{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:28:36Z","timestamp":1770899316945,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Military Infectious Diseases Research Program (MIDRP)-Rickettsial Disease","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Recently, an intradermal inoculation of the rhesus macaque model of scrub typhus has been characterized at our institution. The current project was to establish a rhesus macaque model of scrub typhus using the naturally infected chigger challenge method that faithfully mimics the natural route of pathogen transmission to fully understand the host-pathogen-vector interactions influencing pathogen transmission. Unlike the needle-based inoculation route, Orientia tsutsugamushi-infected chiggers introduce both pathogen and chigger saliva into the host epidermis at the bite site. However, information on the interaction or influence of chigger saliva on pathogenesis and immunity of host has been limited, consequently hindering vaccine development and transmission-blocking studies. To characterize chigger inoculated O. tsutsugamushi in rhesus macaques, we determined the minimum chigger attachment time required to efficiently transmit O. tsutsugamushi to the immunocompetent hosts and preliminary assessed clinical parameters, course of bacterial infection, and host\u2019s immunological response to identifying potential factors influencing pathogen infection. Chigger infestation on hosts resulted in: (i) Rapid transmission of O. tsutsugamushi within 1 h and (ii) antigen-specific type I and II T-cell responses were markedly increased during the acute phase of infection, suggesting that both systems play critical roles in response to the pathogen control during the primary infection. In summary, we demonstrate that O. tsutsugamushi infection in rhesus macaques via chigger challenge recapitulates the time of disease onset and bacteremia observed in scrub typhus patients. Levels of proinflammatory cytokines and chemokines were positively correlated with bacteremia.<\/jats:p>","DOI":"10.3390\/pathogens10081028","type":"journal-article","created":{"date-parts":[[2021,8,15]],"date-time":"2021-08-15T22:51:27Z","timestamp":1629067887000},"page":"1028","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal Orientia tsutsugamushi Transmission Time by Leptotrombidium\u00a0chiangraiensis Chiggers"],"prefix":"10.3390","volume":"10","author":[{"given":"Piyada","family":"Linsuwanon","sequence":"first","affiliation":[{"name":"Department of Entomology, USAMD-AFRIMS, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sirima","family":"Wongwairot","sequence":"additional","affiliation":[{"name":"Department of Entomology, USAMD-AFRIMS, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nutthanun","family":"Auysawasdi","sequence":"additional","affiliation":[{"name":"Department of Entomology, USAMD-AFRIMS, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taweesak","family":"Monkanna","sequence":"additional","affiliation":[{"name":"Department of Entomology, USAMD-AFRIMS, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1065-429X","authenticated-orcid":false,"given":"Allen L.","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine and Biostatistics, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surachai","family":"Leepitakrat","sequence":"additional","affiliation":[{"name":"Department of Entomology, USAMD-AFRIMS, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piyanate","family":"Sunyakumthorn","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, USAMD-AFRIMS, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rawiwan","family":"Im-Erbsin","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, USAMD-AFRIMS, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie","family":"Poole-Smith","sequence":"additional","affiliation":[{"name":"Department of Entomology, USAMD-AFRIMS, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6322-7892","authenticated-orcid":false,"given":"Patrick","family":"McCardle","sequence":"additional","affiliation":[{"name":"Department of Entomology, USAMD-AFRIMS, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.3201\/eid2609.200918","article-title":"Molecular Description of a Novel Orientia Species Causing Scrub Typhus in Chile","volume":"26","author":"Abarca","year":"2020","journal-title":"Emerg. 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