Taylor, Steve M, Levitt, Brandt, Freedman, Betsy, Madanitsa, Mwayiwawo, Thwai, Kyaw-Lay, Kalilani-Phiri, Linda, Khairallah, Carole, Mwapasa, Victor, terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617 and Meshnick, Steven R (2020) 'Interactions between antenatal sulfadoxine-pyrimethamine, drug-resistant Plasmodium falciparum parasites and delivery outcomes in Malawi.'. Journal of Infectious Disease, Vol 222, Issue 4, pp. 661-669.
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Abstract
BACKGROUND
Sulfadoxine-pyrimethamine (SP) is used as intermittent preventive therapy in pregnancy (IPTp) for malaria in sub-Saharan Africa. The resistance marker dhps A581G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP-recipients.
METHODS
We measured SP-resistance allele frequencies in Malawian women participating in a trial (www.isrctn.com/ISRCTN69800930) comparing IPTp with SP against intermittent screening by rapid diagnostic tests (ISTp). We genotyped PCR-detected parasites using deep sequencing of SP-resistance alleles.
RESULTS
Among 125 placental infections, A581G-bearing parasites were associated with reduced birthweight (mean difference[MD]:252g, 95% CI:46,457, p=0.017). Relative to ISTp, IPTp-SP was associated with higher birthweights in women with wildtype parasites (MD:116g, 95% CI:-40,272; p=0.142) and lower birthweights in women with A581G-bearing parasites (MD:192g, 95% CI:-264,648; p=0.385) (pinteraction=0.033). Similar associations were noted on gestational age (pinteraction=0.075). Amongst only IPTp-SP recipients, relative to women who last received SP >4 weeks before delivery, recent SP receipt was associated with lower birthweight in women with wildtype parasites (MD:118g, 95% CI:-376,139; p=0.361) and higher birthweight in women with A581G-bearing parasites (MD:783g, 95% CI:-20,1586; p=0.054) (pinteraction=0.005).
CONCLUSIONS
The effectiveness on birthweight of IPTp-SP is compromised by A581G-bearing parasites, but there was no evidence that the adverse effects of these parasites are exacerbated by antenatal SP.
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