Dihydroartemisinin-Piperaquine Treatment of Multidrug Resistant Falciparum and Vivax Malaria in Pregnancy

Jeanne Rini Poespoprodjo, Wendelina Fobia, Enny Kenangalem, Daniel Lampah, Paulus Sugiarto, Emiliana Tjitra, Nicholas Anstey, Ric Price

Research output: Contribution to journalArticleResearchpeer-review

6 Downloads (Pure)

Abstract

Background: Artemisinin combination therapy (ACT) is recommended for the treatment of multidrug resistant malaria in the second and third trimesters of pregnancy, but the experience with ACTs is limited. We review the exposure of pregnant women to the combination dihydroartemisinin-piperaquine over a 6 year period.

Methods: From April 2004–June 2009, a prospective hospital-based surveillance screened all pregnant women for malaria and documented maternal and neonatal outcomes.

Results: Data were available on 6519 pregnant women admitted to hospital; 332 (5.1%) women presented in the first trimester, 324 (5.0%) in the second, 5843 (89.6%) in the third, and in 20 women the trimester was undocumented. Peripheral parasitaemia was confirmed in 1682 women, of whom 106 (6.3%) had severe malaria. Of the 1217 women admitted with malaria in the second and third trimesters without an impending adverse outcome, those treated with DHP were more likely to be discharged with an ongoing pregnancy compared to those treated with a non-ACT regimen (Odds Ratio OR = 2.48 [1.26–4.86]); p = 0.006. However in the first trimester 63% (5/8) of women treated with oral DHP miscarried compared to 2.6% (1/38) of those receiving oral quinine; p<0.001. Of the 847 women admitted for delivery those reporting a history of malaria during their pregnancy who had been treated with quinine-based regimens rather than DHP had a higher risk of malaria at delivery (adjusted OR = 1.56 (95%CI 0.97–2.5), p = 0.068) and perinatal mortality (adjusted OR = 3.17 [95%CI: 1.17–8.60]; p = 0.023).

Conclusions: In the second and third trimesters of pregnancy, a three day course of DHP simplified antimalarial treatment and had significant benefits over quinine-based regimens in reducing recurrent malaria and poor fetal outcome. These data provide reassuring evidence for the rational design of prospective randomized clinical trials and pharmacokinetic studies.
Original languageEnglish
Article numbere84976
Pages (from-to)1-9
Number of pages9
JournalPLoS One
Volume9
Issue number1
DOIs
Publication statusPublished - 17 Jan 2014

Fingerprint

dihydroartemisinin
Vivax Malaria
Quinine
Falciparum Malaria
malaria
Malaria
pregnancy
Pregnancy
quinine
Third Pregnancy Trimester
Second Pregnancy Trimester
pregnant women
Pharmacokinetics
Pregnant Women
Antimalarials
First Pregnancy Trimester
Therapeutics
mouth
artemisinin
therapeutics

Cite this

Poespoprodjo, J. R., Fobia, W., Kenangalem, E., Lampah, D., Sugiarto, P., Tjitra, E., ... Price, R. (2014). Dihydroartemisinin-Piperaquine Treatment of Multidrug Resistant Falciparum and Vivax Malaria in Pregnancy. PLoS One, 9(1), 1-9. [e84976]. https://doi.org/10.1371/journal.pone.0084976
Poespoprodjo, Jeanne Rini ; Fobia, Wendelina ; Kenangalem, Enny ; Lampah, Daniel ; Sugiarto, Paulus ; Tjitra, Emiliana ; Anstey, Nicholas ; Price, Ric. / Dihydroartemisinin-Piperaquine Treatment of Multidrug Resistant Falciparum and Vivax Malaria in Pregnancy. In: PLoS One. 2014 ; Vol. 9, No. 1. pp. 1-9.
@article{92f763c90ccd4513892295cacdb6db7d,
title = "Dihydroartemisinin-Piperaquine Treatment of Multidrug Resistant Falciparum and Vivax Malaria in Pregnancy",
abstract = "Background: Artemisinin combination therapy (ACT) is recommended for the treatment of multidrug resistant malaria in the second and third trimesters of pregnancy, but the experience with ACTs is limited. We review the exposure of pregnant women to the combination dihydroartemisinin-piperaquine over a 6 year period.Methods: From April 2004–June 2009, a prospective hospital-based surveillance screened all pregnant women for malaria and documented maternal and neonatal outcomes.Results: Data were available on 6519 pregnant women admitted to hospital; 332 (5.1{\%}) women presented in the first trimester, 324 (5.0{\%}) in the second, 5843 (89.6{\%}) in the third, and in 20 women the trimester was undocumented. Peripheral parasitaemia was confirmed in 1682 women, of whom 106 (6.3{\%}) had severe malaria. Of the 1217 women admitted with malaria in the second and third trimesters without an impending adverse outcome, those treated with DHP were more likely to be discharged with an ongoing pregnancy compared to those treated with a non-ACT regimen (Odds Ratio OR = 2.48 [1.26–4.86]); p = 0.006. However in the first trimester 63{\%} (5/8) of women treated with oral DHP miscarried compared to 2.6{\%} (1/38) of those receiving oral quinine; p<0.001. Of the 847 women admitted for delivery those reporting a history of malaria during their pregnancy who had been treated with quinine-based regimens rather than DHP had a higher risk of malaria at delivery (adjusted OR = 1.56 (95{\%}CI 0.97–2.5), p = 0.068) and perinatal mortality (adjusted OR = 3.17 [95{\%}CI: 1.17–8.60]; p = 0.023).Conclusions: In the second and third trimesters of pregnancy, a three day course of DHP simplified antimalarial treatment and had significant benefits over quinine-based regimens in reducing recurrent malaria and poor fetal outcome. These data provide reassuring evidence for the rational design of prospective randomized clinical trials and pharmacokinetic studies.",
keywords = "artesunate, clindamycin, dihydroartemisinin plus piperaquine, quinine, adult, adverse outcome, article, controlled study, delivery, disease severity, drug exposure, female, fetus outcome, first trimester pregnancy, high risk population, hospital patient, human, major clinical study, malaria falciparum, maternal care, medical history, multidrug resistance, parasitemia, perinatal mortality, Plasmodium vivax malaria, pregnancy, pregnancy outcome, pregnant woman, prospective study, second trimester pregnancy, third trimester pregnancy, treatment duration, Acute Disease, Antimalarials, Artemisinins, Drug Resistance, Multiple, Female, Humans, Malaria, Falciparum, Malaria, Vivax, Parasitemia, Pregnancy, Pregnancy Complications, Parasitic, Pregnancy Outcome, Quinolines",
author = "Poespoprodjo, {Jeanne Rini} and Wendelina Fobia and Enny Kenangalem and Daniel Lampah and Paulus Sugiarto and Emiliana Tjitra and Nicholas Anstey and Ric Price",
year = "2014",
month = "1",
day = "17",
doi = "10.1371/journal.pone.0084976",
language = "English",
volume = "9",
pages = "1--9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science (PLoS)",
number = "1",

}

Poespoprodjo, JR, Fobia, W, Kenangalem, E, Lampah, D, Sugiarto, P, Tjitra, E, Anstey, N & Price, R 2014, 'Dihydroartemisinin-Piperaquine Treatment of Multidrug Resistant Falciparum and Vivax Malaria in Pregnancy', PLoS One, vol. 9, no. 1, e84976, pp. 1-9. https://doi.org/10.1371/journal.pone.0084976

Dihydroartemisinin-Piperaquine Treatment of Multidrug Resistant Falciparum and Vivax Malaria in Pregnancy. / Poespoprodjo, Jeanne Rini; Fobia, Wendelina; Kenangalem, Enny; Lampah, Daniel; Sugiarto, Paulus; Tjitra, Emiliana; Anstey, Nicholas; Price, Ric.

In: PLoS One, Vol. 9, No. 1, e84976, 17.01.2014, p. 1-9.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Dihydroartemisinin-Piperaquine Treatment of Multidrug Resistant Falciparum and Vivax Malaria in Pregnancy

AU - Poespoprodjo, Jeanne Rini

AU - Fobia, Wendelina

AU - Kenangalem, Enny

AU - Lampah, Daniel

AU - Sugiarto, Paulus

AU - Tjitra, Emiliana

AU - Anstey, Nicholas

AU - Price, Ric

PY - 2014/1/17

Y1 - 2014/1/17

N2 - Background: Artemisinin combination therapy (ACT) is recommended for the treatment of multidrug resistant malaria in the second and third trimesters of pregnancy, but the experience with ACTs is limited. We review the exposure of pregnant women to the combination dihydroartemisinin-piperaquine over a 6 year period.Methods: From April 2004–June 2009, a prospective hospital-based surveillance screened all pregnant women for malaria and documented maternal and neonatal outcomes.Results: Data were available on 6519 pregnant women admitted to hospital; 332 (5.1%) women presented in the first trimester, 324 (5.0%) in the second, 5843 (89.6%) in the third, and in 20 women the trimester was undocumented. Peripheral parasitaemia was confirmed in 1682 women, of whom 106 (6.3%) had severe malaria. Of the 1217 women admitted with malaria in the second and third trimesters without an impending adverse outcome, those treated with DHP were more likely to be discharged with an ongoing pregnancy compared to those treated with a non-ACT regimen (Odds Ratio OR = 2.48 [1.26–4.86]); p = 0.006. However in the first trimester 63% (5/8) of women treated with oral DHP miscarried compared to 2.6% (1/38) of those receiving oral quinine; p<0.001. Of the 847 women admitted for delivery those reporting a history of malaria during their pregnancy who had been treated with quinine-based regimens rather than DHP had a higher risk of malaria at delivery (adjusted OR = 1.56 (95%CI 0.97–2.5), p = 0.068) and perinatal mortality (adjusted OR = 3.17 [95%CI: 1.17–8.60]; p = 0.023).Conclusions: In the second and third trimesters of pregnancy, a three day course of DHP simplified antimalarial treatment and had significant benefits over quinine-based regimens in reducing recurrent malaria and poor fetal outcome. These data provide reassuring evidence for the rational design of prospective randomized clinical trials and pharmacokinetic studies.

AB - Background: Artemisinin combination therapy (ACT) is recommended for the treatment of multidrug resistant malaria in the second and third trimesters of pregnancy, but the experience with ACTs is limited. We review the exposure of pregnant women to the combination dihydroartemisinin-piperaquine over a 6 year period.Methods: From April 2004–June 2009, a prospective hospital-based surveillance screened all pregnant women for malaria and documented maternal and neonatal outcomes.Results: Data were available on 6519 pregnant women admitted to hospital; 332 (5.1%) women presented in the first trimester, 324 (5.0%) in the second, 5843 (89.6%) in the third, and in 20 women the trimester was undocumented. Peripheral parasitaemia was confirmed in 1682 women, of whom 106 (6.3%) had severe malaria. Of the 1217 women admitted with malaria in the second and third trimesters without an impending adverse outcome, those treated with DHP were more likely to be discharged with an ongoing pregnancy compared to those treated with a non-ACT regimen (Odds Ratio OR = 2.48 [1.26–4.86]); p = 0.006. However in the first trimester 63% (5/8) of women treated with oral DHP miscarried compared to 2.6% (1/38) of those receiving oral quinine; p<0.001. Of the 847 women admitted for delivery those reporting a history of malaria during their pregnancy who had been treated with quinine-based regimens rather than DHP had a higher risk of malaria at delivery (adjusted OR = 1.56 (95%CI 0.97–2.5), p = 0.068) and perinatal mortality (adjusted OR = 3.17 [95%CI: 1.17–8.60]; p = 0.023).Conclusions: In the second and third trimesters of pregnancy, a three day course of DHP simplified antimalarial treatment and had significant benefits over quinine-based regimens in reducing recurrent malaria and poor fetal outcome. These data provide reassuring evidence for the rational design of prospective randomized clinical trials and pharmacokinetic studies.

KW - artesunate

KW - clindamycin

KW - dihydroartemisinin plus piperaquine

KW - quinine

KW - adult

KW - adverse outcome

KW - article

KW - controlled study

KW - delivery

KW - disease severity

KW - drug exposure

KW - female

KW - fetus outcome

KW - first trimester pregnancy

KW - high risk population

KW - hospital patient

KW - human

KW - major clinical study

KW - malaria falciparum

KW - maternal care

KW - medical history

KW - multidrug resistance

KW - parasitemia

KW - perinatal mortality

KW - Plasmodium vivax malaria

KW - pregnancy

KW - pregnancy outcome

KW - pregnant woman

KW - prospective study

KW - second trimester pregnancy

KW - third trimester pregnancy

KW - treatment duration

KW - Acute Disease

KW - Antimalarials

KW - Artemisinins

KW - Drug Resistance, Multiple

KW - Female

KW - Humans

KW - Malaria, Falciparum

KW - Malaria, Vivax

KW - Parasitemia

KW - Pregnancy

KW - Pregnancy Complications, Parasitic

KW - Pregnancy Outcome

KW - Quinolines

UR - http://www.scopus.com/inward/record.url?scp=84898426433&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0084976

DO - 10.1371/journal.pone.0084976

M3 - Article

VL - 9

SP - 1

EP - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e84976

ER -

Poespoprodjo JR, Fobia W, Kenangalem E, Lampah D, Sugiarto P, Tjitra E et al. Dihydroartemisinin-Piperaquine Treatment of Multidrug Resistant Falciparum and Vivax Malaria in Pregnancy. PLoS One. 2014 Jan 17;9(1):1-9. e84976. https://doi.org/10.1371/journal.pone.0084976