Diagnosis of Crimean-Congo hemorrhagic fever

Abstract

Crimean-Congo hemorrhagic fever (CCHF) virus is the most extensive tick-borne virus, it causes a severe infection, which occurs widely in Africa, Eastern Europe and Asia. In recent years, the dramatic increase in the global distribution of CCHF, with the high mortality rates, highlights the importance of improving diagnostic capacity. Clinical and epidemiological data play a crucial role for early recognition of CCHF. However, CCHF is clinically difficult to diagnose and to distinguish, a rapid and reliable laboratory confirmation is necessary. Confirmation of infection in the acute phase of the disease can be made by detection of viral nucleic acid using reverse transcription-PCR, by demonstration of viral antigen or by virus isolation. In the convalescent phase of the disease, the diagnosis is confirmed by demonstration of an antibody response. The consideration of viral replication kinetics and antiviral humoral immune responses facilitates the selection of appropriate laboratory tests and accurate interpretation of laboratory findings.

Keywords:

• clinical diagnosis
• Crimean-Congo hemorrhagic fever
• epidemiological data
• laboratory diagnosis
• tick-borne virus

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Early diagnosis of Crimean-Congo hemorrhagic fever (CCHF) is essential for proper management of the patient and prevention of potential transmission to healthcare workers caring for the patient.

• Clinical and epidemiological data play a crucial role in early recognition of CCHF. The clinicians should think about CCHF when there is a sudden onset of febrile illness with a short incubation period, after exposure to tick bite, or blood or other tissues of infected livestock or human patients, especially in patients living in or visiting a CCHF endemic region.

• Since the symptoms, signs and laboratory abnormalities in the early phase of CCHF are nonspecific and can overlap with several diseases, the definitive diagnosis of CCHFV relies mainly on laboratory testing.

• Viral replication kinetics and antiviral humoral immune response, as well as clinical pathology, the onset date of symptoms, and outcome of the disease should be considered when selecting appropriate laboratory tests and interpreting laboratory findings.

• Viremia is usually detectable during the first week of illness (range 1–12 days), and viral nucleic acid (RNA) can be detectable in serum samples by RT-PCR for up to 18 days. Antibody response is generally detectable from about 7 days after the onset of disease and is rarely detectable in fatal cases of CCHF.

• Confirmation of infection in the acute phase of the disease can be made by detection of viral nucleic acid using RT-PCR, by virus isolation or by demonstration of viral antigen. In the convalescent phase of the disease, the diagnosis is confirmed by demonstration of an antibody response.

• Recent or current CCHF infection is confirmed by demonstration of seroconversion, a fourfold or greater rise in the titers of IgG antibody in paired sera, or the presence of IgM antibody in a single specimen.

• Due to difficulties in accurate establishment of the symptom onset time and duration of illness, the detection of viral RNA combined with detection of IgM antibodies is the most applied approach for diagnosis of CCHF.

Notes