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The Global Pandemic of Falsified Medicines: Laboratory and Field Innovations and Policy Implications
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

In 2003, a stratified random sample survey was conducted in the Lao People's Democratic Republic (Laos) to study the availability and quality of antimalarials in the private sector. In 2012, this survey was repeated to allow a statistically valid analysis of change through time. The counterfeit detection device 3 (CD-3) was used to assess packaging quality in the field and HPLC and mass spectroscopy analysis chemical analysis performed. The availability of oral artesunate monotherapies had significantly decreased from 22.9% (22) of 96 outlets in southern Laos in 2003 to 4.8% (7) of 144 outlets in 2012 ( < 0.0001). All the samples collected in the 2012 survey contained the correct active pharmaceutical ingredients (APIs) in contrast to the 21 (84%) falsified artesunate samples found in the 2003 survey. Although none of the medicines found in 2012 survey had evidence for falsification, 25.4% (37) of the samples were outside the 90–110% pharmacopeial limits of the label claim, suggesting that they were substandard or degraded. Results obtained from this survey show that patients are still exposed to poorly manufactured drugs or to ineffective medicines such as chloroquine. The quality of artemisinin-based combination therapies (ACTs) used in Laos needs to be monitored, since falsified ACTs would have devastating consequences in public health.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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2015-06-03
2017-11-22
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References

  1. Khan MH, Hatanaka K, Sovannarith T, Nivanna N, Casas LCC, Yoshida N, Tsuboi H, Tanimoto T, Kimura K, , 2013. Effects of packaging and storage conditions on the quality of amoxicillin-clavulanic acid—an analysis of Cambodian samples. BMC Pharmacol Toxicol 14: 33.[Crossref]
  2. Delepierre A, Gayot A, Carpentier A, , 2012. Update on counterfeit antibiotics worldwide; public health risks. Med Mal Infect 42: 247255.[Crossref]
  3. Laserson KF, Kenyon AS, Kenyon TA, Layloff T, Binkin NJ, , 2001. Substandard tuberculosis drugs on the global market and their simple detection. Int J Tuberc Lung Dis 5: 448454.
  4. Newton PN, Tabernero P, Dwivedi P, Culzoni MJ, Monge ME, Swamidoss I, Mildenhall D, Green MD, Jähnke R, de Oliveira M d S, Simao J, White NJ, Fernández FM, , 2014. Falsified medicines in Africa: all talk, no action. The Lancet Global Health 2: e509e510.[Crossref]
  5. Tabernero P, Fernandez F, Green M, Guerin P, Newton PN, , 2014. Mind the gaps—the epidemiology of poor-quality anti-malarials in the malarious world—analysis of the WorldWide Antimalarial Resistance Network database. Malar J 13: 139.[Crossref]
  6. White N, Pongtavornpinyo W, Maude R, Saralamba S, Aguas R, Stepniewska K, Lee S, Dondorp A, White L, Day N, , 2009. Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance. Malar J 8: 253.[Crossref]
  7. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NPJ, Lindegardh N, Socheat D, White NJ, , 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455467.[Crossref]
  8. Dondorp AM, Fairhurst RM, Slutsker L, MacArthur MDJGB, Jr Guerin PJ, Wellems TE, Ringwald P, Newman RD, Plowe CV, , 2011. The threat of artemisinin-resistant malaria. N Engl J Med 365: 10731075.[Crossref]
  9. Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Mao S, Sam B, Sopha C, Chuor CM, Nguon C, Sovannaroth S, Pukrittayakamee S, Jittamala P, Chotivanich K, Chutasmit K, Suchatsoonthorn C, Runcharoen R, Hien TT, Thuy-Nhien NT, Thanh NV, Phu NH, Htut Y, Han K-T, Aye KH, Mokuolu OA, Olaosebikan RR, Folaranmi OO, Mayxay M, Khanthavong M, Hongvanthong B, Newton PN, Onyamboko MA, Fanello CI, Tshefu AK, Mishra N, Valecha N, Phyo AP, Nosten F, Yi P, Tripura R, Borrmann S, Bashraheil M, Peshu J, Faiz MA, Ghose A, Hossain MA, Samad R, Rahman MR, Hasan MM, Islam A, Miotto O, Amato R, MacInnis B, Stalker J, Kwiatkowski DP, Bozdech Z, Jeeyapant A, Cheah PY, Sakulthaew T, Chalk J, Intharabut B, Silamut K, Lee SJ, Vihokhern B, Kunasol C, Imwong M, Tarning J, Taylor WJ, Yeung S, Woodrow CJ, Flegg JA, Das D, Smith J, Venkatesan M, Plowe CV, Stepniewska K, Guerin PJ, Dondorp AM, Day NP, White NJ, , 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411423.[Crossref]
  10. World Health Organization, 2011. Global Plan for Artemisinin Resistance Containment (GPARC). Geneva, Switzerland: WHO, 87. Available at: http://www.who.int/malaria/publications/atoz/9789241500838/en/.
  11. World Health Organization, 2010. Global Report on Antimalarial Efficacy and Drug Resistance: 2000–2010. Available at: http://www.who.int/malaria/publications/atoz/9789241500470/en/.
  12. World Health Organization, 2013. World Malaria Report 2013. Country Profile: Lao People's Democratic Republic. Available at: http://www.who.int/malaria/publications/country-profiles/profile_lao_en.pdf.
  13. Mayxay M, Khanthavong M, Chanthongthip O, Imwong M, Pongvongsa T, Hongvanthong B, Phompida S, Vanisaveth V, White NJ, Newton PN, , 2012. Efficacy of artemether-lumefantrine, the nationally-recommended artemisinin combination for the treatment of uncomplicated falciparum malaria, in southern Laos. Malar J 11: 184.[Crossref]
  14. WHO/MMP and Ministry of Public Health Lao PDR, 2010. National Strategy for Malaria Control and Pre-elimination: Laos PDR 2011–2015. Lao PDR: Ministry of Public Health, 64. Available at: http://apmen.org/storage/country-partner/Lao%20PDR_National%20Strategy%20for%20Malaria%20Control%20and%20Pre-elimination.pdf.
  15. Pongvongsa T, Ha H, Thanh L, Marchand R, Nonaka D, Tojo B, Phongmany P, Moji K, Kobayashi J, , 2012. Joint malaria surveys lead towards improved cross-border cooperation between Savannakhet Province, Laos and Quang Tri Province, Vietnam. Malar J 11: 262.[Crossref]
  16. Jorgensen P, Nambanya S, Gopinath D, Hongvanthong B, Luangphengsouk K, Bell D, Phompida S, Phetsouvanh R, , 2010. High heterogeneity in Plasmodium falciparum risk illustrates the need for detailed mapping to guide resource allocation: a new malaria risk map of the Lao People's Democratic Republic. Malar J 9: 59.[Crossref]
  17. Syhakhang L, Lundborg CS, Lindgren B, Tomson G, , 2004. The quality of drugs in private pharmacies in Lao PDR: a repeat study in 1997 and 1999. Pharm World Sci 26: 333338.[Crossref]
  18. Stenson B, Syhakhang L, Eriksson B, , 2001. Real world pharmacy: assessing the quality of private pharmacy practice in the Lao People's Democratic Republic. Soc Sci Med 52: 393404.[Crossref]
  19. Stenson B, Lindgren BH, Syhakhang L, Tomson G, , 1998. The quality of drugs in private pharmacies in the Lao People's Democratic Republic. International Journal of Risk and Safety in Medicine 11: 243249.
  20. United States Pharmacopeial Convention, 2004. A Review of Drug Quality in Asia with Focus on Anti-Infectives. Drug Quality and Information Program. Available at: http://pdf.usaid.gov/pdf_docs/PNADH154.pdf.
  21. Newton P, Proux S, Green M, Smithuis F, Rozendaal J, Prakongpan S, Chotivanich K, Mayxay M, Looareesuwan S, Farrar J, Nosten F, White NJ, , 2001. Fake artesunate in southeast Asia. Lancet 357: 19481950.[Crossref]
  22. Newton PN, Fernandez FM, Plancon 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, , 2008. A collaborative epidemiological investigation into the criminal fake artesunate trade in south east Asia. PLoS Med 5: e32.[Crossref]
  23. Dondorp AM, Newton PN, Mayxay M, Van Damme W, Smithuis FM, Yeung S, Petit A, Lynam AJ, Johnson A, Hien TT, McGready R, Farrar JJ, Looareesuwan S, Day NP, Green MD, White NJ, , 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 Health 9: 12411246.[Crossref]
  24. Phanouvong S, , 2005. Why Be Concerned About the Quality of Antimalarial and ARV Drugs? Poster presented at the 7th International Congress on AIDS in Asia and the Pacific. Kobe Convention Center, Japan.
  25. Keoluangkhot V, Green MD, Nyadong L, Fernandez FM, Mayxay M, Newton PN, , 2008. Impaired clinical response in a patient with uncomplicated falciparum malaria who received poor-quality and underdosed intramuscular artemether. Am J Trop Med Hyg 78: 552555.
  26. Aldhous P, , 2005. Counterfeit pharmaceuticals: murder by medicine. Nature 434: 132136.[Crossref]
  27. Newton PN, Lee SJ, Goodman C, Fernandez FM, Yeung S, Phanouvong S, Kaur H, Amin AA, Whitty CJM, Kokwaro GO, Lindegardh N, Lukulay P, White LJ, Day NPJ, Green MD, White NJ, , 2009. Guidelines for field surveys of the quality of medicines: a proposal. PLoS Med 6: 252257.[Crossref]
  28. Sengaloundeth S, Green MD, Fernandez FM, Manolin O, Phommavong K, Insixiengmay V, Hampton CY, Nyadong L, Mildenhall DC, Hostetler D, Khounsaknalath L, Vongsack L, Phompida S, Vanisaveth V, Syhakhang L, Newton PN, , 2009. A stratified random survey of the proportion of poor quality oral artesunate sold at medicine outlets in the Lao PDR—implications for therapeutic failure and drug resistance. Malar J 8: 172.[Crossref]
  29. Mayxay M, Khanthavong M, Chanthongthip O, Imwong M, Lee SJ, Stepniewska K, Soonthornsata B, Pongvongsa T, Phompida S, Hongvanthong B, Ringwald P, White NJ, Newton PN, , 2012. No evidence for spread of Plasmodium falciparum artemisinin resistance to Savannakhet Province, southern Laos. Am J Trop Med Hyg 86: 403408.[Crossref]
  30. Ranieri N, Tabernero P, Green MD, Verbois L, Herrington J, Sampson E, Satzger RD, Phonlavong C, Thao K, Newton PN, Witkowski MR, , 2014. Evaluation of a new handheld instrument for the detection of counterfeit artesunate by visual fluorescence comparison. Am J Trop Med Hyg 91: 920924.[Crossref]
  31. Stenson BO, Tomson G, Syhakhang L, , 1997. Pharmaceutical regulation in context: the case of Lao People's Democratic Republic. Health Policy Plan 12: 329339.[Crossref]
  32. World Health Organization, 2014. What Are Substandard Medicines? Essential Medicines and Health Products. Counterfeit Medicines. Frequently asked questions. Available at: http://www.who.int/medicines/services/counterfeit/faqs/06/en/.
  33. Fernandez FM, Hostetler D, Powell K, Kaur H, Green MD, Mildenhall DC, Newton PN, , 2010. Poor quality drugs: grand challenges in high throughput detection, countrywide sampling, and forensics in developing countries. The Royal Society of Chemistry 136: 30733082.
  34. Fernández FM, Cody RB, Green MD, Hampton CY, McGready R, Sengaloundeth S, White NJ, Newton PN, , 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: 702705.[Crossref]
  35. Green MD, Nettey H, Rojas OV, Pamanivong C, Khounsaknalath L, Ortiz MG, Newton PN, Fernández FM, Vongsack L, Manolin O, , 2007. Use of refractometry and colorimetry as field methods to rapidly assess antimalarial drug quality. J Pharm Biomed Anal 43: 105110.[Crossref]
  36. British Pharmacopoeia Comission, 1998. British Pharmacopoeia. The Stationery Office Limited.
  37. European Pharmacopoeia, 2008. European Pharmacopoeia 6.0. 1 1084.
  38. US Pharmacopeia, 2011. Chapter 905: Uniformity of Dosage Units. Available at: http://www.pharmacopeia.cn/v29240/usp29nf24s0_c905.html. Accessed February 27, 2014.
  39. United States Pharmacopeial Convention, 2003. The United States Pharmacopeia. The National Formulary.
  40. World Health Organization, 2006. The International Pharmacopoeia [online]. 4th edition.
  41. Newton PN, Hampton CY, Alter-Hall K, Teerwarakulpana T, Prakongpan S, Ruangveerayuth R, White NJ, Day NPJ, Tudino MB, Mancuso N, Fernandez FM, , 2008. Characterization of “Yaa Chud” medicine on the Thailand-Myanmar border: selecting for drug-resistant malaria and threatening public health. Am J Trop Med Hyg 79: 662669.
  42. WHO, 2013. WHO project for the surveillance and monitoring of SSFFC medical products. Quality and safety of medicines. WHO Drug Information, 115. Available at: http://www.who.int/medicines/publications/druginformation/issues/DrugInformation2013_Vol27-2/en/index.html.
  43. World Health Organization, 2014. Rapid Alert System for Combating Counterfeit Medicines. WHO Western Pacific Region. Available at: http://www.counterfeitmedalert.info/.
  44. Tabernero P, Newton PN, , 2012. The WWARN antimalarial quality surveyor. Pathogens and Global Health 106: 7778.[Crossref]
  45. United States Pharmacopeial Convention, 2009. Country Report on Medicines Quality Monitoring Program in Laos (2005–2009). PQM: Promoting the Quality of Medicines in Developing Countries. Available at: http://www.usp.org/app/worldwide/medQualityDatabase/documents.html.
  46. The Global Fund to Fight AIDS Tuberculosis and Malaria, 2012. Audit of Global Fund Grants to the Lao People's Democratic Republic. The Office of the Inspector General, GF-OIG-10-012. Available at: http://www.theglobalfund.org/documents/oig/OIG_GFOIG10012AuditLao_Report_en/.
  47. The Global Fund to Fight AIDS Tuberculosis and Malaria, 2006. Six Call for Proposals. Country Coordinating Mechanism Lao PDR. Available at: http://www.theglobalfund.org/en/publications/.
  48. Ratanawijitrasin S, Phanouvong S, Hartmann A, Moreau L-A, , 2014. The State of Medicine Quality in the Mekong Sub-Region in the 2000s and the Challenges Ahead. , ed. Institut de Recherche sur l'Asie du Sud-Est Contemporaine (IRASEC). Available at: http://www.irasec.com/ouvrage115.
  49. Torres C, , 2010. Counterfeiting goes cinematic in public campaigns. Nat Med 16: 363.[Crossref]
  50. World Health Organization, 2003. WHO launches campaign against counterfeit medicines. Bull World Health Organ 81: 921922.
  51. Burns W, , 2006. WHO launches taskforce to fight counterfeit drugs. Bull World Health Organ 84: 689690.
  52. World Health Organization, 2008. Counterfeit Drugs Kill IMPACT. Available at: http://www.who.int/impact/FinalBrochureWHA2008a.pdf?ua=1.
  53. Venhuis BJ, Zwaagstra ME, Keizers PHJ, de Kaste D, , 2014. Dose-to-dose variations with single packages of counterfeit medicines and adulterated dietary supplements as a potential source of false negatives and inaccurate health risk assessments. J Pharm Biomed Anal 89: 158165.[Crossref]
  54. Phetsouvanh R, Phongmany S, Newton P, Mayxay M, Ramsay A, Wuthiekanun V, White NJ, , 2001. Melioidosis and Pandora's box in the Lao People's Democratic Republic. Clin Infect Dis 32: 653654.[Crossref]
  55. AccessRx.com Hiers M, , 2012. Most Popular Countries for Counterfeit Viagra and How to Protect Yourself. , ed. Available at: http://www.accessrx.com/blog/erectile-dysfunction/viagra/most-popular-countries-for-counterfeit-viagra-m1102/.
  56. Frosch AEP, Laufer MK, Mathanga DP, Takala-Harrison S, Skarbinski J, Claassen CW, Dzinjalamala FK, Plowe CV, , 2014. Return of widespread chloroquine-sensitive Plasmodium falciparum to Malawi. J Infect Dis 210: 11101114.[Crossref]
  57. World Health Organization, 2010. Guidelines for the Treatment of Malaria, 2nd Edition. Geneva, Switzerland: WHO, 194. Available at: http://www.who.int/malaria/publications/atoz/9789241547925/en/.
  58. Ravinetto RM, Boelaert M, Jacobs J, Pouget C, Luyckx C, , 2012. Poor-quality medical products: time to address substandards, not only counterfeits. Trop Med Int Health 17: 14121416.[Crossref]
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  • Received : 21 Jan 2015
  • Accepted : 03 Apr 2015

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