diagnosis

Last edited 03/2021 and last reviewed 03/2021

The diagnosis is based on the isolation of Salmonella typhi or S. paratyphi from one or more blood cultures.

Cultures are positive during the bacteraemic phase of the illness usually during the first two weeks. However, they may be negative when the patient has been treated with antibiotics, in which case bone marrow culture often remains positive.

The isolation of organisms from the stool or urine is also helpful, with cultures usually becoming increasingly positive from the second week of the onset of symptoms. In the absence of positive blood or bone marrow cultures, stool or urine culture is only diagnostic in the presence of a compatible clinical picture, since the presence of organisms in the stool and/or urine may signify that the individual is a chronic carrier and not suffering an acute infection.

Further evidence of infection, whether acute or chronic, can be obtained using the Widal agglutination titres.

Also urine ELISA tests after the first 10 days of illness (for the Vi antigen specific for the bacteria) may be helpful .

Other laboratory investigations that may be employed in diagnosis include indirect hemagglutination, indirect fluorescent Vi antibody, and indirect enzyme-linked immunosorbent assay for immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to S typhi polysaccharide.

PHE define (1):

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

Notes (2):

• serological tests, including the Widal test and newer rapid diagnostic tests, are not confirmatory in the acute phase of illness
  • Widal test measures antibodies against O and H antigens of S Typhi and S Paratyphi A
    • lacks sensitivity and specificity
    • single measurement in the acute phase of the illness may be false negative or false positive
  • other commercially available, point-of-care rapid diagnostic tests detect IgM antibodies against S Typhi antigens
    • insufficiently accurate to be useful in diagnosis
  • novel assays to detect antibodies, antigens, and DNA in blood are being developed

Reference:

• PHE (2019). Recommendations for the Public Health Management of Gastrointestinal Infections
• Basnyat B et al. Enteric Fever. BMJ 2021;372:n437 http://dx.doi.org/10.1136/bmj.n437