Study groups
WWARN facilitates a number of collaborative Study Groups to undertake individual patient data meta-analyses to answer specific research questions about malaria treatments and antimalarial drug resistance. Gathering and combining data sets from multiple studies increases sample sizes, so that effects, including smaller effects, and effects on sub-populations can be identified with greater certainty. Working together and combining data from different regions and populations is improving our understanding of drug resistance and strengthening global efforts to control and eventually eliminate malaria.
Primaquine Methaemoglobin Study Group
A pooled analysis of methaemoglobin as a marker of primaquine antihypnozoite activity in Plasmodium vivax malaria
Safety and tolerability of Artesunate-Pyronaridine and Artesunate-Amodiaquine for the treatment of uncomplicated or asymptomatic malaria
We are undertaking an individual patient data (IPD) meta-analysis to compare the safety and tolerability of artesunate-pyronaridine vs artesunate-amodiaquine, which is expected to inform a better understanding of the safety and tolerability of artesunate-pyronaridine relative to the related combination artesunate-amodiaquine that is currently more widely used in Africa.
Correlation between K13 mutations and clinical phenotype Study Group
A pooled analysis on the relationship between K13 molecular marker and parasite clearance data. The Study Group has been reopened in March 2023, with an objective to update repository with recent studies and rerun the analysis on the updated dataset. In the last few years several studies which identified a number of low frequency K13- propeller mutations and few reports of artemisinin resistance have been published in Africa. Systematic review was conducted to identified relevant studies (PROSPERO CRD42019133366, WWARN Clinical Trials Library). For further information, please contact Kasia Stepniewska kasia [dot] stepniewska [at] wwarn [dot] org
WWARN Primaquine Indian Region Study Group
An individual patient data meta-analysis from India and regional countries to inform the local safety, tolerability and efficacy of primaquine regimens for radical cure of P. vivax
Paediatric Primaquine
A series of individual patient data meta-analyses to investigate the safety, tolerability and efficacy of primaquine in paediatric patients with P. falciparum, P. vivax or P. ovale malaria.
Vivax Adherence Study Group
Analysis of the effect of adherence to primaquine on the risk of recurrence in patients with Plasmodium vivax malaria.
Vivax Haematological Study Group: Part 2
An analysis of the effect of recurrences and primaquine dose on haematological recovery.
Plasmodium vivax Fever Study Group
The Plasmodium vivax fever study group aims to estimate parasitaemia thresholds for febrile patients who present for treatment and determine the pyrogenic density of vivax parasitaemia in recurrent infections.
Primaquine Efficacy, Safety and Tolerability Study Group
Analysis of the effect of primaquine dose on the efficacy, safety and tolerability in patients with Plasmodium vivax malaria
Dihydroartemisinin-Piperaquine for Intermittent Preventive Treatment in Pregnancy (IPTp-DP) Study Group
The Dihydroartemisinin-Piperaquine for Intermittent Preventive Treatment in Pregnancy Study Group aims to determine the safety and efficacy of intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) compared to IPTp with sulfadoxine-pyrimethamine (SP), for the prevention of malaria and adverse birth outcomes among pregnant women in sub-Saharan Africa.
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Clinical Trials Methodology Study Group for P. falciparum
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 2018.
Ivermectin Exposure in Small Children Study Group
The Ivermectin Exposure in Small Children Study Group aims to assess safety profile of ivermectin exposure in children less than 15 kilograms
Vivax Haematology Study Group
Analysis of the consequences of symptomatic Plasmodium vivax infections on anaemia before and after antimalarial treatment
Antimalarial – Lumefantrine POP/PK Study Group
Determining the optimal Artemether-lumefantrine antimalarial dosing for young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis.
Vivax Recurrence Study Group
Analysis of risk factors of Plasmodium vivax early and late recurrence. Published in July 2018.
Amodiaquine PK/PD Study Group
Analysing PK/PD data to identify inadequate drug exposure and inform antimalarial dosage
A pooled pharmacokinetic/pharmacodynamics (PK/PD) analysis of amodiaquine (AQ) is complete. The analysis focused on a population pharmacokinetic/pharmacodynamic model of amodiaquine and its active metabolite desethyl-amodiaquine in patients who received either amodiaquine as a monotherapy regimen or in combination with artesunate. The full covariate analysis explored the effects of fixed versus loose dose formulations, age, nutrition status, baseline parasitemia and sample matrix.
Publication: WWARN Amodiaquine PK Study Group. Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis to Optimise Dosing. Denti et al. Antimicrobial Agents and Chemotherapy. 2018, Sept 24:62(10)
Piperaquine PK/PD Study Group
Analysing PK/PD data to identify inadequate drug exposure and inform dosage
A pooled piperaquine pharmacokinetic analysed the exposure to piperaquine in different populations in order to identify patient groups at particular risk of treatment failure, such as young children and pregnant women. The model can be used to optimise the dose in these vulnerable populations in order to give all patients an equal chance of cure.
The pharmacokinetic analysis has been finalised and published.
Gametocyte Carriage Study Group
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 uncomplicated Plasmodium 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
Lumefantrine PK/PD Study Group
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.
Publication details:
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.
Follow-on analysis:
Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis. Published in PLOS Medicine June 2018. 15 (6): 1-27. Doi: 10.1371/journal.pmed.1002579 PMID: 29894518
ACT Africa Baseline Study Group
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.
Publication details:
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
