bluuebunny/crossref_metadata_2025 huggingface dataset:
PILOTING DHIS2 SYSTEM IN VISCERAL LEISHMANIASIS SURVEILLANCE
Authors: Okeyo Seth , Omollo Raymond , Kimutai Robert , Ochieng Michael , Egondi Thaddaeus
Published: February 2017

Background

The District Health Information System 2 (DHIS2) is a tool for collection, validation, analysis and presentation of both individual (tracker) and aggregated data tailored to integrated health information management activities. DHIS2, developed by the Health Information Systems Programme (HISP) in collaboration with University of Oslo, is a modular web-based software package built with open source Java frameworks. Visceral leishmaniasis (VL) is not captured in the DHIS2 regional database, and therefore coming up with the modalities of aggregating available data from clinical trials and general patient records into the DHIS2 national database is crucial for surveillance.

Methods

DHIS2 runs on Tomcat Server and PostgreSQL. We set up the VL surveillance program with different stages: enrolment and demographics, initial treatment outcome and follow-up visits. In this system, a patient is enrolled into the system and data is collected in individual data elements; data Indicators are built to help aggregate the data and thereafter used for report generation. It is programmed to visualise data and display reports in the system dashboard which can then be used to present data.

Results

Piloting DHIS2 has enabled us to set up a system that uses the set indicators programmed to aggregate data, thus able to produce reports on the data and the user is also able to select the type of report in the form of pivot tables, charts and graphs and also in GIS mapped data.

Conclusions

DHIS2 system is an open source that can be customised and expanded to capture detailed individual surveillance data and shared in reports. This data is useful for tracking neglected tropical diseases such as VL. Data can be handled in the following modalities: i) use of off-line data synchronisation. ii) remote data collection using mobile devices iii) data aggregation and organisation iv) data visualisation and presentation through charts, graphs and pivot tables.
MATERNAL UROGENITAL SCHISTOSOMIASIS, MONITORING DISEASE MORBIDITY BY SIMPLE REAGENT STRIPS
Authors: Oyeyemi Oyetunde , Odaibo Alexander
Published: February 2017

Background

Urine analysis is one of the recommended antenatal guidelines for early diagnosis of pregnancy-associated complications. While urine analysis by dipstick had been used in practice to provide useful information on other urinary tract infections, its application for early detection of urogenital schistosomiasis in pregnant women is often downplayed in most endemic areas. Our study therefore assessed the performance of some common urinalysis parameters in the diagnosis of maternal urogenital schistosomiasis in endemic rural communities of Nigeria.

Methods

The cross-sectional epidemiological survey of urogenital schistosomiasis was conducted among pregnant women in Yewa North Local Government, Ogun State, Nigeria. The women were examined for infection withSchistosoma haematobiummicroscopically and screened for macrohaematuria, microhaematuria and proteinuria using standard urine chemical reagent strips.

Results

Of 261 volunteer participants, 19.9% tested positive forS. haematobiuminfection. The proportion of microhaematuria (23.8%) was significantly higher than that of macrohaematuria (3.8%) and proteinuria (16.8%) (p<0.05). Microhaematuria with sensitivity (82.7%) and specificity (89.0%) was the best diagnostic indicator of urogenital schistosomiasis.

Macrohaematuria with the least sensitivity (11.8%) was however the most specific (98.1%) for diagnosing urogenital schistosomiasis in pregnant women. Maximum microhaematuria sensitivity (100.0%) was observed in women between 15–19 years but sensitivity was consistently low in other older age groups. Maximum sensitivity, specificity and predictive values (100.0%) were recorded for microhaematuria in first trimester women. Diagnostic efficiency of proteinuria and macrohaematuria was also better in first trimester women except the 25.0% specificity recorded for proteinuria. The overall diagnostic performance of microhaematuria and proteinuria was best in secundigravidae.

Conclusions

Microhaematuria can be used for early detection of urogenital schistosomiasis in endemic areas especially in younger and first trimester women. Treatment with praziquantel is recommended for the women in their late trimester in order to avert associated adverse pregnancy outcomes.
THE EFFECT OF HELMINTH CO-INFECTION ON MALARIA-SPECIFIC IMMUNOGLOBULIN G RESPONSES
Authors: Njua-Yafi Clarisse , Nkuo-Akenji Theresa , Anchang-Kimbi Judith , Apinjoh Tobias , Mugri Regina , Chi Hanesh , Tata Rolland , Njumkeng Charles , Dodoo Daniel , Theisen Michael , Achidi Eric
Published: February 2017

Background

Malaria and helminthiases overlap extensively in their epidemiological distributions, and co-infections are common. Helminth infection has a profound effect on the immune system such as the induction of immuno-regulatory mechanisms such as potent regulatory T cell responses known to suppress cellular effector mechanisms.

Methods

The prevalence of malaria parasitaemia, intestinal helminths, co-infection and anaemia was determined in a cross-sectional study (March 2011) of 372 children aged 6 months to 10 years resident in Mutengene in south-western Cameroon. Plasma total IgG and IgG1–4 subclass antibody levels toP. falciparumapical membrane antigen 1 (AMA1), the N-terminal non-repeat region (GLURP R0) and the C-terminal repeat region of glutamate rich protein (GLURP R2) and merozoite surface protein 3 (MSP3) were measured by standardised ELISA.

Results

Prevalence was as follows: malaria parasitaemia (mp) 18%, pyrexia 25.4%, helminths 19.7%, and anaemia 71.5%. Amongst those who were mp-positive, 25.4% were symptomatic (4.5% overall). Almost all helminth infections were the soil-transmitted helminthsAscaris,Trichurisand hookworm (96.4%) with a few cases ofHymenolepisandEnterobius. Haemoglobin concentration (g/dl) correlated positively with age and negatively with mp density (p≤0.001). The mean haemoglobin (g/dl) level of participants co-infected with both parasites (3.4%) was higher compared to participants infected with eitherPlasmodium(15.8%) or helminths (16.1%) alone (p< 0.01). IgG and IgG1–4 subclass antibody levels to all recombinant antigens correlated positively with age (p< 0.01). Total IgG, IgG1, 2 & 3 levels to all the antigens tested were significantly (except MSP3 IgG2, p=0.08) higher in participants infected withPlasmodiumalone, compared to the co-infection, helminths only and no infection groups. Decreased levels of AMA1 IgG associated significantly with co-infection (OR=0.27, 95% CI:0.11–0.68). Increased MSP3 IgG and IgG1–4 levels were significantly associated with children infected withPlasmodiumalone compared to children co-infected with both parasites.

Conclusions

Infection with intestinal helminths stifles protective anti-plasmodial antibody responses.
THE IMMUNE TRYPANOLYSIS TEST: AN ACCURATE SEROLOGICAL MARKER TO MANAGE ELIMINATION OFT.B. GAMBIENSEHUMAN AFRICAN TRYPANOSOMIASIS
Authors: Emilie Dama , Camara Oumou , Mathurin Koffi , Guiguigbaza-Kossigan Dayo , Philippe Büscher , Regassa Fikru , Hassane Sakande , Bienvenu Somda Martin , Ilboudo Hamidou , Fabrice Courtin , Ouédraogo Elie , Kouakou Lingue , Kaba Dramane , Camara Mamady , Bucheton Bruno , Lejon Veerle , Jamonneau Vincent
Published: February 2017

Background

Continued post-elimination monitoring is required to ensure sustainability of zero transmission of human African trypanosomosis (HAT) and to avoid re-emergence caused by potential remainingTrypanosoma brucei gambiensereservoirs (animal and/or human). Until now, no tool is able to attest or validate elimination. Increasingly, the serological immune trypanolysis test is being implemented in the decision algorithms to characterise parasitological unconfirmed CATT or RDT seropositive subjects. Therefore, we wanted to assess further the high specificity of immune trypanolysis.

Methods

We first tested samples from domestic animals from a tsetse-infested area in Ethiopia, a country where noT. b. gambienseexists, but where bovine trypanosomosis is prevalent. Then, we tested cattle and human samples from the south-west of Burkina Faso, a historical focus ofgambienseHAT that still shelters tsetse flies populations and animal trypanosomosis. Lastly, we were interested in testing human samples from active foci in Côte d'Ivoire and Guinea.

Results

Our results showed zero trypanolysis-positive animals from Ethiopia while in the historical HAT foci in Burkina Faso, 4.89% (14/286) of cattle were trypanolysis-positive. In humans, zero samples over 729 were trypanolysis-positive in Burkina Faso, while the percentage of positives was 3.77% (44/1166) in Guinea, including 7 new cases diagnosed during the sampling and 1.3% in Côte d'Ivoire (8/598).

Conclusions

Considering results from this study, we think that trypanolysis test, confirmed to be a very specific test in human, can be a tool able to certify HAT elimination in a given area. It also suggests that the risk of the reintroduction ofT. b. gambiensein Burkina Faso is real, especially in the south-west which shelters a high density of tsetse populations, in addition to the possible presence ofT. b. gambiense in domestic animals. However, further studies on the specificity of the trypanolysis test regardingT. b. gambiensein animals should be conducted.
HIV INFECTION AND CARDIOVASCULAR RISK PROFILE IN A RURAL SOUTH AFRICAN POPULATION: THE NDLOVU COHORT STUDY
Authors: Vos Alinda , Devillé Walter , Barth Roos , Klipstein-Grobusch Kerstin , Tempelman Hugo , Venter François , Coutinho Roel , Grobbee Diederick
Published: February 2017

Background

Life expectancy increased in HIV-infected populations due to antiretroviral treatment (ART). Whether HIV-infection and/or ART increase cardiovascular risk against a background of increasing prevalence of obesity, hypertension and diabetes in low- and middle-income countries is not yet clear. To answer this question in a rural South-African population, the Ndlovu Cohort Study was designed. We describe the baseline distribution of cardiovascular risk factors in relation to HIV and ART.

Methods

The Ndlovu Cohort Study is a prospective cohort study of 1000 HIV-positive and 1000 HIV-negative adults from the Moutse area, Limpopo, South Africa with an intended follow-up duration of ten years. Information is collected on demographics, anthropometrics, life-style, kidney and liver function, CRP, glucose and proteinuria. Carotid intima-media thickness (CIMT) and pulse wave velocity (PWV) measurements are used to assess subclinical atherosclerosis, respectively arterial stiffness. Cardiovascular risk factors were compared between HIV-negative and HIV – positive participants, whether or not on ART. Data were adjusted for gender and age.

Results

By December 2015, 1053 participants were included, 66% women; 345 (32.8%) women were HIV-positive of whom 235 (68.1%) received ART. HIV-infected participants were significantly older (40.0 versus 37.3 years), and mainly women (73%). HIV was associated with a lower body mass index, lower total – and LDL cholesterol and a lower prevalence of hypertension and diabetes. ART was associated with increased HDL and triglyceride levels. Current smoking did not differ between groups (23.6%), HIV and ART were associated with higher CRP values. Framingham risk scores (FRS) did not differ between HIV+/HIV- and/or ART use.

Conclusions

HIV infection is accompanied by a lower prevalence of cardiovascular risk factors, although the level of inflammation is increased. So far, we found no evidence that the 10-year cardiovascular disease risk according to FRS is influenced by HIV infection or HIV treatment.
POINT-OF-NEED DIAGNOSTICS: BIOSURVEILLANCE WITH A DEVICE2CLOUD CAPABILITY IN SIERRA LEONE
Authors: Ansumana Rashid , Taitt C. , Lamin J.M. , Jacobsen K.H. , Mulvaney S.P. , Leski T. , Bangura U. , Stenger D.
Published: February 2017

Background

Infectious diseases contribute to a high burden of diseases globally. Surveillance using low-cost technology, combined with cutting edge platforms offers a path for understanding the disease ecology of locations of interest in resource-poor countries. Our goal was to pilot a bio surveillance system comprising of rapid lateral flow immunoassays, rapid PCR and a cloud database.

Methods

The study was carried out in Bo, Sierra Leone at the Mercy Hospital. We recruited 1570 subjects over a period of two years. Inclusion criteria for the study were being febrile, being at least five years of age, living within the city of Bo or its neighbouring villages and agreeing to participate in the study. The assays used included a DPP multiplex lateral flow assay for dengue,Burkholderia pseudomallei,Yersinia pestis, malaria Pf/Pan, a Film Array PCR platform with multiplex Biothreat and SASFI panels that together detect over 30 pathogen targets. We used a Deki Reader to upload lateral flow images to the cloud database. The Deki reader quantitates test results, such that scores at ≥1.75 are considered positive. A special computer program was designed to upload pdf images of PCR results to the cloud database. The cloud database was designed for automated quality assessment and remote monitoring.

Results

Preliminary results show that out of 1570 samples processed by DPP, 30(1.9%) were positive for Burkholderia, 41(2.6%) were positive for Dengue NS1 antigen, 22(1.4%) were positive forYesinia pestisfraction 1 antigen, and 340(21.7%) were positive for malaria. When a cross-section of results obtained by eye was compared with results automatically detected by the D2C platform, there was 95.2% concordance between results obtained by eye and those obtained automatically by the Deki reader to the cloud database.

Conclusions

Active disease surveillance and the ability to remotely monitor activities in peripheral health units are critical needs in many poor countries. Our results provide additional perspectives on the twin problem of surveillance and remote quality assessment.
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

Background

Mass 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.

Methods

We 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).

Results

MDA 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.

Conclusions

MDA 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

Background

The 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.

Methods

A 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.

Results

The 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).

Conclusions

Our 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

Background

Several 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.

Methods

From 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.

Results

A 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.

Conclusions

Artesunate 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

Background

Appropriate 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).

Methods

Using 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.

Results

The 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.

Conclusions

The 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

Background

With 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.

Methods

The 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.

Results

A 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.

Conclusions

Adding 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

Background

SAR97276A, 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.

Methods

This 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).

Results

In 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.

Conclusion

Both 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

Background

Hyperparasitaemia 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.

Methods

A 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.

Results

A 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).

Conclusions

From 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

Background

Artemisinin-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.

Methods

A 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.

Results

A 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.

Conclusions

The 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

Background

As 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.

Methods

A 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.

Results

We 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.

Conclusions

This study shows no change either inP. falciparumgenetic diversity or in MOI 10 years after the introduction of ACTs.
ASSESSING THE COMMITMENT, MATURATION AND INFECTIVITY OF SEXUAL STAGES OF MALARIA PARASITES IN SCHOOLCHILDREN LIVING IN A HIGH MALARIA TRANSMISSION AREA OF BURKINA FASO
Authors: Barry Aissata , Tiono Alfred , Sirima Sodiomon , Bousema Teun
Published: February 2017

Background

With the move towards malaria elimination, it becomes essential to understand the contribution of asymptomatic parasite carriers to disease transmission. However, the dynamics of infection and gametocyte development are poorly understood in asymptomatic versus symptomatic malaria infections. This was addressed in a longitudinal study of school children in Balonghin, district of Saponé, Burkina Faso.

Methods

The study involved healthy schoolchildren (with no malaria parasite at microscopy) age 5–10 years. For the first year survey, children were cleared for subpatent infections using standard malaria therapy. No clearance will occur for the second year survey. Children are followed up for 6 months during which repeated finger prick blood samples for the detection and characterisation of infections are collected. Also at three occasions a venous blood sample is collected for direct membrane feeding assay (DMFA) to assess infectiousness to mosquitoes.

Results

The first year survey was completed. Fifty (50) children were recruited and followed up. Almost all the children develop infection and symptomatic malaria during the follow-up period post clearance of initial infection. None of the children has infected mosquitoes during the DMFA assays. The second year survey is in process. The full results will be presented during the forum.

Conclusions

These data will be pivotal in understanding human infectious reservoir. This will help designing interventions to tackle the spread of malaria from symptomatic and asymptomatic malaria individuals towards global in eliminating malaria.
MALARIA PREVENTION PRACTICES AMONG PREGNANT MOTHERS IN OSOGBO, NIGERIA
Authors: Tijani Adelani
Published: February 2017

Background

Pregnant women are susceptible to symptomatic malaria due to invasion of the placenta byPlasmodium. The study aimed to find out the preventive measures put in place by pregnant mothers against malaria.

Methods

It is a descriptive cross-sectional survey comprising 294 pregnant women selected randomly in three hospitals in Osogbo. The instrument used for data collection was a self-developed, structured questionnaire with reliability of 0.802 using Cronbach's alpha coefficient.

Results

The results show that 87.8% of the respondents had adequate knowledge about malaria in pregnancy and 75.5% of them were knowledgeable about various available measures in malaria prevention. However, only 34.4% used the insecticide treated nets (ITNs) and 21.4% used intermittent preventive therapy (IPTp). Findings also revealed that the respondents practiced other preventive measures such as clearing of surrounding bushes (12.8%), maintenance of drainages and netting of windows and doors (15.4%). The results of the study revealed that various barriers to the use of ITNs were deficient knowhow (45.9%), spousal disapproval (36.7%), socio-cultural misconceptions about sleeping under ITNs (18.8%) and unaffordability of ITNs (45.5%). The hypotheses were tested using Pearson's chi-square method at 0.05 level of significance. There is no significant relationship between the pregnant mothers' knowledge and their practice of malaria prevention. However, there are respective significant relationships between the age, parity and educational status and practice of malaria prevention.

Conclusions

It was concluded that the practice of malaria prevention was generally low among the respondents. It was therefore recommended that concerted effort be put in place by the nurses, more especially public health nurses to address the barriers to utilisation of the universally accepted effective methods of malaria prevention. This could be done through mass health education to market women at regular interval.
INNOVATIVE CLINICAL TRIAL DESIGNS
Authors: Phillips Patrick
Published: February 2017

Since the middle of the 20th century, randomised controlled trials have provided the strongest level of evidence to inform the treatment of all diseases. In particular, trials in the 1970s and 1980s in Africa led to a highly efficacious 6-month regimen for the treatment of TB; these were followed by trials in the 1990s and 2000s which resulted in today's HAART regimens that are recommended for all patients living with HIV.

These diseases, however, still cause 1.3 million deaths every year in Africa, and further trials are needed to improve treatment and develop control strategies that will ultimately end the epidemics. Furthermore, there are many neglected diseases where few if any trials have been conducted and therefore the evidence base for treatment is extremely weak.

The randomised clinical trial is an indispensable tool for defeating poverty-related and neglected diseases in Africa, but it should not be seen as a static instrument that has remained unchanged since its first introduction in the 1940s. Innovations in clinical trial design can overcome many barriers, facilitating more efficient trials where alternatives are prohibitively long or resource-intensive. For example, adding multiple intervention arms or sequential randomisations allows for more questions being answered in a single trial, and adaptive designs permit modifications to ongoing trials in light of internal or external data, thereby making better use of limited resources.

This presentation covers the opportunities for innovation in clinical trial design in poverty-related and neglected diseases. Recent developments relate to multi-arm multi-stage and other adaptive trial designs, interpretation of non-inferiority trials, choice of comparator arms, the role of pragmatic trials, and treatment strategy trials. Specific examples will be presented, including recent TB, HIV and Ebola trials, in addition to other areas for possible progress, all with the ultimate goal of faster patient benefit.
PLASMODIUM FALCIPARUMPARASITE DYNAMICS DETERMINED BY QPCR AFTER CONTROLLED HUMAN MALARIA INFECTION IN SEMI-IMMUNES FROM GABON
Authors: Honkpehedji Yabo , Agobe Jean Claude Dejon , Zinsou Frejus , Mengue Juliana , Adegnika Ayola , Richie Thomas , Mordmüller Benjamin , Kremsner Peter , Hoffman Stephen , Lell Bertrand
Published: February 2017

Background

Characterising the effect of natural acquired immunity and sickle cell anaemia on the pattern ofPlasmodium falciparumparasitaemia may be useful to understand the pathophysiological mechanisms of protection against malaria. Controlled human malaria infection (CHMI) by direct venous inoculation of aseptic, purified, cryopreserved sporozoites (Pf-SPZ challenge) is a new tool which can be used to investigate the pathophysiology of malaria.

Methods

The study was performed in Lambarene, Gabon, one of seven African partners in the EDCTP-funded CHMI platform. Adults aged 18–35 from three groups NI: 5 non-immune (NI), 11 semi-immunes with haemoglobin AA (IA), and 9 semi-immunes with haemoglobin AS (IS) received 3,200 sporozoites after a curative treatment course with clindamycin. Capillary blood samples were taken daily up to Day 28 to determine parasitaemia by real-time quantitative polymerase chain reaction (RT-qPCR). Treatment was administered for a malaria episode or at Day 28, whichever came first.

Results

Parasitaemia was detected in 5 (100%) subjects in the NI group, 9 (82%) in the IA group and 7 (78%) in the IS group. All volunteers in the NI group showed similar patterns with parasitaemia starting around Day 8 and rising quickly. Patterns for parasitaemia in the immune groups (IA and IS) were highly heterogeneous. Although time points of initial parasitaemia and duration of parasitaemia varied, all semi-immunes managed to control parasitaemia for at least several days. There were no discernible differences in patterns between the IS and IA group, including the area under curve of parasitaemia over time.

Conclusions

No parasitaemia was detected in 20% of the semi-immunes, likely due to liver stage immunity. The highly variable patterns of parasitaemia did not allow us to discern immune mechanisms against blood stages. Haemoglobin AS had no visible effect on parasite dynamics at the low parasitaemia encountered.
MYCOBACTERIUM TUBERCULOSISRESISTANCE TO ISONIAZID AND RIFAMPICIN IN A HIV-1 ENDEMIC POPULATION IN WESTERN KENYA IN 2014
Authors: Likhovole Clement , Ouma Collins , Vulule John , Musau Susan , Khayumbi Jeremiah , Okumu Albert , Murithi Wilfred
Published: February 2017

Background

The spread of mono-resistant and multi-drug resistant tuberculosis (MDR-TB) has been enhanced by delays in the identification of resistant strains. However, resistance gene patterns and the extent and distribution of mono-resistant TB and MDR-TB is unknown, particularly for western Kenya where Human Immunodeficiency Virus (HIV) is common. As such, the overall objective of the current study was to identify cases of mono-resistant TB and MDR-TB among enrolled patients in health facilities in western Kenya.

Methods

Patients with a suspected TB history were referred by clinicians to the health facilities for TB and HIV diagnosis. HIV testing was done using the Unigold and Abbott Determine kits. Early morning sputum samples were collected and cultured onMycobacteriagrowth indicator tubes (MGIT) and incubated at 37°C. Drug susceptibility testing (DST) using the SIRE® kit was done on ZN smear positive MGIT tubes and line probe assay (LPA) performed to identify specific mutations on therpoB,katG andinhA genes. Mutations on discordant samples were confirmed by the BigDye® Terminator v3.1 Cycle Sequencing Kit.

Results

The proportion of MDR-TB, RIF mono-resistant (RMR) TB and INH mono-resistant TB as estimated by LPA and DST, was as follows: MDR-TB: 1.38% / 1.26%; RMR-TB: 1.2% / 0.72%; INH mono-resistant TB: 2.1% / 2.4%, respectively. Our study showed that the H526YrpoB and S315T1kat Gmutations were common in HIV-positive patients (8% and 18% respectively) and that the S3I5T1 and S531L was the most common mutation in MDR-TB strains in both HIV-positive and HIV-negative patients (5% and 8% respectively). Binary logistic regression, indicated that RMR-TB significantly predicted HIV status (p=0.025).

Conclusions

Our findings show that RIF mono-resistant TB predicts HIV infection.