Identification of clinical, laboratory, and epidemiological characteristics to accelerate diagnosis of Crimean-Congo Hemorrhagic Fever in patients presenting to health centres in low-resource endemic settings: a systematic literature review

Background

Crimean-Congo Hemorrhagic Fever (CCHF) is a viral hemorrhagic fever caused by an orthonairovirus transmitted to humans by infected ticks. The incidence of CCHF is vastly underestimated, in part due to frequent misdiagnosis and poor surveillance infrastructure in endemic regions. The nonspecific presentation of CCHF makes diagnosis very challenging, especially in low-resource settings where diagnostic technologies, such as PCR, are scarce. The present study aimed to identify simple clinical, laboratory, and epidemiological characteristics that are predictive of CCHF diagnosis in the early stages of disease progression and have the potential to bridge this technological gap.

Methodology

A systematic search was conducted in Medline, Embase, Global Health, PubMed, and the Cochrane Library to identify eligible articles (PROSPERO ID: CRD42023434872). Studies comparing the characteristics of suspected CCHF-positive and CCHF-negative groups in countries where CCHF is endemic were included. Titles and abstracts were screened, with eligible full texts being reviewed by two reviewers. Included studies underwent data extraction of patient characteristics found to be present in significantly different levels in CCHF-positive patients. Odds ratios were calculated where possible.

The search identified 2,585 scientific studies, 14 of which were selected for this review. A total of 2,025 participants were included in the final analysis. Patient characteristics found to be most predictive of CCHF diagnosis were: transaminitis, headache, nausea/vomiting, CK elevation, fever, LDH elevation and recorded tick bites. In addition, leukopenia and thrombocytopenia were found to be especially predictive of CCHF diagnosis.

Conclusions

This review summarises characteristics of CCHF patients that may be of diagnostic utility. Similar findings in the literature support this study, although there are notable limitations concerning study design heterogeneity. These findings may be used to inform interim guidance until sensitive diagnostic technologies are made more available in remote/low-resource areas.

Author Summary

Crimean-Congo Hemorrhagic Fever (CCHF) is a serious infection caused by a virus that is spread through tick bites. It is often misdiagnosed as early symptoms are non-specific. Diagnostic tools are also limited in regions where the disease is common.

We carried out a systematic review of published studies to find out whether there are simple signs, symptoms, and routine blood test results that can help distinguish patients with this infection from other illnesses.

From over 2,000 studies identified, 14 were selected. The review found several key predictors of CCHF, including headache, nausea/vomiting, fever, elevated liver enzymes and recent tick bites. The strongest predictors of CCHF, however, were lower white blood cell and platelet counts in patients with CCHF.

Our findings bring together available evidence on practical indicators that could help frontline health workers recognise this neglected disease more quickly, especially in areas where advanced testing is not available.