One of the best indicators of artesunate drug resistance is a delay in the reduction of malaria parasite numbers in the patient’s blood after treatment. However, there are factors other than drug resistance that can affect this parasite clearance rate, such as immunity levels, initial parasite biomass, drug dosage and partner drug efficacy. The extent to which these factors affect parasite clearance rate is not completely understood.
In a new study published in Malaria Journal, the WWARN Parasite Clearance Study Group pooled data from 24 studies undertaken over 18 years; these studies included nearly 7,000 patients in whom parasites had been counted frequently in the first few days after treatment. This large volume of data allowed the team to compare the impact of patient characteristics and study design on reported parasite clearance rates and to assess the geographical, physiological and external factors that can also influence the rate.
“There are many factors other than just drug resistance that can vary or slow parasite clearance after treatment, but a thorough investigation into the influence of these factors had not previously been undertaken,” says Prof Philippe Guérin, Director of WWARN.
“By analysing these data pooled from sources in several endemic regions, we were able to extract critical baseline information about the factors that can affect parasite clearance rate. This baseline information can now be used to support early identification of artemisinin resistance in malaria endemic countries, and inform the design of future studies.”
The team found that the variations in parasite clearance estimates were often due to differences in study design. These included infrequency of sampling, and the inclusion of patients with relatively low initial levels of parasites in the blood so that there were not enough data points to estimate the rate of clearance accurately. The treatment dose, the patient’s age, and the patient’s level of immunity were also identified as factors that influenced the clearance.
“The parasite clearance rate is considered to be the most robust measure of antimalarial efficacy,” says Dr Rick Fairhurst, Chief, Malaria Pathogenesis and Human Immunity Unit, National Institute of Allergy and Infectious Diseases. “These pooled data provide vital information on the factors that affect this rate, and therefore offer a much needed resource for clinical researchers to compare future parasite clearance rate estimates with older data to ensure consistency and confirm the presence of antimalarial drug resistance more accurately.”
“The study highlights the importance of having standardised parasite clearance data in one location,” says Dr Kasia Stepniewska, Head of Statistics at WWARN. “We will make all of the summary information available on the WWARN website as a resource that researchers can use to compare against their own parasite clearance data.
“We would like to build on this critical information and encourage researchers to use our Parasite Clearance Estimator and share their parasite clearance estimation data with the community, so that there will be standardised, comparable summary level results that can be used by the research community.”
This information will enable researchers to control for the effects of partner drugs, study design or patient characteristics, so that true artemisinin resistance can be identified and temporal changes identified.
The WWARN Parasite Clearance Estimator provides malaria researchers managing malaria control programmes with a valuable tool that standardises analysis of parasite counts determined frequently during the first days after treatment. It provides an automated report for each patient and converts the counted data into a single estimate of parasite clearance, the half-time of decline. The tool is freely available on the WWARN website.
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