3.2 Parallel session: Maternal and child health
When you say the 14 minutes just in case because 14 14 minut it’s 1 14 14 14 yes yes yes you say question is is it time no 44 minutes oops good morning everyone uh bonu um we are about to start uh this parallel session in maternal and child
Health and we would like to welcome to another interesting and we hope and we are confident very inspiring um session and um we have this H this H session is a little bit shorter my name is monserat blz Domingo I’m a project a senior project officer working for edctp and
I’m um a base in the H in the secretar at Bas in the H and I would like to invite my co-chair to introduce herself and uh thank you um good morning everyone uh my name is Andis wasito I am a project officer as well um in the Cape
Town IDP office um so I would just like to inform that um the presentations will be allocated 14 minutes each speaker and we’ll allow two questions um per presentation um in the interest of time so um we’d like to welcome the first Speaker of the day and that is Dr
Hamandi um from Bina Faso thank [Applause] you thank you good morning everyone uh I would like to thank adtp for giving me the opportunity to present result of this study looking at the association between prenatal malaria exposure maternal antibodies at Birth and malaria susceptibility during the first year of life in Bina
Faso the old Mark of plasmodium fpar infection is the inter individual variation insusceptibility when an individual get infected it can control the infections with rapid clearance of the parasite and in some cases the parasite can uh be carried during a long period and in other individuals they
Will develop symptoms which could be in complicated malaria and in some cases uh it will become severe which is life-threatening and several factors including environmental immunological and genetics uh dve this erogen I was particular particularly interested in in that erogeneity in infants uh because they are specific
Population group um due to the immature adaptive immune system uh because the literature says that they are protected by maternal antibodies and but also there is quite a number of studies reporting that uh placental malaria increased the risk during uh the first months of life and we previously uh
Reported that different categories of uh prenatal malaria exposure which are acute chronic and past plastal malaria but also so when the uh mothers has been infected during pregnancy but with no evidence of placental malaria at Birth and we show that uh the different categories of pral Malia exposure have
Different effect on their susceptibility during the first months of life we also reported that um preventive treatment uh have a protective effect in infants and we also look at oogenetic background where we identify some mutation in the genes related to the human system Sy uh that were protective so I would say what
Was missing in this puzzle was uh the lack of data on the martinal antibodies at Birth and thanks to edctp we were able to assess this uh through the objective uh being to determine how different categories of Parental Mar exposure influence level of maternal antibodies in the core blood at
Birth and the subse risk during the first months of life the study was conducted in nuro in Bina Faso within the health and demography s system cment area uh of The Clinical Research Unit of nanoro so actually we conducted a birth Court of 734 infants uh nested to an
Ongoing trial known as Cosmic uh assessing the effectiveness of uh preventive treatment and the intervention was based of the combination of the standard intermittent preventive treatment with sxin pamin um plus uh a monthly screening and treatment when they were infected and the control group eded the S
Iptps the infants were follow up during 12 months and the clinical cases were detected through lunal surveys we also conducted cross cross-sectional surveys at R 69 and 12 months and uh thanks to to the cosmic trial were able to have the peripheral infections uh in the mothers during the pregnancy and as well
As plenter biopsies and C blood samples for the immunological asset and out of the seven 134 U children were able to collect uh 661 cor blood samples uh which were pre-processed in the nanoro and Shi to ice Global uh in Barcelona where we process the quantitative suspension area
Technology uh in the flex map 3D platform to detect uh antibodies and we have a panel of 15 antibodies including pre- errotic antibodies the csps full length the C Terminus and the namp uh 10 blood stage antigens and two markers of placental malaria and we targeted IG and the
Subclasses IG 1 2 3 three and four first we look at the antibodies profile in the core Bloods and here in this graph we have the aggs in red the ig1 in Green Olive ig2 in green uh the ig3 in blue and the uh ig4 in
Purple and as you can see the antibodies were detected in Core Blood at different levels uh depending on the antigen as represented here and through the different profile for the csps the msps and the markers of uh placental malaria and these antibodies were predominantly uh cytophilic antibodies
A1 and ig3 and followed by ig2 and ig4 the correlation uh Matrix showed a positive but a moderate correlation between antibodies on the top left for IGS we can see that the strongest were observed for the antibodies against the csps and those against the placental malaria biom
Market and the same pattern was observed for the r subclasses looking at the variation of Martin antibodies level by pral Maria exposure categories uh we compare each of the exposure category to the non-exposed uh control group and we can see for IG that pasty malaria uh and
Acute PL Cal Malia was associated with higher levels of some antigen PR rrotic antigen and blood antigens while for the markers of plal malaria all the um exposure categories were associated with higher levels of the antibodies for the cilic antibod you can observe that the same pattern was observed but with different exposure
Associated with higher levels of the antibodies that was also the case for the non cytophilic antibodies so looking at the association between maternal antibodies and birth at Birth and Malia susceptibility uh this cap uh shows the analysis of the CATE where we identify the preventive treatment bir season low birth weight
And patal exposure as the coar sequently associated with malaria and of not um in our C uh 60% of the infants experience at at least one clinical episode as detected by qpcr so now looking at the association between the antibodies and Val susceptibility we identify four uh antigens uh associated with Mala
Protections which were IBA 140 IBA 175 MSP 142 and MSP 5 and the antibodies were IG igg1 and ig3 and as you can see none of the non cytophilic antibodies were associated with protections uh by contrast we have IG ig1 and ig2 uh which were associated with uh an increased
Risk uh during the first months of life so then the question was in the context like Bina F where we have the high transmission most of the children are been exposed during um pregnancy and in this score 75% of them were indeed exposed so what’s the the meaningful of having both
Uh antibodies ass with risk and the ones associated with uh protection uh like in this cases so we analyze the effect of ratio between protective antibodies and antibodies associated with increased risk in the a panel we have the ratio of IGG against IBA 140 and ones against
Dbl2 where we can see that uh there is a significant delay time to First clinical episode uh during the first 12 months of Life the same result were observed in the B and the C panel for the ratio G against IA 175 and IG against dpl1 2 and
In the C ig1 against MSP 142 and the one uh2 so at the end uh despite the exposure of uh a child when he has uh high level of protective antibodies it can uh get protected so to conclude these fundings indicate that different patal Maria EXP exposure categories have different
Effect on maternal D antibodies to malaria antigen at Birth and this might drive erogeneity to clinical Mal suceptibility in early childhood and these fundings are also calling for uh studies seeking to identify the combined signatures that are predictive of malaria susceptibility or resistance instead of the single antibody approach applied in this
Study to finish I would like to thank the study part ipants uh the mothers and the children the colleagues across the different institutions uh the founders uh the Belgium development corporations the European social fs and the last but not definitely not the the least edctp for their support through uh a carer
Development grants and thanks for your attention um thank you so much um Dr hamandi for this um very interesting um presentation so we are going to allow two questions um for the speaker um is there anyone who has a question to us thank you my name is Adrien luy from IR in
Paris it’s a lovely talk I really enjoyed it as you probably know it’s one of my favorite topics um you went through uh um the different types of um exposure possible I I didn’t maybe I missed it but I don’t know if you told us how you classified between chronic and acute and
The others that’s just one point you could clarify very quickly the the comment and maybe bit another question it’s to do with intuitively you might think that chronic infection was is most likely to have the most effect and again intuitively you might expect that antiv var2 CSA antibodies in the context of chronic
Infection would be most prevalent in the placenta and might be um overloading the transplacental plan transfer system if you see what I mean and I think at the end there was some indication in your in your in your in your graphs that that that could be the
Case maybe you’d like to comment on that okay thank you uh indeed I didn’t uh talk about details about how we categorize the parental Mala exposure actually U the acute chronic and past placental Maria were based on placental histology and the acute were the cases where we have uh parasite only uh
Without malaria pigments in The Chronic ones we have both parasite and Malia pigment um when talking about Mal pigment is osin and uh lastly for The Chronic ones uh it’s when you have uh only malaria uh pigment osin and in addition we have uh the case of uh
Pregnant women who have uh no evidence of plas Mara at uh delivery but with uh data on uh the infection during uh the cost of the the pregnancy and this we also consider and in the in the result we presented we can see that uh this were also asso with uh High antibodies
Label against the placental Maria biomarkers yeah uh yeah indeed I totally agree with your comment and no I don’t have more to add all right um thank you so much is there another question on the floor all right thanks then I’ll will hand over to my
Co-chair um indeed I have a question um are you planning to follow those children and see for how long they will keep the maternal protection that they got against malaria know that we don’t have any chance to follow up the children anymore because uh the study U finished uh in
2017 and yes uh we don’t have chance to to do that but uh one of the perspectives was to uh also uh consider in another Cort how we can assess uh the the wining of maternal antibodies and the build up of the acquired imunity in uh children in our uh
Settings thank you thank you very much okay our next speaker I’m very pleased to introduce to all of you uh Dr Raquel Gonzalez um working at the is global and also um happy to to introduce someone that indeed I have been following the ground for the last four years so please
Ra the the floor is yours thank you very much monat and thank you very much edctp for giving uh us the opportunity to present the results of the mama trial I am presenting on behalf of a very large team sorry um from mosambi uh Gabon Austria Germany and
Spain so as you all know together with children under five years of age pregnant women are vulnerable population to malaria and in this slide you can see the cycle of plasmodium fipar in the pregnant woman um there are several hypothesis trying to explain explain the increased vulnerability of pregnant woman to
Infection and one of them is the one based on the evidence that infected electrocytes tend to accumulate in the intervenous spaces of the placenta in fact during pregnancy this Disney organ and um we know that um it’s uh where the parasites tend to accumulate so the effects of malarian pregnancy can be
Seen not just on the in the mother with increased risk of severe anemia severe disease maternal death but also in the development of the fetus with um fatal growth restriction increased risk of adverse pregnancy outcomes namely steel birs miscarriage prain birth and very importantly also lweight these are the current control
Strategies to recommended by W for the control of malarian pregnancy the administration of I PTP intermittent preventive treatment in pregnancy of sulfoxy pramin which is recommended to be given at each schedule anal care visit from the second trimester of gestation onwards and this is done on
The uh on the direct as a direct observe therapy by the health workers at the anal care services the second is the use of insecticide treated Nets and third a prompt and effective case management in case of malaria however in hi infected pregnant woman that take coool prophylaxis for
Prevention of opportunistic infections a SP cannot be given because of potential drug interactions between the two drugs because they are part of the same family and also we need to remember that H infected PR andum also receive anti retroviral drugs for uh their own treatment and also for prevention of
Mother to child transmission of HIV so these population are subject to possible drug interactions that is the reason why in the last years there have been some studies looking to find a drug that could be used for prevention of malaria in woman taking kimox asol prophylaxis these are the drugs that
Have been so far tested in HIV infected pregnant woman mefo Queen uh was evaluated in this trial which was also funded by the dctp uh in the first program this was the midat trial that enrolled over 1,000 women in Kenya mosambique and Tanzania and we found that mequin was very effective as for
Prevention of malarian pregnancy it reduced the risk of maternal paramia placental infection and Hospital admissions but the durability of the drug was not very good and more importantly we found that woman that received mphin had a twofold increased risk of transmitting the HIV to to the to the
Baby and so that was the reason why mefin was not recommended for iptp in this uh population and more recently there has been another Tri evaluating the drtim in pepaquin in Uganda in among 200 women and they didn’t find significant results however uh this drug theis in pipera
Queen that I will be calling DP has very good characteris sticks that makes it as a suitable candidate to be used for prevention of malarian pregnancy because it has a good tolerability uh at long half life which will enable monthly iptp Administration it it is safe also in pregnancy and a
Possibility a limitation will be that it is a three-day course treatment so it could um um raise some challenges in terms of compliance for the three-day treatment it is in this context that we designed the mama trial which is an edctp 2 uh funded project coordinated at the Barcelona Institute for Global health
And in partnership with all these institutions with mmv the Bernard not Institute of of Hamburg tubingen in Germany and Vienna University and um these are the objectives of the study to evaluate the safety and efficacy of the drug as iptp for malarian pre prevention among HIV infected pregnant woman that take coool
Prophylaxis and that receive anti retroviral drugs and also we wanted to assess the effects of the drug on the risk of modal transmission there is also nested in the study a pharmacokinetic study that it is uh ongoing and so in my presentation I will be Focus focusing in the two first objectives
The trial was conducted in Gabon and mosambik at the SEL and at the central investigation Saud in manisa mosambik these are the list of study Imports being peripheral maternal paremia delivery and then we have a long list of HIV related and malaria related outcomes and also very importantly also
We assess the safety the durability of the drug and um the risk of adverse pregnancy outcomes this is the trial design basically woman uh attending the first anal care visit will check uh for inclusion in the study and if they met the inclusion criteria they offer participation and uh randomized to
Either receive iptp with Placebo or iptp with DP and all of them receive that the standard of care which is coim oxol prophylaxis plus anti retroviral drugs we uh administer at PTP at each Schedule andal Care visit from the second trimester onwards following following W recommendations then we follow the woman
Until one months after the end of pregnancy and their infants until one year of age iptp Administration was always done under direct OB observation including those doses received on the second and third day of the treatment course so this was done either at the household level or at the health facility if the
Woman had to return and the dosage was based on the weight of the woman at the first iptp intake apart from iptp we also administer coim mool and the retroviral drugs and an ITN and the first woman was enrolled in September 2019 and uh enrollment was completed
After two years in November 2021 and the last uh visit of study children occurred in June this year so overall we screen uh more than 8,100 pregnant women and randomi 666 334 in uh in the placebo group and 332 in the DP group and here you can see
The number of iptp doses received uh by study arms and for the primary endpoint maternal paramia at delivery we managed to get information from 308 woman in the Placo group and 294 in the intervention group in this table you can see participants Baseline characteristics with not uh differences across study
Groups most of the woman were multi-gravity and uh the mean age the me gional age at inclusion was 18 weeks 18 weeks so meaning that that most of them were already in the second trimester of gestation when attending the first anal care visit and the prevalence of anemia at enrollment was over
50% in the two study groups in this other table you can see the HIV related um characteristics so most of the woman 60% of the woman in the two study arms had undetectable viral Lo at the time of delivery and More than 70% of them were already on antiretroviral treatment and the regimen
Most of them were on the L based regiments in this table you can already see the results uh at the time of delivery so we follow the woman during all the pregnancy and at the time of delivery we collected samples in order to measure maternal paremia which was
The F the primary endpoint and unexpectantly we only found one woman in the intervention group that was found to be um infected with malaria by microscopy at the time of delivery if we look at the PCR um analysis we find five woman in the control group and three
Woman in the intervention group however the the proportion of wom with placental infection tended to be increased in the control group and also the proportion of woman with maternal um anemia or though the difference was were not statistical significant between the study groups we did see this trend and in the rest of
Outcomes we didn’t we didn’t see any Trend and any differences in terms of lower weight cor blood parisia and um anemia H in this graphic you can see the incidence of clinical malaria pregnancy by study arms in green um the intervention and in blue the placebo and
Here we did see a sign significant decreased risk of infection of clinical malaria episodes during pregnancy in the intervention group and when we look at the composite outcomes so looking for the the overall risk of malaria infection and we compare it by by groups we did see a significant decrease risk of
Overall malaria infection including smear detection and PCR placental infection and clinical malaria in the inter vention group and the same happens when we look at the composite outcome on maternal malaria and or anemia and for placental infection maternal anemia even if they didn’t reach a statistical
Significance we did see we do see a similar Trend favoring the intervention compared to the control and in this table you can see the HIV related outcomes that we wanted also to monitor based on the previous trials on miin and we we didn’t see difference in terms of
Levels of CD4 counts and viral loads and also no differences in the risk of mod transmission between study arms uh looking at the adance of coool prophylaxis and anti viral we we see a more than 90% uh adherance to the study drugs and the same percentages in the two study
Arms and this is the last table uh reporting the safety outcomes we did we didn’t see differences in the prevalence proportion of serious Adverse Events and adverse pregnancy outcomes including miscarriages steel birds and prematurity between study arms so as conclusion we can say that in a context of low malaria transmission
Adding iptp with DP to kimox asol prophylaxis in HIV pregnant women on anti retroviral therapy is safe with no increased risk of adverse pregnancy outcomes and serious ad Adverse Events and it is associated with a decreased risk of clinical malaria and overall plasmodium infection in pregnancy so this strategy could eventually be
Considered to optimize malaria control in a infected pregnant women Who Remain the least protected and I would like to finish by acknowledging the study participants all invest vators field workers safety and data team and also the mama DNB apart from the funds thank you very much so thank you Raquel for really
Keeping us on top of the findings of this Consortium and this large scale H study uh we have time for a couple of questions so Peter kemner and I see another SE first thank you very much for this very interesting and wonderful talk and although you didn’t just meet your
Expected outcome when it come came to the primary end point uh I would like to summarize the following that you did a near to perfect study and this is why you didn’t meet uh these outcome measures if you do such a study under very strict conditions as you have
Defined uh and this obviously took place with a lot of impact on the use of the Nets and the use of prompt diagnosis and treatment and also adherence to the prophylaxis like cazol so then you will not find a lot of maternal parasitemias congratulations to this very good execution of the the
Study thank [Applause] you right um thank you my name is Noble from Nigeria I also join Prof to tell you I’m quite impressed with the results I we did a similar study in Nigeria because I know that your was in a low transmission have you considered doing
That in a higher transmission area like Nigeria because and then the my second question is is um what is the level of SP um resistance to sadine in Gabon because I know that in some eastern and southern Africa and there is a lot of report of resistance and so but which could have
Affected this but I’m very very happy that your prevalence was your positivity was very very low almost near to zero so two questions have you considered trying this in a higher malaria transmission area and then what was the level of SP resistant which is the what is used for
The normal HP in gbon thank you thank you very much for the question and regarding the if if we have considered doing this in a in a another transmission intensity area H I must I must say that uh when we designed the study that was six or seven
Years ago uh malaria transmission was maybe not that low as uh we found so actually we our estimations in terms of sample size were based on previous uh transmission rates in the area and and and in principle we should have been powered to detect differences but it’s
True that in the last decades there have been many interventions ongoing in the in the ders and so the malaria has decreased but I must say there is another trial a very similar trial that has been conducted that is also a DC dctp funded project the improved project and this is
Has been done in I think in Kenya Malawi and I don’t remember the other country I think in the three countries uh well H well they they have more malaria transmission there and they have managed to see also a similar impact and they did they did find differences uh more differences across
Route because it was more powered and regarding the speed resistance markers of resistance in in Gabon I don’t I don’t have the information I don’t know if Peter of someone in from the Gabon team has it sorry I don’t I don’t know we are going to allow an
Exceptional third question but it has to be very precise and the answer has to be also no thank you very much it’s not it’s not actually it’s not a question so you don’t need to answer that but it’s just more a comment to Professor cner who is absolutely right what he said
That the study was very well done which is what all want to do a very well done studies is not an it was not a pragmatic study although it was in the middle of coid you didn’t mention that but I think it was that was one of the challenges as
For many people in in were doing trials at that time but just to say I think you I think you mentioned that already that H the previous the previous study we in the same uh area um that with methling was also well done but we found a difference so the compliance with kosol
And anals at that time was also very high but there was a difference so I think that needs to be I mean we need to understand a little bit better the differences between trials in similar areas or identical areas but where uh malaria has changed fortunately over the
Past years and then to understand how we can better H appli the methodologies that we have now that probably were not there 10 years ago but thank you for your comment Peter because it’s true it was very well done in both in Gabon and and and mosambi so congratulations to
The team thank you you thank you very much all right um thank you so much for that um great presentation and so now we’ll hand over to our third speaker which is Dr Karim um the floor is yours spe oh yeah it’s okay okay thank you very much for giving
Us the opportunity to share some of our preliminary data of our work on the Dynamics of molecular and resistance marker prevalence of P fipar during the seasonal malaria chema prevention campaign in school a children in banag Mali so the implementation of uh malaria seasonal CH preventions at large scales
In malaria endemic areas has contributed to reduce signifant malaria burden in children under 5 years but this is contrasting with increasing cases in children above five years and in recommendation of wh uh wh has recommended to extend SMC to Children above 5 years as well as the possibility of using timing combination
Therapy for SMC so in this context there is need to generate fied data to support these recommendations and to assess what impact using SMC at Large Scale in Mass drug administrations what impact this could have on uh selection of drug resistance markers so we conducted a study randomized clinical trial to
Assess the safety and efficacy of DP compared to SP AMU Jakin in school AG children in Mali and we also investigated the potential role of using uh acts in SMC on the selection of resistance markers so from uh September 2020 to August 2021 we conducted a randomized clinical trials with
355 participant from 6 to 15 years old and the participant were randomized in three treatment arms to receive either suxin peramine plus Amin or DP and a control group who receive only albendazol but to reduce a potential bias of albendazol the treatment group SP Ai and d and DP group
Also re save albendazol and we conducted four SMC runs from September to December and participant were followed for 12 months we also conducted two cross-sectional studies at month 6 and 12 and we collected uh Dr specimen blood uh uh at Baseline and before each SMC C and we
Also collected uh DBS at 7 days after each SMC to assess the molecular prevalence of pipar and the resistance markers so the study was conducted at banaga Banjara is one of MTC clinical resar site located at 700 kilm from the capital city and the site has uh been conducting clinical trial since
2003 uh despite the recent clinical the recent insecurity issues in the country and in particular uh at banaga uh the study was successfully conducted and uh the site is uh contining conducted clinical trial and epidemiological studies for molecular Assi we uh the DNA was extracted from the DBS collected
During the the the clinical trials and parasite genomic was extracted from this DBS and Amplified uh using one negative control and one positive control which was the PF 3d7 DNA we also investigated uh the mutation in some uh resistance markers particularly the PF dhar dhps and PFC genes so we
Amplified these genes from uh the the the the the DNA extracted from DBS and the amplification was done by nested PCR and the PC Product was purified then sequenced by bofedal and the analysis was done by bio edit software so in this paper we have documented the uh efficacy and the
Safety of uh DP compared to SP AQ in a non inferiority analysis and this paper he’s just published for molecular asset this analysis survival analysis show the decrease the significant decrease of parasitemia uh from Baseline to uh SMC 4 and in control group we see that uh
There was a remaining aritmia after the run for through the followup period comparing the result of microscopy to uh uh the molecular assai we found that persistence sub micros microscopic parasitemia was noted in uh DP Group after the SMC uh from day 61 to day 365 so this sub microscopic parasitemia
Could constitute a factor to maintain the transmission of malaria during SMC campaign for now we are investigating the resistance markers so uh we have sequenced 57 samples for dfar 55 samples for uh dhps and 607 sample for uh pfcrt so the sequence of DFA and of dhps
And pf30 are uh we are the analysis is ongoing uh but the sequence of PFD shafar uh already analyzed we read find any mutations for now uh but the limitation is that we have small samples and the analysis is ongoing for uh on large
Samples to see if this is the the Str or if it’s to small sample size so in conclusion we can say that DP is uh DP and SP IQ are effective in SMC but the Persistence of submicroscopic parasitemia during SMC could constitute a factor to maintain uh the transmission of malaria during
SMC and uh but we also noted a decrease of paramia in control arms so we don’t know exactly why this uh there is decrease but maybe it it is because the case were detected and treated during the followup and uh no mutation is detected for now in the shfa uh samples but the
Assessment is ongoing for more sample size to investigate the issues so I would like to thank edcp for funding this project through the senior Fellowship I would like also Al to uh thanks the population of banaga our research team and our institutions and our health authorities the national program of malaria control
Who provided the study drugs and our partner malaria Research Unit at University CL Berner of Leon thank you very much thank you very much Dr Karim um i’ would like to open the floor for questions all right yes you may go ahead thank you very much felicit and again I would like
To congratulate this is uh extraordinary under such circumstances as you said yourself in bandaga you have kept on going and you did the work you did the study under this severe uh circumstances and this shows how hard work and perseverance pays off thank you very much this is very very good and I’m
Grateful that you showed that it is possible uh one question what is your recommendation now in Mali is it SP P to use further on okay thank you for the comment and the question actually uh the national recommendation for SMC is sp a so maybe with the result uh DP may be
Used in the future but now the recommendation is sp thank you very much I join Peter to congratulate you on a well conducted study I want to ask about the safety profile of the participant especially in the intervention HS those that receive spaq andq and alender Zone what was the
Adverse event like and um the also the demographics because I don’t know whether you included participants above the age of five you alluded to it at the beginning so what the AG profile like and was there a kind of a imbalance or balanced a safety profile across the participant thank
You okay thank you for the question your question is about the use of alband for safety profile I want to know yes exactly okay uh for safety result as I said the result are publish in this and in the paper that I show but for adverse event uh the
Adverse event were more frequent in Sp AQ group compared to DP and control um thank you very much um do you have a question okay um can I please ask that you keep it short in the interest of time thank you you can work to that mic
There’s a mic just behind you thank you okay very quick one um I just want to ask uh there’s uh concern about the non application of mutant Gene so did you check your uh PC procedure very well or do you check amplification in your um gel electr fores to confirm that was
Actual amplification before your sequence okay um the the PC the PC for uh for dhfr dhps and uh PC and CRT uh was nested PCR and the PCR product was purified uh then sequen it I don’t know if I answer to question yeah yeah okay thank you so the control
The positive control was DNA of 3d7 strange and uh the positive control was also sequenced and use as reference sequence for analysis uh um all right thank you so much um for all your questions and thank you very much Dr Kim for your presentation [Applause]
Um I would just also like to inform you that um there will be time for more um questions after this the session so you can interact and connect and ask more questions to the to the presenters so thank you so much I’ll hand over to my coach
Here okay now we are in the fourth presentation we have a slightly change the uh presenter will be um not Paul S but uh a colleague very close colleague berer cabore so please come to the stage from [Applause] Bina okay thank you good morning everyone so thank you for this
Opportunity to share our uh the result of our study entitled the inance effect of seasonal Mar Cho prevention when coupled with nutrients supplementation for preventing malaria in and the five children in bukina Faso so we in this study we deal with malaria so I don’t think I have much to
Say say regarding malaria because it’s well known that is a a major public health concern in most subsaharan African countries and because of this High burden so the wh recommended the seasonal Mar Kim prevention strategy and that strategy was adopted and implemented in bukas since 2014 and although this is well
Implemented and uh we ensure that there is a a very effective so the full potential of this intervention may have not been yet achieved after several year of implementation despite a reported good cover in adance so that suggest that there is obviously a POS hiding factors that jiz the efficacy of the
Strategy and therefore there is a need for Innovative approaches to help improve the strategy of the SMC so we also deal with h sorry we also deal with malnutrition which is not an infectious diseases but also a major health issue in uh uh subsaharan African countries and with high morbility and mortality in
Childhood so we also found that during the SMC period this period also coincide with the period of food sortage in our settings and in bukina Faso most of the children receiving the SMC strategies are also under nourish so because of the malnutrition that weaken the human
System of the child and then leading to worsening Malia infection so a lot of study also shown that uh uh treating children with macron macronutrient deficiency can help improve malar relative morbidity and mortality So based on this background we hypothetized that combining the strategy of SMC with the micronutrient supplementation could
Better prevent both Malia and malnutrition in children so thank to edctp so we were able to set up a study called the SMC project with the overall objective to assess in a randomized control trial with SMC plus nutrients supplementation is more effective and safe in reducing in complicated malaria
Incidents and also severe malaria compared to the routine SMC alone so how did we set up this study so has I pr said it’s it was a randomiz control trial conducted between July 2020 and June 2021 in the N health district in B so in this study we had
Three arms two intervention arms and one control arm on the the intervention arm we add the arm of the plumed do where we add the child receive in addition to the SMC they received a plumpy do on the daily base one packet so during the entire period of the SMC
Intervention and the second intervention group was the Zen group where we also add to the SMC strategy a daily based tablet so each children receive a tablet which is 10 milligram of element zinc on the basis on Bas of one tablet per day for six day uh per week so During the
Antire period of the intervention and the other group was the routine strategy so we compare all the group and at the beginning of the intervention we did a baseline census where we collect all the social demographic and clinical anthrop anthrop anthropometric data and also we did Malia test with the rapid diotic test
And also microscopy and we follow all the children for the 12 month and for the first six months we follow them actively and with a monthly home visit where we also collect demographic clinic anthropometric and also malaria data with rdt and the we also add a followup after the six month the second
Half of uh the the followup was passive and then where we recommended the parents to bring the child to the health facility for any health issue so here is the study flow chart so we randomiz more than a thousand children and then they were equally distributed in the three
Study um and at the end we roughly have the same uh study sample size in each study arm around 300 and 40 so here we are showing the Baseline sensus data and as you can see we have a relatively High malaria rate with the ADT around 22% and
Also 10% based on microscopy and we can see that almost half of the participant were stuned and uh more than 20% were underweight here is the cumulative incidence of in complicated Mala and as you can see on the curve in green is the plumo group
Arm in red the Zen arm and the control arm in blue so you can see that there is there were less cases in pidos group in comparison to the other group and statistically we found that uh there’s a there was a reduction of 80% and 2 23%
Respectively in the Zen group and the plumose group and regarding the cever malaria cases so on the bottom the bottom uh the the last row you can see for the plumo group that there was a significant reduction of Mal sever Malia cases around 52% in comp compon to the other
Group des and the rtin arm so as I said we also did uh a monthly followup active followup where we did a ad test so here we are showing the the positivity rate during those visit and then we here we in like the clinical Malia situation so there is no
Significant difference between the different arms and lastly we look on the all causes of morbidity across the different arms and as you can see here in green the plumed do where the Zen the Zen group and the the control group in blue so we also found that there was a there was less
Incidence of all cases morbidity in PID do group compared to the zinc and also the control group so in conclusion we can say that there was a positive impact of this intervention SMC plus plumy do so with a reduction around 20 3% and 52% respectively in in complicated and sever malaria and this
Intervention plos plus SMC was better in comparison to the zc and also the routine intervention so we can say that adding nutritional supplement to SMC significantly increase the impact in preventing clinical malaria and other childhood infection so that was my last SL and I would like to thanks all the
Participant the kids and the mothers and also edctp for the funding through the career development Fellowship the our institution the irss and Clinical Research Unit of Nutri ID war and our direction for nutrition B thank you so thank you Dr cabore for this great presentation and for explaining to
Us the effect of Nutri Nutri nutrients supplements in the incidence of malaria so we have time for o two questions and the third you will see but please be precise in your in your formulation of the questions thank you thank you thank you I want to congratulate the team
Firstly for uh having this idea of combined interventions not focus only in malaria and my question is regarding the supplement the composition maybe I I I missed that to see exactly what is in this supplement and the cost how this cost for the program I think this could be helpful also to
Balance how we can also Implement thank you okay thank you for your question so uh this study was an yeah it was an Interventional study and then we benefit for uh Nutri set the the supplementation the plum do it is not in the our routine program yeah it was a part because of
This study so that we get the support from the NRI set and we unfortunately we didn’t add uh a a cost like a economical study to see how it might cost to if we want to to put it in uh uh the routine study so this is uh
Yeah there was just a try so probably we will see how we can do it uh in the future yeah and also for the uh the composition so I don’t have the exact composition right in in mind but yeah I can share it with you thank you okay thank you uh for the
Presentation my name is Dar a research coordinator at the University of Global he Randa on nutrition project so I’m asking two small question one is about uh like how we were measuring the compliance you said that you provided one tablet per day and the second one is
About how were you doing the kind of confounders because you were providing kind of interven so to be sure that how intervention is making an impact so I would like to hear how you were dealing those kind of confounders in your intervention thank you so much
Okay thank you for your question for the first for the first one um regarding the supplementation yes uh as you can see the sample size it wasn’t possible for us to do like a direct observation of the treatment and also for the the the supplementation so
We thought about that and has its a clinical trial it’s based on the threat between the the the study team and also the the community so at the beginning when we were delivering or we are doing the conent process we explain to the matters and how what we want to do and
The objective and we try to put or to build a trust between the community and also uh the study staff to make sure that the intervention yeah for for instance for the plumose it will not be given to other children in the community so we know that that’s possible but we
Build the the the trust and then we try to well explain them the objective of the study and why it might be dangerous or to to give it to other people had a children so that was what we did but we know that it might be yeah it’s a limitation because we didn’t
Control for that and also regarding the other confounding factors so we did a study in the quite the same study area to make sure that we have the population our study population is are living we are living almost in the same condition and also when we show the the Baseline
Sensus we did so we can see that the like the condition we sharing almost the same conditions and to make sure that with our intervention the differences we will see might be linked to our intervention and also the other confounding factors we didn’t show all the statistics we did so
We take into account how we to correct all the for the other confounding factors so we can probably continue the discussion and then can show you how how all the the statistic behind the result we found thank you thank you very much Dr C and I agree
Totally with him H the further this can be a further discussion with anyone that has more questions also some ethical implications for not giving the other children the supplement which is a hard thing to do okay thank you very much um all right thank you so much now we’ll
Hand over to our next speaker um Dr wendo from Zambia the floor is yours uh good morning though it’s at the brim of um afternoon um my name is wendo I’m delighted to present and um stand here on behalf of the empirical clinical trial team um I will be presenting on
High mortality in African infants living with HIV hospitalized with severe pneumonia so for the background um basically we all know of course that children with Advanced HIV disease are at an increased risk of morbidity and mortality with pneumonia being the main cause of the death so wh guidelines to
Treat severe pneumonia um in HIV infected infants include empirical treatment of um common bacterial pneumonias and also additionally pyus Jovi pneumonia this has led to a reduction of course in um the overall mortality in these infants but as we all know the mortality Still Remains unacceptably High autopsy studies in Africa actually
Do show um that cyto myala virus um infection and tuberculosis still contribute quite highly to the causes of death in this very very vulnerable population of children of course they are both underdiagnosed and undertreated each accounting for up to 20% of mortalities in these infants so the death rates for infants
Hospitalized with severe pneumonia are not very well described and as a group we really aimed to describe mortality rates um among these infants who have advanced HIV disease and are hospitalized with severe pneumonia so for the methods this is an ongoing uh phase two Open Labor randomized factorial 2x two trial
Basically assessing the impact of empirical treatment against CMV and TB in infants living with HIV hospitalized with severe pneumonia our study population here is children who are aged 1 month to just under a year living with HIV and have to be hospitalized and diagnosed with severe pneumonia so the primary end point for
Uh this study is all CS mortality at day 15 and 12 months post enrollment so with the study methods basically would have the screening and um these children would be subjected to find out whether they of course um are eligible for the study and would go through the inclusion criteria which was
Namely just HIV positivity the age group that I’ve mentioned and having being hospitalized with severe pneumonia so would go on to the screening and consent procedures and once trial um once informed consent is taken then the child would be enrolled into the study and undergo randomization as depicted in the
Slide so the randomization had four arms and so these children would be randomized to receive um the standard of care also the next option would be standard of care and valan cyclo which was treatment against CMV the next arm would be possibly standard of care and TB treatment and
The last arm would be both TB treatment vagan cyclo treatment against CMV and the standard of care so of course as mentioned the standard of care would include um antibiotics and um treatment for pneumocytic durov pneumonia which would include um high doses of C Moxy and um
Steroids the trial is um still ongoing and we are recruiting an end recruitment next year January we have six countries that are participating in this trial um that’s Uganda Coto Zambia Zimbabwe Malawi and mosm Beek of course our coordination is occurring in Spain and in Italy and we
Have our other partners in Netherlands France and the United Kingdom that are assisting with the PK studies and as well as the laboratory results so for this flowchart this is just depicting um the how the recruitment has been as of March 2023 we had a total of 431 patients that were
Enrolled and two were actually excluded from analysis um this was purely because some of the them were found to have probably positivity of tuberculosis and so were dropped out of that analysis and the 429 that went on into the analysis of these we had a total of
196 deaths and 45% of these um that accounted for the total cohort of the deaths 56% of the de deaths actually occurred in the initial hospitalization and 43% after after discharge all the deaths of occurred within a six-month period um currently we still have some patients that are in active followup and
Some that have also completed the study when we look at the Baseline characteristics of the 429 um enrolled children we had a median age of about 4 months and with the gender we had almost equal predisposition of 49% female um in terms of history of
Pmtct we had a total about 164 that did have um pmtct um in their records and those that were newly diagnosed on enrollment accounted for 71% of of the the participants we can also look at the clinical parameters that should show how ill these children were and most of them
Had chest inur growing as you can see 92% of them um some were unable to breastfeed severe malnutrition accounted for about 25% in terms of the laboratory parameters we can see very very high viral loads um and a low CD4 of up to 14.4% and when we look at the median
Hemoglobin that was about 9.2 in terms of the causes of death um pneumonia accounted for the majority of the deaths at 48% followed by sepsis and then we had unknown causes at that attributed to 15% those that died from gastroenteritis accounted for 7% tuberculosis accounted for five and the other causes this was
Listed as meningitis so some children had crypto cocal menitis some had some severe forms of DIC some also had encal and those were the other causes that um are under that 8% for the K May curve um this just depicts of course how high the mortality
Was in the initial um admission in terms of the days and it just depicts of course the high mortality as I mentioned in the first few 30 days of of of admission so to conclude basically children living with HIV and severe pneumonia really do have a very very high mortality both during the
Initial and um after Hospital discharge so the measures that should be focused on early identification and treatment as well as de decreasing the postd discharge mortality are really really urgently needed so the empirical team will report on the survival benefits of the CMV and tuberculosis treatment of course at trial conclusion
And emphasis really needs to look at addressing the missed opportunities for pmtct strengthening of course the early infant diagnosis and anti-retroviral initiation for those who really do fail pmtct I would like to thank all the children and families who’ve participated in this study and contined to do so as we continue with our
Recruitments I would like to also thank the empirical trial team who is here some of the members are present I would also like to um thank all the um the coordinating partners and edctp more importantly for funding this this project and also for according me the opportunity to come and stand and
Present these preliminary findings thank you very much for your attention um thank you very much um Dr Renda for sharing these amazing results from your study um so I’d like to open the floor for um a few questions thank thank you very much for that uh very insightful presentation my
Name is y I work for the clal access initiative uh two question first uh do we know the vaccination status uh for the for those infants they get their PCV vaccine and then secondly um how did you actually diagnose uh um uh pneumonia did you have like a specific way of saying
This is a bacterial pneumonia this is a viral pneumonia thank you okay thank you very much for your questions I think I’ll start with the last question that you’ve mentioned um in terms of the diagnosis we we for us to be able to diagnose the pneumonia it
Was actually clinical first of all and it was who um guidelines that we used in terms of just diagnosing them for the cut off in terms of even in the inclusion and in um and I’m I’m just wondering if you’re also wondering is it as a as the
Mortality for the confirmation in terms of the mortalities so for the mortalities we also do have some children that have been subjected to the minimally invasive um autopsies and we’re able to send these um uh results to the lab and we we we did collect some specimens so in terms of
The ICD classification some of them that just died um from the pneumonia if it was unspecified we labeled it as unspecified but those that were able to collect results we were able to then know whether it’s a viral origin or a bacterial origin I don’t know if that Mak sense is that
Okay he’s like no yes so the vaccination status I think we’ll be able to um answer that as we continue to refine the data I’m not very specific on the the the numbers that were vaccinated I can I can give you that information yes sir thank you for the
Question um thank you Benda I’m I’m David Mo from South Africa a very important findings from your study and congratulations on conducting such a a difficult trial I’m really anxiously awaiting the publication of the final results of the trial um I was just wanting to ask a couple of questions the
First was the the Baseline characteristics of your children about 60% of them had uh uh saturation recorders being less than 90% was that in room air or was that on supplemental oxygen um so that’s just one question and then the other was what sort of intensive care or high care support that
These children get and was there any um uh facility for invasive mechanical ventilation in some of these children thank you thank you very much for the questions so this was at room air yes and then We additionally gave the supplemental oxygen um through the nasal prongs or depending on of course what
They needed if someone needed high flow oxygen it was on a Case by case basis but the initial um clinical findings were on room room air then um when it comes to your second question in terms of the mechanical ventilation I think this was available should they have have required it in
Many of the centers but um at the moment we didn’t have any who needed to yeah um just to mention of course the children were very ill these are very very sick children as you can imagine because they already HIV infected and they do have severe
Pneumonia so we would the care the most of them would be nursed in the hdu or the ICU most of the time hi Frederick from University of Capon I’m I’m interested in the long-term consequences of of the infectious disease in the acute phase we all understand why people die um and and
Children so um you had a lot of unknowns there um are those the ones who died after discharge um can you talk a little bit more about the cause of death after discharge in the first year so with the unknowns because remember like I mentioned the children were very
Ill cuz some of them we would we would probably have these children enrolled and then they die suddenly just maybe very shortly after enrollment so those would account for their unknowns um most of these children would still stay for a very long time a very long stay in the
Hospital if they do if they did survive um but that being said most of them as I said accounted for the the majority of the deaths within the initial admissions most of them it was higher as I already explained um and they accounted for the unknowns but there were some patients of
Course post discharge that still did die and there was a very there was a very small percentage that would account for their unknowns from that cohort of patients but yeah I think it was just spread out post discharge post discharge okay I would have to give you the the data um very very Refinely’ because a lot of these children despite having that option being available would refuse to the parents would refuse to have it done so you would have to have a lot of clinical correlations and the results that you had when when reviewing these children yeah but I’m happy to share the
The information I think after the presentation yeah all right um thank you and also thanks for availing yourself for after the presentation um thank you very much for all the questions now I’ll hand over to my co-chair thank you Dr W okay and now I’m very pleased to
Introduce and uh to you uh Professor David Mo from the University of uh bat Waters rant uh from South Africa so please talk to Professor good morning everybody um thank you very much to the scientific committee for giving me the opportunity to present some of the preliminary findings from the screening process on
The Pedic cup study which is an edctp sponsored clinical trial which is currently being conducted in five subsaharan African countries as I will explain during the course of this talk um the talk is in entitled receipt of intervenous C Moxy clave challenged eligibility screening for the picap trial in Johannesburg South Africa
You’ll just notice one change to the title there I’ve changed from challenges to challenged um because thankfully we were able to complete um enrollment into the trial across all five sites in the middle of September 2023 um antimicrobial resistance driven in part by over prescription of antibiotics to treat sorry presumed
Bacterial infections poses a major threat to human health um these figures are from the global burden of bacterial antimicrobial resistance study which was published in 2019 and modeled estimates suggested that there were 5 million deaths attributable to antibiotic resistant bacterial infections with mortality rates highest in subsaharan Africa and
Lowest in Southeast Asia East Asia and Oceania the lowest uh the lower respiri tract infections uh where among the most frequently treated conditions associated with microb antimicrobial resistance worldwide in 2019 moving to another Global uh burden of disease study and that which published on findings from the global under five mortality rates these
Indicated that under um mortality rates decreased substantially from 71.2 deaths per uh thousand life births in 20 in 2000 to 37.1 per thousand live births in 2019 um while neonatal mortality rates decline more slowly in children under 5 years of age lower tract infections diarrheal diseases congenital birth
Defects and malaria were the leading causes of death outside the neonatal age group and low respiratory tract infections specifically accounted for 13.3% of the 5 million under five deaths in 2019 Global burden of disease estimates for the number of under five low respiratory tract infection deaths globally in 2019 ranged from 1,600
Deaths in high inome countries to over 35 350,000 deaths in subsaharan Africa with the highest mortality rates uh clustering in subsaharan Africa and you can see that rate there of 435 per 100,000 children under 5 years of age these burden of disease and mortality estimates justify ongoing concerted efforts at exploring ways in
Which lower respir to tract infection hospitalizations can be prevented and managed appropriately particularly in Subs subsaharan Africa and South Asia guideline recommendations for the treatment of low spot tract infections in South African children were updated in 2020 um and the recommendation is that we administer intravenus or oral moxilin
Clavulanate or Co moxiclav to Children requiring hospitalization for severe uh pneumonia and these recommendations were based on two important pneumonia iology studies which were conducted in South Africa the perch study of South Africa being one of the contributing countries as well as the gerenstein um study which was conducted as a longitudinal birth
Both Birth Cohort study in the Western Cape and both of these um studies found that the bacterial isolates amongst children that were um hospitalized with severe pneumonia um were those such as hemophilus influenza and St staphilococcus orius which would tend to respond U more um adequately to treatment with Co moxiclav compared to
Amoxicilin or ampicillin as was as per the previous guidelines um one of my uh Master student conducted a survey at our Hospital looking at how clinicians treat children hospitalized with severe low respiratory tract infections and during the course of her project she screened 183 children and enrolled um 8 85 of
These um and noted that amongst the children that were enrolled um nearly 90% had received antimicrobial therapy according to um the clinician prescriptions what was also very concerning from her study was that amongst the children with an admission diagnosis of bronchiolitis which we know is um a clinical syndrome driven
Particularly by respiratory viruses and notably by respiratory s virus a large proportion of those children had been initiated on empiric antimicrobial therapy um at the U at at uh at at um admission to hospital and that um of those children that had a formal laboratory uh C reactive protein sub uh
Submitted for um investigation as to whether a child might potentially have a viral or bacterial illness um that 90% of those with uh CRP which ended up being less than 10 milligrams per liter or more suggestive of viral infections um 90% of these children received antibiotics um in collaboration with
Some of my colleagues working at academic uh pediatric academic centers in quaz Natal and in uh ptor um South Africa um we contributed to a point prevalent survey which was recently published in the Pediatric infectious disease Journal um which we chose to title as uh Healthcare Associated infections Drive antimicrobial prescribing in pediatric
Departments at three academic hospitals in South Africa in this point prevalence survey which in which we utilize World Health Organization methodology to conduct the study we screened uh 5,200 pediatric inpatients and found that just under um 1,200 them or of 22.9% had received a pediatric um uh had received
Antimicrobials with quite varying um prevalence of antimicrobial prescribing across the sites you can see that hospital C had a very low prevalence of prescribing compared to hospital um a and Hospital B what was quite concerning as well in the course of the study was that uh we
Found that 45.6 of all the prescriptions were for Hospital acquired infections um and that lower respirat detection infection in children contributed to around 8% of the antimicrobial prescribing so we now turn our Focus to the picap trial which is an edctp sponsored trial and uh funded trial and sponsored by the penta um
Um um and this is a trial which is looking at rationalizing the um dependence on uh antimicrobial therapy Europe in children hospitalized with severe pneumonia in subsaharan Africa it is a a 2×5 uh factorial trial um which is looking at the step down to either disposable amoxicilin tablets or
Dispersible co co moxiclav tablets has a formulation of 7 to one um of amoxil to clavulanate um compared to um the 5 day uh routine use of wh recommended uh injectable um treatment for children requiring hospital lization for severe pneumonia and those who recommended regimens are intravenous ampicilin gent
Gyin or uh intravenous penicillin or intravenous krion or keot taxine of note in the uh clinical trial um is that the who recommended invest uh injectable regimens does not include intravenous Co Moxy clav the other aspect of the factorial design of this trial is to look at differing um durations of
Antimicrobial step down ranging from 4 to 8 Days the inclusion criteria for picap I’ll just quickly Breeze through the slide um is a child age between 2 months and six years of age in an appropriate weight band for the study and admitted to hospital with sever pneumonia requiring at least 24 hours of
Antibiotics I’ve highlighted in red on this slide that the children are about to initiate or initiate a intravenous antibiotic therapy using wh recommended therapy for severe pneumonia which as I highlighted in my discussion in the previous slide excludes um receipt of intravenous Co Moxy clave so another important aspect was
The exclusion criteria which is anticipated need for systemic treatment with an antibiotic other than the trial regimen and this would obviously exclude children that have been treated with intravenous Co moxiclav so we aims to describe how the South African guidance on severe pneumonia case management impacted on pyap screening and enrollment at the
Johannesburg picap site we maintained a line list of all hospitalizations to the general pediatric WS at our Hospital the chrisan baragan academic hospital we screened all age eligible children with resp spatry admission diagnosis and we appraised the extent to which receipts of IV coxic have impacted on participant recruitment into the
Trial so this is the enrollment uh uh flow chart um from the 14th to July 2021 to the 31st of October 2023 um we’ve screened over uh or nearly 15,000 uh pediatric Admissions and of those with that were age eligible for picap um so 8,603 um children at that were age
Eligible and admitted on pediatric on Pedic cap screening days accounted for about 70% of all of the age eligible children um uh with low respirator tract infections uh so that were admitted during the course of the uh the study period um of those 50% nearly 3,000 had respiratory uh
Hospitalizations um 66 16 were screened and we were able to enroll 287 into the study so important reasons for for not being enrolled into the study um was that the children were either not on antibiotic therapy um or they were on oral antibiotics already but importantly
As well one of the major drivers as to why we weren’t able to screen into the study was that children had been administered intravenous K moxiclav as per the South African African guide uh pneumonia guidance for children and that accounted for 355 of the children we interrogated the formal
Laboratory C reactive protein levels in the children uh according to the different strategies um the the different categories and you can see amongst the children that were enrolled into picap the um the laboratory uh CRP at Baseline was um 2 Mig per liter and significantly higher than the the
Laboratory um CRP uh I um which was um present in those that were not enrolled into the study because they were given intravenous coloxyl and for amongst children not enrolled for other reasons um most of those or many of those having been treated for instance with oral antibiotic therapy the C reactive
Protein was also significantly lower these are concerning showing that children um treated with intravenous Moxy clave might in fact not be um warranting such broad broads spectrum antibiotic therapy we also looked at the length of hospitalization and the outcomes in terms of deaths amongst the children and uh there was no significant difference
Amongst the um stratified by according to the whether children were enrolled into the study or those given intravenous anti coxic La between the length of hospitalized Hospital stay and also importantly no significant difference in terms of the um survival in hospital outcomes uh so death case ferality rates were were statistically
Uh similar between the groups so in uh discussion around our findings with the children hospitalized for severe pneumonia in South Africa frequently receive coox clav ivi as per Lo local guidelines um and that in picap where receipt of intervenous Co Marx laab was an exclusion Criterion for participation
12% of those screened had received this inter intervention and therefore could not be considered for enrollment into the trial children administered IV coox had significantly lower serum CRP levels a baseline compared to those that were enrolled into the trial and length of stay and survival outcomes were similar
Into the children who were administered IV car Moxy clav C these observations open up potential new avenues for antimicrobial stewardship in our setting and um I was posing the question as to whether this might not help us to prompt the design and set of a multinational studies in
Africa to evaluate the impact of point of care biomarker tests to guide clinicians in rationalizing prescribing practices i’ just like to acknowledge my study team at this at the cusani bar site edctp for the funding of the study for uh to Penta my colleagues at Vitz
University and to Mike charin at the UCL MRC clinical trial unit who’s guided us through the um uh the trial um very very expertly and um uh during during the course of our engagement with the trial thank you very much [Applause] thank you David for this excellent
Presentation and uh we have time for a couple of questions and of course please take the um lunch time to make a lot of questions to to your to your presenters thank you thanks David um in routine practice outside of the pdap study are point of care uh inflammatory tests available at
Your hospital and are those us used for admission treatment decisions thanks Chris um so point of care tests are not available um there has been some preliminary work published from Uganda and specifically um yeah so so from Uganda looking at outpatient use of of point of care tests to guide clinician
Antimicrobial prescribing um but uh I feel that this might be a a really um a nice step forward to try and look at the impact on antimicrobials prescribing in children requiring hospitalization I didn’t mention that as part of the routine procedures in picap we do a
Point of care uh CRP test and only children with a CR point of care CRP test of greater than 10 milligrams per liter on semi-quantitative test would be enrolled thank you any more questions any postpone questions from the previous presentation yes um my name is y I just want to like
Ask question to the malaria team yeah particularly about the generalizability of the data that generating uh that could be used to inform U Public Health policy so I think um yeah I’ve done research clinical triers a lot and I also do a lot of program implementation so in the space
Of malaria I think they have this what they call the malaria data repository and they do uh Public Health Systems do conduct an exerise which they call stratification so when they go to they collect all the data this is a big data set from efficacy trials anology and so
On and also resistance data and then they put this in a database and then they use that data to do a stratification so and produce some sort of heat maps that would tell you that this position at this this particular location in the country you have high resistance for for for this antimalaria
You have high resistance for this bed net you have a uh high transmission and then you need seasonal chemoprophylaxis in these other areas and so on so my question is um Can this sort of Public Health tools be used to inform clinical trial designs and selection of Trials
And um if yes what could be like the best approach and if not how confident are we that the data that they are generating without taking into consideration the publical interventions that are being implemented by government and and Global fund taking into consideration this um this uh stratification exercises how confident
Are we that their results are not biased any of the malaria experts please Adrian I don’t want to put you on the spot not but but any of the malaria expert would like to to to answer these question I mean I can comment on edctp uh perspective um our strategy malaria is
Really well align with the wh but of course maybe we have not done uh going that far um in a stratification of data but we know there are other organizations and for me because I didn’t pick up your your the organization you are working with with
Um but worm is collecting a lot of data in that sense H we know that um but of course I’m not an expert in malaria ER and this is why I would like to invite any experts here if would like to comment on this
This is way out in left field for me um but maybe I can speak to one aspect of your question which is which has to do with with with trial design and I think I what we heard this morning for example from buchina Faso is a very good example
Of where a trial design uh was I guess obliged to incorporate all the current uh currently applied uh means and methods of intervention in their trial yeah including uh bed nets and including uh prophylaxis and chemo prevention and all the rest so uh I have the impression that in any case currently
Clinical trials in the malaria context uh do take into account these aspects because because they’re somehow obliged to I don’t know if that helps to answer the question but that’s that’s what I can contribute okay I think um this session is about finishing and um we want to
Thank all the presenters for keeping to the time maybe the chairs have not keep into the time in the questions H but H for a great job and also to the audience for being so engaged and so interested so please continue your discussions offline and um let us know if you want
To to be connected to some particular and I pass to my co-chair in case I have missed something thank you no you basically um have wrapped it up well um cooch um we’d like to thank everyone for participating in this um session we’ll see you lunchtime yeah thank you thank you
Well well well thank you very