ABSTRACT: BACKGROUND: Interest in developing physically active pediculicides has identified new active substances. The objective was to evaluate a new treatment for clinical efficacy. METHODS AND FINDINGS: We describe the selection of 1,2-octanediol as a potential pediculicide. Clinical studies were community based. The main outcome measure was no live lice, after two treatments, with follow up visits over 14 days. Study 1 was a proof of concept with 18/20 (90%) participants cured. Study 2 was a multicentre, parallel, randomised, observer-blind study (520 participants) that compared 0.5% malathion liquid with 1,2-octanediol lotion (20% alcohol) applied 2-2.5 hours or 8 hours/overnight. 1,2-octanediol lotion was significantly (p<0.0005) more effective with success for 124/175 (70.9%) RR?=?1.50 (97.5% CI, 1.22 to 1.85) for 2-2.5 hours, and 153/174 (87.9%) RR?=?1.86 (97.5% CI, 1.54 to 2.26) for 8 hours/overnight compared with 81/171 (47.4%) for malathion. Study 3, a two centre, parallel, randomised, observer-blind study (121 participants), compared 1,2-octanediol lotion, 2-2.5 hours with 1,2-octanediol alcohol free mousse applied for 2-2.5 hours or 8 hours/overnight. The mousse applied for 8 hours/overnight cured 31/40 (77.5%), compared with 24/40 (60.0%) for lotion (RR?=?1.29, 95% CI, 0.95 to 1.75; NNT?=?5.7) but mousse applied for 2-2.5 hours 17/41 (41.5%) was less effective than lotion (RR?=?0.69, 95% CI, 0.44 to 1.08). Adverse events were more common using 1,2-octanediol lotion at both 2-2.5 hours (12.0%, p?=?0.001) and 8 hours/overnight (14.9%, p<0.0005), compared with 0.5% malathion (2.3%). Similar reactions were more frequent (p<0.045) using lotion compared with mousse. CONCLUSIONS: 1,2-octanediol was found to eliminate head louse infestation. It is believed to disrupt the insect's cuticular lipid, resulting in dehydration. The alcohol free mousse is more acceptable exhibiting significantly fewer adverse reactions. TRIAL REGISTRATIONS: Controlled-Trials.com ISRCTN66611560, ISRCTN91870666, ISRCTN28722846.
