Clinic in Bamako, Mail

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.

Credit: Lindsay Mgbor/Department for International Development
Malaria in Pregnancy Infant Study Group

Exploring the impact of malaria during pregnancy on infant anaemia, malaria, morbidity and growth – an individual participant meta-analysis. 

Credit: Arne Hoel / World Bank
Vivax Adherence Study Group

The Vivax Adherence Study Group aims to assess the effect of variable adherence on P. vivax efficacy and to develop a pharmacokinetic-pharmacodynamic within-host mathematical model for P. vivax treatment. 

Credit: Dominic Chavez, World Bank
Intermittent preventive treatment in pregnancy (IPTp) and SP-resistance-associated mutations Study Group

The overall aim of the IPTp and SP-resistance-associated mutations Study Group is to quantify how parasites with the SP resistance-associated sextuple mutant haplotype modify the effect of IPTp on maternal and infant outcomes.

Mother with baby, Zambia. Credit: John & Penny Hubley. CC BY
Alternative strategies to prevent malaria in pregnancy Study Group

The Alternative Malaria in Pregnancy 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 dihydroartemisinin-piperaquine (DP) or artemether-lumefantrine (AL) in sub-Saharan Africa.

Lymphocyte with red blood cells. Credit: University of Edinburgh
White Blood Cell Count in Malaria Study Group

Determining what affects White Blood Cell (WBC) count at baseline and during acute phase of malaria infection.

SEM of red blood corpuscles. Credit: David Gregory & Debbie Marshall
Haemoglobin-Haematocrit Relationship in Malaria Study Group

Assessment of relationship between Haemoglobin (Hb) and Haematocrit (Hct) measurements.

Malaria in Pregnancy. Photo: LSTMH
Piperaquine Pharmacokinetics in Pregnancy Study Group

Determining the effects of pregnancy on piperaquine pharmacokinetics. The analysis aims to contribute evidence needed to inform recommendations on the use and optimal dosing of piperaquine in pregnant women.
Determining the effects of pregnancy on piperaquine pharmacokinetics. The analysis aims to contribute evidence needed to inform recommendations on the use and optimal dosing of piperaquine in pregnant women.

Malaria in Pregnancy Treatment Efficacy Study Group

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.

Red blood cells
Falciparum Haematology Study Group

Analysis of haematological response before and after antimalarial treatment. 
A pooled analysis to understand the normal haematological response and recovery following the treatment of uncomplicated malaria. The group will work together to quantify the risks and benefits of different treatment options of both ACTs and other antimalarials.
Data gathering and curation has started. Data meeting the inclusion criteria has already been collected and standardised from over 70,000 patients. Data analysis was conducted in 2015. A manuscript is in draft and is expected to be submitted for publication in 2019.

Vivax After Falciparum Study Group

This Study Group will explore the link between P. vivax recurrence and prior P. falciparum treatment, including increased risk of vivax parasitaemia due to acute malaria infection.


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 closed to new participants in December 2015. The analysis was completed between 2016–2018 and the group published in January 2019. WWARN K13 Genotype-Phenotype Study Group. Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments—a WWARN individual patient data meta-analysis. BMC Medicine. January 17, 2019.

(c) UNICEF Pierre Holz 2007
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.

Pipetting of blood in a biosafety cabinet
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)

Blood sample from child
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.

Plasmodium falciparum Gametocyte
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

A mother and child receiving malaria medication in Angola
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

Malaria microscopist in health care facility in Tanzania
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

Finger-prick of child for malaria blood slide
DP Dose Impact Study Group

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.
Related publications:
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

Mother and child in malaria clinic
AL Dose Impact Study Group

The AL Dose Impact Study Group was first established in 2011. The Study Group first met in December 2011 at the ASTMH Annual Meeting to discuss the Study Group governance and publication policy. The Study Group closed in March 2013. The latest results were presented at the 2014 ASTMH Annual Meeting in New Orleans, USA.
The artemether-lumefantrine (AL) Dose Impact Study Group found that the efficacy of the combination was lowest in young children from Asia and young underweight children from Africa, suggesting that a higher dose regimen should be evaluated in these groups. The manuscript for this Study Group was published by the Lancet Infectious Diseases in March 2015: The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data. 
Briefly, data from 66 clinical trials (n=15,529) conducted between 1998 and 2012, including eight unpublished studies and 58 published, studies representing 59 per cent of the targeted published literature on AL treatment were shared with WWARN. 61 studies (14,327 patients) were included in the final analysis. Of those patients included in the final analysis, 82.4 per cent were from Africa, 16.5 per cent from Asia and 1.1 per cent from South America.
Download a presentation from the AL Dose Impact Study Group.