bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF ARTESUNATE MONOTHERAPY ONPLASMODIUM FALCIPARUMIN VIVO GENOMIC EXPRESSION
Authors: Kone Aminatou , Dara Antoine , Niangaly Amadou , Sinha Indranil , Brodin David , Fofana Bakary , Dama Souleymane , Dembele Demba , Sidibe Bakary , Diallo Nouhoum , Thera Mahamadou , Sagara Issaka , Wright Karin , Björkman Anders , Gil Jose , Doumbo Ogobara , Djimde Abdoulaye 
Published: February 2017

BackgroundArtemisinin-based combination therapies (ACTs) are the main treatment for malaria in endemic countries.Plasmodium falciparumresistance to artemisinins is described as delayed parasite clearance, which is associated with mutations on the parasite K13 propeller gene. Both the mechanisms of action and mechanisms of resistance to artemisinins are poorly understood. Transcriptomic studies can help in improving our understanding of these processes. Here we exploreP. falciparum in vivoRNA expression profile after a curative dose of artesunate monotherapy.MethodsDuring a prospective study of the efficacy of artesunate in monotherapy in children aged 1–10 years and presenting uncomplicatedP. falciparummalaria in Bougoula-Hameau, Mali, venous blood was collected on PAXgen blood RNA tubes before treatment (H0) and one (H1), two (H2) and three hours (H3) after treatment. RNA was extracted from these respective blood samples and used for microarray experiments withPlasmodium/AnophelesGeneChips and the Affymetrix® platform.ResultsA total of 23 samples from 6 patients were included in the final analysis after quality control using Affimetrix® and Qlucore® softwares. With a 2-groups comparison of H0/H after treatment, 236 genes were identified as differentially expressed. Overall 42 genes were up-regulated including a knob-associated histidine-rich protein, rifins (pf.12.409.0, pf.13_399.0), stevors (pf.3.184.0), RESA-like proteins with DNAJ domain and thioredoxins. Heat shock protein (Pf.5.258.0), a number of AP2 domain-containing genes (Pf.6.27.0, Pf.11.99.0), an ABC transporter (Pf.12.250.0), genes involved in cell cycle regulation and many exported protein genes with unknown function and membrane proteins genes were among the 194 down-regulated genes.ConclusionsOur data support a role for these genes in thein vivoresponse ofP. falciparumto artesunate administration.
THE QUEST FOR BUILDING LABORATORY CAPACITY TO SUPPORT CONTROLLED HUMAN MALARIA INFECTION (CHMI) STUDIES IN SUB-SAHARAN AFRICA: EXPERIENCE WITH FIVE SITES
Authors: Awuondo Kennedy , Njenga Daniel , Nyakarungu Elizabeth , Titus Pauline , Sutamihardja Awalludin , Lowe Brett , Ogutu Bernhards , Billingsley Peter 
Published: February 2017

BackgroundConducting Controlled Human Malaria Infection (CHMI) studies in sub-Saharan Africa presents unique challenges yet it provides enormous opportunities for fast-tracking malaria vaccine and drug development. Sanaria Inc. USA, has devised methods of producing, characterising and shipping aseptic, purified, cryopreservedPlasmodium falciparumsporozoites (PfSPZ). Unlike in the past, the sporozoites can be shipped to any field site including malaria-endemic countries in sub-Saharan Africa. CHMI studies need cutting-edge laboratory capacity to allow screening of potential study participants for their eligibility, perform safety tests, efficacy testing of the investigation product, and determine immune markers, responses and parasite kinetics.MethodsThe sites were identified within sub-Saharan Africa, based on local population, malaria epidemiology status and clinical research capacity. The laboratory assays, equipment and consumables were identified. The methods and procedures were optimised, standardised and documented. The laboratory technical team were selected and trained. EDCTP provided financial support whilst Sanaria Inc. provided technical support.ResultsThe capacity strengthening successfully supported CHMI studies in five sites in Africa namely; IHI, Bagamoyo, Tanzania; KEMRI CRC, Nairobi, Kenya; EGMVI, Malabo Equatorial Guinea; CERMEL, Lambarane, Gabon; KEMRI-CDC, Siaya-Kenya and KEMRI-WT, Kilifi Kenya. Capacity strengthening was aimed at clinical and immunology laboratory systems required for CHMI studies.ConclusionsAs more CHMI studies are anticipated, vigorous capacity strengthening will be required for laboratory facilities in Africa to accelerate the evaluation of malaria vaccines, anti-malaria drugs, diagnostic assays and assessment of host immune response to malaria infection.
EFFICACY AND TOLERABILITY OF REPEATED ADMINISTRATION OF ACTS OVER A PERIOD OF TWO YEARS IN CHILDREN AND ADULT PATIENTS WITH ACUTE UNCOMPLICATED MALARIA IN BURKINA FASO
Authors: Soulama Issiaka , Kaboré Moïse , Coulibaly Aboubacar , Ouattara Maurice , Sanon Souleymane , Diarra Amidou , Bougouma Edith , Ouedraogo Alphonse , Sombie Benjamin , Ouedraogo Amidou , Kargougou Désiré , Ouattara Daouda , Issa Nebie , Tiono Alfred , Sirima Sodiomon 
Published: February 2017

BackgroundAccording to the guidelines of the Burkina Faso National Malaria Control Programme, artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first-line drugs for uncomplicated malaria treatments. However, in some contexts where individuals will experience more than 1 episode of clinical malaria per year, it is unknown to what extent giving any of these ACTs repeatedly is safe. In the framework of the activities of the West African Network for Antimalarial Drugs (WANECAM) network, we have compared the efficacy and tolerability of repeated use of dihydroartemisinin-piperaquine (DHA-PQ) or artesunate-pyronaridine (PYR) with artesunate-amodiaquine (ASAQ).MethodsA randomised open-label parallel 3 arms trial was conducted to compare the efficacy of a three-day regimen of DHA-PQ and PYR with ASAQ. The trial involved children and adults with uncomplicated falciparum malaria. Participants were randomly assigned to one of the three treatment arms at the first clinical episode. During the subsequent clinical episodes, the same drug was administered. Follow-up duration was 42 days for each episode. Study duration was two years for each participant. Primary endpoints were the incidence rate of uncomplicated malaria over a period of 2 years and PCR corrected/uncorrected ACPR at day 28 and day 42. Safety parameters were also assessed.ResultsOf the 763 patients enrolled, the incidence rate of clinical malaria was 1.4, 1.2, and 1.5 episodes / person-year at risk in the ASAQ, DHA-PQ and PYRAMAX arms, respectively. The PCR-uncorrected efficacy at day 28 versus day 42 was: ASAQ 93.4%vs79.5%; PYR 98.1%vs74.8%; and DHA-PQ 99.5%vs95.2%. Bronchitis, rhinitis, abdominal pain, cough, QTc prolongation, headache, and vomiting were registered as the main adverse events in each of the three groups.ConclusionsThe findings from our study support the current recommendations for using artemisinin-based combinations in the treatment of uncomplicated malaria in areas of high malaria transmission such as Burkina Faso.
COMPARISON OF AUTOMATIC AND MANUAL MEASUREMENT OF QT AND QTC INTERVALS DURING A CLINICAL PHASE III-B/ IV IN KOLLE, MALI
Authors: Dao François , Dara Nianwalou , Sidibe Bouran , Coulibaly Moctar , Tolo Allaye , Maiga Hamma , Ouologuem Nouhoum , Niangaly Hamidou , Sagara Issaka , Djimde Abdoulaye 
Published: February 2017

BackgroundThe detailed assessment of the QT and corrected QT (QTc) intervals prolongation is recommended when testing new drugs. The electrocardiograph automatically displays generally reliable values of the QT interval and corrected QT but morphological variations of the T wave may cause reading errors, hence the use of the manual measurement as an alternative method. Our objective was to evaluate the correlation between the automatic and manual measurement of QT values.MethodsIn Kolle from March 2012 to December 2015, an open randomised, phase III-b/IV study comparing dihydroartemisinine-piperaquine, pyronaridine-artesunate and artemether-lumefantrine was conducted. An electrocardiograph cartridge 12 electrodes coupled to a computer with the Tele Touch software was used for the electrocardiogram on Day 0 before the study drugs administration and on Day 2, 2–4 hours after the administration of the last dose of the antimalarial. The manual measurement of QT and QTc was made using the Bazett method [QTcB_m=(Number leaded×0.04×QTcF) / QTcB]. For prolonged QTc cases on Day 2, another measurement was done during the next scheduled visit (Days 7, 14, 21, 28, 35 and 42) until the QTc normalisation.ResultsA total of 764 ECG was recorded with 398 participants. Different automatic and manual values of QT and QTc are scattered around different medium. Comparisons of different values of QT (p=0.1245) and QTc (p<0.001) showed a statistically significant differences and the concordance between automatic and manual tests was QT: Rho_c=0.77 and QTc: Rho_c=0.46.ConclusionsOur results indicate no perfect match between automatic and manual methods for QT and QTc. Manual reading remains important to correct any machine errors during clinical studies.
SEASONAL MALARIA CHEMOPREVENTION WITH SULPHADOXINE-PYRIMETHAMINE AND AMODIAQUINE SELECTS DHFR-DHPS QUINTUPLE MUTANT GENOTYPE IN MALI
Authors: Maiga Hamma , Lasry Estrella , Diarra Modibo , Sagara Issaka , Bamadio Amadou , Traore Aliou , Coumare Samba , Soma Bahonan , Dicko Yeyia , Diallo Nouhoum , Sangare Boubou , Tembely Aly , Traore Djibril , Niangaly Hamidou , Dao François , Haidara Aboubecrin , Dicko Alassane , Doumbo Ogobara , Djimde Abdoulaye 
Published: February 2017

BackgroundSeasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP)+amodiaquine (AQ) is being scaled up in countries of the Sahel in West Africa. However, the potential development ofPlasmodium falciparumresistance to the respective component drugs is a major concern.MethodsTwo cross-sectional surveys were conducted before (August 2012) and after (June 2014) a pilot implementation of SMC in Koutiala, Mali. Children aged 3–59 months received 7 rounds of curative doses of SP+AQ over two malaria seasons. Genotypes ofP. falciparumdhfr codons 51, 59 and 108; dhps codons 437 and 540, pfcrt codon 76 and pfmdr1codon 86 were analysed by PCR on DNA from samples collected before and after SMC, and in non-SMC controls.ResultsIn the SMC population 191/662 (28.9%) and 85/670 (13.7%) of children wereP. falciparum-positive by microscopy and were included in the molecular analysis before (2012) and after SMC implementation (2014), respectively. In the control population 220/310 (71%) were successfully PCR analysed. In the SMC children the prevalence of all molecular markers of SP resistance increased significantly after SMC including the dhfr-dhps quintuple mutant genotype, which was 1.6% before but 7.1% after SMC (p=0.02). The prevalence of Pfmdr1–86Y significantly decreased from 26.7% to 15.3% (p=0.04) while no significant change was seen for pfcrt K76T. In 2014, prevalence of all molecular markers of SP resistance were significantly higher among SMC children compared to the non-SMC control population (p<0.01). No dhfr – 164 mutation was found neither at baseline nor post SMC.ConclusionsSMC increased the prevalence of molecular markers ofP. falciparumresistance to SP in the treated children. However, there was no significant flow of these resistance genes into the general parasite population after 2 years and 7 rounds of SMC.
IMPACT OF TREATMENT OF UNCOMPLICATED MALARIA BY AMODIAQUINE−ARTESUNATE (AS-AQ) ON PFCRT 76T AND PFMDR1 86Y MUTATIONS SELECTION INPLASMODIUM FALCIPARUMISOLATES, REPUBLIC OF GUINEA
Authors: Diawara Elisabeth , Beavogui Abdoul , Camara Daouda , Sylla Malick , Yattara Mohamed , Sow Amadou , Camara Gnèpou Camara , Diallo Saliou , Doumbo Ogobara , Djimde Abdoulaye 
Published: February 2017

BackgroundThe use of Amodiaquine monotherapy is associated with the selection of resistance markers (PfcrtandPfmdr1). The decrease in sensitivity and the emergence ofPlasmodium falciparum-resistant strains have been reported.It is therefore important to know the impact of treatment of uncomplicated malaria with amodiaquine−artesunate (AQ−AS) onPfcrt76T andPfmdr1 86Y mutations strains ofP. falciparum.MethodsWe applied the standard protocol of 28 days of WHO 2003, to determine thein vivoefficacy of the combination AQ−AS. In total 170 subjects were included in the study. Molecular analysis focused on 168 dried blood spots. The aims were to determine the frequency ofPfcrt76T andPfmdr1 86Y mutations, to determine the rates of reinfection using polymorphism markers MSP1, MSP2, and microsatellite CA1, Ta87, TA99. Nested PCR followed in some cases by a restriction enzyme.ResultsThe level ofP. falciparumclinical response was 92.85% (156/168) of ACPR before molecular correction and 7% (12/170) LPF. The ACPR after molecular was 97.01% (163/168). The frequency of mutation pointPfcrt76T was 76.19% (128/168) before treatment and 100% (7/7) after treatment, p=0.14. ForPfmdr1 mutation the frequency was 27.97% (47/168) before treatment and 60% (6/10) after treatment, p=0.03. Rate ofPfcrt76T +Pmdr1 86Y was 22.02% (37/168) before and 50% (6/12) after treatment p=0.003.ConclusionsDespite the combination of AQ with AS, the treatment selectedPfcrt76T andPfmdr1 86Y mutations in Guinea.
TO VALUE THE EFFICIENCY OF PYRONARIDINE-ARTESUNATE AND ARTEMETHER-LUMEFANTRINE IN THE TREATMENT OF UNCOMPLICATED MALARIA OFPLASMODIUMSPP. IN BURKINA FASO
Authors: Barry Nouhoun , Kaboré Naomie , Kabré Zachari , Fofana Aminata , Nikèma Fréderic , Compaoré Daniel , Somé Fabrice , Zongo Issaka , Djimdé Abdoulaye , Ouédraogo Jean 
Published: February 2017

BackgroundNo safe and highly effective malaria vaccine is available today. The treatment drugs currently in use remain insufficient. Moreover, resistance to these drugs makes malaria control difficult. The development of new therapeutic drugs is required. This abstract is part of a survey from the WANECAM study entitled ‘Randomised trial to assess the effect of repeated treatment of pyronaridine-artesunate (PA), dihydroartemisinin-piperaquine (DHA-PQ) and artemether-lumefantrine (AL) in patients presenting uncomplicated malaria in Bobo-Dioulasso, Burkina Faso’. We present here the analysis of the first episodes on the therapeutic efficiency of PA compared to AL, which is the first-line antimarial used in Burkina Faso.MethodsA total of 448 subjects were randomised to receive treatment (224 subjects in each arm). Malaria diagnosis was assessed by microscopy. Subjects were follow-up during 42 days. Treatment response was measured according to standard of care as per WHO guidelines of 2003. The correction of the cases of treatment failure by molecular biology techniques is under analysis.ResultsOn Day 28, the therapeutic failures were 3.35% in the PA group as against 18,10% for the AL group. On Day 42, a significant increase of the treatment failures in every group is observed with a higher rate in the AL group (31.43%), against 17.22% in the PA group.ConclusionsThis survey shows that less cases of treatment failure occurred in the patients' group treated with PA compared to the group treated with AL. These findings contributed to evidence base for a change in malaria treatment policy guidelines for uncomplicated malaria in Burkina Faso.
ADVERSE EVENT (AE) REPORTING FROM MALARIA MASS DRUG ADMINISTRATION (MDA) ROUNDS CONDUCTED IN SOUTHERN ZAMBIA
Authors: Chalwe Victor , Miller John 
Published: February 2017

BackgroundThe National Malaria Control Centre (NMCC) of the Ministry of Health in Zambia is conducting a large-scale mass drug administration (MDA) community randomised-controlled trial to evaluate the effectiveness of different MDA distribution strategies on reducing malaria parasitaemia. The trial involved two MDA strategies: MDA, where all eligible individuals were treated with dihydroartemisinin and piperaquine (DHAp), and focal MDA (fMDA), where all eligible individuals residing in a household with at least one positive member (rapid diagnostic test) were treated with DHAp. This provides an opportunity to document the extent to which potential safety issues are reported or adverse events occur given the level of exposure to treatments.MethodsField teams comprised of community health workers, enumerators and adherence monitors, and supervised by facility-based staff, received standardised training on the treatment campaign procedures, use of DHAp for eligible participants, adverse event monitoring, grading of events, and emergency and event handling procedures by grade. Adverse events were recorded on standard forms and in line with the national pharmacovigilance network recommendations. The principle aim of this data collection activity was to document and follow up on all adverse events (AEs) and serious adverse events (SAEs) occurring during the course of the MDA trial for individuals taking DHAp.ResultsFour rounds of MDA were conducted over 2 years. During the first two intervention rounds, 280,638 participants were tested, 159,696 were treated with dihydroartemisinin-piperaquine (DHAp) in 40 health catchment areas. During the second two intervention rounds, 261,814 participants took part. A total of 687 AEs (0.13% of participants and 0.24% of treatments) were reported; four were recorded as serious adverse events (SAEs). The most common AE reported were gastrointestinal disturbances (diarrhoea, abdominal pain and nausea) 31.20%; dizziness 19.8%; vomiting 17.35%; headache 16.03%; and general body weakness at 11.37%.ConclusionsDuring this large MDA trial, the use of DHAp for malaria treatment was generally safe and well tolerated.
TIME TO SECOND AND THIRD EPISODES OF MALARIA OF DIHYDROARTEMISININ−PIPERAQUINEVSARTESUNATE−AMODIAQUINE AND ARTESUNATE−PYRONARIDINEVSARTEMETER−LUMEFANTRINE IN BOUGOULA HAMEAU, MALI
Authors: Fofana Bakary , Djimde Abdoulaye , Diakité Hamadoun , Sagara Issaka , Doumbo Ogobara , Toure Sekou , Sanogo Kassim 
Published: February 2017

BackgroundCurrently, five artemisinin combination therapies (ACTs) are recommended by WHO for treatment of uncomplicated malaria in Africa. While artemisinin derivatives have a short half-life, the partner drugs give rise to differing durations of post-treatment prophylaxis. The pharmacokinetic and pharmacodynamic properties of drug regimens have implications for the public health benefit of the drugs. The development of new antimalarials is ongoing. The objective of this work is to evaluate the prophylactic effect of artesunate−pyronaridine (Pyramax) and dihydroartemisinin−piperaquine (Eurartesim)vsartemether−lumefantrine (AR_L) and artesunate-amodiaquine (ASAQ), respectively in Bougoula Hameau.MethodsThrough the phase IIIb/IV clinical trial of the West African Network of clinical trial of antimalarial drugs (WANECAM) in Bougoula hameau (Mali) from January 2012 to December 2013, we evaluated the median time of occurrence for the second and third episodes of malaria on patients aged from 6 months to above. After the first randomisation, any other subsequent episodes of malaria as treated by the same ACT initially taken. Treatment failure before day 28 was treated by quinine.ResultsWhilst 448 patients were randomised to receive DHA (224)vsASAQ (224), 428 received PA (214)vsAR_L (214). The median time to second and third episodes of malaria were 116 days and 60.5 with PA versus 82.5 and 56.0 for AR_L, respectively. Otherwise, we found 118 and 98vs82.5 and 60 days as median time to second and third episode for DHA-PQPvsAS/AQ, respectively. DHA-PQP highly prolonged the median time to second and third episode as compared to ASAQ (p=0.003 and p<0.001, respectively).ConclusionsThe ACTs artesunate−pyronaridine and dihydroartemisinine−piperaquine significantly prolonged the median time to second and third episode of malaria as compared to artemether-lumefantrine and artesunate−amodiaquine, respectively.
THE IMPACT PROJECT: IMPROVING THE IMPACT OF EXISTING MALARIA PRODUCTS – ACTS
Authors: Barnes Karen , Guérin Philippe , Hodel Eva Maria , Humphreys Georgina , Pace Cheryl , Banda C.G , Denti Paulo , Allen Elizabeth , Lalloo David , Mwapasa Victor , Terlouw Anja 
Published: February 2017

BackgroundThe antimalarial dihydroartemisinin-piperaquine (DHA-PPQ) is one of the recommended drugs to treat uncomplicatedPlasmodium falciparummalaria. However, DHA-PPQ has a relatively narrow, poorly defined therapeutic dose range and it is unclear whether PPQ concentration-dependent cardio-toxicity (QTc prolongation) poses a clinical risk for specific subgroups. Uncertainty about the exact safe upper PPQ concentration threshold and recognition of the vulnerability of children has led WHO to consider a complex weight-based dosing regimen. These complex dosing schemes may challenge DHA-PPQ introduction into national control programmes. It also highlights the urgent need to standardise the dose optimisation process.MethodsThe IMPACT project aims to determine the frequency and severity of DHA-PPQ cardio-toxicity, and its correlation with dose and drug concentration through WWARN-pooled patient-level pharmacokinetic-pharmaco-dynamic safety analysis, and antiretroviral drug interactions using all available data. Using the established WWARN platform, an open study group has been established to allow data sharing and joint analyses by data contributors and other key stakeholders.ResultsWe will present a progress update of the IMPACT project and associated WWARN DHA-PPQ safety group. Findings will inform an up-to-date safety profile and upper PPQ dose thresholds across key risk groups and identify remaining research priorities. DHA-PPQ dosing challenges, lessons learnt, and opportunities to address these through a more standardised process for antimalarial dose optimisation will be reviewed, and awareness of dose optimisation research priorities will be raised among researchers, funders and control programmes.ConclusionsThis work will help inform policy decisions on DHA-PPQ dosing regimens and help demonstrate the importance of identifying global research priorities for targeted antimalarial safety studies and of integrating pooled individual level safety analyses into WWARN's global efficacy data platform, as a powerful standardised process for dose optimisation.
PLASMODIUM FALCIPARUMINFECTION IN FEBRILE CONGOLESE CHILDREN: PREVALENCE OF CLINICAL MALARIA TEN YEARS AFTER INTRODUCTION OF ARTEMISININ-COMBINATION THERAPIES
Authors: Etoka-Beka Mandingha Kosso , Ntoumi Francine , Kombo Michael , Deibert Julia , Poulain Pierre , Vouvoungui Christevy , Kobawila Simon , Koukouikila-Koussounda Félix 
Published: February 2017

BackgroundThe detailed assessment of the QT and corrected QT interval prolongation is recommended when testing new drugs. Generally the electrocardiograph automatically displays reliable values of the QT interval and corrected QT but morphological variations of the T wave may cause reading errors; hence the use of manual measurement as an alternative method. Our objective was to evaluate the correlation between the automatic and manual measurement of QT values.MethodsIn Kolle from March 2012 to December 2015, an open randomised, phase III-b/IV study comparing dihydroartemisinine-piperaquine and pyronaridine-artesunate artemether-lumefantrine was conducted. An electrocardiograph cartridge with 12 electrodes coupled to a computer with the Tele Touch software was used for the electrocardiogram on Day 0 before the study drugs administration and on Day 2, two to four hours after the administration of the last dose of the antimalarial. The manual measurement of QT and QTc was made using the Bazett method [QTcB_m=(Number leaded×0.04×QTcF) / QTcB]. For prolonged QTc cases on Day 2, another measurement was done during the next scheduled visit (day 7, 14, 21, 28, 35 and 42) until the QTc normalised.ResultsA total of 764 ECG were recorded with 398 participants. Different automatic and manual values of QT and QTc are scattered around different medium. Comparisons of different values of QT: p=0.1245 and QTc: p< 0.001 showed statistically significant differences and the concordance between automatic and manual tests was (QT: Rho_c=0.77 and QTc: Rho_c=0.46).ConclusionsOur results indicate no perfect match between automatic and manual methods for QT and QTc. Manual reading remains important to correct any machine errors during clinical studies.