The probability of a sequential Plasmodium vivax infection following asymptomatic Plasmodium falciparum and P. vivax infections in Myanmar, Vietnam, Cambodia, and Laos

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Adding 8-aminoquinoline to the treatment of falciparum, in addition to vivax malaria, in locations where infections with both species are prevalent could prevent vivax reactivation. The potential risk of haemolysis under a universal radical cure policy using 8-aminoquinoline needs to be weighed against the benefit of preventing repeated vivax episodes. Estimating the frequency of sequential <jats:italic>Plasmodium vivax</jats:italic> infections following either falciparum or vivax malaria episodes is needed for such an assessment.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Quarterly surveillance data collected during a mass drug administration trial in the Greater Mekong Subregion in 2013–17 was used to estimate the probability of asymptomatic sequential infections by the same and different <jats:italic>Plasmodium</jats:italic> species. Asymptomatic <jats:italic>Plasmodium</jats:italic> infections were detected by high-volume ultrasensitive qPCR. Quarterly surveys of asymptomatic <jats:italic>Plasmodium</jats:italic> prevalence were used to estimate the probability of a <jats:italic>P. vivax</jats:italic> infection following <jats:italic>Plasmodium falciparum</jats:italic> and <jats:italic>P. vivax</jats:italic> infections.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>16,959 valid sequential paired test results were available for analysis. Of these, 534 (3%) had an initial <jats:italic>P. falciparum</jats:italic> monoinfection, 1169 (7%) a <jats:italic>P. vivax</jats:italic> monoinfection, 217 (1%) had mixed (<jats:italic>P. falciparum </jats:italic>+ <jats:italic>P. vivax</jats:italic>) infections, and 15,039 (89%) had no <jats:italic>Plasmodium</jats:italic> detected in the initial survey. Participants who had no evidence of a <jats:italic>Plasmodium i</jats:italic>nfection had a 4% probability to be found infected with <jats:italic>P. vivax</jats:italic> during the subsequent survey. Following an asymptomatic <jats:italic>P. falciparum</jats:italic> monoinfection participants had a 9% probability of having a subsequent <jats:italic>P. vivax</jats:italic> infection (RR 2.4; 95% CI 1.8 to 3.2). Following an asymptomatic <jats:italic>P. vivax</jats:italic> monoinfection, the participants had a 45% probability of having a subsequent <jats:italic>P. vivax</jats:italic> infection. The radical cure of 12 asymptomatic <jats:italic>P. falciparum</jats:italic> monoinfections would have prevented one subsequent <jats:italic>P. vivax</jats:italic> infection, whereas treatment of 2 <jats:italic>P. vivax</jats:italic> monoinfections may suffice to prevent one <jats:italic>P. vivax</jats:italic> relapse.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Universal radical cure could play a role in the elimination of vivax malaria. The decision whether to implement universal radical cure for <jats:italic>P. falciparum</jats:italic> as well as for <jats:italic>P. vivax</jats:italic> depends on the prevalence of <jats:italic>P. falciparum</jats:italic> and <jats:italic>P. vivax</jats:italic> infections, the prevalence and severity of G6PD deficiency in the population and the feasibility to administer 8-aminoquinoline regimens safely.</jats:p> <jats:p><jats:italic>Trial registration</jats:italic> ClinicalTrials.gov Identifier: NCT01872702, first posted June 7th 2013, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01872702">https://clinicaltrials.gov/ct2/show/NCT01872702</jats:ext-link>. This study was registered with ClinicalTrials.gov under NCT02802813 on 16th June 2016. <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02802813">https://clinicaltrials.gov/ct2/show/NCT02802813</jats:ext-link></jats:p> </jats:sec>