1921
Volume 98, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Dihydroartemisinin–piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both and infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated and malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days. Clinical and laboratory data were collected daily until parasite clearance and then weekly for 6 weeks. Molecular analysis was undertaken for all patients with recurrent parasitemia. A total of 129 study patients were enrolled in the study. At day 42, the polymerase chain reaction-adjusted efficacy was 97.7% (95% confidence intervals [CI]: 87.4–99.9) in the 61 patients with malaria, and 98.2% [95% CI: 90.3–100] in the 56 patients with malaria. By day 2, 98% (56/57) of patients with and 96.9% (63/65) of those with had cleared their peripheral parasitemia; none of the patients were still parasitaemic on day 3. Molecular analysis of parasites showed that none (0/61) had K13 mutations associated previously with artemisinin resistance or increased copy number of 2–3 (0/61). In the absence of artemisinin resistance, DHP has retained high efficacy for the treatment of uncomplicated malaria despite extensive drug pressure over a 9-year period.

[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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2018-03-07
2018-11-20
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References

  1. Karyana M, ., 2008. Malaria morbidity in Papua, Indonesia, an area with multidrug resistant Plasmodium vivax and Plasmodium falciparum. Malar J 7: 148.
  2. Elyazar IR, Hay SI, Baird JK, , 2011. Malaria distribution, prevalence, drug resistance and control in Indonesia. Adv Parasitol 74: 41175.
  3. Ratcliff A , ., 2007. Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine–pyrimethamine in southern Papua, Indonesia. Trans R Soc Trop Med Hyg 101: 351359.
  4. Ratcliff A, Siswantoro H, Kenangalem E, Maristela R, Wuwung RM, Laihad F, Ebsworth EP, Anstey NM, Tjitra E, Price RN, , 2007. Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison. Lancet 369: 757765.
  5. Dondorp AM, ., 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455467.
  6. Ashley EA, ., 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411423.
  7. WHO, 2016. Artemisinin and Artemisinin Based Combination Therapy Resistance: Status Report. Geneva, Switzerland: World Health Organization.
  8. Amaratunga C, ., 2016. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis 16: 357365.
  9. Poespoprodjo JR, Fobia W, Kenangalem E, Lampah DA, Hasanuddin A, Warikar N, Sugiarto P, Tjitra E, Anstey NM, Price RN, , 2009. Vivax malaria: a major cause of morbidity in early infancy. Clin Infect Dis 48: 17041712.
  10. Kenangalem E, Karyana M, Burdarm L, Yeung S, Simpson JA, Tjitra E, Anstey NM, Poespoprodjo JR, Price RN, Douglas NM, , 2016. Plasmodium vivax infection: a major determinant of severe anaemia in infancy. Malar J 15: 321.
  11. Thio F, Indrawanti R, Price R, , 2013. The Timika Household Survey 2 Databases: Changes in Treatment Seeking Behaviour. Timika, Papua: Timika Research Unit.
  12. Devine A, Kenangalem E, Burdam FH, Anstey NM, Poespoprodjo JR, Price R, Yeung S, , 2018. Treatment-seeking behavior after the implementation of a unified policy of dihydroartemisinin-piperaquine for the treatment of uncomplicated malaria in Papua, Indonesia. Am J Trop Med Hyg 98: 543550.
  13. WHO, 2009. Methods for Surveillance of Antimalarial Drug Efficacy. Available at: http://apps.who.int/iris/bitstream/10665/44048/1/9789241597531_eng.pdf. Accessed March 28, 2017.
  14. WHO, 2013. Management of Severe Malaria. Available at: http://apps.who.int/iris/bitstream/10665/79317/1/9789241548526_eng.pdf?ua=1. Accessed March 28, 2017.
  15. Domingo GJ, ., 2013. G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests. Malar J 12: 391.
  16. Singh B, Bobogare A, Cox-Singh J, Snounou G, Abdullah MS, Rahman HA, , 1999. A genus- and species-specific nested polymerase chain reaction malaria detection assay for epidemiologic studies. Am J Trop Med Hyg 60: 687692.
  17. Boonma P, Christensen PR, Suwanarusk R, Price RN, Russell B, Lek-Uthai U, , 2007. Comparison of three molecular methods for the detection and speciation of Plasmodium vivax and Plasmodium falciparum. Malar J 6: 124.
  18. WHO, 2008. Methods and Techniques for Clinical Trials on Antimalarial Drug Efficacy: Genotyping to Identify Parasite Populations. Geneva, Switzerland: World Health Organization, 1314.
  19. Brockman A, Paul RE, Anderson TJ, Hackford I, Phaiphun L, Looareesuwan S, Nosten F, Day KP, , 1999. Application of genetic markers to the identification of recrudescent Plasmodium falciparum infections on the northwestern border of Thailand. Am J Trop Med Hyg 60: 1421.
  20. Ariey F, ., 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 5055.
  21. Leang R, ., 2015. Evidence of Plasmodium falciparum malaria multidrug resistance to artemisinin and piperaquine in western Cambodia: dihydroartemisinin-piperaquine open-label multicenter clinical assessment. Antimicrob Agents Chemother 59: 47194726.
  22. Amato R, ., 2017. Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study. Lancet Infect Dis 17: 164173.
  23. Witkowski B, ., 2017. A surrogate marker of piperaquine-resistant Plasmodium falciparum malaria: a phenotype-genotype association study. Lancet Infect Dis 17: 174183.
  24. MOH I, 2013. The National Guideline for Malaria Treatment in Indonesia. Available at: http://p2p.kemkes.go.id/_asset/_regulasi/65_PMK No. 5 ttg Pedoman Tata Laksana Malaria.pdf. Accessed March 28, 2017.
  25. WHO, 2015. Guidelines for the Treatment of Malaria: Third Edition. Available at: http://apps.who.int/iris/bitstream/10665/162441/1/9789241549127_eng.pdf?ua=1&ua=1. Accessed March 28, 2017.
  26. Flegg JA, Guerin PJ, White NJ, Stepniewska K, , 2011. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Malar J 10: 339.
  27. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, , 2008. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med 359: 26192620.
  28. Phyo AP, ., 2012. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 379: 19601966.
  29. Tun KM, ., 2015. Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker. Lancet Infect Dis 15: 415421.
  30. Leang R, Barrette A, Bouth DM, Menard D, Abdur R, Duong S, Ringwald P, , 2013. Efficacy of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010. Antimicrob Agents Chemother 57: 818826.
  31. Davis TM, Hung TY, Sim IK, Karunajeewa HA, Ilett KF, , 2005. Piperaquine: a resurgent antimalarial drug. Drugs 65: 7587.
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  • Received : 20 Aug 2017
  • Accepted : 20 Oct 2017

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