A collaborative epidemiological investigation into the criminal fake artesunate trade in South East Asia.
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.
Newton
Paul N
PN
Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom. paul@tropmedres.ac
Fernández
Facundo M
FM
Plançon
Aline
A
Mildenhall
Dallas C
DC
Green
Michael D
MD
Ziyong
Li
L
Christophel
Eva Maria
EM
Phanouvong
Souly
S
Howells
Stephen
S
McIntosh
Eric
E
Laurin
Paul
P
Blum
Nancy
N
Hampton
Christina Y
CY
Faure
Kevin
K
Nyadong
Leonard
L
Soong
C W Ray
CW
Santoso
Budiono
B
Zhiguang
Wang
W
Newton
John
J
Palmer
Kevin
K
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
D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate