What is the initial approach to a patient presenting with intermittent fevers?

Initial Approach to Intermittent Fevers

Begin with a comprehensive travel history and immediate malaria testing if any tropical/subtropical exposure within the past year, as this is the most important potentially fatal cause that requires urgent diagnosis and treatment. 1

Critical First Steps

Travel History Assessment (If Applicable)

• Document exact locations visited, dates of travel and symptom onset, risk activities, timing of any rash relative to fever, immunization history, and malaria prophylaxis use on all laboratory request forms 1
• Malaria testing (both thick blood film and rapid diagnostic test simultaneously) must be performed immediately in all patients with fever who visited tropical/subtropical countries within the past year 1
• If initial malaria tests are negative but clinical suspicion remains, repeat testing: three thick films/RDTs over 72 hours are required to confidently exclude malaria 1
• Most Plasmodium falciparum cases present within 1 month of return but can occur up to 6 months later; other species can present up to a year or longer 1

Mandatory Initial Investigations (All Patients)

• At least two blood cultures should be obtained before starting any antibiotics 2
• Obtain at least one blood culture peripherally by venipuncture 2
• If central venous catheter present, obtain cultures from all lumens 2
• Complete blood count with differential 1
• Renal function and liver function tests 1
• Urinalysis (if clean-catch midstream specimen readily available) 2
• Chest radiography only if respiratory symptoms present 2

Physical Examination Focus

Key Examination Elements

• Meticulous examination for localizing signs including skin lesions, lymphadenopathy, cardiac murmurs, abdominal tenderness, and catheter sites 2
• Assess for rash pattern and distribution, particularly palms and soles involvement which suggests rickettsial infection or secondary syphilis 3
• Evaluate for petechiae/purpura which may indicate meningococcemia or Rocky Mountain spotted fever requiring immediate treatment 3
• Document presence of hepatosplenomegaly, joint involvement, or neurological abnormalities 1

Clinical Context-Specific Approach

If Recent Tropical/Subtropical Travel

Geographic-specific priorities:

• Sub-Saharan Africa: Highest priority is malaria (P. falciparum), also consider typhoid, rickettsial infections, and viral hemorrhagic fevers 1
• South/Southeast Asia: Highest incidence is typhoid/enteric fever, also common are dengue, scrub typhus, and malaria 1
• Start empirical ceftriaxone immediately without waiting for culture results when suspected typhoid with negative malaria tests in clinically unstable patients 1

If No Travel History

• Consider fever of unknown origin (FUO) criteria: temperature >38.3°C on several occasions, lasting ≥3 weeks, lacking clear diagnosis after initial evaluation 4, 5
• Main etiologies include infection (especially tuberculosis), malignancies (especially lymphoma), noninfectious inflammatory diseases (especially adult-onset Still's disease), and miscellaneous causes 4, 5
• Initial testing should evaluate for infectious etiologies, malignancies, inflammatory diseases, and miscellaneous causes such as venous thromboembolism and thyroiditis 4

If Neutropenic or Immunocompromised

• Lower threshold for hospitalization and empiric antimicrobial therapy 1
• May present with atypical or more severe manifestations 1
• Empirical broad-spectrum antibiotics indicated immediately in neutropenic patients 2
• Median time to defervescence with empirical antibiotics is 5 days in hematologic malignancies 2

Critical Pitfalls to Avoid

Do Not Delay Treatment

• Do not withhold empirical treatment while pursuing diagnosis in severely ill patients 1
• Start empirical antibiotics immediately for suspected meningococcemia, Rocky Mountain spotted fever, or typhoid 1
• For suspected RMSF, initiate doxycycline immediately regardless of patient age 3

Avoid Premature Antibiotic Changes

• Persistent fever alone in a stable patient is rarely an indication to alter the antibiotic regimen after 2-4 days 2
• Specific antimicrobial additions or changes should be guided by clinical change or culture results rather than fever pattern alone 2
• Median time to defervescence is 2-5 days depending on risk category; evaluate this timeline before making changes 2

Do Not Assume Low Risk

• Do not assume any geographic location is "low-risk" for tropical diseases 1
• Do not wait for negative malaria tests to start antibiotics in critically ill patients, as fever in returned travelers can be rapidly progressive and lethal 1

When to Consult Specialists

Immediate infectious disease/tropical medicine consultation indicated for:

• Suspected viral hemorrhagic fever 1
• Positive malaria films requiring confirmation and species-specific treatment 1
• Undiagnosed fever after initial workup 1
• Critically ill patients with tropical exposure 1

Reassessment Strategy

If Fever Persists After 3-5 Days

• Review all previous culture results 2
• Repeat meticulous physical examination 2
• Repeat chest radiography 2
• Ascertain status of vascular catheters 2
• Culture additional blood samples and specimens from specific sites 2
• Consider diagnostic imaging (CT, ultrasound) of suspected organs 2
• If patient remains febrile but clinically stable with no new findings, continue initial antibiotic regimen if neutropenia expected to resolve within 5 days 2

Advanced Imaging Considerations

• If erythrocyte sedimentation rate or C-reactive protein elevated and diagnosis not made after initial evaluation, 18F-fluorodeoxyglucose PET-CT may be useful 4
• CT imaging particularly sensitive for demonstrating parenchymal or pleural disease in posterior-inferior lung bases 2
• High-resolution CT valuable in immunocompromised patients for detecting small nodular or cavitary lesions 2