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Volume 30, Number 5—May 2024
CME ACTIVITY - Synopsis

Crimean-Congo Hemorrhagic Fever Virus for Clinicians—Diagnosis, Clinical Management, and Therapeutics

Maria G. FrankComments to Author , Gretchen Weaver, Vanessa Raabe1, and State of the Clinical Science Working Group of the National Emerging Pathogens Training and Education Center’s Special Pathogens Research Network2
Author affiliations: Denver Health and Hospital Authority, Denver, Colorado, USA (M.G. Frank); University of Colorado School of Medicine, Denver (M.G. Frank); University of Massachusetts Chan Medical School, Worchester, Massachusetts, USA (G. Weaver); New York University Grossman School of Medicine, New York, New York, USA (V. Raabe)

Main Article

Table

Advantages and disadvantages of various diagnostic tests for CCHFV*

Test selection Timing Advantages Disadvantages
Viral detection†
Viral culture‡ Early after symptom onset Detects a wide diversity of CCHFV strains Requires BSL-3 or BSL-4 laboratory, which are not readily available in endemic areas. Requires several days to yield a result.
NAAT, RT-PCR <10–12 days after symptom onset If samples are inactivated, then NAAT can be run in BSL-2 or BSL-3 facilities. Several multiplex assays available, and some can quantify viral load. Variable sensitivity depending on match between primers and infecting strain. Sensitivity and specificity can vary by geographic region.
Better sensitivity (80%) when PCR combinations used, e.g., rRT-PCR and conventional PCR or rRT-PCR and nested PCR (17).
Viral IgG detection
ELISA <5­–9 days after symptom onset Timely results. Viral inactivation can be performed. Requires less laboratory specialization. Decreased sensitivity after CCHFV antibodies are detectable.
Immunohistochemistry
 <5­–9 days after symptom onset
 Can assist in retrospective diagnosis for fatal cases.
 Requires biopsy or necropsy samples.
Immune response, serology
IgM ELISA§ or IFA¶ Detectable 7–9 days after symptom onset; peak 2–3 weeks; declines to low levels by month 4 ELISA sensitivity 87.8%, specificity 98.9.
IFA sensitivity 93.9%, specificity 100% (17). 		Commercially available kits for research but not for clinical laboratories; variable geographic sensitivity; IgM might not be detectable in fatal cases
IgG ELISA§, IFA¶, or Luminex xMAP Detectable 1–2 d after IgM, peaks 2 wks–5 mo; detectable for <3 y ELISA sensitivity 80.4%, specificity 100%.
IFA sensitivity 86.1% specificity 100% (17).		 Commercial ELISA and IFA kits available for research but not for clinical laboratories; variable geographic sensitivity; IgM might not be detectable in fatal cases
Neutralizing antibodies# >10 days after illness onset Can be performed in BSL-2 facilities Takes several days to perform. Not routinely used for diagnostic purposes.

*BSL, Biosafety Level; CCHFV, Crimean-Congo hemorrhagic fever virus; RT-PCR, reverse transcription PCR; rRT-PCR, real-time RT-PCR; Ddx, differential diagnoses; IFA: immunofluorescence assays; Nabs, neutralizing antibodies. †Recommended when patient is viremic. Could be performed as cell culture or intracerebral inoculation of mice. ‡RT-PCR could be real-time, conventional, nested or a combination §VectroCrimea-CHF (Vector-Best, https://en.vector-best.ru). ¶Crimean Congo Fever Mosaic 2 (Euroimmun, https://www.euroimmun.com). #Pseudoplaque or plaque reduction neutralization tests for CCHFV viral-like particles.

Main Article

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Main Article

1Current affiliation: Pfizer Inc., New York, New York, USA. These materials reflect only the personal views of the author and may not reflect the views of her employer.

2Members of this group are listed at the end of this article.

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The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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