enteric fevers

Last edited 03/2021 and last reviewed 04/2021

Typhoid and paratyphoid fevers are collectively known as enteric fevers and they are caused respectively by the organisms Salmonella typhi and Salmonella paratyphi (types A, B and C). Both of these organisms are primarily human pathogens, though S. paratyphi type B has been known to infect cattle (1,2,3).

• transmission is primarily via the oral route following ingestion of food or water contaminated by faeces and occasionally the urine of persons acutely ill with typhoid or those who are chronic carriers
  • direct faecal-oral transmission can also occur
  • in healthy individuals, one million or more organisms may be required to cause illness, however, ingestion of fewer organisms may still result in illness, especially in susceptible individuals
    
    
  • incubation period
  • in typhoid fever averages from 10 to 20 (range 3-56) days, depending on host factors and the size of the infecting dose
  • in paratyphoid fever ranges from 1 to 10 days
    
    
  • risk of contracting typhoid fever is highest for travellers to areas of high endemicity. In the Indian subcontinent, a region of high incidence of typhoid fever (more than 100 cases per 100,000 people per year, the attack rate for travellers has been estimated at 1 to 10 per 100,000 journeys
    
    
• following ingestion of contaminated food or water, S. typhi penetrates the intestinal mucosa, replicates and enters the bloodstream
  • severity of symptoms varies. Clinical features range from mild fever, diarrhoea, myalgia and headache to severe disseminated disease with multi-organ involvement in 10–15% of cases
    
    
• case fatality rate (CFR) is less than 1% with prompt antibiotic therapy, but may be as high as 20% in untreated cases
  
  
• routine blood tests and blood culture can aid the diagnosis; serological tests, including the Widal test, are not recommended (3)
  
  
• antimicrobial resistance is common, so refer to national guidelines or formularies for choice of antibiotic (3)
  
  
• PHE have defined criteria for:

  Confirmed Case:

  • A person with S. Typhi or S. Paratyphi infection determined by the Public Health England Gastrointestinal Bacteria Reference Unit
  • OR
  • A person with documented confirmatory evidence from a recognised overseas reference laboratory

  Probable Case:

  • Local laboratory presumptive identification of Salmonella Typhi or Paratyphi on faecal and/or blood culture or culture of another sterile site (e.g. urine), with or without clinical history compatible with enteric fever
  • OR
  • A returning traveller giving a clinical history compatible with enteric fever and documentation of a positive blood/faecal culture (or positive PCR for S.Typhi / S.Paratyphi on blood) and/or treatment for enteric fever overseas

  Possible Case:

  • A person with a clinical history compatible with enteric fever and where the clinician suspects typhoid or paratyphoid as the most likely diagnosis
    OR
  • A person with clinical history of fever and malaise and/or gastrointestinal symptoms with an epidemiological link to a source of enteric fever e.g. if they have ‘Warn and inform’ information
  • OR
  • A returning traveller reporting a diagnosis abroad with positive serological testing or Salmonella PCR from faeces but no documented evidence of a positive blood or faecal culture positive
    
    
• typhoid has previously been thought to be a milder disease in children
  • more recent datat, however, indicates that typhoid can cause significant morbidity in children aged one to five years who reside in endemic countries

Enteric fevers are systemic, bacteraemic illnesses which should not be confused with food poisoning or Salmonellosis. The latter are caused by different species of Salmonella, and unlike enteric fevers they often present with acute diarrhoea.

Both typhoid and paratyphoid are notifiable diseases.

Summary:

Cause:

• Salmonella enterica subsp. enterica serovar Typhi (commonly S. Typhi).
• Salmonella enterica subsp. enterica serovar Paratyphi – A, B, C (commonly S. Paratyphi A, B and C)

Reservoir:

• The main reservoir for both typhoid and paratyphoid is the human intestinal tract

Epidemiology:

• majority of cases (95%) reported in the UK are related to travel to endemic areas
• in developed countries where standards of sanitation are high, the diseases are sporadic and are mainly associated with foreign travel
• in the UK, approximately 55% of enteric fever cases are due to S. Typhi and 45% to S. Paratyphi (majority paratyphoid A)

Transmission:

• primarily faecal-oral following ingestion of food or water contaminated by faeces (or, occasionally, urine) of acutely ill cases or chronic carriers
• direct faecal-oral transmission can also occur in poor hygiene conditions and, rarely, through sexual contact
• risk of contracting typhoid and paratyphoid fever is highest for travellers to areas of high endemicity
• estimated incidence of typhoid among travellers to developing countries is 3-30 cases per 100,000 travellers

Incubation period:

• incubation period depends on host factors and the size of the infectious dose
• S.Typhi: 10 to 20 days (range 3-56)
• S.Paratyphi: usually 1-10 days
• suggested that onset of travel related infection can occur up to 28-60 days after end of travel

Infectivity:

• variable. People are infectious for the duration of excretion of bacteria. Cases are not considered infectious prior to symptom onset
• further risk assessment may be required for convalescent and chronic carriers in risk groups to consider potential ongoing risk to public health, and appropriate interventions
• S.Typhi:
• approximately10% of untreated patients will excrete bacteria for at least 3 months after the onset of acute symptoms
• approximately 2-5% become chronic carriers, which may last many years
• S.Paratyphi:
• most people will excrete bacteria for 5-6 weeks after onset of acute symptoms
• a small minority continue excreting for months or even years

Notes:

• Serovar Paratyphi B var. Java is associated with gastrointestinal disease and is difficult to distinguish by conventional microbiological tests from invasive biotypes associated with paratyphoid fever
• in endemic areas and in returning travellers, consider enteric fever in the differential diagnosis in patients with acute fever, particularly if they have abdominal
  symptoms (3)
• in endemic areas, rule out other causes of acute fever such as malaria and dengue with tests and consider adding empirical treatment with doxycycline (or
  azithromycin) for scrub typhus and leptospirosis (3)

Reference:

1. Immunisation Against Infectious Disease - "The Green Book".Chapter 33 Typhoid (May 2019)
2. PHE (2019). Recommendations for the Public Health Management of Gastrointestinal Infections
3. Basnyat B et al. Enteric Fever. BMJ 2021;372:n437 http://dx.doi.org/10.1136/bmj.n437