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Hypnozoite depletion in successive Plasmodium vivax relapses
Authors:Rintis Noviyanti  Kelly Carey-Ewend  Leily Trianty  Christian Parobek  Agatha Mia Puspitasari  Sujata Balasubramanian  Zackary Park  Nicholas Hathaway  Retno A. S. Utami  Saraswati Soebianto  Jeny Jeny  Frilasita Yudhaputri  Aditya Perkasa  Farah N. Coutrier  Yusrifar K. Tirta  Lenny Ekawati  Bagus Tjahyono  Inge Sutanto  Erni J. Nelwan  Herawati Sudoyo  J. Kevin Baird  Jessica T. Lin
Abstract:Genotyping Plasmodium vivax relapses can provide insights into hypnozoite biology. We performed targeted amplicon sequencing of 127 relapses occurring in Indonesian soldiers returning to malaria-free Java after yearlong deployment in malarious Eastern Indonesia. Hepatic carriage of multiple hypnozoite clones was evident in three-quarters of soldiers with two successive relapses, yet the majority of relapse episodes only displayed one clonal population. The number of clones detected in relapse episodes decreased over time and through successive relapses, especially in individuals who received hypnozoiticidal therapy. Interrogating the multiplicity of infection in this P. vivax relapse cohort reveals evidence of independent activation and slow depletion of hypnozoites over many months by multiple possible mechanisms, including parasite senescence and host immunity.
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