Investigations
1st investigations to order
reverse transcription-polymerase chain reaction (RT-PCR)
Test
Should be ordered in all patients with suspected CCHF infection while the patient is in isolation.
Returns result 24-48 hours before serology.
In developed settings, the test may be available only in regional or national laboratories that have category 4 facilities.
If negative, the test should be repeated within 48 hours because viral load is low and can be undetectable early in the course of the illness. Negative tests should be repeated to rule out a diagnosis if it is strongly suspected (or to confirm resolution of infection).
Result
positive for CCHF virus RNA
malaria investigations
Test
Indicated in malaria-endemic areas or when indicated from travel history.
Giemsa-stained thick and thin blood smears and rapid diagnostic tests are the tests of choice for malaria screening.
May be positive if co-infection.
Result
negative
Investigations to consider
serology
Test
Seroconversion with detection of anti-CCHF virus IgM antibodies or a ≥fourfold increase in antibody titre between two successive blood samples is evidence of a recent infection.[16][17][69]
ELISA is commonly used and has a sensitivity greater than 90%. It has been reported to be more sensitive than immunofluorescence assay (IFA).[71] All native antigens have to be produced in a biosafety level (BSL)-4 laboratory and irradiated prior to use.
IgM and IgG antibodies are usually detected 4-5 days after the onset of symptoms. The maximum IgM titre is at 2-3 weeks after onset of the disease, and generally normalises within 4 months. IgG antibodies remain detectable for several years.[72]
Result
positive for CCHF virus
FBC
Test
Decrease in platelet count and marked lymphopenia can be seen in the initial stages of infection; however, this is not diagnostic. Often followed by neutrophil leukocytosis, along with normalisation of thrombocytopenia. Leukocytosis may persist and show immature forms.
Patients with severe disease may show a progressive decline in platelet count as a manifestation of disseminated intravascular coagulation (DIC).
Result
thrombocytopenia; marked lymphopenia; leukocytosis; decreased haemoglobin (if bleeding manifestations in the later phase of the disease)
coagulation studies
Test
Prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT) is associated with more severe infection and bleeding manifestations such as DIC.
Result
prolonged bleeding time; elevated fibrin degradation products; decreased fibrinogen
LFTs
Test
Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are usually elevated; however, most studies show that AST rises out of proportion to ALT, and this is more suggestive of systemic tissue damage rather than hepatocellular injury.
Abnormal liver function may lead to a poor prognosis.[73]
Result
elevated
serum creatinine and urea
Test
May indicate acute kidney injury.
Especially useful in patients with diarrhoea and vomiting.
Result
may be elevated
urinalysis
Test
Haematuria or proteinuria may be seen in severe disease.
Oliguria that does not respond to fluid resuscitation is a poor prognostic sign.
Result
may show haematuria or proteinuria
serum electrolytes
Test
May be abnormal and may indicate acute kidney injury.
Especially useful in patients with diarrhoea and vomiting.
Useful to guide correction of electrolytes and fluid replacement.
Result
may be deranged
lactate dehydrogenase
Test
A level >4 mmol/L (36 mg/dL) may indicate persistent hypo-perfusion and sepsis.[40]
Result
may be elevated
creatine phosphokinase
Test
Levels more than twice the upper limit of normal may indicate systematic muscular stress.
Result
may be elevated
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