Guidance

Public health operational guidelines for typhoid and paratyphoid (enteric fever)

Updated 3 January 2024

Applies to England

Who this guidance is for

This guidance is to support public health practitioners in England in identifying the sources of typhoid or paratyphoid infection (also known as enteric fever) and reduce the risks of secondary transmission. This guidance provides a framework for health protection teams (HPTs) and environmental health officers or local authorities to help them to respond to laboratory reports and/or clinical notifications of typhoid and paratyphoid infection. Outbreaks should be managed in accordance with agreed national and local outbreak plans and memorandums of understanding. The UK Health Security Agency (UKHSA) national outbreak plan can be found online. Advice on clinical management and treatment is outside the scope of this guidance.

Typhoid and paratyphoid infection is notifiable by Registered Medical Practitioners and laboratories under the Health Protection (Notification) Regulations 2010.

This revised guidance is based on the available evidence for transmission and control of typhoid and paratyphoid and supersedes the 2017 guidance.

Key updates

For cases with a positive clearance sample after one course of antibiotics, it is recommended that a subsequent clearance sample should be taken one week after the positive result. If subsequent sample is positive, then further sampling should be delayed at least by a week.

If samples are persistently positive (for example, after one month from first clearance sample), ensure household contacts have been screened and results are negative prior to further sampling of the case.

For non-travel related cases, all household and close contacts should be screened where an obvious source of illness cannot be identified.

If the case is without recent travel history and has possible carrier status, consider taking a follow up sample (at least 6 weeks after the first antibiotic course) to assess carrier status, even if the case is not in a risk group. No exclusion is required for these cases unless they are symptomatic.

Changes to enhanced surveillance questionnaire (ESQ):

• HPTs are requested to record co-traveller status and risk group of cases and contacts in the ESQ
• more detailed questions on specific travel history and information about pre-travel health advice

Definitions for the public health management of typhoid and paratyphoid

Typhoid and paratyphoid case definitions

Possible case

A possible case is defined as an individual who either:

• has a clinical history compatible with typhoid/paratyphoid and where the clinician suspects typhoid/paratyphoid is the most likely diagnosis
• has a clinical history of fever and malaise and/or gastrointestinal symptoms compatible with typhoid/paratyphoid and an epidemiological link such as contact with a case or a source of typhoid/paratyphoid, for example, from ‘warn and inform’ information
• is a returning traveller reporting a diagnosis made abroad with salmonella PCR from faeces but no documented evidence of a positive blood or faecal culture for typhoid or paratyphoid

Probable case

A probable case is defined as an individual who either:

• has a local laboratory presumptive (locally confirmed) identification of Salmonella Typhi (S. Typhi) or S. Paratyphi on faecal and/or blood culture, or culture of another sterile site (for example, urine), with or without clinical history compatible with typhoid/paratyphoid
• is a returning traveller giving a clinical history compatible with typhoid/paratyphoid and documentation of a positive blood/faecal culture (or positive PCR for S. Typhi / S. Paratyphi on blood)

Confirmed case

A confirmed case is defined as an individual with S. Typhi or S. Paratyphi infection confirmed by the UKHSA Gastrointestinal Bacteria Reference Unit (GBRU) Salmonella Reference Service (SRS).

Travel-related case

A case whose symptoms of typhoid/paratyphoid developed within 28 days of arriving in the UK after travel to an endemic region of the world.

The 28-day period is based on national enhanced surveillance data, 95% of cases with a travel history have onset during travel or within 28 days of travel. The 28-day timeframe should be used as a guide but should not be seen as prescriptive. Cases whose symptoms develop between 28 to 60 days after travel to an endemic region should be assessed with regards to establishing other potential sources. Local professional judgement of likely source is essential, based on the individual details of each case.

Endemic region

Enteric fever is endemic in many countries in Asia and Africa and in parts of Central and South America. Typhoid/paratyphoid may occasionally be acquired from travel to a country outside these regions: see the Travel Health Pro website for country-specific typhoid/paratyphoid risks.

Carrier definitions

Convalescent carrier

A person who is still shedding S. Typhi or S. Paratyphi after 2 or more courses of appropriate antibiotic therapy but has been shedding for less than 12 months.

Chronic carrier

A person who continues to excrete S. Typhi or S. Paratyphi for 12 months or more.

Possible carrier

A person with no recent history of travel and either:

• a previous history of enteric fever-like illness, whether previously confirmed or not
• a history of biliary tract illness
• they were born or previously living in an endemic region

Also consider possible carrier status if the individual has a history of extensive travel to endemic regions.

Contact definitions

Contact

A contact is any person who is believed to have had significant risk of direct or indirect exposure to the excreta of an infectious person.

Household contact

A person who lives, or has stayed overnight, in the same household as the case, who ordinarily shares a bathroom or toilet facilities and ordinarily shares food with the case or had other significant close contact with the case (for example, sexual contact) whilst the case was symptomatic and up to 48 hours after commencement of antibiotics.

Co-traveller

A person who travelled closely with the case and who is likely to have been exposed to the same sources of infection as the case (rather than someone who merely travelled on the same bus or plane or was in the same tour group as the case). They may not necessarily live with the case.

Wider contact tracing

For investigation of non-travel associated cases or in an outbreak scenario or where there is potential evidence of transmission outside the household, wider contact tracing may be considered in the following:

Food handling

A person who has either:

• regularly eaten food prepared by the case during the infectious period
• eaten food prepared by the case on a single occasion during the infectious period if:
  • there is concern about hygiene practices of the case
  • the case was symptomatic when preparing their food

Caring duties

A person who has been involved in nappy changing or toileting assistance of the case, or who has been involved in close physical care of the case during the infectious period.

Shared exposure

A person who has been exposed to the suspected or identified sources of infection. This may include children who have shared bathroom or toilet facilities with the case or have had close contact with the case in a childcare setting during the infectious period.

Definitions of groups at higher risk of transmitting gastrointestinal (GI) infections

Risk group	Description	Additional comment
Group A	Any person who is unable to perform adequate personal hygiene due to their lack of capacity or ability to comply, or lack of access to hygiene facilities.	Risk assessment should consider availability or access to toilets, handwashing or hand drying facilities in the work, educational or social care setting.
Group B	All children aged 5 years old or under (up to sixth birthday) who attend school, pre-school, nursery or other similar childcare or minding groups.	For children aged 5 years and under who do not attend school or other childcare settings, risk assessment for clearance purposes should explore potential for transmission within other settings, for example within the household or attendance at parties.
Group C	People whose work or voluntary activities involve preparing or serving unwrapped ready to eat food (including drinks).	Consider informal food handlers, for example someone who helps to prepare food for charity and community events.
Group D	Clinical, social care or nursery staff or childminders who work with young children, the elderly, or any other particularly vulnerable people, and whose activities increase the risk of transferring infection via the faecal-oral route.	Risk assessments should consider activities such as helping with feeding or handling objects that could be transferred to the mouth.

Algorithms for public health management

There are 2 algorithms to assist with public health management:

• Algorithm 1. Public health management of cases and contacts
• Algorithm 2. Public health management of cases with positive screening or clearance samples and those with previous documented history of enteric fever

Algorithm 1. Public health management of cases and contacts

Algorithm 1 consists of 4 questions which follow, one from the other.

The initial risk assessment (questions 1 and 2) should be completed by a public health practitioner on the same day as notification, including out-of-hours as per local arrangements.

Question 1

Text version of question 1

1a) Does the case fit the case definitions for a possible, probable or confirmed case?

1b) Is the case symptomatic?

1c) Is the case aware of anyone else with the same symptoms?

Refer to section on typhoid and paratyphoid case definitions.

If a possible case, there are 2 options:

Option 1. If acutely ill patient, or symptomatic contacts:

• clinician to arrange diagnostic tests and manage as clinically indicated
• hygiene advice should be given by the clinician managing patient care
• case should be excluded while symptomatic until 48 hours after last symptoms

If positive, manage as probable or confirmed case. If negative, no further action.

Option 2. Recovered asymptomatic patient (for example, returning traveller):

• clinician to give hygiene advice
• in a risk group, clinician to take one faecal sample for public health purposes

Again, if positive, manage as probable or confirmed case, if negative, no further action.

If a probable or confirmed case, clinician to arrange appropriate antibiotic therapy, then complete question 2 and question 3 to determine public health action.

Question 2

Text version of Question 2

Is the patient in a risk group?

If no, carry out the following:

• exclusion until 48 hours after last symptom
• hygiene advice
• warn and inform case and contacts

If yes, carry out the following tasks:

• 3 clearance samples, 48 hours apart, commencing one week after antibiotics completed
• exclude from risk activities +/- redeploy
• hygiene advice
• warn and inform case and contacts

If any positive clearance samples, refer to algorithm 2, box A.

Then ask, was the patient symptomatic at work?

If yes:

• risk assess work hygiene and environment
• warn and inform workplace contacts, for example via a workplace letter

Then go to question 3.

Question 3

Text version of Question 3

Did the case travel to an endemic area? (95% of cases who have a travel history develop symptoms within 28 days of return from an endemic area. See section on typhoid and paratyphoid case definitions for endemic areas).

There are 3 options:

Option 1. Case returned from an endemic area in the past 28 days

If this likely to be travel related then complete enhanced surveillance questionnaire to end of travel section, and:

• identify and screen co-travellers in risk groups (one faecal sample and question about symptoms)
• warn and inform other co-travellers, household and other contacts

If co-traveller has positive sample, manage as probable case (see question 1 of algorithm 1)

If co-traveller or contact is symptomatic, manage as possible case (see question 1 of algorithm 1)

Option 2. Case returned from an endemic area between 28 and 60 days

Complete all of the enhanced surveillance questionnaire.

If this is likely to be travel related, then follow option 1 from:

• identify and screen co-travellers in risk groups (one faecal sample and question about symptoms)
• warn and inform other co-travellers, household and other contacts

If co-traveller has positive sample, manage as probable case (see question 1 of algorithm 1).

If co-traveller or contact is symptomatic, manage as possible case (see question 1 of algorithm 1).

If this is not likely to be travel related, then go to question 4.

Option 3. No recent travel history

Complete all of the enhanced surveillance questionnaire and go to question 4.

Question 4

Text version for Question 4

Note: for cases with no recent travel history and/or for whom travel is an unlikely source of infection, further contact tracing and assessment of source is necessary.

If the case has a documented history of previous enteric fever, go to algorithm 2, box C.

If the case does not have a documented history of previous enteric fever, does the initial risk assessment identify a possible source of transmission? For example, is there a contact with similar symptoms or with a travel history or is there a confirmed epidemiological link with a known case?

There are 2 options:

Option 1: If a possible source is identified:

• screen (sample) suspected source (individual or environment) if not already done
• consider provisional control measures depending on potential source
• escalate if possible outbreak
• update diagnostic note on case management system with possible source identified

If there are no positive samples, is there a need to identify a source or are there concerns of ongoing risk? If there is no ongoing risk, then there is no further public health action.

If there are no positive samples but there is still a need to identify a source or there are concerns of ongoing risk, consider the need for an outbreak control team. Consider if wider risk assessment and screening is required (stone in pond) if:

• source unknown
• source known but has wider implications for transmission, for example, food source
• documented secondary transmission (positive contact)

Undertake a wider risk assessment including:

• Screen all household and other close contacts
• detailed food history (trawling questionnaire)
• detailed history of social gatherings, sexual history
• consider need for wider screening, for example, workplace contacts, food sources

If there are positive samples, manage as new probable case (see algorithm 1, question 1). If asymptomatic, see algorithm 2, box B. Screen all household and close contacts of source case if not already screened. If positive, manage as new probable cases (see algorithm 1, question 1). If asymptomatic, see algorithm 2, box B. If there are no concerns of ongoing risk then there is no further public health action. If there are concerns of ongoing risk:

Consider the need for an outbreak control team. Consider if wider risk assessment and screening is required (stone in pond) if:

• source unknown
• source known but has wider implications for transmission, for example, food source
• documented secondary transmission (positive contact)

Undertake a wider risk assessment including:

• screen all household and other close contacts
• detailed food history (trawling questionnaire)
• detailed history of social gatherings, sexual history
• consider need for wider screening, for example, workplace contacts, food sources

Option 2: If no source is identified:

Undertake a wider risk assessment including:

• screen all household and other close contacts
• detailed food history (trawling questionnaire)
• detailed history of social gatherings, sexual history
• consider need for wider screening, for example, workplace contacts, food sources

The initial risk assessment (questions 1 and 2) should be completed by a public health practitioner on the same day as notification, including out-of-hours as per local arrangements.

Algorithm 2. Public health management of cases with positive screening or clearance samples and those with previous documented history of enteric fever

Accessible text version of the public health management flowchart

Option 1: The case is in a risk group

Treat with antibiotics (treatment course 1)

Then take 3 clearance faecal samples starting one week after completion of treatment, at least 48 hours apart. If all 3 samples are negative, discharge from public health follow up. Clinician to manage if indicated.

If any of the 3 samples are positive (box A), delay subsequent sample by one week and await the result before taking the next sample.

If there are 3 consecutive negative samples then discharge from public health follow up. Clinician to manage if indicated.

If any of the 3 samples are positive, delay subsequent sample at least a week and await the result before taking the next sample.

If there are 3 consecutive negative samples then discharge from public health follow up. Clinician to manage if indicated.

If any of the 3 samples are positive, consider re-treatment (treatment course 2) (second course of antibiotics and/or other treatment options where appropriate), checking antibiotic compliance and sensitivity. Consider screening household contacts prior to re-treatment.

If there are 3 consecutive negative samples then discharge from public health follow up. Clinician to manage if indicated.

If any of the 3 samples are positive, the case becomes a convalescent carrier (box D).

Undertake an individual case risk assessment to assess whether the case presents continuing public health risk. Refer to clinician for clinical management – consider if extended treatment required.

If no, discharge from public health follow up. Clinician to manage if indicated.

If yes, exclude and complete monthly clearance samples.

If one monthly sample is negative, take 2 further follow up samples at least 48 hours apart and await result.

If all 3 samples are negative, discharge from public health follow up. Clinician to manage if indicated.

If any samples are positive: return to monthly samples until next negative sample.

After 12 months of repeat sampling, the case becomes a chronic carrier (box E).

If case has possible or documented history of enteric fever for more than one year (box C), undertake an individual case risk assessment to assess whether the case presents continuing public health risk.

Option 2:

The case is asymptomatic and has been identified through screening.

• Is the case in a risk group or do they undertake risk activities that mean there is an ongoing public health risk?
• Discuss rationale for treatment with the case and relevant clinician.
• Warn and inform contacts

If the case is not in a risk group or does not undertake risk activities that mean there is an ongoing public health risk then discharge from public health follow up. Clinician to manage if indicated.

If the case is in a risk group, follow option 1.

Risk assessment

Formalised local arrangements between the HPT and the local authority should record who is responsible for conducting the initial risk assessment in any particular circumstance.

The initial risk assessment (questions 1 and 2) needs to be performed as soon as possible on the same day as notification, including out-of-hours as per local arrangements. This will allow for the early identification of possible source, exclusion of symptomatic cases in risk groups, and identification and management of symptomatic contacts. To support the risk assessment, complete the national enhanced surveillance questionnaire and use the case definitions and algorithms in this guidance.

Exclusion from workplace, care facility, school or nursery

Risk assessment should not automatically result in exclusions. Redeployment away from activities that involve an unacceptable risk in the workplace or care facility should always be considered as an alternative to exclusion.

Any recommendation for exclusion should be based on a risk assessment of possible secondary transmission arising from the activities undertaken by the individual case in the setting. The assessment should consider the hygiene behaviour of the individual as well as infection control measures in place at the setting (workplace, childcare or care facility).

Use of statutory powers for exclusion

Where it is necessary to exclude an individual from the workplace or other setting to protect public health, the local authority has powers to impose these requirements under the Public Health (Control of Disease) Act 1984 (as amended) and accompanying regulations. Guidance on the use of these provisions is available online. Any exclusion can be arranged by the local authority where the case is resident, or by the local authority of their employment or other occupation, for instance education.

Clearance for public health purposes

Microbiological clearance for public health purposes is demonstrated through culture negative faecal sampling, and in some situations will be required prior to the case or contact being allowed to resume normal occupational activities. The HPT should advise the case or contact about the number and timing of samples they will need to take, as well as the arrangements for delivery or collection.

Risk assessments should be reviewed and updated when new information is obtained, for example, as a result of a ‘warn and inform’ letter.

Microbiological and clinical case management

Microbiological diagnosis and confirmation

Microbiological definitive diagnostic tests

Blood cultures are the investigation of choice for diagnosis of typhoid/paratyphoid, ideally taken before administration of antibiotics. Sampling of less invasive specimens (faeces or rectal swabs, pus, urine) or from other sterile sites for diagnosis are possible. Presumptive (locally confirmed) culture results should be available within 72 hours. Early discussions should be initiated with the local consultant microbiologist if further clarity is necessary about any aspects of diagnosis or investigation. For further information on microbiological diagnosis, refer to the British Infection Association Guidelines for the diagnosis and management of enteric fever in England.

Microbiological confirmation and typing

Local diagnostic laboratories should refer all presumptive isolates to the Salmonella Reference Service (UKHSA SRS) for confirmation and typing. A request form should be fully completed including travel, source of isolate, contact of typhoid/paratyphoid case, clinical information, and presumptive serology, since information is assessed for risk factors of enteric fever.

All Salmonella isolates referred to SRS will be identified and typed using whole genome sequencing (WGS). Data will include confirmation of the serotype, the sequence type (ST) the eBURST group (eBG) and the single nucleotide polymorphism (SNP) address. A typhoidal PCR can be set up for a preliminary result within 24 hours of receipt for high-risk cases (1).

Management of probable cases of paratyphoid B

In some cases, provisional laboratory reports of S. Paratyphi B may subsequently be confirmed by the SRS as Salmonella Java, which causes gastrointestinal illness rather than typhoid or paratyphoid. S. Paratyphi B should be suspected as the most likely cause of illness if:

• the isolate from the original sending laboratory is from blood
• the patient has a clinical picture compatible with typhoid/paratyphoid
• there is a history of travel to an endemic region and/or the case is epidemiologically linked to a probable or confirmed case

If the probable case is in a risk group and/or there is a need for a wide public health investigation, contact the SRS to request that processing of the sample is expedited.

Clinical management

Refer to the British Infection Association Guidelines for the diagnosis and management of enteric fever in England. Clinicians managing a suspected case of typhoid/paratyphoid should get advice from the local microbiology or infectious disease consultant. Antibiotic resistance is increasingly common, particularly in S. Typhi following travel to specific multi-drug resistant (MDR) endemic regions, thus it is essential to ensure appropriate therapy and confirm antibiotic sensitivity. The SRS offers clinical advice for complicated cases and can advise on antimicrobial susceptibility for presumptive multidrug resistant isolates. Referral forms for this service are available online.

Public health management of cases

The public health algorithm contained within this document outlines the recommendations that should be used for the management of a case and contact.

Possible cases

Possible cases of typhoid/paratyphoid may self-report to their GP or attend hospital. This may occur as a result of ‘warn and inform’ information sent to contacts of a probable or confirmed case who subsequently develop symptoms.

A possible case of typhoid/paratyphoid should be managed as follows:

• ‘warn and inform’ information should be given so that the case and contacts are aware of signs and symptoms and the need to contact their GP for a clinical assessment should they become symptomatic
• if acutely ill or symptomatic contacts:
  • clinician should provide hygiene advice
  • clinician should arrange appropriate diagnostic tests and manage as clinically indicated
• if recovered and asymptomatic (for example, a returning traveller reporting a diagnosis abroad without supporting diagnostics)
  • clinician should provide or reinforce hygiene advice
  • if they are in a risk group, clinician should take one faecal sample for screening
• all possible cases should be excluded from work or other high-risk settings while symptomatic and until 48 hours symptom free
• possible cases who are asymptomatic, and have been for at least 48 hours, do not need to be excluded while awaiting the result of a faecal sample
• if the sample is presumptive positive on culture, the case should then be managed as a probable or confirmed case including risk assessment of case and contacts and appropriate clearance or exclusion

Probable and confirmed cases

All cases and their immediate contacts should be provided with comprehensive hygiene advice (by the HPT, GP or local authority depending on local arrangements) especially concerning hand hygiene and preparation of food for household contacts. Advice should preferably be given verbally and confirmed in writing (‘warn and inform’ information) through local arrangements. The advice should include the recommendation of typhoid immunisation for future travel to endemic regions.

For further investigation of the case, refer to algorithm 1, question 2 ‘Is the case in a risk group?’

Based on the risk assessment, a decision should be made as to whether the case is in a risk group for onward transmission of infection:

Cases in a risk group:

• exclusion from risk activities or redeployment until microbiologically cleared
• faecal sampling for clearance purposes should commence one week after completion of antibiotic treatment – for all risk groups (A to D), 3 consecutive negative faecal samples taken at least 48 hours apart are required for clearance, prior to being allowed to resume normal work, school or nursery activities
• cases with positive clearance samples after treatment should be managed according to algorithm 2, box A, with the recommendations outlined in this guidance
• if the case was at work or school while symptomatic, a wider risk assessment of work hygiene, contacts and environment should be undertaken – workplace contacts may need to be given the ‘warn and inform’ leaflet (see companion documents to this guidance for further information)

Cases not in a risk group:

• clearance faecal samples are not required
• cases should be excluded only if symptomatic and should not return to school/work until at least 48 hours symptom free

Refer to algorithm 1, question 3 ‘Did the case travel to an endemic area?’

If the case has developed symptoms of typhoid/paratyphoid within 28 days of travel to an endemic region, consider as a travel-related case. See information on the management of their travel-related contacts.

If travel to an endemic region is identified near the upper limit or outside the 28-day timeframe, consider other possible non-travel-related sources of infection. This should include the possibility of a secondary case from a symptomatic or asymptomatic travel-related case or carrier in the household or a chronic carrier. In these cases, it is worth investigating the possible secondary case or chronic carrier’s relevant travel history to endemic regions, even if this was several years before the onset of symptoms in the current case.

Cases without a travel history and without a confirmed epidemiological link to another case

For cases without a definitive travel history to an endemic region or a confirmed epidemiological link to another case, consider extensive investigation to attempt to identify the source of the infection even if cases are not in a risk group:

Establish if the case has possible carrier status:

• consider taking a follow up sample for possible carriers, even if not in risk group to assess carrier status (at least 6 weeks after first antibiotic course); no exclusion required unless symptomatic – if positive, consider infectious disease referral

Conduct a detailed assessment of contacts and visitors, within a 28-day period, including:

• identifying epidemiological links with other known cases
• ascertaining whether and when household or other contacts have travelled (for example, within last 56 days, so as to cover the 28-day period from infection to onset of symptoms for index case following travel and an additional 28 days for the contact following exposure to index case)
• ascertaining whether household or other contacts such as those handling food have a history of typhoid/paratyphoid-like illness
• consider case’s sexual contacts
• screening household and other close contacts, even if not in a risk group; no exclusion required unless symptomatic
• a ‘stone in the pond’ approach to widen investigation of a possible source of infection should be considered

Consider food history and history of visiting food establishments, as well as any food sources from abroad (imported foodstuffs). Consider attendance at gatherings or events. If necessary, administer the additional trawling questionnaire.

In exceptional instances, such as possible outbreaks involving food handlers, consider the need for food and environmental sampling at the home or workplace.

SNP relatedness with other cases is not helpful in determining epidemiology or time linkage but may only indicate the source region.

Public health management of contacts

Any symptomatic contacts should be managed as possible cases.

Management of contacts of a travel-related case

Refer to algorithm 1, question 3 ‘Did the case travel to an endemic area?’

Co-travelling contacts

Co-travellers in a defined group who travelled with the case and consistently stayed in the same premises or shared food and drinking water (2) and in a risk group should:

• have one faecal sample taken as soon as possible
• be given hygiene advice (‘warn and inform’) so that they are aware of the symptoms of typhoid/paratyphoid and the need to contact their GP for a clinical assessment should they become symptomatic

If their faecal sample is positive, they should be managed as a travel-related case. Those who are symptomatic should be treated as a possible case following the public health management of a case and contact algorithm.

Medical treatment may not always be warranted for asymptomatic co-travellers with a positive sample, but they should be referred for infectious disease consultant advice. If the co-traveller is a probable or confirmed case and in a risk group, they will require exclusion until clearance. Treatment may expedite clearance.

Other co-travellers:

• for larger groups such as travel parties where travellers may not consistently have had similar exposures through their travel, ‘warn and inform’ information should be given to each traveller and their local HPT informed; a line list of travellers should be uploaded in the case management system record of the initial case – the context, for example ‘XXX travel group’, should be added in case management system-specific contexts as a congregation for all cases
• if a positive co-traveller contact from a larger tour party is identified, there may be a need to revisit the initial risk assessment for the co-travelling contacts to decide if the cohort of close co-travellers needs to be redefined

Non-travelling contacts

Contacts who did not travel with the travel related case are unlikely to have been exposed to the same source of infection as the case:

• no sample or exclusion is necessary
• hygiene advice and information about symptoms should be given (‘warn and inform’) so that the contact is aware of the need to contact their GP or the HPT if they become symptomatic

Management of contacts of a non-travel-related case

Refer to algorithm 1, question 4 ‘Does the initial risk assessment identify the likely source of infection?’

Cases with typhoid/paratyphoid infection that is unlikely to be travel-related, without a confirmed epidemiological link to another case and no documented history of previous typhoid/paratyphoid infection require further investigation in an attempt to identify the possible source. The initial investigation will focus on household members or other close contacts in the last 28 days.

If no positive samples or history of illness are found in immediate household contacts, then a ‘stone in pond’ approach should be used to expand the range of likely contacts. In some cases, consider the possibility of a contaminated food source.

Public health management of household and other contacts of non-travel-related cases should include the following:

• a risk assessment to determine history of typhoid-like illness, travel history, food history or visitors from endemic regions
• screening with one faecal sample to ascertain whether there is asymptomatic carriage
• contacts should not be excluded unless they are symptomatic
• hygiene advice and information about symptoms should be given (‘warn and inform’) so contacts are aware of the need to contact their GP or the HPT if they become symptomatic

Public health management of cases with positive screening or clearance samples or with previous documented history of enteric fever

Asymptomatic cases identified on screening

Travel-related asymptomatic cases:

• for asymptomatic co-travellers who are identified on screening, refer to algorithm 1 question 1 and information on possible cases

Non travel-related asymptomatic cases:

• an asymptomatic case may be identified from screening contacts of a non-travel-related case; refer to box B in algorithm 2
• an asymptomatic case may be identified from a history of previously documented enteric fever, in which case, establish that the current infection is the same species and subtype as isolated in the previous infection
• occasionally, cases may be identified incidentally during surgery such as cholecystectomy; establish if the case has a documented history of previous typhoid/paratyphoid, if yes, refer to box C in algorithm 2; if no, manage as a new case using algorithm 1

If secondary transmission to the current case is suspected the following should be assessed:

• risk of further secondary transmission within and outside the household
• activities and behaviours of the cases
• infection control measures to be deployed for home, work or care arrangements

The outcome of this assessment will inform any decision to offer treatment to the individual, based on whether the case is in a risk group or undertakes risk activities. If the risk assessment does highlight ongoing public health risk:

• the case should be offered treatment, and informed of the rationale for treatment
• exclusion from risk activities or redeployment should be considered until microbiologically cleared
• faecal sampling should commence one week after completion of antibiotic treatment; 3 consecutive negative faecal samples taken at least 48 hours apart are required for clearance, prior to being allowed to resume normal work, school or nursery activities

Cases who have a positive clearance sample after one course of treatment

Refer to box A in algorithm 2:

• 5% to 10% of cases may relapse 1 to 3 weeks after the initial infection with a milder disease presentation, thus are likely to need further treatment with the same antibiotic sensitivity (3)
• check antibiotic sensitivities and compliance for all cases who are symptomatic after treatment, or who are still shedding
• stop sampling and wait 7 days before taking the next sample
• if this next sample is positive, then further sampling should be delayed more than a week, even as long as a month

If samples are persistently positive (for example after one month from the first clearance sample):

• ensure household contacts have been screened and their results are negative prior to further sampling of the case
• consider a second course of appropriate antibiotics especially if the case is in a risk group, and poses a public health risk
• a further set of 3 negative faecal samples are required, starting one week after completion of the second course of antibiotic treatment and confirming a negative result from each sample before taking the subsequent sample

Exclusion from risk activities or redeployment should continue until the case is microbiologically cleared.

Cases in risk group B that have positive clearance

A recent audit of confirmed cases in risk group B (children aged 5 years old or under who attend school, pre-school, nursery or other similar childcare or minding groups) between January 2017 and March 2022 found that 24% of these cases had at least one positive sample out of their first 3 clearance samples. In light of this, the following additional steps to the above are recommended for cases in risk group B who have a samples that are persistently positive (for example, after one month from the first clearance sample) after one course of treatment:

• a second course of antibiotics is not usually recommended. However, consider contacting the case’s GP who may make referral to paediatric team to discuss possibility of second course of antibiotics
• consider a multidisciplinary team to assist in the risk assessment; these teams should ideally include HPTs in conjunction with relevant stakeholders, such as public health microbiologists, infectious disease consultants physicians, pediatricians or national experts and environmental health officers, directors of public health, and nursery or school representatives
• after the initial risk assessment, a plan should be made for ongoing risk assessments; results from these risk assessments should inform discussion with parents or guardians and childcare managers to ensure that the public health benefit of continued exclusion is balanced against any potential harm from prolonged periods of exclusion; risk assessments should be regularly reviewed, and a plan agreed for the next assessment

Convalescent carriers

Convalescent carriers are those who are still shedding virus after 2 or more courses of antibiotics, but who have been shedding for less than 12 months (box D in algorithm 2).

Up to 10% of cases may shed initially after treatment, with 1% to 4% shedding at 3 months (4).

If clearance for public health purposes is necessary, consider the following:

• the managing clinician, along with the local microbiologist, should be made aware of the public health implications and the need for clearance; discussion regarding the public health implications and continued shedding should be held with relevant agencies (HPT or local authority); a plan for the management of the case should be agreed which may also include the referral or advice from an infectious disease consultant and possible extended treatment
• the case must be fully informed of the rationale for any further treatment or investigation and all possible steps taken to obtain their agreement; this might include the involvement of other non-medical and non-regulatory agencies
• ensure household contacts have been screened and results are negative prior to further sampling of the case

If the case is assessed to present a continuing public health risk, monthly clearance:

• samples (for up to 12 months) are necessary, and exclusion from risk activities or redeployment should be considered until microbiologically cleared
• faecal sampling: if any monthly sample is negative, then 2 further samples should be taken at a minimum of 48 hours apart, confirming a negative result from each sample before taking the subsequent sample; if all 3 are negative, then the case can be discharged from public health follow up; if any samples are positive, then return to monthly sampling
• the need for strict hygiene both should be reinforced, particularly after using the toilet and before preparing food
• hygiene advice and information about symptoms should be given to contacts of the convalescent carrier (‘warn and inform’) so they are aware of the need to contact their GP or the HPT if they become symptomatic
• contacts in risk groups do not require exclusion
• there should be adherence to confidentiality and ethical principles, subject to robust public health grounds for breaking any confidentiality

Chronic carriers

Chronic carriers (box E in algorithm 2), who have had several unsuccessful treatments, may continue to shed for years. For chronic carriers in a risk group, a risk assessment should be carried out with the case, specialist physician and the relevant agencies (HPT or local authority), to consider:

• safe arrangements for continuing in work or alternative occupations, for example, a food handler may need to be permanently redeployed
• the continuing need for strict hygiene, particularly after using the toilet and before preparing food

In addition:

• hygiene advice and information about symptoms should be given to contacts (‘warn and inform’) so they are aware of the need to contact their GP or the HPT if they become symptomatic
• contacts in risk groups do not require exclusion

The typhoid vaccine should not be recommended for contacts of carriers because there is little evidence of it being effective in these circumstances. It is more effective to advise the family members to seek travel advice and relevant vaccinations before their next visit to an area of high prevalence.

Possible carrier

If a case does not have a recent travel history and has possible carrier status, consider taking a follow-up sample even if they are not in a risk group to assess their carrier status. This should be taken at least 6 weeks after the end of the first antibiotic course. These cases do not require exclusion unless they are symptomatic.

If the follow-up sample is positive, consider referring to an infectious disease consultant.

Primary prevention: role of travel advice and vaccination

Food, water and personal hygiene

Typhoid and paratyphoid are spread from person to person by the faecal-oral route. Therefore, their prevention and control is dependent on good sanitation, clean water and scrupulous personal hygiene. Emphasis needs to be placed on hand washing and sanitary disposal of faeces, hygienic food preparation and proper arrangements for safe water supplies. Further information on food and water hygiene is available from the National Travel Health Network and Centre (NaTHNaC).

10.2 Typhoid vaccine

Typhoid vaccine is indicated for active immunisation against typhoid fever. Two types of typhoid vaccine are available in the UK: a polysaccharide vaccine and an oral, live, attenuated vaccine. Cumulative 3-year efficacy of either vaccine is 65% (5) and protective antibody titres fall over time. Further details are given in the Green Book.

The typhoid vaccines are recommended for:

• travellers visiting typhoid-endemic regions whose planned activities put them at higher risk (check the country information pages from NaTHNaC and Travax); those at increased risk include travellers visiting friends and relatives, and frequent or long-stay travellers to areas where sanitation and food hygiene are likely to be poor
• laboratory personnel who may handle S. Typhi in the course of their work

If typhoid vaccine is recommended for travel, allow at least 4 weeks after full recovery from previous typhoid illness (6).

There is no vaccine for paratyphoid infection. there is some evidence for cross protection against S. Paratyphi B with the oral typhoid vaccine Ty21a.

Because the vaccine offers limited protection against typhoid and some cross protection against paratyphoid, the importance of scrupulous attention to personal, food and water hygiene must still be emphasised for those travelling to endemic regions. Typhoid vaccine is not recommended for household or other contacts of either cases or carriers, or during an outbreak of typhoid fever in the UK (7).

Resources and contacts

National reference material

Typhoid and paratyphoid: guidance, data and analysis (includes links to these guidelines, national surveillance form and national surveillance reports).

OHID Migrant Health Guide: Enteric fevers page; key messages for primary care practitioners.

Visiting friends and relatives abroad: health advice (Arabic, Bengali, French, Gujarati, Hausa, Igbo, Punjabi, Spanish, Swahili, Yoruba, Urdu, Xhosa translations and BSL, large print, braille, Easy Read versions also available).

National Travel Health Network and Centre (NaTHNaC) Travel Health Pro website: Typhoid and paratyphoid factsheet.

Companion documents to this guidance

Template letter and fact sheet for contacts for a case of enteric fever

Enhanced surveillance questionnaire for enteric fevers

Online questionnaire

PDF version

National trawling questionnaire

Contact information

Contact local health protection teams for initial advice on cases or contacts

Travel Health and International Health Regulations (UKHSA)

Salmonella Reference Service (UKHSA)

Appendix A. Background information

Typhoid/paratyphoid is an infection caused by the bacteria called Salmonella enterica subspecies enterica serovar Typhi (commonly S. Typhi) and Paratyphi A, B or C (commonly S. Paratyphi A, B or C).

Epidemiology

International

Globally, there are an estimated 11 to 20 million new cases of typhoid/paratyphoid every year, with 128,000 to 161,000 deaths. The majority of cases occur in parts of Asia and in Africa, as well as in the Americas and Western Pacific. The risk of typhoid/paratyphoid is higher in populations that lack access to clean and safe water and adequate sanitation (8). In countries where standards of sanitation are high, infections are sporadic and are mainly associated with foreign travel.

England, Wales and Northern Ireland (EWNI)

Reports of typhoid and paratyphoid in EWNI have been mostly stable in recent years, with an average of 325 confirmed cases each year between 2012 and 2018. In 2019 there were 515 cases, which was the highest yearly total since 2012, and a 47% increase compared to 2018, the largest increase since 2000. There has been an outbreak of an extensively drug-resistant (XDR) strain of S. Typhi which has been ongoing in Pakistan since 2016, which contributed to an increasing trend of XDR typhoid fever cases imported from Pakistan seen in EWNI, with one case reported in 2017, 6 cases in 2018 and 34 in 2019 (9, 10).

During 2020 and 2021, the COVID-19 pandemic led to a significant decrease in worldwide travel as many countries, including the UK, imposed restrictions on arriving and departing travellers (11). In line with the falling numbers of travellers arriving in the UK, the number of typhoid/paratyphoid cases diagnosed in EWNI also decreased. Typhoid/paratyphoid cases decreased by 62% to 194 in 2020 and then by 16% to 163 in 2021.

On average, since 2012, 60% of cases in England, Wales and Northern Ireland were caused by S. Typhi, 35% S. Paratyphi A, 5% S. Paratyphi B and the rest (less than 1%) were either mixed infections or caused by S. Paratyphi C.

Geographic distribution

On average in each year between 2012 and 2021, England reported 97% of cases, Wales reported 2% and Northern Ireland reported less than 1%. London consistently reports the highest proportion of cases reported in England each year and on average reported 35% of cases between 2012 and 2021.

Demographic breakdown

Of all cases reported between 2012 and 2021 where demographic information was known, there was a slightly higher proportion of males (52%). Just over one-quarter (26%) of all cases were under 15 years old, with the median age being 27 years [range less than 1 year to 95 years]. Where ethnicity was known, the majority of cases (78%) were of Indian, Pakistani or Bangladeshi ethnicity.

Travel history

Where travel history was known, 93% of infections were presumed to have been acquired abroad, among people who travelled abroad from EWNI, who were new entrants to the UK, or were foreign visitors to the UK. The majority of these cases reported travel to India, Pakistan and Bangladesh. Of those cases that travelled abroad from EWNI, 83% reported travelling to visit friends and relatives. No foreign travel was reported for 6% of cases. In line with the general distribution, the highest percentage of these non-travel cases were reported in London (38%).

Clinical features

Typhoid

Typhoid is a systemic bacterial disease with gradual onset of sustained fever, marked headache, malaise, anorexia, relative bradycardia, splenomegaly and non-productive cough. Although some reports state that rose spots are found on the trunk in 25% of white-skinned patients and constipation is seen more often than diarrhoea in adults (12), a 10-year study of typhoid and paratyphoid in a UK regional infectious diseases unit found that fever, headache, diarrhoea and abdominal pain were the main presenting symptoms. Rose spots were observed in only 7% of patients, and symptoms of bradycardia and constipation were rare (13). The clinical picture varies from mild illness with low-grade fever to severe clinical disease with abdominal discomfort and multiple complications. Severity is influenced by factors such as strain virulence, quantity of inoculum ingested, duration of illness before adequate treatment, age and vaccination status.

Complications typically arise in the third week of disease. In the abdomen, ulceration of Peyer’s patches may result in haemorrhage or intestinal perforation (about 1% to 4% of cases), especially for untreated cases. Renal failure can occur in severe cases.

Osteomyelitis may develop, especially in those predisposed by sickle cell disease. Other rare complications include cholecystitis, meningitis and typhoid pneumonia (14).

The case fatality rate of 10% to 20% observed in the pre-antibiotic era has fallen to less than 1% with prompt antimicrobial therapy. Depending on the antimicrobials used, 5% to 10% of patients may experience relapses (generally milder than the initial clinical illness) (2, 3). Some evidence suggests that both faecal carriage and relapse rates in UK patients with typhoid may be less than 3% (15).

Paratyphoid

Paratyphoid is clinically similar to typhoid, although spots are more frequent and brighter red than in typhoid. It is usually less severe than typhoid.

Complications are less common but also typically arise in the third week (12).

Serovar Paratyphi B refers to the invasive biotype that is associated with paratyphoid fever. A variant of Paratyphi B, referred to as serovar Paratyphi B var. Java, is associated with routine gastrointestinal disease rather than paratyphoid.

Relapses may occur in anywhere from 3% (7) to 9% (13) of paratyphoid cases.

S. Paratyphi C infections are rare (7).

Clinical management

Typhoid/paratyphoid can be successfully treated with antibiotic therapy and general medical support. Strains of S. Typhi have become increasingly resistant to antibiotics, particularly in South Asia (13, 16, 17, 18). Refer to the Enteric Fever Treatment Algorithm in the British Infection Association Guidelines for the diagnosis and management of enteric fever in England.

Complex cases can be discussed with the UKHSA regional microbiologist or the Salmonella reference service GBRU. All isolates which appear azithromycin resistant in diagnostic laboratories should be sent to the Salmonella reference service for confirmatory testing.

Reservoir

The main reservoir for both typhoid and paratyphoid is the human intestinal tract of cases and carriers. S. Paratyphi B infections have occasionally been associated with cattle. The organisms can survive for days in ground water, pond water or seawater, and for months in contaminated eggs and frozen oysters (3).

Modes of transmission

Transmission primarily occurs via the oral route following ingestion of food or water contaminated by faeces and, occasionally, the urine of people acutely ill with typhoid or those who are chronic carriers. Direct faecal–oral transmission can also occur in poor hygiene conditions and sexual transmission.

S. Typhi is extremely infectious. Infection may occur with ingestion of fewer than 100,000 organisms (7) especially in susceptible individuals, although one million or more organisms may be required to cause illness in healthy individuals (3, 7). Achlorhydria and disturbance of bowel flora (for example by antibiotics) decrease the minimum infective dose. Splenectomy (for example in sickle cell disease or immune defects) makes it more difficult to eradicate S. Typhi (7). The infective dose for paratyphoid is higher than for typhoid (16).

The risk of contracting typhoid and paratyphoid fever is highest for travellers to areas of high endemicity. In the Indian subcontinent, a region of high incidence of typhoid, the attack rate for travellers has been estimated at 1 to 10 per 100,000 journeys (19). Overall, the estimated incidence of typhoid among travellers to developing countries as a whole is 3 to 30 cases per 100,000 travellers (5, 15, 20).

Imported foodstuffs from endemic regions have also been identified as a source of infection in a number of cases (21, 22, 23).

Incubation period

The incubation periods for S. Typhi and S. Paratyphi depend on host factors and the size of the infecting dose. The mean incubation period of typhoid is reported as between 7 and 21 days. A meta-analysis published in 2018 found the vast majority of typhoid cases developed symptoms within 28 days of exposure, and the longest reported incubation period was 41 days (24). The incubation period for paratyphoid is significantly shorter than for typhoid, usually 1 to 10 days (3).

The incubation period between infection and development of symptoms is important for public health management, including the identification of the likely source of infection. For this reason, time between return from travel and onset of symptoms is significant.

Although the literature cited above suggests that incubation periods differ for typhoid and paratyphoid, the national enhanced surveillance data from England, Wales and Northern Ireland for 2007 to 2010 does not show any significant differences in the dates of onset following return from travel between typhoid and paratyphoid.

In a separate review, of cases between 2012 and 2021 with documented travel history where onset of symptoms and travel dates were known, 97% of cases had an onset date during or within 35 days of return:

• 90% had an onset date during or within 21 days of returning to EWNI travel
• 5% had an onset date between 22 to 28 days
• 2% had an onset date between 29 to 35 days

There was no observable difference between typhoid and paratyphoid in date of onset of symptoms relative to arrival in UK.

Note that less than 1% of cases with documented travel history were asymptomatic.

Therefore, based on this data, this guidance does not give separate definitions of ‘travel-related’ for typhoid and paratyphoid cases, and defines a case of enteric fever as more likely to be acquired abroad (‘travel-related’) if symptoms develop within 28 days of arriving in the UK after travel to an endemic region.

Public health professionals will need to risk assess each case based on whether the case has travelled to an endemic region, and on the dates of travel to determine whether it is likely to be travel-related.

Therefore, 28 days is used as a guide but should not be seen as a prescriptive timeframe: local professional judgement based on the individual details of each case is essential. Individuals who have travelled to an endemic region between 28 and 60 days prior to symptom onset should be investigated if there is a high degree of clinical suspicion.

Infectious period

All patients with typhoid and paratyphoid shed the organisms at some stage during their illness, and the infectious period lasts as long as bacilli are present in the faeces (3). The initial illness is septicaemia, and it is not until around the end of the first week that bacteria are detected in faeces or urine (25, 26). Cases are not usually considered infectious prior to the onset of symptoms.

Approximately 10% of untreated typhoid patients will shed bacteria for at least 3 months after the onset of acute symptoms (3). Approximately 2% to 5% of those infected with S. Typhi become chronic carriers (2, 3). This carrier state may last many years and is more common in females, the elderly and those with gallstones (27, 28). Prevalence studies and clinical review following incidental laboratory isolates have demonstrated that not all patients with chronic carriage have a history of symptomatic typhoid/paratyphoid infection (29, 30). There is less published literature on the excretion of S. Paratyphi. It appears that excretion is similar to most other salmonellae: most people will excrete it for 5 to 6 weeks while a small minority continue excreting for months or even years (31). The issue of prolonged biliary excretion applies in some cases, as in typhoid.

Immune response

Following natural infection with typhoid, an immune response develops that may partially protect against reinfection and severity of disease (32).

References

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8. World Health Organization 2018. Typhoid

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