Risk-Factors of Crimean-Congo Haemorrhagic Fever Across Six Tertiary Hospitals in Afghanistan from 2022 to 2025: Reported Exposures, Healthcare-Worker Clustering, and Ribavirin Treatment-Timing Analyses

Introduction

Crimean-Congo haemorrhagic fever (CCHF) is endemic in Afghanistan, but multi-hospital data characterising reported exposure patterns, healthcare-worker clustering, and ribavirin-mortality associations after accounting for treatment timing are lacking.

Methods

A retrospective cohort study included 737 laboratory-confirmed CCHF patients admitted to six tertiary hospitals in Afghanistan between January 2022 and December 2025. Reported exposures were assessed by occupation and tick-contact history. Clustering of healthcare-worker (HCW) infections during high caseload was assessed by permutation testing. Ribavirin-mortality association was assessed using multivariable Cox regression adjusted for clinical severity, age, sex, hospital, and comorbidity, with sensitivity analyses addressing treatment timing immortal-time bias.

Results

Among 737 patients, the median age was 35 years and 78.3% were male. The hospitalization fatality ratio (HFR) was 27.7% (204/737). Of 574 patients with recorded occupation: 33.6% were livestock handlers, 12.9% slaughterhouse workers or butchers, 24.9% household meat preparers, and only 11.1% reported tick exposure. Nineteen patients were HCWs, and 18 became infected during periods of concurrent CCHF admissions, and clustering exceeded chance (p=0.012), consistent with healthcare-associated exposure during surges. Personal protective equipment (PPE) was used in 728 (98.6%) admissions, but its composition was incomplete: 532 (72.2%) comprised mask and gloves without a gown, and only 205 (27.8%) with mask, gloves, and gown. Isolation rooms were available for only 274 of 737 admissions (37.2%). Among 727 patients in the ribavirin analysis, 85.0% received treatment. Conventional analysis suggested lower mortality (adjusted HR 0.57) but affected by immortal-time bias. The association weakened for same-day treatment versus no treatment (HR 0.63, 95% CI 0.41–0.96; sensitive to model specification) and was absent in time-varying analysis (HR 0.93).

Conclusion

CCHF in this hospitalised Afghan cohort was commonly associated with reported animal and livestock-related exposure, while healthcare-worker infections clustered during outbreak surges. Isolation capacity and caseload may be important correlates of healthcare-associated risk alongside PPE availability. Ribavirin findings were sensitive to treatment-timing adjustment and cannot establish a causal survival benefit.

Key Questions

• What is already known on this topic

  • CCHF is endemic in Afghanistan, but previous studies lacked individual-level multi-hospital data on reported transmission exposures, formal assessment of healthcare-worker clustering, and ribavirin treatment-timing analyses, while evidence from other endemic countries has been inconsistent.

• What this study adds

  • In 737 laboratory-confirmed cases across six tertiary hospitals, reported animal and livestock-related exposure was far more common than reported tick exposure, healthcare-worker infections clustered significantly during periods of high CCHF caseload and where isolation capacity was limited, and the apparent mortality benefit of ribavirin was substantially attenuated after accounting for treatment timing and immortal-time bias.

• How this study might affect research, practice or policy

  • The findings support stronger public health interventions such as One Health prevention at the animal-human interface, investment in dedicated isolation capacity together with complete PPE during outbreak surges, protective equipment during slaughter and butchering, veterinary surveillance of viraemic livestock, and risk-reduction before Eid-al-Adha.