Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Dec 3;19(1):449.
doi: 10.1186/s12936-020-03522-z.

Infant sex modifies associations between placental malaria and risk of malaria in infancy

Abel Kakuru  1   2 , Michelle E Roh  3 , Richard Kajubi  4 , Teddy Ochieng  4 , John Ategeka  4 , Harriet Ochokoru  4 , Miriam Nakalembe  5 , Tamara D Clark  6 , Theodore Ruel  7 , Sarah G Staedke  8 , Daniel Chandramohan  8 , Diane V Havlir  6 , Moses R Kamya  9 , Grant Dorsey  6 , Prasanna Jagannathan  10
Affiliations
Randomized Controlled Trial

Infant sex modifies associations between placental malaria and risk of malaria in infancy

Abel Kakuru et al. Malar J. .

Abstract

Background: Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM.

Methods: Data from a birth cohort of 656 infants born to HIV-uninfected mothers randomised to IPTp with dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) was analysed. PM was categorized as no PM, active PM (presence of parasites), mild-moderate past PM (> 0-20% high powered fields [HPFs] with pigment), or severe past PM (> 20% HPFs with pigment). The association between PM and incidence of malaria in infants stratified by infant sex was examined. Causal mediation analysis was used to test whether IPTp can impact infant malaria incidence via preventing PM.

Results: There were 1088 malaria episodes diagnosed among infants during 596.6 person years of follow-up. Compared to infants born to mothers with no PM, the incidence of malaria was higher among infants born to mothers with active PM (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.00-1.71, p = 0.05) and those born to mothers with severe past PM (aIRR 1.28, 95% CI 0.89-1.83, p = 0.18), but the differences were not statistically significant. However, when stratifying by infant sex, compared to no PM, severe past PM was associated a higher malaria incidence in male (aIRR 2.17, 95% CI 1.45-3.25, p < 0.001), but not female infants (aIRR 0.74, 95% CI 0.46-1.20, p = 0.22). There were no significant associations between active PM or mild-moderate past PM and malaria incidence in male or female infants. Male infants born to mothers given IPTp with DP had significantly less malaria in infancy than males born to mothers given SP, and 89.7% of this effect was mediated through prevention of PM.

Conclusion: PM may have more severe consequences for male infants, and interventions which reduce PM could mitigate these sex-specific adverse outcomes. More research is needed to better understand this sex-bias between PM and infant malaria risk. Trial registration ClinicalTrials.gov, NCT02793622. Registered 8 June 2016, https://clinicaltrials.gov/ct2/show/NCT02793622.

Keywords: Infants; Placental malaria; Plasmodium falciparum; Pregnancy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Study profile. IPTp intermittent preventive treatment in pregnancy, DP dihydroartemisinin–piperaquine, SP sulfadoxine–pyrimethamine
Fig. 2
Fig. 2
Time to first episode of malaria stratified by infant sex. a All infants, b male infants c  female infants. PM placental malaria, mild-mod  mild-moderate, No PM no parasites or pigment detected, active PM parasites detected with or without pigment, past PM (mild-mod) > 0–20% of high-power fields with pigment but no parasites, past PM(severe)  > 20%–60% of high-power fields with pigment but no parasites
See this image and copyright information in PMC

References

    1. Sharma L, Shukla G. Placental malaria: a new insight into the pathophysiology. Front Med (Lausanne). 2017;4:117. doi: 10.3389/fmed.2017.00117. - DOI - PMC - PubMed
    1. Walker PG, ter Kuile FO, Garske T, Menendez C, Ghani AC. Estimated risk of placental infection and low birthweight attributable to Plasmodium falciparum malaria in Africa in 2010: a modelling study. Lancet Glob Health. 2014;2:e460–e467. doi: 10.1016/S2214-109X(14)70256-6. - DOI - PubMed
    1. Moore KA, Simpson JA, Scoullar MJL, McGready R, Fowkes FJI. Quantification of the association between malaria in pregnancy and stillbirth: a systematic review and meta-analysis. Lancet Glob Health. 2017;5:e1101–e1112. doi: 10.1016/S2214-109X(17)30340-6. - DOI - PubMed
    1. Kapisi J, Kakuru A, Jagannathan P, Muhindo MK, Natureeba P, Awori P, et al. Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes. Malar J. 2017;16:400. doi: 10.1186/s12936-017-2040-4. - DOI - PMC - PubMed
    1. Kajubi R, Ochieng T, Kakuru A, Jagannathan P, Nakalembe M, Ruel T, et al. Monthly Sulfadoxine–pyrimethamine versus dihydroartemisinin–piperaquine for intermittent preventive treatment of malaria in pregnancy: a double-blind, randomised, controlled, superiority trial. Lancet. 2019;393:1428–1439. doi: 10.1016/S0140-6736(18)32224-4. - DOI - PubMed

Publication types

MeSH terms

Associated data