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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.

Photo shows women in Ethiopia
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.

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 sextuple mutant pfdhps and pfdhfr 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 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 is under review of study group members and expected to be submitted for publication Q2 2020. 

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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.

ASAQ treatment
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.

Finger-prick for malaria blood slide
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

Malaria medication
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.

Alignment of DNA sequences
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. 

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