Fever and Confusion in a Returning Traveler
A 41-year-old man presents to the emergency department with 4 days of high fever, headache, and confusion that began 2 days ago. He returned 9 days ago from a 3-week trip to a malaria-endemic region and took no chemoprophylaxis. Temperature 39.4 C, pulse 122/min, BP 95/60 mmHg, respiratory rate 26/min, oxygen saturation 94% on room air. He is drowsy but rousable, with neck stiffness and photophobia. A rapid diagnostic test for malaria is negative. Platelets 70,000/microlitre, creatinine 180 micromol/L, glucose 4.8 mmol/L, lactate 3.8 mmol/L. The on-call doctor documents 'malaria excluded; likely viral illness; discharge with paracetamol.'
1. Is 'malaria excluded' a safe conclusion here? What does the negative rapid test mean in this context?
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No - a single negative rapid diagnostic test does not exclude malaria, and this patient has multiple red flags for severe disease: impaired consciousness, hypotension, tachypnea, thrombocytopenia, renal impairment, and elevated lactate.
Reasons a rapid test can be falsely negative:
- Low parasite density early in infection or with partial immunity.
- HRP2 deletions in some parasite strains (test targets the HRP2 antigen).
- Prozone effect at very high parasite densities.
- Test performance varies by product and by whether it detects HRP2, pLDH, or aldolase.
A negative rapid test must be confirmed by thick and thin blood films (repeated if initially negative, ideally every 8–12 hours for up to 3 films) in any patient with this presentation. Until films are negative on repeated testing, malaria remains a leading diagnosis and the patient cannot be discharged.
2. Beyond malaria, what else must be on your differential, and what immediate investigations and treatment do you start?
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Differential for fever plus confusion plus neck stiffness in a returned traveler:
- Bacterial meningitis (pneumococcus, meningococcus) - neck stiffness and photophobia demand immediate attention.
- Meningoencephalitis - viral (e.g., HSV, enteroviruses) or other.
- Severe malaria (cerebral malaria) - still possible.
- Typhoid/enteric fever with encephalopathy.
- Dengue with shock (thrombocytopenia, hypotension) - though usually less CNS involvement.
- Leptospirosis, rickettsial infection, sepsis of any source.
Immediate actions:
- Blood cultures, malaria films (repeated), dengue serology, and a lumbar puncture after excluding raised intracranial pressure (CT head first if focal signs or reduced consciousness - but do not delay antibiotics for it).
- Empirical IV antibiotics covering meningitis (e.g., ceftriaxone plus vancomycin per local protocol) and IV acyclovir if HSV encephalitis is possible - start within the hour.
- Resuscitation for sepsis (fluids, oxygen, lactate monitoring).
- Do not give paracetamol and discharge - this patient is septic and encephalopathic.
3. The lumbar puncture shows raised opening pressure, lymphocytic pleocytosis, high protein, and normal glucose. How does this change management?
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A lymphocytic pleocytosis with raised protein and normal-to-low glucose is consistent with viral or atypical meningoencephalitis - HSV is the key treatable cause, and TB meningitis is a possibility in endemic settings.
Management changes:
- Continue IV acyclovir at appropriate dose until HSV PCR is negative - do not stop early on the basis of CSF alone.
- Reassess antibiotics - if bacterial cultures are negative and the patient is stable, they may be narrowed or stopped, but only after clinical review.
- Consider TB meningitis if the setting is endemic or exposure history is present: send CSF for TB PCR/culture, consider starting anti-tuberculous therapy if the picture fits (subacute course, basal enhancement on imaging, low glucose).
- Supportive care: ICP management (head elevation, avoid hypoxia/hypercapnia), seizure control, and monitoring for deterioration.
The exam point: CSF results refine but rarely end the diagnostic process - clinical trajectory and repeat testing drive decisions.