1921
Volume 86, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

The safety of artemether-lumefantrine in patients with acute, uncomplicated malaria was investigated prospectively using the auditory brainstem response (ABR) and pure-tone thresholds. Secondary outcomes included polymerase chain reaction-corrected cure rates. Patients were randomly assigned in a 3:1:1 ratio to either artemether-lumefantrine ( = 159), atovaquone-proguanil ( = 53), or artesunate-mefloquine ( = 53). The null hypothesis (primary outcome), claiming that the percentage of patients with a baseline to Day-7 ABR Wave III latency increase of > 0.30 msec is ≥ 15% after administration of artemether-lumefantrine, was rejected; 2.6% of patients (95% confidence interval: 0.7–6.6) exceeded 0.30 msec, i.e., significantly below 15% ( < 0.0001). A model-based analysis found no apparent relationship between drug exposure and ABR change. In all three groups, average improvements (2–4 dB) in pure-tone thresholds were observed, and polymerase chain reaction-corrected cure rates were > 95% to Day 42. The results support the continued safe and efficacious use of artemether-lumefantrine in uncomplicated falciparum malaria.

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References

  1. World Health Organization, 2010. Guidelines for the Treatment of Malaria. Second edition. Available at: http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf. Accessed January 20, 2011.
  2. Premji ZG, , 2009. Coartem: the journey to the clinic. Malar J 8 (Suppl 1): S3.[Crossref]
  3. Brewer TG, Peggins JO, Grate SJ, Petras JM, Levine BS, Weina PJ, Swearengen J, Heiffer MH, Schuster BG, , 1994. Neurotoxicity in animals due to arteether and artemether. Trans R Soc Trop Med Hyg 88 (Suppl 1): S33S36.[Crossref]
  4. Brewer TG, Grate SJ, Peggins JO, Weina PJ, Petras JM, Levine BS, Heiffer MH, Schuster BG, , 1994. Fatal neurotoxicity of arteether and artemether. Am J Trop Med Hyg 51: 251259.
  5. Petras JM, Kyle DE, Gettayacamin M, Young GD, Bauman RA, Webster HK, Corcoran KD, Peggins JO, Vane MA, Brewer TG, , 1997. Arteether: risks of two-week administration in Macaca mulatta . Am J Trop Med Hyg 56: 390396.
  6. Ribeiro IR, Olliaro P, , 1998. Safety of artemisinin and its derivatives. A review of published and unpublished clinical trials. Med Trop 58 (Suppl 3): 5053.
  7. Kissinger E, Hien TT, Hung NT, Nam ND, Tuyen NL, Dinh BV, Mann C, Phu NH, Loc PP, Simpson JA, White NJ, Farrar JJ, , 2000. Clinical and neurophysiological study of the effects of multiple doses of artemisinin on brain-stem function in Vietnamese patients. Am J Trop Med Hyg 63: 4855.
  8. Hien TT, Turner GD, Mai NT, Phu NH, Bethell D, Blakemore WF, Cavanagh JB, Dayan A, Medana I, Weller RO, Day NP, White NJ, , 2003. Neuropathological assessment of artemether-treated severe malaria. Lancet 362: 295296.[Crossref]
  9. Toovey S, Jamieson A, , 2004. Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether. Trans R Soc Trop Med Hyg 98: 261267.[Crossref]
  10. World Health Organization, 2000. Management of Severe Malaria: A Practical Handbook. Second edition. Available at: http://www.rollbackmalaria.org/docs/hbsm.pdf. Accessed January 20, 2011.
  11. World Health Organization, 2003. Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Available at: http://whqlibdoc.who.int/hq/2003/WHO_HTM_RBM_2003.50.pdf. Accessed January 20, 2011.
  12. Felger I, Beck HP, Doolan D, , 2002. Genotyping of Plasmodium falciparum: PCR-RFLP analysis. , ed. Malaria Methods and Protocols: Methods in Molecular Medicine. Totawa, NJ: Humana Press, 117129.[Crossref]
  13. Carhart R, Jerger J, , 1959. Preferred method for clinical determination of pure-tone thresholds. J Speech Hear Disord 24: 330345.[Crossref]
  14. Souppart C, Gauducheau N, Sandrenan N, Richard F, , 2002. Development and validation of a high-performance liquid chromatography-mass spectrometry assay for the determination of artemether and its metabolite dihydroartemisinin in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 774: 195203.[Crossref]
  15. Bergqvist Y, Hellgren U, Churchill FC, , 1988. High-performance liquid chromatographic assay for the simultaneous monitoring of mefloquine and its acid metabolite in biological samples using protein precipitation and ion-pair extraction. J Chromatogr A 432: 252263.
  16. Burkard RF, Don M, Eggermont JJ, , 2007. Auditory Evoked Potentials: Basic Principles and Clinical Applications. Philadelphia, PA: Lippincott, Williams & Wilkins.
  17. Fausti SA, Flick CL, Bobal AM, Ellingson RM, Henry JA, Mitchell CR, , 2003. Comparison of ABR stimuli for the early detection of ototoxicity: conventional clicks compared with high frequency clicks and single frequency tone bursts. J Am Acad Audiol 14: 239250.
  18. Don M, Kwong B, Katz J, , 2002. Auditory brainstem response: differential diagnosis. , ed. Handbook of Clinical Audiology. Fifth edition. New York: Lippincott Williams & Wilkins, 274297.
  19. Hecox K, Galambos R, , 1974. Brain stem auditory evoked responses in human infants and adults. Arch Otolaryngol 99: 3033.[Crossref]
  20. Clemis JD, Mc Gee T, , 1979. Brain stem electric response audiometry in the differential diagnosis of acoustic tumors. Laryngoscope 89: 3142.[Crossref]
  21. Bergholtz L, , 1981. Normative data in clinical ABR. Scand Audiol Suppl 13: 7581.
  22. Carrara VI, Phyo AP, Nwee P, Soe M, Htoo H, Arunkamomkiri J, Singhasivanon P, Nosten F, , 2008. Auditory assessment of patients with acute uncomplicated Plasmodium falciparum malaria treated with three-day mefloquine-artesunate on the north-western border of Thailand. Malar J 7: 233.[Crossref]
  23. American Academy of Otolaryngology-Head and Neck Surgery Foundation, 1995. Committee on Hearing and Equilibrium guidelines for the evaluation of hearing preservation in acoustic neuroma (vestibular schwannoma). Otolaryngo Head Neck Surg 113: 179180.[Crossref]
  24. Van Vugt M, Angus BJ, Price RN, Mann C, Simpson JA, Poletto C, Htoo SE, Looareesuwan S, White NJ, Nosten F, , 2000. A case-control auditory evaluation of patients treated with artemisinin derivatives for multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg 62: 6569.
  25. Hutagalung R, Htoo H, Nwee P, Arunkamomkiri J, Zwang J, Carrara VI, Ashley E, Singhasivanon P, White NJ, Nosten F, , 2006. A case-control auditory evaluation of patients treated with artemether-lumefantrine. Am J Trop Med Hyg 74: 211214.
  26. McCall MB, Beynon AJ, Mylanus EA, van der Ven AJ, Sauerwein RW, , 2006. No hearing loss associated with the use of artemether-lumefantrine to treat experimental human malaria. Trans R Soc Trop Med Hyg 100: 10981104.[Crossref]
  27. Gürkov R, Eshetu T, Miranda IB, Berens-Riha N, Mamo Y, Girma T, Krause E, Schmidt M, Hempel JM, Löscher T, , 2008. Ototoxicity of artemether/lumefantrine in the treatment of falciparum malaria: a randomized trial. Malar J 7: 179.[Crossref]
  28. Mueller EA, van Vugt M, Kirch W, Andriano K, Hunt P, de Palacios PI, , 2006. Efficacy and safety of the six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in adolescents and adults: a pooled analysis of individual patient data from randomized clinical trials. Acta Trop 100: 4153.[Crossref]
  29. Mayxay M, Khanthavong M, Lindegårdh N, Keola S, Barends M, Pongvongsa T, Yapom R, Annerberg A, Phompida S, Phetsouvanh R, White NJ, Newton PN, , 2004. Randomized comparison of chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao People's Democratic Republic. Clin Infect Dis 39: 11391147.[Crossref]
  30. Hutagalung R, Paiphun L, Ashley EA, McGready R, Brockman A, Thwai KL, Singhasivanon P, Jelinek T, White NJ, Nosten FH, , 2005. A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand. Malar J 4: 46.[Crossref]
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  • Received : 02 Apr 2011
  • Accepted : 26 Sep 2011

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