Procedures
malaria, illness, fever, ill
STIS, BACTERIAL VAGINOSIS, MALARIA
At enrolment, demographic, socioeconomic, and educational information was collected from the participant on standardised case report forms. Participants had their medical and obstetric history recorded, a venous blood and urine sample collected, and they underwent a routine medical examination and an ultrasound scan to assess their gestational age. The randomly selected subgroup of a third of participants had vaginal swabs taken to assess for the presence of curable STIs and bacterial vaginosis. All participants received a long-lasting insecticide-treated net as part of routine antenatal care.Each sulfadoxine–pyrimethamine course consisted of three tablets containing 500 mg of sulfadoxine and 25 mg of pyrimethamine (unbranded generic sulfadoxine–pyrimethamine, Medopharm, Chennai, India; quality controlled by Durbin, Hayes, UK) given as a single oral dose for 1 day (In Kenya and Tanzania, women were screened for malaria at enrolment using malaria rapid diagnostic tests (RDTs) as per national guidelines. All women who tested negative in all groups received their first course of IPTp at enrolment; women who tested positive in all groups in Kenya and those who tested positive in the IPTp with sulfadoxine–pyrimethamine group in Tanzania received a standard 3-day treatment course with artemether–lumefantrine. The first dose of IPTp was delayed until the next scheduled visit 4 weeks later. In Tanzania, women who tested positive for malaria in both the groups that included dihydroartemisinin–piperaquine received their first course of IPTp with dihydroartemisinin–piperaquine or IPTp with dihydroartemisinin–piperaquine plus azithromycin at enrolment instead of artemether-lumefantrine (Participants attended study clinics every 4 weeks, during which a clinical history of recent illness and drug use was taken and a clinical and obstetric examination was done. A blood sample was taken for malaria microscopy, quantitative PCR (qPCR), and targeted next-generation sequencing for molecular markers of sulfadoxine–pyrimethamine resistance for later examination, not to inform patient care. Haemoglobin and routine urinalysis were assessed during the last scheduled visit in the third trimester. Women were encouraged to make unscheduled visits if they felt ill or were concerned about their pregnancy. Women with documented fever or a history of fever during or between scheduled visits were tested for malaria by RDT. Women who tested positive for malaria in all groups received a 3-day course of artemether–lumefantrine. If this treatment overlapped with a scheduled IPTp visit, the IPTp course was delayed for 4 weeks, until the next scheduled visit. In the random sample of a third of women from each site, fetal weight was estimated by ultrasound scan at enrolment if the gestational age was at least 22 weeks and converted into Z scores using the INTERGROWTH-21 reference (In all participants, a maternal venous blood sample for the same malaria metrics was taken at delivery (during labour where possible), combined with placental and cord-blood samples for placental histology, malaria RDT, microscopy, and qPCR. qPCR samples at enrolment and delivery were analysed for all participants. The qPCR samples taken between enrolment and delivery were analysed in the third of all participants selected for serial ultrasound and third trimester assessment of STIs and bacterial vaginosis described earlier. Newborn babies were weighed as soon as study staff were notified of birth (In a subgroup of 189 women from Malawi and Kenya who were in the two IPTp groups containing dihydroartemisinin–piperaquine, three sets of electrocardiograms were done to assess the heart-rate corrected QT intervals (QTc) before the first daily dose of dihydroartemisinin–piperaquine and 4 h after the third daily dose at enrolment, and twice more during pregnancy (approximately 1–2 and 3–4 months later; 