bluuebunny/crossref_metadata_2025_split huggingface dataset:
OC 8721 WANECAM II – A CLINICAL TRIAL PROGRAMME TO ASSESS SAFETY, EFFICACY AND TRANSMISSION-BLOCKING PROPERTIES OF A NEW ANTIMALARIAL KAF156 (GANAPLACIDE) IN UNCOMPLICATED MALARIA IN WEST AND CENTRAL AFRICA
Authors: Djimde Abdoulaye ,   on behalf of the WANECAM II consortium, Grobusch Martin P , Zoleko Manego Rella , Mombo-Ngoma Ghyslain , Picot Stephane , Sagara Issaka , Sutherland Colin , Kone Aminatou , Doumbo Ogobara K , Pedro Gil Jose , Björkman Anders , Borrmann Steffen , Soulama Issiaka , Fofana Bakary , Duparc Stephan , Dicko Alassane , Hughes David , Winnips Cornelis , Sirima Sodiomon B , Adehossi Eric , Ouedraogo Jean-Bosco , Dembele Laurent , Zongo Issaka , Biguenet Sophie , Ilboudo-Sanogo Edithe , Fofana Aminata 
Published: April 2019

BackgroundDespite major progress in the past decade, malaria remains a major public health problem in sub-Saharan Africa. West and Central Africa account for nearly 2/3 of the burden currently attributable to falciparum malaria. Artemisinin-based combination therapies (ACT) are a cornerstone of our strategy for controlling and eventually eliminating malaria. However, reduced responsiveness/resistance to artemisinin derivatives and to ACTs, an increasing problem in South-East Asia is a major concern. It is of utmost importance to develop new antimalarial drugs from novel chemical classes that can replace ACTs. KAF156, an imidazolepiperazine, is a leading candidate in the antimalarial drug development pipeline. Combination of KAF156 with a Solid Dispersion Formulation of lumefantrine (LUM-SDF) is expected to be fast acting, fully curative, improve patient adherence and can potentially reduce malaria transmission.MethodsWANECAM II proposes to advance the clinical development of KAF156 through clinical trials in adults and children, with integrated capacity building and infrastructure development activities. The trial programme will be undertaken in the context of networking, team-building, leadership development and community engagement schemes that will involve intra-European, European-African and intra-African collaborative activities. WANECAM II will accelerate the clinical study of children less than 2 years of age which are the key target for new antimalarial treatments.ResultsBy the end of the project, the results are expected to contribute to the registration of KAF156/LUM-SDF through stringent regulatory health authorities, increase biomedical research capacity in the consortium and effectively promote networking among the respective teams. A new clinical research team in Niger, a grossly underrepresented country in the African research landscape, will be developed and further increase capacity and infrastructure in the consortium.ConclusionProviding a new antimalarial drug combination that does not contain an artemisinin derivative and is effective against resistantP. falciparumstrains as well as gametocytes and that is likely to be taken in 3 or fewer single doses will be a major advance in the field. The new combination of KAF156 with LUM-SDF is expected to provide such major advance upon successful conclusion of the WANECAM II project.
OC-8722 THE GENERATION AND TESTING OF A GENETICALLY ATTENUATED MALARIA PARASITE (GAP) VACCINE
Authors: Khan Shahid ,   on behalf of the PfSPZ-GA1 Vaccine Consortium
Published: April 2019

BackgroundImmunisation with radiation-attenuatedPlasmodium falciparumsporozoites (SPZ) (Sanaria PfSPZ Vaccine) can protect >90% of vaccinees against controlled human malaria infection (CHMI) and protects against naturally-transmittedP. falciparumin Africa for at least 6 months. Immunisation with sporozoites of genetically attenuated parasites (GAPs), which completely arrest after liver-cell invasion can be potentially safer and more potent than irradiated sporozoite vaccines. As part of a collaboration between two Dutch research groups (LUMC and Radboud University) and the US company, Sanaria, we describe the generation and first-in-man testing of a GAP vaccine,MethodsWe screened single and multiple gene deletion parasites in order to identify parasites that can invade hepatocytes but are unable to complete liver-stage development. Informed by rodent studies we createdP. falciparumdouble gene-deletion mutant, Δb9Δslarp; sporozoites of this line were infective to human hepatocytesin vitroand to humanised mice but they completely arrest after invasion. PfΔslarpΔb9PfSPZ (Sanaria PfSPZ-GA1 Vaccine) was manufactured in compliance with cGMPs and released for human clinical trials in the EU under a conditional release GMO license. This GAP vaccine was used to perform phase I (safety) and phase 2a (efficacy) clinical CHMI trial in the Netherlands.ResultsIn a dose escalating phase I clinical trial, the vaccine showed an excellent safety profile. All adverse events related to the vaccine were mild (grade 1). Based on this indication of safety, vaccine efficacy was examined by CHMI; 48 subjects were subsequently enrolled into phase 2a study and were immunised with either PfSPZ-GA1 or PfSPZ Vaccine or saline placebo.ConclusionsIn conclusion, PfSPZ-GA1 Vaccine is the first injectable genetically attenuated malaria vaccine assessed in humans. The accomplishment to manufacture, obtain regulatory approval and to demonstrate an excellent safety profile for this vaccine is unprecedented and holds a promise for PfSPZ vaccines with increased potency.
OC-8723 CREATING AND ENHANCING TRUSTWORTHY, RESPONSIBLE AND EQUITABLE PARTNERSHIPS IN INTERNATIONAL RESEARCH
Authors: Singh Michelle , Makanga Michael ,   on behalf of the TRUST global ethics consortium EDCTP (South Africa)
Published: April 2019

Achieving equity in international research remains a crucial concern of the 21st century. Despite initiatives by international organisations on governance frameworks and standards to guide research conduct, such efforts remain disparate and lack focus. In an interdisciplinary collaboration between multi-level ethics bodies, policy-advisors, civil society, funders, industry and academic scholars, the TRUST project combines long-standing, highly respected efforts to establish international governance structures along with networking opportunities between Europe, sub-Saharan Africa and Asia.The goal of TRUST is to catalyse a collaborative effort to improve adherence to high ethical standards in global research. The strategic outputs of the project encompass a set of ethics tools developed through participatory engagement traversing all continents: (i) a global code of conduct for funders, (ii) a fair research contracting web-tool (iii) and a compliance and ethics follow-up tool.Since project inception in October 2015, the TRUST consortium has a) created an international network on global research ethics governance to identify generic risks of exporting non-ethical practices; b) established funder and industry platforms; c) identified typical case studies of exporting non-ethical practices and reported on lessons learnt; d) developed a global code of conduct that will be used by the European Commission and like-minded funders to foster ethical research and equitable partnerships; e) designed an online Fair Research Contracting tool to empower vulnerable populations under non-ideal conditions; and f) drafted a compliance and ethics follow-up tool, for conditions of high vulnerability.TRUST envisages to make a tremendous impact on three major issues: a) enhancing the rights of indigenous people who have borne a disproportionate burden of research whilst being potentially highly vulnerable to exploitation; b) increasing civil society engagement and improving uptake of the ethics dimension in research and innovation; and c) improving global awareness of the highest ethical standards along with clear, defined incentives for research competitiveness.
PO 8190 RISK FACTORS OF SEVERE HEPATOTOXICITY AMONG HIV-1 PATIENTS INITIATED ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY IN THE NORTHWEST REGION OF CAMEROON
Authors: Abongwa Lem Edith , Kibera Anthony N , Fokunang Charles , Torimiro Judith , Nshom Emmanuel , Domkam Irénée , Okemo Paul 
Published: April 2019

BackgroundHepatotoxicity due to highly active antiretroviral therapy (HAART) has gained prominent attention since it can be affected by many factors. The aim of this study was to determine the prevalence of hepatotoxicity and related risk factors of severe hepatotoxicity following HAART initiation.MethodsA total of 100 newly diagnosed HIV drug-naive patients within the age range of 18–61 years were recruited and followed up for 24 weeks and were placed on either Tenofovir (TDF)+Lamivudine (3TC)+Efavirenz (EFV) or Zidovudine (AZT) +Lamivudine + Nevirapine (NVP) or Zidovudine +Lamivudine + Efavirenz regimen. Sociodemographic data was obtained using pretested questionnaires. Venous blood samples were collected to measure aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), using colometric enzymatic reaction. Hepatotoxicity was classified based on age and sex. Data was analysed using SPSS.ResultsThe level of significance was set at 5%. A total of 37 (38%) and 49 (49%) patients presented with hepatotoxicity; 15% and 28% of these patients had severe hepatotoxicity at 4 and 24 weeks, respectively. Serum levels of all enzymes increased significantly (p<0.05) with increased treatment duration. Univariate analysis revealed that the risk factor of developing severe hepatotoxicity was significantly (p<0.05) greater in patients<30 years, males, low BMI, low monthly income earners and patient on AZT+3TC +NVP regimen. While multivariate analysis at p<0.09 showed that age <30 years, Low BMI, low monthly income, or the use of AZT+3TC +NVP regimen were independent risk factors.ConclusionLow BMI,<30 years, low monthly income and the use of AZT+3TC+NVP regimen were identifiable risk factors for the development of severe hepatotoxicity. As such, these factors should be considered as important for strategy by clinicians to prevent hepatotoxicity.
PO 8239 BASELINE ASSESSMENT OF LYMPHATIC FILARIASIS IN 18 COMMUNITIES IN WESTERN GHANA BEFORE THE IMPLEMENTATION OF TWICE-YEARLY TREATMENT
Authors: Souza Dziedzom De , Ahorlu Collins Stephen , Otchere Joseph , Mensah Sedzro , Adu-Amankwah Sudan , Boakye Daniel 
Published: April 2019

BackgroundLymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2020, with the main strategy being treatment of entire endemic communities. Since the inception of the Global Programme for the Elimination of LF in 2000, tremendous progress has been made in many endemic countries. However, current observations point to the need for improved treatment regimen, frequency of treatment or drug delivery strategies in order to achieve the elimination goals in certain endemic areas. In this randomised trial, we evaluate the use of twice-yearly treatment with ivermectin and albendazole in 18 LF-endemic communities in Ghana, where despite 15 years of yearly treatment the disease is still above the elimination thresholds.MethodsFollowing demographic data collection,Wuchereria bancroftiantigen, microfilaria and antibody prevalence were assessed in study participants using the Alere FTS kit, nucleopore filtration and Wb123 ELISA, respectively. The study assessed the perspectives of the communities’on persistent transmission of LF in view of implementing effective treatment uptake strategies.ResultsThe baseline assessments revealed antigen prevalence of 8.2% (95% CI=6.8–9.8), with overall microfilaria prevalence of 1.2%. Infections were higher in males and in individuals who spend significant amount of time outdoors for commercial activities. Barriers related to medication, personal, health system, disease and social structure were observed to affect mass drug administration compliance. Community members perceived that they were not susceptible to infection and this together with drug adverse effects strongly affect the ingestion of the drugs.ConclusionWhile this trial is still in an early phase, the baseline assessments reveal programmatic challenges to the implementation of a twice-yearly treatment strategy for the control of LF which must be addressed to enhance implementation success.
PO 8278 BUILDING CAPACITY IN CONDUCTING CLINICAL RESEARCH IN A VIRTUAL SETTING: EXPERIENCES FROM THE EAST AFRICAN CONSORTIUM FOR CLINICAL RESEARCH (EACCR2)
Authors: Nyanzi-Kabuye Emily , Kaleebu Pontiano , Kikaire Benard , Mmbaga Blandina T , Mfinanga Godfrey S , Peshu Norbert , Mukhtar Maowia 
Published: April 2019

BackgroundEACCR2 is an EDCTP-funded, Eastern African-led network established in May 2009, with 23 regional partners from Ehtiopia, Kenya, Sudan, Tanzania, and Uganda, and 8 northern partners from Germany, Netherlands, Norway, Sweden and United Kingdom. The objective is to strengthen capacity to conduct health research to international standards with specific focus on clinical trials on poverty-relevant diseases such as HIV, TB, malaria and neglected infectious diseases. EACCR2 optimises the use of shared research infrastructures and other regional capacity building resources and opportunities.ActivitiesThe activities of the network are implemented in five work packages cutting across ‘nodes’ in different countries. Capacity building programmes and studies funded by EDCTP are implemented by coordinators at the disease nodes. The Uganda Virus Research Institute (UVRI) hosts the secretariat of the consortium of five nodes located in the following institutions: Malaria Node in Kilifi-Kenya Medical Research Institute Wellcome Trust, Tanzania; Training Node in Kilimanjaro Clinical Research Institute, Tanzania; Tuberculosis Node at the National Institute of Medical Research- Muhimbili, Tanzania; the Neglected and Re-Emerging Tropical Diseases Node at the University of Khartoum, Sudan; and the HIV Node at UVRI, Uganda.Coordinators form the project implementation committee which meets via skype or teleconference every quarter to assess progress, share best practice and challenges of the network. Scientific and annual meetings are arranged every year in one of the implementing institutions. During such meetings, students, the nodes and steering committee also meet to minimise travel costs while helping teams to network.EACCR2 learns from the experiences, best practice and challenges of EACCR1 while implementing its current activities. Careful planning and consensus building from all partners has been the driving force to build and implement activities of this virtual network. EACCR2 also works closely with other EDCTP Networks of Excellence, i.e. in Central Africa (CANTAM), West Africa (WANETAM), and Southern Africa (TESA).
PO 8313 PREDICTORS OF HEALTH INSTITUTIONAL READINESS FOR EBOLA EPIDEMIC CONTAINMENT IN NIGERIA: A STRUCTURAL EQUATION MODELLING (SEM) APPROACH
Authors: Adekeye Joshua , Musenge Eustasius , Arulogun Oyedunni 
Published: April 2019

BackgroundThere is paucity of literature on organisational readiness in the health space. Previous studies focus on epidemic preparedness and often depict readiness as a minor element in the implementation space. This study investigated the predictors of health institutional readiness to implement innovations for combating an Ebola epidemic outbreak in Nigeria.MethodsThe cross-sectional, mixed methods design was employed. The study population was 785 health care workers and non-health workers working at University of Port-Harcourt Teaching Hospital (Nigeria). The purposive sampling was used for qualitative study while the stratified random sampling technique was utilised for the quantitative study. Qualitative data were collected from fifteen respondents while a total of 511 questionnaires were administered at the study site. The qualitative data was analysed using inductive thematic analysis. The quantitative data was analysed using structural equation modelling (SEM).ResultsThe qualitative study suggested that quality improvement was perceived as most useful in influencing all the tree sub-components of readiness. Training is perceived as most useful in building readiness while it is perceived to be moderately useful in influencing the sub-component of readiness. The OLS estimates indicates that QI/QA exert a positive and significant effect on motivation (β=0.004, p<0.05) and general capacity score (β=0.28 p<0.05) while it inversely but significantly exerts influence on innovation specific capacity (β=−0.21×10–3, p<0.05). The SEM/pathway analysis shows the direct and indirect routes of interactions among predictors of readiness after adjusting for confounders. All the explanatory variables have significant effect on readiness except gender which was dropped from the final model.ConclusionThe strength of evidence of how an evidence-based system for innovation support can influence readiness was established. Though readiness is a rate-determining step in ensuring robust and effective implementation outcomes for epidemic containment, exploring innovation outcomes and their amplification through explicitly target readiness dynamics requires further investigation.
PO 8372 CULTURE-FREE APPROACHES FOR THE DIAGNOSIS AND MANAGEMENT OF PATIENTS WITH RIFAMPICIN RESISTANT TUBERCULOSIS: THE DIAMA PROJECT
Authors: Massou Faridath , Affolabi Dissou , Merle Corinne , Abebe Gemeda , Bah Sow Oumou , Diarra Bassirou , El Tayeb Osman , Gaye Diallo Ayou , Kaswa Michel , Claude Ngabonziza Semuto Jean , Sander Melissa , Supply Philip , De Jong Bouke 
Published: April 2019

BackgroundRecent advances in molecular diagnostics, especially the Xpert MTB/Rif test, have reduced the time to diagnose rifampicin resistant tuberculosis (RR-TB). However, with this test only rifampicin resistance is diagnosed, leading to presumptive diagnosis of resistance to isoniazid and maybe other drugs. In addition, culture on monthly sputum samples is currently recommended by the World Health Organization (WHO) for follow-up of RR-TB patients under treatment. Unfortunately, culture is often not locally available, and samples need to be shipped from field to culture laboratories. The associated transport delays lead to high rates of contamination and false-negative culture, particularly in laboratories in low-resource settings. Many gaps for the diagnosis and management of RR-TB patients still need to be addressed and the DIAMA project (Diagnostics for multidrug-resistant tuberculosis in Africa) aims to address some of them.MethodsThe TB Supranational Reference Laboratory of Benin leads a consortium of 11 partners involved in multiple-drug resistant TB care in Africa. The DIAMA project will explore the feasibility and accuracy of: i) diagnosing TB resistance to first and second line drugs through novel molecular multiplex assays developed by the company Genoscreen; ii) setting-up alternative culture-free approaches for the monitoring of patients’ response to rifamipcin-resistant treatment; iii) piloting whether the implementation of software by Data2Care Technologies for real-time monitoring of molecular test results can reduce delays between diagnosis and treatment of RR-TB patients. This project is funded by EDCTP for a period of five years.ConclusionTogether, these advances could dramatically improve the currently dismal prognosis of multiple-drug resistant TB in health systems in resource-poor settings. Through this presentation, we will share the background information, the design of this project and its progress.
PO 8381 REGULATING CLINICAL TRIALS DURING AN EBOLA EMERGENCY: THE LIBERIAN EXPERIENCE
Authors: Ndorbor Theophilus , Sumo David , Kercula Juwe D , Hallie Ezekiel F 
Published: April 2019

BackgroundEffective clinical trials oversight is a major function of a fully functional national medical products regulatory system. However, exercising clinical trial oversight in a resource-limited environment is challenging, in particular during an Ebola outbreak or health emergency. Until the devastating Ebola virus disease (EVD) outbreak in 2014, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) had no capacity for effective clinical trial regulation. This presentation describes the main challenges encountered by LMHRA in regulating clinical trials in Liberia during the largest EVD outbreak that affected West Africa in 2014 and 2015.MethodsBy carefully documenting activities during the EVD outbreak, interviewing key stakeholders, and discussions among the LMHRA clinical trial committee, key challenges observed during the outbreak were identified and documented.ResultsLimited financial resources, lack of expertise in clinical trials, inaccurate and insufficient information about the functions of the LMHRA, poor coordination among key stakeholders, and the lack of a well-developed regulatory framework, adversely influenced the LMHRA clinical trial oversight performance during the EVD outbreak.ConclusionIt is true that several challenges need to be addressed when regulating a clinical trial in a limited-resource environment during any disease outbreak or international medical emergency. However, the importance of building local expertise in clinical trials through mentorship and training cannot be overemphasised. By taking advantage of grants from developmental partners, national medicines regulatory authorities in resource-limited environments can develop capacity for clinical research oversight.
PO 8392 SPUTUMMYCOBACTERIUMLOAD AND CYTOKINES BIOMARKER OF STIMULATED WHOLE BLOOD CELLS IN SPUTUM SMEAR-NEGATIVE PULMONARY TUBERCULOSIS SUDANESE PATIENTS
Authors: Omer Mona 
Published: April 2019

BackgroundImprovement of the diagnosis of smear-negative pulmonary tuberculosis (PTB) patients and identification of possible immune factors associated with the negative result of sputum will enable early and accurate diagnosis of smear-negative PTB. This study aimed to measure theMycobacteriumload in sputum samples of smear-negative patients and identify cytokines markers associated with smear-negative active pulmonary tuberculosis.MethodsSputum and heparinised blood samples were collected from 40 smear-negative, 40 smear-positive PTB patients and 21 healthy controls. All sputum samples were analysed by direct ZN stain and conventional PCR to confirm the infection and characterise the bacteria. The load of bacteria in sputum samples was measured using real-time PCR. Blood samples were stimulated with sonicated MTB H37Rv. TH1 (TNF-α, IFN-γ, IL- 1β) and TH2 (IL-10) cytokines were measured using ELISA technique.ResultsEight patients were grade 3+, 23 were grade 2+, 9 were grade 1+ and 40 were negative on smear. 87.5% of smear-negative patients were positive by PCR. Smear-negative PTB patients produced high concentration of IFN-γ compared with smear-positive. IL-10 and TNF-α concentration were significantly lower in smear-negative compared with smear-positive. IL-1β was not significantly different between smear-negatives and smear-positives. Both smear-negative and smear-positive samples produced significantly high IL-10 and TNF-α cytokine compared with the healthy controls, while IFN-γ production was significantly lower in MTB patients. A highly significant correlation between MTB load and cytokines was detected. The mean concentration of IFN-γ was higher in stimulated blood samples of patients with lower bacterial load. In contrast, IL-10 and TNF-α concentration were higher in patients with high bacterial load. The TNF-α and IL-1β were good biomarkers for diagnosis of smear-negatives.ConclusionSmear-negative PTB produced high TH1 cytokine and low regulatory cytokine compared to smear-positive.