What to do if a patient from Sudan with high suspicion of malaria has a negative blood film?

Management of Suspected Malaria with Negative Blood Film in a Patient from Sudan

For a patient from Sudan with high suspicion of malaria but a negative initial blood film, repeat blood films should be performed every 8 hours for 48 hours (option C) to ensure adequate detection of parasites.

Rationale for Serial Testing

The Infectious Diseases Society of America (IDSA) guidelines clearly state that repeat blood samples (≥3 specimens drawn 12–24 hours apart, ideally during febrile episodes) are indicated if the initial film is negative and malaria or babesiosis is strongly suspected 1. This recommendation is particularly important for patients with recent travel to endemic regions like Sudan.

Why a Single Negative Test Is Insufficient

• A significant proportion of malaria cases (nearly 7%) are missed on initial blood film examination 2
• Parasitemia can fluctuate throughout the day, with higher levels often occurring during febrile episodes
• Low-level parasitemia may be present below the detection threshold of a single examination
• Recent antimalarial medication use can temporarily suppress parasite levels while not eliminating the infection

Optimal Testing Strategy

Option C: Repeat Every 8 Hours for 48 Hours

This approach is superior because:

1. It provides multiple opportunities to detect parasites during their cyclical appearance in peripheral blood
2. The 48-hour timeframe covers the complete life cycle of most Plasmodium species
3. Testing during febrile episodes increases the likelihood of detecting parasites
4. It aligns with the IDSA recommendation for at least 3 specimens over a 12-24 hour period 1

Why Not Just Repeat a Single Thick or Thin Film?

• Option A (Repeat thin film): While thin films provide better morphology for species identification, they contain 10-20 times less blood than thick films, making them less sensitive for initial detection 3
• Option B (Repeat thick film): Although thick films are more sensitive than thin films, a single repeat examination still risks missing parasites due to their cyclical appearance in peripheral blood

Examination Technique Considerations

For optimal results when examining blood films:

• Both thick and thin films should be prepared and examined 1
• The laboratorian should examine a minimum of 100 microscopic fields using the 100× objective before reporting a specimen as negative 1
• Additional fields (at least 300) should be examined for patients without previous Plasmodium exposure 1
• Consider the "scratch method" for preparing thick films to improve adherence and prevent sloughing during staining 3

Additional Diagnostic Considerations

If serial blood films remain negative despite high clinical suspicion:

• Consider rapid diagnostic tests (RDTs) as a complementary method, though they may be less sensitive than thick blood films for non-falciparum infections 1
• Nucleic acid amplification tests (NAATs) offer 10-100 times more sensitivity than microscopy and can be useful when blood films are negative 4
• Look for indirect signs of malaria such as thrombocytopenia or malaria pigment in neutrophils and monocytes 1

Important Clinical Caveat

If the patient shows signs of severe illness and cerebral malaria seems likely, do not delay treatment while awaiting diagnostic confirmation. The British Paediatric Allergy, Immunology and Infection Group guidelines recommend that if cerebral malaria seems likely and there will be a delay in obtaining the malaria film result, anti-malarial treatment should be considered and specialist advice obtained 1.

Remember that malaria, particularly falciparum malaria, can rapidly progress to severe disease with significant morbidity and mortality if treatment is delayed.