 Welcome to the presentation of this low-cost, non-invasive thermotherapy device, the HPEC, we want to do in Pakistan. Coutainia las maniasas is one of the las maniasas forms, which is a neglected tropical disease, which is transmitted by the sand fly. And the cutaneous is hopefully the cutaneous form which is affecting the skin and gives severe skin lesions and ulcers. It is affecting worldwide around 1.5 million patients per year globally and mainly in South America, Middle East, North Africa and Central Asia. One country where it's endemic is Pakistan and here in this area is the las mania tropica, the species and in this area is las mania major and in the rural and the provinces of Sindh and Punjab. So here it is not a health priority, it's non-fatal and it's also self-curing, self-curing disease. So we are not quite sure about the numbers but the estimated is 22,000 to 36,000 patients is affecting in Pakistan. The next picture you will see a little bit what it looks like. It is Indian self-curing but the reasons to treat this disease is quite, makes it quite clear on these pictures. You see very harmful lesions which causing a lot of scarring tissue and of course stigma. So when you leave them untreated there will be a reservoir in the community so for further transmission to other patients. The Mesa treatment is by very expensive antimonials which is given by daily intramuscular injections for three weeks or bi-weekly very painful intralisional injections for four to six weeks. So there is another possibility of treatment because this treatment is not available in the governmental hospitals because it's very expensive but the patients they are able to get this treatment on local market or maybe black market they can buy it there for very high cost for around five to ten dollars per ampoule. So you can imagine that it's misuse and under dosing risk is very high and well there are other alternative ways it might be thermotherapy but that's delivered by a very expensive machine the thermomet by radio frequency but also there been a few small pilot studies being done with this simple heat pack which is called the hand-held exothermic crystallization thermotherapy device to treat this gutainous last many years. It seems very affordable because it's only two dollars per pack and it's safe and very easy to use as well because you can also reuse it by boiling up in heating up in boiling water. So it has been studied in another province in Pakistan in Sindh and there it was very effective of 83 percent. So we want to do in another area another province Balochistan where MSF has a project we want to do a larger study to be able to establish further evidence that it's safe and effective and also have feasible treatment way and also because it's very easy and if it's effective and safe and feasible we could maybe roll it out into the peripheral level so that also other patients can have access to this treatment and because we can use it then in the small health clinics. So that's what we did. We had a sample size of Internet sample size of 317 and we treated all the patients for three minutes for seven days in a row and all the patients they came for follow-up for up to six months, 15 days, 30 days, 60 days, three months and 12, six months after the start of the treatment. We measured the temperature because it needs to be the temperature of 52 to 53 degrees Celsius with this infrared thermometer and all the patients with a parasiticologically confirmed CL who sign informed content were included and excluded were all the children under 10 years old or patients with a lot of lesions, more than five or large lesions or patients with uncontrolled diseases, chronic diseases, immunological disorders or pregnant and lactating women we also excluded and we collected some blood samples for species identification. Now, so this is what we studied, effectiveness, safety and visibility. We made pictures from all the lesions on each visit that the patient would come and of course we monitored adverse events and if it was acceptable by the community if they would be happy with this treatment. The results, we found that the species we have here is the lasmania tropica which is a bit as expected. What we did not expect is that more than 80% of the patients after two months were or increasing in size, deteriorating in size of information or they did not improve anything after two months. So we suspended the study and we tried to analyze what could be the cause but we did not find any procedure errors or we did everything as the same as in the successful study in Sint. So therefore the final failure is 94.6% with only three patients that really got cured after six months. Because they were not healing we found a high percentage of patients with a secondary infection. The next slides I'm going to show you some of the patients from the study and it makes it quite clear I think why we had to suspend and stop the study. This is one patient on the face. This is also very striking, very obvious why we had to. So this is on the baseline and this is after three, one month, this is after two months and they are a few days later when we really got the infection very heavily. This is on the face and on the wrist again. So here you can see that the day, the moment they got exited you can see it on this graph. So with the median days of follow-up is after two months, one, no, sorry, median days is 45 days. You would almost forget that it was very, that the adverse events were not really severe. We didn't, the only thing we saw was quite some redness but they didn't last for very long. We didn't see any burns. It was, the pain was, it was painful for the first minute but after it got less. Very easy to use and well yeah. So then what could be the reason? Well the only plausible reason we could think of one of them is the species, the difference in species because in our study we found the altropica which is already known to be less heat sensitive and more difficult to treat with anti-lasmanial drugs. Also it takes much longer to heal if it heals at all because it's also, you can develop into a chronic form. And the L-major which was the very likely possible species in the SIN study, it's less easy to treat and the time for healing is only within six months. So the other study was, the follow-up time was also six months. So it may have biased in that study that all the patients got cured due to spontaneous healing like what has happened with our three patients who got cured. Another thing is that maybe it was not hot enough to penetrate the skin. So yeah, then what's next? It's nothing but next. We need to find another solution to treat this terrible, terrible stigmatizing disease which is patients-centered we had talked about earlier and of low cost because this heat pack was only $2 and the other treatment is very expensive and painful and if we want to make a success from this heat pack then we maybe can find any more research in L-major endemic areas. I need to thank the whole team in Quetta who have been doing this study so well and also of course the capital team and headquarters. Thank you very much. Thank you. Thank you.