WWARN facilitates a number of collaborative groups to undertake pooled analyses of data to answer specific research questions about malaria drug resistance. Pooling data sets from multiple studies increases sample sizes, so that trends or sub-population effects can be identified with greater certainty. By working together and combining data from different regions, the groups aim to improve the understanding of resistance and strengthen global efforts to control and eventually eliminate malaria.
Assessing the efficacy of a range of antimalarials used for the treatment of P. falciparum malaria in all trimesters of pregnancy in Africa and Asia. The MiP Treatment Efficacy Study Group was formed in July 2016, with a call to interested researchers with relevant data sets.
The sulphadoxine-pyrimethamine (SP) resistance Data Access Group’s aim is to provide maps and open access to the most recent data on molecular markers of SP resistance to help policy makers make informed decisions with regard to use of SP for intermittent preventive treatment of malaria in pregnancy (IPTp) or seasonal malaria chemoprevention (SMC).
The Alternative MiP Prevention Strategies (AMPS) Study Group’s aim is to determine the safety and efficacy of novel strategies for the control of malaria in pregnancy, specifically intermittent screening and treatment (ISTp), with an artemisinin-based combination therapy (ACT).
This Study Group is exploring key study design and analytical factors which affects derived clinical efficacy of antimalarials.
Statistical analyses have commenced and preliminary results of ongoing analyses will be shared at EDCTP Forum 2016 (Lusaka, Zambia) and ASTMH 2016 (Atlanta, USA). Publications are expected in 2017/18.
The Subpatent malaria and pregnancy outcome Study Group aims to explore the relationship between subpatent Plasmodium falciparum malaria infection and pregnancy outcome.
Analysis of risk factors of Plasmodium vivax early and late recurrence.
Statistical analysis has commenced in the first quarter of 2017 and a manuscript is expected to be submitted for publication in 2017.
Analysis of the consequences of symptomatic Plasmodium vivax infections on anaemia before and after antimalarial treatment
The Piperaquine Safety Study Group’s aim is to establish the evidence-base and safety profile to inform decision-making on the use and optimal dosing of dihydroartemisinin-piperaquine in all key target populations.
The study group call for contributors opened in June 2016 with a first scoping meeting held in July. Data collection is planned to close by end of 2016, with analysis due at the beginning of 2017.
A pooled analysis on the relationship between K13 molecular marker and parasite clearance data. The Study Group closed to new participants in December 2015 . The Study Group closed to new participants in December 2015. Data analysis and manuscript drafting is currently ongoing and expected to be shared with Study Group members by April 2017. Publication submission is planned for Q3 2017.
An analysis of pooled individual patient data to determine the effect of antiretroviral (ARV) drug-drug interactions and HIV disease on lumefantrine pharmacokinetics (and pharmacodynamics).
This study group has just opened for data collection. If you have any data you would like to share, or if you would like to participate in the project, please contact pharmacology [at] wwarn [dot] org.
A pooled analysis of Plasmodium falciparum gametocyte carriage
The purpose of this Study Group is to assess the risk factors for treatment failure associated with gametocyte carriage and clearance across a range of endemic settings and antimalarial drug treatments. To achieve this requires a standardised database and a set of metrics which are derived in a systemic manner. Data within the WWARN Data Centre provide an excellent opportunity.
Study published on 24 July 2016:
WWARN Gametocyte Study Group. Gametocyte carriage in uncomplicatedPlasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data. BMC Medicine 2016 14:79 DOI: 10.1186/s12916-016-0621-7
Analysing PK/PD data to identify inadequate drug exposure and inform dosage
A pooled lumefantrine pharmacokinetic-pharmacodynamic (PK/PD) analysis is being conducted to evaluate the exposure to lumefantrine in different populations to identify patient groups (such as young children and pregnant women) at particular risk of treatment failure. Further, to identify the pharmacokinetic-pharmacodynamic relationship of lumefantrine in the treatment of uncomplicated falciparum malaria. The group will use the the population PK-PD analysis and model developed to conduct in-silico dose optimisations.
WWARN Lumefantrine PK/PD Study Group. 'Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: a systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data'. Published in BMC Medicine 2015. 13:227 doi:10.1186/s12916-015-0456-7.
Baseline information on parasitological response to ACTs in Africa
A pooled analysis to assess the baseline early parasitological response after artemisinin combination therapy (ACT) treatments in sub-Saharan Africa. The analysis compiles the day 3 parasite positivity rates (PPR) in patients with uncomplicated Plasmodium falciparum malaria enrolled in ACT clinical efficacy trials.
The Study Group closed in March 2013. A draft manuscript has been finalised and shared with the Study Group members in February 2015. The study was published in BMC Medicine in September 2015.
WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group, Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data. BMC Medicine 2015, 13:212 doi:10.1186/s12916-015-0445-x
Effect of DP mg/kg dosing strategies on the risk of treatment failure
A pooled analysis to assess the impact of weight adjusted (mg/kg) dose variations of dihydroartemisinin-piperaquine (DP) on the therapeutic efficacy of both drugs combined. The Study Group assessed if the dose of piperaquine administered to patients was a risk factor for recrudescence, (recurrence of symptoms).
The Study Group closed in March 2013. A paper was published in Plos Medicine in December 2013. Results from this study group provided evidence for the revised recommendations for optimal use of artemisinin combination therapies included in the updated WHO ‘Guidelines for the Treatment of Malaria in June 2015.
The WorldWide Antimalarial Resistance Network (WWARN) DP Study Group (2013) The Effect of Dosing Regimens on the Antimalarial Efficacy of Dihydroartemisinin-Piperaquine: A Pooled Analysis of Individual Patient Data. PLOS Med 10(12): e1001564. doi:10.1371/journal.pmed.1001564
Effect of AL mg/kg dosing strategies on the risk of treatment failure
A pooled analysis to assess the impact of weight adjusted (mg/kg) dose variations of artemether-lumefantrine (AL) on the therapeutic efficacy of both drugs combined. The Study Group assessed if the dose of lumefantrine administered to the patients was a risk factor for recrudescence (recurrence of symptoms).
The study group closed in March 2013. A manuscript was submitted to Lancet Infectious Diseases in June 2014 and accepted for publication in February 2015. The manuscript for Artemether-Lumefantrine (AL) Dose Impact Study Group was published by the Lancet Infectious Diseases in March 2015.
Worldwide Antimalarial Resistance Network (WWARN) AL Does Impact Study Group. The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data. The Lancet Infectious Diseases 2015; D-14-00566R1; DOI 10.1016 S1473-3099 (15)70024-1
Effect of AS-AQ mg/kg dosing strategies on the risk of treatment failure
A pooled analysis to assess the impact of weight adjusted (mg/kg) dose variations of artesunate-amodiaquine (AS-AQ) on therapeutic efficacy of both drugs combined. The Study Group assessed if the dose of amodiaquine administered to the patients was a risk factor for recrudescence(recurrence of symptoms). The results are expected to be published in the BMC Medicine at the end of March 2015.
The study group closed in March 2013. The paper was published in March 2015.
The Worldwide Antimalarial Resistance Network (WWARN) AS-AQ Study Group. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data. BMC Medicine 2015 13:66. Published 31 March 2015 doi: 10.1186/s12916-015-0301-z.
Parasite clearance after treatment with an artemisinin monotherapy or ACT
This Study Group characterises parasite clearance stratified by location, treatment and time and to find optimal restricted sampling schemes for clearance estimation and provides baseline information on parasite clearance.
The latest study, ‘Baseline parasite clearance data in uncomplicated falciparum malaria after treatment with an artemisinin derivative alone or in combination’, has been submitted to Malaria Journal and is currently under review.
Flegg JA, Guerin PJ, Nosten F et al. Optimal sampling designs for estimation of Plasmodium falciparum clearance rates in patients treated with artemisinin derivatives. Malaria Journal, 2013. Doi: 10.1186/1475-2875-12-411. PMID: 24225303
WWARN Parasite Clearance Study Group ‘Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative: an individual patient data meta-analysis’ Published in Malaria Journal 2015. DOI:10.1186/s12936-015-0874-1
Role of candidate molecular markers of lumefantrine and amodiaquine resistance
The Artesunate-Amodiaquine/Artemether Lumefantrine (AS-AQ/AL) Molecular Marker Study Group demonstrated that if patients are infected with malaria parasites that carry particular mutations in genes pfcrt and pfmdr1, they are at higher risk of treatment failure after artemether-lumefantrine (AL).
Venkatesan M, et al. Polymorphisms in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors that Affect Treatment Outcomes for P. falciparum Malaria after Artemether-Lumefantrine and Artesunate-Amodiaquine. Am J Trop Med Hyg. 2014 Oct;91(4):833-43. doi: 10.4269/ajtmh.14-0031.