What is the role of Total Leukocyte Count (TLC) and Differential Leukocyte Count (DLC) in diagnosing malaria?

Role of Total Leukocyte Count (TLC) and Differential Leukocyte Count (DLC) in Diagnosing Malaria

Total Leukocyte Count (TLC) and Differential Leukocyte Count (DLC) have limited diagnostic value for malaria and should not be relied upon as primary diagnostic tests, as microscopic examination of thick and thin blood films remains the gold standard for malaria diagnosis. 1

Laboratory Findings in Malaria

• Thrombocytopenia (<150,000/μL) is the most frequent and significant laboratory finding in malaria, observed in approximately 70-79% of cases regardless of Plasmodium species involved 1
• Thrombocytopenia has a sensitivity of 75% and specificity of 88% for malaria diagnosis, with a positive likelihood ratio of 5.6 1
• Due to its high predictive value, screening all thrombocytopenic samples with <100,000 platelets/μL has been suggested to avoid misdiagnosis of imported malaria in emergency departments 1
• Hyperbilirubinaemia (>1.2 mg/dL) is another laboratory finding with high likelihood ratio (7.3) for malaria diagnosis 1

Leukocyte Findings in Malaria

• While the guidelines do not specifically highlight TLC and DLC as primary diagnostic indicators for malaria, they may show certain patterns 1
• Malaria pigment may sometimes be observed in neutrophils and monocytes, which can serve as a clue to malaria infection, even when blood films are negative for parasites 1
• The presence of malaria pigment in white blood cells should prompt further specific testing for malaria 1

Gold Standard Diagnostic Methods

• Microscopic examination of thick and thin blood films (stained with Giemsa or May-Grunwald-Giemsa) remains the gold standard for diagnosing malaria 1
• Microscopy allows detection of parasites, identification of species, quantification of parasitemia, and differentiation between sexual and asexual forms 1
• Blood films should be examined by two observers, each viewing a minimum of 200 high-power fields 2
• For P. falciparum infections, the percentage of parasitized cells or number of parasites per microliter should be reported 2

Complementary Diagnostic Methods

• Rapid Diagnostic Tests (RDTs) detect parasite antigens (PfHRP2, PfLDH, pLDH, or aldolase) and provide results within 15 minutes 1, 3
• RDTs have high sensitivity (96%) for P. falciparum but may be less sensitive for non-falciparum species 3
• RDTs should be used as supplementary tests, especially when malaria diagnosis is performed by relatively inexperienced staff 2
• All positive RDTs should be confirmed by microscopic examination of blood films 1

Diagnostic Algorithm for Suspected Malaria

1. Initial assessment: Consider malaria in any patient with fever who has traveled to an endemic area 1
2. First-line laboratory tests:
   • Thick and thin blood films (gold standard) 1
   • Complete blood count (to check for thrombocytopenia) 1
   • Rapid diagnostic test as a complementary method 1, 3
3. Follow-up testing:
   • If initial tests are negative but clinical suspicion remains high, repeat blood films (at least 3 specimens drawn 12-24 hours apart) 1, 4
   • Consider molecular methods (PCR, LAMP) in specialized laboratories for confirmation 1

Common Pitfalls and Caveats

• Relying solely on TLC and DLC for malaria diagnosis may lead to missed diagnoses, as these are non-specific findings 1
• A single negative blood film does not exclude malaria; at least three negative films taken 12 hours apart are needed to rule out infection 1
• Recent antimalarial therapy may lead to false-negative results on initial testing 4
• RDTs may remain positive for several days after parasite clearance and should not be used to monitor treatment response 1
• Laboratories without expertise in species identification should make a preliminary diagnosis of "Plasmodium or Babesia parasites" and seek confirmatory testing at a reference laboratory 1