Genomic and Transmission Dynamics of the 2024 Marburg Virus Outbreak in Rwanda

The ongoing outbreak of Marburg virus disease in Rwanda marks the third largest historically, although it has shown the lowest fatality rate. Genomic analysis of samples from 18 cases identified a lineage with limited internal diversity, closely related to a 2014 Ugandan case. Our findings suggest that the Rwandan lineage diverged decades ago from a common ancestor shared with diversity sampled from bats in Uganda. Our genomic data reveal limited genetic variation, consistent with a single zoonotic transmission event and limited human-to-human transmission. Investigations including contact tracing, clinical assessments, sequencing and serology, linked the index case to a mining cave inhabited by Rousettus aegyptiacus. Serology tests identified three individuals seropositive for immunoglobulin G and immunoglobulin M, further supporting the zoonotic origin of the outbreak through human-animal interactions.

References

Abir M, Rahman T, Das A, Naznin Etu S, Nafiz I, Rakib A . Pathogenicity and virulence of Marburg virus. Virulence. 2022; 13(1):609-633. PMC: 8986239. DOI: 10.1080/21505594.2022.2054760. View

Mehedi M, Groseth A, Feldmann H, Ebihara H . Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011; 6(9):1091-1106. PMC: 3201746. DOI: 10.2217/fvl.11.79. View

Srivastava S, Sharma D, Kumar S, Sharma A, Rijal R, Asija A . Emergence of Marburg virus: a global perspective on fatal outbreaks and clinical challenges. Front Microbiol. 2023; 14:1239079. PMC: 10526840. DOI: 10.3389/fmicb.2023.1239079. View

Towner J, Amman B, Sealy T, Carroll S, Comer J, Kemp A . Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog. 2009; 5(7):e1000536. PMC: 2713404. DOI: 10.1371/journal.ppat.1000536. View

Nyakarahuka L, Ojwang J, Tumusiime A, Balinandi S, Whitmer S, Kyazze S . Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014. Emerg Infect Dis. 2017; 23(6):1001-1004. PMC: 5443453. DOI: 10.3201/eid2306.170047. View

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

Carroll S, Towner J, Sealy T, McMullan L, Khristova M, Burt F . Molecular evolution of viruses of the family Filoviridae based on 97 whole-genome sequences. J Virol. 2012; 87(5):2608-16. PMC: 3571414. DOI: 10.1128/JVI.03118-12. View

Chen S . Ultrafast one-pass FASTQ data preprocessing, quality control, and deduplication using fastp. Imeta. 2024; 2(2):e107. PMC: 10989850. DOI: 10.1002/imt2.107. View

Li H . Minimap2: pairwise alignment for nucleotide sequences. Bioinformatics. 2018; 34(18):3094-3100. PMC: 6137996. DOI: 10.1093/bioinformatics/bty191. View

10.

Wei H, Audet J, Wong G, He S, Huang X, Cutts T . Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time. Sci Rep. 2017; 7(1):3390. PMC: 5469859. DOI: 10.1038/s41598-017-03318-3. View

11.

Katoh K, Standley D . MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013; 30(4):772-80. PMC: 3603318. DOI: 10.1093/molbev/mst010. View

12.

Sagulenko P, Puller V, Neher R . TreeTime: Maximum-likelihood phylodynamic analysis. Virus Evol. 2018; 4(1):vex042. PMC: 5758920. DOI: 10.1093/ve/vex042. View

13.

Scarpa F, Bazzani L, Giovanetti M, Ciccozzi A, Benedetti F, Zella D . Update on the Phylodynamic and Genetic Variability of Marburg Virus. Viruses. 2023; 15(8). PMC: 10458864. DOI: 10.3390/v15081721. View

14.

Raab M, Pfadenhauer L, Millimouno T, Hoelscher M, Froeschl G . Knowledge, attitudes and practices towards viral haemorrhagic fevers amongst healthcare workers in urban and rural public healthcare facilities in the N'zérékoré prefecture, Guinea: a cross-sectional study. BMC Public Health. 2020; 20(1):296. PMC: 7059383. DOI: 10.1186/s12889-020-8433-2. View

15.

Amman B, Carroll S, Reed Z, Sealy T, Balinandi S, Swanepoel R . Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection. PLoS Pathog. 2012; 8(10):e1002877. PMC: 3464226. DOI: 10.1371/journal.ppat.1002877. View

16.

Edwards M, Johnson B, Mire C, Xu W, Shabman R, Speller L . The Marburg virus VP24 protein interacts with Keap1 to activate the cytoprotective antioxidant response pathway. Cell Rep. 2014; 6(6):1017-1025. PMC: 3985291. DOI: 10.1016/j.celrep.2014.01.043. View

17.

Towner J, Khristova M, Sealy T, Vincent M, Erickson B, Bawiec D . Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. J Virol. 2006; 80(13):6497-516. PMC: 1488971. DOI: 10.1128/JVI.00069-06. View

18.

Bouckaert R, Heled J, Kuhnert D, Vaughan T, Wu C, Xie D . BEAST 2: a software platform for Bayesian evolutionary analysis. PLoS Comput Biol. 2014; 10(4):e1003537. PMC: 3985171. DOI: 10.1371/journal.pcbi.1003537. View

19.

Minh B, Schmidt H, Chernomor O, Schrempf D, Woodhams M, von Haeseler A . IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era. Mol Biol Evol. 2020; 37(5):1530-1534. PMC: 7182206. DOI: 10.1093/molbev/msaa015. View

20.

Amman B, Schuh A, Albarino C, Towner J . Marburg Virus Persistence on Fruit as a Plausible Route of Bat to Primate Filovirus Transmission. Viruses. 2021; 13(12). PMC: 8708721. DOI: 10.3390/v13122394. View