{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:46:56Z","timestamp":1785210416238,"version":"3.55.0"},"reference-count":63,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["T32AG51108"],"award-info":[{"award-number":["T32AG51108"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32GM144273"],"award-info":[{"award-number":["T32GM144273"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,2]]},"abstract":"<jats:p>Exposure to infectious disease in early life may have long-term ramifications for health and lifespan. However, reducing pathogen exposure may not be uniformly beneficial. The rise of modern sanitation and reduction of infectious diseases has been implicated in increasing levels of allergy and immune dysregulation: termed, the \u201chygiene hypothesis.\u201d This study leverages quasi-experimental variation from combining precampaign hookworm exposure with the Rockefeller Sanitary Commission\u2019s deworming campaign in the early 20th century to rigorously examine the impacts of childhood hookworm exposure on adult lifespan and morbidity. Findings show deworming before age five leads to 2.5 additional months of life in a large sample of adult death records. Further, decreasing hookworm exposure is related to improvements in biomarkers for inflammation and skin-tested allergies, in contrast to predictions of the \u201chygiene hypothesis.\u201d Placebo tests using health outcomes that should not be affected by deworming do not show similar patterns. Overall, childhood deworming leads to improvements in morbidity and lifespan decades later.<\/jats:p>","DOI":"10.1073\/pnas.2504265122","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T17:46:55Z","timestamp":1756230415000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["Early-life infectious disease exposure, the \u201chygiene hypothesis,\u201d and lifespan: Evidence from hookworm disease"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4640-5962","authenticated-orcid":false,"given":"Ralph","family":"Lawton","sequence":"first","affiliation":[{"name":"Interfaculty Initiative in Health Policy, Graduate School of Arts and Sciences","place":["Cambridge"]},{"name":"Harvard University","place":["Cambridge"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","unstructured":"P. J. Hotez et al. The global burden of disease study 2010: Interpretation and implications for the neglected tropical diseases. PLoS Negl. Trop. Dis. 8 e2865 (2014).","DOI":"10.1371\/journal.pntd.0002496"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","unstructured":"E. Miguel M. Kremer Worms: Identifying impacts on education and health in the presence of treatment externalities. Econometrica 72 159\u2013217 (2004) https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1468-0262.2004.00481.x.","DOI":"10.1111\/j.1468-0262.2004.00481.x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1162\/qjec.121.1.73"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","unstructured":"D. C. Taylor-Robinson N. Maayan S. Donegan M. Chaplin P. Garner \u201cPublic health deworming programmes for soil-transmitted helminths in children living in endemic areas\u201d in Cochrane Database Systematic Reviews Cochrane Infectious Diseases Group Ed. (John Wiley & Sons Ltd. 2019).","DOI":"10.1002\/14651858.CD000371.pub7"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","unstructured":"K. Croke et al. Meta-analysis and public policy: Reconciling the evidence on deworming. Proc. Natl. Acad. Sci. U.S.A. 121 e2308733121 (2024).","DOI":"10.1073\/pnas.2308733121"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1257\/jep.25.3.153"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","unstructured":"C. E. Finch E. M. Crimmins Inflammatory exposure and historical changes in human life-spans. Science 305 1736\u20131739 (2004).","DOI":"10.1126\/science.1092556"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","unstructured":"E. M. Crimmins C. E. Finch Infection inflammation height and longevity. Proc. Natl. Acad. Sci. U.S.A. 103 498\u2013503 (2006).","DOI":"10.1073\/pnas.0501470103"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","unstructured":"D. M. Cutler E. Meara \u201cChanges in the age distribution of mortality over the 20th century\u201d (NBER Working Paper 8556 National Bureau of Economic Research Cambridge MA 2001). https:\/\/doi.org\/10.3386\/w8556.","DOI":"10.3386\/w8556"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1353\/dem.2005.0002"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg061"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.4054\/DemRes.2010.22.20"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","unstructured":"M. Myrskyl\u00e4 N. K. Mehta V. W. Chang Early life exposure to the 1918 influenza pandemic and old-age mortality by cause of death. Am. J. Public Heal. 103 e83\u2013e90 (2013).","DOI":"10.2105\/AJPH.2012.301060"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1017\/S2040174409990031"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/719757"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.socscimed.2008.12.010"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","unstructured":"C. Caruso G. Candore G. Colonna-Romano D. Lio C. Franceschi Inflammation and life-span. Science 307 208\u2013209 (2005).","DOI":"10.1126\/science.307.5707.208"},{"key":"e_1_3_4_18_2","unstructured":"C. E. Finch The Biology of Human Longevity: Inflammation Nutrition and Aging in the Evolution of Lifespans (Elsevier 2010)."},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","unstructured":"J. Strauss D. Thomas \u201cChapter 54 health over the life course\u201d in Handbook of Development Economics T. P. Schultz J. A. Strauss Eds. (Elsevier 2007) vol. 4 pp. 3375\u20133474.","DOI":"10.1016\/S1573-4471(07)04054-5"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","unstructured":"D. P. Strachan Hay fever hygiene and household size. BMJ Br. Med. J. 299 1259\u20131260 (1989).","DOI":"10.1136\/bmj.299.6710.1259"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","unstructured":"L. J. Wammes H. Mpairwe A. M. Elliott M. Yazdanbakhsh Helminth therapy or elimination: Epidemiological immunological and clinical considerations. Lancet Infect. Dis. 14 1150\u20131162 (2014).","DOI":"10.1016\/S1473-3099(14)70771-6"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","unstructured":"A. Loukas et al. Hookworm infection. Nat. Rev. Dis. Prim. 2 1\u201318 (2016).","DOI":"10.1038\/nrdp.2016.88"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","unstructured":"N. Briggs J. Weatherhead K. J. Sastry P. J. Hotez The hygiene hypothesis and its inconvenient truths about helminth infections. PLoS Negl. Trop. Dis. 10 e0004944 (2016).","DOI":"10.1371\/journal.pntd.0004944"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","unstructured":"J. Ma et al. Laboratory mice with a wild microbiota generate strong allergic immune responses. Sci. Immunol. 8 eadf7702 (2023).","DOI":"10.1126\/sciimmunol.adf7702"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","unstructured":"D. Ramanan et al. Helminth infection promotes colonization resistance via type 2 immunity. Science 352 608\u2013612 (2016).","DOI":"10.1126\/science.aaf3229"},{"key":"e_1_3_4_26_2","unstructured":"M. M. Stein et al. Innate immunity and asthma risk in Amish and Hutterite farm children. New Engl. J. Med. 375 411\u2013421 (2016) https:\/\/www.nejm.org\/doi\/pdf\/10.1056\/NEJMoa1508749."},{"key":"e_1_3_4_27_2","first-page":"293","article-title":"The combined effects of family size and farm exposure on childhood hay fever and atopy","volume":"24","author":"Genuneit J.","year":"2013","unstructured":"J. Genuneit , The combined effects of family size and farm exposure on childhood hay fever and atopy. Pediatr. Allergy Immunol. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol. 24, 293\u2013298 (2013).","journal-title":"Pediatr. Allergy Immunol. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol."},{"key":"e_1_3_4_28_2","first-page":"669","article-title":"The more the merrier? The effect of family size and birth order on children\u2019s education*","volume":"120","author":"Black S. E.","year":"2005","unstructured":"S. E. Black, P. J. Devereux, K. G. Salvanes, The more the merrier? The effect of family size and birth order on children\u2019s education* Q. J. Econ. 120, 669\u2013700 (2005).","journal-title":"Q. J. Econ."},{"key":"e_1_3_4_29_2","first-page":"1","article-title":"The impacts of hookworm eradication in the American South. A replication study of Bleakley (The Quarterly Journal of Economics, 2007)","volume":"2","author":"Roodman D.","year":"2007","unstructured":"D. Roodman, The impacts of hookworm eradication in the American South. A replication study of Bleakley (The Quarterly Journal of Economics, 2007). IREE 2, 1\u201345 (2007).","journal-title":"IREE"},{"key":"e_1_3_4_30_2","volume-title":"The Rockefeller Sanitary Commission for the Eradication of Hookworm Disease, Fourth Annual Report for the year 1913","author":"Commission R.","year":"1914","unstructured":"R. Commission, The Rockefeller Sanitary Commission for the Eradication of Hookworm Disease, Fourth Annual Report for the year 1913 (HathiTrust, 1914)."},{"key":"e_1_3_4_31_2","unstructured":"P. J. Hotez et al. \u201cHelminth infections: Soil-transmitted helminth infections and schistosomiasis\u201d in Disease Control Priorities in Developing Countries D. T. Jamison et al Eds. (The International Bank for Reconstruction and Development\/The World Bank Washington (DC) ed. 2 2006)."},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","unstructured":"C. Elman R. A. McGuire B. Wittman Extending public health: The rockefeller sanitary commission and hookworm in the American South. Am. J. Public Heal. 104 47\u201358 (2014).","DOI":"10.2105\/AJPH.2013.301472"},{"key":"e_1_3_4_33_2","volume-title":"The Germ of Laziness: Rockefeller Philanthropy and Public Health in the New South","author":"Ettling J.","year":"2013","unstructured":"J. Ettling, The Germ of Laziness: Rockefeller Philanthropy and Public Health in the New South (Harvard University Press, 2013)."},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.4054\/DemRes.2022.47.5"},{"key":"e_1_3_4_35_2","unstructured":"J. Goldstein et al. CenSoc Mortality File: Version 3.0. (University of California Berkeley 2023). https:\/\/censoc.berkeley.edu. Accessed 13 April 2024."},{"key":"e_1_3_4_36_2","first-page":"1","article-title":"United States life tables eliminating certain causes of death, 1999\u20132001","volume":"61","author":"Arias E.","year":"2013","unstructured":"E. Arias, M. Heron, B. Tejada-Vera, United States life tables eliminating certain causes of death, 1999\u20132001. Natl. Vital Stat. Rep. 61, 1\u2013128 (2013).","journal-title":"Natl. Vital Stat. Rep."},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","unstructured":"J. Fletcher H. Noghanibehambari \u201cToxified to the bone: Early-life and childhood exposure to lead and men\u2019s old-age mortality\u201d (NBER Working Paper 31957 National Bureau of Economic Research Cambridge MA 2023). https:\/\/doi.org\/10.3386\/w31957.","DOI":"10.3386\/w31957"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","unstructured":"C. Goldin A. Lleras-Muney XX spsdoigtsps XY?: The changing female advantage in life expectancy J. Heal. Econ. 67 102224 (2019).","DOI":"10.1016\/j.jhealeco.2019.102224"},{"key":"e_1_3_4_39_2","unstructured":"R. Easterlin \u201cInterregional differences in per capita income population and total income 1840\u20131950\u201d in Trends in the American Economy in the Nineteenth Century The Conference on Research in Income and Wealth Ed. (Princeton University Press 1960) pp. 73\u2013140."},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-012-1701-0"},{"key":"e_1_3_4_41_2","unstructured":"D. Thomas et al. \u201cCausal effect of health on labor market outcomes: Experimental evidence\u201d (CCPR On-Line Working Paper Series 070-06 California Center for Population Research University of California Los Angeles 2006)."},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdeveco.2019.04.004"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/125.suppl_4.1127S"},{"key":"e_1_3_4_44_2","unstructured":"J. Strauss D. Thomas Health nutrition and economic development. J. Econ. Lit. 36 766\u2013817 (1998)."},{"key":"e_1_3_4_45_2","volume-title":"An Evaluation of the Impact of PROGRESA on Preschool Child Height","author":"Behrman J. R.","year":"2001","unstructured":"J. R. Behrman, J. F. Hoddinott, An Evaluation of the Impact of PROGRESA on Preschool Child Height (International Food Policy Research Institute, 2001)."},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1257\/0002828041302109"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2018.09.036"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000016596"},{"key":"e_1_3_4_49_2","unstructured":"J. E. Moorman et al. \u201cNational surveillance for asthma\u2014United States 1980\u20132004\u201d in MMWR Surveillance Summaries (CDC 2007) vol. 56 pp. 1\u201354."},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/63.2.196"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2018.09.003"},{"key":"e_1_3_4_52_2","doi-asserted-by":"crossref","unstructured":"A. D. Blackwell et al. Evidence for a peak shift in a humoral response to helminths: Age profiles of IgE in the Shuar of Ecuador the Tsimane of Bolivia and the U.S. NHANES. PLoS Negl. Trop. Dis. 5 e1218 (2011).","DOI":"10.1371\/journal.pntd.0001218"},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","unstructured":"M. K\u0131ska\u00e7 P. Soysal L. Smith E. Capar M. Zorlu What is the optimal body mass index range for older adults? Ann. Geriatr. Med. Res. 26 49 (2022).","DOI":"10.4235\/agmr.22.0012"},{"key":"e_1_3_4_54_2","doi-asserted-by":"crossref","unstructured":"J. A. Kopinska V. Atella J. Bhattacharya G. Miller \u201cThe changing relationship between bodyweight and longevity in high- and low-income countries\u201d (NBER Working Paper 28813 National Bureau of Economic Research Cambridge MA 2021). https:\/\/doi.org\/10.3386\/w28813.","DOI":"10.3386\/w28813"},{"key":"e_1_3_4_55_2","doi-asserted-by":"crossref","unstructured":"R. W. Fogel Economic growth population theory and physiology: The bearing of long-term processes on the making of economic policy. Am. Econ. Rev. 84 369\u2013395 (1994).","DOI":"10.3386\/w4638"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1162\/rest.91.1.52"},{"key":"e_1_3_4_57_2","doi-asserted-by":"crossref","unstructured":"M. Yazdanbakhsh P. G. Kremsner R. van Ree Allergy parasites and the hygiene hypothesis. Science 296 490\u2013494 (2002).","DOI":"10.1126\/science.296.5567.490"},{"key":"e_1_3_4_58_2","doi-asserted-by":"crossref","unstructured":"T. W. McDade Early environments and the ecology of inflammation. Proc. Natl. Acad. Sci. U.S.A. 109 17281\u201317288 (2012).","DOI":"10.1073\/pnas.1202244109"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007085"},{"key":"e_1_3_4_60_2","doi-asserted-by":"crossref","unstructured":"H. Noghanibehambari J. Fletcher \u201cUnhooking the past: Early-life exposure to hookworm eradication and later-life longevity\u201d (NBER Working Paper 33249 National Bureau of Economic Research Cambridge MA 2024). https:\/\/doi.org\/10.3386\/w33249.","DOI":"10.3386\/w33249"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a118027"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1162\/qjec.2008.123.3.1287"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/jeea\/jvad012"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2504265122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T17:47:13Z","timestamp":1756230433000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2504265122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":63,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2025,9,2]]}},"alternative-id":["10.1073\/pnas.2504265122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2504265122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]},"assertion":[{"value":"2025-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2504265122"}}