Reductions in malaria in pregnancy and adverse birth outcomes following indoor residual spraying of insecticide in Uganda

Mary K Muhindo, Abel Kakuru, Paul Natureeba, Patricia Awori, Peter Olwoch, John Ategeka, Patience Nayebare, Tamara D Clark, Atis Muehlenbachs, Michelle Roh, Betty Mpeka, Bryan Greenhouse, Diane V Havlir, Moses R Kamya, Grant Dorsey, Prasanna Jagannathan, Mary K Muhindo, Abel Kakuru, Paul Natureeba, Patricia Awori, Peter Olwoch, John Ategeka, Patience Nayebare, Tamara D Clark, Atis Muehlenbachs, Michelle Roh, Betty Mpeka, Bryan Greenhouse, Diane V Havlir, Moses R Kamya, Grant Dorsey, Prasanna Jagannathan

Abstract

Background: Indoor residual spraying of insecticide (IRS) is a key intervention for reducing the burden of malaria in Africa. However, data on the impact of IRS on malaria in pregnancy and birth outcomes is limited.

Methods: An observational study was conducted within a trial of intermittent preventive therapy during pregnancy in Tororo, Uganda. Women were enrolled at 12-20 weeks of gestation between June and October 2014, provided with insecticide-treated bed nets, and followed through delivery. From December 2014 to February 2015, carbamate-containing IRS was implemented in Tororo district for the first time. Exact spray dates were collected for each household. The exposure of interest was the proportion of time during a woman's pregnancy under protection of IRS, with three categories of protection defined: no IRS protection, >0-20 % IRS protection, and 20-43 % IRS protection. Outcomes assessed included malaria incidence and parasite prevalence during pregnancy, placental malaria, low birth weight (LBW), pre-term delivery, and fetal/neonatal deaths.

Results: Of 289 women followed, 134 had no IRS protection during pregnancy, 90 had >0-20 % IRS protection, and 65 had >20-43 % protection. During pregnancy, malaria incidence (0.49 vs 0.10 episodes ppy, P = 0.02) and parasite prevalence (20.0 vs 8.9 %, P < 0.001) were both significantly lower after IRS. At the time of delivery, the prevalence of placental parasitaemia was significantly higher in women with no IRS protection (16.8 %) compared to women with 0-20 % (1.1 %, P = 0.001) or >20-43 % IRS protection (1.6 %, P = 0.006). Compared to women with no IRS protection, those with >20-43 % IRS protection had a lower risk of LBW (20.9 vs 3.1 %, P = 0.002), pre-term birth (17.2 vs 1.5 %, P = 0.006), and fetal/neonatal deaths (7.5 vs 0 %, P = 0.03).

Conclusion: In this setting, IRS was temporally associated with lower malaria parasite prevalence during pregnancy and at delivery, and improved birth outcomes. IRS may represent an important tool for combating malaria in pregnancy and for improving birth outcomes in malaria-endemic settings. Trial Registration Current Controlled Trials Identifier NCT02163447.

Keywords: Indoor residual spraying; Malaria in pregnancy; Placental malaria; Plasmodium falciparum; Vector-borne disease.

Figures

Fig. 1
Fig. 1
Temporal trends with enrolment, delivery and entomological measures. Shown are the number of women enrolled (blue bars) and number of women delivered (green bars) each month between 2014 and 2015. The red line (2013–2014) and yellow line (2014–2015) represent the number of female anopheline mosquitoes collected per household per night (right y axis) in Tororo district from 100 randomly selected households enrolled in the International Centers of Excellence in Malaria Research cohort [21]
Fig. 2
Fig. 2
Parasite prevalence during pregnancy by calendar month before, during and after IRS. Shown is the predicted probability of having a positive (+) LAMP result during pregnancy, stratified by IPTp arm, after enrolment and initiation of study drugs, over the period of time of the study. Parasite prevalence point estimates and standard errors obtained using generalized estimating equations after adjustment for gravidity, age, and gestational age when study drugs were started. Grey-shaded bar shows the time period of IRS in Tororo district. SP (black): sulfadoxine-pyrimethamine; DP (blue): dihydroartemisinin-piperaquine
Fig. 3
Fig. 3
Impact of IRS on birth weight. Shown are birth weights (clear circles) from infants born to mothers with no IRS exposure (n = 134), >0–20 % exposure (n = 90), and >20–43 % exposure (n = 65). Also shown are model adjusted means and 95 % CI (lines and error bars), and P values comparing birth weights between groups, adjusted for gravidity, gestation age study drugs started, wealth category, LAMP at enrolment, and treatment arm

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