bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHYLOGENETIC AND DEMOGRAPHIC CHARACTERISATION OF HIV-1 TRANSMISSION NETWORKS IN A GENERAL POPULATION COHORT IN UGANDA
Authors: Ssemwanga Deogratius , Lyagoba Frederick , Magambo Brian , Kapaata Anne , Kirangwa Joseph , Nannyonjo Maria , Nassolo Faridah , Nsubuga Rebecca , Yebra Gonzalo , Brown Andrew , Kaleebu Pontiano 
Published: February 2017

BackgroundThe General Population Cohort (GPC) in Southwestern Uganda is a low-risk population with low HIV incidence rates (<1%). Despite several interventions for close to 30 years, new cases of HIV continue to emerge. We set out to use phylogenetics and patients' demographic data to understand the HIV transmission dynamics in this population to inform prevention.MethodsA total of 2049 pol sequences of participants diagnosed from 2003–2015 were included in this analysis; pol sequences were from GPC (n=1049), Central Uganda (n=800) and Eastern Uganda (n=200). Phylogenetic analysis was used to identify transmission networks. The demographic and clinical characteristics of the transmission clusters were analysed.ResultsThe overall subtype distribution was: A (45%), C (3%), D (40%) and others (12%). The subtype distribution by region was for GPC: A (41%), C (2%), D (45%) and others (12%). For Central: A (49%), C (4%), D (35%) and others (12%). Eastern: A (60%), C (3%), D (24%) and others (13%). We identified 233 transmission clusters (cluster size variation 2–10) that comprised of 559 (27%) of the 2049 participants.The majority of clusters comprised transmission pairs (n=186) and triplets (n=30). The majority (∼60%) of the 233 clusters was from the GPC and all 13 large clusters (≥5) were also from the GPC. A significant number of clusters (n=25, 11%) was formed between individuals from different geographic locations. Participants in transmission networks were associated with high-risk sexual behaviour: low condom use, high alcohol use, and partner change even with known HIV-positives.ConclusionsThe transmission networks identified among individuals from the GPC and other populations or geographic regions may imply HIV introductions from outside communities. This suggests that HIV introductions into communities are common and account for a substantial number of new infections in the GPC. HIV prevention efforts should therefore target the broader communities beyond the GPC.
PREVALENCE AND RISK FACTORS FOR EFAVIRENZ-BASED ANTIRETROVIRAL TREATMENT-ASSOCIATED SEVERE VITAMIN D DEFICIENCY: A PROSPECTIVE COHORT STUDY
Authors: Nylén Hanna , Habtewold Abiy , Makonnen Eyasu , Yimer Getnet , Burhenne Jürgen , Diczfalusy Ulf , Aklillu Eleni 
Published: February 2017

BackgroundInitiation of efavirenz-based combination antiretroviral therapy (cART) is associated with Vitamin D deficiency, but the risk factors for cART-induced severe vitamin D deficiency (SVDD) and the impact of anti-tuberculosis (TB) co-treatment is not explored well.MethodsTreatment-naïve HIV patients with (n=102) or without (n=89) tuberculosis co-infection were enrolled prospectively and received efavirenz-based cART. In TB-HIV co-infected patients, rifampicin-based TB treatment was initiated. Plasma 25-hydroxyvitamin D (25(OH)D), cholesterol and 4-beta hydroxycholesterol concentrations were measured at baseline, and weeks 4, 16 and 48 of cART. Plasma efavirenz concentrations were determined at week 4 and 16 of cART. Genotyping for CYP2B6, CYP3A5, ABCB1, SLCO1B1, and UGT2B7 were done.ResultsTB-HIV patients had significantly lower plasma 25(OH)D3 levels than HIV-only patients at baseline. TB co-infection, low Karnofsky score, high viral load and high CYP3A activity as measured by plasma 4-beta hydroxycholesterol/ cholesterol ratios were significant predictors of low 25(OH) D3 levels at baseline. In HIV-only patients, initiation of efavirenz-based cART increased the prevalence of SVVD from 27% at baseline to 76%, 79% and 43% at weeks 4, 16 and 48 of cART, respectively. The median 25(OH)D3 levels declined from baseline by –40%, –50% and –14% at weeks 4, 16 and 48 of cART, respectively. In TB-HIV patients, prior TB therapy had no influence on 25(OH)D3 levels, but the initiation of efavirenz-based cART increased the prevalence of SVDD from 57% at baseline to 70% and 72% at weeks 4 and 16 of cART, respectively. Whereas the median plasma 25(OH)D3 declined from baseline by –17% and –21% at week 4 and 16 of cART, respectively. None of the genotypes were significantly associated with SVDD.ConclusionsLow plasma cholesterol, high CYP3A activity, and high plasma efavirenz concentrations are significant predictors of early efavirenz-based cART-induced SVDD. Low plasma 25(OH)D3 level at baseline is associated with TB co-infection and HIV diseases progression.
THE BURDEN AND FUTURE SCOPE FOR IMPORTANT VIRAL ENTERIC PATHOGENS IN AFRICA
Authors: Steele Duncan 
Published: February 2017

BackgroundThe burden of viral enteric infections in Africa is enormous, although poorly described. Some, such as rotavirus, are well recognized, whereas others including norovirus or enteric adenovirus (EAd), show high burden which is only now being described. Hepatitis E virus (HEV) is a neglected enteric viral infection although is on WHO's radar screen as an important pathogen which needs further evaluation in Africa and Asia. This presentation will focus on these four enteric viral pathogens describing our current understanding of disease burden and the potential for vaccines as potential interventions.Manycountries in Africa have documented the high burden of rotavirus. Almost 30 countries have introduced rotavirus vaccines with or without Gavi support, and recent studies document dramatic reductions in diarrhoeal hospitalizations and diarrhoeal deaths post introduction.Norovirusis a ubiquitous virus causing diarrhoeal disease in all age ranges, although the incidence is highest in young children. Although a common cause of diarrhoea, norovirus is often associated with asymptomatic shedding making it difficult to ascertain the true burden of the disease. Nevertheless, advances towards understanding the epidemiology and diversity of norovirus in Africa are important to inform future vaccine efforts.EAdshave recently been described as one of the top 5 pathogens associated with acute severe diarrhoea in young children <5 years in Africa and Asia. Coupled with the high prevalence of EAds in HIV-infected children requires more focused research, although there is very limited vaccine development currently.HEVis associated with water-borne and zoonotic infections, and is reported in large outbreaks. It has high mortality in pregnant women and is associated with high rates of stillbirths. Little is known of the extent of HEV infection in Africa. A Chinese vaccine against HEV has been licensed and WHO has identified gaps in research that are required for future immunization opportunities.
IMPACT OF TARGETED INTERVENTIONS AGAINST DIARRHOEA IN ZAMBIA
Authors: Chilengi Roma , Simuyandi Michelo , Beres Laura , Bosomprah Samuel 
Published: February 2017

BackgroundDiarrhoea is a leading cause of morbidity and mortality with the brunt of diarrhoea felt most in developing countries like Zambia where 13% of all deaths of children between 1–59 months are attributable to the disease. The Ministry of Health, in partnership with the Centre for Infectious Disease Research in Zambia (CIDRZ) and other stakeholders, implemented the Programme for the Awareness and Elimination of Diarrhoea (PAED) in 2012 to reduce all-cause under-five mortality by 15% in Lusaka Province.MethodsBaseline data were collected in 2012 and endline data were collected 3 years following PAED implementation. The primary outcome of interest was all-cause under-five mortality rate. Additionally, a case-control study to estimate rotavirus vaccine effectiveness (VE) was undertaken.ResultsThe percentage of children under age 5 who had diarrhoea in the last 2 weeks preceding the survey declined from 15.8% (95% CI: 15.2–16.4%) in 2012 to 12.7% (95% CI:12.3–13.%) in 2015. Post-neonatal mortality declined by 34%, from an estimated rate of 29 (95% CI: 26–32) to 19 (95% CI: 16–21) deaths per 1000 live births. The adjusted 2-dose VE was 26% (95% CI: 30%–58%) among children ≥6 months of age. VE against hospitalised children ≥6 months of age was 56% (95% CI, – 34%–86%).ConclusionsWell-packaged preventive and treatment interventions against diarrhoea could reduce probability of death among children aged 1–59 months. VE results from Zambia were consistent with others in the region, and while we observed a higher point estimate for VE against increased severity of illness compared with milder disease, the study was not powered to detect a low level of VE against milder disease.
EVIDENCE-INFORMED POLICY MAKING: CHALLENGES AND OPPORTUNITIES
Authors: Volmink Jimmy 
Published: February 2017

Evidence-informed health policy making depends on the availability of the results of studies that have assessed what works, what does not work, and what may be harmful. However, even where such evidence exists it will not always be embraced by policy makers or other decision makers.This presentation begins by discussing the environment in which policy making takes place and identifying the role of players involved, drawing attention to the complexity of the policy making process. It shows how competing forces, such as beliefs, vested interests, values, habits and financial considerations can lead to important evidence being rejected or ignored by national and international policy makers, sometimes with serious consequences.The talk also explores the role researchers can play in promoting the flow of evidence from research to policy to implementation by focussing on 5 key issues: generating primary research, conducting systematic reviews of evidence, improving access to relevant evidence, enhancing the use of evidence in policy making, and providing information on how best to scale up programmes. Case studies from LMIC settings, relevant to the EDCTP's remit, will be employed to illustrate the various concepts covered in the presentation.
ONE-YEAR SAFETY OF THE RVSV∆G-ZEBOV-GP VACCINE IN ADOLESCENTS AND CHILDREN IN LAMBARENE, GABON
Authors: Bache Bache Emmanuel , Fernandes José F. , Mba Régis M Obiang , Kabwende Anita L. , Grobusch Martin P. , Krishna Sanjeev , Kremsner Peter G. , Todagbe Agnandji Selidji 
Published: February 2017

BackgroundThe rVSV∆G-ZEBOV-GP vaccine was safe and immunogenic in American, European and African adults. Few cases of transient, self-limiting arthritis have been reported in some adult participants in Geneva. We describe one-year safety of a single dose (2×107plaque forming unit (PFU)) of the vaccine administered to adolescents and children living in Lambaréné.MethodsA phase I, open label randomized trial conducted in Lambaréné, Gabon, to assess the clinical safety (adverse events (local/systemic symptoms, and laboratory anomalies)) for 365 days' post injection. The primary objective was to assess the nature, frequency, and severity of adverse events (AEs) and/or serious adverse events (SAEs) associated with the administration of the vaccine.ResultsFrom 08-May 2015 to 07-Jul-2015, a total of 20 adolescents and 20 children aged 13–17 and 6–12 years respectively, were vaccinated with a single intramuscular dose of 2×107PFU rVSV∆G-ZEBOV-GP vaccine. Two serious adverse events (SAE) were reported over one year of follow-up. Two adolescents were hospitalized forPlasmodium falcipariummalaria and pneumonia infection. Up to 12 months' (6 months of extended follow-up) of both active and passive reporting, the most frequently reported symptoms by vaccinees are classified under the following system organ classes (SOC): Gastrointestinal disorders 30%(6/20) and 40%(8/20), respiratory-thoracic and mediasternal disorders 5%(1/20) and 45%(9/20), and infections/infestations 20%(4/20) and 20%(4/20) for adolescents and children respectively. No case of arthritis was observed, few cases 13%(5/40) of mild to moderate arthralgia, unrelated to the vaccine were reported. No delayed reactogenicity symptoms were reported beyond the already mild to moderate intensity symptoms reported during the first 28 days' post injection. No severe (grade 3) adverse event was reported. Median haematology and biochemistry values were within site normal ranges at month 12.ConclusionThe vaccine dose of 2×107PFU showed an acceptable safety and tolerability profile in our volunteers' age 6–17 years, living in a setting endemic for Ebola virus transmission. This acceptable safety profile seen in adolescents and children is similar to that previously reported in adults.
THE ROLE OF CLINICAL TRIALS FOR ELIMINATION OF NEGLECTED INFECTIOUS DISEASES AMENABLE TO MASS DRUG ADMINISTRATION
Authors: Bockarie Moses 
Published: February 2017

BackgroundIn 2012, WHO published a roadmap, for ‘Accelerating Work to Overcome the Global Impact of Neglected Tropical Diseases (NTD)’, which set out control and elimination targets for five NTDs that were considered tools-ready. Lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil-transmitted helminthiasis are amenable to the preventive chemotherapy (PC) strategy and manageable through the implementation of available diagnostic products, and safe and effective medicines. The optimism for achieving the WHO 2020 targets for control and elimination for these PC NTDs was crystallised by the London Declaration of 2012 – a pledge by leaders of several major global health and development organizations, together with industry partners to unite efforts to achieve the targets by 2020. Clinical research involving human subjects is driven primarily by the need for novel products, devices or interventions. The question remains whether clinical trials have a role in the fight against NTDs that are tools-ready. Can an investment case be made for vaccines or new drugs for the five PC NTDs? Four of the five PC NTDs are vector-borne diseases, but clinical trials are not normally designed to measure vector outcomes and there is little information available for the conduct of clinical trials involving entomological tools and products. Moreover, human and laboratory capabilities for conducting clinical trials in the countries most affected by NTDs in sub-Saharan Africa are limited. Nonetheless, alternative intervention strategies based on new drugs, vaccines and novel devices have been proposed as additional tools that could fast-track the fight against the PC NTDs. The role of clinical trials in defining these new strategies will be discussed.
PATTERNS OF MOLECULAR MARKERS OF RESISTANCE IN ‘REAL LIFE’ REPETITIVE DIHYDROARTEMISININ-PIPERAQUINE MALARIA TREATMENT: A MOLECULAR ANALYSIS OF THE WANECAM CLINICAL TRIAL PLATFORM OUTPUT
Authors: Kone Aminatou , Sagara Issaka , Björkman Anders , Djimde Abdoulaye , Gil Jose Pedro 
Published: February 2017

BackgroundThe pharmacologic characteristic of piperaquine (PPQ), namely its very long half-life, raises concerns on the possibility of relatively rapid rise of resistance. Recent unequivocal reports from SE Asia support this worry. Due to its long half-life, conventional follow-up of up to 63 days in efficacy trials misses the low concentrations of PPQ, prone to select less sensitive parasite sub-populations. The WANECAM clinical trials included a follow-up of two years of the same patients, allowing for the first time the analysis of both, the patterns of selection upon an expected large range of PPQ concentrations and the potential effect of residual levels upon repetitive treatments.MethodsWe have successfully determined a random sample of E1 (D0) 151 and 405 (E2-E10) pfcrt K76T genotypes, as well as 151 E1 (D0) and 389 (E2-E10) genotypes for the pfmdr1 E2-E10 episodes. Pfmdr1 N86Y analysis was limited by a large (>90%) prevalence of the 86N allele. Established PCR-RFLP methods were applied, with high precision band analysis being performed through image analysis software (GelEval®). Qui Square and Kruskal Wallis tests were used as applicable.ResultsThe present data analysis was limited to episodes with an intervening period of<180 days. Preliminary conclusions point to recurrences of pfmdr1 carrying 184Y parasites to emerge earlier as compared with 184F (D78vsD89, Kruskal Wallis test, p< 0.01), corresponding to an expected difference of ca. 20 to 10 nM on PPQ blood levels. No significant differences were detected concerning pfcrt K76T.ConclusionsLong-term analysis of molecular markers throughout repetitive treatments is expected to unveil informative patterns concerning early steps of PPQ resistance development. The complete set of data will be presented and analysed in the context of the recent findings of PPQ resistance in SE Asia. Its relevance for the East African settings will be discussed.
THE RESULTS OF THE EV06 DNA-PROTEIN COMBINATION TRIAL AND PLANS FOR GREAT, AN EDCTP2-FUNDED CONSERVED-MOSAIC EPITOPE HIV VACCINE TRIAL
Authors: Kaleebu Pontiano , Levin Jonathan , Nanvubya Annet , Kibengo Freddie , Jaoko Walter , Pala Pietro , Perreau Matthieu , Namuniina Annemarie , Kitandwe Paul , Tapia Gonzalo , Serwanga Jennifer , Yates Nicole , Fast Pat , Mayer Bryan , Montefiori David , Tomaras Georgia , Robb Merlin , Lee Carter , Wagner Ralf , Sanders Edward , Kilembe William , Kiwanuka Noah , Gilmour Jill , Kuipers Hester , Vooij Dani , Chinyenze Kundai , Priddy Frances , Ding Song , Hanke Tom , Pantaleo Giuseppe ,   EV06 study team GREAT study team
Published: February 2017

BackgroundThese two trials under Europe-Africa collaborations aim at addressing two factors relevant for Africa i.e helminth infections and HIV-1 diversity. EV06 used a novel combination of DNA expressing clade C Env, Gag and Pol-nef co-administered with AIDSVAX®B/E Env protein to study the effect ofS. mansonion vaccine responses. GREAT is a recently awarded trial using a 2nd generation improved conserved tHIVConsvX T-cell vaccine candidate combined with bivalent mosaic design to increase breadth and protective epitopes.MethodsEV06 enrolled 72 males and females aged 18–45, half infected withS. mansoni(SM+). In each arm 30 received vaccine and 6 placebo at week 0, 4 and 24. Responses were evaluated at week 0, 6, 26 and 36. Humoral responses were measured as binding IgG against a panel of HIV-1 envelope glycoproteins and as neutralizing antibodies (Nabs), using TZM/ bl cells and tier 1 pseudoviruses. Cellular responses were measured as HIV-specific CD4+ and CD8+ T-cell by IFN-γ ELIS-pot and multi-cytokine intracellular staining flow cytometry. GREAT will be a phase IIa trial and preparation for efficacy trials in Kenya, Uganda and Zambia testing ChAdOx1.tHIVconsv5 and ChAdOx1.tHIVconsv6 followed by MVA.tHIVconsv3 and MVA.tHIVconsv4 on week 2 (Arm 1) or week 8 (Arm 2).ProgressDifferences in binding IgG response rates were observed in vaccinated participants against the vaccine matched clade C V1V2 (gp70–96ZM651.02 V1V2) at week 6: 56% among SM+ versus 86% among SM – (p=0.039). At week 36, response magnitudes were statistically lower in the SM+ against gp120 and gp140 proteins (p=0.04 for both). SM+ also had lower Nabs and ELISpot responses at various time points. Still blinded data on the first 20 volunteers show 80% responders for CD4 T cell at w26 and 70% CD8 responders at w36. These trials will provide more data on challenges facing HIV vaccine development in Africa.
REVIEW OF HIV IN SUB-SAHARAN AFRICA: CURRENT SITUATION, OPPORTUNITIES AND CHALLENGES
Authors: Hankins Catherine 
Published: February 2017

UNAIDS estimates that in 2015, 19 million (17.7–20.5 million) and 6.5 million (5.3–7.8 million) people were living with HIV in Eastern and Southern Africa (ESA) and Western and Central Africa (WCA), respectively. Between 2010 and 2015, new HIV infections declined by 14% in ESA and 8% in WCA, while AIDS-related deaths fell by 38% and 10%, respectively. In ESA, 10.3 million people or 54% (50–58%) of all people living with HIV were accessing antiretroviral therapy (ART), compared to 1.8 million people or 28% (23–34%) of all people living with HIV in WCA. Since 2010, there has been a 66% decline in new HIV infections among children in ESA compared to a 31% decline in WCA.These striking regional differences mask large discrepancies in country progress, sex differences in ART uptake, and a diversity of micro-epidemics across sub-Saharan Africa. The goal to end AIDS as a public health threat by 2030, the UN-AIDS 90–90–90 treatment cascade goal for 2020, and the WHO recommendation to offer ART when HIV is diagnosed regardless of CD4 count are galvanizing public health and community-based responses in Africa. Despite improvements in ART and new prevention tools, including voluntary medical male circumcision and oral pre-exposure prophylaxis, the goals will not be achieved without new tools, including an HIV vaccine and a cure.EDCTP has funded high-impact HIV research that has resulted in, among others, policy change; prequalification of new products; improved treatment strategies, including for children; and strategies to prevent mother-to-child transmission, while building research capacity and clinical trial infrastructures. Promoting African country membership and increased financial contributions from African countries, EDCTP2 aims to leverage co-funding from public/private sources for calls for proposals that address important gaps in HIV prevention and treatment science that can be answered through phase I-IV clinical trials in sub-Saharan Africa.
CHLOROQUINE-SENSITIVEPLASMODIUM FALCIPARUMIN A HIGH-BURDEN MALARIA AREA AFTER OVER A DECADE OF ITS WITHDRAWAL AS FIRST-LINE ANTIMALARIAL MEDICINE: CASE OF NCHELENGE DISTRICT
Authors: Mwanza Sydney , Nambozi Michael , Chileshe Justin , Joshi Sudhaunshu , Malunga Phidelis , Kabuya Jean-Bertin , Hachizovu Sebastian , Manyando Christine , Laufer Miriam , Mulenga Modest 
Published: February 2017

BackgroundPlasmodium falciparum(Pf) resistance to anti-malarial drugs remains a major hindrance to malaria control and elimination.Pfhas developed resistance to nearly all antimalarial drugs including chloroquine, the first most frequently used first-line treatment for uncomplicated malaria. In Zambia, chloroquine was used as treatment for uncomplicated malaria for a long time untilPf-developed resistance and rose to as high as 60% in some parts of the country. This prompted the Ministry of Health to effect a drug policy change in 2003. Recent reports have indicated recovery of chloroquine susceptibility in neighbouring like Malawi, Mozambique and Tanzania. To update the information on chloroquine sensitivity in Zambia we conducted a study that assessed the prevalence of mutantPfin Nchelenge district 10 years post chloroquine withdrawal.MethodsDried blood spots for this study were collected from finger-prick blood of consenting pregnant women. Deoxyribonucleic acid (DNA) was extracted and genotyped forPfcrt-76 resistance marker using specific primers in a nested polymerase chain reaction (PCR). The PCR products obtained were then pyrosequenced and read using PyroMarkTM Q96MD software. The wild-type 3D7 and Dd2 were used as wild-type and mutated controls.ResultsNo chloroquine resistance mutation, Pfcrt 76T was detected in any of the 302 samples that were successfully amplified. This represents a 100% prevalence ofPfthat are sensitive to chloroquine in the study population.ConclusionsThis study demonstrates a total return of chloroquine-sensitivePfin Nchelenge after over a decade of withdrawal of chloroquine. In combination with another drug, chloroquine could be a good substitute for the currently used artemether lumefantrine, and intermittent preventive treatment in pregnancy (IPTp) and children.