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



Widespread availability of monotherapies and falsified antimalarials is thought to have contributed to the historical development of multidrug-resistant malaria in Cambodia. This study aimed to document the quality of artemisinin-containing antimalarials (ACAs) and to compare two methods of collecting antimalarials from drug outlets: through open surveyors and mystery clients (MCs). Few oral artemisinin-based monotherapies and no suspected falsified medicines were found. All 291 samples contained the stated active pharmaceutical ingredient (API) of which 69% were considered good quality by chemical analysis. Overall, medicine quality did not differ by collection method, although open surveyors were less likely to obtain oral artemisinin-based monotherapies than MCs. The results are an encouraging indication of the positive impact of the country's efforts to tackle falsified antimalarials and artemisinin-based monotherapies. However, poor-quality medicines remain an ongoing challenge that demands sustained political will and investment of human and financial resources.

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  1. Wongsrichanalai C, Meshnick SR, , 2008. Declining artesunate-mefloquine efficacy against falciparum malaria on the Cambodia–Thailand border. Emerg Infect Dis 14: 716719.[Crossref]
  2. Yeung S, Patouillard E, Allen H, Socheat D, , 2011. Socially marketed rapid diagnostic tests and ACT in the private sector: ten years of experience in Cambodia. Malar J 10: 243.[Crossref]
  3. Yanagisawa S, Mey V, Wakai S, , 2004. Comparison of health-seeking behaviour between poor and better-off people after health sector reform in Cambodia. Public Health 118: 2130.[Crossref]
  4. Rozendaal J, , 2000. Fake antimalarials circulated in Cambodia. Mekong Malaria Forum 7: 6268.
  5. Cambodia National Malaria Control Programme. Annual Progress Reports 2009–2014. Phnom Penh, Cambodia: Ministry of Health of Cambodia.
  6. Littrell M, Gatakaa H, Phok S, Allen H, Yeung S, Chuor CM, Dysoley L, Socheat D, Spiers A, White C, Shewchuk T, Chavasse D, O'Connell KA, , 2011. Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys. Malar J 10: 328.[Crossref]
  7. Noedl H, Socheat D, Satimai W, , 2009. Artemisinin-resistant malaria in Asia. N Engl J Med 361: 540541.[Crossref]
  8. 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 NP, Lindegardh N, Socheat D, White NJ, , 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455467.[Crossref]
  9. Miotto O, Almagro-Garcia J, Manske M, Macinnis B, Campino S, Rockett KA, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Duong S, Nguon C, Chuor CM, Saunders D, Se Y, Lon C, Fukuda MM, Amenga-Etego L, Hodgson AV, Asoala V, Imwong M, Takala-Harrison S, Nosten F, Su XZ, Ringwald P, Ariey F, Dolecek C, Hien TT, Boni MF, Thai CQ, Amambua-Ngwa A, Conway DJ, Djimde AA, Doumbo OK, Zongo I, Ouedraogo JB, Alcock D, Drury E, Auburn S, Koch O, Sanders M, Hubbart C, Maslen G, Ruano-Rubio V, Jyothi D, Miles A, O'Brien J, Gamble C, Oyola SO, Rayner JC, Newbold CI, Berriman M, Spencer CC, McVean G, Day NP, White NJ, Bethell D, Dondorp AM, Plowe CV, Fairhurst RM, Kwiatkowski DP, , 2013. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nat Genet 45: 648655.[Crossref]
  10. Degardin K, Roggo Y, Margot P, , 2014. Understanding and fighting the medicine counterfeit market. J Pharm Biomed Anal 87: 167175.[Crossref]
  11. Newton PN, Green MD, Fernandez FM, Day NP, White NJ, , 2006. Counterfeit anti-infective drugs. Lancet Infect Dis 6: 602613.[Crossref]
  12. Affum AO, Lowor S, Osae SD, Dickson A, Gyan BA, Tulasi D, , 2013. A pilot study on quality of artesunate and amodiaquine tablets used in the fishing community of Tema, Ghana. Malar J 12: 220.[Crossref]
  13. Pincock S, , 2003. WHO tries to tackle problem of counterfeit medicines in Asia. BMJ 327: 1126.[Crossref]
  14. Cockburn R, Newton PN, Agyarko EK, Akunyili D, White NJ, , 2005. The global threat of counterfeit drugs: why industry and governments must communicate the dangers. PLoS Med 2: e100.[Crossref]
  15. Newton PN, Green MD, Fernandez FM, , 2010. Impact of poor-quality medicines in the ‘developing’ world. Trends Pharmacol Sci 31: 99101.[Crossref]
  16. Hall KA, Newton PN, Green MD, De Veij M, Vandenabeele P, Pizzanelli D, Mayxay M, Dondorp A, Fernandez FM, , 2006. Characterization of counterfeit artesunate antimalarial tablets from southeast Asia. Am J Trop Med Hyg 75: 804811.
  17. Onwujekwe O, Kaur H, Dike N, Shu E, Uzochukwu B, Hanson K, Okoye V, Okonkwo P, , 2009. Quality of anti-malarial drugs provided by public and private healthcare providers in south-east Nigeria. Malar J 8: 22.[Crossref]
  18. Newton PN, McGready R, Fernandez F, Green MD, Sunjio M, Bruneton C, Phanouvong S, Millet P, Whitty CJ, Talisuna AO, Proux S, Christophel EM, Malenga G, Singhasivanon P, Bojang K, Kaur H, Palmer K, Day NP, Greenwood BM, Nosten F, White NJ, , 2006. Manslaughter by fake artesunate in Asia–will Africa be next? PLoS Med 3: e197.[Crossref]
  19. 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]
  20. 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]
  21. Lon CT, Tsuyuoka R, Phanouvong S, Nivanna N, Socheat D, Sokhan C, Blum N, Christophel EM, Smine A, , 2006. Counterfeit and substandard antimalarial drugs in Cambodia. Trans R Soc Trop Med Hyg 100: 10191024.[Crossref]
  22. 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]
  23. 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 southeast Asia. PLoS Med 5: e32.[Crossref]
  24. Aldhous P, , 2005. Counterfeit pharmaceuticals: murder by medicine. Nature 434: 132136.[Crossref]
  25. WHO, 2010. World Malaria Report 2010. Geneva, Switzerland: World Health Organization.
  26. WHO, 2011. Global Plan for Artemisinin Resistance Containment (GPARC). Geneva, Switzerland: World Health Organization.
  27. Odeniyi MA, Adegoke OA, Adereti RB, Odeku OA, Itiola OA, , 2003. Comparative analysis of eight brands of sulfadoxinepyrimethamine tablets. Trop J Pharm Res 2: 161167.
  28. Newton PN, Lee SJ, Goodman C, Fernandez FM, Yeung S, Phanouvong S, Kaur H, Amin AA, Whitty CJ, Kokwaro GO, Lindegardh N, Lukulay P, White LJ, Day NP, Green MD, White NJ, , 2009. Guidelines for field surveys of the quality of medicines: a proposal. PLoS Med 6: e52.[Crossref]
  29. Yeung S, Chandler C, Taberno P, de Souza M, Rada O, Ngoun C, , 2011. Good use of anti-malarials and rapid diagnostic tests in Cambodia (Guard) study report. London, UK: Artemsinin Combination Therapy (ACT) Consortium.
  30. 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]
  31. Phanouvong SBN, Smine A, , 2004. Guidelines for Sampling of Antimalarial Drug Samples in the USP DQI Antimalarial Drug Quality Monitoring Project in Mekong Sub-Region Countries. Rockville, MD: United States Pharmacopeia.
  32. Phanouvong S, Raymond C, Krech L, Dijiba Y, Mam B, Lukulay P, Socheat D, Sovannarith T, Sokhan C, , 2013. The quality of antimalarial medicines in western Cambodia: a case study along the Thai-Cambodian border. Southeast Asian J Trop Med Public Health 44: 349362.
  33. Taylor RB, Shakoor O, Behrens RH, Everard M, Low AS, Wangboonskul J, Reid RG, Kolawole JA, , 2001. Pharmacopoeial quality of drugs supplied by Nigerian pharmacies. Lancet 357: 19331936.[Crossref]
  34. Kaur H, Goodman C, Thompson E, Thompson KA, Masanja I, Kachur SP, Abdulla S, , 2008. A nationwide survey of the quality of antimalarials in retail outlets in Tanzania. PLoS ONE 3: e3403.[Crossref]
  35. Ogwal-Okeng JW, Okello DO, Odyek O, , 1998. Quality of oral and parenteral chloroquine in Kampala. East Afr Med J 75: 692694.
  36. Pribluda VS, Barojas A, Anez A, Lopez CG, Figueroa R, Herrera R, Nakao G, Nogueira FH, Pianetti GA, Povoa MM, Viana GM, Gomes MS, Escobar JP, Sierra OL, Norena SP, Veloz R, Bravo MS, Aldas MR, Hindssemple A, Collins M, Ceron N, Krishnalall K, Adhin M, Bretas G, Hernandez N, Mendoza M, Smine A, Chibwe K, Lukulay P, Evans L, 3rd, 2012. Implementation of basic quality control tests for malaria medicines in Amazon Basin countries: results for the 2005–2010 period. Malar J 11: 202.[Crossref]
  37. Newton PN, Green MD, Mildenhall DC, Plancon A, Nettey H, Nyadong L, Hostetler DM, Swamidoss I, Harris GA, Powell K, Timmermans AE, Amin AA, Opuni SK, Barbereau S, Faurant C, Soong RC, Faure K, Thevanayagam J, Fernandes P, Kaur H, Angus B, Stepniewska K, Guerin PJ, Fernandez FM, , 2011. Poor quality vital anti-malarials in Africa: an urgent neglected public health priority. Malar J 10: 352.[Crossref]
  38. 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.
  39. Nogueira FH, Moreira-Campos LM, Santos RL, Pianetti GA, , 2011. Quality of essential drugs in tropical countries: evaluation of antimalarial drugs in the Brazilian Health System. Rev Soc Bras Med Trop 44: 582586.[Crossref]
  40. Caudron JM, Ford N, Henkens M, Mace C, Kiddle-Monroe R, Pinel J, , 2008. Substandard medicines in resource-poor settings: a problem that can no longer be ignored. Trop Med Int Health 13: 10621072.[Crossref]
  41. Tabernero P, Newton PN, , 2012. The WWARN antimalarial quality surveyor. Pathog Glob Health 106: 7778.[Crossref]
  42. Yeung S, Van Damme W, Socheat D, White NJ, Mills A, , 2008. Access to artemisinin combination therapy for malaria in remote areas of Cambodia. Malar J 7: 96.[Crossref]
  43. Haynes RK, Chan HW, Lung CM, Ng NC, Wong HN, Shek LY, Williams ID, Cartwright A, Gomes MF, , 2007. Artesunate and dihydroartemisinin (DHA): unusual decomposition products formed under mild conditions and comments on the fitness of DHA as an antimalarial drug. ChemMedChem 2: 14481463.[Crossref]
  44. Tawfik L, , 2005. Mosquitoes, Malaria and Malarine: A Qualitative Study on Malaria Drug Use in Cambodia. Arlington, VA: Rational Pharmaceutical Management Plus, Management Sciences for Health.
  45. Khol V, Mao B, Saphonn V, An U, Bruce J, Meek S, Lines J, Cox J, , 2005. Report of the Cambodia National Malaria Baseline Survey, 2004. Phnom Penh, Cambodia: National Institute of Health, Cambodia (NIPH) and Malaria Consortium.
  46. Dysoley L, Rithea L, Bunkea T, Babu S, Sim K, Nguon C, Sochea D, Thompson M, Bruce J, de Beyl CZ, Cox J, Sintasath D, Meek S, , 2010. Cambodia Malaria Survey Report. Phnom Penh, Cambodia: National Institute of Health, Cambodia (NIPH) and Malaria Consortium.
  47. An SU, Mao B, Saphonn V, Bruce J, Meek S, Lines J, Cox J, , 2007. Cambodia Malaria Survey Report. Phnom Penh, Cambodia: National Institute of Health, Cambodia (NIPH) and Malaria Consortium.
  48. PSI, 2011. Kingdom of Cambodia Outlet Survey Report. Washington, DC: ACTwatach Group and Population Services International Cambodia.
  49. Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, Chhaganlal KD, Bojang K, Olaosebikan R, Anunobi N, Maitland K, Kivaya E, Agbenyega T, Nguah SB, Evans J, Gesase S, Kahabuka C, Mtove G, Nadjm B, Deen J, Mwanga-Amumpaire J, Nansumba M, Karema C, Umulisa N, Uwimana A, Mokuolu OA, Adedoyin OT, Johnson WB, Tshefu AK, Onyamboko MA, Sakulthaew T, Ngum WP, Silamut K, Stepniewska K, Woodrow CJ, Bethell D, Wills B, Oneko M, Peto TE, von Seidlein L, Day NP, White NJ, , 2010. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet 376: 16471657.[Crossref]
  50. Dondorp A, Nosten F, Stepniewska K, Day N, White N, , 2005. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 366: 717725.[Crossref]
  51. Bate R, Jin GZ, Mathur A, , 2011. Does price reveal poor-quality drugs? Evidence from 17 countries. J Health Econ 30: 11501163.[Crossref]
  52. Bate R, Jin GZ, Mathur A, , 2012. Counterfeit or Substandard? Assessing Price and Non-Price Signals of Drug Quality. Cambridge, MA: National Bureau of Economic Research.[Crossref]
  53. El-Duah M, Ofori-Kwakye K, , 2012. Substandard artemisinin-based antimalarial medicines in licensed retail pharmaceutical outlets in Ghana. J Vector Borne Dis 49: 131139.
  54. Talisuna AO, Karema C, Ogutu B, Juma E, Logedi J, Nyandigisi A, Mulenga M, Mbacham WF, Roper C, Guerin PJ, D'Alessandro U, Snow RW, , 2012. Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems. Lancet Infect Dis 12: 888896.[Crossref]
  55. Nayyar GM, Breman JG, Newton PN, Herrington J, , 2012. Poor-quality antimalarial drugs in southeast Asia and sub-Saharan Africa. Lancet Infect Dis 12: 488496.[Crossref]
  56. Fernandez FM, Hostetler D, Powell K, Kaur H, Green MD, Mildenhall DC, Newton PN, , 2011. Poor quality drugs: grand challenges in high throughput detection, countrywide sampling, and forensics in developing countries. Analyst (Lond) 136: 30733082.[Crossref]
  57. Ioset JR, Kaur H, , 2009. Simple field assays to check quality of current artemisinin-based antimalarial combination formulations. PLoS ONE 4: e7270.[Crossref]
  58. Deisingh AK, , 2005. Pharmaceutical counterfeiting. Analyst (Lond) 130: 271279.[Crossref]
  59. Bate R, Hess K, , 2010. Anti-malarial drug quality in Lagos and Accra—a comparison of various quality assessments. Malar J 9: 157.[Crossref]
  60. Bate R, Tren R, Mooney L, Hess K, Mitra B, Debroy B, Attaran A, , 2009. Pilot study of essential drug quality in two major cities in India. PLoS ONE 4: e6003.[Crossref]

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  • Received : 25 Jun 2014
  • Accepted : 07 Dec 2014

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