title: Rifampicin/Cotrimoxazole/Isoniazid versus mefloquine or quinine + sulfadoxine- pyrimethamine for malaria: a randomized trial.
abstract: OBJECTIVE
  Previous studies of a fixed combination including cotrimoxazole, rifampicin, and isoniazid (Cotrifazid) showed efficacy against resistant strains of Plasmodium falciparum in animal models and in small-scale human studies. We conducted a multicentric noninferiority trial to assess the safety and efficacy of Cotrifazid against drug-resistant malaria in Papua New Guinea.
  
  
  METHODS
  The trial design was open-label, block-randomised, comparative, and multicentric.
  
  
  METHODS
  The trial was conducted in four primary care health facilities, two in urban and two in rural areas of Madang and East Sepik Province, Papua New Guinea.
  
  
  METHODS
  Patients of all ages with recurrent uncomplicated malaria were included.
  
  
  METHODS
  Patients were randomly assigned to receive Cotrifazid, mefloquine, or the standard treatment of quinine with sulfadoxine-pyrimethamine (SP).
  
  
  METHODS
  Incidence of clinical and laboratory adverse events and rate of clinical and/or parasitological failure at day 14 were recorded.
  
  
  RESULTS
  The safety analysis population included 123 patients assigned to Cotrifazid, 123 to mefloquine, and 123 to quinine + SP. The Cotrifazid group experienced lower overall incidence of adverse events than the other groups. Among the efficacy analysis population (72 Cotrifazid, 71 mefloquine, and 75 quinine + SP), clinical failure rate (symptoms and parasite load) on day 14 was equivalent for the three groups (0% for Cotrifazid and mefloquine; 1% for quinine + SP), but parasitological failure rate (P. falciparum asexual blood-stage) was higher for Cotrifazid than for mefloquine or quinine + SP (9% [PCR corrected 8%] versus 0% and 3%, respectively [p = 0.02]).
  
  
  CONCLUSIONS
  Despite what appears to be short-term clinical equivalence, the notable parasitological failure at day 14 in both P. falciparum and P. vivax makes Cotrifazid in its current formulation and regimen a poor alternative combination therapy for malaria.
authors.affiliation: Swiss Tropical Institute, Basel, Switzerland. Blaise.genton@unibas.ch
authors.forename: Blaise
authors.initials: B
authors.lastname: Genton
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.forename: Inoni
authors.initials: I
authors.lastname: Betuela
authors.forename: Gerard
authors.initials: G
authors.lastname: Casey
authors.forename: Meza
authors.initials: M
authors.lastname: Ginny
authors.forename: Michael P
authors.initials: MP
authors.lastname: Alpers
authors.forename: John C
authors.initials: JC
authors.lastname: Reeder