The use of ultrasensitive quantitative-PCR to assess the impact of primaquine on asymptomatic relapse of Plasmodium vivax infections: a randomized, controlled trial in Lao PDR

• Published in: Malaria Journal
• Main Authors: Koukeo Phommasone, Frank van Leth, Mallika Imwong, Gisela Henriques, Tiengkham Pongvongsa, Bipin Adhikari, Thomas J. Peto, Cholrawee Promnarate, Mehul Dhorda, Pasathorn Sirithiranont, Mavuto Mukaka, Pimnara Peerawaranun, Nicholas P. J. Day, Frank Cobelens, Arjen M. Dondorp, Paul N. Newton, Nicholas J. White, Lorenz von Seidlein, Mayfong Mayxay
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2020
• Subjects: Malaria; P. vivax; PCR; Primaquine; Relapse; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-019-3091-5; https://doaj.org/article/764afa3c29114ddfa3c8ed14837a67e8

Abstract Background Trials to assess the efficacy of the radical cure of Plasmodium vivax malaria with 8-aminoquinolines require that most post-treatment relapses are identified, but there is no consensus on the optimal duration of follow-up in either symptomatic or asymptomatic vivax malaria. The efficacy of a 14-day course of primaquine on the cumulative incidence of recurrent asymptomatic P. vivax infections detected by ultrasensitive quantitative PCR (uPCR) as a primary endpoint was assessed. Methods A randomized, placebo-controlled, single-blind trial was conducted in four villages of the Lao PDR during 2016–2018 nested in a larger project evaluating mass drug administrations (MDA) with dihydroartemisinin-piperaquine (DP) and a single low-dose primaquine to clear Plasmodium falciparum infections. In the nested sub-study, eligible participants with mono- or mixed P. vivax infections detected by uPCR were randomized to receive either 14 days of primaquine (0.5 mg/kg/day) or placebo during the last round of MDA (round 3) through directly observed therapy. Participants were checked monthly for 12 months for parasitaemia using uPCR. The primary outcome was cumulative incidence of participants with at least one recurrent episode of P. vivax infection. Results 20 G6PD-normal participants were randomized in each arm. 5 (29%) of 20 participants in the placebo arm experienced asymptomatic, recurrent P. vivax infections, resulting in a cumulative incidence at month 12 of 29%. None of the 20 participants in the intervention arm had recurrent infections (p = 0.047 Fisher’s exact test). Participants with recurrent P. vivax infections were found to be parasitaemic for between one and five sequential monthly tests. The median time to recurrence of P. vivax parasitaemia was 178 days (range 62–243 days). Conclusions A 14-day course of primaquine in addition to a DP-MDA was safe, well-tolerated, and prevented recurrent asymptomatic P. vivax infections. Long follow-up for up to 12 months is required to capture all recurrences ...