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.
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 sextuple mutant pfdhps and pfdhfr haplotype* modify the effect of IPTp on maternal and infant outcomes.
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.
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.
Haemoglobin-Haematocrit Relationship in Malaria Study Group
Assessment of relationship between Haemoglobin (Hb) and Haematocrit (Hct) measurements.
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.
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 meeting the inclusion criteria has been collected and standardised from over 70,000 patients. Data gathering, curation and data analysis have been completed. A manuscript was published in BMC Medicine in March 2022. Additional analyses are planned to be undertaken and completed in Q2 2023.
Antimalarial–Antiretroviral Analyses
Sub-study groups include the Artemether-Lumefantrine / ARV PK Study Group and the ACT-ARV Safety Study Group.
ACT Malaria and Malnutrition Study Group
A pooled analysis that assessed the effect of various nutritional indicators in treatment outcome in children aged 6-59 months treated with artemisinin based combination therapies for uncomplicated P. falciparum malaria.
This group has published a first manuscript: Complex interactions between malaria and malnutrition: a systematic literature review. Das D et al. BMC Medicine. 2018 Oct 29;16(1):186. Read this news article summarising the results.
Molecular Markers of Resistance in West Africa Study Group
This Study Group aims to bring together and explore the latest evidence on the prevalence of molecular markers associated with antimalarial drug resistance in West African Countries.
ACT-ARV Haematology Study Group
This is an extension of the WWARN Haemoglobin-Haematocrit Relationship in Malaria Study Group and the Antimalarial–Antiretroviral Analyses Study Group. These groups aimed to consider the effect of HIV disease and co-administration of widely-used antiretroviral drugs (ARVs) on artemisinin-based combination therapies (ACTs).
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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
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.
AS-AQ Dose Impact Study Group
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.
Publiction details:
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 Study Group
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.
Related publications:
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
SP PK/PD Study Group
A population pharmacokinetic/pharmacodynamic model of pyrimethamine and sulfadoxine in participants who received either sulfadoxine-pyrimethamine (SP) as a monotherapy regimen or in combination with artesunate is being conducted. The full covariate analysis will explore the effects of participants and/or environmental factors that could influence the pharmacokinetics of pyrimethamine and/or sulfadoxine.
The data collection/curation is complete and the pharmacokinetic-pharmacodynamic analysis is currently ongoing to prepare for publication.
AS-MQ Dose Impact Study Group
A pooled analysis assessing the effect of mg/kg dosing strategies on the risk of treatment failure in patients treated with the currently recommended dose of artesunate-mefloquine (AS-MQ).
Research groups with relevant data have been contacted with data collection and curation still ongoing. Analysis will start in late 2016 and drafting publication in expected in 2018.
AS-AQ/AL Molecular Marker Study Group
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).
Related publications:
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.
Vivax After Falciparum Study Group
Exploration of the link between P. vivax recurrence and prior P. falciparum treatment, including increased risk of vivax parasitaemia due to acute malaria infection.
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.
Low-dose Primaquine Efficacy and Safety Study Groups
Pooled analyses of the efficacy and safety of single low-dose primaquine to interrupt P. falciparum malaria transmission.
Data collection has closed and curation is ongoing. Analysis and draft publications are planned for circulation to the Group by the June of 2017.
