bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIAGNOSTIC TOOLS FOR HUMAN AFRICAN TRYPANOSOMIASIS ELIMINATION AND CLINICAL TRIALS: THE DITECT-HAT PROJECT
Authors: Lejon Veerle , Ilboudo Hamidou , Mumba Dieudonné , Camara Mamady , Kaba Dramane , Lumbala Crispin , Fèvre Eric , Jamonneau Vincent , Bucheton Bruno , Büscher Philippe 
Published: February 2017

BackgroundTrypanosoma brucei gambiense(Tbg) causes human African trypanosomiasis (HAT), one of the neglected tropical diseases targeted for elimination. Integration of diagnosis and case management into the general health system, sustainable monitoring of eliminated foci and development of safe and efficacious drugs, remain important challenges.MethodsThe DiTECT-HAT project tackles these challenges. For passive case detection, we will determine the diagnostic performance and cost of rapid diagnostic tests (RDTs) performed on clinical suspects in peripheral health centres, whether or not combined with serological and/or molecular tests on filter paper done at regional reference centres. Cost-effective diagnostic algorithms with high positive predictive values might allow test-and-treat scenarios without the need for complicated parasitological confirmations. Secondly, health workers performing house to house visits in foci with very low HAT prevalence can easily collect blood on filter paper and send it to regional HAT reference centres for analysis. The feasibility and cost of diagnostic algorithms with RDTs, serological and molecular high-throughput tests for post-elimination monitoring will be determined. An appropriate threshold will be established to trigger active case finding to avoid re-emergence of HAT, without unnecessarily raising the alarm. Finally, the accuracy of neopterin and RNA detection as early test-of-cure will be determined in therapeutic trials.Earlier treatment outcome assessment will speed up the development of new drugs for HAT, and improve management of relapses in routine care.ResultsAn update of ongoing and planned activities is given. The passive case detection sub-project is being set up in DR Congo, Côte d'Ivoire and Guinea. The inclusions for the early test-of-cure sub-project are ongoing in DR Congo.ConclusionsThe proposed research will provide evidence to support policies for improved HAT diagnosis and patient management within a context of disease elimination, and will contribute to successful and sustainable HAT elimination.
ACTIVE PHARMACOVIGILANCE IN CôTE D'IVOIRE
Authors: Djima Mariam Mama 
Published: February 2017

BackgroundIn Africa, pharmacovigilance (PV) is a relatively new science. Yet the African context is favourable to the irrational use of medicines, the circulation of counterfeit drugs, and a high consumption of traditional medicine. This should make PV in African countries a critical and crucial issue to ensure the safe use of treatments available. The collection system used in pharmacovigilance in Africa is predominantly passive. This passive system suffers from significant underreporting because it detects only 1–10% of adverse events. The limit in the passive detection and the growing concerns about security in the long term of drugs widely used in health programs, have stimulated in many countries the implementation of active systems such as actively seeking to improve the development of PV in their countries. In Côte d'Ivoire, pharmacovigilance at the regulatory level started in 1988. What is actually the state of pharmacovigilance and the impact of active research in the development of pharmacovigilance?MethodsThis is an observational descriptive study using a qualitative analysis of interviews in order to provide answers to these questions. The interview guides are constructed from a questionnaire already used in the monitoring of pharmacovigilance activities by the Uppsala Monitoring Center in countries with limited resources.ResultsActive surveillance has several sources. A well-known source is the pharmaceutical industry in the conduct of clinical trials and the risk management plans. The pharmaceutical industry accounts for over 80% of reports of adverse effects at national level. The second data source are research centres, but the reporting of adverse effects is not made at national level. The last source of data comes from active operational research studies which as a source are weak and this should be strengthened.ConclusionsActive pharmacovigilance is to be encouraged in Côte d'Ivoire because it will collect data to improve the safety of medicines consumed by the population.
SCHISTOSOMIASIS, PRAZIQUANTEL AND FOOD: THE CONTROL OF A MALADY AMONG SCHOOL-AGE CHILDREN IN UGANDA
Authors: Muhumuza Simon , Katahoire Anne , Nuwaha Fred , Olsen Annette 
Published: February 2017

BackgroundAnnual school-based mass treatment with praziquantel is the cornerstone for schistosomiasis control among school-age children in Uganda. However, uptake of treatment is low. We evaluated strategies for improved uptake of mass treatment and the effects on the prevalence and mean intensity ofS. mansoniinfectionMethodsThrough serial cross-sectional surveys conducted in 2011 and 2012 in 12 primary schools in Jinja district and a cluster randomised trial conducted in 2013, the levels of uptake of praziquantel and the prevalence and mean intensity ofS. mansoniinfection among school children were determined. Additionally, in 2012, the effect of increased teacher motivation to distribute treatment was assessed. In 2013, the effectiveness of provision of a pre-treatment snack in improving uptake was evaluated.ResultsA total of 1010, 1020 and 1284 randomly selected children were enrolled in 2011, 2012 and 2013, respectively. Uptake of praziquantel was 28.2% (95% CI: 22.9%–33.6%) in 2011. Prevalence and intensity ofS. mansoniinfection was 35.0% (95% CI: 25.4%–37.9%) and 116.1 eggs per gram of stool (epg) (95% CI 98.3–137.1), respectively. With increased teacher motivation in 2012, uptake increased to 48.9% (95% CI: 45.8%–52.0%). The prevalence and intensity ofS. mansoniinfection was 32.6% (95% CI: 29.6%–35.5%) and 133.1 epg (95% CI: 99.0%–167.2%), respectively. Provision of a pre-treatment snack in 2013 increased uptake to 85.5% (95% CI: 82.5%–91.7%) and reduced the prevalence and intensity ofS. mansoniinfection to 8.2% (5.6%–12.2%) and 15.9 epg (95% CI: 12.3%–19.2%), respectively.ConclusionsAlthough teacher motivation increased uptake of mass treatment, the realised uptake was too low to affect the prevalence and intensity of schistosomiasis among school children. Conversely, provision of a pre-treatment snack achieved a high uptake. The increased uptake significantly reduced the prevalence and intensity ofS. mansoniinfection in this age group.
SAFETY OF RVSV EBOLA VACCINE, AFTER 6 MONTHS FOLLOW-UP, IN ADULTS: A PHASE 1 TRIAL CONDUCTED IN LAMBARÉNÉ, GABON
Authors: Fernandes José , Bache Emmanuel B. , Mba Régis M Obiang , Kabwende Anita L. , Mordmüller Benjamin , Krishna Sanjeev , Kremsner Peter G. , Grobusch Martin P. , Todagbe Agnandji Selidji 
Published: February 2017

IntroductionThe Centre de Recherches Médicales de Lambaréné (CERMEL) in Gabon, member of the ‘VSV-EBola CONsortium’ (VEBCON), evaluated safety and immunogenicity of the rVSV∆G-ZEBOV-GP vaccine in African volunteers from an area with previous Ebola outbreaks before its use during the last outbreak in West Africa.MethodsFrom November 2014 to April 2015 we performed an open-label, dose escalation phase 1 trial to assess safety, side-effect profile, and immunogenicity of rVSV-ZEBOV. A total of 115 healthy adults both male and non-pregnant or lactating female volunteers aged 18–50 years old living in Lambaréné (Gabon) were included. Participants were allocated to five vaccine dose groups: 3×103PFU (n=20), 3×104PFU (n=20), 3×105PFU (n=20), 3×106PFU (n=39) and 2×107PFU (n=16). Here, we present data on adverse events (AE) and serious adverse events (SAE) between days 180 and 365 after vaccine injection (Day 0).ResultsFrom Month six to Month 12, the proportion of volunteers with AE as well as number and grade of AEs per volunteer were similar in the five groups. A higher total number of events occurred in the cohort 3×106PFU, the largest group. Most symptoms were mild to moderate. No clinically significant laboratory changes were observed. Three events - two episodes ofP. falciparummalaria and one snake bite - were graded as serious, because they required hospitalizations. Both SAE were judged as non-related to the vaccine and resolved without sequelae. None of the adverse events was related to rVSV-ZEBOV vaccine.ConclusionsOur results confirmed an acceptable profile of safety and tolerability of rVSV-ZEBOV up to 12 months of follow-up. In order to investigate possible late-stage safety signals follow-up period of the study was extended to five years. Integrating data (assessment until 60 months) from all the VEBCON study sites is the next key step allowing a final conclusion about safety of rVSV-ZEBOV. The trial was registered on the Pan African Clinical Trials Network website with the number PACTR201411000919191
R&D TO TACKLE GLOBAL HEALTH CHALLENGES: ROLES AND RESPONSIBILITIES FOR EDCTP
Authors: Tanner Marcel 
Published: February 2017

As well documented, the diseases of poverty and Neglected Tropical Diseases (NTDs) cost the lives of millions of people worldwide and threaten the health of millions more. More than 200 million health years of life are lost every single year due to mortality, morbidity and disability. This not only represents an unacceptable burden for the populations concerned, mainly the most impoverished segments of a population, but also impairs health development and all our efforts to reach the Sustainable Development Goals. NTDs and diseases of poverty are clearly part of the overall neglect of people and health and social systems.The high burden of diseases of poverty and NTDs calls for new efforts in developing effective and efficient approaches to control or even eliminate these diseases. This in turn implies that we must aim at new discoveries and innovations and – at the same time – make most effective use of existing tools as well as of innovative partnerships between the public and the private sectors and between different countries; clearly the niche and responsibility of EDCTP.The presentation will discuss needs and ongoing efforts in diagnosis, drug and vaccine development against diseases of poverty and NTDs and will also discuss (i) obstacles at the level of health and social systems that prevent access of the populations to new and existing efficacious tools as well as (ii) new approaches in R&D to overcome these obstacles and barriers. While there are great hopes and also substantial advances in drug, diagnostics and vaccine development, R&D does not and should not alone focus on developing new tools, but rather on combining existing and new tools for integrated approaches of diseases control and elimination that are tailored to a given endemic setting and are combined with effective capacity building. The outlook and discussion will emphasize the potential, chances and responsibilities of EDCTP to strengthen effective partnership, capacity building and national and global health development.
NEW POSSIBILITIES FOR THE DEVELOPMENT OF A COMBINED VACCINE AGAINST ETEC ANDSHIGELLA
Authors: Walker Richard 
Published: February 2017

BackgroundTogether, enterotoxigenicEscherichia coli(ETEC) andShigellacontribute greatly to the mortality and the morbidity due to diarrhoeal diseases, including a number of negative lifetime health impacts. Vaccines represent a reasonable option to reduce this burden.Vaccinecandidates PATH has reviewed the landscape of vaccine candidates for these diseases and identified two candidates to be moved towards licensure in the near-term as a combined ETEC andShigellavaccine for use on an Expanded Programme on Immunisation (EPI) schedule.ETVAXOne candidate is a formalin-inactivated ETEC vaccine (ETVAX) consisting of fourE. colipreparations, each engineered to hyper-produce the CFA/1, CS3, CS5, and CS6 antigens of ETEC. In addition, the vaccine contains a cholera B subunit modified to be more cross-reactive with the B subunit of ETEC. ETVAX is co-administered with a double-mutant of the ETEC heat-labile toxin (dmLT), which serves as a potent mucosal adjuvant.TSWCThe other candidate includes formalin-killedS. flexneri2a and 3a andS. sonneiprepared as a trivalent vaccine, called TSWC. A prototype of TSWC,S. flexneri2a, was administered to North American volunteers and found to be safe and immunogenic; it is now currently in a challenge trial.Lookingahead Early 2017 in a phase I trial, we will test TSWC given alone and co-administered with ETVAX. ETVAX given alone exceeded expectations for immunogenicity in Swedish volunteers and is projected to be evaluated for safety and early efficacy in Finnish travellers to Benin in early 2017. ETVAX is also currently being tested in a descending-age trial in Bangladesh to determine the optimum safe dose of vaccine and adjuvant to be given to infants as young as 6 to 10 weeks of age. We also hope that the dmLT will have a dose-sparing effect on the vaccine given to this target population.
SAFETY AND IMMUNOGENICITY OF CO-ADMINISTERED HOOKWORM VACCINE CANDIDATES NA-GST-1 AND NA-APR-1 WITH ALHYDROGEL® AND GLUCOPYRANOSYL-LIPID A IN GABONESE ADULTS: INTERIM RESULTS
Authors: Adegnika Ayola , Vries Sophie De , Zinsou Frejus Jeannot , Honkpehedji J , Dejon Jean Claude , Loembe Marguerite Massinga , Bache Bache , Pakker Nadine , Leeuwen Remko Van , Hounkpatin Aurore Bouyoukou , Kremsner Peter , Yazdanbakhsh Maria , Lell Bertrand , Bethony Jeffrey , Hotez Peter , Diemert David , Grobusch Martin 
Published: February 2017

BackgroundHookworm disease is one of the most prevalent of the neglected tropical diseases. To date, the control of hookworm infection has been limited to mass-administration of anthelminthic drugs. Despite this, the global hookworm prevalence does not decrease, thus there is a need for a vaccine. We evaluated the Na-GST-1 and Na-APR-1 hookworm vaccine candidates simultaneously in a hookworm endemic Gabonese population.MethodsEligible healthy Gabonese adults aged 18–50 years were enrolled in a randomised, double blind, controlled phase I trial. The first cohort received 30 µg Na-GST-1 co-administered with 30 µg Na-APR-1. The second cohort received 100 µg Na-GST-1 and 100 µg Na-APR-1. All doses were administered after mixing with 5 µg of an aqueous formulation of glucopyranosyl Lipid A (GLA-AF), a Toll-like Receptor-4 agonist. Hepatitis B vaccination (HBV) was administered as a comparator. Study subjects were vaccinated on days 0, 28 and 180 by intramuscular injection. IgG antibody levels were measured by qualified ELISA. This study evaluated the safety, reactogenicity, and immunogenicity ofNa-GST-1/Alhydrogel® co-administered with Na-APR-1/Alhydrogel®.ResultsThirty-two study participants were enrolled. No serious adverse events or significant changes in haematological, renal or liver function parameters were observed. Mild-to-moderate injection-site pain, headache and fever were common adverse events. Elevated Na-GST-1 and Na-APR-1 IgG antibody levels were detected on day 194. Significant differences in mean antibody levels were observed between dose groups for Na-APR-1 [30 µg: 18 (50–86.9)vs100 µg: 197 (131– 264); p< 0.0001] but not for Na-GST-1 [30 µg: 338 (213–463)vs100 µg: 402.54 (283.65–521); p=0.5].ConclusionsCo-administration of the hookworm vaccine candidates (Na-GST-1 and Na-APR-1) was safe and well tolerated. In order to achieve optimal antibody levels, a series of three high doses needs to be administered. Additional investigations are necessary to consider this combination as a potential bivalent vaccine candidate.
ARTEMISININ-BASED COMBINATION TREATMENTS IN PREGNANT WOMEN IN ZAMBIA: EFFICACY, SAFETY AND RISK OF RECURRENT MALARIA
Authors: Nambozi Michael , Kabuya Jean-Bertin , Hachizovu Sebastian , Mwakazanga David , Kasongo Webster , Buyze Jozefien , Mulenga Modest , Geertruyden Jean-Pierre , D'Alessandro Umberto 
Published: February 2017

BackgroundIn Zambia, malaria is one of the leading causes of morbidity and mortality, especially among under five children and pregnant women. For the latter, WHO recommends the use of Artemisinin-based Combinations Treatments (ACTs) in the second and third trimester of pregnancy. In a context of limited information on ACTs, the safety and efficacy of three ACTs, namely artemether-lumefantrine (AL), mefloquine-artesunate (MQAS) and dihydroartemisinin-piperaquine (DHAPQ) were assessed in malaria-infected pregnant women.MethodsTrial was carried out between July 2010 and August 2013 in Nchelenge district, Luapula Province, an area of high transmission, as part of multi-centre trial. Women in second or third trimester of pregnancy and with malaria were recruited and randomized to one of three study arms. Women were actively followed up for 63 days, and then at delivery and one year post-delivery.ResultsNine hundred pregnant women were included, 300 per arm. PCR-adjusted treatment failure was 4.7% (12/258) (95%CI:2.7–8.0) for AL, 1.3% (3/235) (95%CI:0.4–3.7) for MQAS and 0.8% (2/236) (95%CI:0.2–3.0) for DHAPQ, with significant risk difference between AL and DHAPQ (p=0.01) and between AL and MQAS (p=0.03) treatments. New infections during follow up were more frequent in AL (Hazard Ratio (HR):4.70; 95%CI:3.18–6.94; p<0.01) and MQAS (HR:1.59; 95%CI:1.02–2.46; p=0.04) arms compared to DHAPQ arm. PCR-adjusted treatment failure was significantly associated with women under 20 years [HR5.35 (95%CI:1.07–26.73; p=0.04)] and higher malaria parasite density [3.23 (95%CI:1.03–10.10; p=0.04)], and still women under 20 years [1.78, (95%CI:1.26–2.52; p<0.01)] had a significantly higher risk of new infections. Unadjusted for treatment, low treatment dosage per kg body weight was significantly associated with the risk of new infections (HR:1.72; 95%CI:1.29–2.28; p<0.01). The three treatments were generally well tolerated. Dizziness, nausea, vomiting, headache and asthenia as Adverse Events (AEs) were more common in MQAS than in AL or DHAPQ (p<0.001). Birth outcomes were not significantly different between treatment arms.
RANDOMIZED TRIAL TO ASSESS EFFECT OF REPEATED TREATMENT OF DHA-PQ AND AL ON QTC INTERVAL IN PATIENTS PRESENTING WITH UNCOMPLICATED MALARIA IN BOBO-DIOULASSO, BURKINA FASO
Authors: Kabore Naomie , Barry Nouhoun , Kabre Zachari , Werme Karidia , Fofana Aminata , Compaore Daniel , Nikiema Frederic , Some Fabrice , Djimde Abdoulaye , Zongo Issaka , Ouedraogo Bosco 
Published: February 2017

BackgroundArtemisinin combination therapies (ACTs) are widely used for the management of malaria and even tested for chemoprevention. In single episode efficacy studies, these drugs were clinically well tolerated but cardiac effects over repeated treatment are less investigated.MethodsWe conducted a prospective randomised controlled trial in Bobo-Dioulasso from August to October 2013 where patients aged 6 months and over were randomly allocated to receive either dihydroartemisinin-piperaquine (DHAPQ) or artemether-lumefantrine (AL) on first and subsequent episodes. Each participant was screened against inclusion criteria including the ECG which was repeated again 2 hours after the last dose. We considered that a QTc interval more than 30 ms compared to the baseline value is abnormal, but a prolonged QTc interval over 450 ms was reported as adverse event. QTc values were categorised into less or greater or equal to 450 ms. Drug tolerance was compared using Chi-square test, and p-value of less than 0.5 is significant.ResultsPatients were randomised to receive DHAPQ (n=224) or AL (n=236). During the 2 years follow-up we observed a total of 130 (in 1173 electrocardiogram performed on day 2 monitoring) prolonged QTc more than 450 ms (96/548 for DHAPQ and 34/625 for AL, p< 0.001). Irrespective of the drug, these proportions of prolonged QTc decreased over the subsequent episodes (50 QTc =450 in episode 1 to 0 in episode 8 up to episode 10).ConclusionsThe proportion of prolonged QTc was higher in DHAPQ group compared to the AL group but decreased along with the number of retreatments. Otherwise, DHAPQ and AL were well tolerated despite repeated treatment of malaria, which seemed to improve over consecutive episodes.
IMMUNOGENS DESIGNED FOR TARGETING NEUTRALIZING EPITOPES OF HIV-1 ENVELOPE GLYCOPROTEIN
Authors: Nchinda Godwin , Bopda Alain , Nji Nadesh , Ambada Georgia , Ngu Loveline , Tchadji Jules , Sake Carol , Magagoum Suzanne , Njambe Ghislain D. , Lisom Abel , Park Chae Gyu 
Published: February 2017

BackgroundDue to its unique challenge of establishing lifelong reservoirs a successful HIV-1 vaccine must elicit protective antibodies responses at the portals of entry. Broadly neutralising antibodies (bnAb) have been demonstrated not only to be therapeutic through suppressing viraemia in HIV-1 infected people but also preventive in blocking HIV-1 infection in animal models. This implies that a desirable HIV-1 vaccine candidate should be able to induce HIV-1 specific bnAb with an extensive ability to neutralise a broad range of HIV-1 isolates. Although several bnAb are known to target conserved regions in the HIV-1 envelope glycoprotein, no vaccination strategy has successfully produced such antibodies. Thus, the ability to optimise and deliver HIV envelope immunogens that can induce bnAb has remained a formidable challenge.MethodsTo optimise immunogens for inducing bnAb, our group has pursued two main directions. In the first instance we developed B cell immunogens mimicking the native HIV-1 enveloped gp120 glycoprotein. Supernatants of stably transfected mutant lec1 CHO cells using a flag tag. We next assess antibodies isotypes specific to this immunogen in plasma obtained from antiretroviral naive participants. Secondly, through surface engineering of the evolutionary phage Qbeta we built in several epitopes of bnAbs for effective delivery to the immune system. We next assess in plasma from 648 seropositive participants the abundance of antibody isotypes specific to these B cell immunogens.ResultsThe results obtained showed that all IgG isotypes were detected for both the manosylated and CHO wild-type expressed gp120. Although all IgG antibody isotypes including IgG1, IgG2, IgG3 and IgG4 were dictated, there was no significant difference between antibody titres directed to manosylated gp120 and wild-type gp120. Well over 87% of seropositive participants showed specific antibody responses to conserved B cell epitopes displayed on the surface of Qbeta phage.ConclusionsThese novel immunogens can be used as vaccine candidates.