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This model system has persisted on account of the guinea pig's conduciveness to tick transmission of SFR agents and ability to recapitulate SFR in humans through clinical signs that include fever, unthriftiness, and in some cases the development of an eschar. The guinea pig is the smallest animal model for SFR that allows the collection of multiple blood and skin samples antemortem for longitudinal studies. This unit provides the basic protocols necessary to establish, maintain, and utilize a guinea pig\u2010tick\u2010<jats:italic>Rickettsia<\/jats:italic> model for monitoring the course of infection and immune response to an infection by spotted fever group <jats:italic>Rickettsia<\/jats:italic> (SFGR) that can be studied at biosafety level 2 (BSL\u20102) and arthropod containment level 2 (ACL\u20102); adaptations must be made for BSL\u20103 agents. The protocols cover methods for tick feeding and colony development, laboratory infection of ticks, tick transmission of <jats:italic>Rickettsia<\/jats:italic> to guinea pigs, and monitoring of the course of infection through clinical signs, rickettsial burden, and immune response. It should be feasible to adapt these methods to study other tick\u2010borne pathogens. \u00a9 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.<\/jats:p><jats:p><jats:bold>Basic Protocol 1<\/jats:bold>: Tick transmission of SFGR to guinea pigs<\/jats:p><jats:p><jats:bold>Support Protocol 1<\/jats:bold>: Laboratory infection of ticks by injection<\/jats:p><jats:p><jats:bold>Alternate Protocol 1<\/jats:bold>: Needle inoculation of SFGR to guinea pigs<\/jats:p><jats:p><jats:bold>Basic Protocol 2<\/jats:bold>: Monitoring the course of guinea pig rickettsial infection: clinical signs<\/jats:p><jats:p><jats:bold>Basic Protocol 3<\/jats:bold>: Monitoring the course of guinea pig rickettsial infection: collection of biological specimens<\/jats:p><jats:p><jats:bold>Support Protocol 2<\/jats:bold>: Guinea pig anesthesia<\/jats:p><jats:p><jats:bold>Basic Protocol 4<\/jats:bold>: Monitoring rickettsial burden in guinea pigs by multiplex qPCR<\/jats:p><jats:p><jats:bold>Basic Protocol 5<\/jats:bold>: Monitoring guinea pig immune response to infection: blood leukocytes by flow cytometry<\/jats:p><jats:p><jats:bold>Basic Protocol 6<\/jats:bold>: Monitoring immune response to guinea pig rickettsial infection: leukocyte infiltration of skin at the tick bite site by flow cytometry<\/jats:p><jats:p><jats:bold>Basic Protocol 7<\/jats:bold>: Monitoring the immune response to guinea pig rickettsial infection: antibody titer by ELISA<\/jats:p><jats:p><jats:bold>Support Protocol 4<\/jats:bold>: Coating ELISA Plates<\/jats:p><jats:p><jats:bold>Alternate Protocol 2<\/jats:bold>: Monitoring immune response to guinea pig rickettsial infection: antibody titer by immunofluorescence assay<\/jats:p>","DOI":"10.1002\/cpz1.584","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T14:07:35Z","timestamp":1668607655000},"source":"Crossref","is-referenced-by-count":2,"title":["Evaluating the Clinical and Immune Responses to Spotted Fever Rickettsioses in the Guinea Pig\u2010Tick\u2010<i>Rickettsia<\/i> System"],"prefix":"10.1002","volume":"2","author":[{"given":"John V.","family":"Stokes","sequence":"first","affiliation":[{"name":"Department of Comparative Pathobiology, Cummings School of Veterinary Medicine Tufts University  North Grafton Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael L.","family":"Levin","sequence":"additional","affiliation":[{"name":"Division of Vector\u2010Borne Diseases Centers for Disease Control and Prevention  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire E.","family":"Cross","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Marie L.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences Mississippi State University  Mississippi State Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyssa N.","family":"Snellgrove","sequence":"additional","affiliation":[{"name":"Division of Vector\u2010Borne Diseases Centers for Disease Control and Prevention  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bridget V.","family":"Willeford","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resources Mississippi State University  Mississippi State Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Navatha","family":"Alugubelly","sequence":"additional","affiliation":[{"name":"Attentive Science  Stillwell Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea S.","family":"Varela\u2010Stokes","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology, Cummings School of Veterinary Medicine Tufts University  North Grafton Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"e_1_2_19_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10020088"},{"key":"e_1_2_19_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2018.2431"},{"key":"e_1_2_19_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc03a05s11"},{"key":"e_1_2_19_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2014.11.008"},{"key":"e_1_2_19_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jip.2006.10.003"},{"key":"e_1_2_19_7_1","doi-asserted-by":"publisher","DOI":"10.3791\/51982"},{"key":"e_1_2_19_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2014.1575"},{"key":"e_1_2_19_9_1","unstructured":"Broad_Institute. 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