Molecular characterization of the 2022 Sudan virus disease outbreak in Uganda

Uganda experienced five Ebola disease outbreaks caused by Bundibugyo virus (n = 1) and Sudan virus (SUDV) (n = 4) from 2000 to 2021. On 20 September 2022, Uganda declared a fifth Sudan virus disease outbreak in the Mubende district, resulting in 142 confirmed and 22 probable cases by the end of the outbreak declaration on 11 January 2023. The earliest identified cases, through retrospective case investigations, had onset in early August 2022. From the 142 confirmed cases, we performed unbiased (Illumina) and SUDV-amplicon-specific (Minion) high-throughput sequencing to obtain 120 SUDV genome-and coding-complete sequences, representing 95.4% (104/109) of SVD-confirmed individuals within a sequence-able range (Ct ≤30) and 10 genome sequences outside of this range and 6 duplicate genome sequences. A comparison of the nucleotide genetic relatedness for the newly emerged Mubende variant indicated that it was most closely related to the Nakisamata SUDV sequence from 2011, represented a likely new zoonotic spillover event, and exhibited an inter- and intra-outbreak substitution rate consistent with previous outbreaks. The most recent common ancestor for the Mubende variant was estimated to have occurred in October and November 2021. The Mubende variant glycoprotein amino acid sequences exhibited 99.7% similarity altogether and a maximum of 96.1% glycoprotein similarity compared to historical SUDV strains from 1976. Integrating the genetic sequence and epidemiological data into the response activities generated a broad overview of the outbreak, allowing for quick fact-checking of epidemiological connections between the identified patients. IMPORTANCE: Ebola disease (EBOD) is a public health threat with a high case fatality rate. Most EBOD outbreaks have occurred in remote locations, but the 2013–2016 Western Africa outbreak demonstrated how devastating EBOD can be when it reaches an urban population. Here, the 2022 Sudan virus disease (SVD) outbreak in Mubende District, Uganda, is summarized, and the genetic relatedness of the new variant is evaluated. The Mubende variant exhibited 96% amino acid similarity with historic SUDV sequences from the 1970s and a high degree of conservation throughout the outbreak, which was important for ongoing diagnostics and highly promising for future therapy development. Genetic differences between viruses identified during the Mubende SVD outbreak were linked with epidemiological data to better interpret viral spread and contact tracing chains. This methodology should be used to better integrate discrete epidemiological and sequence data for future viral outbreaks.