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Antimicrobial Agents and Chemotherapy, March 2009, p. 1094-1099, Vol. 53, No. 3
0066-4804/09/$08.00+0 doi:10.1128/AAC.01511-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
In Vivo and In Vitro Efficacy of Amodiaquine Monotherapy for Treatment of Infection by Chloroquine-Resistant Plasmodium vivax
A. R. Hasugian,1
E. Tjitra,1
A. Ratcliff,2
H. Siswantoro,1
E. Kenangalem,3,4
R. M. Wuwung,5
H. L. E. Purba,1
K. A. Piera,2
F. Chalfien,3
J. Marfurt,2
P. M. Penttinen,5,6
B. Russell,2
N. M. Anstey,2 and
R. N. Price2,7*
National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia,1 International Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia,2 Menzies School of Health Research, National Institute of Health Research and Development Malaria Research Program, Timika, Indonesia,3 District Health Office, Timika, Papua, Indonesia,4 Public Health and Malaria Control Department, PT Freeport, Indonesia, Tembagapura, Papua, Indonesia,5 International SOS, Tembagapura, Papua, Indonesia,6 Centre for Vaccinology & Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom7
Received 12 November 2008/ Returned for modification 24 November 2008/ Accepted 16 December 2008
Amodiaquine retains efficacy against infection by chloroquine-resistant Plasmodium falciparum; however, little information is available on its efficacy against infection by chloroquine-resistant Plasmodium vivax. Patients presenting to a rural clinic with a pure P. vivax infection that recurred after recent antimalarial treatment were retreated, this time with amodiaquine monotherapy, and the risk of further recurrence within 4 weeks was assessed. Of the 87 patients with pure P. vivax infection, 15 patients did not complete a full course of treatment, 4 of whom were intolerant to treatment. In the 72 patients completing treatment, 91% (63 of 69) had cleared their parasitemia within 48 h with no early treatment failure. Follow-up to day 28 or recurrent parasitemia was achieved for 56 patients (78%). The cumulative incidence of treatment failure by day 28 was 22.8% (95% confidence interval, 7.3 to 38%). The in vitro sensitivity profile was determined for a separate set of isolates from outpatients with pure P. vivax infection. The median 50% inhibitory concentration of amodiaquine was 11.3 nM (range, 0.37 to 95.8) and was correlated significantly with that of chloroquine (Spearman rank correlation coefficient, 0.602; P < 0.001) Although amodiaquine results in a rapid clinical response, the risk of recurrence by day 28 is unacceptably high, reducing its suitability as an alternative treatment of infection by chloroquine-resistant P. vivax in this region.
* Corresponding author. Mailing address: Menzies School of Health Research, P.O. Box 41096, Casuarina, Darwin, NT 0811, Australia. Phone: (61) 8 8922 8197. Fax: (61) 8 8922 8429. E-mail: rnp{at}menzies.edu.au
Published ahead of print on 22 December 2008.
Antimicrobial Agents and Chemotherapy, March 2009, p. 1094-1099, Vol. 53, No. 3
0066-4804/09/$08.00+0 doi:10.1128/AAC.01511-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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