title: In vivo efficacy of sulphadoxine-pyrimethamine for the treatment of asymptomatic parasitaemia in pregnant women in Machinga District, Malawi.
abstract: BACKGROUND
  The effectiveness of sulphadoxine-pyrimethamine (SP) intermittent preventive treatment of malaria in pregnancy (IPTp) might be compromised by high prevalence of resistance-associated Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations. As a proxy for IPTp-SP effectiveness, the in vivo efficacy of SP to clear parasitaemia and prevent reinfection in asymptomatic parasitaemic pregnant women in an area with high SP resistance prevalence was assessed.
  
  
  METHODS
  Pregnant women 16-26 weeks' gestation with asymptomatic parasitaemia presenting for antenatal care were given IPTp-SP and followed for 42 days. The primary outcome was polymerase chain reaction (PCR) uncorrected 42-day survival rate; the per cent of patients without recrudescence or reinfection by day 42. PCR was used to distinguish recrudescence from reinfection. DNA was sequenced to detect resistance-associated dhfr and dhps mutations.
  
  
  RESULTS
  Of 245 pregnant women included in the intention-to-treat analysis, 93.9% cleared their parasitaemia by day 7. The day 42 PCR-uncorrected survival rate was 58.1% (95% confidence interval (CI) 51.5-65.7) and day 42 PCR-corrected survival was 68.7% (CI 61.4-76.0). Recrudescence was more common among primi- than among multigravid women; recrudescence rate 33.3% (CI 25.1-42.4%) versus 21.4% (CI 15.0-29.0%) (log rank test p-value 0.006). The quintuple mutant was present in nearly all samples (95%), while 2% were sextuple mutants with an additional mutation at dhps A581G.
  
  
  CONCLUSIONS
  SP efficacy for acute malaria treatment has been compromised by resistance, but SP retains partial activity among pregnant women with asymptomatic parasitaemia, and thus might be useful for IPTp. Nonetheless, research on non-SP IPTp regimens should continue.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01120145 .
authors.affiliation: Malaria Branch, Division of Parasitic Diseases & Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA. jgutman@cdc.gov.
authors.forename: Julie
authors.initials: J
authors.lastname: Gutman
authors.affiliation: Malaria Alert Centre, University of Malawi College of Medicine, Blantyre, Malawi. dmwandama@mac.medcol.mw.
authors.forename: Dyson
authors.initials: D
authors.lastname: Mwandama
authors.affiliation: Malaria Branch, Division of Parasitic Diseases & Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA. fwk2@cdc.gov.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Wiegand
authors.affiliation: Rwanda Zambia HIV Research Group, Emory University, Atlanta, GA, USA. joseph.farahat.abdallah@emory.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Abdallah
authors.affiliation: Malaria Branch, Division of Parasitic Diseases & Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA. iqd4@cdc.gov.
authors.forename: Nnaemeka C
authors.initials: NC
authors.lastname: Iriemenam
authors.affiliation: Malaria Branch, Division of Parasitic Diseases & Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA. yps0@cdc.gov.
authors.forename: Ya Ping
authors.initials: YP
authors.lastname: Shi
authors.affiliation: Malaria Alert Centre, University of Malawi College of Medicine, Blantyre, Malawi. dmathang@mac.medcol.mw.|Department of Community Health, College of Medicine, Lilongwe, Malawi. dmathang@mac.medcol.mw.
authors.forename: Don P
authors.initials: DP
authors.lastname: Mathanga
authors.affiliation: Malaria Branch, Division of Parasitic Diseases & Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA. dvo5@cdc.gov.
authors.forename: Jacek
authors.initials: J
authors.lastname: Skarbinski
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D058345:Asymptomatic Infections; D004094:Dihydropteroate Synthase / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008295:Malawi / Q000453:epidemiology; D018512:Parasitemia / Q000188:drug therapy* / Q000469:parasitology; D010298:Parity; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine