title: Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia.
abstract: BACKGROUND
  Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) decreases adverse effects of malaria during pregnancy. Zambia implemented its IPTp-SP programme in 2003. Emergence of SP-resistant Plasmodium falciparum threatens this strategy. The quintuple mutant haplotype (substitutions in N51I, C59R, S108N in dhfr and A437G and K540E in dhps genes), is associated with SP treatment failure in non-pregnant patients with malaria. This study examined efficacy of IPTp-SP and presence of the quintuple mutant among pregnant women in Mansa, Zambia.
  
  
  METHODS
  In Mansa, an area with high malaria transmission, HIV-negative pregnant women presenting to two antenatal clinics for the 1st dose of IPTp-SP with asymptomatic parasitaemia were enrolled and microscopy for parasitaemia was done weekly for five weeks. Outcomes were parasitological failure and adequate parasitological response (no parasitaemia during follow-up). Polymerase chain reaction assays were employed to distinguish recrudescence from reinfection, and identify molecular markers of SP resistance. Survival analysis included those who had reinfection and incomplete follow-up (missed at least one follow-up).
  
  
  RESULTS
  Of the 109 women included in the study, 58 (53%) completed all follow-up, 34 (31%) had incomplete follow-up, and 17 (16%) were lost to follow-up after day 0. Of those who had complete follow-up, 15 (26%, 95% confidence interval [CI] [16-38]) had parasitological failure. For the 92 women included in the survival analysis, median age was 20 years (interquartile range [IQR] 18-22), median gestational age was 22 weeks (IQR range 20-24), and 57% were primigravid. There was no difference in time to failure in primigravid versus multigravid women. Of the 84 women with complete haplotype data for the aforementioned loci of the dhfr and dhps genes, 53 (63%, 95% CI [50-70]) had quintuple mutants (two with an additional mutation in A581G of dhps). Among women with complete follow-up and quintuple mutants, 22% had parasitological failure versus 0% without (p = 0.44).
  
  
  CONCLUSIONS
  While underpowered, this study found 26% failure rates of SP given the moderate prevalence of the quintuple mutant haplotype. Despite the presence of resistance, SP retained some efficacy in clearing parasites in pregnant women, and may remain a viable option for IPTp in Zambia.
authors.affiliation: Malaria Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA. ktan@cdc.gov.
authors.forename: Kathrine R
authors.initials: KR
authors.lastname: Tan
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Katalenich
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Mace
authors.forename: Michael
authors.initials: M
authors.lastname: Nambozi
authors.forename: Steve M
authors.initials: SM
authors.lastname: Taylor
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Wiegand
authors.forename: Victor
authors.initials: V
authors.lastname: Chalwe
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Filler
authors.forename: Mulakwa
authors.initials: M
authors.lastname: Kamuliwo
authors.forename: Allen S
authors.initials: AS
authors.lastname: Craig
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D004338:Drug Combinations; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000517:prevention & control*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control*; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D016019:Survival Analysis; D017211:Treatment Failure; D055815:Young Adult; D015024:Zambia
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine