bluuebunny/crossref_metadata_2025_split huggingface dataset:
MASS DRUG ADMINISTRATION (MDA) INTEGRATED MALARIA ELIMINATION IN A HYPO-ENDEMIC ISLAND IN LAKE VICTORIA, KENYA
Authors: Gitaka Jesse , Chan Chim , Kongere James , Kagaya Wataru , Kaneko Akira 
Published: February 2017

BackgroundMass drug administration (MDA) for malaria elimination has been proposed as a feasible weapon especially for low endemicity settings. Nonetheless, the concept has not been tried for hypo-endemic areas of inland Africa. We conducted MDA using artemisinin-piperaquine and low dose primaquine with insecticide-treated bed nets (ITN) in Ngodhe Island, Lake Victoria, Kenya, aiming to reduce prevalence to below 1% in 6 months post MDA.MethodsWe conducted 2 rounds of MDA on days 0, 1, 35 and 36. We employed strong community linkages to ensure robust engagement with the community using workshops, feedback sessions and involvement of community health volunteers previously set up by the Ministry of Health and community fieldworkers. The MDA was administered (directly observed) and participants followed up for possible side effects. Participants were not tested for glucose-6-phosphate dehydrogenase deficiency. Malaria infection was determined by microscopy and polymerase chain reaction (PCR).ResultsMDA coverage was 90% for round 1 and 89% for round 2, with no major drug side effects or haemolytic emergencies. The mean haemoglobin decrease after MDA was not significant. Prevalence by microscopy decreased from 3.1% on day 0 to 0% on day 8. Prevalence was 1.1% on day 35, and 0.21% on day 120. Importation of malaria was noted to pose a challenge in maintaining malaria freedom.ConclusionsMDA led to a rapid reduction in malaria prevalence in a hypo-endemic setting in Western Kenya demonstrating feasibility when combined with strong community engagement. Primaquine was well tolerated with no haemolytic emergencies. Nonetheless, strategies to mitigate imported malaria need to be developed for long-term sustainability.
LIMITED IMPACT OF TREATMENT AND RE-TREATMENT WITH ARTEMETHER-LUMEFANTRINE AND ARTESUNATE-AMODIAQUINE ON THE SELECTION OFPLASMODIUM FALCIPARUMMULTIDRUG RESISTANCE-1 ALLELES
Authors: Baraka Vito , Nabasumba Carolyn , Francis Filbert , Lutumba Pascal , Mavoko Hypolite , Alifrangis Michael , Geertruyden Jean-Pierre Van 
Published: February 2017

BackgroundThe emergence of resistance against artemisinin combination treatment (ACTs) is a major concern for malaria control. ACTs are recommended as rescue treatment; however, there is limited evidence on the impact of treatment and re-treatment with ACTs on selection for drug-resistant parasites. We aimed to investigate the impact of treatment and re-treatment using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) on the selection ofPlasmodium falciparummultidrug resistance-1 (Pfmdr1) alleles.MethodsA total of 776 isolates were collected in 28-days follow-up involving children aged 0–59 months in a clinical trial in the Democratic Republic of Congo and Uganda. Nested PCR and RPFL was used to detectPfmdr1single-nucleotide polymorphisms at codons N86Y, F184Y, and D1246Y. The analysis comparedPfmdr1 alleles in the pre-randomisation (pre-RCT), randomisation (RCT) and post-randomisation (post-RCT) phases of the trial.ResultsThe pre-treatment prevalence ofPfmdr1 (N86 and D1246Y) in the RCT phase varied significantly between the sites.Pfmdr1NYDhaplotype was significantly higher in Uganda while haplotypeYYDwas higher in the Democratic Republic of Congo, (p<0.001). Comparison between pre-treatment and post-treatment adequate clinical and parasitological response (ACPR) or PCR-adjusted treatment failure did not indicate increased selection ofPfmdr1 N86, D1246 and Y184 in either AL or ASAQ arm in the pre-RCT, RCT and post-RCT phases. The relative risk (RR) of treatment failure (TF) in patients harbouringPfmdr1 N86 did not significantly increase in patients treated with AL (RR=0.2, 95% CI: 0.11–1.05, p=0.061) or ASAQ (RR=1.03, 95% CI: 0.47–2.26, p=0.94).ConclusionsOur findings suggest the limited impact of treatment and re-treatment with AL or ASAQ on selection forPfmdr1variants and haplotypes associated with resistance to partner drugs. These findings support the recent WHO recommendation to use ACTs as alternative rescue therapy forP. falciparummalaria. However, enhanced resistance monitoring is warranted to maintain the drug's effectiveness in endemic settings.
PF3D7_1343700 KELCH PROPELLER (K13-PROPELLER) POLYMORPHISMS AND ARTESUNATE MONOTHERAPY EFFICACY IN UNCOMPLICATED MALARIA TREATMENT IN MALI
Authors: Sissoko Sekou , Kone Aminatou , Fofana Bakary , Sangaré Cheick , Dembele Demba , Toure Sekou , Sanogo Kassim , Diakite Hamadoun , Toure Siaka , Doumbia Diagassan , Haidara Kadiatou , Doumbo Ogobara , Djimde Abdoulaye 
Published: February 2017

BackgroundSeveral mutations in the PF3D7_1343700 kelch propeller (K13-propeller) were recently described as associated with artemisinin resistancein vivoandin vitroin Southeast Asia. In Mali, a preliminary study on artesunate efficacy in 2011 found no delay in parasite clearance. A larger study including two sites in Mali is conducted here in the context of regular monitoring of artemisinin resistance.MethodsFrom October 2015 to March 2016, we conducted a prospective study on artesunate monotherapy in Bougoula-Hameau and Faladje on uncomplicated malaria patients aged more than 6 months. Patients were treated for 7 days and followed up for 28 days. Blood smear was performed for parasite evaluation every 8 hours until three consecutive slides were negatives. MSP2, Ca1 and TA99 polymorphisms were used to distinguish new infections from recurrent parasites. The PfK13 mutations were genotyped using direct sequencing of PCR amplicons from dried blood spots of pre and post-treatmentfalciparumparasites. The results were compared with the studies conducted in a same area on 2011.ResultsA total of 100 and 120 patients were enrolled in Bougoula-Hameau and Faladje, respectively. The uncorrected adequate clinical and parasitological responses (ACPR) were 92.0% in Bougoula-Hameau and 78.3% in Faladje. After molecular correction, we obtained 100% cACPR in both sites. The prevalence of the non-synonymous single nucleotide polymorphisms (SNPs)K13was 2% in Bougoula (found only at enrolment) but null in Faladje. However SNPs were 3% and 7% in Bougoula-Hameau and Faladje, respectively.ConclusionsArtesunate monotherapy remains effective onP. falciparumin Mali and there are only low levels of PfK13 mutations.
VARIABILITY IN CLINICAL RESEARCH DATA MANAGEMENT PRACTICES: LESSONS FROM THE MALARIA COMMUNITY
Authors: Julé Amélie , Ashurst Hazel , Merson Laura , Olliaro Piero , Marsh Vicki , Lang Trudie , Guérin Philippe 
Published: February 2017

BackgroundAppropriate data management (DM) is critical to produce valuable research data, especially with growing prospects for long-term archiving, sharing and individual patient data meta-analysis. The experience of the WorldWide Antimalarial Resistance Network (WWARN) in handling data from clinical studies is that DM practices vary greatly, which affects curation and optimal use of shared data. Our work explores how clinical trial data are usually managed and why this varies. We aim to understand the needs in DM systems (DMS) for resource-limited research settings within low- and middle-income countries (LMICs).MethodsUsing published literature and discussions with key informants, we developed a semi-quantitative instrument to assess the robustness of the initial DMS and the resulting ‘re-usability’ of clinical research data. We also defined study covariates which could account for the observed variability (e.g. type of sponsor/funding, partners involved, trial phase). The strength of correlations between indicators of good DM practices, resulting data quality and study context will be tested through statistical modelling.ResultsThe instrument covers the following dimensions of data robustness: meta-data availability, comprehensiveness and exhaustiveness; dataset completeness; and data accuracy. It is currently being piloted on a subset of 20 studies (about 5% of the total WWARN database), to test its applicability in highlighting DM practices' variations and in capturing other relevant study characteristics. After finalisation of the instrument, the analysis will be rolled out to 150 studies. We will present the patterns and correlations between specific indicators and study covariates we observe within this randomly selected sample, and discuss their implications in terms of DM capacity-strengthening.ConclusionsThe significance of quantitative findings will be challenged using qualitative interviews and visits at institutions for in-depth case studies of DM practices. Results of the overall mixed-methods work could inform strategies for clinical research DM capacity-strengthening in LMICs, including initiatives relevant to the European & Developing Countries Clinical Trials Partnership (EDCTP).
GAMETOCYTE CARRIAGE AFTER A TREATMENT WITH PRIMAQUINE COMBINED WITH DIHYDROARTEMISININ-PIPERAQUINE IN MALARIA-INFECTED, ASYMPTOMATIC INDIVIDUALS
Authors: Dabira Edgard 
Published: February 2017

BackgroundWith the decrease of malaria burden, additional interventions capable of interrupting transmission from human to mosquitoes are required to achieve malaria elimination. Primaquine (PQ) is the only antimalarial drug recommended against mature gametocytes; however, its use has been limited because it causes a dose-dependent haemolytic anaemia. A clinical trial was conducted in The Gambia to evaluate the impact of dihydroartemisinin-piperaquine (DP) with and without PQ on gametocyte carriage and infectiousness to mosquitoes. As an ancillary study, we compared the efficacy of the four different treatments in asymptomaticPlasmodium falciparum-infected individuals.MethodsThe main study was a four-arm, open label, randomised-controlled trial comparing the effect of three different single doses of PQ (0.75 mg/kg, 0.4 mg/kg, and 0.2 mg/ kg) on gametocyte carriage in malaria-infected, asymptomatic individuals with normal glucose-6-phosphate dehydrogenase status. All treatment arms received DP with the fourth arm acting as control. Our ancillary study aimed to determine the duration of gametocyte carriage in the PQ groups compared to the control group and to assess the adequate and clinical response of treatment (ACPR) at day 42 of follow-up.ResultsA total of 694 individuals were enrolled; 175 were randomised to the control, 172 to the 0.75PQ, 175 to the 0.4PQ, and 172 to the 0.2PQ arms. The hazard ratio (HR) of gametocytes carriage was significantly longer in the control group compared to each of the PQ arms; 1.8 (1.2–2.6 p=0.002) in 0.75PQ, 1.5 (1.0–2.1 p=0.03) in 0.4PQ and 1.5 (1.0–2.1 p=0.04) in 0.2PQ. At day 42, ACPR was 97.04%; 95.48%; 92.45%; 99.37% in DP group; 0.75PQ; 0.4PQ and 0.2 PQ, respectively.ConclusionsAdding PQ to DP shortens the duration of gametocyte carriage and the adequate and clinical response of treatment (ACPR) is high.
SAFETY AND EFFICACY OF SAR97276A FOR TREATING MALARIA: TWO OPEN-LABEL MULTICENTER PHASE II CLINICAL STUDIES IN AFRICAN CHILDREN AND ADULTS
Authors: Held Jana , Supan Christian , Salazar Carmen L. Ospina , Tinto Halidou , Bonkian Léa Nadège , Nahum Alain , Sié Ali , Abdulla Salim , Cantalloube Cathy , Djeriou Elhadj , Bouyou-Akotet Marielle , Ogutu Bernhards , Mordmüller Benjamin , Siribie Mohamadou , Sirima Sodiomon B. , Kremsner Peter G. 
Published: February 2017

BackgroundSAR97276A, is a choline analogue inhibiting the phospholipid biosynthesis ofPlasmodium falciparum.Treatment options for severe malaria are limited and SAR97276A represents a drug candidate for this indication.MethodsThis is a report on two consecutive trials evaluating safety and efficacy of parenterally administered SAR97276A for the treatment of malaria.The first study was a phase 2, multicenter, open-label study at six African hospitals (NCT00739206). At first adults with uncomplicated malaria were included receiving a single dose SAR97296A (IM: 0.18 mg/kg or IV: 0.14 mg/kg) followed by repeated dosing with daily administration of the IM dose for three days in case of lack of efficacy of the single-dose regimen before age de-escalation.The second study was a phase 2, multicenter, randomized, controlled open label study at five African hospitals assessing safety and efficacy of a higher dose of SAR97276A IM once (0.5 mg/kg) or twice (0.25 mg/kg) daily for 3-days compared to artemether-lumefantrine in children 12–17 years before age de-escalation to younger children (NCT01445938).ResultsIn the first study 113 patients received SAR97276A: 30 adults single-dose IV, 34 adults single-dose IM, 30 adults 3-day dose IM and 19 children 3-day dose IM. SAR97276A given as a single-dose to adult patients showed insufficient efficacy by IM route (20 cured of 34; and IV route (23/30 cured). The 3-day treatment showed a sufficient level of efficacy when given IM to adults (27/30 cured) but not when given to children 7–17 years (13/19 cured).In the second study 20 patients were recruited and randomly assigned (2:2:1 ratio) to receive once-daily SAR97276A, twice-daily SAR97276A or artemether-lumefantrine. All patients receiving SAR97276A once-daily and 5/8 patients receiving SAR97276A twice-daily required rescue therapy. All patients in the control group were cured.ConclusionBoth studies were stopped due to lack of efficacy. SAR97276A given as monotherapy up to three days is not efficaciously curing malaria.The studies were funded by Sanofi.
COMPARATIVE PROTECTIVE EFFECT OF REPEATED ADMINISTRATION OVER A TWO YEAR PERIOD OF 3 ACTS ON THE EMERGENCE OF HYPERPARASITEMIA IN MALARIA PATIENTS
Authors: Ouattara San Maurice , Soulama Issiaka , Coulibaly Sam , Kabore Jean Moïse , Ouedraogo Alphonse , Bougouma Edith , Sanon Souleymane , Amidou Diarra , Sombie Benjamin , Ouedraogo Amidou , Kargougou Désiré , Ouattara Daouda , Issa Nebie , Tiono Alfred , Sirima Sodiomon 
Published: February 2017

BackgroundHyperparasitaemia in malaria infection represents a worsening circumstance of the patient's condition; however, it still remains a concept with a controversial definition and seems likely to be understudied. The present study in the framework of the WANECAM activities aimed to assess the protective effect of 3ACTs on the emergence of the hyper-parasitaemia when repeatedly administrated over a period of two years to patients with uncomplicated malaria.MethodsA two-year prospective longitudinal study (763 adults and children) was conducted in a malaria endemic area of Burkina Faso. Passive detection of malaria cases with parasitaemia ≥200000 trophozoites/µl was done. Malaria smear was performed for hyperparasitaemia confirmation; a clinical examination and demographic data were recorded. Each patient was repeatedly treated with one of the three anti-malarials, pyronaridine-artesunate, dihydroartemisinin-piperaquine or artesunate-amodiaquine, at any uncomplicated malaria episode.ResultsA total of 107 cases of malaria with hyperparasitaemia were diagnosed; 63.55% occurred in under-five years children. The geometric mean of parasite density was 283366 trophozoites/µl (CI 95%: 264644–302087). The 46 cases recorded in the pyronaridine-artesunate treatment arm (224 patients) was higher compared to the 39 cases in the artesunate-amodiaquine arm (315 patients), (p=0.0024) and to the 22 cases in the dihydroartemisinin-piperaquine arm (224 patients), (p=0.0022). The difference between dihydroartemisinin-piperaquine and artesunate-amodiaquine treatment arms was not statistically significant (p=0.40).ConclusionsFrom this study, children under five year of age were mostly at risk of hyperparasitaemia. Dihydroartemisinin-piperaquine and artesunate-amodiaquine seem the most protective antimalarial against the occurrence of hyperparasitaemia.
ASSESSMENT OF SAFETY PARAMETERS FOLLOWING REPEATED ARTEMISIN-BASED TREATMENTS OF MALARIA-INFECTED PATIENT LIVING IN ENDEMIC AREA OF BURKINA FASO
Authors: Coulibaly Sam , Soulama Issiaka , Kabore Jean Moïse , Ouattara San Maurice , Bougouma Edith , Ouedraogo Alphonse , Sanon Souleymane , Amidou Diarra , Sombie Benjamin , Ouedraogo Amidou , Kargougou Désiré , Ouattara Daouda , Issa Nebie , Tiono Alfred , Sirima Sodiomon 
Published: February 2017

BackgroundArtemisinin-based combination therapies (ACTs) constitute the worldwide recommended antimalarial drug as first-line treatment of uncomplicated malaria. However, the safety of repeated administration of a given ACT is poorly documented. The aim of this study was to evaluate the safety of repeated administration of ACTs in malaria patients over a period of 2 years.MethodsA randomised, open-label phase IIIb/IV comparative three arms trial comparing pyronaridine tetraphosphate/artesunate (PA), dihydroartemisinine-pipéraquine (DHA-PQP) and artesunate-amodiaquine (ASAQ) was carried out in Burkina Faso site as part of the WANECAM (West African Network for Clinical Trials of Antimalarial Drugs) global study. The study involved patients from 6 months of age presenting with uncomplicated malaria (fever/history of fever andPlasmodiumspp. density <200,000). The patients were treated repeatedly with the same ACT they were assigned to at enrolment. Safety assessments consisted with electrocardiographic and laboratory evaluations.ResultsA total of 763 participants with uncomplicated microscopically confirmedPlasmodiumspp. malaria were included. The proportion in ASAQ treated patients with creatinin abnormal value did not differ significantly between episode 1 and repeated malaria episodes (16.14% versus 13.98%, p=0.31). The proportion of patients with abnormal value of ALAT decreased significantly from baseline (25/234 versus 16/787, p< 0.01), but there is no difference in haemoglobin mean between the different episode (p>0.05) within each treatment arms. No evidence was found in the risk of QTc interval prolongation during repeated treatment in any arm.ConclusionsThe findings showed that safety was similar on first malaria treatment versus retreatment of subsequent episodes. The safety parameters were also comparable between the 3 treatment arms. These results support the repeated use of the three ACTs in uncomplicated malaria patients in Burkina Faso.
NEGLECTED INFECTIOUS DISEASES
Authors: Strub-Wourgaft Nathalie 
Published: February 2017

Achievement of the UN's Sustainable Development Goals (SDGs) will only be possible if the burden of neglected tropical diseases (NTDs) is significantly reduced. NTDs have an impact on population health, and are a drain on community resources, hindering economic development. The burden is particularly high in Africa, and urgent action is required on NTDs to enable the attainment of the SDGs.The World Health Organization has listed 17 NTDs that impact one billion people worldwide and produced overwhelming evidence to show that their impact may be effectively controlled and, in many cases, eliminated or eradicated. The WHO Strategic and Technical Advisory Group for NTDs and partners adopted a roadmap for control, elimination and eradication which set targets for 2012–2020.In its systematic assessment of the drug and vaccine landscape for neglected diseases up to 2011, DNDi found a persistent insufficiency in drug and vaccine development, and that new therapeutic products urgently need to be developed and delivered to improve control and potentially achieve elimination. It is significant that the second EDCTP programme includes neglected infectious diseases and more trial phases. DNDis focusses on the needs of neglected patients, and is developing treatments for sleeping sickness, leishmaniasis, Chagas disease, filariasis, HCV, paediatric HIV, and Mycetoma. In Africa there is an acute need for treatments for visceral leishmaniasis (VL), HIV-VL coinfection, post kalaazar dermal leishmaniasis, and cutaneous leishmaniasis. Mycetoma was recognized as an NTD by the WHA in 2016; this devastating disease affects remote populations; is poorly understood and lacks effective treatment. In Africa, 115 million people are at risk of onchocerciasis and 410 million people require preventive chemotherapy for lymphatic filariasis; mass administration programs are hampered by drugs that only kill the juvenile form of the worms, leaving only temporarily sterilized adults, requiring repeated administration over a period of decades.
PLASMODIUM FALCIPARUMMEROZOITE SURFACE PROTEIN-1 GENETIC DIVERSITY AND MULTIPLICITY OF INFECTION IN ISOLATES FROM CONGOLESE CHILDREN CONSULTING IN A PAEDIATRIC HOSPITAL IN BRAZZAVILLE
Authors: Gueye Nerly Gampio , Vouvoungui Christevy , Koukouikila-Koussounda Felix , Kobawila Simon , Ntoumi Francine 
Published: February 2017

BackgroundAs in many countries in sub-Saharan Africa, the burden of malaria has been reduced in the Republic of Congo as a result of massive deployment of insecticide-treated nets and availability of artemisinin combination therapies.However, limited data are available on the impact of these interventions on parasite populations. In this study, we investigated theP. falciparumgenetic diversity and multiplicity of infection in isolates from Congolese young patients and we compared the results to previous studies conducted before the introduction of ACTs.MethodsA total of 229 children were enrolled at the paediatric hospital located in Northern part of Brazzaville. Inclusion criterion was fever (T°>=37.5°C); then thick and thin blood smears were done to detect malaria parasites and determine parasite density as well as plasmodial species. In order to identify sub-microscopic infection,P. falciparum msp1gene was used as molecular marker. The genetic diversity and the multiplicity of infection (MOI) were determined.ResultsWe found 22 children with positive blood smear, therefore diagnosed with uncomplicated malaria (UM, 9.6%). Among the 216 microscopy-negative children, using msp1 marker, 57 were shown to harbour submicroscopic malaria infection (27,5%). In the age group 1–5 years, MOI was 1.4 and 2.4 in submicroscopic and UM children, respectively while in the age group >= 5 years, MOI was 1.7 and 3 in submicroscopic and UM children, respectively. The number ofmsp1alleles in isolates was 15 and 18 in SM and UM group, respectively. We observed that new alleles were detected only in isolates from UM children. Data are further analysed to investigate any association with age, living area, haemoglobin type carriage, and haemoglobin rate.ConclusionsThis study shows no change either inP. falciparumgenetic diversity or in MOI 10 years after the introduction of ACTs.