Comparison Of Diagnostic Performances Of Ten Different Immunoassays Detecting Anti-Cchfv Igm And Igg Antibodies From Acute To Subsided Phases Of Crimean-Congo Hemorrhagic Fever

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a geographically widespread tick-borne arbovirus that has been recognized by the WHO as an emerging pathogen needing urgent attention to ensure preparedness for potential outbreaks. Therefore, availability of accurate diagnostic tools for identification of acute cases is necessary.A panel comprising 121 sequential serum samples collected during acute, convalescent and subsided phase of PCR-proven CCHFV infection from 16 Kosovar patients was used to assess sensitivity. Serum samples from 60 healthy Kosovar blood donors were used to assess specificity. All samples were tested with two IgM/IgG immunofluorescence assays (IFA) from BNITM, the CCHFV Mosaic 2 IgG and IgM indirect immunofluorescence tests (IIFT) from EUROIMMUN, two BlackBox ELISAs for the detection of CCHFV-specific IgM and IgG antibodies (BNITM), two Anti-CCHFV ELISAs IgM and IgG from EUROIMMUN using recombinant structural proteins of CCHFV antigens, and two ELISAs from Vector-Best (IgM: mu-capture ELISA, IgG: indirect ELISA using immobilized CCHFV antigen). Diagnostic performances were compared between methods using sensitivity, specificity, concordance and degree of agreement with particular focus on the phase of the infection.In early and convalescent phases of infection, the sensitivities for detecting specific IgG antibodies differed for the ELISA test. The BlackBox IgG ELISA yielded the highest, followed by the EUROIMMUN IgG ELISA and finally the VectorBest IgG ELISA with the lowest sensitivities. In the subsided phase, the VectorBest IgM ELISA detected a high rate of samples that were positive for anti-CCHFV IgM antibodies. Both test systems based on immunofluorescence showed an identical sensitivity for detection of anti-CCHFV IgM antibodies in acute and convalescent phases of infection.Available serological test systems detect anti-CCHFV IgM and IgG antibodies accurately, but their diagnostic performances vary with respect to the phase of the infection.Author summaryThe Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is the geographically most widespread tick-borne arbovirus and it is endemic in several countries. Because of its high case fatality rates, its potential for nosocomial outbreaks and the difficulties in treatment and prevention, CCHFV has been included in the WHO's R&D Blueprint for Action to Prevent Epidemics. For fast implementation of infection control measures in CCHFV-affected countries, reliable diagnosis utilizing qualified molecular and serological tests is essential.Here we compared diagnostic performances of ten serological tests based on detection of IgM and IgG antibodies against CCHFV using samples from CCHFV patients and samples from healthy blood donors collected in Kosovo. The analyses focused on the phase of infection, because IgM and IgG tests have differing intended purposes. We concluded that the tests are suitable for accurate detection of anti-CCHFV IgM and IgG antibodies, but varied in their respective diagnostic performances with respect to the phase of the infection. IgM tests are mainly intended to support the diagnosis of acute infections and performed well in the early and convalescent phases of infection. IgG tests become relevant at later stages of disease progression and for disease surveillance and reached highest sensitivities in the subsided phase of infection.