bluuebunny/crossref_metadata_2025_split huggingface dataset:
PO 8575 EVOLUTION OF MALARIA MORBIDITY IN TWO VILLAGES IN KOROGWE, TANZANIA
Authors: Lusingu John , Minja Daniel , Theander Thor 
Published: April 2019

BackgroundThe malaria burden has decreased significantly in recent years in sub-Saharan Africa due to targeted interventions aimed at parasites and vectors. However, studies have shown that a limited number of infective bites makes individuals in malaria-endemic regions more susceptible to subsequent malaria infection as they grow older due to waning or lost immunity. This study investigated the evolution of malaria morbidity for 14 years in Korogwe, Tanzania since 2003.MethodsA longitudinal study was carried out in Korogwe over 14 years, from January 2003 to December 2017 whereby community health workers (CHWs) passively monitored malaria episodes at a village health post. They evaluated febrile episodes and collected blood smears from all residents of the community who presented with fever. The blood smears were processed and read at the Korogwe field station by two independent microscopists. Artemisinin combination therapy (ACT) and malaria rapid diagnostic tests were introduced in the community in 2007. Uncomplicated malaria cases were treated with sulphadoxine-pyrimethamine (SP) from 2003 to 2006, then with artemether-lumefantrine (ALu) from 2007.ResultsA total of 20,841 attendances were documented by CHWs between 2003 and 2017. Malaria parasitaemia was documented in 5043 consultations [24.1% (95% confidence interval (CI): 23.6% to 24.8%)]. Interestingly, malaria episodes declined markedly from 38.12% to 10.42% between 2003 and 2017. The highest reduction was documented in 2010 (at 3.1%) but thereafter, there was an increase in malaria in 2015 to 32.2% which decreased to 10.42% in 2017. Use of long-lasting insecticide-treated nets (LLINs) was associated with reduction of malaria episodes by 34% (95% CI: 26% to 42%).ConclusionPrompt diagnosis at village level, use of ACT and LLINs has contributed to the reduced number of malaria episodes in Korogwe. However, the malaria resurgences raised concerns about malaria elimination in these communities.
PO 8580 TREATMENT RESPONSE AMONG CAMEROONIAN ADOLESCENTS RECEIVING ANTIRETROVIRAL THERAPY IN URBAN AND RURAL SETTINGS: PRELIMINARY FINDINGS FROM THE READY STUDY
Authors: Fokam Joseph , Takou Desire , Santoro Maria , Nangmo Armanda , Sosso Samuel M , Teto Georges , Colizzi Vittorio , Perno Carlo-Federico , Ndjolo Alexis 
Published: April 2019

BackgroundTransitioning from paediatric to adult healthcare requires successful antiretroviral treatment (ART) for adolescents living with HIV (ADLHIV). Implementing such a policy implies monitoring ART response and selecting for therapeutic options for ADLHIV in resource-limited settings (RLS) like Cameroon.MethodsThe Ready study (EDCTP-CDF-1027) is conducted amongst ART-experienced ADLHIV (10–19 years old) in the Centre region, Cameroon. WHO-clinical staging, CD4-counts and viraemia were determined; in case of virological failure [VF] (viraemia ≥1000 copies/ml), HIV drug resistance (HIVDR) and subtyping were performed, and p<0.05 considered significant.ResultsOut of 279 ADLHIV (212 urban vs 67 rural), the gender distribution was similar (54.5% female); median age was higher in urban (15 [IQR: 13–17] years) compared to rural (13 [IQR: 11–17] years), as well as the median duration on ART (7 [IQR: 3–10] years compared to 4 [IQR: 2–7] years, respectively); and the majority was on first-line ART (79.4% [162/204] urban vs 98.5% [66/67] rural, p<0.0004). Following treatment response, clinical failure (WHO-stage 3/4) was similarly low in both urban (5.7% [12/210]) and rural (4.5% [3/67]), p=0.938; CD4 increased similarly (p=0.298) from ART-initiation (370 cells/mm3[urban] vs 332 cells/mm3[rural]) to 6 years after initiation (938 cells/mm3[urban] vs 548 cells/mm3[rural]) and rate of immunodeficiency (<500 CD4 cells/mm3) was 41.0% (87/208) in urban vs 47.5% (29/61) in rural, p=0.428. VF was 43.2% (41/95) in urban vs 60.9% (14/23) in rural, p=0.126. Among nine (9) sequences available from those experiencing VF, overall HIVDR was found in 88.8%, with 77.7% NNRTI, 55.6% NRTI and 22.2% PI/r. All were HIV-1 group M, with 55.6% CRF02_AG, 22.0% F1 and 22.4% others.ConclusionADLHIV appear clinically asymptomatic, with considerable immune recovery overtime. Despite differences in ART duration between urban and rural settings, VF was similarly high, associated with HIVDR mainly to NNRTI-based regimens. Thus, NNRTI-sparing regimens might be highly convenient when transitioning ADLHIV to adult ART-regimens in RLS like Cameroon.
OC 8469 REVIEWING INVESTIGATIONAL PRODUCT’S QUALITY ASSURANCE DOCUMENTATION IN MAJOR CLINICAL TRIAL REGISTRIES FOR POST-MARKETING CLINICAL TRIAL STUDIES
Authors: Doua Joachim , Dominicus Hanneke 
Published: April 2019

BackgroundThe proven worrisome quality of medicines marketed in developing countries also affects clinical trials (CTs) as they may be used as Investigational Medicinal Products (IMPs). By regulation, CT sponsors should assure IMP’s quality and describe their quality measures in CT protocols that should be registered in a CT Registry (CTR). To check compliance with this regulation, we reviewed major CTRs to assess the availabilities of data fields on IMP quality for post-marketing CTs.MethodsTwo reviewers independently assessed English versions of CTRs of International Committee of Medical Journal Editors (ICJME) and WHO platforms in July 2017. Each CTR was checked for availability of data fields on: brand name; manufacturer’s name; regulatory approval status; approving regulator; manufacturer’s compliance with Good Manufacturing Practices (cGMP); and quality testing (IMP appearance, impurities, microbial contamination, dosing). In case of discrepancy, consensus was sought.ResultsOf 19 CTRs identified, 8 and 6 belonged to WHO and ICMJE, respectively, and 5 were equally part of both platforms. All CTRs had an ‘intervention’ data field to capture data on IMPs and IMP comparators. Unlike all others, the Canadian CTR used ‘drug name’ rather than ‘intervention’. Only the EU CTR had data fields for ‘manufacturer’s name’, ‘product approval status’, and ‘approving authority’. None of the CTRs had data fields on ‘cGMP’ or ‘quality testing’.ConclusionNone of the CTRs of ICMJE and ICTRP has adequate data fields to establish that the source of post-marketing IMPs is of assured quality. This is astonishing given the extensive requirements in WHO and ICMJE guidelines. The gap of quality assurance fields should be bridged by adding them to CTRs. Specifically, IMP quality testing should be conducted before, during, and after clinical trial completion. Until adoption of these measures, EU-CTR should be favoured for registration of CTs conducted in developing countries.
OC 8491 PREPVACC: A PHASE III, MAMS ADAPTIVE PROPHYLACTIC HIV VACCINE TRIAL WITH A SECOND RANDOMISATION TO COMPARE F/TAF WITH TDF/FTC PREP
Authors: Joseph Sarah , Kaleebu Pontiano , Ruzagira Eugene , Hansen Christian Holm , Seeley Janet , Basajja Vincent , Weber Jonathan , Fox Julie , Kingsley Cherry , Aboud Said , Lyamuya Eligius , Maganga Lucas , Pamba Doreen , Ramjee Gita , Yssel Justin , Viegas Edna , Jani Ilesh , Priddy Fran , Nilsson Charlotta , Kroidl Arne , Pantaleo Giuseppe , Robb Merlin , Crook Angela , Dunne David , Mccormack Sheena 
Published: April 2019

BackgroundThere remains an urgent need for a prophylactic HIV vaccine to control generalised epidemics. PrEP has demonstrated effectiveness of 86% and is recommended by WHO; uptake is generally high, but retention is disappointing in some settings. The EDCTP2 project PrEPVacc will assess the efficacy of two combination prophylactic vaccine regimens (DNA, MVA and Env protein/adjuvant) each compared to placebo and the proportion of infections averted by F/TAF in comparison to TDF/FTC. A Registration Cohort, recruiting HIV negative volunteers at risk of HIV will precede the trial.MethodsThe PrEPVacc partnership agreed that 70% vaccine efficacy had public health relevance. The trial usesnstagesoftware for multi-arm, multi-stage designs (MAMS) and the averted infections ratio (AIR) methodology with participants randomised (i) 1:1:1 to active product or placebo (ii) 1:1 to TDF/FTC : F/TAF until week 26 (presumed peak immunogenicity). Access to PrEP in the Registration Cohort and after week 26 will be standard of care. HIV seroconversions occurring between weeks 0–26 will inform the PrEP analysis, incorporating HIV incidence amongst those who do not take up PrEP locally in the Registration Cohort. Seroconversions after week 26 will inform vaccine analyses.ResultsUp to 556 participants per group affords 92% power to detect vaccine efficacy of 70% at the final analysis, assuming incidence of 4/100-person years and 10% loss with 81% and 97% power to conclude that F/TAF can avert half or more of the infections prevented by TDF/FTC if effectiveness of TDF/FTC is 70% and 80%, respectively.ConclusionPrEPVacc adopts a pragmatic approach to uncertainties around HIV incidence in settings where PrEP is increasingly available. This innovative adaptive trial design uses validated software to determine vaccine efficacy and a novel methodology to evaluate a new PrEP agent, overcoming the challenge of demonstrating non-inferiority when adherence to TDF/FTC is high and the number of outcome events very low.
OC 8521 PRELIMINARY REPORT ON SAFETY OF CO-ADMINISTERED HUMAN HOOKWORM VACCINE CANDIDATESNA-APR-1 (M74)/ALHYDROGEL®ANDNA-GST-1/ALHYDROGEL®IN GABONESE CHILDREN
Authors: Zinsou Jeannot Fréjus , Honpkehedji Josiane , Agobe Jean Claude Dejon , Adegbite Bayodé R , Ronald Edoa Jean , Van Leeuwen Remko , Diemert David , Elena Botazzi Maria , Kremsner Peter G , Yazdanbakhsh Maria , Hotez Peter , P Grobusch Martin , Akim Adegnika Ayola , De Vries Sophie 
Published: April 2019

BackgroundHuman hookworm infection is a major public health issue in tropical low and middle-income countries with severe consequences. To date, improvement of water supply, sanitation, and hygiene is the major contributor to disease control, and additional control tools are needed. Here, we assess a phase I trial of a new hookworm vaccine candidateNa-APR-1 (M74)/Alhydrogel andNa-GST-1/Alhydrogel in Gabonese school-age children.MethodsA double-blind, randomised, controlled, dose-escalation phase I clinical trial that aims to evaluate safety, reactogenicity and immunogenicity ofNa-APR-1 (M74)/Alhydrogel co-administered withNa-GST-1/Alhydrogel hookworm vaccines in children aged 6 to 10 years living in hookworm-endemic area of Lambaréné, compared to the hepatitis B vaccine (ENGERIX-B). Children received three doses of assigned vaccines, delivered intramuscularly (deltoid) on Days 0, 56, and 112 or 180. Safety is measured from Day 0 through Day 14 by the occurrence of solicited injection site and systemic reactogenicity events. Clinical laboratory evaluations were performed approximately 14 days after each immunisation. Unsolicited adverse events were collected from Day 0 through approximately 1 month after each vaccination.ResultsA total of 135 children were screened, and 60, aged 6 to 10 years old, were randomised into 3 groups and received 10 µg, 30 µg or 100 µg ofNa-APR-1 (M74)/Alhydrogel andNa-GST-1 Alhydrogel, respectively, compared to ENGERIX-B. At baseline, the mean age of the study population was 7.4 years and the sex ratio 1.3 (male: female). From Day 0 up to Day 14 after vaccination, the main solicited adverse events were pain and swelling at injection sites with 135 (26 of grade 2 and 1 of grade 3) and 9 events, respectively. Regarding systemic adverse events, 3 occurrences of grade 1 headache were recorded. Immunogenicity analyses are underway.ConclusionThe preliminary results confirm that co-administration of the two hookworm vaccine candidates is safe and well-tolerated in Gabonese children.
OC 8535 AN OVERVIEW OF RESEARCH ETHICS COMMITTEES OPERATING IN LUSOPHONE AFRICAN COUNTRIES
Authors: Rosário Oliveira Martins Maria , Schwalbach João , Sevene Esperança , Martins Antonieta , Candida Branco Fernandes Ema , Ines Araujo Isabel , Pereira De Melo Helena , Bernardo Tome Da Silva Amilcar , Catumbela Emanuel , Sacarlal Jahit , Seixas Jorge , Chimpolo Maria , Nala Rassul , Tazi Nimi Maria , Rodrigues Amabelia 
Published: April 2019

BackgroundIn 2017, a North-South partnership was created, to strengthen Bioethics Committees in African Lusophone African countries (LAC), by joining the forces of National and Institutional Research Ethics Committees (REC) and Universities in Angola, Cape Verde, Mozambique and Portugal. This study is part of an EDCTP2-funded project and aims to describe key RECs operating in LAC, its establishment dates and further characteristics.MethodsDocument analysis and interviews with REC representatives of five LAC were conducted in April 2018. Legal documents were obtained through official national sources.ResultsWe identified four National Ethics Committees, created between 2000 and 2008 by ministerial or governmental decree; only S. Tomé e Principe does not have an established REC. In Angola, the National REC was created in 2000, and since 2007, seven Institutional Committees were implemented at faculty level. National REC in Cape Verde and Guinee-Bissau (CNES) are unique and were founded in 2007 and 2009 respectively. In Mozambique, National REC (CNBS) dates to 2002, and since 2011, 8 Institutional Committees were formed; they functioned as a network under the umbrella of CNBS. Most National REC have representatives from health professional associations, lawyers, civil society and religious communities and have regular meetings (usually monthly). The number of members ranges between 6 (CNES) and 13 (CNBS). In 2007, around 200 protocols were reviewed by CNBS and 29 by CNES. Most of the National REC members attended training activities in bioethics but at different levels.ConclusionFew publications described REC operating in LAC; this study fills this gap by reporting historical and functional characteristics of RECs in five Lusophone African countries. Additional tools based on quantitative and qualitative approaches are being developed to assess more in-depth REC operational characteristics and to identify their needs in order to target training and capacity building initiatives underlying our project.
OC 8552 EFFICACY OF THE CHAD63-MVC ME-TRAP VECTORED MALARIA VACCINE CANDIDATE IN 5–17 MONTHS OLD INFANTS AND CHILDREN IN BURKINA FASO
Authors: Tiono Alfred B , Nebie Issa , Anagnostou Nicholas , Coulibaly Sam A , Lawrie Alison , Bougouma Edith C , Ouedraogo Alphonse , Yaro Jean Baptist , Barry Aïssata , Roberts Rachel , Ouedraogo Amidou , Ewer Katie J , Viebig Nicola K , Diarra Amidou , Leroy Odile , Bejon Philip , Hill Adrian , Sirima Sodiomon B 
Published: April 2019

BackgroundHeterologous prime-boost immunisation with chimpanzee adenovirus 63 (ChAd63) and Modified Vaccinia Virus Ankara (MVA)-vectored vaccines is a strategy previously shown to provide substantial protective efficacy againstP. falciparuminfection in a UK adult phase IIa sporozoite challenge study, and in a trial in Kenyan adults.MethodsWe conducted the first phase IIb clinical trial assessing the safety, immunogenicity and efficacy of ChAd63-MVA ME-TRAP in 700 healthy malaria exposed children aged 5–17 months in a highly malaria-endemic area of Burkina Faso.Participants were randomly assigned to received either ChAd63 ME-TRAP followed eight weeks later by MVA ME-TRAP or 2 doses of rabies vaccine. Monitoring of solicited adverse events was performed for seven days after each vaccination. Unsolicited adverse events were recorded until one month post each vaccination. Serious adverse events and malaria episodes were monitored throughout the study duration. Blood samples were collected at predefined timepoints to assess vaccine immunogenicity.ResultsChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses [median 326 SFU/106 PBMC (95% CI 290–387)]. However, non-significant low efficacy was observed against clinical malaria during the follow-up period, with efficacy against primary endpoint estimated by proportional analysis being 10.7% (95% CI: −44.2 to 44.7%) at sixth months post MVA ME-TRAP and 3.1% (95% CI −15.0 to 18.3; p=0.72) by cox regression.ConclusionThis study has confirmed ChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in children and infants with prior exposure to malaria. No significant protective efficacy was observed in this highly endemic context.
OC 8568 A RANDOMISED CONTROLLED TRIAL OF ORAL IRON FOR TREATMENT OF POST-MALARIA ANAEMIA IN MALAWIAN CHILDREN COMPARING IMMEDIATE VERSUS DELAYED ADMINISTRATION
Authors: Phiri Kamija , Longwe Herbert , White Sarah , Esan Michael , Kuile Feiko Ter , Brabin Bernard 
Published: April 2019

BackgroundAlthough universal provision of iron supplements to children is recommended by the WHO, it is not yet clear whether the administration of the supplements poses a risk in children in malaria-endemic areas. We investigate the effects of iron supplementation in children with post-malaria anaemia and haematological response with immediate and delayed (2weeks) iron administration.MethodsA randomised double-blind clinical trial was conducted in Zomba and Blantyre between 2009 and 2013. All children aged 4 to 36 months with uncomplicated malaria and with iron deficiency were enrolled into the study. Malaria treatment was administered to all the children and they were randomly assigned to 3 groups as follows: immediate iron administration, delayed iron administration, or placebo. The children were followed up for 10 weeks, with their haematological recovery indices and adverse effects being monitored at 2, 4, 8 and 10 weeks. The primary outcome of the study was the proportion of children without anaemia (defined as Hb >10.9 g/dl) at the end of the iron supplementation period.ResultsA total of 538 participants were randomised to immediate iron administration (n=183), delayed iron administration (n=183), or placebo (n=172). The incidence rate ratio (IRR) of being non-anaemic at the end of the follow-up period (10 weeks post-malaria infection) was 1.51 (95% CI 1.17–1.94, p<0.001) among immediate group versus the placebo group. There was no significant difference between delayed and placebo group (IRR 1.18, 95% CI 0.91–1.55). Secondary analysis of risk of malaria and bacterial infection and iron markers at the end of the intervention period is underway and shall be presented at the conference.ConclusionThe results so far support the administration of iron immediately after completing antimalarial treatment in anaemic children, however safety results will be needed to be reviewed before conclusive recommendations.
OC 8582 A PHASE IA/B STUDY TO ASSESS SAFETY AND IMMUNOGENICITY OF PLACENTAL MALARIA VACCINE CANDIDATE: PRELIMINARY RESULTS OF THE PRIMALVAC TRIAL
Authors: Konate Amadou , Richert Laura , Chêne Arnaud , Semblat Jean-Philippe , Roguet Gwenaelle , Benhamouda Nadine , Bahuaud Mathilde , Havelange Nicolas , Kuppers Alexis , Campion Cécilia , Boilet Valérie , Gueguen Sonia , Loulergue Pierre , Leroy Odile , Batteux Frederic , Tartour Eric , Viebig Nicola K , Thiebaut Rodolphe , Sirima Sodiomon B , Launay Odile , Gamain Benoit 
Published: April 2019

BackgroundAdhesion ofP. falciparum-infected erythrocytes (PEs) to placental chondroitin-4-sulfate (CSA) has been linked to severe placental malaria (PM) outcomes. Evidence strongly supports the VAR2CSA variant surface antigen mediating PEs CSA-binding phenotype as the leading candidate for a PM vaccine. This study was conducted to assess the safety and immunogenicity of 3 different dosages (20 µg, 50 µg and 100 µg) of the recombinant VAR2CSA protein (PRIMVAC), formulated with Alhydrogel or GLA-SE administered at days 0, 28 and 56.MethodsA randomised double-blind phase Ia/Ib dose-escalation vaccine trial was conducted in healthy adult women. Within 4 sequential cohorts, volunteers were randomised to 2 arms (PRIMVAC adjuvanted with Alhydrogel or GLA-SE) in the first phase conducted in France and then to 3 arms (PRIMVAC with Alhydrogel or GLA-SE or placebo) in Burkina Faso. Enrolled volunteers were observed for at least 1 hour following each vaccination then seen at 1 day and 7 days later for safety evaluations. Serious adverse events (SAE) were recorded throughout the study duration. Routine clinical laboratory safety analyses were performed prior to first injection and at each subsequent visit.ResultsA total of 68 subjects were recruited in the four study cohorts. No SAE was reported in any of the cohort A volunteers and enrolment in cohort B was started. A Data Safety Monitoring Board (DSMB) reviewed the safety data for cohorts A (20 µg) and B (50 µg) before the trial was initiated in Burkina Faso. The DSMB also reviewed the safety data in Burkina to authorise the progression from the cohort C (50 µg) to cohort D (100 µg). The last vaccination of the last subject occurred in September 2017.ConclusionThis was the first placental malaria vaccine phase Ia/b clinical trial conducted in France and Burkina Faso. No serious adverse events have been recorded. Preliminary safety and immunogenicity results will be presented.
PO 8179 MEAN LEVELS OF ENDOPLASMIC RETICULUM STRESS CHAPERONE PROTEIN – BINDING IMMUNOGLOBULIN PROTEIN (BIP) DECREASES FOLLOWING SUCCESSFUL TB TREATMENT
Authors: Motaung Bongani , Loxton Andre G 
Published: April 2019

BackgroundMycobacterium tuberculosis(Mtb) infection is one of the leading causes of mortality worldwide. Even though treatment is readily available the emergence of drug resistance amongst Mtb strains highlights the need for new advances in the TB field such as host-directed therapies (HDT). Recent studies have highlighted the importance of BiP in cells, which can become a target in many diagnostic settings as it has been implicated in conditions including arthritis, cancer, bacterial infection and autoimmune diseases. In our studies, we are aiming to identify expression differences of BiP in different Mtb infection stages to help us understand the change of function in immune cells in relation to infection stress.MethodBiP secretion levels were assessed in plasma samples using ELISA technique. This included participants at TB diagnosis (TBDx), TB treatment group (Week 1, Month 2 and Month 6) and healthy (unexposed) participants. BiP concentration results were analysed using GraphPad Prism 7.ResultsSecretion of BiP was comparable between newly diagnosed untreated TB cases and healthy unexposed controls, with levels obtained in healthy group (42.64 µg/ml) and in TBDx (40.88 µg/ml). Highest levels of plasma BiP during treated TB was observed by Week 1 (mean 68.57 µg/ml) and declined by Month 2 with 60.92 µg/ml and Month 6 with 51.40 µg/ml.ConclusionDetection of BiP in plasma samples indicated metabolic change in immune cells due to stress posed onto cells by Mtb burden. This is due to the amount of protein product required by the immune system to mitigate the spread of the pathogen. Even though not significant, we observed a decrease in the mean levels of BiP over the course of TB treatment which correlates with a reduction in the accumulation of unfolded polypeptides in the endoplasmatic reticulum. This observation requires further testing in larger prospective studies.