Largest-ever IPD meta-analysis of malaria patients to inform haemoglobin changes

Artemisinin-based combination therapy is the first-line antimalarial treatment for uncomplicated falciparum malaria in most endemic countries but can suppress the bone marrow response and also contribute to haemolysis.

This individual patient data pooled analysis quantifies the underlying haematological response following P. falciparum infection to better understand the comparative benefits and risks of different antimalarial treatments. The paper, Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data, involved data from 70,226 patients, from 200 studies conducted between 1991 and 2013, with 72.4% enrolled in Africa, 26.3% in Asia and 1.3% in South America.

The paper determined the main factors associated with haematological fall and recovery following uncomplicated malaria and its treatment. The study highlights patients at greatest risk of severe anaemia who would warrant closer follow up and also whether some treatment regimens offer advantages over others with regard to fast recovery and prevention of anaemia.

WWARN researchers highlighted five main findings:

• A haemoglobin of <7 g/dL is present in 8.4% of people from Africa, 3.3% of people from Asia-Pacific and 0.1% of people from South America
• The majority of patients with uncomplicated falciparum malaria have a modest fall in haemoglobin following treatment before subsequently improving with recovery
• Young children are at a particularly high risk of developing malarial anaemia
• The risk of anaemia during recovery is exacerbated with a slower parasite clearance
• In Asia, people treated with an artemisinin-based regimen are at a greater risk of anaemia during recovery compared with those treated with a non-artemisinin-based regimen.

Dr Rob Commons, Postdoctoral Researcher in WWARN’s Asia-Pacific Regional Centre - Australia and one of the authors, said: “The finding that artemisinin-based treatment was potentially associated with increased anaemia in Asia is important for both clinicians and policymakers and requires more investigation. In our next study we plan to investigate whether different artemisinin derivatives and doses are associated with differing degrees of anaemia.”

Senior author Dr Kasia Stepniewska, Head of Statistics at WWARN, said: “Our analysis is the largest meta-analysis to date of patients treated for malaria in both Africa and Asia. This unprecedented data collection ensures robust parameter estimates and minimises the risk of inclusion bias.

“We are grateful to everyone who contributed their data to enable this important research. By aggregating and standardising global data we can maximise the use of available data, increase the statistical power of analyses and optimise the efficiency of research to better inform treatments for malaria.”

In the field of poverty-related infectious diseases, data are scarce and scattered across institutions around the world. Over the last decade, WWARN has been collating and standardising anonymised individual patient data (IPD) from many trials and studies conducted across the endemic regions so that they can then be harmonised and analysed as a single dataset, increasing the statistical power needed to answer key questions in malaria research. This IPD meta-analysis was the largest WWARN and its collaborators had ever undertaken and it has enabled researchers to provide more precise estimates for people who were more at risk of anaemia during recovery from antimalarial treatment.

Malaria remains a major cause of anaemia in malaria-endemic countries, compounded by malnutrition, helminth carriage and a range of blood disorders. This study analysed data from patients with malaria to explore how their haemoglobin changes following treatment of falciparum malaria to identify patients at risk of anaemia at presentation and during follow up and better understand the comparative benefits and risks of different antimalarial treatments.

Read the full paper

About WWARN

The WorldWide Antimalarial Research Network (WWARN) generates innovative tools and reliable evidence to inform the malaria community on the factors affecting the efficacy of antimalarial medicines. WWARN works with collaborators to optimise the efficacy of antimalarial medicines and treatment regimens, especially for vulnerable groups including pregnant women, infants and malnourished children, and provides evidence to inform the development of new antimalarial drugs.

WWARN’s repository now holds more than 180,000 individual malaria patient data files from around 600 different databases and makes it available for re-use by the research community. This includes clinical, in vitro, molecular and pharmacological data, as well as data on the quality of medicines.  Find out more at info@wwarn.org.