New data regarding safety of artemisinin combination therapy for pregnant women with malaria

December 22, 2008

A trial conducted in northwest Thailand has found that it is safe to use artemisinin combination therapy (ACT) to treat pregnant women with malaria, but that efficacy is inferior to single-drug artesunate treatment. The study, published in next week's PLoS Medicine, suggests that the ACT evaluated in the trial, artemether-lumefantrine (AL), may have lower efficacy because drug concentrations were seen to be reduced during pregnancy. The authors suggest that longer, or more frequent, regimens of the drug combination should be evaluated for treatment of pregnant women.

ACT - the combination of two antimalarial drugs to reduce the chance of malaria becoming resistant to either - is now the primary form of treatment for Plasmodium falciparum malaria, which kills nearly one million people per year. ACT may soon be the only effective treatment for malaria, given that the disease has become resistant to many of the older antimalarial drugs, and it has shown to be safe and effective in non-pregnant women. For pragmatic reasons the World Health Organisation (WHO) also recommends that ACT is also used to treat malaria in mid-late pregnancy, despite the fact that little is known about how well it works in pregnant women. This trial was conducted on the Thai-Burmese border, an area where malaria transmission is low but highly drug-resistant, meaning that pregnant women who contract the disease are at risk of developing severe malaria that can be fatal to both the mother and her unborn child.

Rose McGready, of the Shoklo Malaria Research Unit in Thailand, and colleagues sought to compare the safety and efficacy of the most widely used ACT, artemether-lumefantrine (AL), with artesunate, a single artemisinin-derived drug. The 253 women enrolled in the trial had uncomplicated malaria - the stage before the patient needs treatment with intravenous drugs - and were in the second and third trimesters of pregnancy. Using a measure called the PCR adjusted cure rate to assess how each type of treatment cured new infections, they found that artesunate outperformed AL (89.7% compared to 81.2%), although neither course of treatment achieved the 95% cure rate recommended by the WHO. Few side effects were found with either type of treatment, and the health and development of infants at birth and at one-year of age were similar irrespective of the type of treatment their mothers received.

This is the first trial that examined the use of ACT to treat pregnant women and the finding that it is safe and well-tolerated in the second and third trimesters of pregnancy is significant and welcome. Despite the fact that ACT did not perform as well as in studies of non-pregnant women with uncomplicated malaria, the researchers are careful to warn that this does not mean it cannot be used to treat pregnant women effectively in other endemic regions. Low drug blood levels were observed in the women seven days after treatment, which may explain the reduced efficacy of ACT in this area of Thailand with highly drug-resistant parasites. The researchers conclude by suggesting a higher-dose ACT regimen should now be evaluated for the treatment of pregnant women with uncomplicated malaria.
-end-
This study received financial support from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Medicine (TDR) and was part of the Mahidol University Oxford Tropical Medicine Research Programme funded by the Wellcome Trust.

Citation: McGready R, Tan SO, Ashley EA, Pimanpanarak M, Viladpai-nguen J, et al. (2008) A randomised controlled trial of artemether-lumefantrine versus artesunate for uncomplicated Plasmodium falciparum treatment in pregnancy. PLoS Med 5(12): e253. doi:10.1371/journal.pmed.0050253

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050253

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-12-mcgready.pdf

READ THE EDITORS' SUMMARY OF THE PAPER: http://www.plos.org/press/plme-05-12-mcgready-summary.pdf

CONTACT:
Rose McGready
Shoklo Malaria Research Unit (SMRU)
Mahidol Oxford Tropical Medicine Research Unit (MORU)
PO Box 46
Mae Sot
Tak 63110
Thailand
+66 55 545 021
+66 55 545 020 (fax)
rose@shoklo-unit.com

PLOS

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.