Typhoid is a potentially life-threatening infection caused by exposure to the bacterium Salmonella Typhi. It is usually spread via contaminated food or water. Once Salmonella Typhi bacteria are ingested, they infiltrate intestinal mucosa, multiply and spread into the bloodstream (UK Health Security Agency (UKHSA), 2020; World Health Organization (WHO), 2023).
Paratyphoid fever is a clinically similar illness caused by Salmonella Typhi A, B and C (UKHSA, 2020). These bacteria only occur in humans (UKHSA, 2023; US Centers for Disease Control (CDC), 2023) and no animal or environmental reservoirs have been identified (US CDC, 2023).
Transmission
Typhoid is almost exclusively transmitted by eating or drinking food and water contaminated with human faeces and urine from infected people or carriers. In addition, shellfish taken from sewage-contaminated water, vegetables fertilised with night-soil (human waste) eaten raw, and contaminated milk and dairy products have been shown to be sources of infection (WHO, 2023). Salmonella Typhi or Salmonella Paratyphi bacteria can enter the food chain and water supply if personal hygiene and general sanitation is poor (NaTHNaC, 2022).
Exposure to food or water that has been heavily contaminated (10 or more organisms) is usually needed to cause illness (UKHSA, 2023). People can transmit typhoid as long as the bacteria remains in their body. Most people are infectious prior to and during the first week of convalescence, but 10% of untreated patients will discharge bacteria for up to 3 months (WHO, 2023). Sexual contact, particularly among men who have sex with men, has been documented as a rare route of transmission (US CDC, 2023).
Symptoms
Symptoms usually develop 1–3 weeks after exposure, and may be mild or severe. They include high fever, malaise, headache, constipation or diarrhoea, rose-coloured spots on the chest, and an enlarged spleen and liver (WHO, 2023). Severe disseminated disease with multi-organ involvement occurs in 10–15% of cases. Case fatality rate is less than 1% with prompt antibiotic therapy, but may be as high as 20% in untreated cases, or if inappropriate antibiotics are prescribed (UKHSA, 2020).
Epidemiology
Risk of typhoid exposure is higher in countries that lack access to safe water and adequate sanitation, with children at greatest risk. The WHO estimates that, as of 2019, there are 9 million cases of typhoid fever annually worldwide, causing approximately 110 000 deaths every year. Improved living conditions and antibiotics have resulted in a drastic reduction of typhoid fever illness (morbidity) and deaths (mortality) in industrialised countries such as the UK. However, typhoid remains a public health problem in many developing areas of Africa, the eastern Mediterranean, south-east Asia and the Western Pacific (WHO, 2023).
Typhoid is rare in resource-rich countries with high standards of sanitation. Cases of typhoid and paratyphoid disease reported in England, Wales and Northern Ireland are usually imported due to foreign travel or contact with somebody who has travelled (UKHSA, 2020).
Antibiotic-resistant typhoid strains have developed since 1987 in endemic regions such as China, south-east Asia and the Indian sub-continent. Drug-resistant typhoid has been seen in the UK in returned travellers, and an extensively drug-resistant typhoid strain has been reported in Pakistan (NaTHNaC, 2022).
In the US, cases of extensively drug-resistant typhoid associated with travel to Pakistan were diagnosed in 2018. By 2021, over 70 extensively drug-resistant typhoid infections had been reported in US residents, including nine cases in people who had not travelled abroad in the 30 days before their illness began. Ceftriaxone resistance has also been identified in Typhi isolates from Americans returning from Iraq. Additionally, resistance to azithromycin has been identified among Typhi and Paratyphi strains isolated from patients in Bangladesh, Cambodia, India, Nepal, Pakistan, Saudi Arabia and the US (US CDC, 2023).
Typhoid risk for UK travellers
Typhoid is not now considered a significant risk in the UK, although in the past there were outbreaks. The last UK outbreak was reported in Aberdeen in 1964 and was linked to contaminated meat imported from South America (BBC Scotland, 2014). The UKHSA (formerly Public Health England) advises that the risk of contracting typhoid fever is highest for UK travellers visiting areas of high endemicity, such as the Indian subcontinent (UKHSA, 2020).
In 2021, most of the confirmed typhoid cases (where travel history was known) in England, Northern Ireland and Wales were reported in people who travelled to countries in Southern Asia to visit friends or relatives in Bangladesh, India or Pakistan (UKHSA, 2023). This is consistent with previous reports of typhoid cases in returning UK-based travellers (UKHSA, 2017).
Other European countries also report typhoid cases in returning travellers. Like the UK, typhoid and paratyphoid fevers are relatively rare in EU/European Economic Area (EEA) countries and are mainly acquired during travel to countries outside the EU/EEA, particularly South Asia. In 2018 (latest available data), a total of 1118 confirmed typhoid and paratyphoid cases were reported from 29 EU/EEA countries and the UK (in 2018 the UK still reported heath data to ECDC). The EU/EEA notification rate was 0.29 confirmed cases of typhoid and paratyphoid fever per 100 000 population. Highest notification rates were reported in France, the UK and Norway. Of the 833 cases with available information, 90.8% were travel related (ECDC, 2023).
Accessing information about typhoid, risk countries and current UK typhoid vaccine recommendations
Travel health practitioners must maintain their skills and knowledge in order to deliver a safe and effective service (Faculty of Travel Medicine of the Royal College of Physicians and Surgeons of Glasgow, 2020). One of the aims of this article is to direct UK travel health professionals involved in prescribing travel vaccines to appropriate, evidence-based national guidance. The rationale behind this is that typhoid risks and recommendations can change (sometimes rapidly) in response to outbreaks or changes in epidemiology. Also, vaccine products may be withdrawn or new vaccines introduced. Prescribers must ensure they are familiar with non-commercial, NHS-funded UK resources such as TRAVAX and the National Travel Health Network and Centre (NaTHNaC).
NaTHNaC's TravelHealthPro website country information pages provide destination-specific travel health advice. All typhoid vaccine advice and country recommendations are consistent with current UKHSA/guidance: https://travelhealthpro.org.uk/countries. TRAVAX is an interactive NHS website providing up-to-date travel health information. It is maintained and updated by the Travel and International Health Team of Public Health Scotland. Details of how to register are available here: https://www.travax.nhs.uk/about-travax.
Pre-travel typhoid risk assessment
Use of a pre-travel tool, such as a checklist as part of the risk assessment process, facilitates information gathering and helps to ensure that the traveller offers a comprehensive medical history. NaTHNaC provides a downloadable travel risk assessment form: https://travelhealthpro.org.uk/factsheet/61/risk-assessment--risk-management-checklist.
Travellers at greatest risk of typhoid exposure and infection
- Those visiting low- and middle-income countries where typhoid and paratyphoid fever are endemic, including regions in Africa, Latin America and Asia (greatest risk for infection is South Asia)
- Travellers visiting friends and relatives in endemic countries
- Travellers attending mass gatherings in endemic regions (US CDC, 2023).
Recommendations for typhoid vaccine
Recommendations should consider:
- Typhoid risk at destination
- Reason for travel and length of trip
- Medical history – are they immunosuppressed?
- Pregnancy
- Age of traveller.
No travel health consultation should take place in isolation without consideration of other travel-related risks and documenting information. Travellers must be given a clear written record of any vaccines given and advised to inform their GP surgery (Royal College of Nursing (RCN), 2023).
Non-medical prescribers
In the UK, doctors remain the largest group of prescribers. However, the medical profession has been joined by non-medical independent and supplementary prescribers from a range of other health professions, including nurses and pharmacists. A nurse or pharmacist independent/supplementary prescriber can prescribe all travel vaccines, as long as travel medicine care is within their scope of practice (RCN, 2023).
Non-medical health professionals can only prescribe within their scope of practice after they have completed an approved education programme. Such prescribers must take responsibility for practising within their own scope of practice and competence, including delegating when appropriate, seeking support if required and using their acquired knowledge, skills and professional judgement appropriately (Royal Pharmaceutical Society (RPS), 2021). This extension of prescribing responsibilities to other professional groups outside the medical profession is likely to continue in circumstances where it is safe to do so and there is a clear patient benefit (RCN, 2023).
Pharmacists
The RPS provides specific guidance for UK pharmacist prescribers: https://www.rpharms.com/resources/pharmacy-guides/pharmacist-prescribers-guide.
Box 1.Resources
- NaTHNaC Topic in brief, typhoid fever: https://travelhealthpro.org.uk/disease/184/typhoid-fever
- Travelling to visit friends and relatives: https://travelhealthpro.org.uk/factsheet/91/travelling-to-visit-friends-and-relatives
- NHS Typhoid fever: https://www.nhs.uk/conditions/typhoid-fever/
- Nursing and Midwifery Council Useful information for prescribers: https://www.nmc.org.uk/standards/standards-for-post-registration/standards-for-prescribers/useful-information-for-prescribers/
- RPS Pharmacist Independent Prescribers: https://www.rpharms.com/recognition/all-our-campaigns/policy-a-z/pharmacist-independent-prescribers
- UK Health Security Agency Typhoid: health advice for travellers. Advice on typhoid and paratyphoid (enteric fever) for health professionals to give to travellers, available in Bengali, Gujarati, Punjabi, Urdu and English: https://www.gov.uk/government/publications/typhoid-health-advice-for-travellers
- Travelling abroad to visit friends and relatives, advice for travellers: https://www.youtube.com/watch?v=bLRVao3-sRI
Nurses
Nurse prescribing can improve care as it helps to ensure timely access to medicines and increases flexibility for those who would otherwise need to wait to see a doctor (RCN, 2014). This is particularly relevant for last-minute travellers who may not be able to access GP services before travel. In order to prescribe medicines, including vaccines, nurses must have recorded their prescriber qualification on the Nursing and Midwifery Council (NMC) register (NMC, 2023).
Vi polysaccharide vaccine (Typhim Vi)
One of the typhoid vaccines available in the UK is an inactivated injection composed of purified Vi capsular polysaccharide from S. typhi. Each 0.5 ml dose contains 25 μg of antigen. A four-fold rise in antibody against Vi antigen has been detected 7 days following primary immunisation with Vi vaccine. Maximum antibody response is achieved one month following vaccination and persists for about 3 years (UKHSA, 2020).
Babies and young children are at increased risk of deteriorating quickly if they become ill during travel. Therefore, while young children may show a sub-optimal response to polysaccharide antigen vaccines such as Typhim Vi, it is appropriate to offer this vaccine from the age of 12 months if they are at risk. When children are too young to benefit fully from typhoid vaccination, parents or guardians must be advised that scrupulous attention to personal, food and water hygiene measures is crucial during travel (UKSHA, 2020).
Specific guidance on the contraindications and precautions associated with Typhim Vi is available from the manufacturer's summary of product characteristics: https://www.medicines.org.uk/emc/product/1393/smpc.
Oral typhoid vaccine (Ty21a) (Vivotif)
This oral typhoid vaccine contains a live, attenuated strain of S. typhi (Ty21a) in an enteric coated capsule. It is contraindicated in immunosuppression and pregnancy. Large scale field trials in Chile and Indonesia estimated a vaccine effectiveness of 33–67% for the three-dose course after 3 years (UKHSA, 2020).
Specific guidance on the contraindications and precautions associated with Vivotif typhoid vaccine can be found in the manufacturer's summary of product characteristics: https://www.medicines.org.uk/emc/medicine/30294.
Contraindications
Typhoid Vi vaccine should not be given to people who have had:
- A confirmed anaphylactic reaction to a Vi-antigen-containing vaccine
- Severe reactions to a previous dose of non-Vi typhoid vaccine do not contraindicate the subsequent use of a Vi vaccine.
Ty21a vaccine should not be given to those who:
- Are immunosuppressed
- Have had a confirmed anaphylactic reaction to any component of the Ty21a vaccine or enteric-coated capsule, including gelatine (National Institute for Health and Care Excellence (NICE), 2023).
Pregnancy
The effect of gastrointestinal illness in pregnancy can be significant for both mother and foetus. Careful food, water and personal hygiene should be emphasised. Inactivated (non-live vaccines) are not contraindicated in pregnancy and certain inactivated vaccines, such as pertussis (whooping cough) vaccine are offered routinely to pregnant women the UK (NaTHNaC, 2023). If, after a careful risk assessment, the pregnant traveller's risk of typhoid fever is considered high, an inactivated typhoid vaccine such as Typhim Vi can be offered.
Travel consultations must also allow consideration of other destination specific hazards (Faculty of Travel Medicine of the Royal College of Physicians and Surgeons of Glasgow, 2020). As well as typhoid there could be other infectious communicable diseases and insect-spread illnesses like malaria or Zika at her destination, and she is likely to need other travel-related vaccines and risk reduction advice.
People visiting friends and family
The UKHSA provides specific free information and advice for travellers visiting friends and relatives in a variety of languages including English, Arabic, Bengali, French, Gujarati, Hausa, Igbo, Punjabi, Spanish, Swahili, Yoruba, Urdu, Xhosa and in British Sign Language, large print, braille and Easy Read: https://www.gov.uk/government/publications/travelling-overseas-to-visit-friends-and-relatives-health-advice/visiting-friends-and-relatives-abroad-advice-for-travellers.
Conclusion
While the focus of this article is on prescribing typhoid vaccines, it should be emphasised that vaccination is only one aspect of pre-travel advice. Protection from typhoid vaccines may be less if a large number of infective organisms are ingested (UKHSA, 2020). Travellers must be informed that due to limited protection offered by the vaccine and increasing prevalence of antibiotic-resistant typhoid worldwide, vaccination is just one component in an overall typhoid prevention strategy. As well appropriate typhoid vaccine prescribing, a focus on good food, water and personal hygiene measures must be emphasised to all travellers to typhoid endemic regions.
Key Points
- Prescribers have a duty of care to ensure appropriate vaccine is offered to travellers at risk of typhoid
- Pre-typhoid vaccine risk assessment must consider the traveller's medical history and planned destination
- Travellers need to provide a full medical history, including all medication and information about their reason for travel and planned destination
- Live typhoid vaccine is contraindicated in immunosuppression and pregnancy
- Health professionals must keep updated with changes in typhoid vaccine recommendations and country specific advice using the appropriate resources
CPD reflective questions
- Arkanj, 35, is going to visit family in Goa for 2 weeks. He has never been to India before, but his parents are originally from Goa and he will be meeting a lot of his extended family for the first time. He has a long history of ulcerative colitis, which is well controlled on oral azathioprine. What type of typhoid vaccine would you prescribe for him? What concerns might you have about his travel plans generally?
- Ronan, 23, is going on a stag weekend to Dubai and is asking for a typhoid vaccine – he says all his friends have had it. What would you advise him about his risk of typhoid? Would you prescribe him a typhoid vaccine?
- Kay is 78 and will be spending the winter with her sister in Delhi. She is diabetic and has poorly controlled hypertension. She does not think she needs a typhoid vaccine as she grew up in India. What would you advise her?
- Emily, 18, is fit and well. She is planning a gap year before she goes to university and will be backpacking around South America. Her mum says that when she had her baby vaccines she had a reaction. She has not had any other vaccine since. What information would you need before assessing her before prescribing a typhoid vaccine? Given her travel plans, what other concerns might you have about her vaccine history?
- Lee, 56, has raised cholesterol and hypertension, but is otherwise well. He is a buyer for a large UK clothing retailer and travels to Bangladesh frequently for work. He has declined a typhoid vaccine. He feels he is not at risk as he only goes for short business trips and stays in ‘top-quality’ hotels. How would you encourage him to consider having a typhoid vaccine before his next trip?
- Nelle, 27, is a midwife and she has taken a career break to volunteer with VSO in Zimbabwe. She has family in Harare that she will visit, but she will be living in a remote rural area. Apart from offering vaccination, how would you advise her to protect herself against typhoid?
- Ayesha's father is seriously ill in Karachi, Pakistan and she is flying out as soon as she can. She is 33 years old and is fit and well, but she is 4 months pregnant with her third child. She is also taking her 14-month-old son Asad with her. She thinks she had a typhoid vaccine 2.5 years ago when she last visited Pakistan, but has no records. Would you be happy to prescribe a typhoid vaccine for her? What about Asad? What advice would you give her about travelling in pregnancy with a small child? What advice and information could you share with travellers about how to protect themselves and their families against typhoid?