Research
A stratified random survey of the proportion of poor quality oral artesunate sold at medicine outlets in the Lao PDR – implications for therapeutic failure and drug resistance
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* Corresponding author: Paul N Newton paul@tropmedres.ac
1 Food and Drug Department, Ministry of Health, Government of the Lao PDR, Vientiane, Lao PDR
2 Division of Parasitic Diseases, US Centres for Disease Control and Prevention, Atlanta, USA
3 School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA
4 Food and Drug Quality Control Centre, Ministry of Health, Government of the Lao PDR, Vientiane, Lao PDR
5 GNS Science, Lower Hutt, New Zealand
6 Centre for Malariology, Parasitology & Entomology, Government of the Lao PDR, Vientiane, Lao PDR
7 Wellcome Trust – Mahosot Hospital – Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
8 Center for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, UK
Malaria Journal 2009, 8:172 doi:10.1186/1475-2875-8-172
Published: 28 July 2009Abstract
Background
Counterfeit oral artesunate has been a major public health problem in mainland SE Asia, impeding malaria control. A countrywide stratified random survey was performed to determine the availability and quality of oral artesunate in pharmacies and outlets (shops selling medicines) in the Lao PDR (Laos).
Methods
In 2003, 'mystery' shoppers were asked to buy artesunate tablets from 180 outlets in 12 of the 18 Lao provinces. Outlets were selected using stratified random sampling by investigators not involved in sampling. Samples were analysed for packaging characteristics, by the Fast Red Dye test, high-performance liquid chromatography (HPLC), mass spectrometry (MS), X-ray diffractometry and pollen analysis.
Results
Of 180 outlets sampled, 25 (13.9%) sold oral artesunate. Outlets selling artesunate were more commonly found in the more malarious southern Laos. Of the 25 outlets, 22 (88%; 95%CI 68–97%) sold counterfeit artesunate, as defined by packaging and chemistry. No artesunate was detected in the counterfeits by any of the chemical analysis techniques and analysis of the packaging demonstrated seven different counterfeit types. There was complete agreement between the Fast Red dye test, HPLC and MS analysis. A wide variety of wrong active ingredients were found by MS. Of great concern, 4/27 (14.8%) fakes contained detectable amounts of artemisinin (0.26–115.7 mg/tablet).
Conclusion
This random survey confirms results from previous convenience surveys that counterfeit artesunate is a severe public health problem. The presence of artemisinin in counterfeits may encourage malaria resistance to artemisinin derivatives. With increasing accessibility of artemisinin-derivative combination therapy (ACT) in Laos, the removal of artesunate monotherapy from pharmacies may be an effective intervention.