What is the significance of Total Leukocyte Count (TLC) and Differential Leukocyte Count (DLC) in typhoid fever?

Significance of TLC and DLC in Typhoid Fever

In typhoid fever, the most significant CBC findings are leukopenia (low white blood cell count) with relative lymphocytosis, though this pattern is only present in about 25% of cases. Monocytosis is also commonly observed and highly suggestive of typhoid fever.

Characteristic CBC Findings in Typhoid Fever

• Total Leukocyte Count (TLC): Leukopenia (WBC count <10,000 cells/mm³) is present in approximately 25% of typhoid fever cases, not the majority as traditionally believed 1, 2
• Differential Leukocyte Count (DLC): Neutropenia with relative lymphocytosis is the classic pattern, though absolute lymphocytosis is rare 3, 2
• Monocytosis: Predominance of monocytes is highly suggestive of intracellular pathogens like Salmonella Typhi 3
• Platelet count: Thrombocytopenia may be present 3

Diagnostic Significance

• A normal to low WBC count (<10,000 cells/mm³) in a febrile patient with appropriate travel or exposure history significantly increases the likelihood of typhoid fever (odds ratio 30.2) 2
• Leukocytosis (WBC >14,000 cells/mm³) strongly argues against typhoid fever diagnosis (odds ratio 0.03) 2
• CBC findings alone are insufficient for diagnosis but can guide further testing 3
• Blood culture remains the gold standard diagnostic test for typhoid fever 3, 4

Clinical Implications

• Higher white cell counts (>8,000 cells/mm³) in typhoid fever are associated with increased complication rates (up to 70%) 1
• Hemophagocytosis in bone marrow may be responsible for the hematological abnormalities in typhoid fever, including neutropenia, anemia, and thrombocytopenia 5
• Cell-mediated immune response is critical for recovery in typhoid fever, with complicated cases showing imbalances in T lymphocyte subpopulations 6

Comparison with Viral Fevers

• Both typhoid fever and viral fevers can present with leukopenia, making differentiation challenging 3
• Monocytosis is more suggestive of typhoid fever, while viral fevers typically show lymphocytic predominance 3
• Persistent fever with relative bradycardia and normal to low WBC count should raise suspicion for typhoid fever in patients returning from endemic areas 3

Diagnostic Algorithm

1. Obtain complete blood count with differential in all patients with suspected infection 7
2. Consider typhoid fever if:
   • Normal to low WBC count (<10,000 cells/mm³) 2
   • Neutropenia with relative lymphocytosis 3, 2
   • Monocytosis 3
   • History of travel to endemic areas or appropriate exposure 7
3. Proceed to confirmatory testing:
   • Blood cultures (at least two sets before antibiotics) 7
   • Bone marrow culture if blood cultures are negative or antibiotics have been administered 3

Pitfalls to Avoid

• Relying solely on the classic finding of leukopenia, as it occurs in only about 25% of typhoid fever cases 1, 2
• Dismissing typhoid fever in patients with normal WBC counts 1
• Using serologic tests like the Widal test for diagnosis due to poor performance characteristics 3, 4
• Failing to consider typhoid fever in patients with persistent fever and normal to low WBC counts, especially with relevant travel history 7