CCDR: Volume 40-4, February 20, 2014

Canada Communicable Disease Report CCDR

ISSN 1481-8531 (On-line)

Summary of the Statement on International Travellers and Typhoid by the Committee to Advise on Tropical Medicine and Travel CATMAT

Greenaway C,Author Footnote IAuthor Footnote * Schofield S,Author Footnote II Henteleff A,Author Footnote III Plourde P,Author Footnote IV Geduld J,Author Footnote V Abdel-Motagally MAuthor Footnote V and Bryson MAuthor Footnote V on behalf of CATMAT

Author Footnotes

Author Footnote 1

Department of Microbiology, McGill University, Montreal, QC

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Author Footnote 2

Department of National Defense, Ottawa, ON

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Author Footnote 3

Innovative Solutions - Health Plus, Winnipeg, MB

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Author Footnote 4

Winnipeg Regional Health Authority, Winnipeg, MB

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Author Footnote 5

Public Health Agency of Canada, Ottawa, ON

Return to author footnote V referrer

Author Footnote *

Corresponding author:

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Background: Typhoid fever is an enteric febrile illness with symptoms that range from mild to potentially fatal. Among Canadians it is usually acquired during travel to typhoid endemic countries. The Committee to Advise on Tropical Medicine and Travel (CATMAT) assembled a typhoid working group to update recommendations on typhoid and international travel. This document is a summary of the new typhoid statement.

Methods: Following a systematic review of the literature, typhoid vaccine recommendations were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to evaluate data quality, benefits and harms, and values and preferences. The literature search focused on systematic reviews of typhoid vaccine efficacy and identified studies of disease burden, pathogenesis, risk factors and prevention. Other recommendations were based on a review of the retrieved literature and expert opinion.

Results: Typhoid vaccine is moderately effective (~50%), well tolerated, with very low risk of serious adverse events. Studies of typhoid vaccine efficacy, morbidity or mortality among travellers were not found, although studies on populations in typhoid endemic countries were identified. Among travellers, destination of travel is the strongest and most consistent typhoid risk predictor; the highest risk was for travel to South Asia. Confidence in effect estimates for other potential risk factors was very low.

Recommendations: CATMAT suggests that typhoid vaccine (Ty21a or Vi polysaccharide vaccine) be used for most Canadian travellers visiting South Asia and not used for most Canadian travellers visiting destinations other than South Asia. The recommendations are conditional, due to the moderate confidence in the effect estimate. For destinations other than South Asia, providers should discuss risks and vaccine benefits and harms with the traveller as well as recommend basic hygiene precautions.


Typhoid fever is an enteric febrile illness caused by Salmonella enterica subsp. enterica serovars Typhi (S. typhi)Footnote 1Footnote 2. Humans are the only reservoir for this disease and exposure to the causative pathogen is usually through ingestion of water or food that has been contaminated by feces from an ill individual or a chronic carrierFootnote 3Footnote 4. Prevention involves vaccination, personal hygiene and food and water precautions.

The World Health Organization (WHO) estimates 21 million typhoid cases and 210,000 to 840,000 deaths annually worldwideFootnote 5Footnote 6. In endemic countries, widespread transmission is facilitated by poorly developed sanitation infrastructure Footnote 7. Most cases and deaths (more than 90%) occur in Asian countries, predominantly in South AsiaFootnote 5. Incidence in high income countries is low (e.g., <15/100,000 persons per year)Footnote 1Footnote 3Footnote 8 and usually acquired during travelFootnote 9Footnote 10Footnote 11Footnote 12.

The clinical course of typhoid ranges from mild illness (low-grade fever) to severe systemic potentially fatal diseaseFootnote 2Footnote 3. The case fatality rate is approximately 10% for untreated cases in low income settings and <1% for patients receiving care in high income countriesFootnote 13 Footnote 14 Footnote 15 Footnote 16 Footnote 17 .

The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada with ongoing and timely medical, scientific, and public health advice relating to tropical infectious disease and health risks associated with international travel. This is a summary of the CATMAT Statement on International Travellers and Typhoid where a full description of the evidence and recommendations is availableFootnote 18.


This is the first CATMAT statement to use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to develop recommendationsFootnote 19. GRADE is a new method of grading the quality of the evidence and strength of recommendations in guidelines used by many international organizations.

Literature search and identification

An analytic framework identifying clinical preventive actions (interventions) for typhoid and risk factors for typhoid disease was developed. Key questions to define the magnitude of benefits and harms were identified as well as the following key "PICO" (population of interest, intervention, comparison and outcome) question:

Among Canadian travellers, does the administration of typhoid vaccine versus no vaccine decrease the incidence of typhoid and the associated morbidity and mortality?

Two types of typhoid vaccine are licensed in Canada, a live oral vaccine (Ty21a), and injectable Vi polysaccharide vaccines (See Table 1). Only evidence for these types of vaccines was reviewed.

Relevant literature was identified by searching Ovid MEDLINE and Embase electronic databases using the terms "typhoid fever" and "travel". The search spanned publications from January 1, 2000 to August 14, 2012. In addition, the Cochrane Database of Systematic Reviews was searched using the term "typhoid" from the start of the database up to and including July 2012. For all searches, only English and/or French articles were retained.

Systematic reviews that addressed the efficacy of typhoid vaccine were specifically sought. Studies that addressed burden of disease (incidence, morbidity, mortality, hospitalizations), especially for travellers; disease pathogenesis; population-specific risk factors (e.g., age, travellers visiting friends and relatives (VFR)); itinerary-specific risk factors (e.g., destination, duration of travel); efficacy of preventive measures (e.g., sanitation and hygiene); and/or disease treatment/management were also identified.

Table 1: Typhoid vaccines licensed for use in Canada
Vaccine Parenteral, capsular polysaccharide vaccines (Typh-I) Oral, live attenuated vaccine (Typh-O) Combined vaccine
Brand Name

Typhim Vi®Footnote 20 (Sanofi Pasteur)
TYPHERIX®Footnote 21 (GlaxoSmithKline Inc)

Vivotif ® (capsules)Footnote 22
(Crucell Switzerland Ltd)

ViVAXIM®Footnote 23 (Sanofi Pasteur)
(combination of purified Vi polysaccharide typhoid with inactivated hepatitis A)

Authorized for use in persons

> 2 years of age

adults and children > 5 years of age

≥16 years of age

Protection begins

14 days following vaccination

7 days following vaccination

14 days following vaccination


0.5 ml

4 enteric-coated capsules taken on alternate days

1.0 ml


Single intramuscular injection

Orally in a series of doses

Single intramuscular injection


A severe local or systemic reaction to a previous dose of the vaccine

Individuals with hypersensitivity to any component of the vaccine or the enteric-coated capsule.
Persons with an acute gastrointestinal condition or inflammatory bowel disease.
Vaccine should not be administered to persons deficient in their ability to mount a humoral or cell-mediated response due to either a congenital or acquired immunodeficient state including treatment with immunosuppressive or antimitotic drugs.

Known systemic hypersensitivity reaction to any component of ViVAXIM® or a life-threatening reaction after previous administration of the vaccine or a vaccine containing one or more of the same components

Drug Interactions

There are no known interactions

Antibiotics: Ty21a vaccination should be completed 3 days before commencing treatment with sulfonamides or other antibiotics.

Antibiotic exceptions: Chloroquine, Mefloquine and Malarone do not influence the immune response of Ty21A and can be administered at any interval.

When using any other antimalarial, immunization with Vivotif ® should precede antimalarial prophylaxis using the 3 day interval.

Adverse Events

Typhim Vi®:Pain at injection site, edema, redness, headache and malaise Footnote 20
TYPHERIX®: Pain at injection site, fever, headache, general aches, malaise, nausea and itching.
These mild reactions occur in less than 10% of individuals vaccinated Footnote 21.

Adverse reactions are infrequent and mild; nausea, abdominal pain, headache, fever, diarrhea, vomiting and skin rash.

Pain, edema or erythema at the injection site, myalgia, headache, fever, malaise, nausea and diarrhea Footnote 23.

Efficacy with immunosuppression

Immunocompromised persons (whether from disease or treatment) may not obtain the expected immune response.

RevaccinationTable 1 Footnote a

TyphimVi – every 3 years
TYPHERIX® - every 3 years

Vivotif ® - every 7 yearsTable 1 Footnote b

Hepatitis A - Boost with a single dose of inactivated hepatitis A vaccine 6-36 months later for long term protection.
Typhoid - Revaccination with a single dose of purified Vi polysaccharide vaccine can be given at an interval of not more than 3 years.

Interchangeability Although there are no data regarding the interchangeability of typhoid vaccines, it is presumed that re-immunization can be performed with any of the available formulations regardless of the vaccine used initially.
Safety in Pregnancy Safety in pregnancy has not been studied for any of the typhoid vaccines. Therefore, the benefits of vaccination must be carefully weighed against potential adverse events before it is given to pregnant women. Vaccine should only be used in pregnancy when there is a high risk of infection. There is no expected effect with purified polysaccharide vaccines.

Sources:Footnote 20 Footnote 21 Footnote 22 Footnote 23

Table 1 Footnote a

Revaccination should be carried out when subjects remain at risk in conditions of repeated or continuous exposure. The Cochrane review presented data that sero protection continues for up to three years after immunization in endemic populations; there are data to indicate that protection from Ty21a extends to 7 yearsFootnote 24. There are no data on continued protection in travellers.

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Table 1 Footnote b

CATMAT is aware that The Yellow Book - CDC Health Information for International Travellers 2012 advises repeat immunization with oral live attenuated Ty21a vaccine every 5 years however the CATMAT statement is consistent with the Health Canada Biologics and Genetic Therapies Directorate vaccine approval for re-immunization every 7 years.

Return to table 1 footnote b referrer

Assessment of evidence

Full details on GRADE methodology are described elsewhereFootnote 25. Briefly, the GRADE approach rates the quality of the evidence for specific clinical outcomes across studies, not study by study, by addressing flaws in methodology, consistency and generalizability of results and demonstrated effectiveness of the treatmentFootnote 26 Footnote 27. The GRADE approach takes into consideration the balance of benefits (efficacy) and harms of typhoid vaccine, the confidence in the estimates of effect for vaccination (high, moderate, low or very low), and what is believed to be the values and preferences of the traveller. GRADE quality assessments of studies of typhoid vaccine efficacy, vaccine adverse events and typhoid risk by destination region were performed, and results were collated into evidence profile and summary of findings tablesFootnote 18.

In this statement, recommendations are expressed as strong or conditional as outlined in the Appendix. Other recommendations, not using the GRADE approach, do not use this terminology. These recommendations were based on evaluation of the relevant literature and expert opinion.


In total, 147 articles met the language and relevancy criteria and were included. Two additional studies on baseline riskFootnote 28Footnote 29 were identified after the initial literature review.

Vaccine efficacy

No studies that addressed efficacy of typhoid vaccine in travellers or associated reductions in morbidity and mortality for this population were found. All included vaccine efficacy studies were conducted in populations living in typhoid endemic countries. A 2006 Cochrane Collaboration systematic review assessed 17 randomized or quasi-randomized trialsFootnote 30 of typhoid vaccine among residents of endemic areas. An additional three randomized or quasi-randomized controlled clinical trials published after this systematic review were also identified and included in this analysisFootnote 31Footnote 32 Footnote 33.

Expressed as three year cumulative risk of typhoid, persons receiving typhoid vaccine (Ty21a or Vi polysaccharide) were significantly less likely to develop typhoid fever than those who did not (Relative Risk (RR), 95% CI =0.51 (0.42 to 0.62)). For the same outcome, but measured as a two year cumulative risk of typhoid, RR was lower at 0.43 (0.34 to 0.54). Expressed by vaccine type, estimates ranged from RR=0.34 (0.19 to 0.60) for Ty21a after two years of follow-up to 0.53 (0.43 to 0.54) for Ty 21a after three years of follow-up; efficacy of Vi polysaccharide vaccine was intermediate to these values. Vaccine efficacy for different age groups was assessed separately by vaccine type as results were reported with different age stratifications. For both types of vaccine, the RR estimate was lower in older than in younger persons. However, these differences were not significant.

Estimates of effect were without serious risk of bias; but were rated down for indirectness as they only included residents of endemic areas (not travellers) and often were limited to younger age groups. There was moderate confidence in the estimate of effect for vaccine efficacy. No data on the impact of typhoid vaccination on morbidity and mortality were found.

Adverse events associated with vaccine

Based on clinical trial data, adverse events (AE) associated with typhoid vaccines are generally mild and not significantly different from controls for: fever, vomiting, diarrhea, headaches, rash, or erythema. With Vi polysaccharide, pain at the injection site was more common among the vaccine recipients (RR=3.68; (1.96 to 6.93)). For enteric coated Ty21a, there was increased risk of: any mild adverse event (RR=1.78; (1.08 to 2.95)) Footnote 30 and nausea or abdominal pain (RR=2.13; (1.33 to 3.41)). Based on these data, it was estimated that there would be one additional AE due to pain for every 13 persons receiving Vi polysaccharide vaccine; and one mild AE and one nausea and abdominal pain AE for every 18 and 31 persons, respectively, receiving Ty21a.

Risk factors

The strongest and most consistent predictor of typhoid risk in travellers is destination of travel. The estimated risk of developing travel associated typhoid is about: 1/3,000 travellers for travel to the South Asia (high risk), 1/50,000-100,000 for travel to Sub-Saharan Africa, North Africa and the Middle East, or South America (intermediate risk), and < 1/300,000 for travel to the Caribbean and Central America (low risk). South Asia is defined as Afghanistan, Bangladesh, Bhutan, India, Nepal, Maldives, Pakistan, and Sri Lanka. Among these countries, the large majority (≥ 90%) of cases of typhoid among travellers were reported from India, Pakistan and Bangladesh.

The confidence in the baseline estimates of typhoid risk by destination was reduced from high to moderate because of risk of bias due to possible under-ascertainment of cases and imprecision (i.e. unable to calculate confidence intervals due to incomplete stratified denominator data).

Several studies have identified other factors that increase the risk of travel associated typhoid, including travelling children, those visiting friends and relatives (VFRs), the presence of achlorhydria or use of acid suppression therapy and longer duration of travel. The incremental magnitude of risk that these factors contribute in addition to travel destination is unclear.

Values and preferences

There is evidence that typhoid vaccine is cost effective for residents of some endemic areasFootnote 34Footnote 35. However, cumulative risk is much higher among resident populations, and it is not appropriate to extrapolate cost-effectiveness to travellers paying for their own vaccine. No studies on traveller values and preferences or "Willingness to Pay" for typhoidFootnote 36 or other travel-related immunizations were identified. In the absence of data, it was estimated that the majority of Canadian travellers would consider typhoid vaccine use worth the cost and inconvenience where the risk of typhoid is estimated to be greater than 1 in 10,000 travellers, although at the individual level this decision may be influenced by other risk factors.


The WHO considers fluoroquinolones to be the first line agents for typhoid treatmentFootnote 37Footnote 38. In a 2011 Cochrane review, fluoroquinolones were found to result in fewer clinical failures compared to chloramphenicol, co-trimoxazole, amoxicillin and ampicillinFootnote 37. When the performance of quinolones was compared to other agents including cephalosporins (ceftriaxone and cefixime) or azithromycin, clinical outcomes appeared to be equivalent in most studies. Definitive conclusions could not be made as most of the data came from small underpowered studies and resistance patterns differ between geographic regions and over time. When deciding on the optimal empiric therapy for typhoid, antibiotic resistance patterns in the travel destination countries should be consideredFootnote 3Footnote 39. Of particular importance is the increasing prevalence of fluoroquinolone resistance among Salmonella tyhpi isolates from AsiaFootnote 37.

Hygiene interventions

Interventions such as hand washing and avoiding high risk foods entail minimal or no risk, inconvenience, or cost, and there is appreciable indirect evidence of benefit in terms of reducing typhoid incidenceFootnote 38.

Typhoid vaccine and Salmonella paratyphi

Paratyphoid fever, caused by Salmonella enterica serovar Paratyphi A, B and C, is a systemic disease with clinical features indistinguishable from typhoid fever. The global burden, estimated at 5.4 million cases annually, may be increasingFootnote 6; as is the prevalence of antibiotic resistance and the number of travel-related cases. It is unlikely that injectable Vi vaccines would provide protection because the vaccine elicits antibodies for an antigen that is not present in S. paratyphi A and B. In contrast, Ty21a vaccines elicit serum and mucosal antibodies to S. typhi O, H and other antigens, which are shared with S. paratyphi. However, current evidence is not sufficient to recommend oral typhoid vaccine (Ty21a) for protection against paratyphoid.

Recommendations and conclusions

The risk of typhoid to travellers is generally low and varies by region. It is highest for travellers to South Asia. The low risk of typhoid combined with the moderate efficacy of the vaccine mean that the benefits of vaccination are modest (efficacy ~50%); however, the vaccines have a good safety profile. Following the review of all evidence and taking into consideration the vaccine efficacy, risk for typhoid and safety profile, CATMAT suggests that the majority of travellers to the South Asia be given typhoid vaccine (Ty21a or Vi polysaccharide vaccine) and not be used for travellers to all other endemic areas (See Table 2). The recommendations are conditional, due to the moderate confidence in the effect estimate.

Table 2: Recommendations on the use of typhoid vaccine for Canadian travellers
Typhoid vaccine
CATMAT suggests
  • that typhoid vaccine (Ty21a or Vi polysaccharide vaccine) be used for Canadian travellers visiting South AsiaTable 2 Footnote *; Conditional recommendation, moderate confidence in estimate of effect.
  • that typhoid vaccine (Ty21a or Vi polysaccharide vaccine) not be used for Canadian travellers visiting destinations other than the South Asia; Conditional recommendation against immunization, moderate confidence in estimate of effect.
"Best practice" or "common sense" recommendations:
CATMAT suggests
  • Practitioners should advise travellers to adhere to basic sanitation and food and water precautions.
  • Providers should discuss with the traveller the anticipated benefits and harms (including financial costs) associated with vaccination, and support the traveller in reaching a decision that is consistent with his/her values and preferences.
  • While there is evidence that suggests Ty21a protects against paratyphoid, it is not sufficient to recommend this vaccine (as an unlabelled use) for this purpose.
  • The first line drug of choice to treat typhoid are fluoroquinolones however, local antimicrobial resistance patterns in the country of travel need to be considered when choosing empiric therapy.
Table 2 Footnote *

For destinations other than South Asia, typhoid vaccination decisions might be influenced by other factors associated with risk of travel acquired typhoid. Providers should discuss associated risk factors and anticipated vaccination benefits and harms with the traveller.

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Footnote 1

Bhutta ZA. Typhoid fever: current concepts. Infect Dis Clin Pract 2006 Sep;14(5):266-72.

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Footnote 2

World Health Organization. International travel and health. Italy: World Health Organization; 2011.

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Footnote 3

American Public Health Association. Control of communicable diseases manual, 19th Edition, edited by Heymann, D.L. 19th ed. Washington: American Public Health Association; 2008.

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Footnote 4

Thaver D, Zaidi A, Critchley J, Azmatullah A, Madni S, Bhutta Z. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database Syst Rev 2008;4 CD004530.

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Footnote 5

Crump JA, Luby SP, Mintz ED. The global burden of typhoid fever. Bull World Health Organ 2004 May;82(5):346-53.

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Footnote 6

Crump JA, Mintz ED. Global trends in typhoid and paratyphoid fever. Clin Infect Dis 2010 Jan 15;50(2):241-6.

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Footnote 7

Luxemburger C, Duc CM, Lanh MN, Wain J, Hien TT, Simpson JA, et al. Risk factors for typhoid fever in the Mekong delta, southern Viet Nam: a case-control study. Trans R Soc Trop Med Hyg 2001;95(1):19-23.

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Footnote 8

Connor BA, Schwartz E. Typhoid and paratyphoid fevers in travellers. Lancet Infect Dis 2005 Oct;5(10):623-8.

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Footnote 9

Gupta SK, Medalla F, Omondi MW, Whichard JM, Fields PI, Gerner-Smidt P, et al. Laboratory-based surveillance of paratyphoid fever in the United States: travel and antimicrobial resistance. Clin Infect Dis 2008 Jun 1;46(11):1656-63.

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Footnote 10

Keddy KH, Smith AM, Sooka A, Ismail H, Oliver S. Fluoroquinolone-resistant typhoid, South Africa. Emerg Infect Dis 2010 May;16(5):879-80.

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Footnote 11

Luxemburger C, Dutta AK. Overlapping epidemiologies of hepatitis A and typhoid fever: the needs of the traveler. J Travel Med 2005 Apr;12(Suppl 1):S12-S21.

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Footnote 12

Steele D. The importance of generating evidence on typhoid fever for implementing vaccination strategies. J Infect Dev Ctries 2000 Aug 30;2(4):250-2.

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Footnote 13

Mermin JH, Townes MJ, Gerber M, Dolan N, Mintz ED, Tauxe RV. Typhoid fever in the United States, 1985-1994. Arch Intern Med 1998 Mar 23;158(6):633-8.

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Footnote 14

Lynch MF, Blanton EM, Bulens S, Polyak C, Vojdani J, Stevenson J, et al. Typhoid fever in the United States, 1999-2006. JAMA 2009 Aug 26;302(8):859-65.

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Footnote 15

Gil R, Alvarez JL, Gomez C, Alvaro A, Gil A. Epidemiology of typhoid and paratyphoid fever hospitalizations in Spain (1997-2005). Hum Vaccin 2009 Jun;5(6):420-4.

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Footnote 16

Delmas G, Vaillant V, Jourdan N, Hello S., Weill F-X, Valk H. Les fièvres typhoïdes et paratyphoïdes en France entre 2004 et 2009. Bulletin épidémiologique hebdomadaire 2011;2(25 janvier 2011):9-13.

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Footnote 17

Stuart BM, Pullen RL. Typhoid: clinical analysis of three hundred and sixty cases. Arch Intern Med 1946 Dec;78(6):629-61.

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Footnote 18

Committee to Advise on Tropical Medicine and Travel (CATMAT). . 2014.

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Footnote 19

Guyatt GH, Oxman AD, Schunemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol 2011 Apr;64(4):380-2.

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Footnote 20

sanofi pasteur. Typhim Vi Product Monograph. Sanofi Pasteur Limited; 2005.

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Footnote 21

GlaxoSmithKline Inc. Typherix Product Monograph. GlaxoSmithKline Inc; 2011.

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Footnote 22

Crucell Switzerland LTD. Vivotif® Product Monograph. 2010.

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Footnote 23

sanofi pasteur. ViVaxim Product Monograph. Sanofi Pasteur Limited; 2010.

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Footnote 24

Levine MM, Ferreccio C, Abrego P, San MO, Ortiz E, Cryz S. Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine 1999;17:S22-S27.

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Footnote 25

Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 2011 Apr;64(4):401-6.

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Footnote 26

Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines 12. Preparing Summary of Findings tables-binary outcomes. J Clin Epidemiol 2012 May 18.

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Footnote 27

Guyatt GH, Oxman AD, Sultan S, Glasziou P, Akl EA, Alonso-Coello P, et al. GRADE guidelines: 9. Rating up the quality of evidence. J Clin Epidemiol 2011 Dec;64(12):1311-6.

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Footnote 28

Baaten GG, Sonder GJ, Van Der Loeff MF, Coutinho RA, Van Den Hoek A. Fecal-orally transmitted diseases among travelers are decreasing due to better hygienic standards at travel destination. J Travel Med 2010 Sep;17(5):322-8.

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Footnote 29

Keller A, Frey M, Schmid H, Steffen R, Walker T, Schlagenhauf P. Imported typhoid fever in Switzerland, 1993 to 2004. J Travel Med 2008;15(4):248-51.

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Footnote 30

Fraser A, Goldberg E, Acosta CJ, Paul M, Leibovici L. Vaccines for preventing typhoid fever (Review). Cochrane Database Syst Rev 2007;3 CD001261.

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Footnote 31

Sur D, Ochiai RL, Bhattacharya SK, Ganguly NK, Ali M, Manna B, et al. A cluster-randomized effectiveness trial of Vi typhoid vaccine in India. N Engl J Med 2009 Jul 23;361(4):335-44.

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Footnote 32

Zhou WZ, Koo HW, Wang XY, Zhang J, Park JK, Zhu F, et al. Revaccination with locally-produced Vi typhoid polysaccharide vaccine among Chinese school-aged children: safety and immunogenicity findings. Pediatr Infect Dis J 2007 Nov;26(11):1001-5.

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Footnote 33

Khan MI, Soofi SB, Ochiai RL, Habib MA, Sahito SM, Nizami SQ, et al. Effectiveness of Vi capsular polysaccharide typhoid vaccine among children: a cluster randomized trial in Karachi, Pakistan. Vaccine 2012 Aug 3;30(36):5389-95.

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Footnote 34

Cook J, Sur D, Clemens J, Whittington D. Evaluating investments in typhoid vaccines in two slums in Kolkata, India. J Health Popul Nutr 2009 Dec;27(6):711-24.

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Footnote 35

Cook J, Jeuland M, Whittington D, Poulos C, Clemens J, Sur D, et al. The cost-effectiveness of typhoid Vi vaccination programs: calculations for four urban sites in four Asian countries. Vaccine 2008 Nov 25;26(50):6305-16.

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Footnote 36

Whittington D, Sur D, Cook J, Chatterjee S, Maskery B, Lahiri M, et al. Rethinking Cholera and Typhoid Vaccination Policies for the Poor: Private Demand in Kolkata, India. World Development 2009;37(2):399-409.

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Footnote 37

Effa EE, Lassi ZS, Critchley JA, Garner P, Sinclair D, Olliaro PL, et al. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database Syst Rev 2011;(10):CD004530.

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Footnote 38

World Health Organization. Background document: The diagnosis, treatment and prevention of typhoid fever.  2003.

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Footnote 39

World Health Organization. Typhoid vaccines: WHO position paper. Wkly Epidemiol Rec 2008;6(83):49-60.

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Footnote 40

Schunemann HJ, Brozek J, Oxman AD, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Version 3.2 [updated March 2009]. 2009. The GRADE Working Group.

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Footnote 41

Andrews J, Guyatt G, Oxman AD, Alderson P, Dahm P, Falck-Ytter Y, et al. GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol 2013 Jul;66(7):719-25.

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Footnote 42

Andrews JC, Schunemann HJ, Oxman AD, Pottie K, Meerpohl JJ, Coello PA, et al. GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation's direction and strength. J Clin Epidemiol 2013 Jul;66(7):726-35.

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CATMAT acknowledges and appreciates the contribution of Dr. Gordon Guyatt, Distinguished Professor of Medicine, McMaster University, GRADE methodological support.

CATMAT Members: Dr. A. McCarthy (Chair), Dr. A. Boggild, Dr. J Brophy, Dr. Y. Bui, Dr. M. Crockett, Dr. W. Ghesquiere, Dr. C. Greenaway, Ms A. Henteleff, Dr. M. Libman, Dr. P. Teitelbaum.

Liaison members: Dr. C. Hui (Canadian Paediatric Society), Dr. G. Brunette (US Centers for Disease Control and Prevention).

Ex-officio members: Dr. P. MacDonald (Division of Anti-Infective Drugs, Health Canada), Dr. M. Tepper (Directorate of Force Health Protection, Department of National Defence), Dr. P. Charlebois (Canadian Forces Health Services Centre, Department of National Defence), Dr. S. Schofield (Directorate of Force Health Protection, Department of National Defence).

Member Emeritus: Dr. C.W.L. Jeanes.

Conflict of interest

There are no conflicts of interest to declare.


This work was supported by the Public Health Agency of Canada.


Table 3: Recommendation categories
Strongtable 3 Footnote *-recommendation for The committee believes that all or almost all well informed people would want the recommended course of action and only a small number would not.
Implication for practitioners: The balance of risks and benefits are such that most travellers would choose the intervention.
Strong-recommendation against The committee believes that all or almost all well informed people would not want the recommended course of action and only a small number would.
Implication for practitioners: The balance of risks and benefits are such that most travellers would not choose the intervention.
Conditionaltable 3 Footnote ** recommendation for The committee believes that the majority of well-informed people would want the recommended course of action, but a minority (perhaps a large minority) would not.
Implication for practitioners: With a conditional recommendation different travellers may make different choices. Practitioners should present the risks and benefits of the intervention and help each traveller make a decision consistent with his/her values and preferences. 
Conditional recommendation against The committee believes that the majority of well-informed people would not want the recommended course of action, but a minority (perhaps a large minority) would.
Implication for practitioners: With a conditional recommendation different travellers may make different choices. Practitioners should present the risks and benefits of the intervention and help each traveller make a decision consistent with his/her values and preferences.

Adapted from the GRADE handbook for grading quality of evidence and strength of recommendations and GRADE guidelines 14 and 15Footnote 40Footnote 41Footnote 42.

table 3 Footnote *

The GRADE working group suggests that if a recommendation is "strong", then it is expected that 90% or more of informed individuals would choose (or not choose) the recommended course of action.

Return to table 3 footnote * referrer

table 3 Footnote **

The GRADE working group suggests that if a recommendation is "conditional", then it is expected that less than 90% of informed individuals would choose (or not choose) the recommended course of action.

Return to table 3 footnote ** referrer

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