title: A collaborative epidemiological investigation into the criminal fake artesunate trade in South East Asia.
abstract: BACKGROUND
  Since 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.
  
  
  RESULTS
  With 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 approximately 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.
  
  
  CONCLUSIONS
  An 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.
authors.affiliation: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom. paul@tropmedres.ac
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Fernández
authors.forename: Aline
authors.initials: A
authors.lastname: Plançon
authors.forename: Dallas C
authors.initials: DC
authors.lastname: Mildenhall
authors.forename: Michael D
authors.initials: MD
authors.lastname: Green
authors.forename: Li
authors.initials: L
authors.lastname: Ziyong
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Christophel
authors.forename: Souly
authors.initials: S
authors.lastname: Phanouvong
authors.forename: Stephen
authors.initials: S
authors.lastname: Howells
authors.forename: Eric
authors.initials: E
authors.lastname: McIntosh
authors.forename: Paul
authors.initials: P
authors.lastname: Laurin
authors.forename: Nancy
authors.initials: N
authors.lastname: Blum
authors.forename: Christina Y
authors.initials: CY
authors.lastname: Hampton
authors.forename: Kevin
authors.initials: K
authors.lastname: Faure
authors.forename: Leonard
authors.initials: L
authors.lastname: Nyadong
authors.forename: C W Ray
authors.initials: CW
authors.lastname: Soong
authors.forename: Budiono
authors.initials: B
authors.lastname: Santoso
authors.forename: Wang
authors.initials: W
authors.lastname: Zhiguang
authors.forename: John
authors.initials: J
authors.lastname: Newton
authors.forename: Kevin
authors.initials: K
authors.lastname: Palmer
mesh_terms: D019306:Artemisia / Q000737:chemistry*; D037621:Artemisinins / Q000032:analysis* / Q000737:chemistry* / Q000627:therapeutic use; D000077332:Artesunate; D001210:Asia, Southeastern / Q000453:epidemiology; D004340:Drug Contamination / Q000331:legislation & jurisprudence / Q000517:prevention & control; D005607:Fraud / Q000331:legislation & jurisprudence* / Q000517:prevention & control; D006801:Humans; D038622:Internationality / Q000331:legislation & jurisprudence*; D008288:Malaria / Q000188:drug therapy / Q000453:epidemiology; D012717:Sesquiterpenes / Q000032:analysis* / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate