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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.

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 ∼ 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.


Vyšlo v časopise: A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia. PLoS Med 5(2): e32. doi:10.1371/journal.pmed.0050032
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.0050032

Souhrn

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 ∼ 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.


Zdroje

1. World Health Organisation

2006

World Malaria Report – 2005

Available: http://www.rbm.who.int/wmr2005/html/1–2.htm. Accessed 22 July 2007.

2. Anon

2007

Malaria. World Health Organisation Media Centre

Available: http://www.who.int/mediacentre/factsheets/fs094/en/index.html. Accessed 10 August 2007.

3. ArrowKJPanosianCBGelbandH

2004

Saving lives, buying time: economics of malaria drugs in an age of resistance

Washington (DC)

Institute of Medicine of the National Academies

Available: http://www.nap.edu/books/0309092183/html/. Accessed 5 August 2007.

4. NewtonPNGreenMDFernándezFMDayNJPWhiteNJ

2006

Counterfeit anti-infective medicines.

Lancet Infect Dis

6

602

613

5. World Health Organisation

2006

WHO guidelines for the treatment of malaria

Geneva

WHO

Available: www.who.int/malaria/docs/TreatmentGuidelines2006.pdf. Accessed 26 January 2006.

6. Anon.

Table recording ACT producers – Artepal Project

Available: http://www.artepal.org/index.php?option=com_docman&task=doc_download&gid=13&Itemid=60. Accessed 5 August 2007.

7. RozendaalJ

2000

Fake antimalarials circulating in Cambodia.

Bull Mekong Malaria Forum

7

62

68

8. NewtonPNProuxSGreenMSmithuisFRozendaalJ

2001

Fake artesunate in southeast Asia.

Lancet

357

1948

1950

9. NewtonPNDondorpAMGreenMMayxayMWhiteNJ

2003

Counterfeit artesunate antimalarials.

Lancet

362

169

10. NewtonPNMcGreadyRFernándezFGreenMDSunjioM

2006

Manslaughter by fake artesunate in Asia—will Africa be next.

PLoS Medicine

3

e197

doi:10.1371/journal.pmed.0030197

11. DondorpAMNewtonPNMayxayMVan DammeWSmithuisFM

2004

Fake antimalarials in Southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials.

Trop Med Int Hlth

9

1241

1246

12. LonCTTsuyuokaRPhanouvongSNivannaNSocheatC

2006

Counterfeit and substandard antimalarial drugs in Cambodia.

Trans R Soc Trop Med Hyg

100

1019

1024

13. HallKANewtonPNGreenMDDe VeijMVandenaabeleP

2006

Characterization of counterfeit artesunate antimalarial tablets from southeast Asia.

Am J Trop Med Hyg

75

804

811

14. USP

2004

Fake antimalarials found in Yunnan Province, China, 2004

Available: http://www.usp.org/pdf/EN/dqi/yunnanTesting.pdf. Accessed 2 September 2007.

15. OyeniranM

NAFDAC seizes N3M malaria drugs. Nigeria Tribune 2006 Sept 28

Available: http://www.tribune.com.ng/28092006/news/news13.html. Accessed 3 November 2006.

16. AtemnkengMADe CockKPlaizier-VercammenJ

2007

Quality control of active ingredients in artemisinin derivative antimalarials within Kenya and DR Congo.

Trop Med Int Hlth

12

68

74

17. [No authors listed]

2007

Malaria drugs recalled in Kenya

Available: http://news.bbc.co.uk/1/hi/world/africa/6951586.stm. Accessed 20 August 2007.

18. HaysSIGuerraCATatemAJNoorAMSnowRW

2004

The global distribution and population at risk of malaria: past, present, and future.

Lancet Infect Dis

4

327

336

19. World Health Organisation Regional Office for the Western Pacific

2005

Dealers in death. Video documentary.

A film by Harrikrisna Anenden

A WHO production

Manila

Available: http://www.wpro.who.int/sites/mvp/documents/dealersindeath.htm. Accessed 2 September 2007.

20. GreenMDDwightLMWirtzRAWhiteNJ

2000

A colorimetric field method to assess the authenticity of drugs sold as the antimalarial artesunate.

J Pharm Biomed Anal

24

65

70

21. FernándezFMCodyRBGreenMDHamptonCYMcGreadyR

2006

Characterization of solid counterfeit drug samples by desorption electrospray ionization and direct-analysis-in-real-time coupled to time-of-flight mass spectrometry.

ChemMedChem

1

702

705

22. NyadongLGreenMDDe JesusVRNewtonPNFernándezFM

2007

Reactive desorption electrospray ionization linear ion trap mass spectrometry of latest-generation counterfeit antimalarials via noncovalent complex formation.

Anal Chem

79

2150

2157

23. RicciCNyadongLFernándezFMNewtonPNKazarianSG

2007

Combined fourier transform infrared imaging and desorption electrospray ionization linear ion trap mass spectrometry for the analysis of counterfeit antimalarial tablets.

Anal Bioanalytic Chem

387

551

559

24. de VeijMVandenabeelePHallKAFernándezFMGreenMD

2007

Fast detection and identification of counterfeit antimalarial tablets by Raman spectroscopy.

J Raman Spectrosc

38

181

187

25. GreenMDNetteyHVillalva-RojasOPamanivangCKhounsaknalathL

2007

Use of refractometry and colorimetry as field methods to rapidly assess antimalarial drug quality.

J Pharm Biomed Anal

43

105

110

26. McCreaJM

1950

On the isotopic chemistry of carbonates and palaeo-temperature scale.

J Chem Physics

18

849

857

27. HoefsJ

1996

Stable isotope geochemistry, 4th edition

New York

Springer-Verlag

201

28. HuangTC

1972

Pollen flora of Taiwan

Tapei

Ching-Hwa Press Co. Ltd

222

29. HuangTC

1981

Spore flora of Taiwan

Taipei

Tah-Jinn Press Co. Ltd

111

30. WangFSChienHFZhangYLYangHQ

1995

Pollen flora of China, 2nd edition

Beijing

Institute of Botany, Academia Sinica

461

31. BulalacaoLJ

1997

Pollen flora of the Philippines volume 1

Taguig Metro Manila

Department of Science and Technology

266

32. YeSTQiaoBSWangLGYinJNiuZP

2004

Color atlas of air-borne pollens and plants in China

Beijing

Peking Union Medical College Press

385

33. HeywoodVH

1978

Flowering plants of the world

Oxford

Oxford University Press

335

34. United Nations

1988

United Nations convention against illicit traffic in narcotic drugs and psychotropic substances

Available: http://www.unodc.org/pdf/convention_1988_en.pdf. Accessed 11 August 2007.

35. ChenDZQingHRYangC

2004

Multistage hydrothermal dolomites in the Middle Devonian (Givetian) carbonates from the Guilin area, South China.

Sedimentology

51

1029

1051

36. International Agency for Research on Cancer

2007

Overall evaluations of carcinogenicity to humans

Available: http://monographs.iarc.fr/ENG/Classification/crthalllist.php. Accessed 11 August 2007.

37. MildenhallDC

1990

Forensic palynology in New Zealand.

Rev Palaeobot Palynol

64

227

234

38. MilneLABryantVMMildenhallDC

2004

Forensic palynology.

In:

CoyleHM

Forensic botany

Boca Raton, USA

CRC Press

217

252

39. BryantVMJonesJGMildenhallDC

1996

Forensic studies in palynology.

In:

JansoniusJMcGregorDC

Palynology: principles and applications

Am Assoc Strat Palynol Found

3

957

959

40. StanleyEA

1992

Application of palynology to establish the provenance and travel history of illicit drugs.

Microscope

40

149

152

41. LiuXWangJYWangQF

2005

Current status and conservation strategies for Isoetes in China: a case study for the conservation of threatened aquatic plants.

Oryx

39

335

338

42. Anon.

GlaxoSmithKline case study (7 April 2003). Judicial Protection of IPR in China

Available: http://www.chinaiprlaw.com/english/news/news14.htm. Accessed 5 August 2007.

43. AminAAKokwaroGO

2007

Antimalarial drug quality in Africa.

J Clin Pharm Ther

32

429

440

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