TY - JOUR
T1 - Interactions between antenatal sulfadoxine-pyrimethamine, drug-resistant Plasmodium falciparum parasites and delivery outcomes in Malawi.
AU - Taylor, Steve M.
AU - Levitt, Brandt
AU - Freedman, Betsy
AU - Madanitsa, Mwayiwawo
AU - Thwai, Kyaw Lay
AU - Kalilani-Phiri, Linda
AU - Khairallah, Carole
AU - Mwapasa, Victor
AU - Ter Kuile, Feiko
AU - Meshnick, Steven R.
PY - 2020/8/15
Y1 - 2020/8/15
N2 - BACKGROUNDSulfadoxine-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.METHODSWe 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.RESULTSAmong 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).CONCLUSIONSThe 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.
AB - BACKGROUNDSulfadoxine-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.METHODSWe 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.RESULTSAmong 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).CONCLUSIONSThe 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.
KW - Drug resistance
KW - Malaria
KW - Malaria in pregnancy
KW - Placental malaria
KW - Prevention
U2 - 10.1093/infdis/jiaa145
DO - 10.1093/infdis/jiaa145
M3 - Article
SN - 0022-1899
VL - 222
SP - 661
EP - 669
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -
