What are the characteristic findings on a blood picture in a case of suspected fungal infection?

Blood Picture in Fungal Infection

The blood picture in fungal infection is typically nonspecific and cannot reliably differentiate fungal from bacterial sepsis, but specific serological biomarkers including (1,3)-β-D-glucan, galactomannan antigen, and mannan antigen/antibodies provide the most useful blood-based diagnostic information. 1

Routine Hematologic Findings (Nonspecific)

The standard complete blood count findings in invasive fungal infections are indistinguishable from bacterial infections and include: 1

• Thrombocytopenia (platelet count <100,000/mm³) - common but nonspecific 1
• Leukocytosis or abnormal white blood cell count - variable and nonspecific 1
• Elevated C-reactive protein (CRP) - nonspecific inflammatory marker 1
• Prolonged granulocytopenia (<0.5 × 10⁹/L for >10 days) - represents a risk factor rather than a diagnostic finding 2

Critical pitfall: Bacterial and fungal bloodstream infections cannot be clinically or hematologically differentiated based on routine blood counts alone. 1

Specific Serological Biomarkers (Diagnostic)

(1,3)-β-D-Glucan (BDG)

BDG is the most broadly useful blood biomarker for invasive fungal infections, detecting Candida, Aspergillus, Fusarium, Acremonium, and Pneumocystis species. 1

• Sensitivity: 81-89% and specificity: 60-80% depending on threshold used 1, 3
• At 120 pg/mL threshold: sensitivity 81% (71-88%), specificity 80% (67-88%) 1
• For proven neonatal invasive candidiasis: sensitivity reaches 99% (93-100%) 1
• Routine screening recommended in high-risk hematological patients 1
• Important limitation: BDG is typically low or absent in cryptococcal infections and absent in mucormycosis (Mucorales do not produce β-D-glucan) 1
• False positives can occur from β-glucans in plastic tubes, water, or dust 1

Galactomannan (GM) Antigen for Aspergillosis

For invasive aspergillosis in immunocompromised patients, serum galactomannan is highly specific and should be used for routine screening. 1

• Serum GM sensitivity: 71% (64-78%) and specificity: 89% (84-92%) 3
• Optimal cutoff: 1.0 optical density index 3
• Specificity: 90-100% and sensitivity: 80-100% in granulocytopenic patients 1
• Negative predictive value >90% for excluding invasive aspergillosis 1
• May be positive before clinical suspicion and useful for monitoring therapeutic response 1
• Routine antigen detection with galactomannan ELISA is advisable in high-risk patients 1

Mannan Antigen and Anti-Mannan Antibodies for Candidiasis

Combined mannan antigen and anti-mannan antibody testing significantly improves diagnostic accuracy for invasive candidiasis compared to either test alone. 1

• Mannan antigen alone: sensitivity 58% (53-62%), specificity 93% (91-94%) 1
• Anti-mannan antibodies alone: sensitivity 59% (54-65%), specificity 83% (79-97%) 1
• Combined Mn/A-Mn: sensitivity 83% (79-87%), specificity 86% (82-90%) 1
• Time advantage: positive 6-7 days before blood culture results in 73% of candidemia cases 1
• In hepatosplenic candidiasis: 86% had positive results at median 16 days before radiological detection 1
• Sensitivity varies by species: highest for C. albicans, followed by C. glabrata and C. tropicalis 1

Cryptococcal Antigen

Cryptococcal antigen detection in blood and/or CSF is highly indicative (>95% sensitivity) of cryptococcal meningitis and should be tested in parallel. 1

• Both serum and CSF should be tested simultaneously 1
• Highly reliable in both AIDS patients and hematological malignancy patients 1

Blood Culture Findings

Blood cultures remain the gold standard for proven invasive candidiasis but have poor sensitivity (21-71% in adults, even lower in neonates) and require 2-5 days for results. 1, 4

• Neonatal samples often <1 mL, further reducing sensitivity 1
• Cultures should be obtained before antibiotics from normally sterile sites 4
• Moulds (Aspergillus) are more difficult to isolate than Candida species from blood 1

Diagnostic Algorithm

1. Obtain blood cultures immediately before starting antifungal therapy 4
2. Order (1,3)-β-D-glucan as broad screening test for most invasive fungal infections (except Cryptococcus and Mucorales) 1
3. Add galactomannan if invasive aspergillosis suspected in immunocompromised patients 1
4. Add combined mannan antigen/anti-mannan antibodies if invasive candidiasis suspected 1
5. Add cryptococcal antigen (serum and CSF) if meningitis suspected 1
6. Do NOT rely on routine CBC parameters (WBC, platelets, CRP) to differentiate fungal from bacterial infection 1

Critical caveat: Antibody tests for Aspergillus are frequently undetectable in immunocompromised patients and should not be used. 1