title: A retrospective analysis of the protective efficacy of tafenoquine and mefloquine as prophylactic anti-malarials in non-immune individuals during deployment to a malaria-endemic area.
abstract: BACKGROUND
  In 2000/2001, the Australian Defense Forces (ADF), in collaboration with SmithKline Beecham and the United States Army, conducted a field trial to evaluate the safety, tolerability and efficacy of tafenoquine and mefloquine/primaquine for the prophylaxis of malaria amongst non-immune Australian soldiers deployed to East Timor (now called Timor Leste) for peacekeeping operations. The lack of a concurrent placebo control arm prevented an internal estimate of the malaria attack rate and so the protective efficacy of the study regimens was not determined at the time.
  
  
  METHODS
  In a retrospective analysis of the trial results, the all species malaria attack rate was estimated for the prophylactic phase of the study which was defined as the period between administration of the first prophylactic dose and the first dose of post-deployment medication. First, the Plasmodium vivax attack rate was estimated during the prophylactic phase of the deployment by adjusting the observed P. vivax relapse rate during post-deployment to account for the known anti-relapse efficacies (or effectiveness) of the study medications (determined from prior studies). The all species malaria attack rate (P. vivax and Plasmodium falciparum) was then determined by adjusting the P. vivax attack rate based on the ratio of P. falciparum to P. vivax observed during prior ADF deployments to Timor Leste. This estimated all species malaria attack rate was then used as the 'constant estimated attack rate' in the calculation of the protective efficacy of tafenoquine and mefloquine during the prophylactic phase of the deployment.
  
  
  RESULTS
  The estimated attack rate during the prophylactic phase of the study was determined to be 7.88%. The protective efficacies of tafenoquine and mefloquine, with corresponding 95% confidence intervals (95% CI), were determined to be 100% (93%-100%) and 100% (79%-100%) respectively.
  
  
  CONCLUSIONS
  The protective efficacy of tafenoquine (200 mg per day for three days, followed by weekly 200 mg maintenance doses) is similar to that of the weekly standard of care (mefloquine, 250 mg).
authors: United States Army Medical Materiel Development Activity, 1430 Veterans Drive, Fort Detrick, Maryland 21702, USA. geoffdow@hotmail.com.
authors: Geoffrey S
authors: GS
authors: Dow
authors: William F
authors: WF
authors: McCarthy
authors: Mark
authors: M
authors: Reid
authors: Bryan
authors: B
authors: Smith
authors: Douglas
authors: D
authors: Tang
authors: G Dennis
authors: GD
authors: Shanks
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D001315:Australia; D018890:Chemoprevention / Q000379:methods*; D019353:Endemic Diseases; D006801:Humans; D015994:Incidence; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000517:prevention & control*; D016780:Malaria, Vivax / Q000453:epidemiology / Q000517:prevention & control*; D015767:Mefloquine / Q000008:administration & dosage* / Q000009:adverse effects; D008889:Military Personnel; D012189:Retrospective Studies; D049648:Timor-Leste; D014195:Travel; D016896:Treatment Outcome; D014481:United States
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; C055852:tafenoquine; D015767:Mefloquine