bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Background

Plasmodium 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.

Methods

Dried 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.

Results

No 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.

Conclusions

This 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.
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

Background

Artemisinin-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.

Methods

During 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.

Results

A 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.

Conclusions

Our 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

Background

Conducting 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.

Methods

The 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.

Results

The 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.

Conclusions

As 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

Background

According 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).

Methods

A 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.

Results

Of 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.

Conclusions

The 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

Background

The 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.

Methods

In 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.

Results

A 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.

Conclusions

Our 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

Background

Seasonal 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.

Methods

Two 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.

Results

In 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.

Conclusions

SMC 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

Background

The 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.

Methods

We 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.

Results

The 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.

Conclusions

Despite 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

Background

No 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.

Methods

A 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.

Results

On 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.

Conclusions

This 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

Background

The 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.

Methods

Field 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.

Results

Four 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%.

Conclusions

During 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

Background

Currently, 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.

Methods

Through 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.

Results

Whilst 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).

Conclusions

The 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

Background

The 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.

Methods

The 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.

Results

We 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.

Conclusions

This 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

Background

The 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.

Methods

In 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.

Results

A 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).

Conclusions

Our 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 ABUNDANCE AND SPOROZOITE RATES IN MALARIA VECTORS IN NCHELENGE INCLUDING ISLANDS OF LAKE MWERU AN AREA WITH A HIGH BURDEN OF MALARIA IN NORTHERN ZAMBIA
Authors: Muleba Mbanga , Stevenson Jennifer , Mbata Keith , Mulenga Modest , Coetzee Maureen , Norris Douglas
Published: February 2017

Background

Nchelenge district is a holoendemic malaria transmission zone in northern Zambia. The district occurs in a region characterised by a mix of water, marshes, islands and lagoons presenting a uniquely suitable ecology for mosquitoes. Annual indoor residual spraying (IRS) campaigns are carried out between September and December synchronised with other regions in the country with different environmental conditions. Targeted vector control interventions have been applied since 2008 without appreciable impact on disease burden. The timing and targeting of vector control measures are not guided by an informed entomological baseline. This study was aimed at providing entomological information on the seasonal abundance, spatial distribution andPlasmodium falciparumsporozoite infections in the local malaria vector species in order to guide implementation of vector control in the district.

Methods

Entomological studies were conducted intermittently spanning the rainy, cold-dry, and hot-dry seasons from 2015–2016. Mosquitoes were collected by CDC light traps, identified to species both morphologically and by PCR techniques. Circumsporozoite ELISA assay was used to detectP. falciparumin mosquito salivary glands.

Results

A total of 5437 femaleAnopheles funestusandAn. gambiaeand over 6000 culicines, mostlyMansoniamosquitoes were collected. The peak number of theAn. funestusfrom all sites occurred in July. OverallP. falciparuminfection rates inAn. funestuswere Kilwa island 2.7% (4/146), Mainland 2.5% (3/122), Chisenga island 0.4% (1/220), Isokwe 5.9% (2/34) and inAn. leesonifrom Kilwa 33% (1/3). The highest number ofAn. gambiaewas collected from Kilwa and none was found infected withP. falciparumregardless of collection site.

Conclusions

The annual IRS conducted between September and December may be ineffective in controlling malaria as this misses the vector peak abundance and peak transmission season. Two rounds of IRS covering more areas would be needed to control the two vector species with different population peak seasons and malaria transmission.
WEIGHT STATUS ROLE ON ANTIMALARIAL DRUG EFFICACY AND SAFETY IN SUBURBAN CHILD POPULATION IN MALI
Authors: Djimde Moussa , Vaillant Michel , Samouda Hanen , Sagara Issaka , Djimde Abdoulaye , Doumbo Ogobara
Published: February 2017

Background

Malnutrition andPlasmodium falciparummalaria are two major public health problems in sub-Saharan Africa. In this study, we described as our primary outcome the proportion of presence ofP. falciparumduring follow-up and explore the relationships between malaria drug safety and nutritional inadequacies.

Methods

This was a secondary analysis of anin vivoprospective randomised control trial conducted in Bougoula-Hameau, Mali. Our analysis concerned 749 children followed during 28 days. We determined the BMI status of each child according to the cut-offs defined by WHO in 2007. R-software was used for statistical analysis.

Results

The median of parasite density was higher in thin and severely thin children (17800). The median of haemoglobin levels at enrolment was lower in children who were thin and severely thin (9.85) compared to the children with normal weight, overweight and obesity. At 21 days, there was no parasite in thin and severely thin children. At the same point of follow-up, 7.5% of children with normal weight had parasites versus 8.4% of overweight and obese children. Between the three groups the difference was significant (p=0.03). On day 7 the highest ASAT level was observed in children with normal weight (p=0.03). We didn't observed differences between weight status groups regarding the level of creatinine. The p-value was respectively 0.99, 0.41 and 0.07 at enrolment, day 7 and day 14.

Conclusions

This study showed that children with BMI deficiency had a higher parasite density and lowest haemoglobin level at enrolment. However, we did not observe a relationship between weight deficiency and the safety of antimalarial drugs used in our study.
IMMUNOGENICITY OF MALARIA-VECTORED VACCINES IS NOT AFFECTED BY CO-ADMINISTRATION WITH ROUTINE EPI VACCINES IN A RANDOMISED CONTROLLED TRIAL IN GAMBIAN INFANTS AND NEONATES
Authors: Afolabi Muhammed , Mensah Victorine , Roetynck Sophie , Kanteh Ebrima , Bowyer Georgina , Ndaw Amy , Oko Francis , Bliss Carly , Jagne Ya Jankey , Cortese Riccardo , Nicosia Alfredo , Roberts Rachel , D'Alessio Flavia , Leroy Odile , Faye Babacar , Kampmann Beate , Cisse Badara , Bojang Kalifa , Gerry Stephen , Viebig Nicola , Lawrie Alison , Clarke Ed , Ewer Katie , Imoukhuede Egeruan , Hill Adrian
Published: February 2017

Background

Recent global estimates show thatP. falciparummalaria still constitutes an enormous public health concern. Chief amongst desirable interventions is an effective vaccine that could complement existing control measures. Heterologous prime-boost vaccinations involving chimpanzee adenovirus 63 (ChAd63) and modified vaccinia Ankara (MVA) encoding ME-TRAP have consistently shown acceptable safety, excellent immunogenicity and substantial efficacy in African adult and paediatric populations. When licensed, malaria vaccines would preferably be given to infants receiving routine childhood immunisations. Nevertheless, no studies have evaluated the interference of ChAd63/MVA ME-TRAP when co-administered with routine Expanded Programme Immunisation (EPI) vaccines.

Methods

We enrolled 65 Gambian infants and neonates in an age de-escalating fashion, priming at 4 months, 8 weeks or 1 week of age, and randomised them to vaccine or control (EPI vaccines only) arm. Safety was assessed by the description of vaccine-related adverse events ascertained through clinical assessments, biochemical and haematological tests. Immunogenicity was evaluated by IgG ELISA, interferon-gamma ELISPOT, intra-cellular cytokine staining and flow cytometry. Antibody testing was performed to assess any interference of the EPI vaccines with responses to ChAd63/MVA ME-TRAP.

Results

Overall, the vaccination regimes were well tolerated in all age groups with no vaccine-related serious adverse events. High level IgG and antigen-specific T cell responses were generated after boosting with MVA, with T cell responses highest in the infants 8 week old at priming dose. EPI vaccines retained unchanged antibody levels in all age groups.

Conclusions

Potent humoral and cellular immunity induced by heterologous prime-boost immunisation with ChAd63 and MVA ME-TRAP did not interfere with the immunogenicity of co-administered routine EPI vaccines in infants and neonates. Potent T cell induction was again observed with the vectored malaria vaccines despite co-administration with EPI vaccines.
A MALARIA VACCINE SITE CHARACTERISATION: PREVALENCE AND SPECIES DISTRIBUTION OFPLASMODIUMMALARIA IN A MALARIA ENDEMIC SETTING OF BURKINA FASO (WEST AFRICA)
Authors: Diarra Amidou , Nebie Issa , Tiono Alfred B , Sanou Guillaume , Ouedraogo Alphonse , Konate Amadou T , Yaro Baptiste J , Soulama Issiaka , Sodiomon Sirima
Published: February 2017

Background

Any development of a vaccine strategy or its implementation is based on a good knowledge of the biology of the pathogen and its temporal and spatial distribution. In the case of malaria, the main four species responsible for the disease though having a similar biological structure are not equally represented spatially due to factors such as environment and susceptibility of human to species.

Methods

In order to characterise a site for a future malaria vaccine implementation in terms of malaria prevalence and its species distribution, two cross sectional studies were conducted in October and March corresponding to the high and low malaria transmission season, respectively, in the Banfora Health District. A total of 1203 volunteers aged from 0.5 to 45 years consented to participate in the study. During each survey, after a brief physical examination, blood was taken from each volunteer by finger prick to perform thick and thin blood film examination. Blood smears collected were air dry and the thin film fixed with methanol. Dry smears were then stained with controlled PH Giemsa buffer solution and checked for malaria parasite using light microscope.

Results

Malaria prevalence was markedly high during high malaria transmission: 54.26% compared to low malaria transmission season 39, 40%.Plasmodiumindex was 46.8% with a gametocyte index of 11%. Main species present in the study area wereP. falciparum,P. malariae and P. ovale. Species distribution was almost the same across the two seasons with P.falciparumbeing more prevalent compared to other species with respectively 97.8% and 98.7%.

Conclusions

P. falciparum,P. malariaeandP. ovaleare the three main species in the study area with almost the same distribution across the two seasons.
CORRELATION OF HIV-1 P24 ASSAY WITH CD4 T-CELL COUNT, HIV, HBV AND HCV CO-INFECTIONS AND ITS IMPLICATION FOR ART MONITORING IN VASTLY HIV-INFECTED POPULATION OF NIGERIA
Authors: Okonko Iheanyi , Okerentugba Phillip , Opaleye Oluyinka , Awujo Ezinwanne , Frank-Peterside Nnenna
Published: February 2017

Background

Reports indicate that extensive genetic diversity of HIV-1 impacts almost every aspect of HIV-1 epidemiology, including laboratory detection, ART/resistance, monitoring of ART and vaccine development. Therefore, in order to support the scale-up of access to HAART to mitigate the HIV-1 scourge, prompt, accurate and cost-effective diagnosis and monitoring of ART is crucial in Nigeria (a resource-limited country).

Methods

Plasma of 200 confirmed HIV-1 patients on a specified and uniform ART regimen was monitored with P24 antigen assay and CD4 T-cell count as virologic and immunologic assessments of response to ART. The results of the assays (P24 and CD4 count) were compared to assess sensitivity, turn-around time and financial advantages of P24 over the CD4 count. Serological analysis of HBV and HCV were performed according to the manufacturer's instructions. Enumeration of CD4+ levels was done with a Partec flow cytometer.

Results

Of these patients, 77.5% had HIV only, 14.5% had HIV−HBV and 11.5% had HIV-HCV. Evaluation of levels of P24 antigen revealed that lower limits for P24 antigen 0.577–2.308 were detected in the subjects with CD4 cell count >500. However, higher limits for P24 antigen 2.308–2.885 were detected in subjects with CD4 cell count within the range of 200–499. Correlation analysis showed an inverse relationship between CD4 count and level of P24 antigen (CD4 count of 200–499 cells/µl versus 2.308–2.885 of P24, r=–0.319, CD4 count≥500 cells/µl versus 0.577–2.307 of P24, r=–0.088).

Conclusions

This study suggests that p24 could serve as one of such diagnostic and monitoring facilities that could be used in a resource-limited area like Nigeria. This will in turn lead to selection of more specific ARV options that best suppress viraemia during initiation of ART, as well as for monitoring HIV-1 patients in Nigeria, knowing that the virus subtype impacts effectiveness of ART.
A RAPID SEROLOGICAL TRIAGE TEST FOR DETECTING ACTIVE TUBERCULOSIS
Authors: Borain Nick , Petersen Lizette , Plessis Julianne Du , Theron Grant , Holm-Hansen Carol
Published: February 2017

Background

A rapid screening test for active tuberculosis (TB) will reduce diagnostic delay and expedite referral for confirmatory testing and treatment. Antigen detection tests, which may utilise a rapid lateral flow (LF) platform suited to point-of-care use, offer a promising alternative to conventional methods for TB diagnosis. To date, the lack of accurate biomarkers has precluded the development of a serological assay.

Methods

Sera and saliva were obtained by our consortium partners from culture-positive TB cases and healthy asymptomatic controls in high-burden settings.Mycobacterium tuberculosis(Mtb) antigens with diagnostic potential were expressed in eukaryotic and prokaryotic systems, and antigen combinations evaluated for sensitivity/specificity on multiplex, ELISA and LF platforms.

Results

Based on a comparison of proteins recognised by antibodies from patients and controls, we have identified a combination of secreted and membrane-associated antigens involved in cell wall/cell processes and lipid metabolism that differentiate between active disease and latent infection. Sensitivities of 84–94% among TB cases and specificities of 97–100% among healthy endemic controls were obtained by screening over 300 samples against combinations of eukaryotic-expressed antigens on different platforms. Results indicating active TB were also observed among samples from symptomatic smear/culture-negative TB suspects. Antibody reactivity was not Mtb strain-specific. Sera from Norwegian latent TB controls yielded negative results. Our LF assay detects TB in the context of HIV co-infection, and is currently being optimised using sera from well-characterised TB suspects in Cape Town.

Conclusions

Screening our sample sets against a selected combination of Mtb antigens by multiplex and LF prototype assays yielded sensitivities and specificities superior to that obtained by sputum smear microscopy. Our LF prototype conforms to the WHO target product profile criteria for a community-based triage test. Modification of the lateral flow platform for finger-stick blood and/or saliva samples will further increase assay suitability for use at the health post level.
EMERGENCE OF NONTUBERCULOUS MYCOBACTERIUM PULMONARY INFECTIONS, ANALYSIS OF ISOLATES FROM PREVIOUSLY TREATED TB CASES
Authors: Kudzawu Samuel , Atiadeve Samuel , Hilmann Doris
Published: February 2017

Background

The main objective of this study was to characterise supposed non-tuberculous mycobacteria (NTM) found in previously treated tuberculosis (TB) cases to inform policy on inclusion of NTM diagnosis and management as a differential in TB care. In addition, the objective was to test the sensitivity or otherwise of the identification algorithm used in Ghana to declare an isolate an NTM.

Methods

Thirty-one supposed NTM isolates from previously treated TB patients were collected. The NTM identification was based on culture positivity by BD MGIT 960TM, smear positivity for acid fast bacilli and finally by BD MGIT TB-cIDTM test kit. DNA was extracted using the Hain Lifescience GMBH GenolyseTM kit. The specimens were further subjected to sequencing.

Results

Five (16%) of the previously treated cases wereMycobacterium tuberculosis complex (MTBC);two (6.5%) wereM. abscesus/cholenae;1 case (3.2%) forM. fortuitumandM. gordonaeeach. One (3.2%) was an unknown mycobacterium and 4 (12.9%) were other bacteria. Streptomyces and Brevibacteria were 8 (25.8%) and 6 (19.4%), respectively. There were three incidences of mixture with other bacteria; 2 MTBCs (6.5%) and 1 NTM (3.2%).

Conclusions

There is some evidence to suggest the prevalence of NTM colonisation and disease in previously treated TB patients. There is the possibility of some smear positive new cases being NTM lung diseases but may be put on TB treatment. Emphasis on differentiation of AFB positive smears before treatment especially for retreatment cases must be made. The rapid deployment of new molecular methods has the potential of bridging the gap. There is the need for a definite diagnostic algorithm that can detect both NTMs and MTBCs. Further studies are encouraged to determinate whether the other organisms identified are relevant possible pathogens or contaminants.
VITAMIN D FOR TREATMENT AND PREVENTION OF TB-HIV
Authors: Coussens Anna , Naude Celeste , Chaplin George , Noursadeghi Mahdad , Martineau Adrian , Jablonski Nina , Wilkinson Robert
Published: February 2017

Background

Susceptibility to reactivate tuberculosis infection is influenced by immunosuppression. Amongst the greatest risk factors for active TB are HIV-1 infection and vitamin D deficiency. These risks factors are not mutually exclusive and may exacerbate each other. However, the phenotype of immunodeficiency induced by each is different. Vitamin D deficiency not only associates with TB risks, but it is greater in HIV-co-infected patients. The effects of vitamin D on the immune system are pleiotropic, being both anti-inflammatory and antimicrobial. Evidence suggests that vitamin D may not only reduce risk of TB by increasing anti-mycobacterial immunity and reducing inflammation, but it may also reduce HIV replication and the associated effects on innate and adaptive immunity; thus concomitantly reducing the associated risk of HIV on TB.

Methods

We investigatedin vitroandex vivothe effect of vitamin D supplementation on the response of monocyte-derived macrophages (MDM) and peripheral blood mononuclear cells (PBMC), respectively, to HIV-M. tuberculosis(Mtb)co-infection. The effects of pathogen growth and susceptibility to infection were correlated to cytokine, chemokine and antimicrobial peptide production, by expression, secretion and flow cytometry analysis.

Results

MDM differentiated in the presence of vitamin D metabolites, significantly restricted HIV-1 replication, alone and during co-infection withMtb. Type 2 MDM were considerably more susceptible to HIV-1 infection than type 1. This correlated with the level of CCL2 production, which was significantly inhibited by vitamin D metabolites. PBMC isolated from healthy individuals in summer and in winter after receiving vitamin D, significantly restricted HIV-1 infection, compared to PBMC collected in winter before supplementation. There was a significant difference in circulating cell populations and serum cytokines/chemokines in summer, compared to winter, and these were investigated for correlations with HIV replication.

Conclusions

Vitamin D may prove a cheap, effective, tool for preventing TB-HIV disease progression and clinical trials are warranted in at-risk populations.
Measurement properties of self-report physical activity assessment tools in stroke: a protocol for a systematic review
Authors: Martins Júlia Caetano , Aguiar Larissa Tavares , Nadeau Sylvie , Scianni Aline Alvim , Teixeira-Salmela Luci Fuscaldi , Faria Christina Danielli Coelho de Morais
Published: February 2017

Introduction

Self-report physical activity assessment tools are commonly used for the evaluation of physical activity levels in individuals with stroke. A great variety of these tools have been developed and widely used in recent years, which justify the need to examine their measurement properties and clinical utility. Therefore, the main objectives of this systematic review are to examine the measurement properties and clinical utility of self-report measures of physical activity and discuss the strengths and limitations of the identified tools.

Methods and analysis

A systematic review of studies that investigated the measurement properties and/or clinical utility of self-report physical activity assessment tools in stroke will be conducted. Electronic searches will be performed in five databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) (PubMed), Excerpta Medica Database (EMBASE), Physiotherapy Evidence Database (PEDro),Literatura Latino-Americana e do Caribe em Ciências da Saúde(LILACS) and Scientific Electronic Library Online (SciELO), followed by hand searches of the reference lists of the included studies. Two independent reviewers will screen all retrieve titles, abstracts, and full texts, according to the inclusion criteria and will also extract the data. A third reviewer will be referred to solve any disagreement. A descriptive summary of the included studies will contain the design, participants, as well as the characteristics, measurement properties, and clinical utility of the self-report tools. The methodological quality of the studies will be evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and the clinical utility of the identified tools will be assessed considering predefined criteria. This systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement.

Discussion

This systematic review will provide an extensive review of the measurement properties and clinical utility of self-report physical activity assessment tools used in individuals with stroke, which would benefit clinicians and researchers.

Trial registration number

PROSPERO CRD42016037146.