Crimean-Congo hemorrhagic fever cases diagnosed during an outbreak of Sudan virus disease in Uganda, 2022–23
Authors: Balinandi Stephen , Mulei Sophia , Whitmer Shannon , Nyakarahuka Luke , Cossaboom Caitlin M. , Shedroff Elizabeth , Morales-Betoulle Maria , Krapiunaya Inna , Tumusiime Alex , Kyondo Jackson , Baluku Jimmy , Namanya Dianah , Torach Calvin R. , Mutesi Joanita , Kiconco Jocelyn , Pimundu Godfrey , Muyigi Tonny , Rowland Jessica , Nsawotebba Andrew , Ssewanyana Isaac , Muwanguzi David , Kadobera Daniel , Harris Julie R. , Ario Alex R. , Atek Kagirita , Kyobe Henry B. , Nabadda Susan , Kaleebu Pontiano , Mwebesa Henry G. , Montgomery Joel M. , Shoemaker Trevor R. , Lutwama Julius J. , Klena John D. 
Published: October 2024

Background
In September 2022, Uganda experienced an outbreak of Sudan virus disease (SVD), mainly in central Uganda. As a result of enhanced surveillance activities for Ebola disease, samples from several patients with suspected viral hemorrhagic fever (VHF) were sent to the VHF Program at Uganda Virus Research Institute (UVRI), Entebbe, Uganda, and identified with infections caused by other viral etiologies. Herein, we report the epidemiologic and laboratory findings of Crimean-Congo hemorrhagic fever (CCHF) cases that were detected during the SVD outbreak response.

Methodology
Whole blood samples from VHF suspected cases were tested for Sudan virus (SUDV) by real-time reverse transcription–polymerase chain reaction (RT-PCR); and if negative, were tested for CCHF virus (CCHFV) by RT-PCR. CCHFV genomic sequences generated by metagenomic next generation sequencing were analyzed to ascertain strain relationships.

Principal findings
Between September 2022 and January 2023, a total of 2,626 samples were submitted for VHF testing at UVRI. Overall, 13 CCHF cases (including 7 deaths; case fatality rate of 53.8%), aged 4 to 60 years, were identified from 10 districts, including several districts affected by the SVD outbreak. Four cases were identified within the Ebola Treatment Unit (ETU) at Mubende Hospital. Most CCHF cases were males engaged in livestock farming or had exposure to wildlife (n = 8; 61.5%). Among confirmed cases, the most common clinical symptoms were hemorrhage (n = 12; 92.3%), fever (n = 11; 84.6%), anorexia (n = 10; 76.9%), fatigue (n = 9; 69.2%), abdominal pain (n = 9; 69.2%) and vomiting (n = 9; 69.2%). Sequencing analysis showed that the majority of identified CCHFV strains belonged to the Africa II clade previously identified in Uganda. Two samples, however, were identified with greater similarity to a CCHFV strain that was last reported in Uganda in 1958, suggesting possible reemergence.

Conclusions/Significance
Identifying CCHFV from individuals initially suspected to be infected with SUDV emphasizes the need for comprehensive VHF testing during filovirus outbreak responses in VHF endemic countries. Without expanded testing, CCHFV-infected patients would have posed a risk to health care workers and others while receiving treatment after a negative filovirus diagnosis, thereby complicating response dynamics. Additionally, CCHFV-infected cases could acquire an Ebola infection while in the ETU, and upon release because of a negative Ebola virus result, have the potential to spread these infections in the community.