Date Published: February 12, 2008
Publisher: Public Library of Science
Author(s): Paul N Newton, Facundo M Fernández, Aline Plançon, Dallas C Mildenhall, Michael D Green, Li Ziyong, Eva Maria Christophel, Souly Phanouvong, Stephen Howells, Eric McIntosh, Paul Laurin, Nancy Blum, Christina Y Hampton, Kevin Faure, Leonard Nyadong, C. W. Ray Soong, Budiono Santoso, Wang Zhiguang, John Newton, Kevin Palmer, Marcus Reidenberg
Abstract: BackgroundSince 1998 the serious public health problem in South East Asia of counterfeit artesunate, containing no or subtherapeutic amounts of the active antimalarial ingredient, has led to deaths from untreated malaria, reduced confidence in this vital drug, large economic losses for the legitimate manufacturers, and concerns that artemisinin resistance might be engendered.Methods and FindingsWith evidence of a deteriorating situation, a group of police, criminal analysts, chemists, palynologists, and health workers collaborated to determine the source of these counterfeits under the auspices of the International Criminal Police Organization (INTERPOL) and the Western Pacific World Health Organization Regional Office. A total of 391 samples of genuine and counterfeit artesunate collected in Vietnam (75), Cambodia (48), Lao PDR (115), Myanmar (Burma) (137) and the Thai/Myanmar border (16), were available for analysis. Sixteen different fake hologram types were identified. High-performance liquid chromatography and/or mass spectrometry confirmed that all specimens thought to be counterfeit (195/391, 49.9%) on the basis of packaging contained no or small quantities of artesunate (up to 12 mg per tablet as opposed to ∼ 50 mg per genuine tablet). Chemical analysis demonstrated a wide diversity of wrong active ingredients, including banned pharmaceuticals, such as metamizole, and safrole, a carcinogen, and raw material for manufacture of methylenedioxymethamphetamine (‘ecstasy’). Evidence from chemical, mineralogical, biological, and packaging analysis suggested that at least some of the counterfeits were manufactured in southeast People’s Republic of China. This evidence prompted the Chinese Government to act quickly against the criminal traders with arrests and seizures.ConclusionsAn international multi-disciplinary group obtained evidence that some of the counterfeit artesunate was manufactured in China, and this prompted a criminal investigation. International cross-disciplinary collaborations may be appropriate in the investigation of other serious counterfeit medicine public health problems elsewhere, but strengthening of international collaborations and forensic and drug regulatory authority capacity will be required.
Partial Text: Malaria still claims over one million lives each year and is a risk for some 40% of the world’s population [1,2]. Most patients with malaria would survive if they had timely access to efficacious medicines that they could afford. With the global spread of drug resistance and the practical difficulties in delivering health care to rural communities, most of those at risk of malaria have not had such access . However, with the development of artemisinin derivative combination therapy (ACT) and international financial support to allow inexpensive or free distribution to those in need, hope of controlling malaria has been rekindled . A major obstacle to malaria control, which has received woefully insignificant attention in the past, is the poor quality of antimalarial medicines available in much of the tropics. The available data strongly suggest that antimalarials have been particularly targeted by counterfeiters, who have deliberately and fraudulently produced copies for profit, usually containing no active ingredients and therefore lacking antimalarial activity .
The Jupiter group of scientists, criminal analysts, and health workers was formed in an attempt to provide information that could be used to control the epidemic of counterfeit artesunate in SE Asia which had not been curbed by pre-existing collaborations and institutions. The forensic evidence suggested that at least some of the counterfeit artesunate were coming from southern China, and that there are at least two origins of this ‘product’—with westerly and easterly origins and Laos in the middle as an area of overlap afflicted by types of both groups. This evidence precipitated a police investigation by the Chinese Government. Shortcomings of the evidence include that the artesunate collections were ad hoc and not collected with a legal chain of evidence and only a small subset of the collection could be analysed due to financial constraints. However, the samples analysed did point to the apparent source of the fakes and it is unlikely that a larger sample size would have changed the outcome.