title: Impact of daily cotrimoxazole on clinical malaria and asymptomatic parasitemias in HIV-exposed, uninfected infants.
abstract: BACKGROUND
  Cotrimoxazole preventive therapy (CPT) is recommended for all human immunodeficiency virus (HIV)-exposed infants to avoid opportunistic infections. Cotrimoxazole has antimalarial effects and appears to reduce clinical malaria infections, but the impact on asymptomatic malaria infections is unknown.
  
  
  METHODS
  We conducted an observational cohort study using data and dried blood spots (DBSs) from the Breastfeeding, Antiretrovirals and Nutrition study to evaluate the impact of CPT on malaria infection during peak malaria season in Lilongwe, Malawi. We compared malaria incidence 1 year before and after CPT implementation (292 and 682 CPT-unexposed and CPT-exposed infants, respectively), including only infants who remained HIV negative by 36 weeks of age. Malaria was defined as clinical, asymptomatic (using DBSs at 12, 24, and 36 weeks), or a composite outcome of clinical or asymptomatic. Linear and binomial regression with generalized estimating equations were used to estimate the association between CPT and malaria. Differences in characteristics of parasitemias and drug resistance polymorphisms by CPT status were also assessed in the asymptomatic infections.
  
  
  RESULTS
  CPT was associated with a 70% (95% confidence interval, 53%-81%) relative reduction in the risk of asymptomatic infection between 6 and 36 weeks of age. CPT appeared to provide temporary protection against clinical malaria and more sustained protection against asymptomatic infections, with no difference in parasitemia characteristics.
  
  
  CONCLUSIONS
  CPT appears to reduce overall malaria infections, with more prolonged impacts on asymptomatic infections. Asymptomatic infections are potentially important reservoirs for malaria transmission. Therefore, CPT prophylaxis may have important individual and public health benefits.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Davis
authors.affiliation: Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Barnett
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill.
authors.forename: William C
authors.initials: WC
authors.lastname: Miller
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health.
authors.forename: Anna
authors.initials: A
authors.lastname: Dow
authors.affiliation: Division of Epidemiology and Biostatistics, School of Public Health, University of Witwatersrand, Parktown, South Africa.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Chasela
authors.affiliation: Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.affiliation: University of North Carolina, UNC Project, Lilongwe, Malawi.
authors.forename: Dumbani
authors.initials: D
authors.lastname: Kayira
authors.affiliation: University of North Carolina, UNC Project, Lilongwe, Malawi.
authors.forename: Gerald
authors.initials: G
authors.lastname: Tegha
authors.affiliation: Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Sascha R
authors.initials: SR
authors.lastname: Ellington
authors.affiliation: Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Athena P
authors.initials: AP
authors.lastname: Kourtis
authors.affiliation: Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill.
authors.forename: Charles
authors.initials: C
authors.lastname: van der Horst
authors.affiliation: Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Jamieson
authors.affiliation: Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Juliano
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D058345:Asymptomatic Infections; D004351:Drug Resistance; D005260:Female; D015658:HIV Infections; D006801:Humans; D007223:Infant; D008288:Malaria / Q000188:drug therapy* / Q000453:epidemiology* / Q000469:parasitology; D008295:Malawi / Q000453:epidemiology; D008297:Male; D018512:Parasitemia / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D011897:Random Allocation; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
keywords: HIV; antifolate resistance; cotrimoxazole; infant; malaria