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Typhoid and paratyphoid

Introduction

Epidemiology

Risk for travellers

Transmission

Signs and symptoms

Treatment

Prevention

Vaccine information

References

Further reading

 

Introduction

Typhoid fever is a systemic disease contracted by ingestion of contaminated food or water.  It is caused by the bacterium Salmonella enterica serovar Typhi, which is a pathogen only of humans. The illness may be mild or severe.

Paratyphoid is a clinically similar illness (though often less severe), caused by Salmonella enterica serovar Paratyphi A, B or C.

These conditions are sometimes referred to collectively as enteric fever.

 

Epidemiology

Global epidemiology

Typhoid and paratyphoid mainly affect low income regions of the world, where sanitation and clean water are lacking. The World Health Organization (WHO) conservatively estimates that 21 million cases of typhoid fever occur each year with a case fatality of 1-4% [1]. In endemic countries, most cases occur in school age children. In 2000, the global incidence of paratyphoid was estimated to be 5.4 million cases [2].

The majority of typhoid occurs in Asia; however, typhoid continues to be a public health concern in many other low income countries including in Africa and parts of South America [1, 3]. Although rare, outbreaks have also been reported in European countries including Italy, Tajikistan, Turkey, Russia and the Ukraine [4-7].

Large outbreaks are less common, but have occurred in Democratic Republic of Congo in 2005 (42 564 cases and 214 deaths) [8] and, more recently, in Zimbabwe in 2011 [9].

 

Typhoid and paratyphoid in travellers from England, Wales, and Northern Ireland

In the UK, typhoid and paratyphoid usually occur in travellers who have visited or have arrived from endemic areas. Occasionally cases occur following transmission from a returned traveller/new entrant/foreign visitor (usually within family or household settings), or more rarely, from chronic carriers.

The Travel and Migrant Health Section at the Health Protection Agency (HPA) has been conducting national enhanced surveillance of enteric fevers since May 2006 [10]. Between 2007 and 2011, approximately 500 cases of enteric fever have been reported in England, Wales and Northern Ireland each year [Figure 1], just over half of these were caused by S. Typhi.

 

Figure 1 Laboratory-confirmed cases of enteric fever in England, Wales and Northern Ireland: 2007-2011

 

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Between 2007 and 2011, enhanced surveillance questionnaires were received for 86% (2124/2470) of cases; however travel history for those with no enhanced surveillance form is supplemented with information from laboratory reports if available.

Where travel history was known (N=2343), 2184 (93%) stated they had been abroad before their illness; 80% (1749/2184) were UK residents who had travelled abroad from the UK as opposed to new entrants (136/2184, 6%) or foreign visitors (81/2184, 4%) to the UK. Of cases that travelled abroad from the UK, 83% (1458/1749) were visiting friends and relatives [Figure 2].

 

Figure 2 Laboratory-confirmed cases of enteric fever in England, Wales and Northern Ireland by reason for travel: 2007-2011 (N=1749)

*Five VFR cases had also travelled for holiday; one VFR case had also travelled for business.

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Country of travel was available for 99% individual cases (1741/1749) that had travelled abroad from the UK; the majority of countries of travel reported were in the Indian subcontinent [Table 1].

 

Table 1 Laboratory-confirmed cases of enteric fever in England, Wales and Northern Ireland by region for travel: 2007-2011 (cases that had travelled abroad from the UK only)

World region of travel

Cases

Indian sub continent

1607

Sub-Saharan and southern Africa

58

South east Asia and far east

51

North Africa and the Middle East

46

South America

43

Europe

30

Not stated

8

Central America

3

Pacific

2

Caribbean

1

North America
1

Total

1850

 

Note that the total in the table is higher than the number of cases as some cases travelled to more than country. Further information about enteric fever in the UK is available from the HPA enteric fever and Migrant Health reports [10-12].

Typhoid and paratyphoid fever in the UK are notifiable infections [13].

 

Risk for travellers

In endemic countries, risk-factors for contracting enteric fever include eating or drinking contaminated food or water, inadequate sanitation and sub-standard living conditions, poor personal hygiene, and close contact with those infected with S. Typhi or Paratyphi.  

The risk of contracting typhoid fever is variable and depends on the country visited, but is highest (17.3 cases per 100,000 travellers) for travellers to the Indian sub-continent (Bangladesh, India and Pakistan) [14]. The risk of acquiring typhoid and paratyphoid fever in high income countries is considered to be low [15].

 

Transmission

Transmission occurs following the ingestion of food or water that has been heavily contaminated (105 or more organisms may be required to cause illness) by the bacterium S. Typhi (typhoid) or S. Paratyphi (paratyphoid). S. Typhi can be passed in the faeces of persons who are acutely ill with typhoid fever or are chronic carriers. The bacteria can then enter the food chain and water supply if sanitation is inadequate. Direct faecal-oral transmission also occurs. 

Ingestion of vegetables fertilized with human waste (night soil) and eaten raw, shellfish harvested from sewage-contaminated beds, and contaminated milk products can result in typhoid infection [16].

 

Signs and symptoms

Typhoid

Typhoid is a systemic disease that varies in severity, but nearly all patients experience fever and headache. Young children may experience a mild illness, but they can also suffer from severe disease. 

The incubation period for typhoid fever is usually 7-14 days, but can be shorter or longer depending upon how many bacteria are ingested. Symptoms include low-grade fever (which typically becomes higher as the illness progresses), chills, headache, myalgia, malaise, anorexia and nausea. There can be abdominal discomfort and constipation, and diarrhoea can occur early in the course. Moderate enlargement of the liver and/or spleen occurs in about 50% of cases. In some cases, a macular rash (rose spots) consisting of pink lesions which fade on pressure under a glass, will appear on the trunk. The rash may be difficult to see in dark-skinned individuals. 

Complications occur in 10-15% of all cases and are more likely in untreated cases or cases that present late in the course of the illness. Complications include intestinal haemorrhage and perforation, toxic myocarditis, pneumonia, seizures, typhoid encephalopathy, and meningitis (usually in young children).

The case fatality is usually less than 1% with prompt antibiotic therapy, but may be as high as 20% in untreated cases.

Following recovery, convalescing patients may continue to excrete S. Typhi in their faeces.  Between 1-3% will become long-term carriers, continuing to excrete the organism for more than one year after the initial illness [17]. The carrier state is more common in women and those with billiary tract abnormality [16, 17]. Chronic carriers require prolonged courses of antibiotics to clear the organism.

 

Paratyphoid fever

Paratyphoid is clinically similar, but the disease may be more mild and of shorter duration [17].

 

Treatment

From its introduction in 1948, chloramphenicol was the drug of choice to treat typhoid [18], but in the early 1970s, chloramphenicol-resistant strains of S. Typhi began to emerge. Large outbreaks of resistant S. Typhi occurred in Mexico and India, and resistant S. Typhi became endemic in many countries of south and South East Asia [19]. Other antibiotics such as ampicillin and co-trimoxazole have been used to treat typhoid, but resistance to multiple antibiotics has developed since 1987 in endemic regions such as China, South East Asia and the Indian sub-continent [19]. In 1997, a large outbreak of multi-drug resistant typhoid was reported in Dushanbe, Tajikistan involving 8,901 cases and 95 deaths [20].

Drug-resistant strains have been seen in the UK in returned travellers [21]. Of 692 samples taken from cases of typhoid fever imported into the UK between 2000 and 2003, 22% were multi-drug resistant and 39% were resistant to fluoroquinolone antibiotics (e.g. ciprofloxacin) [22]. During  enhanced surveillance for enteric fever, more than two thirds of all cases had isolates of S. Typhi or S. Paratyphi A that were less susceptible to ciprofloxacin, representing an increase since 2001 [23].

Typhoid can be successfully treated with appropriate antibiotics. Treatment is usually with fluoroquinolones, cephalosporins [24], or azithromycin in cases that are resistant to fluoroquinolones [25].

Relapse will occur in less than 10% of patients treated with antibiotics. Relapse illness is usually milder and of shorter duration than the original illness. Those successfully treated with fluoroquinolones are less likely to suffer relapse or become chronic carriers.

 

Prevention

All travellers should practise food and water hygiene precautions.

Typhoid

Vaccination is recommended for travellers whose planned activities put them at higher risk for typhoid in areas where sanitation and food hygiene are likely to be poor.  

Paratyphoid

There is currently no vaccine available against paratyphoid. 

A typhoid leaflet giving advice about prevention is available for patients in English and four south Asian languages: Guajarati, Bengali, Urdu and Punjabi [27].

 

Vaccine Information

Indications for use of vaccine

Typhoid vaccine is recommended for:

  • Travellers visiting typhoid-endemic areas whose planned activities put them at higher risk including travellers visiting friends and relatives, young children, long-term travellers, and those exposed to conditions of poor sanitation
  • Laboratory personnel who may handle S. Typhi in the course of their work

Vaccine recommendations for specific countries can be found on the NaTHNaC Country Information Pages: http://www.nathnac.org/ds/map_world.aspx   

Typhoid vaccine is not recommended for those identified as close contacts of known cases or those who are typhoid carriers [26].

Availability of vaccine

Availability of typhoid vaccines is subject to change. See NaTHNaC Clinical Updates for current information.

 

Vaccine

Manufacturer/

distributor

Schedule Length of protection Age range
Typhim Vi* Sanofi Pasteur MSD Single dose 3 years Adults & children from 2 years of age
Typherix GlaxoSmithKline UK Single dose 3 years Adults & children from 2 years of age
Vivotif**

Janssen/MASTA

3 capsules

1st on day 1, 2nd day 3, 3rd day 5

An optimal immune response may not be achieved unless the immunisation

schedule of three vaccine capsules is completed. Protection commences about

seven to ten days after completion of the third dose [26, 30]

 

3 years Adults and children from 6 years of age
Viatim (combined hepatitis A and typhoid vaccine*) Sanofi Pasteur MSD Single dose of combined vaccine Typhoid

3 years

Hepatitis A

1 year Booster dose of inactivated hepatitis A vaccine at 6-12 months after first dose

Adults from 16 years of age
Hepatyrix* GlaxoSmithKline Single dose of combined vaccine

Typhoid
3 years

 

Hepatitis A
1 year
Booster dose of inactivated hepatitis A vaccine at 6-12 months after first dose

From 15 years of age

*A single dose of Vi vaccine should be administered at three-year intervals in adults and children over two years of age who remain at risk from typhoid fever [26].

 

** In the case of travel from a non-endemic area to an area where typhoid is endemic, a booster consisting of three doses is recommended every three years [26].

 

Contraindications

  • Hypersensitivity to any constituent of vaccine (both of the combined Hepatitis A/Typhoid contain traces of neomycin)
  •  Individuals who develop symptoms of hypersensitivity after vaccination should not receive further doses
  • Specific contraindications for Vivotif: congenital or acquired immune deficiency, including patients receiving immunosuppressive or antimitotic drugs
  • Acute febrile illness or during an acute gastrointestinal illness
  • Persons known to be hypersensitive to any component of the vaccine or the enteric-coated capsule

The Summary of Product Characteristics (SmPC) for the individual vaccine should be consulted for specific information relating to the product [28-30].

 

References

1. World Health Organization. Typhoid: WHO Position Paper. 83 (6):49-59. Geneva: WHO; 2008. [Accessed 20 September 2012]. Available at: http://www.who.int/wer/2008/wer8306.pdf

2. Crump JA, Luby SP, Mintz ED. The global burden of typhoid fever. Bull World Health Org 2004; 82:346-53.

3. World Health Organization. Initiative for Vaccine Research. Diarrhoeal Diseases (2009). [Accessed 20 September 2012]. Available at: http://www.who.int/vaccine_research/diseases/diarrhoeal/en/

index7.html#disease burden

4. International Society for Infectious Diseases (ISID). ProMED-mail [online]. Boston: ISID; 2001. Available online at www.promedmail.org.

5. Aypak A, Celik AK, Aypak C et al. Multidrug resistant typhoid fever outbreak in Ercek Village-Van, Eastern Anatolia, Turkey: clinical profile, sensitivity patterns and response to antimicrobials. Trop Doct. 2010 Jul;40(3):160-2.

6. Rizzo C, Santantonio M, Coscia MF et al. Typhoid Fever in Italy, 2000-2006. J Infect Dev Ctries. 2008 Dec 1;2 (6):466-8.

7. World Health Organization. 1996 Typhoid Fever in Tajikistan – Update (Disease Outbreak News) [Accessed 20 September 2012]. Geneva. WHO; 2006. Available at: http://www.who.int/csr/don/1996_08_06a/en/index.html 

8. World Health Organization. Global Alert Response. Typhoid in Democratic Republic of Congo. [Accessed 20 September 2012].Available at: http://www.who.int/csr/don/2004_12_15/en/

9.  World Health Organization. Zimbabwe Weekly Epidemiological Bulletin 2011 Number 146. [Accessed 20 September 2012]. Available at: http://reliefweb.int/sites/reliefweb.int/files/resources/

Full_Report_4165.pdf

10. Health Protection Agency. Enhance surveillance of enteric fever. [Accessed 20 September 2012].Available at: http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/

TravelHealth/GeneralInformation/trav30

Enhancedsurveillanceofentericfever/

11. Health Protection Agency. Enteric Fever. [Accessed 20 September 2012].Available at: http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/

TravelHealth/EpidemiologicalData/GastrointestinalInfections/

travEntericfever/

12. Health Protection Agency. Migrant Health: Infectious diseases in non-UK born populations in the UK. [Accessed 20 September 2012].Available at: http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/

HPAweb_C/1317131996733

13.  Health Protection Agency. Notifications of Infectious Diseases. [Accessed 20 September 2012]. Available at: http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/

NotificationsOfInfectiousDiseases/

14. Connor BA, Schwartz E. Typhoid and paratyphoid fever in travellers. Lancet 2005;5:623-28.

15. World Health Organization. Diarrhoeal diseases. Updated February, 2009. Available at: http://www.who.int/vaccine_research/diseases/diarrhoeal/

en/index7.html

16. Heyman D. Control of Communicable Diseases Manual. 18th Edn. Washington DC. American Public Health Association; 2004.

17. Gillespie S. Salmonella infections. In Manson’s Tropical Diseases. Eds. Cook G, Zumla A. Edinburgh. Saunders; 2003.

18. Woodward TE, Smadel JE, Ley HL, Green R, Maniker DS. Preliminary report on the beneficial effect of chloromycetin on the treatment of typhoid fever. Ann Intern Med 1948;29:131-3.

19. Mirza SH, Beeching NJ, Hart CA. Multi-drug resistant typhoid: a global problem. J Med Microbiol 1996;44:317-9.

20. Mermin JH, Villar R, Carpenter J et al. A massive epidemic of multi-drug resistant typhoid fever in Tajikstan associated with consumption of municipal water. J Inf Dis 1999;179:1416-22.

21. Threlfall EJ, Rowe B, Ward LR. Occurrence and treatment of multi-resistant Salmonella typhi in the UK. PHLS Microbiology Digest 1991;8:56-9.21.

22. Cooke FJ, Day M, Wain J, Ward LR, Threlfall EJ. Cases of typhoid fever imported into England, Scotland and Wales (2000 - 2003). Trans R Soc Trop Med Hyg. 2007April; 10(4):398-404

23.Health Protection Agency. Pilot of enhanced surveillance of enteric fever in England, Wales, and Northern Ireland, 1 May 2006 to 30 April 2007. London, 2008. [Accessed 20 September 2012]. Available at: http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/

1206575041711

24. Effa EE, Lassi ZS, Critchley JA et al. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database Syst Rev. 2011 Oct 5;(10):CD004530.

25. Parry CM, Threlfall EJ. Antimicrobial resistance in typhoidal and nontyphoidal salmonellae. Curr Opin Infect Dis. 2008 Oct;21(5):531-8. [Accessed 20 September 2012]. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18725804

26. Department of Health. Typhoid. Chapter 33: Immunisation against infectious disease. [Accessed 4 November 2014]. Available at: http://immunisation.dh.gov.uk/green-book-chapters/chapter-33/

27. Health Protection Agency. Typhoid- health advice for travellers

[Accessed 20 September 2012]. Available at: http://www.hpa.org.uk/Publications/InfectiousDiseases/

Factsheets/factTyphoid/

28. Summary of Product Characteristics. Typherix. GlaxoSmithKline UK. Available at  http://www.medicines.org.uk/searchresult.aspx?search=typherix

29. Summary of Product Characteristics. Typhim Vi. Sanofi Pasteur MSD. Available at http://www.medicines.org.uk/

30. Summary of Product Characteristics. Vivotif. Janssen-Cilag/MASTA. [Accessed 4 November 2014]. Available at https://www.medicines.org.uk/emc/medicine/26276

 

Further reading

World Health Organization. Water-related diseases: typhoid and paratyphoid enteric fevers. Available at http://www.who.int/water_sanitation_health/diseases/typhoid/

en/

S. Balasegaram, A.L. Potter, D. Grynszpan et al. Guidelines for the public health management of typhoid and paratyphoid in England. Practice guidelines from the National Typhoid and Paratyphoid Reference Group. Journal of Infection 2012; 65, 197-213.

 

Advice current at: November 2014