Typhoid and Paratyphoid Fever

Typhoid and paratyphoid fever is a systemic febrile illness caused by Salmonella enterica serotype Typhi (typhoid fever) or, less commonly and generally producing milder disease, serotypes Paratyphi A, B or C (paratyphoid fever). It is transmitted via the faecal oral route through contaminated food or water.

It remains a significant cause of morbidity and mortality in regions with inadequate water and sanitation infrastructure, and is an important consideration in the febrile returning traveller.

Pathophysiology

Following ingestion, the organism invades the intestinal mucosa, is taken up by macrophages, and disseminates via the lymphatic and haematogenous routes to the reticuloendothelial system (liver, spleen, bone marrow).

Intracellular survival and replication within macrophages underlies the characteristic prolonged, relapsing febrile illness. Subsequent seeding of Peyer patches in the terminal ileum accounts for the risk of intestinal haemorrhage and perforation in more advanced, untreated disease.

• A stepwise rising fever over the first week, together with headache, malaise, abdominal discomfort and relative bradycardia (a classically described though inconsistently present feature), characterises the early presentation.
• Constipation is more common than diarrhoea in the initial stage, particularly in adults.
• Rose spots are faint salmon coloured blanching macules, typically on the trunk. They appear in a minority of patients during the first or second week.
• Though a classic finding, rose spots are inconsistently present and often subtle or absent, particularly in darker skinned individuals.
• Hepatosplenomegaly, relative bradycardia and a coated tongue are commonly described examination findings. Abdominal distension and tenderness reflect the underlying intestinal involvement.
• Without treatment, the illness can progress into a second and third week with sustained high fever and increasing toxicity.
• Serious complications include intestinal haemorrhage and perforation (reflecting Peyer patch ulceration in the terminal ileum), encephalopathy, and, less commonly, myocarditis or other focal complications.
• Actively seek a relevant travel history to an endemic region, or, in endemic settings, exposure to potentially contaminated food or water, in any patient with a compatible prolonged febrile illness.

• Blood culture is the primary diagnostic test and should be obtained in every suspected case. Sensitivity is highest in the first week of illness (when bacteraemia is most pronounced) and declines thereafter. A negative blood culture later in the illness does not exclude the diagnosis.
• Bone marrow culture offers higher sensitivity than blood culture, particularly useful where prior antibiotic exposure may have reduced blood culture yield. It is more invasive and generally reserved for diagnostically uncertain cases.
• Stool and urine culture may also yield the organism, particularly later in the illness, and can additionally identify the chronic carrier state where relevant.
• The historical Widal serological test has poor sensitivity and specificity and is now generally regarded as unreliable for individual patient diagnosis.
• It continues to be used in some resource limited settings given limited access to culture facilities. Interpret results cautiously and always in the context of the overall clinical picture.
• Full blood count typically shows a normal or low white cell count. Relative leucopenia is a notable and somewhat counterintuitive finding given the febrile, systemically unwell presentation.
• Liver function tests are frequently mildly deranged.

• Antibiotic choice must account for increasing global antimicrobial resistance. This includes widespread fluoroquinolone resistance in many endemic regions and the emergence of extensively drug resistant strains in specific geographical areas.
• Local resistance data and travel history to specific regions should inform empirical choice wherever possible.
• Ceftriaxone 2 g intravenously once daily (or 60 mg per kg once daily in children, to a maximum of 2 g) for ten to fourteen days is a reliable empirical choice, given generally preserved susceptibility. It is particularly appropriate where fluoroquinolone resistance is a concern or in more severe disease requiring intravenous therapy.
• Azithromycin 500 mg orally once daily (or 20 mg per kg once daily in children, to a maximum of 1000 mg) for seven days is an effective oral option for uncomplicated disease. It is particularly useful given increasing fluoroquinolone resistance and the practical advantage of oral administration for milder, ambulatory presentations.
• Ciprofloxacin 500 mg orally twice daily for seven to ten days remains appropriate where local susceptibility data confirm fluoroquinolone sensitivity.
• Do not use it empirically in regions, or in patients with travel history to regions, with known high fluoroquinolone resistance rates, notably parts of South Asia.
• Severe disease with complications, altered consciousness or shock (typhoid encephalopathy or severe toxaemia) warrants consideration of adjunctive dexamethasone alongside appropriate antibiotic therapy.
• The dexamethasone dose is 3 mg per kg as an initial dose, followed by 1 mg per kg every six hours for eight further doses. There is evidence of mortality benefit in this severe subgroup, but it is reserved for genuinely severe presentations rather than routine disease.
• Intestinal perforation requires urgent surgical assessment and intervention alongside continued antibiotic therapy.
• Significant intestinal haemorrhage requires transfusion support and close monitoring, with surgical intervention considered for ongoing significant bleeding.
• Supportive care, including adequate hydration and antipyretics, accompanies antibiotic treatment throughout.
• Relapse occurs in a proportion of patients, typically within two to three weeks of apparent recovery. It is managed with a further course of appropriate antibiotic therapy.
• A small proportion of patients become chronic biliary carriers, particularly those with underlying gallbladder pathology such as gallstones. They shed the organism in stool for a year or more.
• Carriage is identified through persistent positive stool culture and managed with a prolonged antibiotic course (commonly ciprofloxacin where susceptible, for four to six weeks). Consider cholecystectomy in refractory cases, given the gallbladder as the typical reservoir site.
• Typhoid vaccination (either injectable Vi polysaccharide vaccine or oral live attenuated vaccine, according to availability and specific travel context) is recommended for travellers to endemic regions. It forms part of public health control strategies in endemic settings.
• Vaccination does not provide complete protection, so ongoing food and water safety precautions remain important even in vaccinated individuals.
• Notification to public health authorities is required, given the potential for point source outbreaks and the importance of identifying and addressing any chronic carrier source within affected communities.