In Vivo and In Vitro Efficacy of Amodiaquine Monotherapy for Treatment of Infection by Chloroquine-Resistant Plasmodium vivax

A HASUGIAN, E TJITRA, A RATCLIFF, H SISWANTORO, Enny Kenangalem, R WUWUNG, H PURBA, Kim Piera, Ferryanto Chalfein, Jutta Marfurt, P PENTTINEN, Bruce Russell, Nicholas Anstey, Ric Price

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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. Copyright � 2009, American Society for Microbiology. All Rights Reserved.
Original languageEnglish
Pages (from-to)1094-1099
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number3
Publication statusPublished - 2009

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Amodiaquine
Plasmodium vivax
Chloroquine
Malaria
Infection
Parasitemia
Treatment Failure
Therapeutics
Recurrence
Antimalarials
Plasmodium falciparum
Nonparametric Statistics
Microbiology
Inhibitory Concentration 50
Outpatients
In Vitro Techniques
Confidence Intervals
Incidence

Cite this

HASUGIAN, A ; TJITRA, E ; RATCLIFF, A ; SISWANTORO, H ; Kenangalem, Enny ; WUWUNG, R ; PURBA, H ; Piera, Kim ; Chalfein, Ferryanto ; Marfurt, Jutta ; PENTTINEN, P ; Russell, Bruce ; Anstey, Nicholas ; Price, Ric. / In Vivo and In Vitro Efficacy of Amodiaquine Monotherapy for Treatment of Infection by Chloroquine-Resistant Plasmodium vivax. In: Antimicrobial Agents and Chemotherapy. 2009 ; Vol. 53, No. 3. pp. 1094-1099.
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HASUGIAN, A, TJITRA, E, RATCLIFF, A, SISWANTORO, H, Kenangalem, E, WUWUNG, R, PURBA, H, Piera, K, Chalfein, F, Marfurt, J, PENTTINEN, P, Russell, B, Anstey, N & Price, R 2009, 'In Vivo and In Vitro Efficacy of Amodiaquine Monotherapy for Treatment of Infection by Chloroquine-Resistant Plasmodium vivax', Antimicrobial Agents and Chemotherapy, vol. 53, no. 3, pp. 1094-1099.

In Vivo and In Vitro Efficacy of Amodiaquine Monotherapy for Treatment of Infection by Chloroquine-Resistant Plasmodium vivax. / HASUGIAN, A; TJITRA, E; RATCLIFF, A; SISWANTORO, H; Kenangalem, Enny; WUWUNG, R; PURBA, H; Piera, Kim; Chalfein, Ferryanto; Marfurt, Jutta; PENTTINEN, P; Russell, Bruce; Anstey, Nicholas; Price, Ric.

In: Antimicrobial Agents and Chemotherapy, Vol. 53, No. 3, 2009, p. 1094-1099.

Research output: Contribution to journalArticleResearchpeer-review

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AU - HASUGIAN, A

AU - TJITRA, E

AU - RATCLIFF, A

AU - SISWANTORO, H

AU - Kenangalem, Enny

AU - WUWUNG, R

AU - PURBA, H

AU - Piera, Kim

AU - Chalfein, Ferryanto

AU - Marfurt, Jutta

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AU - Price, Ric

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N2 - 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. Copyright � 2009, American Society for Microbiology. All Rights Reserved.

AB - 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. Copyright � 2009, American Society for Microbiology. All Rights Reserved.

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