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A collaborative epidemiological investigation into the criminal fake artesunate trade in South East Asia.

Newton PN, Fernández FM, Plançon A, Mildenhall DC, Green MD, Ziyong L, Christophel EM, Phanouvong S, Howells S, McIntosh E, Laurin P, Blum N, Hampton CY, Faure K, Nyadong L, Soong CW, Santoso B, Zhiguang W, Newton J, Palmer K - PLoS Med. (2008)

Bottom Line: 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.An international multi-disciplinary group obtained evidence that some of the counterfeit artesunate was manufactured in China, and this prompted a criminal investigation.

View Article: PubMed Central - PubMed

Affiliation: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom. paul@tropmedres.ac

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.

Methods and findings: 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.

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Examples of Genuine and Counterfeit Holograms(A) Genuine Guilin Pharmaceutical artesunate blister pack hologram.(B) A type 2 sticker copy.(C) A type 10 hologram copy with the fake ‘X-52′ stamp as seen under UV light.(D) Type 15 hologram copy from the seized counterfeit artesunate from the China/Myanmar border.For a full description of the 16 types of fake packaging see Figure S1 (updated from [10]). Types 15 and 16 have been only recently described and were not included in the pre-seizure analysis presented here. Photographs by Paul Newton.
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pmed-0050032-g002: Examples of Genuine and Counterfeit Holograms(A) Genuine Guilin Pharmaceutical artesunate blister pack hologram.(B) A type 2 sticker copy.(C) A type 10 hologram copy with the fake ‘X-52′ stamp as seen under UV light.(D) Type 15 hologram copy from the seized counterfeit artesunate from the China/Myanmar border.For a full description of the 16 types of fake packaging see Figure S1 (updated from [10]). Types 15 and 16 have been only recently described and were not included in the pre-seizure analysis presented here. Photographs by Paul Newton.

Mentions: Since 1998 an epidemic of multiple types of counterfeit artesunate tablets, both primitive and highly sophisticated copies, have affected patients with malaria in mainland SE Asia (Figures 1, 2, and S1). Ad hoc surveys since 2000 in Burma (Myanmar), the Thai/Myanmar border, the Lao People's Democratic Republic (Lao PDR, Laos), Cambodia, and Vietnam, the most malarious countries in mainland SE Asia, suggested that 33%–53% of bought artesunate was counterfeit, containing either no or subtherapeutic quantities of artesunate (Figure 1) [7–13]. In Thailand, which has only a small number of malaria cases, the threat of counterfeit artesunate has been largely averted: such counterfeits have only been described from the central Thai/Myanmar border area around the Western border town of Mae Sot. Counterfeit artesunate has been recently described from southern China [14]. In Asia the product of one major producer of artesunate, Guilin Pharmaceutical (Guilin, Guangxi autonomous region, China), has been exclusively targeted. The recent description of counterfeit artemisinin derivatives in four sub-Saharan African countries is of enormous public health concern [10,15–17].


A collaborative epidemiological investigation into the criminal fake artesunate trade in South East Asia.

Newton PN, Fernández FM, Plançon A, Mildenhall DC, Green MD, Ziyong L, Christophel EM, Phanouvong S, Howells S, McIntosh E, Laurin P, Blum N, Hampton CY, Faure K, Nyadong L, Soong CW, Santoso B, Zhiguang W, Newton J, Palmer K - PLoS Med. (2008)

Examples of Genuine and Counterfeit Holograms(A) Genuine Guilin Pharmaceutical artesunate blister pack hologram.(B) A type 2 sticker copy.(C) A type 10 hologram copy with the fake ‘X-52′ stamp as seen under UV light.(D) Type 15 hologram copy from the seized counterfeit artesunate from the China/Myanmar border.For a full description of the 16 types of fake packaging see Figure S1 (updated from [10]). Types 15 and 16 have been only recently described and were not included in the pre-seizure analysis presented here. Photographs by Paul Newton.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2235893&req=5

pmed-0050032-g002: Examples of Genuine and Counterfeit Holograms(A) Genuine Guilin Pharmaceutical artesunate blister pack hologram.(B) A type 2 sticker copy.(C) A type 10 hologram copy with the fake ‘X-52′ stamp as seen under UV light.(D) Type 15 hologram copy from the seized counterfeit artesunate from the China/Myanmar border.For a full description of the 16 types of fake packaging see Figure S1 (updated from [10]). Types 15 and 16 have been only recently described and were not included in the pre-seizure analysis presented here. Photographs by Paul Newton.
Mentions: Since 1998 an epidemic of multiple types of counterfeit artesunate tablets, both primitive and highly sophisticated copies, have affected patients with malaria in mainland SE Asia (Figures 1, 2, and S1). Ad hoc surveys since 2000 in Burma (Myanmar), the Thai/Myanmar border, the Lao People's Democratic Republic (Lao PDR, Laos), Cambodia, and Vietnam, the most malarious countries in mainland SE Asia, suggested that 33%–53% of bought artesunate was counterfeit, containing either no or subtherapeutic quantities of artesunate (Figure 1) [7–13]. In Thailand, which has only a small number of malaria cases, the threat of counterfeit artesunate has been largely averted: such counterfeits have only been described from the central Thai/Myanmar border area around the Western border town of Mae Sot. Counterfeit artesunate has been recently described from southern China [14]. In Asia the product of one major producer of artesunate, Guilin Pharmaceutical (Guilin, Guangxi autonomous region, China), has been exclusively targeted. The recent description of counterfeit artemisinin derivatives in four sub-Saharan African countries is of enormous public health concern [10,15–17].

Bottom Line: 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.An international multi-disciplinary group obtained evidence that some of the counterfeit artesunate was manufactured in China, and this prompted a criminal investigation.

View Article: PubMed Central - PubMed

Affiliation: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom. paul@tropmedres.ac

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.

Methods and findings: 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.

Show MeSH
Related in: MedlinePlus