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Diphtheria vaccine
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<h2 id="history">History</h2> <p>In 1890, <a href="/facts/Kitasato_Shibasabur%C5%8D/LeC09mc1">Kitasato Shibasaburō</a> and <a href="/facts/Emil_von_Behring/bk06nMKy">Emil von Behring</a> at the <a href="/facts/University_of_Berlin/QE2lhhkd">University of Berlin</a> reported the development of 'antitoxins' against diphtheria and tetanus. Their method involved injecting the respective toxins into animals and then purifying antibodies from their blood. Behring called this method '<a href="/facts/Serotherapy/zt7McfLV">serum therapy</a>'. While effective against the pathogen, initial tests on humans were unsuccessful.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> By 1894, the production of antibodies had been optimised with help from <a href="/facts/Paul_Ehrlich/6XM57Clc">Paul Ehrlich</a>, and the treatment started to show success in humans.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> The serum therapy reduced mortality to 1–5%, although there were also reports of severe adverse reactions, including at least one death. Behring won the very first <a href="/facts/Nobel_Prize_in_Physiology_or_Medicine/rlnpJX84">Nobel Prize in Physiology or Medicine</a> for this discovery. Kitasato, however, was not awarded.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> </p><p>By 1913, Behring had created Antitoxin-Toxin (antibody-antigen) complexes to produce the diphtheria AT vaccine. In the 1920s, <a href="/facts/Gaston_Ramon/UhACXKT4">Gaston Ramon</a> developed a cheaper version by using formaldehyde-inactivated toxins.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> As the use of these vaccines spread across the world, the number of diphtheria cases was greatly reduced. In the United States alone, the number of cases fell from 100,000 to 200,000 per year in the 1920s to 19,000 in 1945 and 14 in the period 1996–2018.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> </p> <h2 id="effectiveness">Effectiveness</h2> <p>About 95% of people vaccinated develop immunity, and vaccination against diphtheria has resulted in a more than 90% decrease in number of cases globally between 1980 and 2000.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> About 86% of the world population was vaccinated as of 2016.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> </p> <h2 id="side-effects">Side effects</h2> <p>Severe side effects from diphtheria <a href="/facts/Toxoid/qFAvxp7C">toxoid</a> are rare.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> Pain may occur at the injection site.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> A bump may form at the site of injection that lasts a few weeks.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> The vaccine is safe during pregnancy and among those who have a <a href="/facts/Immunosuppression/22GHUHkr">poor immune function</a>.<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> DTP vaccines may cause additional adverse effects such as fever, irritability, drowsiness, loss of appetite, and, in 6–13% of vaccine recipients, vomiting.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> Severe adverse effects of DTP vaccines include fever over 40.5 °C/104.9 °F (1 in 333 doses), <a href="/facts/Febrile_seizures/KTMYwpBo">febrile seizures</a> (1 in 12,500 doses), and <a href="/facts/Hypotonic-hyporesponsive_episode/zSpCz0b5">hypotonic-hyporesponsive episodes</a> (1 in 1,750 doses).<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a><a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> Side effects of DTaP vaccines are similar but less frequent.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> Tetanus toxoid containing vaccines (Td, DT, DTP and DTaP) may cause <a href="/facts/Brachial_neuritis/JNqsE9lj">brachial neuritis</a> at a rate of 0.5 to 1 case per 100,000 toxoid recipients.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a><a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> </p> <h2 id="recommendations">Recommendations</h2> <p>The World Health Organization has recommended vaccination against diphtheria since 1974.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> The first dose is recommended at six weeks of age with two additional doses four weeks apart, after receiving these three doses about 95% of people are immune.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> Three further doses are recommended during childhood.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> Booster doses every ten years are no longer recommended if this vaccination scheme of 3 doses + 3 booster doses is followed.<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> Injection of 3 doses + 1 booster dose, provides immunity for 25 years after the last dose.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a> If only three initial doses are given, booster doses are needed to ensure continuing protection.<a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Bundaberg_tragedy/LnhLgv1F">Bundaberg tragedy</a></li> <li><a href="/facts/DTP-HepB_vaccine/4nIB9b2p">DTP-HepB vaccine</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Ramsay M, ed. (2013). <a href="https://www.gov.uk/government/publications/diphtheria-the-green-book-chapter-15">"Chapter 15: Diphtheria"</a>. <a href="https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the-green-book"><i>Immunisation against infectious disease</i></a>. Public Health England.</li> <li>Acosta AM, Moro PL, Hariri S, Tiwari TS (2021). <a href="https://www.cdc.gov/vaccines/pubs/pinkbook/dip.html">"Chapter 7: Diphtheria"</a>. In Hall E, Wodi AP, Hamborsky J, Morelli V, Schillie S (eds.). <a href="https://www.cdc.gov/vaccines/pubs/pinkbook/index.html"><i>Epidemiology and Prevention of Vaccine-Preventable Diseases</i></a> (14th ed.). Washington D.C.: U.S. <a href="/facts/Centers_for_Disease_Control_and_Prevention/NmoJNDV5">Centers for Disease Control and Prevention</a> (CDC).</li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="http://www.fda.gov/vaccines-blood-biologics/vaccines/infanrix">"Infanrix"</a>. <i>U.S. <a href="/facts/Food_and_Drug_Administration/rCEnh9WB">Food and Drug Administration</a> (FDA)</i>. 6 November 2019.</li> <li><a href="http://www.fda.gov/vaccines-blood-biologics/vaccines/daptacel">"Daptacel"</a>. <i>U.S. <a href="/facts/Food_and_Drug_Administration/rCEnh9WB">Food and Drug Administration</a> (FDA)</i>. 22 July 2017.</li> <li><a href="https://meshb.nlm.nih.gov/record/ui?name=Diphtheria+Toxoid">Diphtheria Toxoid</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Donahue ML, Eberly MD (2022). "Chapter 2: Diphtheria and tetanus". In Jong EC, Stevens DL (eds.). Netter's Infectious Diseases (2nd ed.). Philadelphia: Elsevier. pp. 5–10. ISBN 978-0-323-71159-3. <a href="978-0-323-71159-3" target="_blank">978-0-323-71159-3</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Atkinson W (May 2012). Diphtheria Epidemiology and Prevention of Vaccine-Preventable Diseases (12th ed.). Public Health Foundation. pp. 215–230. ISBN 9780983263135. Archived from the original on 15 September 2016. <a href="9780983263135" target="_blank">9780983263135</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Atkinson W (May 2012). Diphtheria Epidemiology and Prevention of Vaccine-Preventable Diseases (12th ed.). Public Health Foundation. pp. 215–230. ISBN 9780983263135. Archived from the original on 15 September 2016. <a href="9780983263135" target="_blank">9780983263135</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>"Diphtheria Vaccination". Centers for Disease Control and Prevention (CDC). Archived from the original on 2 November 2011. Retrieved 8 November 2011. <a href="https://web.archive.org/web/20111102042325/http://www.cdc.gov/vaccines/vpd-vac/diphtheria/default.htm#vacc" target="_blank">https://web.archive.org/web/20111102042325/http://www.cdc.gov/vaccines/vpd-vac/diphtheria/default.htm#vacc</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>"Diphtheria". World Health Organization (WHO). 3 September 2014. Archived from the original on 2 April 2015. Retrieved 27 March 2015. <a href="https://web.archive.org/web/20150402121723/http://www.who.int/immunization/monitoring_surveillance/burden/diphtheria/en/" target="_blank">https://web.archive.org/web/20150402121723/http://www.who.int/immunization/monitoring_surveillance/burden/diphtheria/en/</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Atkinson W (May 2012). Diphtheria Epidemiology and Prevention of Vaccine-Preventable Diseases (12th ed.). Public Health Foundation. pp. 215–230. ISBN 9780983263135. Archived from the original on 15 September 2016. <a href="9780983263135" target="_blank">9780983263135</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Macera C (2012). Introduction to Epidemiology: Distribution and Determinants of Disease. Nelson Education. p. 251. ISBN 9781285687148. Archived from the original on 5 March 2016. <a href="9781285687148" target="_blank">9781285687148</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02. <a href="/wiki/World_Health_Organization" target="_blank">/wiki/World_Health_Organization</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>"A Diphtheria Cure, 1894". New York Times. 10 May 2010. <a href="https://www.nytimes.com/2010/05/11/health/11first.html" target="_blank">https://www.nytimes.com/2010/05/11/health/11first.html</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> <li id="fn:20"><p>Kaufmann SH (February 2017). "Remembering Emil von Behring: from Tetanus Treatment to Antibody Cooperation with Phagocytes". mBio. 8 (1): e00117–17. doi:10.1128/mbio.00117-17. PMC 5347343. PMID 28246359. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347343" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347343</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></p></li> <li id="fn:21"><p>Kaufmann SH (February 2017). "Remembering Emil von Behring: from Tetanus Treatment to Antibody Cooperation with Phagocytes". mBio. 8 (1): e00117–17. doi:10.1128/mbio.00117-17. PMC 5347343. PMID 28246359. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347343" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347343</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></p></li> <li id="fn:22"><p>Kaufmann SH (February 2017). "Remembering Emil von Behring: from Tetanus Treatment to Antibody Cooperation with Phagocytes". mBio. 8 (1): e00117–17. doi:10.1128/mbio.00117-17. PMC 5347343. PMID 28246359. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347343" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347343</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></p></li> <li id="fn:23"><p>"Diphtheria". Centers for Disease Control and Prevention. 19 October 2022. <a href="https://www.cdc.gov/vaccines/pubs/pinkbook/dip.html" target="_blank">https://www.cdc.gov/vaccines/pubs/pinkbook/dip.html</a> <a href="#fnref:23" class="footnote-back-ref">↩</a></p></li> <li id="fn:24"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:24" class="footnote-back-ref">↩</a></p></li> <li id="fn:25"><p>"Diphtheria". World Health Organization (WHO). 3 September 2014. Archived from the original on 2 April 2015. Retrieved 27 March 2015. <a href="https://web.archive.org/web/20150402121723/http://www.who.int/immunization/monitoring_surveillance/burden/diphtheria/en/" target="_blank">https://web.archive.org/web/20150402121723/http://www.who.int/immunization/monitoring_surveillance/burden/diphtheria/en/</a> <a href="#fnref:25" class="footnote-back-ref">↩</a></p></li> <li id="fn:26"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:26" class="footnote-back-ref">↩</a></p></li> <li id="fn:27"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:27" class="footnote-back-ref">↩</a></p></li> <li id="fn:28"><p>Atkinson W (May 2012). Diphtheria Epidemiology and Prevention of Vaccine-Preventable Diseases (12th ed.). Public Health Foundation. pp. 215–230. ISBN 9780983263135. Archived from the original on 15 September 2016. <a href="9780983263135" target="_blank">9780983263135</a> <a href="#fnref:28" class="footnote-back-ref">↩</a></p></li> <li id="fn:29"><p>Atkinson W (May 2012). Diphtheria Epidemiology and Prevention of Vaccine-Preventable Diseases (12th ed.). Public Health Foundation. pp. 215–230. ISBN 9780983263135. Archived from the original on 15 September 2016. <a href="9780983263135" target="_blank">9780983263135</a> <a href="#fnref:29" class="footnote-back-ref">↩</a></p></li> <li id="fn:30"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:30" class="footnote-back-ref">↩</a></p></li> <li id="fn:31"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:31" class="footnote-back-ref">↩</a></p></li> <li id="fn:32"><p>DuVernoy TS, Braun MM, et al. (The VAERS Working Group) (October 2000). "Hypotonic-hyporesponsive episodes reported to the Vaccine Adverse Event Reporting System (VAERS), 1996-1998". Pediatrics. 106 (4): E52. doi:10.1542/peds.106.4.e52. PMID 11015547. S2CID 12743062. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:32" class="footnote-back-ref">↩</a></p></li> <li id="fn:33"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. 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PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:36" class="footnote-back-ref">↩</a></p></li> <li id="fn:37"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. PMID 28776357. <a href="http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1" target="_blank">http://apps.who.int/iris/bitstream/10665/258681/1/WER9231.pdf?ua=1</a> <a href="#fnref:37" class="footnote-back-ref">↩</a></p></li> <li id="fn:38"><p>"Diphtheria vaccine: WHO position paper – August 2017" (PDF). Relevé Épidémiologique Hebdomadaire. 92 (31): 417–435. August 2017. hdl:10665/258681. 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