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

Abstract

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.

Figure 1

Map of the Lao PDR showing distribution of collection sites with number of pharmacies selling counterfeit artesunate/number of pharmacies selling artesunate. Provinces with red borders are those sampled in the first collection and stars indicate urban districts and solid circles indicate rural districts. Cities sampled in the second collection are shown as blue triangles. Provinces in grey were not sampled. Geographical names follow [44].

Figure 2

Plot of slide positivity rate (SPR%) against the percentage of outlets selling artesunate for 12 Lao provinces. R² = 0.60, P = 0.01. Circles indicate the first collection and triangles the second collection.