Impact of Sulfadoxine-Pyrimethamine resistance on effectiveness of intermittent preventive therapy for malaria in pregnancy at clearing infections and preventing low birth weight

TY - JOUR

T1 - Impact of Sulfadoxine-Pyrimethamine resistance on effectiveness of intermittent preventive therapy for malaria in pregnancy at clearing infections and preventing low birth weight

AU - Desai, Meghna

AU - Gutman, Julie

AU - Taylor, Steve M.

AU - Wiegand, Ryan E

AU - Khairallah, Carole

AU - Kayentao, Kassoum

AU - Ouma, Peter

AU - Coulibaly, Sheick O.

AU - Kalilani, Linda

AU - Mace, Kimberly E.

AU - Arinaitwe, Emmanuel

AU - Mathanga, Don P.

AU - Doumbo, Ogobara

AU - Otieno, Kephas

AU - Edgar, Dabira

AU - Chaluluka, Ebbie

AU - Kamuliwo, Mulakwa

AU - Ades, Veronica

AU - Skarbinski, Jacek

AU - Shi, Ya Ping

AU - Magnussen, Pascal

AU - Meshnick, Steve

AU - Kuile, Feiko O. ter

N1 - Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Background. Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial. Methods. Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. Results. Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI],. 69-.88; P <. 001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI,. 67-.97; P =. 02). Conclusions. The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

AB - Background. Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial. Methods. Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. Results. Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI],. 69-.88; P <. 001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI,. 67-.97; P =. 02). Conclusions. The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

U2 - 10.1093/cid/civ881

DO - 10.1093/cid/civ881

M3 - Journal article

C2 - 26486699

SN - 1058-4838

VL - 62

SP - 323

EP - 233

JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

IS - 3

ER -