it when they had the card present if we did a sensitivity analysis and excluded these individuals we still had the same results and I think we have to remember juba and Saïsudan is not color is not new so there's a potential that the people who were included in this study have have experienced cholera have been exposed to cholera in the past and in this way the vaccine could be a booster if you like so it may not be the same results if you're looking at a population that's completely naive to this disease so for the discussion I think you'll find this is important evidence for deciding on vaccine strategy especially given the the limited supply of OCV in the world today we can see that a single dose of oral cholera vaccine offers a high level of protection against severe cholera so medically attended cholera and this is both at the direct level and also indirect protection caused by herd immunity we should remember that a single dose is also logically simpler so if we're working in emergencies finding the same people 14 days later could be quite challenging so until sufficient doses of OCV we are available flexible alternative vaccination strategies are needed and highly targeted campaigns in in urban populations are possible and single dose regime should be considered our results from an outbreak in an urban context show both are feasible and effective so lastly just to mention all of the people that collaborated in this study we have Evison to John Hopkins Saïsudan Ministry of Health Faster Institute the WHO in Saïsudan and also all of the people in MSF and the field teams which have the picture behind