{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:56:22Z","timestamp":1789710982669,"version":"4.0.1"},"reference-count":60,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2014,7,17]]},"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Malaria due to\n                      <jats:italic>Plasmodium knowlesi<\/jats:italic>\n                      is reported throughout South-East Asia, and is the commonest cause of it in Malaysia.\n                      <jats:italic>P. knowlesi<\/jats:italic>\n                      replicates every 24\u2005h and can cause severe disease and death. Current 2010 WHO Malaria Treatment Guidelines have no recommendations for the optimal treatment of non-severe knowlesi malaria. Artemisinin-combination therapies (ACT) and chloroquine have each been successfully used to treat knowlesi malaria; however, the rapidity of parasite clearance has not been prospectively compared. Malaysia's national policy for malaria pre-elimination involves mandatory hospital admission for confirmed malaria cases with discharge only after two negative blood films; use of a more rapidly acting antimalarial agent would have health cost benefits.\n                      <jats:italic>P. knowlesi<\/jats:italic>\n                      is commonly microscopically misreported as\n                      <jats:italic>P. malariae<\/jats:italic>\n                      ,\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      or\n                      <jats:italic>P. vivax<\/jats:italic>\n                      , with a high proportion of the latter two species being chloroquine-resistant in Malaysia. A unified ACT-treatment protocol would provide effective blood stage malaria treatment for all\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      species.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      ACT KNOW, the first randomised controlled trial ever performed in knowlesi malaria, is a two-arm open-label trial with enrolments over a 2-year period at three district sites in Sabah, powered to show a difference in proportion of patients negative for malaria by microscopy at 24\u2005h between treatment arms (clinicaltrials.gov #\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT01708876\">NCT01708876<\/jats:ext-link>\n                      ). Enrolments started in December 2012, with completion expected by September 2014. A total sample size of 228 is required to give 90% power (\u03b1 0.05) to determine the primary end point using intention-to-treat analysis. Secondary end points include parasite clearance time, rates of recurrent infection\/treatment failure to day 42, gametocyte carriage throughout follow-up and rates of anaemia at day 28, as determined by survival analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study has been approved by relevant institutional ethics committees in Malaysia and Australia. Results will be disseminated to inform knowlesi malaria treatment policy in this region through peer-reviewed publications and academic presentations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NCT01708876.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2014-006005","type":"journal-article","created":{"date-parts":[[2014,8,20]],"date-time":"2014-08-20T01:51:22Z","timestamp":1408499482000},"page":"e006005","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["A study protocol for a randomised open-label clinical trial of artesunate-mefloquine versus chloroquine in patients with non-severe\n                    <i>Plasmodium knowlesi<\/i>\n                    malaria in Sabah, Malaysia (ACT KNOW trial)"],"prefix":"10.1136","volume":"4","clinical-trial-number":[{"clinical-trial-number":"nct01708876","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01708876","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01708876","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"M J","family":"Grigg","sequence":"first","affiliation":[{"name":"Global Health and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia"},{"name":"Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, KotaKinabalu, Sabah, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"William","sequence":"additional","affiliation":[{"name":"Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, KotaKinabalu, Sabah, Malaysia"},{"name":"Infectious Diseases Unit, Clinical Research Centre, 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