Dihydroartemisinin-Piperaquine Versus Chloroquine in the Treatment of Plasmodium vivax Malaria in Thailand

A Randomized Controlled Trial

Aung Pyae Phyo, Khin Manug Lwin, Ric Price, Elizabeth Ashley, Bruce Russell, Kanlaya Siprawat, N LINDEGARDH, Niklas Lindegardh, Pratap Singhasivanon, Nicholas J White, François Nosten

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Chloroquine (CQ) remains the treatment of choice for Plasmodium vivax malaria. Initially confined to parts of Indonesia and Papua, resistance of P. vivax to CQ seems to be spreading, and alternative treatments are required.

Methods: We conducted a randomized controlled study to compare the efficacy and the tolerability of CQ and dihydroartemisinin-piperaquine (DP) in 500 adults and children with acute vivax malaria on the Northwestern border of Thailand.

Results: Both drugs were well tolerated. Fever and parasite clearance times were slower in the CQ than in the DP group (P <. 001). By day 28, recurrent infections had emerged in 18 of 207 CQ recipients compared with 5 of 230 treated with DP (relative risk, 4.0; 95% confidence interval [CI], 1.51-10.58; P =. 0046). The cumulative risk of recurrence with P. vivax at 9 weeks was 79.1% (95% CI, 73.5%-84.8%) in patients treated with CQ compared with 54.9% (95% CI, 48.2%-61.6%) in those receiving DP (hazard ratio [HR], 2.27; 95% CI, 1.8-2.9; P <. 001). Children <5 years old were at greater risk of recurrent P. vivax infection (74.4%; 95% CI, 63.2%-85.6%) than older patients (55.3% [95% CI, 50.2%-60.4%]; HR, 1.58 [95% CI, 1.1-2.2]; P =. 005). In vitro susceptibility testing showed that 13% of the tested isolates had a CQ median inhibitory concentration >100 nmol/L, suggesting reduced susceptibility.

Conclusions: The efficacy of CQ in the treatment of P. vivax infections is declining on the Thai-Myanmar border. DP is an effective alternative treatment.
Original languageEnglish
Pages (from-to)977-984
Number of pages8
JournalClinical Infectious Diseases
Volume53
Issue number10
DOIs
Publication statusPublished - 2011

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dihydroartemisinin
Vivax Malaria
Chloroquine
Thailand
Randomized Controlled Trials
Plasmodium vivax
Myanmar
Therapeutics
Indonesia
Malaria
Parasites
Fever
piperaquine

Cite this

Phyo, Aung Pyae ; Lwin, Khin Manug ; Price, Ric ; Ashley, Elizabeth ; Russell, Bruce ; Siprawat, Kanlaya ; LINDEGARDH, N ; Lindegardh, Niklas ; Singhasivanon, Pratap ; White, Nicholas J ; Nosten, François. / Dihydroartemisinin-Piperaquine Versus Chloroquine in the Treatment of Plasmodium vivax Malaria in Thailand : A Randomized Controlled Trial. In: Clinical Infectious Diseases. 2011 ; Vol. 53, No. 10. pp. 977-984.
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title = "Dihydroartemisinin-Piperaquine Versus Chloroquine in the Treatment of Plasmodium vivax Malaria in Thailand: A Randomized Controlled Trial",
abstract = "Background: Chloroquine (CQ) remains the treatment of choice for Plasmodium vivax malaria. Initially confined to parts of Indonesia and Papua, resistance of P. vivax to CQ seems to be spreading, and alternative treatments are required. Methods: We conducted a randomized controlled study to compare the efficacy and the tolerability of CQ and dihydroartemisinin-piperaquine (DP) in 500 adults and children with acute vivax malaria on the Northwestern border of Thailand. Results: Both drugs were well tolerated. Fever and parasite clearance times were slower in the CQ than in the DP group (P <. 001). By day 28, recurrent infections had emerged in 18 of 207 CQ recipients compared with 5 of 230 treated with DP (relative risk, 4.0; 95{\%} confidence interval [CI], 1.51-10.58; P =. 0046). The cumulative risk of recurrence with P. vivax at 9 weeks was 79.1{\%} (95{\%} CI, 73.5{\%}-84.8{\%}) in patients treated with CQ compared with 54.9{\%} (95{\%} CI, 48.2{\%}-61.6{\%}) in those receiving DP (hazard ratio [HR], 2.27; 95{\%} CI, 1.8-2.9; P <. 001). Children <5 years old were at greater risk of recurrent P. vivax infection (74.4{\%}; 95{\%} CI, 63.2{\%}-85.6{\%}) than older patients (55.3{\%} [95{\%} CI, 50.2{\%}-60.4{\%}]; HR, 1.58 [95{\%} CI, 1.1-2.2]; P =. 005). In vitro susceptibility testing showed that 13{\%} of the tested isolates had a CQ median inhibitory concentration >100 nmol/L, suggesting reduced susceptibility. Conclusions: The efficacy of CQ in the treatment of P. vivax infections is declining on the Thai-Myanmar border. DP is an effective alternative treatment.",
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author = "Phyo, {Aung Pyae} and Lwin, {Khin Manug} and Ric Price and Elizabeth Ashley and Bruce Russell and Kanlaya Siprawat and N LINDEGARDH and Niklas Lindegardh and Pratap Singhasivanon and White, {Nicholas J} and Fran{\~A}§ois Nosten",
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Phyo, AP, Lwin, KM, Price, R, Ashley, E, Russell, B, Siprawat, K, LINDEGARDH, N, Lindegardh, N, Singhasivanon, P, White, NJ & Nosten, F 2011, 'Dihydroartemisinin-Piperaquine Versus Chloroquine in the Treatment of Plasmodium vivax Malaria in Thailand: A Randomized Controlled Trial', Clinical Infectious Diseases, vol. 53, no. 10, pp. 977-984. https://doi.org/10.1093/cid/cir631

Dihydroartemisinin-Piperaquine Versus Chloroquine in the Treatment of Plasmodium vivax Malaria in Thailand : A Randomized Controlled Trial. / Phyo, Aung Pyae; Lwin, Khin Manug; Price, Ric; Ashley, Elizabeth; Russell, Bruce; Siprawat, Kanlaya; LINDEGARDH, N; Lindegardh, Niklas; Singhasivanon, Pratap; White, Nicholas J; Nosten, François.

In: Clinical Infectious Diseases, Vol. 53, No. 10, 2011, p. 977-984.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Dihydroartemisinin-Piperaquine Versus Chloroquine in the Treatment of Plasmodium vivax Malaria in Thailand

T2 - A Randomized Controlled Trial

AU - Phyo, Aung Pyae

AU - Lwin, Khin Manug

AU - Price, Ric

AU - Ashley, Elizabeth

AU - Russell, Bruce

AU - Siprawat, Kanlaya

AU - LINDEGARDH, N

AU - Lindegardh, Niklas

AU - Singhasivanon, Pratap

AU - White, Nicholas J

AU - Nosten, François

PY - 2011

Y1 - 2011

N2 - Background: Chloroquine (CQ) remains the treatment of choice for Plasmodium vivax malaria. Initially confined to parts of Indonesia and Papua, resistance of P. vivax to CQ seems to be spreading, and alternative treatments are required. Methods: We conducted a randomized controlled study to compare the efficacy and the tolerability of CQ and dihydroartemisinin-piperaquine (DP) in 500 adults and children with acute vivax malaria on the Northwestern border of Thailand. Results: Both drugs were well tolerated. Fever and parasite clearance times were slower in the CQ than in the DP group (P <. 001). By day 28, recurrent infections had emerged in 18 of 207 CQ recipients compared with 5 of 230 treated with DP (relative risk, 4.0; 95% confidence interval [CI], 1.51-10.58; P =. 0046). The cumulative risk of recurrence with P. vivax at 9 weeks was 79.1% (95% CI, 73.5%-84.8%) in patients treated with CQ compared with 54.9% (95% CI, 48.2%-61.6%) in those receiving DP (hazard ratio [HR], 2.27; 95% CI, 1.8-2.9; P <. 001). Children <5 years old were at greater risk of recurrent P. vivax infection (74.4%; 95% CI, 63.2%-85.6%) than older patients (55.3% [95% CI, 50.2%-60.4%]; HR, 1.58 [95% CI, 1.1-2.2]; P =. 005). In vitro susceptibility testing showed that 13% of the tested isolates had a CQ median inhibitory concentration >100 nmol/L, suggesting reduced susceptibility. Conclusions: The efficacy of CQ in the treatment of P. vivax infections is declining on the Thai-Myanmar border. DP is an effective alternative treatment.

AB - Background: Chloroquine (CQ) remains the treatment of choice for Plasmodium vivax malaria. Initially confined to parts of Indonesia and Papua, resistance of P. vivax to CQ seems to be spreading, and alternative treatments are required. Methods: We conducted a randomized controlled study to compare the efficacy and the tolerability of CQ and dihydroartemisinin-piperaquine (DP) in 500 adults and children with acute vivax malaria on the Northwestern border of Thailand. Results: Both drugs were well tolerated. Fever and parasite clearance times were slower in the CQ than in the DP group (P <. 001). By day 28, recurrent infections had emerged in 18 of 207 CQ recipients compared with 5 of 230 treated with DP (relative risk, 4.0; 95% confidence interval [CI], 1.51-10.58; P =. 0046). The cumulative risk of recurrence with P. vivax at 9 weeks was 79.1% (95% CI, 73.5%-84.8%) in patients treated with CQ compared with 54.9% (95% CI, 48.2%-61.6%) in those receiving DP (hazard ratio [HR], 2.27; 95% CI, 1.8-2.9; P <. 001). Children <5 years old were at greater risk of recurrent P. vivax infection (74.4%; 95% CI, 63.2%-85.6%) than older patients (55.3% [95% CI, 50.2%-60.4%]; HR, 1.58 [95% CI, 1.1-2.2]; P =. 005). In vitro susceptibility testing showed that 13% of the tested isolates had a CQ median inhibitory concentration >100 nmol/L, suggesting reduced susceptibility. Conclusions: The efficacy of CQ in the treatment of P. vivax infections is declining on the Thai-Myanmar border. DP is an effective alternative treatment.

KW - chloroquine

KW - dihydroartemisinin plus piperaquine

KW - duocotexin

KW - unclassified drug

KW - adolescent

KW - adult

KW - child

KW - controlled study

KW - drug tolerability

KW - female

KW - fever

KW - human

KW - major clinical study

KW - male

KW - parasite clearance

KW - Plasmodium vivax malaria

KW - preschool child

KW - priority journal

KW - randomized controlled trial

KW - recurrent infection

KW - review

KW - school child

KW - Thailand

KW - Adolescent

KW - Adult

KW - Antimalarials

KW - Artemisinins

KW - Child

KW - Child, Preschool

KW - Chloroquine

KW - Female

KW - Humans

KW - Infant

KW - Malaria, Vivax

KW - Male

KW - Middle Aged

KW - Parasitic Sensitivity Tests

KW - Plasmodium vivax

KW - Quinolines

KW - Recurrence

KW - Risk Factors

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1093/cid/cir631

DO - 10.1093/cid/cir631

M3 - Article

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SP - 977

EP - 984

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

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ER -