{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T19:59:31Z","timestamp":1779134371360,"version":"3.51.4"},"reference-count":24,"publisher":"The Royal Society","issue":"3","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["Foundation Grant, Awarded to MAB; MFE-152448"],"award-info":[{"award-number":["Foundation Grant, Awarded to MAB; MFE-152448"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI113287"],"award-info":[{"award-number":["R01AI113287"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["F31GM120985"],"award-info":[{"award-number":["F31GM120985"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["U01GM087728"],"award-info":[{"award-number":["U01GM087728"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH Research Training for Computation and Informatics","award":["NIH T15 LM007359"],"award-info":[{"award-number":["NIH T15 LM007359"]}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["R. Soc. open sci."],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>\n                    A recent study reported on a tuberculosis (TB) outbreak in a largely Inuit village. Among newly infected individuals, exposure to additional active cases was associated with an increasing probability of developing active disease within a year. Using binomial risk models, we evaluated two potential mechanisms by which multiple infections during the first year following initial infection could account for increasing disease risk with increasing exposures. In the\n                    <jats:italic>reinfection model<\/jats:italic>\n                    , each infectious contact confers an independent risk of an infection, and infections contribute independently to active disease. In the\n                    <jats:italic>threshold model<\/jats:italic>\n                    , disease risk follows a sigmoidal function with small numbers of infectious contacts conferring a low risk of active disease and large numbers of contacts conferring a high risk. To determine the dynamic impact of reinfection during the early phase of infection, we performed simulations from a modified Reed\u2013Frost model of TB dynamics following spread from an initial number of cases. We parametrized this model with the maximum-likelihood estimates from the reinfection and threshold models in addition to the observed distribution of exposures among new infections. We find that both models can plausibly account for the observed increase in disease risk with increasing infectious contacts, but the threshold model confers a better fit than a nested model without a threshold (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.04). Our simulations indicate that multiple exposures to infectious individuals during this critical time period can lead to dramatic increases in outbreak size. In order to decrease TB burden in high-prevalence settings, it may be necessary to implement measures aimed at preventing repeated exposures, in addition to preventing primary infection.\n                  <\/jats:p>","DOI":"10.1098\/rsos.180999","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T08:17:51Z","timestamp":1553069871000},"page":"180999","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Multiple exposures, reinfection and risk of progression to active tuberculosis"],"prefix":"10.1098","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-6063","authenticated-orcid":true,"given":"Sarah F.","family":"Ackley","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA"},{"name":"Proctor Foundation, University of California, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard University, School of Public Health, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Worden","sequence":"additional","affiliation":[{"name":"Proctor Foundation, University of California, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Zwick","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, University of Wisconsin \u2013 Madison, School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Travis C.","family":"Porco","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA"},{"name":"Proctor Foundation, University of California, San Francisco, CA, USA"},{"name":"Department of Ophthalmology, University of California, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel A.","family":"Behr","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University, Montreal, Quebec, Canada"},{"name":"McGill International TB Centre, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin S.","family":"Pepperell","sequence":"additional","affiliation":[{"name":"Medicine and Medical Microbiology and Immunology, University of Wisconsin \u2013 Madison, Madison, WI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2019,3,20]]},"reference":[{"key":"e_1_3_6_2_2","volume-title":"The chief public health officer's report on the state of public health in Canada 2013 \u2013 tuberculosis \u2013 past and present","author":"Public Health Agency of Canada","year":"2013"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00893-2016"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00120908"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201406-1159OC"},{"key":"e_1_3_6_6_2","first-page":"731","article-title":"A study of the risk of attack among contacts in tuberculous families in a rural area","volume":"22","author":"Downes J","year":"1935","journal-title":"Am. 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Hyg."},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-008-8087-y"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/28.2.327"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/tpbi.2000.1451"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200401020-00010"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201208-1422OC"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw199"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-017-2675-3"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv011"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.1237"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.3934\/mbe.2004.1.361"},{"key":"e_1_3_6_17_2","first-page":"201","article-title":"An examination of the Reed-Frost theory of epidemics","volume":"24","author":"Abbey H","year":"1952","journal-title":"Hum. 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Lung Dis."},{"key":"e_1_3_6_21_2","volume-title":"Tuberculosis among the Indians of the great Canadian plains","author":"Ferguson RG","year":"1928"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir162"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007305"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200409-1200OC"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy127"}],"container-title":["Royal Society Open Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsos.180999","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsos.180999","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsos.180999","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T23:07:44Z","timestamp":1613603264000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsos.180999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1098\/rsos.180999"],"URL":"https:\/\/doi.org\/10.1098\/rsos.180999","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/398271","asserted-by":"object"}]},"ISSN":["2054-5703"],"issn-type":[{"value":"2054-5703","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"2018-06-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}