COMMUNICABLE DISEASE CONTROL

AND PROVINCIAL LABORATORY SERVICES

KWAZULU NATAL DEPARTMENT OF HEALTH

Guideline for the laboratory diagnosis and antibiotic treatment of

individuals with suspected typhoid fever

The definitive diagnosis of typhoid fever requires the isolation of Salmonella typhi from blood, bone
marrow or a specific anatomical lesion. The presence of clinical symptoms and/or an antibody response
is suggestive of the diagnosis but not confirmatory. The mainstay of laboratory diagnosis is the blood
culture. Stool cultures may only be positive after the first week of illness and a positive stool culture can
occur in carriers as well as cases.

Recommended specimens:

Blood culture:

This is the diagnostic test of choice.

If blood culture and other facilities for diagnostic tests are not available on site, these specimens should
be transferred urgently to the nearest available laboratory.
Specimens should be processed as soon as possible.

Storage & transportation

Once blood culture bottles have been inoculated they should be incubated immediately at 370C or taken
to the laboratory immediately.
Blood culture bottles should not be refrigerated while awaiting processing.

The volume of blood should ideally be 10-15ml with 5ml inoculated into each bottle (if using the Bactec
system). At least 2 Aerobic bottles should be inoculated for adults and schoolchildren (5ml in each bottle).
In toddlers and preschool children, 2-5ml is required.

It is essential that clinicians liase with the laboratory for specific volumes requirements as these may differ
depending on the commercial system in use. Blood cultures should be performed using strict aseptic
techniques. Ideally 2 sets of blood culture should be drawn. A set comprises 2 bottles. Sets are taken at
different times and from different sites. Blood cultures should be incubated for 7 days and processed in
accordance with the system in use. Terminal sub-culture of negative bottles on day 7 can be performed in
certain cases. Blood cultures are an important guide for antimicrobial treatment of typhoid fever.

Serology

This should not be relied upon for diagnosis

Serology can be performed using the Widal test. 3-5ml of blood in a tube without preservative can be
submitted. Interpretation of results is difficult. The sensitivity and specificity of the test is moderate and
may be negative in up to 30% of culture proven cases. False positive results can be caused by cross
reaction with other Salmonella spp. and with malaria, bacteraemia and cirrhosis.

It is difficult to determine an appropriate cut-off titre in areas with endemic typhoid fever, a number of
patients may have raised titres from previous infection, and a raised titre may not indicate acute typhoid
fever. Paired sera should be done. One taken acutely (at time of first presentation) and then repeated at
day 7-14. A four fold rise in titre is then diagnostic. A single positive serology specimen is not diagnostic
but may support the diagnosis with consistent clinical features and other laboratory parameters e.g.:
leukopaenia. Serological testing is not required if the organism has been isolated already from a sterile
site. Serology does not provide any information regarding antibiotic susceptibilities and therefore culture
remains essential.
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Stool and rectal swabs
st
Stool specimens may be useful for the diagnosis but are usually positive only after the 1 week of illness.
Stool culture does not replace blood culture as a diagnostic specimen as the sensitivity is limited in early
illness. Specimens should be processed within 2 hours of collection. If delays are anticipated, the sample
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should be refrigerated at 4 C or placed in a cool box with freezer packs.

If a stool sample cannot be obtained, rectal swabs can be submitted in Cary Blair transport medium but
the yield on rectal swabs is reduced. Stool cultures are important to exclude carriage, particularly if the
patient has been treated with older antimicrobials, such as ampicillin or chloramphenicol, as these are
less effective antibiotics in treating the carriage state.

Choice of Antibiotic treatment

Depending on the known antibiotic susceptibility results treatment may need to be adjusted accordingly.
Currently in SA the following is/are recommended where no known resistance is identified.

The fluoroquinolones such as ciprofloxacin have several advantages and would be the drug of
choice for treatment, especially in an outbreak situation when large numbers of patients require
treatment. Advantages of ciprofloxacin include:

- Ease of use – twice daily dosing

- Rapid clearance of fever and symptoms
- Low rate of post treatment carriage, ideal in an outbreak or public health setting
- Shorter duration of therapy (see table)
- May be given orally if the patient can take oral fluids
- Is readily available in clinics as it is used for treatment of sexually transmitted infections

In children, ciprofloxacin is not registered for use but has been widely used to treat typhoid fever in
endemic areas with no clear evidence of complications. Suitable alternatives in children may include
ceftriaxone/cefotaxime or ampicillin (where intravenous Rx is required). In pregnant women, treatment
with ceftriaxone is recommended.
Ideally the alternative therapy should have as many advantages in common with the treatment of choice.
Ceftriaxone is also used as short-term treatment, but must be given intravenously. In other aspects, it is
comparable to ciprofloxacin in clearance of the organisms from the gut and as a short-term treatment.
The disadvantage of alternatives such as co-trimoxazole (bactrim) and ampicillin/amoxicillin is the
requirement for a prolonged duration of treatment (at least 14 days) and difficulty in compliance. In
addition, these drugs are not as effective in clearing gut organisms which is a significant disadvantage in
an outbreak situation.

Recommended treatment for uncomplicated typhoid fever during this outbreak:

Drug of choice in all age Alternative

groups – uncomplicated
disease

Ciprofloxacin for 7 days Ceftriaxone for 7-14 days

15mg/kg/day given in 2 divided 50-75mg/kg/day given in 1-2 divided
doses doses

Adult oral dose of ciprofloxacin Adult dose: 2-4g daily (up to 2g BD

usually 500-750mg BD OR in severe disease)
400mg 12hrly ivi
Amoxicillin for 14 days
In pregnancy: 75-100mg/kg/day usually given in 3
Ceftriaxone for 10-14 days divided doses
Adult dose: 2-4g daily
(up to 2g BD in severe disease)

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Patients with complicated/severe disease require intravenous antibiotics with either ciprofloxacin
or ceftriaxone for a minimum of 10-14 days.

Patients with confirmed typhoid fever may remain pyrexial for up to 5 days despite adequate antimicrobial
treatment. However clinicians should use their clinical judgment in assessing such patients with persistent
fever and manage accordingly.

NOTE: Re: use of ciprofloxacin in children

Concern has been expressed regarding the use of ciprofloxacin in the treatment of children. In preclinical
testing, the fluoroquinolones damaged the articular cartilage of young beagles. However, ciprofloxacin
has since been used long-term in children with cystic fibrosis and short-term for the treatment of typhoid
fever and bacillary dysentery in children. There has been no evidence of bone or joint toxicity, tendon
rupture, or, in long-term follow up, impairment of growth. Thus, ciprofloxacin would be considered the
drug of choice for typhoid fever in non-pregnant individuals of all ages.

Prepared by: Dr Nagpal and Mr. H.V.Sithebe

Adapted from: Background document: The diagnosis, treatment and prevention of typhoid fever. World
Health Organisation. Available on line: http://www.who.int/vaccines-documents/DoxGen/H5-DCA.htm
Parry et al.Typhoid fever. N Engl J Med 2002; 347:1770-1782. And NHLS guidelines for lab diagnosis &
antibiotic treatment of individuals with suspected typhoid fever