What labs should be ordered to rule out chronic infection in an immunocompromised person?

Diagnostic Laboratory Testing for Chronic Infections in Immunocompromised Patients

In immunocompromised patients with suspected chronic infection, a broad diagnostic approach using invasively obtained specimens is strongly recommended, with testing tailored to the specific immune defect and clinical presentation. 1

Core Laboratory Tests for All Immunocompromised Patients

Blood Tests

• Complete blood count with differential
• Blood cultures (at least two sets)
  • Essential for patients with signs of septicemia, systemic manifestations, or fever of unknown origin 1
• HIV testing (if status unknown)
• Liver function tests
• Renal function tests

Microbiological Testing

• Viral Studies:

  • CSF PCR for HSV 1 & 2, VZV, and enteroviruses
  • CSF PCR for EBV and CMV
  • EBV viral load in peripheral blood (for suspected lymphoproliferative disease) 1
  • HHV-6 and HHV-7 PCR (if clinically indicated) 1
  • JC/BK virus PCR (if neurological symptoms present) 1

• Bacterial Studies:

  • CSF acid-fast bacillus staining and culture for Mycobacterium tuberculosis
  • CSF and blood culture for Listeria monocytogenes
  • First morning sputum for culture (for respiratory symptoms) 1

• Fungal Studies:

  • Indian ink staining and/or cryptococcal antigen (CRAG) testing of CSF and serum
  • Fungal cultures from appropriate specimens
  • Consider testing for Coccidioides species and Histoplasma species 1
  • Note: Cross-reactivity can occur between fungal antigen tests (e.g., Talaromyces marneffei may cross-react with Histoplasma and Blastomyces tests) 2

• Parasitic Studies:

  • Antibody testing for Toxoplasma gondii in serum and CSF PCR if positive 1
  • For persistent diarrhea: stool examination for Cryptosporidium, Cyclospora, Cystoisospora, and microsporidia 1

Imaging Studies

• MRI should be performed promptly in patients with neurological symptoms 1
• Chest imaging for respiratory symptoms

Tailored Testing Based on Clinical Presentation

Neurological Symptoms

• Lumbar puncture for CSF analysis (cell count, protein, glucose)
• CSF testing as outlined above
• Consider antibody-mediated encephalitis testing 1

Gastrointestinal Symptoms

• Stool testing for bacterial pathogens (Salmonella, Shigella, Campylobacter, Yersinia, C. difficile, STEC)
• For AIDS patients with persistent diarrhea: additional testing for Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex, and cytomegalovirus 1
• Consider endoscopic biopsies for tissue diagnosis

Respiratory Symptoms

• First morning sputum cultures
• Bronchoscopy with bronchoalveolar lavage for culture and PCR testing
• Consider testing for mycobacterial and fungal pathogens in cystic fibrosis patients 1

Important Considerations

Specimen Collection

• Blood cultures should not be obtained through indwelling vascular devices if possible 3
• Calcium alginate swabs are not acceptable for nucleic acid amplification testing 1
• Contact the laboratory for specific instructions prior to collection for fastidious pathogens 1

Interpretation Challenges

• CSF may be acellular despite infection in immunocompromised patients 1
• False negative results are more common in immunocompromised patients
• Multiple-pathogen nucleic acid amplification tests detect DNA, not necessarily viable organisms 1

Common Pitfalls to Avoid

1. Not testing broadly enough - Immunocompromised patients can harbor unusual or multiple pathogens simultaneously
2. Relying solely on non-invasive specimens - Invasively obtained specimens often provide higher diagnostic yield
3. Stopping the workup after one positive result - Co-infections are common in immunocompromised hosts
4. Dismissing low-virulence organisms - Organisms typically considered contaminants can cause true infection in immunocompromised patients 3
5. Waiting for fever or leukocytosis - Immunocompromised patients may not mount typical inflammatory responses; infection should be considered even without fever or elevated white blood cell count 1

Algorithm for Diagnostic Approach

1. Assess type and severity of immunocompromise (HIV/AIDS, transplant, cancer, etc.)
2. Evaluate clinical presentation and target organ systems
3. Obtain appropriate specimens for culture and molecular testing
4. Consider invasive procedures for tissue diagnosis when non-invasive tests are negative
5. Repeat testing if clinical suspicion remains high despite negative initial results

By following this comprehensive diagnostic approach, clinicians can effectively identify chronic infections in immunocompromised patients, leading to appropriate treatment and improved outcomes.