bluuebunny/crossref_metadata_2025_split huggingface dataset:
PO 8590 COMPARATIVE ANALYSIS OF IGG RESPONSES TO RECOMBINANT Qβ PHAGE DISPLAYED MSP3 AND UBO5 IN DUAL HIV/MALARIA-CO-INFECTED ADULTS
Authors: Nchinda Godwin , Lissom Abel , Ouambo Herve , Okeke Malachy I , Tchouangueu Thibeau F , Tchouangueu Loveline N , Okoli Arinze S , Achidi Eric , Mbacham Wilfred , Kaptue Lazare , Esimone Charles O , Leke Rose F , Waffo Alain B 
Published: April 2019

BackgroundImmunoglobulin G (IgG)-specific responses againstPlasmodium falciparummerozoite antigens such as the merozoite surface protein 3 (MSP3) and UBO5 are known to play critical roles in parasitaemia control and protection from symptomatic illness. However, when there is intense perennial malaria transmission coupled with concurrent infection with the human immunodeficiency virus type 1 (HIV), knowledge of IgG antibody response profiles is limited.In this study we assessed the impact of dual HIV/malaria infections on IgG subclass responses to MSP3 (QβMSP3) and UBO5 (QβUB05) in individuals living in two areas of Cameroon differing in malaria transmission intensity.MethodsIgG and IgG subclass responses specific to either MSP3 or UBO5 were determined in plasma from study participant by ELISA. To improve reactivity with their respective antibodies the antigens were displayed upon the surface of the RNA coliphage Qβ.ResultsWe observed differences in antigen-specific IgG and IgG subclass responses which were dependent upon the antigen type, malaria transmission intensity, HIV infection, malaria infection and dual HIV/malaria infections. Individuals living in areas with high malaria transmission, had irrespective of HIV or malaria status significantly higher IgG responses to both antigens (p=0.0001 for QβMSP3, p=0.0001 for QβUB05) than their counterpart from areas with low transmission. When dual HIV/malaria infection is considered, significantly higher QβMSP3 specific IgG1 (p=0.0001) and IgG3 (p=0.04) responses in double-negative individuals was associated with protection against malaria in areas with low transmission. Superior QβUBO5 specific IgG1 responses (p=0.0001) in double-negative individuals were associated with protection in areas with high transmission in contrast to significantly higher IgG3 responses to QβUBO5 (p=0.0001) which were more relevant to protection in areas with low malaria transmission in the same population.ConclusionThus, understanding immune responses to QβUBO5 and QβMSP3 could facilitate the development of immunotherapeutic strategies suitable for areas differing in malaria transmission intensity.
PO 8594 VALIDATION OF A VERBAL AUTOPSY QUESTIONNAIRE APPLIED TO A CASE-CONTROL STUDY OF CEREBRAL MALARIA IN BANDIAGARA AND BAMAKO, MALI
Authors: Traore Karim , Coulibaly Drissy , Kone Abdoulaye K , Thera Ali , Guindo Boureima , Tangara Bourama M , Diawara Aichatou A , Doumbo Ogobara K , Thera Mahamadou A 
Published: April 2019

BackgroundMalaria remains a leading cause of child mortality in sub-Saharan Africa. Severe malaria is the main pathway to death caused by malaria. A study of factors associated with protection against severe malaria is best achieved using a case-control design. However, these studies are affected by the quality and appropriateness of the choice of controls that may introduce important bias in study design and definitively alter the conclusions from the studies. It is of paramount importance that the presence or absence of an episode of severe malaria in the history of the controls is ascertained. In settings with reliable medical data this is easily tracked back from hospital records. In settings like Bandiagara, with weak health care systems, a dedicated approach is needed to track history of severe malaria. We used an adapted verbal autopsy questionnaire to identify presence of cerebral malaria in the history of controls in a case-control study of severe malaria in Bandiagara.We have assessed the sensitivity, specificity and predictive positive and negative values of the questionnaire.MethodsFrom January through August 2018 we enrolled 450 children with or without known confirmed cerebral malaria selected at health care centers in Bandiagara and Bamako, with archived medical records. Parents of enrolled children were identified, located and interviewed using the adapted verbal autopsy questionnaire. Interviewers were not aware of children’s diagnosis. We compared the diagnosis derived from the verbal autopsy questionnaire to the confirmed biological diagnosis from the medical records.ResultsWe will present full results on the sensitivity, specificity, the predictive positive and negative values of the verbal questionnaire, and the Kappa coefficient of agreement.ConclusionA good verbal questionnaire will enhance the quality of the choice of controls in case-control studies of severe malaria and overall will improve the quality and relevance of inferences from such studies.
PO 8595 FACTORS ASSOCIATED WITH VIROLOGIC FAILURE AMONG WOMEN WITH PRIOR EXPOSURE TO ANTIRETROVIRAL DRUGS FOR PMTCT, KISUMU, KENYA
Authors: Angira Francis , Awuonda Eucabeth , Oruko Jacinter , Boaz Oyaro , Asadhi Elijah , Olilo George 
Published: April 2019

BackgroundUse of antiretroviral drugs (ARVs) for a discrete period for Preventing Mother-to-Child HIV transmission (PMTCT) only may be compared to Structured Treatment Interruption, which has been associated with virologic failure (VF). We sought to determine factors associated with VF among women on Antiretroviral Therapy (ART) but with prior exposure to short-term ARVs for PMTCT.MethodsHIV-infected women presenting for ART initiation in three HIV care clinics in Kisumu County, Kenya were enrolled in the KiBS follow-up study (2010–2013) if they had previously received triple ARVs for PMTCT (Group 1) or short-course ARVs for PMTCT (Group 2) or were ARVs-naïve (Group 3). First-line ART was provided as per 2010 WHO treatment guidelines and viral load (VL) tests were conducted every six months for 24 months. VF was defined as any confirmed VL value ≥400 copies/ml after 6 months of ART initiation. Frequencies and proportions were used in the descriptive analysis while Pearson’s Chi-square/Fisher’s exact test was used to determine the association between VF and eight independent variables. Univariate and Multivariate Cox-proportional regression model was fitted to investigate factors associated with VF.ResultsOut of 284 participants data for 245 were analysed (Group 1: 27; Group 2: 107; Group 3: 111). Majority were aged 25–29 years and over 60% had primary/lesser education. There were 39 (Group 1: 5; Group 2: 16; Group 3: 18) VFs with a total VF incidence of 8.12 [95% CI (5.96, 11.17)] per 1000 Person months of observation (PMOs). Group 2 had the lowest VF incidence. Baseline CD4 <349 cells/mm3and initiation/use of TDF/3TC/EFV were associated with virologic failure (VF).ConclusionWomen at risk of VF based on the identified risk factors should be identified and targeted with appropriate intervention. Further studies are needed to verify and understand the mechanisms of association between VF and TDF/3TC/EFV which is a WHO-recommended first-line ART regimen.
PO 8719 INTRODUCING A NEW AFRICA MENINGITIS NETWORK – A NORTH-SOUTH COLLABORATION
Authors: Mosepele Mosepele , Kanyama Cecilia , Meya David , Cresswell Fiona , Chammard Timothee , Mwandumba Henry , Meintjes Graeme , Mfinanga Godfrey S , Ndhlovu Chiratidzo , Jarvis Joseph 
Published: April 2019

BackgroundCentral nervous system infections, including meningitis, continue to cause significant morbidity in Africa. HIV has contributed to the epidemiology of CNS infections in this setting. Notable advances in the study of CNS infections by several groups have demonstrated the utility of new diagnostic strategies and impact of novel treatment strategies. However, efforts to coordinate meningitis research in Africa, and between Africa and the rest of the world remain very limited.MethodsIn a bid to promote a coordinated study of CNS infections across Africa, and in collaboration with other meningitis groups globally, the researchers of the AMBITION study (High Dose Ambisome on a Fluconazole Backbone for Cryptococcal Meningitis Induction Therapy in Sub-saharan Africa: A Randomised Controlled Non-inferiority Trial) are leveraging the EDCTP support for the AMBITION trial to set up an Africa Meningitis Trials Network.ResultsThe Africa Meningitis Trials Network (AMNET) was launched in Malawi in early 2018. Main achievements since the launch of the network, include an internal review of meningitis research across network sites and launch of the network website. The network also has two study protocols pending ethics review at all sites. These studies will provide much needed information on resources available for meningitis care, research and provide a baseline epidemiology of meningitis in Africa.ConclusionAMNET provides a rare opportunity for investigators interested in meningitis research to leverage the ongoing AMBITION trial to conduct Africa-wide preliminary research on meningitis. The network is recruiting additional members in Africa and globally to collaborate on meningitis research, and also apply for research funding to support meningitis work. Anyone interested in knowing more about the network should contact the AMNET communications officer, Ms Phum’lani Machao,phumlani.machao@gmail.com
PO 8720 IMPACT OF EXPANDED USE OF AN ONLINE ETHICS REVIEW SYSTEM IN AFRICA: A PARTNERSHIP BETWEEN IAVI, COHRED, AND EDCTP WITH NATIONAL REGULATORY AGENCIES
Authors: Kombe Francis , Haskins Marzelle , Salim Amina Mkonje , Ayebazibwe Flavia , IJsselmuiden Carel 
Published: April 2019

BackgroundRHInnO Ethics is a cloud-based online ethics review system that enables Reseach Ethics Committees (RECs) to receive, review and approve applications online. Over the last five years, RHInnO Ethics has been installed in 40 RECs that operate in 12 African countries.MethodsPharma Ethics (South Africa), Strathmore University (Kenya) and Uganda Virus Research Institute-UVRI (Uganda) started using RHInnO Ethics in 2014, 2015 and 2017 respectively. Although the platform is currently installed in 40 RECs in Africa, only 1 systematic evaluation has been done to objectively assess its impact on the quality and efficiency of ethics review. Here, we present the experiences of using RHInnO Ethics from three RECs situated in East Africa (2 RECs) and South Africa (1 REC).ResultsStrathmore University started using the online ethics review system since the beginning of its operation, while Pharma Ethics and UVRI transitioned from a manual to an electronic system. Benefits associated with the use of the platform include improved efficiency in communication among key players of the ethics review processes, improved quality of review through standardisation and harmonisation of ethics review procedures, easy management of information, increased submissions and improved turnaround time. The progress of review can also be tracked any time by all users. Challenges include change management from the manual to the online system, difficulties in learning new versions of the system and training new reviewers not conversant with the system, interruption of internet access and limited ability to personalise the platform.ConclusionThere is a need to get buy-in from regulatory authorities to enforce the adaption of the system to all RECs in order to make research coordination in Africa easier. RHInnO Ethics has been shown to improve efficiency and quality of reviews. However, the transition to and full adoption of the online system continues to be slow. To accelerate and scale up the adoption of RHInnO Ethics, there is a need for developers, RECs and sponsors of RECs to engage with REC regulatory authorities, and identify responsive models of financing and funding RECs in order to increase efficiency and quality of ethics review in sub-Saharan Africa.
OC 8477 MAKING RESEARCH EASIER, BETTER AND FASTER THROUGH KNOWLEDGE SHARING AND BUILDING COMMUNITIES OF PRACTICE
Authors: Abade Leandro 
Published: April 2019

BackgroundThe Global Health Network improves the health research capacity of low- and middle-income countries (LMICs) by facilitating know-how and knowledge exchange between organisations, disease areas, regions and roles. We show how we use the sharing phenomenon to transform and drive health research in resource-limited settings.MethodsWe harnessed cutting-edge technology that facilitates engagement of medical researchers and healthcare professionals in low-resource settings and creates opportunity for knowledge exchange and capacity development in global health. We built highly functional digital communities of practice (CoPs) that serve as learning and sharing tools for researchers, and a gateway for sharing experience about disease research. These CoPs are intertwined with regional activities such as training workshops with health care professionals, which helps to enhance engagement and impact.ResultsWe disseminate resources with collaborators to enable research in LMICs via 37 CoPs. The data derived from these CoPs is used to identify knowledge-gaps in research capacity, as well as a guide to the development of resources and tools, such as standardised outcome measures. The network has developed 25 free peer-reviewed e-learning courses covering a wide range of topics, as well as high-quality professional development tools. We highlight the WHO-TDR Professional Development Scheme that tracks and guides training and career development. The network has trained over 33 500 professionals (with >400 k courses taken) across 119 LMICs on the principles of good clinical practices ensuring the safety of research participants and the integrity and validity of research data.ConclusionThe Global Health Network is enabling research in areas where data is missing by providing tools, training, and resources whilst supporting and training research teams. The next step is to widen this impact and invite new researchers to drive and enable more and better clinical research in places and situations where evidence is still woefully lacking.
OC 8215 DIAGNOSTIC ACCURACY OF XPERT MTB/RIF ULTRA FOR PULMONARY TUBERCULOSIS IN CHILDREN: A MULTICENTRE COMPARATIVE STUDY
Authors: Sabi Issa , Rachow Andrea , Mapamba Daniel , Clowes Petra , Ntinginya Nyanda E , Sasamalo Mohamed , Kamwela Lujeko , Haraka Frederick , Hoelscher Michael , Paris Daniel , Saathoff Elmar , Reither Klaus 
Published: April 2019

BackgroundXpert® MTB/RIF (Xpert) has suboptimal sensitivity for the diagnosis of pulmonary tuberculosis in children. The next-generation Xpert MTB/RIF Ultra assay (Xpert Ultra) is substantially more sensitive than Xpert and may allow improved detection of paediatric tuberculosis. We evaluated the diagnostic accuracy of Xpert Ultra versus Xpert in the detection of pulmonary tuberculosis in children.MethodsFrom May 2011 to September 2012, children with presumptive pulmonary tuberculosis were enrolled at two Tanzanian research sites in the EDCTP-funded TB CHILD project. Sputum samples were collected and examined for tuberculosis using sputum smear, Xpert and culture. Xpert Ultra analysis was performed between January and June 2017 at both sites using decontaminated sputum pellets which had been stored at −80°C. The diagnostic accuracy of Xpert and Xpert Ultra was determined using well-defined case definitions as reference standard.ResultsIn total, 215 children were included in the analysis. The median age was 5.4 years (IQR, 1.5 to 9.9), the HIV prevalence was 52%, and 28 children (13%) had culture-confirmed pulmonary tuberculosis. When only the first available sample of each patient was considered, the sensitivity of Xpert Ultra was 64.3% (95% CI: 44.1 to 81.4) while that of Xpert was 53.6% (95% CI: 33.9 to 72.5). The specificity of Xpert Ultra based on the analysis of all available samples was 98.1% (95% CI: 93.4 to 99.7), whereas that of Xpert was 100%.ConclusionIn settings with a high burden of tuberculosis and HIV, Xpert Ultra had a better sensitivity than Xpert in children. However, the specificity was slightly lower than that of Xpert. Thus, Xpert Ultra has the potential to increase the reliability and the speed of tuberculosis diagnosis in children.
OC 8586 INSTITUTIONAL RESEARCH CAPACITY BUILDING FOR MULTI-DISCIPLINARY HEALTH RESEARCH TO SUPPORT THE HEALTH SYSTEM REBUILDING PHASE IN SIERRA LEONE
Authors: Haja Wurie 
Published: April 2019

BackgroundThe EDCTP-funded project ‘Institutional capacity development for multi-disciplinary health research to support the health system rebuilding phase in Sierra Leone’ (RECAP-SL) created a solid platform on which sustainable research capacity can be built at the College of Medicine and Allied Health Sciences (COMAHS) at the University of Sierra Leone. This in turn will support the much-needed evidence-based health systems reconstruction phase in Sierra Leone and support the evolution of the research landscape at COMAHS.Methods and resultsWe established a research centre at COMAHS and conducted a research needs assessment. This informed the development of short- and long-term action plans to support sustainable institutional research capacity development and enabled the development of a four-year research strategy. These plans also served as a guide for subsequent research partnerships in terms of capacity building efforts to address identified challenges.We also focused on training four research fellows and developed a wider student engagement platform to help cultivate a research culture. The research fellows will support other researchers at COMAHS, thus promoting sustainability of the research centre. Continued professional development opportunities for the fellows are also being actively sought, to develop them up to doctoral level, which addresses one of the gaps identified in the capacity assessment report.ConclusionTo support sustainability, capacity building efforts are being designed to ensure that these gains are maintained over time, with international and national research partners and funders recognising the importance of further developing local research capacity. Through a multi-pronged approach, health systems research capacity has been strengthened in Sierra Leone. This will support the generation of evidence that will inform building sustainable health systems fit for responding cohesively to outbreaks and for delivering services across the country, especially for the most disadvantaged populations.
OC 8711 EARLY BIOMARKERS OF LUNG INFLAMMATION AND FUNCTION IN TRIALS OF HOST-DIRECTED TUBERCULOSIS THERAPIES (TB-HDT)
Authors: Wallis Robert , Beattie Trevor , Likoti Morongwe , Ahidjo Bintou , Edward Vinodh , Rassool Mohammed , Ahmed Khatija , Ginindza Sibuse , Fielding Katherine , Churchyard Gavin , Vangu Mboyo 
Published: April 2019

BackgroundPermanent lung injury and impaired function are common despite TB cure. Host-directed anti-inflammatory therapies may prevent this injury. Early biomarkers of lung inflammation and function can facilitate their evaluation.MethodsIn an ongoing study supported by the Bill and Melinda Gates Foundation, HIV-uninfected patients with radiographically moderately or far advanced sputum smear-positive pulmonary tuberculosis receive rifabutin-substituted standard therapy plus either CC-11050 (phosphodiesterase inhibitor), everolimus (mTOR inhibitor), auranofin (gold salt), cholecalciferol, or control, during months 1–4. Study leadership is blinded as to assigned treatments. 18F-fluorodeoxyglucose positron emision tomography (PET) and computed tomography (CT) are performed at baseline and at week 8. Total lung glycolytic activity (SUVbw*ml) and radiodensity (modified HU*ml) are measured using MIM software. Sputum culture, spirometry, 6 min walk test (6MWT), and other biomarkers are performed at multiple time points. Follow-up continues to month 18. This analysis includes only baseline and week 8 data.ResultsPresently, 160/200 participants are enrolled. At baseline, patients have a high burden of infection (median time to detection [TTD] in automated liquid culture 5 days). Median baseline FEV1% of predicted (63%) and 6MWT (402 meters) are typical of moderate to severe chronic lung disease. Baseline TTD, PET, CT, FEV1% and 6MWT are all highly correlated (median rank test p=0.0018). All 5 parameters changed significantly during 8 weeks of treatment (p<0.001). Analysis of adjusted log change from baseline shows PET and CT remain highly correlated (p<0.001), and weakly correlated with FEV1% and 6MWT. TTD shows no correlation with any other endpoint.ConclusionQuantitative markers of infection, inflammation, and function are markedly abnormal and highly correlated at baseline in patients with pulmonary tuberculosis. Quantitative CT may substitute for PET as a more readily-performed measure of lung inflammation. The dissociation of microbiologic responses from inflammation and function supports a role for HDTs in TB.
OC 8717 TRANSFER OF LEADERSHIP, WHAT DO WE NEED?
Authors: Mpagama Stellah 
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 investigating novel and existing agents to shorten and simplify TB treatment. One of the objectives of the programme is to foster leadership development in sub-Saharan TB-endemic countries to move leadership to African partners in the PanACEA research programmes.Methods and resultsIn PanACEA 1 the participation of the sites on the consortium board was important to foster leadership development. African investigators now make up a large part of the consortium leadership and are actively developing new concepts. Delegates of the sites visited the annual PanACEA General Assembly meetings, where they could gain knowledge, actively participate in the meetings and discussions and network with others from the TB research community. Various sites participated at TB research community conferences (e.g. CROI, Lung Health Meeting) where PanACEA members gave presentations and could collaborate with other TB trial networks.In PanACEA 2 all clinical trials are co-led by a European established researcher and an African Principal Investigator (PI), to ensure that African scientists are trained and mentored to lead in every aspect essential to clinical trial delivery, from trial and data management to statistical analysis and trial design, and from financial management to laboratory science. The capacity development cores, which serve as operational support for all PanACEA studies and provide high level oversight, also use the European and African countersystem, including senior and junior co-chairs among the African trial sites.An example of leadership transfer is a large EDCTP application for the development of a new compound in MDR TB (FACE-MDR-TB) in which Stellah Mpagama is the lead applicant.ConclusionThe PanACEA consortium has actively facilitated a transfer of leadership programme which may be successful in future consortia.