bluuebunny/crossref_metadata_2025 huggingface dataset:
PO 8597 NEUTRALISING AND NON-NEUTRALISING ANTIBODIES RESPONSE IN HIV-1-INFECTED INDIVIDUALS FROM MOZAMBIQUE
Authors: Gonçalves Paloma , Martin Francisco , Borges Patricia , Santo Maria Espirito , Taveira Nuno , Marcelino José
Published: April 2019

Background

A vaccine that protects against the different HIV subtypes circulating around the world is essential to control and eliminate HIV infection. The immunogens are the key to develop an effective HIV vaccine. In this study, we characterised the antibody response against recombinant C2V3C3 polypeptides from several HIV-1 subtypes and evaluated the neutralising antibody response.

Methods

Plasmas from HIV-1-infected individuals under treatment (n=39) and drugs-naïve individuals (n=8) were tested in an ELISA assay to determine the presence of antibodies against polypeptides from HIV-1 subtypes (CRF02_AG, B, C, G and H). The neutralising activity of plasma was evaluated with a panel of six HIV-1 viruses from a reference panel, [one tier 1 (NL4.3), and five tier 2 (PCH119_CRF07, PCE1176_C, TRO11_B, 246 F3_AC and CRF07_BJOX2000)] in a TZM-bl cells-based assay.

Results

Out of 48 plasmas, 44 (89.6%) reacted at least with one polypeptide and four (10.4%) did not react with any polypeptide. Interestingly, 56% of the plasmas recognise ≥3 peptides and 6 reacted with all polypeptides. The polypeptide from virus CRF02_AG was the most antigenic (77%) followed by the polypeptide C (58.3%), G (58.3%), H (50%) and B (35.4%). There was a positive correlation between polypeptides number recognised and binding antibody reactivity (r=0.4895, p=0.0111). All plasmas from drugs-naïve individuals neutralised at least one virus with neutralising activity between 39.3% and 95.7%. Four plasmas showed neutralising activity >50% against five viruses. The virus 249 F3 was the easiest to neutralise (median, 65.7%), whereas PCH119_CRF07 was the most difficult to neutralise (median, 43.6%). Neutralising activity of plasmas from patients under treatment are ongoing.

Conclusion

In summary, these polypeptides could be useful in vaccine design once they are very antigenic and we observed a heterologous neutralising antibody response in naïve patients that expressed positive antibody-response anti-peptides.
PO 8607 DETECTION OFPLASMODIUM FALCIPARUMHISTIDINE-RICH PROTEIN 2/3(PFHRP-2/PFHRP-3) GENES DELETION AND AMINO ACID NUCLEOTIDE SEQUENCE VARIABILITY IN NIGERIA
Authors: Funwei Roland , Falade Catherine O , Ojurongbe Olusola
Published: April 2019

Background

Prompt diagnosis and appropriate treatment remain the hallmark needed to reduce malaria-related mortality in areas of high transmission. Rapid diagnostic tests (RDTs) that target the Pfhrp-2 gene, are essential in resource-limited settings where microscopy is not available. However, Pfhrp-2 gene deletion is implicated in limiting RDT sensitivity. Studies evaluating Pfhrp-2 and Pfhrp-3 deletion and the amino acid sequence diversity has not been investigated in Nigeria. We therefore hypothesised that malaria parasites in Nigeria are lacking Pfhrp-2/Pfhrp-3 genes with variable amino acid repeats sequences.

Methods

The study was part of a prospective cohort study evaluating RDTs performance. We pooled 66 samples comprising false negatives (n=31) and true positives (n=35) to elucidate Pfhrp-2/Pfhrp-3 gene deletion, RDT cross-reactivity with Pfhrp-3 antigen and amino acid sequence diversity. The 18SrRNA, msp 1, msp2 and glurp genes were amplified to establish activePlasmodium falciparuminfection and the exon-2 regions of Pfhrp-2 and Pfhrp-3 genes were amplified to determine the presence or absence of Pfhrp-2 and Pfhrp-3 genes. Isolates with conserved Pfhrp-2/Pfhrp-3 were sequenced.

Results

All 66 samples were positive for 18SrRNA, msp1, msp2 and glurp, indicating activeP. falciparuminfection. However, 16.7% and 6.0% of the samples were lacking Pfhrp-2 and Pfhrp-3 genes. Of the false negative samples, 25.8% and 12.9% has Pfhrp-2 and Pfhrp-3 deletions. Three Pfhrp-3 conserved antigens cross reacted to give RDT positive results. An extensive diversity in the amino acid sequence was observed.

Conclusion

Plasmodium falciparumparasites in Nigeria lack Pfhrp-2 and Pfhrp-3 genes. However, the proportion of deletions is low compared to reports from other malaria-endemic regions. In addition, a high amino acid tandem repeat was observed. A combination of pLDH and Pfhrp-2 based RDTs is recommended for accurate malaria diagnosis.
OC 8465 THE DEVELOPMENT OF A CONJUGATE VACCINE AGAINST GROUP B STREPTOCOCCUS: AN AFRICAN PERSPECTIVE
Authors: Wilson Seanette , Tippoo Patrick
Published: April 2019

Background

Streptococcus agalactiae,or group B streptococcus (GBS), is a gram-positive streptococcal bacterium that is well-recognised as one of the leading causes of infant death, particularly in the early neonatal period (the first week of life). An estimated one in five pregnant women around the world carries GBS bacteria in their gastrointestinal or genitourinary tracts and vertical transmission from colonised mothers can lead to invasive disease in their offspring. A recent study conservatively estimated that out of 410,000 GBS cases globally every year, there are at least 1 47 000 stillbirths and infant deaths. Despite being home to only 13% of the world’s population, Africa has the highest GBS disease burden, with 54% of estimated cases and 65% of stillbirths and infant deaths.

An effective GBS vaccine, given during pregnancy, is a promising strategy to protect against GBS disease. Currently, no licensed vaccine exists to prevent it, but scientific evaluation of feasibility is favourable. The leading vaccine candidates are capsular polysaccharide-protein conjugate vaccines. Evidence suggests maternal immunisation with a safe and effective GBS vaccine may reduce the disease risk in neonates and young infants.

The Biovac Institute was established as a private-public partnership and is the only Southern African vaccine manufacturer. Located in Cape Town, South Africa, Biovac’s mission is to become a leading vaccine developer and producer in South Africa to increase capacity in Africa which only has four other vaccine manufacturers.

In collaboration with PATH, an international health organisation, and other partners, Biovac is developing a multivalent conjugate vaccine against GBS. The first stage of the project involves the development of biopharmaceutical manufacturing processes and analytical tests, the preparation of clinical trial product, and execution of a first-in-human clinical trial.

This presentation will provide an overview of the project, progress to date, and the path to commercialisation.
OC 8173 RAPID DETECTION OFMYCOBACTERIUM ULCERANSBY RECOMBINASE POLYMERASE AMPLIFICATION
Authors: Frimpong Michael , Ahor Hubert , Sarpong Francisca , Laing Ken , Wansbrough-Jones Mark , Phillips Richard
Published: April 2019

Background

There are no primary measures to prevent people from contracting Buruli ulcer, mainly due to poor understanding of its epidemiology. The current control strategy emphasises early diagnosis and prompt treatment, with the goal of avoiding the complications associated with advanced stages of the disease. There is no diagnostic test for the disease appropriate for use at the primary health care level where most cases are detected and treated. Diagnosis based on clinical signs is unreliable in inexperienced hands and complicated by infections that have similar presentations. This study was to develop and evaluate the use of recombinase polymerase amplification (RPA) assay for the detection ofMycobacterium ulceransat the point of patient care.

Methods

A specific fragment of IS2404 ofM. ulceranswas amplified in 15 min at a constant temperature of 42°C, using the RPA assay and analysed on a portable fluorometre. Themethod was tested for sensitivity and specificity with molecular standard of IS2404 DNA fragment, variousM.ulceransstrains, other mycobacteria and environmentally associated bacteria. Additionally, the assay performance as a diagnostic tool was tested with archived DNA from symptomatic patients. All results were compared with that of a highly sensitive IS2404 PCR.

Results

The detection limit was 50 copies of IS2404 in 15 min using plasmid standard and 125 fg with genomicMuDNA equivalent 25 genomic copies. The assay was highly specific in detecting all strains ofM. ulceranswith no observed cross reactivity with other mycobacteria and common skin colonising bacteria. The clinical sensitivity and specificity of the BU-RPA assay using clinical samples was 86% and 100% respectively.

Conclusion

We have developed a real-time isothermal RPA assay for the detection ofM. ulceransas a cheaper alternative to PCR. Combining this assay with a simple extraction protocol will maximise its use as point-of-care test for Buruli ulcer.
OC 8499 THE T-CELL VACCINE STRATEGY: GLOBALLY RELEVANT AIDS VACCINE EUROPE-AFRICA TRIALS PARTNERSHIP (GREAT)
Authors: Hanke Tomáš , Fast Patricia , Kaleebu Pontiano , Jaoko Walter , Sanders Eduard , Kilembe William , Kuipers Hester , Okech Brenda , Gilmour Jill
Published: April 2019

Background

Remarkable progress has been achieved in decreasing AIDS-related deaths and HIV-1 transmission through ART. Nevertheless, an affordable, effective and durable HIV-1 vaccine protection remains the best solution for halting the AIDS epidemic.

Our aim is to develop a vaccine inducing cytotoxic T lymphocytes (CTL), which effectively inhibit HIV-1 replication and complement bnAbs for prevention; such T cells are likely critical for a successful cure. Central to our strategy is to focus HIV-1-specific CTL on the most functionally conserved regions (not a string of epitopes and not full-length proteins) common to most HIV-1 variants, which HIV-1 typically cannot change without losing fitness. These conserved regions were defined by bioinformatics, and a bivalent mosaic was computationally designed to increase the vaccine perfect match of potential T-cell epitopes to 80% of global HIV-1 variants; if successful, the vaccine will be suitable for global deployment. Furthermore, we maximised the inclusion of protective epitopes associated with viral control in treatment-naive HIV-1-positive individuals defined on 4 continents. These immunogens are delivered by the non-replicating simian adenovirus ChAdOx1 prime and non-replicating poxvirus MVA boost regimen, clinically proven safe and potent.

Methods

The GREAT consortium has been established to build capacity for a future efficacy trial in Zambia, around Lake Victoria and in Kenya by engaging populations at documented high risk for HIV-1 infection, despite preventive interventions, by diverse clades. We will conduct a phase I/IIa clinical trial HIV-CORE 006 to assess the safety and immunogenicity of the conserved-region vaccines, in preparation for an efficacy trial in these at-risk populations.

Conclusion

The aims of the GREAT consortium are to ensure that at the completion of the programme grant, the vaccine regimen will be proven safe and potent, and the sites will be prepared to launch an appropriately designed trial to prove vaccine efficacy.
OC 8566 THE UNIVERSIDADE EDUARDO MONDLANE AND UNIVERSITY OF CALIFORNIA SAN DIEGO PARTNERSHIP, A PARADIGM FOR INSTITUTIONAL AND HUMAN RESOURCES CAPACITY BUILDING
Authors: Noormahomed Emilia , Scooley Robert
Published: April 2019

Background

Collaborations between lower- and middle-income countries (LMICs) and high-income countries (HICs) are often scientifically and structurally driven by the HICs. Here we aim to describe a paradigm shift in collaboration, exemplified by the collaboration between the Universidade Eduardo Mondlane and University of California, San Diego through the Medical Education Partnership Initiative (MEPI), in which the formulation of priorities and administrative infrastructure reside in the LMICs.

Methods

We outline critical features of the MEPI partnership and compare with traditional models of collaboration, key features of success, lessons learned and the way forward.

Results

LMIC programme partners translate broad programme goals and define metrics into priorities tailored to local conditions. Programme funds flow to a LMIC-based leadership group that contracts with HIC-based peers to provide technical and scientific advice and consultation in a reverse funds flow model. Emphasis is placed on strengthening administrative capacity within LMIC institutions and on creating communities of practice with common goals that resulted in expanded collaboration with European, Latin American, and African institutions. A rigorous monitoring and evaluation process modify programme priorities based on evolving opportunities to maximise programme impact.

Over five years, more than 63 research projects were designed, 19 of which received external funding and more than 40 manuscripts were published. Mozambican first-authored publications rose from 29% in 2001–2010% to 38% in 2011–2013.

Eighteen (18) residents completed internal medicine specialty training between 2010 and 2014. This represents a fourfold increase from over 1991 to 2000. Three (3) Master’s programmes were created at Lurio University and 50 students successfully finished dissertations.

Conclusion

Vesting LMIC partners with the responsibility for programme leadership and building administrative capacity in LMIC institutions substantially enhances programme relevance, impact and sustainability, and facilitates continuing acquisition of research and training funds to support professional development and institutional capacity building.
OC 8715 GOING FURTHER TOGETHER: THE ROLE OF THE EU IN SUPPORTING REGULATORY HARMONISATION OF HEALTH TOOLS IN AFRICA
Authors: Martin Lasanta Agustin
Published: April 2019

Background

On May 20, 2018, African governments adopted the Treaty for the establishment of the African Medicines Agency (AMA) as a stepping stone in the strengthening and harmonising of medical products regulation on the continent. Many countries in Africa lack robust and comprehensive regulatory systems supporting the research and registration of health products, hampering the translation of health research and innovation into public health impacts. The AMA could substantially improve the access to quality-assured, safe andeffective health solutions and technologies in Africa and around the world. As the main trade partner and donor to Africa, the European Union (EU) has a key role to play in supporting this effort.

Method

Desk research and case-study analyses of key initiatives to strengthen medicinesregulation in Africa were conducted. Specifically, the EDCTP, the African Vaccine Regulatory Forum (AVAREF), the African Medicines Regulatory Harmonisation Programme (AMRH) and the Zazibona Process; to assess the gaps, needs and opportunities for EU collaboration using actual and reconfigured EU-Africa funding and policy cooperation mechanisms.

Results and conclusions

This presentation will explore initiatives aimed at regulatory strengthening and harmonisation in Africa and propose policy recommendations on how to improve EU efforts in order to support these initiatives in a more systematic and synergetic manner. The recommendations fall into four categories: EU-Africa priority-setting, coordination, funding and capacity-building actions. Recommendations explore, for instance, advancing the national implementation of the African Union Model Law on Medical Products Regulation by all African countries, enlarging the scope of EDCTP regulatory strengthening actions to include Africa’s Regional Centres of Regulatory Excellence (RCOREs) or improving the attractiveness and incentive system of the EMA’s article 58 procedure for African governments, researchers and manufacturers.
OC-8724 NEW VACCINES FOR A SAFER WORLD
Authors: Imbault Nathalie , Grant Rachel
Published: April 2019

CEPI is an innovative partnership between public, private, philanthropic and civil organisations founded in Davos in 2017 to develop vaccines to stop future epidemics. To date, CEPI has received multi-year funding from Norway, Germany, Japan, the Bill & Melinda Gates Foundation, and the Wellcome Trust. CEPI has also received single-year investments from the governments of Australia, Belgium, and Canada. It has reached $630 million of its $1 billion funding target. The European Commission has announced a contribution in kind of €250 million that will support relevant projects through EC mechanisms. Since its launch in January 2017, CEPI has announced two Calls for Proposals. The first was for candidate vaccines against MERS-CoV, Nipah and Lassa viruses. The second was for the development of platforms that can be used for rapid vaccine development against unknown pathogens. From the first call, CEPI has, so far, announced six partnership agreements and this means 4 lassa vaccine candidates, 3 MERS-CoV vaccine candidates and 1 Nipah vaccine candidate have been selected for development. Learn more atCEPI.net. Follow us at@CEPIvaccines.
PO 7167 IMPROVING USE OF LONG-LASTING INSECTICIDAL NETS IN KAYANGE COMMUNITY OF NORTH-WESTERN BURUNDI: A QUALITY IMPROVEMENT STUDY
Authors: Habonimana Desire , Ndayisaba Gabriel , Nimako Gideon
Published: April 2019

Background

The use of long-lasting insecticidal nets (LLINs) for malaria prevention is a cost-effective intervention. WHO recommends universal coverage and use of LLINs. In lower- and middle-income countries, LLINs are provided free of charge but are either not used or misused. Our study sought to improve LLIN use in Kayange community of north-western Burundi by using a model for improvement (MFI).

Methods

A one-group, pre/post-test study was conducted. LLIN weekly use was assessed for four weeks before intervention and for another four weeks after intervention. The study was conducted in 96 households. The intervention consisted of testing four different weekly small change actions by using the MFI.

Results

Of the 96 households, 83 households (87%) owned at least one LLIN. However, only 40 households (42%) owned at least one LLIN for every two people. After intervention, the number of LLINs used increased from 32 to 75 per cent (134% increase) and the number of persons (general population) sleeping under LLIN from 35 to 73 per cent (108% increase). The number of children under 5 years old sleeping under LLIN increased from 31 to 76 per cent (145% increase) and the number of pregnant women who slept under LLIN from 43 to 73 per cent (69% increase). Also, the averages of the number of nights in each week that the general population slept under LLIN increased from 2.13 to 5.11 (140% increase), children under 5 years old slept under LLIN from 1.68 to 4.78 (184% increase) and pregnant women slept under LLIN from 1.56 to 4.47 (186% increase).

Conclusion

Our intervention led to significant increase in all outcome indicators. This increase is the result of a combination of an enabling context and an effective implementation of an evidence-based quality improvement intervention. Small tests of change at the community level have the potential for achieving improved outcomes.
PO 8168 CLINICAL UTILITY OF XPERT MTB/RIF ASSAY FOR THE DIAGNOSIS OF EXTRAPULMONARY TUBERCULOSIS IN ETHIOPIA
Authors: Tadesse Mulualem , Abebe Gemeda , Yilma Danie , Apers Ludwig , Jong Bouke De , Rigouts Leen
Published: April 2019

Background

The diagnosis of extrapulmonary tuberculosis (EPTB) is often made on clinical suspicion alone, and many people receive the wrong diagnosis leading to unnecessary TB treatment or poor outcomes from untreated EPTB. In this study, we evaluated the clinical utility of the Xpert MTB/RIF assay on routinely collected extra-pulmonary specimens in Ethiopia.

Methods

This study was carried out at Jimma University Specialized Hospital, Southwest Ethiopia from September 2015 to June 2017. Extra-pulmonary specimens were collected from 572 patients clinically suspected of suffering from EPTB. All specimens were tested for TB by smear-microscopy, culture and Xpert MTB/RIF. The diagnostic accuracy of Xpert MTB/RIF was calculated compared to a composite reference standard (CRS), composed of liquid culture and anti-TB treatment response.

Results

In total, 572 extra-pulmonary specimens (279 lymph node, 159 pleural, 80 peritoneal, 45 cerebrospinal and 9 pericardial fluids) were tested. The pooled sensitivity and specificity of Xpert MTB/RIF were calculated to be 91% and 90.6% respectively when compared to culture. The pooled sensitivity of Xpert MTB/RIF was decreased to 75% and the specificity was improved to 98% when Xpert MTB/RIF was compared to the CRS. The sensitivities among the specimen types differed markedly. The highest sensitivity was documented for lymph node (90%), moderate sensitivity for cerebrospinal (53%), while the sensitivity was lowest for pleural (30%) and peritoneal (32%) fluids. Xpert MTB/RIF, in addition, detected rifampicin resistance in 13 patients in perfect agreement with line probe assay.

Conclusion

Our study showed that Xpert MTB/RIF is likely to be of greatest utility when testing lymph node specimens. A negative Xpert MTB/RIF result on fluid specimens does not exclude the diagnosis of EPTB and patients with a high clinical probability of EPTB should be started on anti-TB treatment.
PO 8194 OPTIMISED INFORMED CONSENT FOR PARTICIPANTS IN A RANDOMISED CONTROLLED TRIAL IN RURAL UGANDA: A COMPARATIVE PROSPECTIVE COHORT STUDY
Authors: Ditai James , Kanyago Jesca , Nambozo Rachael , Kanyago Nathan , Abeso Julian , Olupot Peter , Carrol Enitan , Gladstone Melissa , Weeks Andrew , Faragher Brian , Medina-Lara Antonietta , Storr Julie
Published: April 2019

Background

Poor participant understanding of research information can be a problem in community interventional studies in rural African women where levels of illiteracy, dependency and compliance are high. We assessed the impact of alternative consent models on participants’ understanding of the clinical trial information and its contribution to the informed consent process in rural Uganda.

Methods

This was a prospective comparative cohort, nested within a pilot study of community distribution of alcohol-based hand rub to prevent neonatal sepsis (BabyGel). As part of the informed consent process, information about the trial was presented using one of three consent methods: standard researcher-read information; a ‘slide show’ using illustrated text on a flip chart; and a video showing the patient information sheet (PIS) being read as if by a newsreader in either English or the local language. In addition, all women received a written PIS in their preferred language. Each information method was used for 1 week of recruitment. Two days after recruitment, women’s understanding of the clinical trial was evaluated.

Results

A total of 30 pregnant women from 13 villages in Mbale participated in this study. Majority 90% (27/30) were assessed for recall of trial information within planned 48 hours. The slide-show was the most popular, with a mean score not less than 4.2 highest [mean (sd) range: 4.8 (0.6) [4–5]] by women who had been recruited using any of the three models. The slide show was preferred by 63% of the women (19/30), compared with 17% (5/30) and 20% (6/30) who preferred the standard and video show message, respectively. Reasons given included the benefits of having pictures to aid understanding, and the logical progression of the information.

Conclusion

Our results suggest that a slide-show message is an effective and popular alternative way of presenting trial information to women in rural Uganda, many of whom had little or no literacy.
PO 8254 LESSONS LEARNT FROM SCALING UP AN ONLINE SYSTEM FOR REVIEW AND MANAGEMENT OF PROTOCOLS IN SUB-SAHARAN AFRICA
Authors: Ngongo Prince B , Kombe Francis , Kamali Anatoli , IJsselmuiden Carel
Published: April 2019

Background

The transition from paper-based to online submission of health research protocols using the RHinnOEthics(RE) platform has been shown to improve efficiency and quality of ethics reviews. However, despite these documented benefits, there are only a total of 40 installations in 12 out of the 54 countries in Africa. We analysed facilitators and barriers to adoption of RE by Researc Ethics Committees.

Methods

We used a retrospective analysis to identify determinants of adoption or rejection of RE by grouping feedback from users into key emerging themes identified through three stages of RE adoption: 1) contractual 2) trial 3) full implementation.

Results

A total of 3947 protocols have been managed through RE by March 2018. Of those reached, 25 per cent adopted and continue to use RE. Of those that rejected, 14 per cent rejected after the trial. At the contractual stage, the key determinants of adoption were the guarantee of sustainable funding, pre-existing good IT infrastructure, and the assurance of technical assistance from the providers. The key determinants of rejection were concerns of cyber security, limited control and ownership by Researc Ethics Committees and cost of the annual subscription. At the trial stage, the determinants of continued adoption and use were continued IT support from providers and a proven comparative advantage over the paper-based system. The key determinant of rejection was limited support from organisation leadership. Those who have continued through the implementation stage emphasised financial sustainability and continuous improvement of the RE as key determinants.

Conclusion

Accelerated adoption of RE will require increased adaptability of the platform, decrease in cost of annual subscription, improved confidence in security and ownership of data. Developers, Research Ethics Committees and sponsors of RE need to develop a cost-effective funding strategy to increase efficiency, economies of scale and benefits related to harmonised and standardised digital platforms.
PO 8264 QUALITY CARE CRITERIA IN A CLINICAL TRIAL CONTEXT: PATIENT AND DAFRA AND NANORO CMA HEALTH WORKER PERCEPTIONS IN BURKINA FASO
Authors: Nourou Barry , Toe Léa Pare , Toe Patrice
Published: April 2019

Background

Participants in clinical trials as well as researchers conducting them, establish a close link between clinical trial and quality care. However, what understanding do they have of the concept of quality of care? This study aimed to answer this question by presenting the criteria which define for them quality care in the context of clinical research.

Methods

The data were collected from the participants involved in these clinical trials as well as from the health workers (research teams and other health workers) using a qualitative approach with 70 in-depth interviews. Direct observations of the participants partaking in care activities were also made in both health districts. The data were recorded, transcribed and then analysed on the thematic content basis.

Results

For the health workers interviewed, the clinical trials are conducted in optimal conditions which highly contribute to ensure a good quality of care. To them, quality of care in the process of the trial implementation is evident from some availability of qualified human resources, quality medico-technical equipment, as well as good clinical practice strictly adhered to by the researchers.

As for the participants, the quality of care in clinical trials meets specific criteria. To them, quality care delivered by the research team became tangible through laboratory tests before any treatment proposal, the promptness in taking care of any discomfort, as well as the regular and permanent follow-up of the patient until recovery of his health. Blood sampling for laboratory examinations was highly appreciated and mentioned by our respondents as the main indicator of the quality of care provided by the research teams.

Conclusion

The quality of care according to the criteria the participants and the health workers assigned to it, is intrinsically linked to clinical trials.
PO 8290 INFLUENCE OF THE SICKLE CELL TRAIT ONPLASMODIUM FALCIPARUMTRANSMISSION IN ASYMPTOMATIC CHILDREN
Authors: Maffo Christelle Ngou , Berry Antoine , Morlais Isabelle , B Feufack Donfack Lionnel , Bayibeki Ngano Albert , E Nsango Sandrine , Milo Sarah-Matio Elangwe , Ayong Lawrence
Published: April 2019

Background

The sickle cell trait is associated with protection against severe malaria. Recently, it has been shown that the genetic protection conferred by the sickle cell trait has no effect on the transmission ofPlasmodiumspecies from humans to vectors. Our study aimed to investigate the putative association between the sickle cell trait AS and the susceptibility to malaria infection of both the human host and the insect vector.

Methods

The study was conducted from June to November 2017 among asymptomatic children living in Cameroon. The samples were collected on microscopy slides, Whatman FTA and grade 17 paper for the selection of gametocyte carriers by microscopy, the molecular diagnosis ofPlasmodiumspecies, and sickle cell trait (PCR- RFLP), respectively. Infectivity of the mosquito was measured by experimental infections on gametocyte-containing blood from naturally infected carrier. Genetic diversity was measured using microsatellite markers.

Results

A total of 1557 children were recruited; the prevalence ofPlasmodiuminfection among this group was 58% and the AS sickle cell trait 20%. No significant difference in the prevalence ofP. falciparuminfection was observed according to the sickle cell trait carriage and this irrespective of the parasite stage (p>0.05). The level of infectivity of the mosquito was higher when feedings were performed on blood from HbAS genotypes compared to HbAA genotype blood, and the difference was even more significant when the blood pellet was resuspended with non-immune AB plasma (p<0.0001). No significant difference was observed in the infection complexity between HbAS and HbAA genotypes (p>0.05).

Conclusion

Plasmodiuminfection is not influenced by HbAS genotype regardless of parasite stage; the risk of anopheles infection is higher with blood from gametocyte carriers with sickle cell trait (HbAS). The sickle cell trait does not affect the multiplicity of infection.
PO 8300 REGIONAL CENTER FOR REGULATORY EXCELLENCE IN CLINICAL TRIAL OVERSIGHT – TRAINING 2017
Authors: Darko Delese , Adu-Boahen Yvonne
Published: April 2019

Background

The competencies of the various national medicines regulatory agencies (NMRAs) in Africa vary which leads to generally porous regulatory systems for clinical trial oversight. Consequently, many trials have been conducted under unacceptable conditions compromising participants’ safety and data credibility and resulted in questionable outcomes that are used for making scientific judgement in addressing issues of public health in Africa.

To improve the safety and quality of health technologies in Africa, the New Partnership for African Development (NEPAD) agency launched a programme to designate Regional Centres of Regulatory Excellence (RCOREs) with the specific objective of bridging existing gaps between African NMRAs through strengthening regulatory capacity of African Union member states. The Food and Drugs Authority (FDA), Ghana, was designated as RCORE for Clinical Trials oversight in May 2014.

Methods

To achieve the RCORE objectives, the FDA collaborated with the School of Public Health (SPH), University of Ghana to develop a training manual and piloted a training programme with funds from the International AIDS Vaccine Initiative (IAVI) through NEPAD.

The programme, consisting of 4 compulsory modules, was organised from 6–30 November 2017 for 10 participants from Zambia, Sierra Leone, Liberia, Rwanda and Ghana. Interactive training methods in the form of theoretical and practical sessions were employed.

Results

The pilot RCORE training was successful with expected training objectives achieved. Participants gained hands-on experience through activities like observing Good Clinical Practice inspection and a Technical Advisory Committee Meeting. Participants were given template tools to assist in developing regulatory guidelines and forms in their respective countries.

A follow-up questionnaire was circulated to participants to assess the impact of the training on their work. Feedback indicates that regulation of clinical trials has improved in their respective institutions.

Conclusion

This pilot fellowship training was successful, leading to the improvement of clinical trial regulation in the participating countries.
PO 8355 HOST GENETIC POLYMORPHISMS AND ASYMPTOMATIC MALARIA IN SOUTHERN GHANA
Authors: Otu Paulina , Lo Aminata Colle , Gyan Ben , Afrane Yaw , Amoah Linda Eva
Published: April 2019

Background

Despite several interventions through malaria control programmes, asymptomatic malaria is a major barrier to control as asymptomatic individuals serve as reservoirs from which others are re-infected. The mechanism by which these individuals remain asymptomatic is not well understood. Much work has been done in relation to human genes and their association to severe, mild and uncomplicated malaria. However, there is limited knowledge regarding host genetic factors and asymptomatic malaria.

Method

In this study, we investigated the association between host genetic polymorphisms of glucose-6-phosphate dehydrogenase gene (G6PD), mannose binding lectin (MBLG54A), tumor necrotic factor alpha (TNF-G308A) and nitric oxide synthase 2 (NOS2-G954C) and the outcome of asymptomaticP. falciparummalaria in 150 healthy individuals in southern Ghana.

Results

We found a significant association between G6PDd and asymptomatic malaria with a prevalence of 9.6% (p=0.035, by chi-square test). All the individuals who were heterozygous and hemizygote deficient (5.3% and 4.3%) were found to be asymptomatic. Individuals homozygous (GG) for TNF (G308A) were found to be highly asymptomatic (p=0.019, by chi-square test). Regarding MBL (G54A) and NOS (G954C), no significant association was found between these markers and asymptomatic malaria.

Conclusion

Upon reviewing our data with other data from published work, we conclude that both heterozygous and hemizygous individuals with G6PD A- and homozygous individuals (GG) of TNF (G308A) polymorphisms could be predisposed genetically to asymptomatic malaria.
OC 8378 REQUIREMENTS FOR THE ETHICAL CONDUCT OF CLINICAL RESEARCH IN CAMEROON, SUB-SAHARAN AFRICA: THE IMPORTANCE OF ACTIVE MONITORING
Authors: Ngounoue Marceline Djuidje , Ateudjieu Jerome , Fokunang Charles , Chi Primus Che , Ndje Mireille Ndje , Nolna Sylvie Kwedi , Magne Gisele , Kaptue Lazare
Published: April 2019

Background

Previous evaluation of the state of ethics regulation in Cameroon revealed: law regulating clinical research is lacking; existing committees lack infrastructure and financial support to sustainably review and effectively monitor approved protocols. The present Cameroon National Ethics Committee (CNEC)-EDCTP project aimed at implementing and evaluating active monitoring of clinical research in Cameroon.

Methods

Between 2011–2013, approved clinical trials and protocols involving transfer of biological materials abroad were consecutively monitored. The monitoring tool, a questionnaire on the conformity of key documents e.g. research protocols, ethical clearance, informed consent documents, investigator’s brochure, with a focus on GCP standards was sent to promoters/investigators ten days prior to the field visit. Teams of two-three monitors, made up of CNEC members and independent consultants, were mobilised per site (hospital/research institute/NGO). Reports with key recommendations were submitted to CNEC for review and approval, to different promoters/investigators, and the Regulatory Authority for action; the monitoring summary was submitted to EDCTP.

Results

Up to 22 site visits were done throughout the country, monitoring about 30 protocols within 11 hospitals, 9 research institutes, a National Programme and a non-governmental organisation. All sites had ethical clearance and administrative authorisation for research. From the registered number of research participants, less than half of the signed consent forms were available. Other issues were the lack of full involvement of local investigators, inexistence of material transfer and data sharing agreements with collaborative studies, non-implication of study communities/participants. As educators-consultants, monitors formulated recommendations to investigators, ethics committees and regulatory authority, insisting on the implication of local PI/collaborators with defined percentages of time to be devoted for research and good participatory practice among research communities/participants.

Conclusion

Active monitoring shows some formality in the application of ethical/administrative clearance in Cameroon. However, complex issues raised confirm the necessity of continuous monitoring to meet the high standards for clinical research ethics in Cameroon.
PO 8388 THE GLOBAL HEALTH TRAINING CENTRE PROFESSIONAL DEVELOPMENT SCHEME: CAPACITY DEVELOPMENT AND CAREER TRACKING FOR RESEARCHERS
Authors: Rapa Elizabeth
Published: April 2019

Background

Health researchers need a free, online and reliable mechanism to record their skill set, track their career development, and identify gaps in their knowledge. Research teams also require ways to monitor and report their team’s capacity development over time. The Global Health Network, a trusted and respected digital platform, is now able to provide researchers with these tools (www.globalhealthtrainingcentre.org/pds).

Methods

The Global Health Network compared diverse data types and took into account user feedback to create a professional development scheme (PDS). Together with TDR (The Special Programme for Research and Training in Tropical Diseases), a framework was developed with a list of the core competencies that a research team needs to demonstrate to carry out a study succesfully. A multi-functional dashboard was designed for team coordinators to assess the capacity development of individuals and groups.

Results

The PDS provides researchers with a step by step process for recording their career and core competencies. The core competency framework can be applied to any research study, regardless of size of the team, place, disease focus or type of research. Team coordinators can quickly and easily produce visual records of the strengths and weaknesses in the competencies of their team and implement plans to address these gaps. Together with supporting tools in the PDS, research teams can plan staffing requirements for a study, carry out appraisals and guide the career development and training programme of research staff.

Conclusion

The Global Health Network has created a flexible method and set of tools (PDS) to support researchers and teams to document their professional career and core competencies. It enables individuals and groups to easily identify and track capacity development; an essential requirement for conducting effective health research.
PO 8438 KNOWLEDGE, ATTITUDE AND PERCEPTIONS ON ADVERSE DRUG EVENTS REPORTING AMONG PATIENTS AND HEALTHCARE PROVIDERS IN RURAL UGANDA
Authors: Ndagije Helen , Nambasa Victoria , Kajungu Dan
Published: April 2019

Background

Drug regulatory authorities promote patient safety by, among other ways, monitoring adverse drug events (ADEs). Reporting of ADEs in Uganda is below the average for a well-performing system. Enhancing patients’ understanding of and involving them in reporting ADEs improves drug safety and treatment outcome monitoring. The objective of this study was to describe the knowledge, attitude, and practice of patients and healthcare workers regarding ADEs and ADEs reporting.

Methods

A cross-sectional survey was carried out among 1034 respondents from randomly selected households and 327 health workers at health facilities in the Iganga Mayuge Health and Demographic Surveillance Site (IMHDSS). The IMHDSS, located in Uganda, covers 90,000 people living in 17,000 households.

Results

Over half of respondents (59%) sought treatment from private drug shops, 37% from either clinic, health center or hospital, while 4% sought treatment from herbalists, friends or relatives. Over half (56%) were aware of ADEs, 57% expressed willingness to report an ADE while 43% did not know what to do when it occurs. Almost half (46%) could not differentiate between an ADE and the symptoms, and for those who could, the majority (76%) were willing to report it. Only 34% had ever reported an ADE when it occurred to them. Of those who reported, 43% had their drugs changed, 31% were only counseled while 11.5% continued taking the same medication. Among healthcare workers, 95% knew about ADEs, but only 35% had ever reported. Reasons for not reporting were: fear of being victimised or sued (35%); lack of adequate knowledge about ADE (26%); 20% thought it would disappear shortly; and 14% did not find it necessary to report.

Conclusion

Patients seek their treatment from private providers. Patients want to report ADEs, but they do not have adequate knowledge. Healthcare workers’ reasons for not reporting are subjective. Dedicated pharmacovigilance-related interventions at community level would improve community members’ knowledge and hence ADE reporting rate.
Transverse momentum and nuclear modification factor distributions of charged particles in p + Pb and p+p collisions at s NN = 5.02 TeV
Authors: Ali Q. , Ali Y. , Haseeb M. , Ajaz M.
Published: April 2019

Transverse momentum distributions and nuclear modification factor of integrated charged particles yield produced in p[Formula: see text]+[Formula: see text]Pb collisions at [Formula: see text] = 5.02 TeV are investigated in mid-rapidity regions of [Formula: see text] at one event multiplicity class 0–5% in the transverse momentum range of [Formula: see text]20 GeV/c. Simulations with EPOS-1.99, EPOS-LHC and QGSJETII-04 are compared with the ALICE data. All three models are in good agreement with each other up to [Formula: see text]3 GeV/c for transverse momentum distributions but after that QGSJETII-04 overpredicts the experimental data. EPOS-LHC seems to describe the experimental data quite well as compared to the other two models. The ratios of the kaons to pions and protons to pions are also presented where again EPOS-LHC provides good agreement with the ALICE data. In case of the nuclear modification factor, for (anti) pions and (anti) kaons, the model distribution is around 1, whereas it is greater than 1 in case of (anti) protons which shows Cronin enhancement.
A Modified Similarity Metric for Unit Testing of Object-Oriented Software Based on Adaptive Random Testing
Authors: Chen Jinfu , Kudjo Patrick Kwaku , Zhang Zufa , Su Chenfei , Guo Yuchi , Huang Rubing , Song Heping
Published: April 2019

Finding an effective method for testing object-oriented software (OOS) has proven elusive in the software community due to the rapid development of object-oriented programming (OOP) technology. Although significant progress has been made by previous studies, challenges still exist in relation to the object distance measurement of OOS using Adaptive Random Testing (ART). This is partly due to the unique features of OOS such as encapsulation, inheritance and polymorphism. In a previous work, we proposed a new similarity metric called the Object and Method Invocation Sequence Similarity (OMISS) metric to facilitate multi-class level testing using ART. In this paper, we broaden the set of models in the metric (OMISS) by considering the method parameter and adding the weight in the metric to develop a new distance metric to improve unit testing of OOS. We used the new distance metric to calculate the distance between the set of objects and the distance between the method sequences of the test cases. Additionally, we integrate the new metric in unit testing with ART and applied it to six open source subject programs. The experimental result shows that the proposed method with method parameter considered in this study is better than previous methods without the method parameter in the case of the single method. Our finding further shows that the proposed unit testing approach is a promising direction for assisting software engineers who seek to improve the failure-detection effectiveness of OOS testing.
Characterization of nonlinear optical refractive index for graphene oxide–silicon oxide nanohybrid composite
Authors: Darabi Hamid , Adelifard Mehdi , Rajabi Yasser
Published: April 2019

In this work, Silicon oxide (SiO2) nanoparticles, graphene oxide nanosheet (GO) and GO–SiO2 nanohybrid composites have been synthesized. The role of GO concentration in the starting solution was investigated and correlated to the morphological, structural and optical properties of the studied samples. The structural studies for nanohybrid composites showed that by increasing GO:weight ratio from 0.5 to 2.0, not only does the SiO2 crystalline phase change from cubic to orthorhombic, but the structure of GO also transformed to RGO. The related FESEM images indicate that GO sheets are well-covered by SiO2 nanoparticles with very small grain size and that the accumulation of nanoparticles on each sheet has a high density. Linear Optical measurements showed two optical band gaps of [Formula: see text][Formula: see text]eV and 5.3[Formula: see text]eV for SiO2 nanoparticles, and band gap value of 4.15[Formula: see text]eV for GO nanosheets, which it reduces to 3.3[Formula: see text]eV after formation of the nanohybrid composite with GO: SiO2 weight ratio of 2.0. The nonlinear optical properties of GO–SiO2 with different weight ratio are measured using Z-scan technique. The results showed that the nonlinear refractive index of SiO2 and GO nanoparticles and nanohybrid composite (0.5:1,1:1,2:1) ([Formula: see text]–[Formula: see text]) changed and has a negative sign. It was observed that the nonlinear refractive index changes in different ratios of compounds. Experimental results show that after the formation of the composite, the nonlinear refractive index shows a significant increase in the presence and effectiveness of the GO.
The limit of blockchains
Authors: Wang Yongge , Malluhi Qutaibah M.
Published: April 2019

Although smart contracts are Turing complete, it is a misconception that they can fulfill all routine contracts.
Net neutrality
Authors: Kuzmanovic Aleksandar
Published: April 2019

Cloud-delivery networks could dramatically improve blockchains' scalability, but clouds must be provably neutral first.
Continuity and change in internet law
Authors: Grimmelmann James
Published: April 2019

The fundamentals of the field of Internet law have remained consistent, but details have evolved in response to technological innovation.
Early Binaural Hearing: The Comparison of Temporal Differences at the Two Ears
Authors: Joris Philip X. , van der Heijden Marcel
Published: April 2019

Many mammals, including humans, are exquisitely sensitive to tiny time differences between sounds at the two ears. These interaural time differences are an important source of information for sound detection, for sound localization in space, and for environmental awareness. Two brainstem circuits are involved in the initial temporal comparisons between the ears, centered on the medial and lateral superior olive. Cells in these nuclei, as well as their afferents, display a large number of striking physiological and anatomical specializations to enable submillisecond sensitivity. As such, they provide an important model system to study temporal processing in the central nervous system. We review the progress that has been made in characterizing these primary binaural circuits as well as the variety of mechanisms that have been proposed to underlie their function.