TY - JOUR
T1 - Hypnozoite depletion in successive Plasmodium vivax relapses
AU - Noviyanti, Rintis
AU - Carey-Ewend, Kelly
AU - Trianty, Leily
AU - Parobek, Christian
AU - Puspitasari, Agatha Mia
AU - Balasubramanian, Sujata
AU - Park, Zackary
AU - Hathaway, Nicholas
AU - Utami, Retno A.S.
AU - Soebianto, Saraswati
AU - Jeny, Jeny
AU - Yudhaputri, Frilasita
AU - Perkasa, Aditya
AU - Coutrier, Farah N.
AU - Tirta, Yusrifar K.
AU - Ekawati, Lenny
AU - Tjahyono, Bagus
AU - Sutanto, Inge
AU - Nelwan, Erni J.
AU - Sudoyo, Herawati
AU - Baird, J. Kevin
AU - Lin, Jessica T.
N1 - Funding Information:
This work was supported by the Wellcome Trust Africa Asia Program Vietnam (https://wellcome.org/what-we-do/our-work/ programmes-and-initiatives-africa-and-asia), Medicines for Malaria Venture (https://www.mmv. org/), Ministry of Research and Technology-the Republic of Indonesia, the Alumni Grant Scheme-the Australia Awards in Indonesia (https:// australiaawardsindonesia.org/) to RN, and the National Institute of Allergy and Infectious Diseases (https://www.niaid.nih.gov/) at the National Institutes of Health through grants K08AI110651 and R21AI152260 to JTL. The funders had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript.We thank Dorothya R. Lestari, the study participants, and the study staff at the Indonesian Armed Forces and Eijkman-Oxford Clinical Research Unit for their support.
Publisher Copyright:
© 2022 Noviyanti et al.
PY - 2022/7
Y1 - 2022/7
N2 - 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 pop-ulation. 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.
AB - 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 pop-ulation. 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.
UR - http://www.scopus.com/inward/record.url?scp=85135466697&partnerID=8YFLogxK
U2 - 10.1371/journal.pntd.0010648
DO - 10.1371/journal.pntd.0010648
M3 - Article
C2 - 35867730
AN - SCOPUS:85135466697
SN - 1935-2727
VL - 16
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 7
M1 - e0010648
ER -
