According to estimates from the World Health Organization, there are between 11 and 21 million cases of typhoid and 128,000 to 161,000 typhoid-related deaths annually worldwide.[1]World Health Organization. Typhoid vaccines position paper. Mar 2018 [internet publication].
https://www.who.int/publications/i/item/whio-wer9313
The 2017 Global Burden of Disease study reported 14.3 million cases of typhoid and paratyphoid fever in 2017, which was a 44.6% decline from 25.9 million in 1990; there were an estimated 135,900 deaths from typhoid and paratyphoid fever in 2017, which was a 41.0% decline from 230,500 in 1990.[2]GBD 2017 Typhoid and Paratyphoid Collaborators. The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect Dis. 2019 Apr;19(4):369-81.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30685-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30792131?tool=bestpractice.com
The majority of infections (around 70%) are reported from South/South-East Asia, and Sub-Saharan Africa.[2]GBD 2017 Typhoid and Paratyphoid Collaborators. The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect Dis. 2019 Apr;19(4):369-81.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30685-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30792131?tool=bestpractice.com
[3]DeRoeck D, Jodar L, Clemens J. Putting typhoid vaccination on the global health agenda. N Engl J Med. 2007 Sep 13;357(11):1069-71.
https://www.nejm.org/doi/10.1056/NEJMp078144?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
http://www.ncbi.nlm.nih.gov/pubmed/17855666?tool=bestpractice.com
[4]Wain J, Hendriksen RS, Mikoleit ML, et al. Typhoid fever. Lancet. 2015 Mar 21;385(9973):1136-45.
http://www.ncbi.nlm.nih.gov/pubmed/25458731?tool=bestpractice.com
[Figure caption and citation for the preceding image starts]: Incidence rates (per 100 000) of typhoid and paratyphoid fevers, by country, in 2017GBD 2017 Typhoid and Paratyphoid Collaborators. Lancet Infect Dis 2019 Apr;19(4):369-381; used with permission [Citation ends].
The age-standardized incidence rate in south Asia in 2017 was reported as 549 per 100,000, and globally it was 198 per 100,000.[2]GBD 2017 Typhoid and Paratyphoid Collaborators. The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect Dis. 2019 Apr;19(4):369-81.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30685-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30792131?tool=bestpractice.com
The incidence may vary considerably even within a country or city, where it predominantly affects the urban slums.[3]DeRoeck D, Jodar L, Clemens J. Putting typhoid vaccination on the global health agenda. N Engl J Med. 2007 Sep 13;357(11):1069-71.
https://www.nejm.org/doi/10.1056/NEJMp078144?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
http://www.ncbi.nlm.nih.gov/pubmed/17855666?tool=bestpractice.com
In high-income countries, enteric fever is predominantly a travel-associated disease.
[Figure caption and citation for the preceding image starts]: Incidence of typhoid infection (left) and the percentage of travelers (right)CDC image library [Citation ends].
In the US, for example, the annual incidence dropped from 7.5 per 100,000 in 1940 to 0.2 per 100,000 in the 1990s, and the proportion of cases related to foreign travel increased from 33% in 1967 to 72% to 81% in 1996 to 1997.[5]Mermin JH, Townes JM, Gerber M, et al. Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance. Arch Intern Med. 1998 Mar 23;158(6):633-8.
http://archinte.jamanetwork.com/article.aspx?articleid=191653
http://www.ncbi.nlm.nih.gov/pubmed/9521228?tool=bestpractice.com
[6]Taylor DN, Pollard RA, Blake PA. Typhoid in the United States and the risk to the international traveler. J Infect Dis. 1983 Sep;148(3):599-602.
http://www.ncbi.nlm.nih.gov/pubmed/6311917?tool=bestpractice.com
[7]Ryan CA, Hargrett-Bean NT, Blake PA. Salmonella typhi infections in the United States, 1975-1984: increasing role of foreign travel. Rev Infect Dis. Jan-Feb 1989;11(1):1-8.
http://www.ncbi.nlm.nih.gov/pubmed/2916092?tool=bestpractice.com
In Israel the change is even more marked, with an annual incidence of 90 per 100,000 in the early 1950s that had dropped to 0.23 per 100,000 in 2003; 57% of these cases were acquired abroad.[8]Meltzer E, Yossepowitch O, Sadik C, et al. Epidemiology and clinical aspects of enteric fever in Israel. Am J Trop Med Hyg. 2006 Apr;74(4):540-5.
http://www.ajtmh.org/content/74/4/540.full
http://www.ncbi.nlm.nih.gov/pubmed/16606981?tool=bestpractice.com
The overall range of reported annual incidence in industrialized countries ranges from 0.13 to 1.2 cases per 100,000 population, with the overwhelming majority being imported.[5]Mermin JH, Townes JM, Gerber M, et al. Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance. Arch Intern Med. 1998 Mar 23;158(6):633-8.
http://archinte.jamanetwork.com/article.aspx?articleid=191653
http://www.ncbi.nlm.nih.gov/pubmed/9521228?tool=bestpractice.com
[9]Lester A, Mygind O, Jensen KT, et al. Typhoid and paratyphoid fever in Denmark 1986-1990: epidemiologic aspects and the extent of bacteriological follow-up of patients. Ugeskr Laeger. 1994 Jun 20;156(25):3770-5.
http://www.ncbi.nlm.nih.gov/pubmed/8059456?tool=bestpractice.com
[10]Yew FS, Goh KT, Lim YS. Epidemiology of typhoid fever in Singapore. Epidemiol Infect. 1993 Feb;110(1):63-70.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2271965
http://www.ncbi.nlm.nih.gov/pubmed/8432324?tool=bestpractice.com
The risk to travelers appears to vary by geographic region visited.[11]Crump JA, Luby SP, Mintz ED. The global burden of typhoid fever. Bull World Health Organ. 2004 May;82(5):346-53.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2622843
http://www.ncbi.nlm.nih.gov/pubmed/15298225?tool=bestpractice.com
[12]Acharya IL, Lowe CU, Thapa R, et al. Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi. A preliminary report. N Engl J Med. 1987 Oct 29;317(18):1101-4.
http://www.ncbi.nlm.nih.gov/pubmed/3657877?tool=bestpractice.com
[13]Manesh A, Meltzer E, Jin C, et al. Typhoid and paratyphoid fever: a clinical seminar. J Travel Med. 2021 Apr 14;28(3):taab012.
https://academic.oup.com/jtm/article/28/3/taab012/6129661
http://www.ncbi.nlm.nih.gov/pubmed/33550411?tool=bestpractice.com
Several reports indicate that the Indian subcontinent poses the highest risk for acquiring typhoid infection. While the incidence of typhoid infection among US travelers to Mexico, for example, decreased from 0.19 to 0.13 per 100,000 between 1985 and 1994, the incidence among travelers to the Indian subcontinent increased from 23.4 to 81.2 per 100,000. The overall risk of typhoid infection in travel to the Indian subcontinent is 18 times higher than to any other geographic area.[5]Mermin JH, Townes JM, Gerber M, et al. Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance. Arch Intern Med. 1998 Mar 23;158(6):633-8.
http://archinte.jamanetwork.com/article.aspx?articleid=191653
http://www.ncbi.nlm.nih.gov/pubmed/9521228?tool=bestpractice.com
In Israel, 74% of imported typhoid infection cases were acquired in India and the calculated attack rate was 24 per 100,000 travelers, a figure 100 times higher than those for travelers to Thailand or the Middle East.[14]Meltzer E, Sadik C, Schwartz E. Enteric fever in Israeli travelers: a nationwide study. J Travel Med. Sep-Oct 2005;12(5):275-81.
https://academic.oup.com/jtm/article/12/5/275/1840680
http://www.ncbi.nlm.nih.gov/pubmed/16256052?tool=bestpractice.com
Reports from France and Germany also indicate the Indian subcontinent as the main geographic source.[15]Caumes E, Ehya N, Nguyen J, et al. Typhoid and paratyphoid fever: a 10-year retrospective study of 41 cases in a Parisian hospital. J Travel Med. Nov-Dec 2001;8(6):293-7.
https://academic.oup.com/jtm/article/8/6/293/1800101
http://www.ncbi.nlm.nih.gov/pubmed/11726293?tool=bestpractice.com
[16]Jelinek T, Nothdurft HD, von Sonnenburg F, et al. Risk factors for typhoid fever in travelers. J Travel Med. 1996 Dec 1;3(4):200-3.
https://academic.oup.com/jtm/article/3/4/200/1806400
http://www.ncbi.nlm.nih.gov/pubmed/9815456?tool=bestpractice.com
A special group with increased risk are those travelers visiting friends and relatives (VFRs): that is, immigrants who return to visit their homeland. In addition to more travel to rural areas, VFR travelers are less likely to have received pre-travel advice, are less likely to keep food and water precautions, and do not receive typhoid vaccine prior to travel.[17]Angell SY, Cetron MS. Health disparities among travelers visiting friends and relatives abroad. Ann Intern Med. 2005 Jan 4;142(1):67-72.
http://annals.org/article.aspx?articleid=718052
http://www.ncbi.nlm.nih.gov/pubmed/15630110?tool=bestpractice.com
Death is rare in short-term travelers. A review of Centers for Disease Control and Prevention surveillance data from 1985 to 1994 included 2445 cases of typhoid and found a mortality rate of 0.4%. Deaths occurred exclusively in immigrants rather than short-term travelers.[5]Mermin JH, Townes JM, Gerber M, et al. Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance. Arch Intern Med. 1998 Mar 23;158(6):633-8.
http://archinte.jamanetwork.com/article.aspx?articleid=191653
http://www.ncbi.nlm.nih.gov/pubmed/9521228?tool=bestpractice.com
Reports of typhoid infection in hospitalized returning travelers in France, Germany, Israel, and Nepal showed no events of mortality.[14]Meltzer E, Sadik C, Schwartz E. Enteric fever in Israeli travelers: a nationwide study. J Travel Med. Sep-Oct 2005;12(5):275-81.
https://academic.oup.com/jtm/article/12/5/275/1840680
http://www.ncbi.nlm.nih.gov/pubmed/16256052?tool=bestpractice.com
[15]Caumes E, Ehya N, Nguyen J, et al. Typhoid and paratyphoid fever: a 10-year retrospective study of 41 cases in a Parisian hospital. J Travel Med. Nov-Dec 2001;8(6):293-7.
https://academic.oup.com/jtm/article/8/6/293/1800101
http://www.ncbi.nlm.nih.gov/pubmed/11726293?tool=bestpractice.com
[16]Jelinek T, Nothdurft HD, von Sonnenburg F, et al. Risk factors for typhoid fever in travelers. J Travel Med. 1996 Dec 1;3(4):200-3.
https://academic.oup.com/jtm/article/3/4/200/1806400
http://www.ncbi.nlm.nih.gov/pubmed/9815456?tool=bestpractice.com
[18]Boggild AK, Castelli F, Gautret P, et al. Vaccine preventable diseases in returned international travelers: results from the GeoSentinel Surveillance Network. Vaccine. 2010 Oct 28;28(46):7389-95.
http://www.ncbi.nlm.nih.gov/pubmed/20851081?tool=bestpractice.com
An outbreak of typhoid fever caused by a strain of Salmonella typhi resistant to chloramphenicol, ampicillin, trimethoprim/sulfamethoxazole, fluoroquinolones, and ceftriaxone emerged in Pakistan in 2016.[19]Klemm EJ, Shakoor S, Page AJ, et al. Emergence of an extensively drug-resistant Salmonella enterica serovar typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins. mBio. 2018 Feb 20;9(1):e00105-18.
https://mbio.asm.org/content/9/1/e00105-18.long
http://www.ncbi.nlm.nih.gov/pubmed/29463654?tool=bestpractice.com
Extensively drug-resistant (XDR) S typhi has since been documented among travelers, mostly associated with travel to Pakistan.[13]Manesh A, Meltzer E, Jin C, et al. Typhoid and paratyphoid fever: a clinical seminar. J Travel Med. 2021 Apr 14;28(3):taab012.
https://academic.oup.com/jtm/article/28/3/taab012/6129661
http://www.ncbi.nlm.nih.gov/pubmed/33550411?tool=bestpractice.com
[20]Chatham-Stephens K, Medalla F, Hughes M, et al. Emergence of extensively drug-resistant Salmonella typhi infections among travelers to or from Pakistan - United States, 2016-2018. MMWR Morb Mortal Wkly Rep. 2019 Jan 11;68(1):11-3.
https://www.cdc.gov/mmwr/volumes/68/wr/mm6801a3.htm
http://www.ncbi.nlm.nih.gov/pubmed/30629573?tool=bestpractice.com
[21]François Watkins LK, Winstead A, Appiah GD, et al. Update on extensively drug-resistant Salmonella serotype typhi infections among travelers to or from Pakistan and report of ceftriaxone-resistant Salmonella serotype typhi infections among travelers to Iraq - United States, 2018-2019. MMWR Morb Mortal Wkly Rep. 2020 May 22;69(20):618-22.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6920a2.htm
http://www.ncbi.nlm.nih.gov/pubmed/32437343?tool=bestpractice.com
[22]Engsbro AL, Riis Jespersen HS, Goldschmidt MI, et al. Ceftriaxone-resistant Salmonella enterica serotype typhi in a pregnant traveller returning from Karachi, Pakistan to Denmark, 2019. Euro Surveill. 2019 May;24(21):1900289.
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2019.24.21.1900289
http://www.ncbi.nlm.nih.gov/pubmed/31138366?tool=bestpractice.com
[23]Wong W, Rawahi HA, Patel S, et al. The first Canadian pediatric case of extensively drug-resistant Salmonella typhi originating from an outbreak in Pakistan and its implication for empiric antimicrobial choices. IDCases. 2019 Jan 15;15:e00492.
https://www.sciencedirect.com/science/article/pii/S2214250918302282
http://www.ncbi.nlm.nih.gov/pubmed/30815359?tool=bestpractice.com
In the US, between February 2018 and March 2021, 76 XDR and XDR variant S typhi infections were identified. Of these patients, 67 reported travel to or from Pakistan, but nine had no history of international travel in the 30 days before their sickness and also did not report having close contact with anyone sick.[24]Hughes MJ, Birhane MG, Dorough L, et al. Extensively drug-resistant typhoid fever in the United States. Open Forum Infect Dis. 2021 Dec;8(12):ofab572.
https://academic.oup.com/ofid/article/8/12/ofab572/6429216
http://www.ncbi.nlm.nih.gov/pubmed/34917695?tool=bestpractice.com
No source for infection in the patients who had not traveled has been identified and surveillance for XDR typhoid fever is ongoing.[24]Hughes MJ, Birhane MG, Dorough L, et al. Extensively drug-resistant typhoid fever in the United States. Open Forum Infect Dis. 2021 Dec;8(12):ofab572.
https://academic.oup.com/ofid/article/8/12/ofab572/6429216
http://www.ncbi.nlm.nih.gov/pubmed/34917695?tool=bestpractice.com
Enteric fever is a notifiable disease in many countries, with local or national guidelines indicating the reporting requirements.