• Death rates from malaria epidemics, Burundi and Ethiopia.

      Guthmann, J P; Bonnet, M; Ahoua, L; Dantoine, F; Balkan, S; Van Herp, M; Tamrat, A; Legros, D; Brown, V; Checchi, F; et al. (2007-01)
      Death rates exceeded emergency thresholds at 4 sites during epidemics of Plasmodium falciparum malaria in Burundi (2000-2001) and in Ethiopia (2003-2004). Deaths likely from malaria ranged from 1,000 to 8,900, depending on site, and accounted for 52% to 78% of total deaths. Earlier detection of malaria and better case management are needed.
    • Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial

      Bassat, Quique; Mulenga, Modest; Tinto, Halidou; Piola, Patrice; Borrmann, Steffen; Menéndez, Clara; Nambozi, Michael; Valéa, Innocent; Nabasumba, Carolyn; Sasi, Philip; et al. (2009-11-17)
      BACKGROUND: Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS: The non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6-59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2:1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of -5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were -2.80% and -2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE: DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com ISRCTN16263443.
    • In vivo assessment of drug efficacy against Plasmodium falciparum malaria: duration of follow-up.

      Stepniewska, K; Taylor, W R J; Mayxay, M; Price, R; Smithuis, F; Guthmann, J P; Barnes, K; Myint, H Y; Adjuik, M; Olliaro, P; et al. (2004-11)
      To determine the optimum duration of follow-up for the assessment of drug efficacy against Plasmodium falciparum malaria, 96 trial arms from randomized controlled trials (RCTs) with follow-up of 28 days or longer that were conducted between 1990 and 2003 were analyzed. These trials enrolled 13,772 patients, and participating patients comprised 23% of all patients enrolled in RCTs over the past 40 years; 61 (64%) trial arms were conducted in areas where the rate of malaria transmission was low, and 58 (50%) trial arms were supported by parasite genotyping to distinguish true recrudescences from reinfections. The median overall failure rate reported was 10% (range, 0 to 47%). The widely used day 14 assessment had a sensitivity of between 0 and 37% in identifying treatment failures and had no predictive value. Assessment at day 28 had a sensitivity of 66% overall (28 to 100% in individual trials) but could be used to predict the true failure rate if either parasite genotyping was performed (r(2) = 0.94) or if the entomological inoculation rate was known. In the assessment of drug efficacy against falciparum malaria, 28 days should be the minimum period of follow-up.
    • Plasmodium falciparum: sensitivity in vivo to chloroquine, pyrimethamine/sulfadoxine and mefloquine in western Myanmar.

      Smithuis, F; Monti, F; Grundl, M; Oo, A Z; Kyaw, T T; Phe, O; White, N J; Artsen Zonder Grenzen, Médecins Sans Frontières-Holland, Yangon, Myanmar, Thailand. (Elsevier, 2008-02-07)
      In Rakhine State, on the western border of Myanmar, the efficacy of chloroquine (CQ) and pyrimethamine/ sulfadoxine (PS), the current treatments for uncomplicated Plasmodium falciparum malaria in this area, was evaluated in an open comparative study of 289 patients, stratified prospectively into 3 age groups. Chloroquine treatment was associated with more rapid clinical recovery (P = 0.03), but the overall cure rates were worse than for PS treatment; failure to clear parasitaemia or recrudescence within 14 d occurred in 72% (102/141) of cases treated with CQ compared to 47% (69/148) of those who received PS (P < 0.0001, adjusted for age). Failure rates at day 28 increased to 82% (116/141) in the CQ group and 67% (99/148) in the PS group (P = 0.003). The risk of treatment failure was significantly higher in children under 15 years old than in adults for both CQ (relative risk [RR] = 2.6; 95% confidence interval [95% CI] 1.3-5.2) and PS (RR = 2.2; 95% CI 1.4-3.3). Mefloquine (15 mg base/kg) proved to be highly effective as a treatment for CQ and PS resistant P. falciparum; only 2 of 75 patients (3%) had early treatment failures (< or = day 7), and the overall failure rate by day 42 was 7%. There is a very high level of chloroquine and PS resistance in P.falciparum on the western border of Myanmar, but mefloquine was effective in the area.