Sustained High Cure Rate of Artemether–Lumefantrine against Uncomplicated Plasmodium falciparum Malaria after 8 Years of Its Wide-Scale Use in Bagamoyo District, Tanzania

Abstract

We assessed the temporal trend of artemether-lumefantrine (AL) cure rate after 8 years of its wide-scale use for treatment of uncomplicated <i>Plasmodium falciparum</i> malaria from 2006 to 2014 in Bagamoyo district, Tanzania. Trend analysis was performed for four studies conducted in 2006, 2007-2008, 2012-2013, and 2014. Patients with acute uncomplicated <i>P. falciparum</i> malaria were enrolled, treated with standard AL regimen and followed-up for 3 (2006), 28 (2014), 42 (2012-2013), or 56 (2007-2008) days for clinical and laboratory evaluation. Primary outcome was day 28 polymerase chain reaction (PCR)-adjusted cure rate across years from 2007 to 2014. Parasite clearance was slower for the 2006 and 2007-2008 cohorts with less than 50% of patients cleared of parasitemia on day 1, but was rapid for the 2012-2013 and 2014 cohorts. Day 28 PCR-adjusted cure rate was 168/170 (98.8%) (95% confidence interval [CI], 97.2-100), 122/127 (96.1%) (95% CI, 92.6-99.5), and 206/207 (99.5%) (95% CI, 98.6-100) in 2007-2008, 2012-2013, and 2014, respectively. There was no significant change in the trend of cure rate between 2007 and 2014 (χ²_trend test = 0.06, <i>P</i> = 0.90). Pretreatment <i>P. falciparum</i> multidrug-resistant gene 1 (<i>Pfmdr1</i>) N86 prevalence increased significantly across years from 13/48 (27.1%) in 2006 to 183/213 (85.9%) in 2014 (<i>P</i> < 0.001), and <i>P. falciparum</i> chloroquine resistance transporter gene (<i>Pfcrt</i>) K76 prevalence increased significantly from 24/47 (51.1%) in 2006 to 198/205 (96.6%) in 2014 (<i>P</i> < 0.001). The AL cure rate remained high after 8 years of its wide-scale use in Bagamoyo district for the treatment of uncomplicated <i>P. falciparum</i> malaria despite an increase in prevalence of pretreatment <i>Pfmdr1</i> N86 and <i>Pfcrt</i> K76 between 2006 and 2014.