Crimean-Congo hemorrhagic fever cases diagnosed during an outbreak of Sudan virus disease in Uganda, 2022-23

Abstract

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.

Fig 1. Map of Uganda showing the geographic location of Crimean-Congo hemorrhagic fever cases in relation to Sudan virus disease outbreak, September 2022- January 2023.

This map was created using QGIS, v 3.22.5, a free and open-source geographic information system available at: https://qgis.org/project/overview/. The Uganda map base layers were accessed from Humanitarian Data exchange v.1.83.2 (Uganda administrative boundaries - UGANDA BOUNDARIES SHAPEFILES AS OF 17 08 2018.zip - Humanitarian Data Exchange (humdata.org).

Fig 2. Trends of viral hemorrhagic fever suspected samples received and cases of Ebola disease (SUDV) and Crimean-Congo hemorrhagic fever identified between June 2022 to May 2023 at Uganda Virus Research Institute, Entebbe, Uganda.

Fig 3. Inferred evolutionary relationships for all available full length CCHFV genomes, including recent and historic CCHFV genomes from Uganda.

Historic (1956–2019) genomes are highlighted green, and recent (March-December 2022) genomes are highlighted blue. The S-segment phylogenetic tree contains two recent Ugandan-specific clades, in addition to a third clade containing two sequences from the 1950s and one from 2022. The M-segment phylogenetic tree includes Ugandan sequences split onto two clades. Two recent sequences (2022001211 and 2022005897) cluster with historic Ugandan sequences from the 1950s. While the L-segment phylogenetic tree includes a Uganda/DRC specific Africa 2 clade.