{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:19:54Z","timestamp":1790623194021,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["N01-AI-30061"],"award-info":[{"award-number":["N01-AI-30061"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272201700012I"],"award-info":[{"award-number":["HHSN272201700012I"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Battelle Biomedical Research Center","award":["HHSN266200400095I"],"award-info":[{"award-number":["HHSN266200400095I"]}]},{"name":"Lovelace Respiratory Research Institute","award":["Y1-3753"],"award-info":[{"award-number":["Y1-3753"]}]},{"DOI":"10.13039\/100010201","name":"United States Army Medical Research Institute of Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010201","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Additional treatment options for pneumonic plague, the most severe form of infection by Yersinia pestis, are needed, as past US Food and Drug Administration (FDA) approvals were not based on clinical trials that meet today\u2019s standards, and multiple drugs are sought to counter resistance or use in special populations. Due to the sporadic nature of outbreaks and the low number of pneumonic cases of disease, we sought FDA approval of antimicrobials for treatment under the Animal Efficacy Rule, where efficacy can be demonstrated in 1 or more well-characterized animal models that sufficiently represent human disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A model was developed in African green monkeys (AGMs) after challenge with a lethal dose of Y. pestis delivered as an aerosol, in 4 independent studies in 3 laboratories. The primary data points were bacteremia (daily), body temperature and heart rate (continuously monitored by telemetry), and survival. In antimicrobial efficacy studies, human-equivalent doses of gentamicin, ciprofloxacin, levofloxacin, and doxycycline were administered upon fever onset for 10 days.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Disease in AGMs was similar to case reports of human disease. Fever was determined to be a reliable sign of disease and selected as a treatment trigger. Gentamicin was 60%\u201380% effective depending on the dose given to animals. Ciprofloxacin and levofloxacin were found to be &amp;gt;90% efficacious. These data were submitted to FDA and plague indications were approved. Doxycycline was less effective.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The AGM model of pneumonic plague is reproducible, well-characterized, and mimics human disease. It has been used to support plague indications for fluoroquinolones and to test the efficacy of additional antimicrobials.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciz1233","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T20:19:43Z","timestamp":1578082783000},"page":"S51-S59","source":"Crossref","is-referenced-by-count":12,"title":["The African Green Monkey Model of Pneumonic Plague and US Food and Drug Administration Approval of Antimicrobials Under the Animal Rule"],"prefix":"10.1093","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0907-7437","authenticated-orcid":false,"given":"Judith A","family":"Hewitt","sequence":"first","affiliation":[{"name":"Office of Biodefense, Research Resources and Translational Research , Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda L","family":"Lanning","sequence":"first","affiliation":[{"name":"Office of Regulatory Affairs, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L","family":"Campbell","sequence":"first","affiliation":[{"name":"Office of Biodefense, Research Resources and Translational Research , Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,21]]},"reference":[{"key":"2020052103181638200_CIT0001"},{"key":"2020052103181638200_CIT0002"},{"key":"2020052103181638200_CIT0003","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/j.1600-0684.2010.00443.x","article-title":"Primary pneumonic plague in the African green monkey as a model for treatment efficacy evaluation","volume":"40","author":"Layton","year":"2011","journal-title":"J Med Primatol"},{"key":"2020052103181638200_CIT0004","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.1093\/infdis\/129.Supplement_1.S85","article-title":"Live, attenuated Yersinia pestis vaccine: virulent in nonhuman primates, harmless to guinea pigs","volume":"129","author":"Meyer","year":"1974","journal-title":"J Infect Dis"},{"key":"2020052103181638200_CIT0005","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4269\/ajtmh.1994.51.109","article-title":"Cat-transmitted fatal pneumonic plague in a person who traveled from Colorado to Arizona","volume":"51","author":"Doll","year":"1994","journal-title":"Am J Trop Med Hyg"},{"key":"2020052103181638200_CIT0006","first-page":"737","article-title":"Pneumonic plague\u2014Arizona, 1992","volume":"41","author":"Opulski","year":"1992","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2020052103181638200_CIT0007","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3201\/eid1203.051051","article-title":"Pneumonic plague cluster, Uganda, 2004","volume":"12","author":"Begier","year":"2006","journal-title":"Emerg Infect Dis"},{"key":"2020052103181638200_CIT0008","doi-asserted-by":"crossref","first-page":"789","DOI":"10.7326\/0003-4819-56-5-789","article-title":"Laboratory-acquired pneumonic plague. 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