Can typhoid fever cause psychosis in patients, particularly those with a history of travel to endemic areas or underlying neurological/psychiatric conditions?

Typhoid Fever and Psychosis

Yes, typhoid fever can cause psychosis, and this neuropsychiatric complication occurs in a substantial proportion of patients—historically reported in up to 50% of cases with neuropsychiatric manifestations. 1, 2

Clinical Presentation and Frequency

Typhoid-associated psychosis presents in two distinct patterns:

• Acute onset: Patients develop confusional states, delirium, or frank psychosis concurrent with fever and systemic symptoms 2
• Insidious onset: Psychotic symptoms may appear before fever develops, masquerading as primary psychiatric illness and delaying correct diagnosis 1

The neuropsychiatric manifestations of typhoid are increasingly recognized, with one series documenting 124 of 246 cases (50%) presenting with confusional states, delirium, coma, myoclonus, Parkinsonian rigidity, or psychoses 2. Importantly, these psychiatric symptoms can be the initial presenting feature with minimal impairment of consciousness, occurring well before fever appears 1.

Specific Psychotic Presentations

Documented presentations include:

• Functional-type psychosis without obvious organic features initially 1
• Acute psychotic symptoms with hallucinations and delusions 3
• Rare delusional disorders such as Fregoli syndrome (persecutory delusions with misidentification) 4
• Behavioral disturbances requiring psychiatric evaluation before infectious etiology is recognized 1

Diagnostic Approach in Suspected Cases

When evaluating psychosis in patients with travel history to endemic areas:

• Obtain blood cultures immediately before antibiotics, as they have 40-80% sensitivity in the first week 5
• Check complete blood count looking for leukopenia with relative lymphocytosis and thrombocytopenia 5, 6
• Monitor for fever development even if absent initially, as psychosis may precede pyrexia by days 1
• Consider bone marrow culture if blood cultures are negative but suspicion remains high (sensitivity 35-65% vs blood culture) 5
• Perform neurological examination to assess for other CNS complications like reduced muscle tone or cerebellar signs 3, 7
• Brain imaging (CT) is typically normal but helps exclude other pathology 3

Critical Management Considerations

Start empiric IV ceftriaxone immediately after obtaining cultures in hospitalized patients with suspected typhoid psychosis, especially those from Asia where >70% of isolates are fluoroquinolone-resistant 5, 8. Treatment duration should be 14 days to reduce relapse risk 5.

Hospitalization Criteria

Admit patients with:

• Altered mental status or psychosis indicating severe disease requiring inpatient monitoring 8
• Fever ≥38.5°C in travelers from endemic areas with documented severe illness 8
• Inability to tolerate oral medications or maintain hydration 8

Treatment Response

Psychotic symptoms typically resolve with appropriate antibiotic therapy:

• One documented case showed complete resolution after one week of IV ceftriaxone followed by oral ciprofloxacin 3
• Neuropsychiatric symptoms are reversible with timely treatment 1, 3

Important Pitfalls to Avoid

Do not dismiss psychiatric symptoms as primary psychiatric illness in patients with recent travel to endemic areas (South Asia, sub-Saharan Africa, Southeast Asia), even if fever is absent initially 1. The functional appearance of psychosis without obvious organic features can lead to misdiagnosis and delayed treatment 1.

Maintain high index of suspicion when evaluating "functional psychosis" in patients from or traveling to endemic regions, as typhoid can present with psychiatric symptoms before classic fever develops 1. Most tropical infections become symptomatic within 21 days of exposure 5.

Consider chloramphenicol toxicity as an additional cause of psychosis if this antibiotic is used, as it can cause reversible marrow suppression, cerebellar signs, and psychosis independent of the infection itself 7.

Underlying Mechanisms

The pathophysiology likely involves:

• Bacterial endotoxins affecting brain biochemistry 2
• Direct CNS involvement though neuroimaging is typically normal 3
• Metabolic derangements potentially exacerbated by poor nutrition 2
• Inflammatory cascade affecting neurotransmitter systems 2

The apparent increase in neuropsychiatric complications may represent changing pathogenicity of S. typhi, increased recognition of biochemical defects caused by endotoxins, or both 2.