1921
The Global Pandemic of Falsified Medicines: Laboratory and Field Innovations and Policy Implications
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

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.

[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.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.14-0391
2015-06-03
2019-01-17
Loading full text...

Full text loading...

/deliver/fulltext/14761645/92/6_Suppl/39.html?itemId=/content/journals/10.4269/ajtmh.14-0391&mimeType=html&fmt=ahah

References

  1. Wongsrichanalai C, Meshnick SR, , 2008. Declining artesunate-mefloquine efficacy against falciparum malaria on the Cambodia–Thailand border. Emerg Infect Dis 14: 716719.[Crossref] [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  4. Rozendaal J, , 2000. Fake antimalarials circulated in Cambodia. Mekong Malaria Forum 7: 6268. [Google Scholar]
  5. Cambodia National Malaria Control Programme. Annual Progress Reports 2009–2014. Phnom Penh, Cambodia: Ministry of Health of Cambodia. [Google Scholar]
  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] [Google Scholar]
  7. Noedl H, Socheat D, Satimai W, , 2009. Artemisinin-resistant malaria in Asia. N Engl J Med 361: 540541.[Crossref] [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  10. Degardin K, Roggo Y, Margot P, , 2014. Understanding and fighting the medicine counterfeit market. J Pharm Biomed Anal 87: 167175.[Crossref] [Google Scholar]
  11. Newton PN, Green MD, Fernandez FM, Day NP, White NJ, , 2006. Counterfeit anti-infective drugs. Lancet Infect Dis 6: 602613.[Crossref] [Google Scholar]
  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] [Google Scholar]
  13. Pincock S, , 2003. WHO tries to tackle problem of counterfeit medicines in Asia. BMJ 327: 1126.[Crossref] [Google Scholar]
  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] [Google Scholar]
  15. Newton PN, Green MD, Fernandez FM, , 2010. Impact of poor-quality medicines in the ‘developing’ world. Trends Pharmacol Sci 31: 99101.[Crossref] [Google Scholar]
  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. [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  24. Aldhous P, , 2005. Counterfeit pharmaceuticals: murder by medicine. Nature 434: 132136.[Crossref] [Google Scholar]
  25. WHO, 2010. World Malaria Report 2010. Geneva, Switzerland: World Health Organization. [Google Scholar]
  26. WHO, 2011. Global Plan for Artemisinin Resistance Containment (GPARC). Geneva, Switzerland: World Health Organization. [Google Scholar]
  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. [Google Scholar]
  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] [Google Scholar]
  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. [Google Scholar]
  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] [Google Scholar]
  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. [Google Scholar]
  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. [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  35. Ogwal-Okeng JW, Okello DO, Odyek O, , 1998. Quality of oral and parenteral chloroquine in Kampala. East Afr Med J 75: 692694. [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  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. [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  41. Tabernero P, Newton PN, , 2012. The WWARN antimalarial quality surveyor. Pathog Glob Health 106: 7778.[Crossref] [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  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. [Google Scholar]
  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. [Google Scholar]
  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. [Google Scholar]
  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. [Google Scholar]
  48. PSI, 2011. Kingdom of Cambodia Outlet Survey Report. Washington, DC: ACTwatach Group and Population Services International Cambodia. [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  51. Bate R, Jin GZ, Mathur A, , 2011. Does price reveal poor-quality drugs? Evidence from 17 countries. J Health Econ 30: 11501163.[Crossref] [Google Scholar]
  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] [Google Scholar]
  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. [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
  57. Ioset JR, Kaur H, , 2009. Simple field assays to check quality of current artemisinin-based antimalarial combination formulations. PLoS ONE 4: e7270.[Crossref] [Google Scholar]
  58. Deisingh AK, , 2005. Pharmaceutical counterfeiting. Analyst (Lond) 130: 271279.[Crossref] [Google Scholar]
  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] [Google Scholar]
  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] [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.14-0391
Loading
/content/journals/10.4269/ajtmh.14-0391
Loading

Data & Media loading...

Supplementary PDF

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

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error