bluuebunny/crossref_metadata_2025_split huggingface dataset:
PO 8609 PREVALENCE AND RISK FACTORS FOR GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY IN TWOP. VIVAXMALARIA-ENDEMIC AREAS IN SUDAN
Authors: Hamid Muzamil Mahdi Abdel , Albsheer Musab , Muneer Mohamed , Altinae Lina , Lover Andrew A 
Published: April 2019

BackgroundPlasmodium vivaxmalaria is a major health problem in Sudan and the parasite has become widely distributed in the recent years. The WHO recommends the use of primaquine as radical cure for liver dormant stage, the hypnozoite. However, prior its use, a test for Glucose-6-phosphate Dehydrogenase (G6PD) should be performed. The objective of the current study was to determine prevalence and risk factors for G6PD deficiency in twoP. vivaxmalaria-endemic areas in Sudan.MethodsA cross-sectional study recruiting 557 subjects from two malaria-endemic areas in Sudan was conducted. Demographic data and blood samples were collected. G6PD activity was measured by spectrometry using SPINREACT enzymatic-UV kit.ResultsThe measured G6PD activities for both sites ranged from 0.6 to 37.7 U/g Hb, with a median value of 12.8 U/g Hb. There was a significant difference in enzyme activity by study site (p<0.001), but not by sex (p=0.91). Overall, across the two study sites, 22 (3.9%) is G6PDd (<30%). Prevalence of G6PDd (<30%) in Khartoum is 1.8% (4/230) compared to 4.8% (16/327) in New Hafla. In univariate analysis predictors of G6PDd were study site (odds ratio of G6PD activity <3.8, Khartoum relative to New Halfa=0.22 (95% CI: 0.08 to 0.66), p=0.006), and recent antibiotic use (OR=2.45 (95% CI: 1.1 to 5.5), p=0.027). In multivariate analysis, the only factor that was significant was the individual’s weight in kilograms, with an OR of 0.97 (95% CI 0.95 to 0.99, p=0.014).ConclusionG6PD deficiency is less prevalent among Sudanese population and this indicates that the use of primaquine for radical cure ofP. vivaxmalaria is safe.
OC 8474 ASSESSMENT OF ETHICS REVIEW FRAMEWORKS FOR HEALTH RESEARCH IN EAST AFRICA FOR PURPOSES OF HARMONISATION
Authors: Kibiki Gibson S , Twungubumwe Novat , Kombe Francis , IJsselmuiden Carel , Bahati Prince N , Kamali Anatoli , Ngirabega Jean De Dieu 
Published: April 2019

BackgroundCapacity in health research ethics review is key in Africa, given the increase in research activities, complexity, and use of advanced technologies. Harmonising ethics review frameworks can address challenges attributable to these complexities. Establishing an effective harmonised framework that is optimum or protection of the research subjects requires assessment of review capacity.The East African Health Research Commission commissioned a study to assess the capacity of Review Ethics Committees (RECs) in the East African Community (EAC) countries, as a step towards strengthening and harmonising the regions’ capacity and review frameworks.MethodsA desktop review of documentation (national and institutional guidelines, policies and SOPs) was conducted in five EAC countries. Semi-structured questionnaires were used to collect data from key informants. Qualitative interviews were used to collect views on stakeholders’ perception of benefits, opportunities and challenges of harmonisation.ResultsSixty-nine (69) accredited RECs were mapped. All countries had national ethics guidelines and National Research Regulatory Authorities, whose mandates varied across countries. 57% of RECs reviewed local and international research, 43% reviewed local studies only. On average, 91 protocols were reviewed annually across all RECs (range 15 to 200). Membership ranged from 6 to 22 members per REC, with age range of 29 to 75 years.Annual budget allocation ranged from $3000 to $2.9 million financed through review fees (84%) or/and institutional budget (14%). 71% of RECs had education policy but 41%had members with training in ethics. Review turn-around time ranged from 14 to 90 days. All RECs supported harmonisation and attributed it to improved efficiency, quality and standardised costs.ConclusionSimilarities and dissimilarities were noted in the EAC countries’ ethics review frameworks. Harmonisation should consider 1) harmonisation of policy frameworks and tools; 2) institutionalisation of regional joint review mechanisms, 3) standardisation of training and capacity strengthening, 4) Review of the REC operational and financing models.
OC 8494 DRIVING REDUCED AIDS-ASSOCIATED MENINGO-ENCEPHALITIS MORTALITY
Authors: Loyse Angela , Mfinanga Godfrey S , Kanyama Cecilia , Kounfack Charles , Lesikari Sokoine , Chawinga Chimwemwe , Stack Muirgen , Molloy Sile 
Published: April 2019

BackgroundDREAMM is an implementation study aiming to reduce meningo-encephalitis related mortality. Delays in diagnosis and treatment through poor access to diagnostics and treatments are significant contributing factors to the ongoing high mortality of HIV-associated central nervous system (CNS) infections, causing up to 25% of all HIV-related deaths in sub-Saharan Africa.MethodsA before-after design is being implemented across 3 sites in Africa; Lilongwe, Malawi, Dar Es Salaam, Tanzania and Yaoundé, Cameroon. The study is composed of 3 phases: Observation, Training and Implementation.ResultsThe observation phase (audit of practice) happened between November 2016 – May 2017 in Malawi and Tanzania. Overall, 110 patients were included. Ten-week all-cause mortality was 64% (42/66) in Tanzania and 37% (13/35) in Malawi. Approximately 75% of patients were ART experienced. Across sites, 76.6% of patients presented with abnormal mental status, with a median baseline CD4 count of 50 cells/µL. Only 2/75 patients in Tanzania had a lumbar puncture ordered compared to 27/35 in Malawi. All patients in Tanzania received empirical Fluconazole monotherapy whereas almost 1/3 patients in Malawi (11/35) were treated with Amphotericin B which is not readily available in both countries.The training phase (completed in November 2017 for Malawi and Tanzania) used the train-the-trainer approach. Interactive workshops on using rapid diagnostic tests (RDTs), performing basic microbiological techniques and safe administration of medicines were chosen as the most pertinent to reducing mortality. Patient and laboratory pathways were optimised afterwards by increasing the routine laboratory capacity, performing CSF analysis, providing infectious diseases mentorship for clinicians and procuring RDTs and reagents not locally available.Implementation is underway in Malawi and Tanzania and the audit phase is scheduled for autumn in Cameroon. Upon completion, the project is expected to create a sustainable approach to reduce the high mortality of HIV-related meningo-encephalitis with the optimised patient and laboratory pathways embedded within routine care.
OC 8510 BIOTRANSFORMATION OF PRAZIQUANTEL FOR THE PHARMACOKINETIC OPTIMISATION OF PRAZIQUANTEL USE IN MASS DRUG ADMINISTRATION AND DEVELOPMENT OF NEW PAEDIATRIC FORMULATIONS
Authors: Thelingwani Roslyn S , Kapungu Nyasha , Li Xueqing , Kanji Comfort , Mutiti Chenai , Reinhard-Rupp Wilma J , Masimirembwa Collen 
Published: April 2019

BackgroundPraziquantel (PZQ) is the only drug available for the treatment of all forms of schistosomiasis. New paediatric formulations for the active enantiomer R-PZQ and the racemate PZQ are currently under development. There is however limited drug metabolism and pharmacokinetic data on PZQ available to support these initiatives. Detailed knowledge of PZQ metabolism will enable the use of PBPK modelling to determine appropriate doses for the new formulations in paediatric patients and to predict risks for drug-drug interactions in mass drug administration.MethodsBiotransformation studies on PZQ were conducted in human liver microsomes and recombinant Cytochrome P450s (CYPs). Structure elucidation was inferred from mass spectra. Enzyme kinetic studies to determine the Michaelis-Menten kinetics, Km and Vmax, of the formation of the main metabolites and analysis of clinical samples were determined by LC-MS/MS.ResultsCYP reaction phenotyping studies with HLM and r-CYPs indicate major involvement of CYP1A2, 2 C19, 2D6 and 3A4/5 in the metabolism of R- and S-PZQ. Biotransformation studies showed that PZQ is metabolised to cis-4-OH-PZQ mainly by CYP1A2 and CYP2C19. CYP3A4/5 metabolises PZQ to a mono-hydroxyl metabolite (X-OH-PZQ) whilst CYP2D6 metabolises PZQ to minor novel mono-hydroxyl metabolite (Y-OH-PZQ) both pending structural elucidation by nuclear magnetic resonance. R-PZQ was more rapidly cleared than S–PZQ with variable interindividual AUC and Cmax.Discussion and conclusionThe differential role of CYP1A2 and CYP2C19 and of CYP3A4 and CYP3A5 in the formation the 4-OH-PZQ and the novel X-OH-PZQ respectively are intriguing findings as this has not been reported before in humans.In vitro, cis and not trans 4-OH-PZQ formation has been observed contraryin vivoreports in humans which indicate trans 4-OH-PZQ as the main metabolite. The data will enable us to understand the rapid clearance of PZQ and predict potential drug-drug-gene interactions which mayexplain the inter-individual variability of PZQ pharmacokinetics.
OC 8713 MAXIMISING RESEARCH IMPACT TO STRENGTHEN PUBLIC HEALTHCARE
Authors: Sabiiti Wilber , Ntinginya Nyanda E , Msoka Elizabeth Fb , Orina Fred , Mwebaza Ivan , Mwanyonga Simeon , Miheso Barbara , Sanga Erica , Liyoyo Aliphonce , Meme Helen , Mmbaga Blandina T , Chirnside Ewan , Joloba Moses , Amukoye Evans , Okwera Alphonse , Kibiki Gibson S , Gillespie Stephen H , Mwebaza Wilber , Msoka Nyanda E 
Published: April 2019

BackgroundBillions of dollars are spent on research globally every year, yet little is translated to public use through policy and/or commercialisation. For the few research findings that make it to policy, evidence in most LMICs shows they hardly see the light of implementation. Our EDCTP-funded TWENDE consortium used implementation of tuberculosis (TB) molecular diagnostics as a model to investigate the barriers, and opportunities to unlock them in order to maximise uptake of health research innovations into policy and practice.MethodsMixed methods approach including surveys, audits, in-depth interviews and focus group discussions (FGDs), policymaker dialogues to unravel the bottlenecks and how to overcome them.Results1119 respondents representing from Uganda, Kenya and Tanzania participated in the study. 19% were district/county health officers, 12% healthcare audits, 58% one-on-one interviews and FGDs with healthcare practitioners, community leaders, TB patients and survivors, and care givers, and 11% policymaker workshops. Barriers: government poverty, family/individual poverty, incompatibility of technologies to existing infrastructure, low awareness and socio-cultural beliefs in the community were found. Stigma at community and healthcare levels was rife. Consequently, TB diagnostics were underimplemented and underutilised. Xpert MTB/RIF test was fully utilised in ∼10% of healthcare facilities (conducting 8 tests per day) whilst Line probe assay was implemented in less than 1% of the facilities.ConclusionBased on our findings, we believe overcoming the barriers presents the opportunity to maximise research impact of public healthcare. This could be achieved through sustained public and practitioners’ sensitisation to remove stigma to increase demand and utilisation of services; early interaction of researchers and policymakers to increase sense of ownership and acceptability of research innovations; early communication between developers and end-users to align the tools with the needs and existing infrastructure capacity; and increased affordability of innovations through socioeconomic empowerment programmes.
OC 8718 WHAT DID WE LEARN FROM PANACEA 1 CLINICAL TRIALS?
Authors: Ntinginya Nyanda E 
Published: April 2019

BackgroundThe Pan African Consortium for the Evaluation of Anti-Tuberculosis Antibiotics (PanACEA) was designed to build clinical tuberculosis (TB) trial capacity whilst conducting clinical trials on novel and existing agents to shorten and simplify TB treatment. One of the objectives was to conduct, mentor and monitor observational and clinical studies at sites in 6 Sub-Saharan TB-endemic countries (Gabon, Kenya, South Africa, Tanzania, Uganda and Zambia)MethodsLearning through experience. All centres in the 6 countries self-assessed their requirements for capacity development in the following fields: a) clinical staff availability and experience; b) TB laboratory infrastructure and staff; c) safety laboratory infrastructure and staff; d) clinical site facilities and equipment; e) pharmacy facilities and staff; IT facilities; and f) overall training needs of site personnel.ResultsFrom March 2011 – June 2014, we conducted four epidemiological studies (characterising TB patient populations in preparation for future studies) and five phase II studies (GCP standard intervention trials).By working together in epidemiological and clinical trials, the sites identified their needs for resources and training as well as developing capabilities to perform independent large-scale TB clinical trials beyond PanACEA-initiated trials. Through the ReMoxTB study, for example, laboratories were brought to an international standard for safety and mycobacterial expertise. Furthermore, through developing skill-sets related to EBA studies, sites have since then attracted other sponsors for further studies.Sites could be mentored to perform GCP-compliant clinical TB trials that is built on sound physical infrastructure, training and strong on-site leadership.ConclusionThe learning-by-doing approach meant that staff could be trained whilst acquiring new core competencies and revealing operational gaps. Our experience of conducting TB trials within an environment of mentoring, networking and training has provided a platform for establishing future sustainable research centres that has capacities to conduct highly regulated studies.
PO 7151 COMPARING TWO BED NET DELIVERY MODELS IN’RURAL DISTRICTS OF MOZAMBIQUE
Authors: Arroz Jorge 
Published: April 2019

BackgroundThe use of long-lasting insecticidal nets (LLINs) is associated with a reduction in malaria transmission. In 2015, a new delivery strategy (intervention) for universal coverage campaign was tested and compared with standard strategy (control). The objective is to compare two bed net delivery models in rural districts of Mozambique.MethodsTwo districts served as intervention, and two as control. The following study design was used: 1) before and after; and 2) cost-effectiveness analysis. Three core implementation strategies were tested: 1) use of coupons during household registration, 2) use of stickers to identify registered houses, and 3) a new LLINs allocation criterion. The main endpoints measured were: i) percentage of distributed LLINs; ii) LLINs ownership and use coverage; iii) percentage of households that achieved universal coverage; iv) incremental cost-effectiveness ratio (ICER); v) incremental net benefit (INB).ResultsApproximately 88% (302,648) of LLINs were distributed in intervention districts compared to 77% (219,613) in control districts [OR: 2.14 (95% CI: 2.11–2.16)]. Six months after the 2015 campaign, 98.8% of the 760 households surveyed in the intervention districts had at least one LLIN; 89.6% of the 787 households surveyed in the control districts had at least one LLIN [OR: 9.7, (95% CI: 5.25–22.76)]. Near 95% and 87% of respondents who had at least one LLIN, reported having slept under the LLIN the previous night in the intervention and control districts, respectively [OR: 3.2; (95% CI 2.12–4.69)]; 71% of the households surveyed achieved universal coverage in the intervention districts against 59.6% in the control districts [OR: 1.6; (95% CI: 1.33–2.03)]. ICER per distributed LLIN was US$ 0.68. INB was positive.ConclusionIntervention districts had greater LLINs availability, greater LLINs ownership and use coverage, and a better progression toward reaching universal coverage targets. The new strategy was more cost-effective than the previous strategy.
OC 8259 THE VALIDATE NETWORK: EXPLOITING SYNERGIES BETWEEN COMPLEX INTRACELLULAR NEGLECTED PATHOGENS TO EXPEDITE VACCINE R&D FOR TUBERCULOSIS, LEISHMANIASIS, LEPROSY AND MELIOIDOSIS
Authors: Vermaak Samantha , Fletcher Helen , McShane Helen 
Published: April 2019

BackgroundThe VALIDATE ‘VAccine deveLopment for complex Intracellular neglecteD pAThogEns’ Network is a Global Challenges Research Fund (GCRF) Network, funded by the UK MRC and BBSRC and led by the University of Oxford and the London School of Hygiene and Tropical Medicine. It aims to accelerate vaccine development for four intracellular pathogens,Mycobacterium tuberculosis,Leishmaniaspp,Mycobacterium lepraeandBurkholderia pseudomallei, by creating a network of scientists from around the world in an interactive community, sharing information, learning from synergies and differences, and forming new collaborations promoting cross-disciplinary, cross-pathogen, and cross-continent research.MembershipCurrently VALIDATE has 125 members from 66 institutes in 28 countries, including world leading scientists, post-doctoral researchers, postgraduate students, and interested lay members from academia, governmental agencies, industry, and non-profits.ActivitiesVALIDATE has four activity streams: 1) providing funding to its members, including pump-priming grants for excellent research, training grants for early career researchers, and fellowships to transition post-doctoral researchers to independence, 2) a members’ data-sharing portal, to encourage real-time sharing of data, catalysing the application of insights from one field into another, with an in-house Research Data Analyst working on cross-pathogen applications, 3) providing CPD opportunities for our members, including workshops, seminars and a mentoring scheme, and 4) speeding the dissemination of useful and relevant information via a hub website (www.validate-network.org) and social media (@NetworkValidate) where our members can easily find information about new research, relevant funding calls, events, and training, mentoring and other opportunities. Interested parties can read about our funded work, while a searchable directory of members on our website and a free annual meeting facilitates the formation of new collaborations.VALIDATE is free to join and has an inclusive membership. This network would be of interest to researchers at the EDCTP Forum working on vaccine development for tuberculosis, leishmaniasis, leprosy and melioidosis.
PO 8248 DETERMINANTS OF ACCEPTABILITY OF MALARIA RAPID DIAGNOSTIC TEST AMONG HEALTH WORKERS IN KINTAMPO NORTH MUNICIPALITY, GHANA
Authors: Anaba Michael , Ae-Ngebisi Kenneth , Agyei Seth Owusu , Ibisomi Latifat 
Published: April 2019

BackgroundGhana rolled out the policy in 2013 with the use of malaria rapid diagnostic test (mRDT) promoted to facilitate diagnosis. However, health workers who are at the centre of mRDT implementation still treat half of febrile patients with negative mRDT results with antimalarial drugs, suggesting limited or lack of acceptability of the innovation.MethodsWe conducted a cross-sectional study to examine determinants of mRDT among health workers in Kintampo North Municipality (KNM) in Ghana. Data were collected from 110 health workers in KNM involved in malaria management from February to April 2017. The survey tool was based on two frameworks – the Technology Acceptance Model (TAM) and Normalisation Process Theory (NPT). Acceptability was measured by ease of use, perceived usefulness and intention to use.We hypothesised that acceptability was influenced by coherence, cognitive participation, collective action, reflexive monitoring and respondent characteristics. A composite acceptability score was computed from a 21-item questionnaire for each respondent. The respondents were divided into three groups of low, moderate and high acceptability for ordered logistic regression to examine the relationship between acceptability and its determinants.ResultsThe median acceptability score was 84(Q1, Q3:68, 103). About 34% of health workers had low acceptability while 37% and 29% had moderate and high acceptability respectively. In the multivariable analysis, coherence (OR=1.23, 95%CI=1.11–1.37), cognitive participation (OR=1.35, 95%CI=1.10–1.66), health workers in rural health facilities (OR=6.99, 95%CI=1.82–26.84) and health workers with more than three years’ experience (OR=5.53, 95%CI=1.98–15.42) were more likely to have high mRDT acceptability.ConclusionAcceptability of mRDT was moderate among the majority. This can be improved by enhancing health workers’ coherence on the benefits of mRDT through policy building or dissemination of information, promoting health workers’ cognitive participation in the mRDT implementation process through recruitment of local ‘champions’ to promote ‘buy-in’ and providing incentives to health workers to embed and sustain the use of the health technology.
PO 8269 SELECTION OF SEVEN-MUTATION PFCRT-PFMDR1 GENOTYPE AFTER SCALING-UP SEASONAL MALARIA CHEMOPREVENTION WITH SULPHADOXINE-PYRIMETHAMINE AND AMODIAQUINE IN MALI
Authors: Maiga Hamma , Bamadio Amadou , Traore Aliou , Diallo Nouhoum , Diarra Modibo , Sagara Issaka , Niangaly Hamidou , Coumare Samba , Sangare Boubou , Traore Djibril , Vaillant Michel , Dicko Alassane , Doumbo Ogobara K , Djimde Abdoulaye 
Published: April 2019

BackgroundWHO recommended seasonal malaria chemoprevention (SMC) in 2012 for Sahel countries in Africa with the aim to reduce malaria among children under 5 years old by using sulphadoxine-pyrimethamine and amodiaquine (SP+AQ). This strategy was scaled up in Mali from 2012. The use of millions of doses of SP+AQ could generate potentialPlasmodium falciparumresistance in mutant parasites. The aim of this study was to monitor the prevalence ofPfdhfr +Pfdhps+pfcrt +pfmdr1mutations in parasites infecting the target population.MethodsTwo cross-sectional surveys were conducted before (August 2012, n=662) and after (June 2014, n=670) a pilot implementation of SMC in the health district of Koutiala. Children aged 3–59 months received 3 and 4 rounds of curative doses of SP+AQ over two malaria seasons in 2012 and 2013, respectively. Genotypes ofP. falciparum Pfdhfrcodons 51, 59, 108 and 164;Pfdhpscodons 437 and 540,Pfcrtcodon 76 andPfmdr1codon 86 were analysed by PCR on DNA of parasites from SMC population blood samples (after and before) and non-SMC patients aged 7 years or above (November 2014, n=500).ResultsIn the SMC population 191 and 85 children before and after SMC implementation, respectively, were included inthe molecular analysis. In the non-SMC patients, 220 weresuccessfully PCR analysed. In the SMC population, theprevalence of the six-mutationPfcrt[Pfdhfr-dhpsquintuple +Pfcrt-76T] genotype increased significantly after SMC implementation, from 0.0% to 7.1% (p=0.0008). The post-intervention prevalence of the six-mutationPfmdr1[Pfdhfr-dhpsquintuple +Pfmdr1–86Y] and the seven-mutationPfcrt +Pfmdr1[Pfdhfr-dhpsquintuple +Pfmdr1–86Y+Pfcrt-76T] genotypes were both 1.2% among the SMC population. No six-mutation and seven-mutation genotypes were observed among SMC population at baseline nor in the non-SMC patient population (p=0.30).ConclusionSMC increased the prevalence of the six-mutationPfcrtgenotype ofP. falciparumthat can lead to resistance in a population exposed to SMC with SP+AQ.