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PLOS ONE 2014

Quality of Antimalarial Drugs and Antibiotics in Papua New Guinea: A Survey of the Health Facility Supply Chain

DOI: 10.1371/journal.pone.0096810

Manuel W. Hetzel, Madhu Page-Sharp, Nancy Bala, Justin Pulford, Inoni Betuela, Timothy M. E. Davis, Evelyn K. Lavu

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Abstract:

Background Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG. Methods and Findings Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions. Conclusions This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of poor-quality medicines should include limiting procurement to WHO prequalified products and implementing routine quality testing.

References

[1]	World Health Organization (2010) Guidelines for the treatment of Malaria. Geneva: World Health Organization.
[2]	World Health Organization (2012) T3: Test. Treat. Track. Scaling up diagnostic testing, treatment and surveillance for malaria. Geneva: World Health Organization.
[3]	Nayyar GM, Breman JG, Newton PN, Herrington J (2012) Poor-quality antimalarial drugs in southeast Asia and sub-Saharan Africa. Lancet Infect Dis 12: 488–496.
[4]	Newton PN, Green MD, Mildenhall DC, Plancon A, Nettey H, et al. (2011) Poor quality vital anti-malarials in Africa - an urgent neglected public health priority. Malar J 10: 352.
[5]	Maponga C, Ondari C (2003) The quality of antimalarials: a study in selected African countries. Geneva World Health Organization.
[6]	Evans L 3rd, Coignez V, Barojas A, Bempong D, Bradby S, et al. (2012) Quality of anti-malarials collected in the private and informal sectors in Guyana and Suriname. Malar J 11: 203.
[7]	Almuzaini T, Choonara I, Sammons H (2013) Substandard and counterfeit medicines: a systematic review of the literature. BMJ Open 3: e002923.
[8]	Newton PN, Green MD, Fernandez FM, Day NP, White NJ (2006) Counterfeit anti-infective drugs. Lancet Infect Dis 6: 602–613.
[9]	Bate R, Jensen P, Hess K, Mooney L, Milligan J (2013) Substandard and falsified anti-tuberculosis drugs: a preliminary field analysis. Int J Tuberc Lung Dis 17: 308–311.
[10]	Fernandez FM, Hostetler D, Powell K, Kaur H, Green MD, et al. (2011) Poor quality drugs: grand challenges in high throughput detection, countrywide sampling, and forensics in developing countries. Analyst 136: 3073–3082.
[11]	Attaran A, Barry D, Basheer S, Bate R, Benton D, et al. (2012) How to achieve international action on falsified and substandard medicines. BMJ 345: e7381.
[12]	World Health Organization (2010) Medicines: counterfeit medicines. Fact sheet No. 275. Geneva: World Health Organization. Available: http://www.who.int/mediacentre/factsheet？s/fs275/en/.
[13]	Newton PN, Green MD, Fernandez FM (2010) Impact of poor-quality medicines in the ‘developing’ world. Trends Pharmacol Sci 31: 99–101.
[14]	Faucon B, Murphy C, Whalen J (2013) Africa’s Malaria Battle: Fake Drug Pipeline Undercuts Progress. The Wall Street Journal. Available: http://online.wsj.com/article/SB10001424？127887324474004578444942841728204.html.
[15]	World Health Organization (2006) Counterfeit medicines. Geneva: World Health Organization. Available: http://www.who.int/medicines/services/co？unterfeit/impact/ImpactF_S/en/. Accessed: 12 August 2013.
[16]	Chaccour CJ, Kaur H, Mabey D, Del Pozo JL (2012) Travel and fake artesunate: a risky business. Lancet 380: 1120.
[17]	Newton PN, Lee SJ, Goodman C, Fernandez FM, Yeung S, et al. (2009) Guidelines for field surveys of the quality of medicines: a proposal. PLoS Med 6: e52.
[18]	Gostin LO, Buckley GJ, Kelley PW (2013) Stemming the global trade in falsified and substandard medicines. JAMA 309: 1693–1694.
[19]	White NJ, Pongtavornpinyo W, Maude RJ, Saralamba S, Aguas R, et al. (2009) Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance. Malar J 8: 253.
[20]	Kazura JW, Siba PM, Betuela I, Mueller I (2011) Research challenges and gaps in malaria knowledge in Papua New Guinea. Acta Trop 121: 274–280.
[21]	Papua New Guinea Department of Health (2009) National Malaria Treatment Protocol. Port Moresby: Department of Health.
[22]	Pulford J, Kurumop SF, Ura Y, Siba PM, Mueller I, et al. (2013) Malaria case management in Papua New Guinea following the introduction of a revised treatment protocol. Malar J 12: 433.
[23]	World Health Organization and Papua New Guinea Department of Health (2012) Health Services Delivery Profile Papua New Guinea. Port Moresby: Department of Health.
[24]	Davy CP, Sicuri E, Ome M, Lawrence-Wood E, Siba P, et al. (2010) Seeking treatment for symptomatic malaria in Papua New Guinea. Malar J 9: 268.
[25]	Hetzel MW, Gideon G, Mueller I, Siba PM (2010) Papua New Guinea/The Global Fund Round 3 Malaria Control Programme Evaluation 2008/2009: Results from Cross-Sectional Surveys and Sentinel Sites. Goroka: Papua New Guinea Institute of Medical Research.
[26]	Angwin A, Hetzel MW, Mueller I, Siba PM, Pulford J (2014) A qualitative study of how affected individuals or their caregivers respond to suspected malaria infection in rural Papua New Guinea. P N G Med J 56 (in press).
[27]	Papua New Guinea Department of Health (2012) Papua New Guinea Pharmaceutical Country Profile. Waigani: Ministry of Health & World Health Organization.
[28]	The Global Fund (2013) Malaria Control in Papua New Guinea: Scaling up for Impact. The Global Fund. Available: http://portfolio.theglobalfund.org/en/Gr？ant/Index/PNG-809-G04-M. Accessed: 24.05.2013.
[29]	Nair A, Strauch S, Lauwo J, J？hnke RWO, Dressman J (2011) Are counterfeit or substandard anti-infective products the cause of treatment failure in Papua New Guinea? J Pharm Sci 100: 5059–5068.
[30]	Kaur H, Goodman C, Thompson E, Thompson KA, Masanja I, et al. (2008) A nationwide survey of the quality of antimalarials in retail outlets in Tanzania. PLoS One 3: e3403.
[31]	Pulford J, Mueller I, Siba PM, Hetzel MW (2012) Malaria case management in Papua New Guinea prior to the introduction of a revised treatment protocol. Malar J 11: 157.
[32]	Paediatric Society of Papua New Guinea (2005) Standard Treatment for the common illnesses of children in Papua New Guinea: A Manual for Nurses, Community Health Workers, Health Extension Officers and Doctors. Eighth Edition. Port Moresby: Department of Health.
[33]	Papua New Guinea Department of Health (2005) Standard Treatment for Common Illnesses of Adults in Papua New Guinea: A Manual for Nurses, Community Health Workers, Health Extension Officers and Doctors. Port Moresby: Department of Health.
[34]	Papua New Guinea Department of Health (2012) National Medicines Formulary. Port Moresby: Department of Health.
[35]	Page-Sharp M, Ilett KF, Betuela I, Davis TM, Batty KT (2012) Simultaneous determination of primaquine and carboxyprimaquine in plasma using solid phase extraction and LC-MS assay. J Chromatogr B Analyt Technol Biomed Life Sci 902: 142–146.
[36]	World Health Organization (2013) WHO List of Prequalified Medicinal Products. Geneva: World Health Organization. Available: http://apps.who.int/prequal/. Accessed: 13 December 2013.
[37]	Hehonah NT, Popon J, Willie N (2010) Using High Performance Liquid Chromatography to Quantitate Artemether and Artesunate Anti-Malarial Tablets in the National Capital District, Papua New Guinea. Pacific Journal of Medical Sciences 7: 4–13.
[38]	Achan J, Talisuna AO, Erhart A, Yeka A, Tibenderana JK, et al. (2011) Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar J 10: 144.
[39]	WHO Malaria Policy Advisory Committee and Secretariat (2012) Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of September 2012 meeting. Malar J 11: 424.
[40]	Galappaththy GN, Tharyan P, Kirubakaran R (2013) Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine. The Cochrane database of systematic reviews 10: CD004389.
[41]	Shekalaghe S, Drakeley C, Gosling R, Ndaro A, van Meegeren M, et al. (2007) Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. PLoS One 2: e1023.
[42]	White NJ (2013) Primaquine to prevent transmission of falciparum malaria. Lancet Infect Dis 13: 175–181.
[43]	Graves PM, Gelband H, Garner P (2012) Primaquine for reducing Plasmodium falciparum transmission. The Cochrane database of systematic reviews 9: CD008152.
[44]	World Health Organization (2011) Global plan for artemisinin resistance containment. Geneva: Global Malaria Program, World Health Organization.
[45]	Howes RE, Battle KE, Satyagraha AW, Baird JK, Hay SI (2013) G6PD deficiency: global distribution, genetic variants and primaquine therapy. Adv Parasitol 81: 133–201.
[46]	Carmona-Fonseca J, Alvarez G, Maestre A (2009) Methemoglobinemia and adverse events in Plasmodium vivax malaria patients associated with high doses of primaquine treatment. Am J Trop Med Hyg 80: 188–193.
[47]	Pribluda V, Barojas A, Anez A, Lopez C, Figueroa R, et al. (2012) Implementation of basic quality control tests for malaria medicines in Amazon Basin countries: results for the 2005–2010 period. Malar J 11: 202.
[48]	Phanouvong S, Dijiba Y, Vijaykadga S, Raymond C, Krech L, et al. (2013) The quality of antimalarial medicines in eastern Thailand: a case study along the Thai-Cambodian border. Southeast Asian J Trop Med Public Health 44: 363–373.
[49]	Phanouvong S, Raymond C, Krech L, Dijiba Y, Mam B, et al. (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: 349–362.
[50]	United States Pharmacopeia Drug Quality and Information Program (2007) Ensuring the Quality of Medicines in Resource-Limited Countries: An Operational Guide. Rockville, Md.: The United States Pharmacopeial Convention.
[51]	Amin AA, Snow RW, Kokwaro GO (2005) The quality of sulphadoxine-pyrimethamine and amodiaquine products in the Kenyan retail sector. J Clin Pharm Ther 30: 559–565.
[52]	Onwujekwe O, Kaur H, Dike N, Shu E, Uzochukwu B, et al. (2009) Quality of anti-malarial drugs provided by public and private healthcare providers in south-east Nigeria. Malar J 8: 22.
[53]	Dondorp AM, Newton PN, Mayxay M, Van Damme W, Smithuis FM, et al. (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: 1241–1246.
[54]	Newton PN, Amin AA, Bird C, Passmore P, Dukes G, et al. (2011) The primacy of public health considerations in defining poor quality medicines. PLoS Med 8: e1001139.
[55]	Bate R, Hess K (2010) Anti-malarial drug quality in Lagos and Accra - a comparison of various quality assessments. Malar J 9: 157.
[56]	Moore BR, Page-Sharp M, Stoney JR, Ilett KF, Jago JD, et al. (2011) Pharmacokinetics, pharmacodynamics, and allometric scaling of chloroquine in a murine malaria model. Antimicrob Agents Chemother 55: 3899–3907.
[57]	Arayne MS, Sultana N, Siddiqui FA, Naseem S, Qureshi F (2010) Simultaneous determination of pyrimethamine, sulfadoxine, mefloquine, and ibuprofen in pharmaceutical formulations by RP-HPLC. Med Chem Res 19: 1043–1054.
[58]	Cruz AP, Bertol CD, Murakami FS, Silva MAS (2008) Development and Validation of RP- HPLC Method for Determination of Primaquine in Extended Release Tablets. Latin American Journal of Pharmacy 27: 415–418.
[59]	Gaudiano MC, Antoniella E, Bertocchi P, Valvo L (2006) Development and validation of a reversed-phase LC method for analysing potentially counterfeit antimalarial medicines. J Pharm Biomed Anal 42: 132–135.
[60]	Ahmed M, Babu SG, Shetty A SK (2011) Development and validation of amoxicillin by RP-HPLC method in bulk drug and pharmaceutical dosage forms. International Journal of ChemTech Research 3: 1037–1041.
[61]	Kogawa AC, Salgado HR (2012) Quantification of Doxycycline Hyclate in Tablets by HPLC-UV Method. J Chromatogr Sci 51: 919–925.
[62]	Ranher SS, Gandhi SV, Kadukar SS, Ranjane PN (2010) A validated HPLC method for determination of artesunate in bulk and tablet formulation. Journal of Analytical Chemistry 65: 507–510.
[63]	Arun R, Anton Smith A (2011) Simultaneous HPLC-UV method for the estimation of artemether and lumefantrine in tablet dosage form. International Journal of Pharmaceutical and Biomedical Research 2: 201–205.
[64]	Salman S, Page-Sharp M, Griffin S, Kose K, Siba PM, et al. (2011) Population pharmacokinetics of artemether, lumefantrine, and their respective metabolites in Papua New Guinean children with uncomplicated malaria. Antimicrob Agents Chemother 55: 5306–5313.

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