bluuebunny/crossref_metadata_2025_split huggingface dataset:
OC 8405 IDENTIFICATION OF AN MTB-SPECIFIC SOLUBLE HOST SIGNATURE FOR RISK OF DEVELOPMENT OF ACTIVE TB IN HIV-POSITIVE MTB-EXPOSED CONTACTS
Authors: Mendy Joseph , Chegou Novel N , Mayanja-Kizza Harriet , Stanley Kim , Thiel Bonnie , Ottenhoff Tom , Kaufmann Stefan , Boom Henry , Walzl Gerhard , Sutherland Jayne 
Published: April 2019

BackgroundWith 2 billion people infected withMycobacterium tuberculosis(Mtb) worldwide, identification of those most at-risk of progressing to active disease would provide a targeted, cost-effective approach for preventative therapy strategies. The GC6–74 project recruited Mtb-exposed HIV-positive (HIV+) contacts from 5 African countries with the aim of identifying molecular and protein signatures for identification of ‘at-risk’ subjects by comparing those who progressed to active disease (progressors) to those who remained asymptomatic (controls).MethodsFor this arm of the project, we analysed longitudinal samples from 12 HIV +progressors and 28 HIV +matched controls from Uganda (Makerere University, MAK) and South Africa (Stellenbosch University, SUN). Diluted whole blood was stimulated for 7 days with 7 Mtb-specific antigens plus controls. Supernatant was collected and a 38-plex multiplex assay performed following identification of confirmed progressors and controls.ResultsThe median time to progression to active disease was 510 days for SUN and 425 days for MAK participants. Baseline CD4 counts were 163 cells/µl for progressors and 154 cells/µl for controls. Baseline responses showed significantly lower IL-4 production in progressors following ESAT-6/CFP-10 (EC) stimulation (p=0.0309) and significantly higher macrophage-derived chemokine (MDC) following both Rv3019 and TB10.4 stimulation. For the time-point closest to progression, IL-10 production following EC stimulation and IFN-γ production following Rv3019 stimulation were significantly higher in progressors than controls (p=0.0024 and p=0.0028 respectively). A combination of 12 analytes following EC and TB10.4 stimulation gave 84.4% and 91.1% correct classification respectively.ConclusionWe have defined a soluble signature for detecting likely progression to active TB in HIV +subjects 1 year prior to progression. Following validation in other cohorts, this could be exploited for development of a field-friendly test for targeted interventional therapy.
PO 8448 ADVERSE DRUG REACTION TO TWO ARTEMISININ-BASED COMBINATION THERAPIES, ARTEMETHER-LUMEFANTRINE AND ARTEMISININ-PIPERAQUINE, IN CHILDREN WITH ACUTE UNCOMPLICATED MALARIA IN IBADAN, NIGERIA
Authors: Anjorin Oluwafunmibi , Falade Catherine O 
Published: April 2019

BackgroundMalaria remains a public health problem in sub-Saharan Africa, especially amongst children and pregnant women. Artemisinin-based combination therapy (ACT) is now the treatment of choice. Adverse drug reactions (ADR) have been observed to ACTs. This study aims to determine the incidence, pattern of presentation and factors associated with ADRs to artemether-lumefantrine (AL) and artemisinin-piperaquine (AP) among children with acute uncomplicated malaria in Ibadan, Nigeria.MethodsChildren aged 2–10 years with acute uncomplicated malaria who met the inclusion criteria, were enrolled, randomised to receive one of the study drugs (AL or AP) and followed up for 28 days. Monitoring for ADR was based on history from the parent/guardian and/or child regarding occurrences of treatment emergent signs and symptoms and on abnormalities of laboratory investigations (full blood count and blood chemistry). Causality assessment for the ADR was by the Naranjo algorithm scale while the severity was assessed using the Hartwig’s severity scale.ResultsA total of 114 children were enrolled; six defaulted and were not available for follow-up. There were 61 (56.5%) males. The mean age of enrollees was 65.1±30.0 months. Fever was the most prevalent presenting complaint occurring in 108 (100%) enrollees. Observed ADRs were cough, diarrhoea, loss of appetite, abdominal pain, rash, fever, irritability, insomnia and headache but the differences were not statistically significant between the two groups. The incidence of ADR to both ACTs was 12/1000 patients per day. Prevalence of ADR to AL was 14% and for AP 11%; this was not statistically significant. All ADRs were mild. No notable associated factor to ADR was detected in this study.ConclusionBoth AL and AP were found to be safe in the study population.
PO 8460 PANDORA-ID NET (PAN-AFRICAN NETWORK FOR RAPID RESEARCH, RESPONSE, RELIEF AND PREPAREDNESS FOR INFECTIOUS DISEASES EPIDEMICS)
Authors: Ntoumi Francine , Zumla Francine , Ippolito Giuseppe , Vairo Francesco 
Published: April 2019

BackgroundNew and re-emerging infectious disease outbreaks continue to cause much human suffering and loss of life worldwide. Since Africa has experienced repeated outbreaks of zoonotic infections, an important need exists to improve local and regional capacities to identify and respond to zoonotic outbreaks. PANDORA ID-NET is an EDCTP-supported ‘ONE Human and Animal HEALTH’ multidisciplinary consortium of 24 partner institutions (15 African and 9 European) in 9 African and 4 European countries.MethodsOur overall aim is to strengthen regional and pan-African capacities and systems for enabling a rapid and effective response to infectious diseases with epidemic potential, arising from within Africa or imported from overseas. We aim to build laboratory and public health capabilites for rapid detection and surveillance of pathogens from human and animal sources. This will include obtaining accelerated evidence for optimal clinical management of patients, infection control measures, and public health response during outbreaks. Capacities will be built: a) for performing multisite clinical trials (evaluating rapid diagnostics, biomarkers, a range of treatments, vaccines and operational research studies) and, b) for timely collection, analysis and communication of information.ConclusionOur activities will be aligned to EDCTP regional Networks of Excellence, Africa CDC and other relevant global and regional initiatives, thus maximizing complementarity and achieving a multiplier effect, facilitating rapid policy implementation of outputs.
PO 8468 DETERMINE TB–LAM LATERAL FLOW ASSAY: DOESM. TUBERCULOSISLINEAGE INFLUENCE ITS PERFORMANCE?
Authors: Ssengooba Willy , Nakiyingi Lydia , Moses Joloba 
Published: April 2019

BackgroundAmong HIV-positive individuals with CD4 ≤100 cells/mm3,M. tuberculosis(Mtb) bacteraemia is associated with a positive tuberculosis urine lipoarabinomannan (LAM) test. We conducted a retrospective study, to determine the effect of Mtb lineage on the performance of the Determine TB LAM lateral flow (LF-LAM) assay.MethodsThis was nested in a prospective TB diagnostics accuracy study among HIV-positive presumptive TB patients from Mulago National Referral Hospital, Kampala, Uganda, including both inpatients and outpatients. We considered data of 51 HIV-positive individuals with both pulmonary and Mtb bacteraemia. We also evaluated the effect of having mixed Mtb strains using both spoligotyping and MIRU-VNTR 24 loci methods.ResultsLF-LAM was; negative among 4 (7.8%; 95% CI, 2.17% to 18.8%), positive among 39 (76.5%; 95% CI, 62.5% to 87.2%) and indeterminate among 8 (15.7%; 95% CI, 7.0% to 28.5%) participants. Mtb lineages from blood samples were: Central Asian Strain (CAS; L3) 10/51 (19.6%) and Euro-American lineage (L4) 41/51 (80.4%). Mtb lineages from sputum samples were 7/51 (13.7%) L3 and 44/51 (86.3%) were L4. Among participants with L3 in blood, LFLAM was positive in 9 (90%; 95% CI, 55.4%–99.7%) whereas those with L4, LF-LAM was positive among 30 (73.2% 95% CI, 57.0% to 85.7%). For those with L3 in sputum, LF-LAM was positive among 7 (100%) and those with L4 was 32 (72.7%; 95% CI 57.2% to 85.0%). Two participants had mixed Mtb strains (all L4) and all LF-LAM positive (2+ and 4+).ConclusionOur study shows thatM. tuberculosislineage 3 may have more sensitivity to LF-LAM assay than lineage 4. The high number of indeterminate results with L4 requires more investigations. Our findings suggest that LF-LAM performance may differ by geographical regions depending on the dominantM. tuberculosislineage.
OC 8431 CLINICAL RESEARCH AND SUSTAINABLE DEVELOPMENT IN SUB-SAHARAN AFRICA: THE IMPACT OF NORTH-SOUTH PARTNERSHIPS
Authors: Saint-Raymond Agnes , Harvey Martin , Cavaller Maria 
Published: April 2019

BackgroundThe European legislation introduced in 2004 (under article 58) a collaboration tool to increase access to high quality and effective medicines in low- and middle-income countries. The European Medicines Agency (EMA) can provide scientific opinions on medicines intended for significant public health needs, in partnership with the World Health Organisation (WHO) and the relevant ‘target’ non-EU regulatory authorities. This EU-Medicines4all (EU-M4all) initiative contributes to the broader Global Health Mandate of the EU.MethodsWe contacted the pharmaceutical companies holding ‘article 58’ scientific opinions and compiled the number of actual approvals based on these opinions.ResultsNine medicines have been assessed so far, most of them for HIV/AIDS, tuberculosis, malaria and maternal/new-born health. Although this figure may appear low, the impact of the corresponding scientific opinions is much wider. Approvals were granted in 66 different countries worldwide, 38 of which are in Africa, based on these opinions.DiscussionSuch scientific opinions on the quality, safety and efficacy of the medicines are provided by the EMA’s Committee for Medicinal Products for Human Use (CHMP). Prior to this, it is recommended to agree on the data to be generated through scientific advice. The opinions are based on the same standards as used for those approved for Europe, with considerations for local conditions of use. To promote reliance on EMA scientific outputs and awareness of the procedure, two training events with regulators from Southern and from Western Africa are organised in partnership with WHO, NEPAD and local regulators in June 2018.ConclusionWe have shown that this ‘article 58’ procedure has a true impact and we encourage applications by companies developing medicines, aimed to prevent or treat diseases of significant public health interest, to be marketed outside the EU. This will ensure timely access of medicines by patients in target countries all over the world.
OC 8432 EVALUATION OF AN ANTIBODY-DETECTING POINT-OF-CARE TEST FOR THE DIAGNOSIS OFTAENIA SOLIUMTAENIASIS AND NEUROCYSTICERCOSIS/CYSTICERCOSIS IN AN ENDEMIC AREA
Authors: Mubanga Chishimba , Mwape Kabemba , Zulu Gideon , Phiri Isaac , Trevisan Chiara , Dorny Pierre , Gabriel Sarah , Damme Inge Van 
Published: April 2019

BackgroundTaenia soliumtaeniasis/(neuro)cysticercosis is a neglected parasitic zoonosis with significant economic and public health impacts. Neurocysticercosis is responsible for 30% cases of acquired epilepsy in endemic areas. Diagnosis and case management of neurocysticercosis/taeniasis in resource-limited endemic countries is challenging. Reliable, inexpensive and easy to use diagnostic tools with sufficient sensitivity and specificity are currently not available. A new point-of-care (POC) test based on recombinant rT24H and rES33 proteins developed by the Centre for Disease Control in Atlanta (US) which combines diagnosis of taeniasis and cysticercosis has been developed, however, its performance at community level is not known. The aim of this study is therefore, to evaluate the diagnostic performance of this test in a community setting.MethodsThe study site is Mtandaza community, Sinda district, Eastern Province of Zambia. The diagnostic accuracy is being evaluated for taeniasis and (neuro) cysticercosis in 1200 randomly selected participants in a community-based study. The performance characteristics (sensitivity and specificity) for neurocysticercosis will be computed by cross-tabulating of POC results with those of the ‘neurocysticercosis diagnosis’ while a Bayesian approach will be used for cysticercosis and taeniasis to compare the performance of the index test with reference tests (enzyme-linked immuno-electrotransfer blot (EITB), B158/B60 Ag-ELISA, Ab-ELISA, Copro-Ag ELISA, PCR).ResultsPreliminary results of 505 POC tests so far conducted show that 0.8% were positive for taeniasis, 9.1% for cysticercosis and, 4.6% were invalid or unclear. Except for Copro-Ag and B158/B60 Ag-ELISA for taeniasis and cysticercosis respectively, reference tests are yet to be conducted.ConclusionResults will show the diagnostic value of the POC test and its applicability for use at community level in endemic areas. If successful, implementation of the tool will enable early detection of taeniasis and suspected neurocysticercosis cases and lead to improved patient management and treatment outcomes.
PO 8527 GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY AND ASSOCIATION WITH UNCOMPLICATED MALARIA IN CONGOLESE CHILDREN CONSULTING IN A PAEDIATRIC HOSPITAL IN BRAZZAVILLE
Authors: S Gampio Gueye Nerly , P Thirumalaisamy Velavan , Vouvoungui Christevy , Ch Kobawila Simon , Nderu David , Koukouikila-Koussounda Félix , Ntoumi Francine 
Published: April 2019

BackgroundMalaria remains a public health problem in Republic of the Congo. The sub-microscopic infection including gametocytaemia constitutes a parasite reservoir that is recognised to contribute to malaria transmission. It is known that primaquine, an 8-aminoquinoline, is effective to eliminatePlasmodium falciparum(Pf) gametocytes. However, it induces haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). It has been reported G6PDd also confers protection against severe malaria. To know the prevalence of G6PDd in the Congolese population is important in the case of future utilisation of this drug in the country. Therefore, in this study, we investigated 1) the prevalence of G6PDd in children infected withPfand 2) the possible association between the presence of malaria, the presence of G6PD mutation and haemoglobin concentration.Methods229 children aged 1 to 10 years old presenting with fever (axillary T°≥37.5°C) were enrolled at the paediatric hospital Marien Ngouabi in Brazzaville. Thick and thin blood smears were done to detect and identify malaria parasites and determine parasite density. To detect the different glucose-6-phosphate dehydrogenase genotypes, a 968 bp fragment of the G6PD gene containing the polymorphisms 202G&gt1;A and 376&gt1;G was amplified by PCR followed by sequencing.ResultsMalaria prevalence was 22 (10%). With regard to G6PD analysis, it was found that 206 patients had G6PD genotype available including 74.8% (154/206) with G6PD normal, 12.1% (25/206) with heterozygous genotypes and 13.1% (27/206) with G6PD deficiency [11.6% (24/206) were male hemizygous and 1.4% (3/206) were female homozygous]. Data are further analysed to investigate the association between G6PD genotype, uncomplicated malaria, haemoglobin concentration as well as parasite densities.ConclusionA high prevalence of G6PD deficiency is reported for these Congolese children. Further investigation with larger sample size in different areas of the country is needed to design future and adapted interventions.
PO 8550 NATURE AND PREVALENCE OF MULTI-MORBIDITY IN FISHING COMMUNITIES ON LAKE VICTORIA, KENYA
Authors: Kwena Zachary , Ondondo Raphael , Makokha Catherine , Bukusi Elizabeth 
Published: April 2019

IntroductionMultimorbidity, coexistence of two or more chronic conditions, is becoming more common across different demographic groups in sub-Saharan Africa. We investigate the nature and prevalence of multimorbidity in fishing communities on Lake Victoria in Kenya.MethodsWe conducted a cross-sectional survey enrolling 679participants in the fishing communities to establish theprevalence of HIV and non-communicable diseases (NCDs)and associated risk factors. The NCDs targeted included diabetes mellitus detected by random blood glucose (RBG) and kidney dysfuction detected by serum creatinine level and proteniuria. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg. Diabetes mellitus was defined as RBG >7.8 mmol/L and renal dysfunction was defined as estimated glomerular filtration rate (eGFR) <60 mL/min or proteinuria. HIV was tested using rapid Determine assays and reactive results confirmed with UniGold assays. Additionally, participants were determined as having the condition if they reported being on medication for the condition. We analysed the results using descriptive statistics and used Chi-square test to discern if there were statistically significant differences by gender.ResultsOverall, HIV prevalence was 36% while 15%, 12% and 8% of the participants were suspected to have kidney dysfuction, hypertension and diabetes mellitus, respectively. Overall, 12% of the participants had multimorbidity. The most common multimorbidity among those with any of the four chronic conditions was HIV and kidney dysfunction (29%), followed by hypertension and kidney dysfuction (22%), HIV and hypertension (20%), HIV and diabetes (18%), diabetes and kidney disease (6%) and, lastly, diabetes and hypertension (5%). Apart from HIV, we observed no statistically significant gender differences for any of the NCDs or various multimorbidity conditions.ConclusionThese fishing communities have a high burden of both HIV and NCDs resulting in high prevalence of different multimorbidities.
PO 8564 WHAT IS CLINICAL TRIAL QUALITY? A QUALITATIVE STUDY BASED ON INTERVIEWS WITH DIFFERENT STAKEHOLDERS CONDUCTING CLINICAL TRIALS IN SUB-SAHARAN AFRICA
Authors: Lazarova Angela , Fuchs Claudia , Burri Christian 
Published: April 2019

BackgroundThere is no unified, broad definition for quality in clinical trials (CTs). Besides the explicit quality requirements in international guidelines and national legislation, however, there are broader factors to consider, including specific setting-related aspects influencing quality needs, quality perception and local implementation of guidelines. Our objective was to identify these factors from a resource-limited settings perspective (in this case, sub-Saharan Africa).MethodsIn March-April 2018, we conducted a qualitative study based on semi-structured interviews with participants from three stakeholder groups (monitors, sponsors, and investigators) conducting CTs in sub-Saharan Africa. We identified the interviewees either through CT registry platforms, a web search or by reference. We aimed to include 10–20 participants per stakeholder group. After consent, the interviews were held in person (via Skype or telephone), recorded, and transcribed verbatim. The interview questionnaire addressed a CT quality definition and quality factors during the CT process. We performed the analysis using the framework method.ResultsSo far, we included 21 participants (17 investigators, two sponsors, two monitors). Eight (8) (from sub-Saharan Africa) and 13 (not from sub-Saharan Africa) who contributed to CTs in 19 different countries in sub-Saharan Africa. Quality definitions mentioned so far were variable. A repeated statement was that the quality definition should be broad and include a system of multiple aspects and layers. We will interview more experts with sponsor and monitor experience in May 2018 and elaborate these quality aspects and layers. We will discuss these results with regards to a comprehensive quality framework for CTs currently under development for Northern countries by another Swiss research team.ConclusionCT quality was perceived in variable ways, as was the relevance of the aspects across different CT steps. Structuring the multifaceted layers of CT quality will facilitate appropriate and efficient CT quality management in sub-Saharan Africa.
PO 8565 PREVALENCE AND CLINICAL SIGNIFICANCE OF RESPIRATORY VIRUSES AND BACTERIA DETECTED IN TUBERCULOSIS PATIENTS COMPARED TO HOUSEHOLD CONTACT CONTROLS IN TANZANIA
Authors: Mhimbira Francis , Hella Jerry , Hiza Hellen , Mbuba Emmanuel , Chiryamkubi Magreth , Gagneux Sebastien , Fenner Lukas 
Published: April 2019

BackgroundThe study aim is to describe the prevalence of respiratory pathogens in tuberculosis (TB) patients and in their household contact controls, and to determine the clinical significance of respiratory pathogens in TB patients.MethodsWe studied 489 smear-positive adult TB patients and 305 household contact controls without TB with nasopharyngeal swab samples within an ongoing prospective cohort study in Dar es Salaam, Tanzania, between 2013 and 2015. We used multiplex real-time PCR to detect 16 respiratory viruses and seven bacterial pathogens from nasopharyngeal swabs.ResultsThe median age of the study participants was 33 years; 61% (484/794) were men, and 21% (168/794) were HIV-positive. TB patients had a higher prevalence of HIV (28.6%; 140/489) than controls (9.2%; 28/305). Overall prevalence of respiratory viral pathogens was 20.4% (160/794; 95% CI 17.7%–23.3%) and of bacterial pathogens 38.2% (303/794; 95% CI 34.9%–41.6%). TB patients and controls did not differ in the prevalence of respiratory viruses (Odds Ratio [OR] 1.00, 95% CI 0.71–1.44), but respiratory bacteria were less frequently detected in TB patients (OR 0.70, 95% CI 0.53–0.94). TB patients with both respiratory viruses and respiratory bacteria were likely to have more severe disease (adjusted OR [aOR] 1.6, 95% CI 1.1–2.4; p 0.011). TB patients with respiratory viruses tended to have more frequent lung cavitations (aOR 1.6, 95% CI 0.93–2.7; p 0.089).ConclusionRespiratory viruses are common for both TB patients and household controls. TB patients may present with more severe TB disease, particularly when they are co-infected with both bacteria and viruses.
PO 8571 CYTOKINE PROFILE IN ASYMPTOMATIC SCHOOL CHILDREN CO-INFECTED WITH HELMINTHS ANDPLASMODIUM FALCIPARUMIN IBADAN, SOUTH-WEST NIGERIA
Authors: Ademowo George , Rabiu Olawunmi , Arinola Ganiyu , Falade Catherine O 
Published: April 2019

BackgroundIntestinal helminths and malaria are among the most prevalent infectious diseases in the tropics. The effect of co-infections on immune response is not clearly understood. We therefore investigated the immune response profile in children with and without symptoms.MethodsA total of 78 afebrile school children (20 helminth/malaria-co-infected, 17 helminth-infected, 19 malaria-infected and 22 uninfected) and 75 febrile children (14 helminth/malaria-co-infected, 16 helminth-infected, 20 malaria-infected and 25 uninfected) were recruited into the study. Helminths were screened using Kato Katz method while malaria parasite screening was done using Giemsa-stained thick blood films. Circulating TNF-α, IFN-γ, IL-1, IL-10 and IL-6 concentrations were assessed by ELISA from serum samples. Data were analysed using analysis of variance.ResultsAmong the afebrile school children, IL-10 was significantly increased in helminth-infected children compared with helminth/malaria-co-infected, malaria-infected and uninfected groups (p<0.05). IFN-γ was significantly elevated in malaria and malaria/helminth-co-infection relative to helminth alone (p<0.05). IL-1 level was significantly higher in single infection of helminth and malaria relative to co-infection and the uninfected groups (p<0.05). An insignificant difference was observed for IL-6 and TNF-α concentrations across all the four groups while among febrile children. IL-6 was significantly increased among helminth alone and helminth/malaria-co-infection relative to malaria-infected group (p<0.05). IL-10 was significantly elevated in co-infected group compared with helminth- or malaria-infected group while TNF-α was significantly increased in helminth and helminth-malaria co-infection compared with uninfected or malaria-infected group (p<0.05). IFN-γ level was insignificant in the infection groups relative to uninfected group (p<0.05); IL-1 level similar across the groups.ConclusionHelminth infection seems to upregulate the Th2 immune response among children with symptomatic uncomplicated malaria while there were no significant changes in Th immune response among afebrile children.