Clade I Mpox virus genomic diversity in the Democratic Republic of the Congo, 2018 - 2024: Predominance of Zoonotic Transmission

  1. Eddy Kinganda-Lusamaki
  2. Adrienne Amuri-Aziza
  3. Nicolas Fernandez
  4. Jean-Claude Makangara-Cigolo
  5. Catherine Pratt
  6. Emmanuel Hasivirwe Vakaniaki
  7. Nicole A. Hoff
  8. Gradi Luakanda
  9. Prince Akil-Bandali
  10. Sabin Sabiti Nundu
  11. Noella Mulopo-Mukanya
  12. Michel Ngimba
  13. Brigitte Modadra-Madakpa
  14. Ruth Diavita
  15. Princesse Paku
  16. Elisabeth Pukuta-Simbu
  17. Sydney Merritt
  18. Áine O’Toole
  19. Nicola Low
  20. Antoine Nkuba-Ndaye
  21. Hugo Kavunga-Membo
  22. Robert Shongo
  23. Laurens Liesenborghs
  24. Tony Wawina-Bokalanga
  25. Koen Vercauteren
  26. Daniel Mukadi-Bamuleka
  27. Lorenzo Subissi
  28. Jean-Jacques Muyembe
  29. Jason Kindrachuk
  30. Ahidjo Ayouba
  31. Andrew Rambaut
  32. Eric Delaporte
  33. Sofonias Tessema
  34. Eric D’Ortenzio
  35. Anne W. Rimoin
  36. Lisa E. Hensley
  37. Placide Mbala-Kingebeni
  38. Martine Peeters
  39. Steve Ahuka-Mundeke
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Abstract

Background

Recent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC), with increasing case counts, sexual contact-mediated clusters, and sustained human-to-human transmission driven by a novel monkeypox virus (MPXV) subclade, clade Ib. However, only a limited number of clade I MPXV genomes have been characterized so far, from a limited number of regions.

Methods

We conducted whole genome sequencing of 603 mpox-positive samples that were collected from 581 patients between 2018-2024 in 17 of the 26 provinces of the DRC.

Results

Genome coverage was at least 70% for 429/603 (71.1%) samples and near full-length MPXV genomes (>90% coverage) were obtained for 348/603 (57.7%) samples from 337 patients. All newly generated MPXV sequences belonged to clade I, among which 17 were clade Ib strains, all from patients infected in 2024 in the South-Kivu province. The large majority (>95%) of the new strains fall within previously described clade Ia groups and potential new groups have also been observed. The low number of APOBEC3 mutations found among clade Ia suggests that most human mpox cases are probably linked to zoonotic transmissions. Genetically diverse MPXV lineages co-circulate in small geographic areas during the same outbreak suggesting multiple zoonotic introductions over a short period from one or multiple reservoir species. Recent identification of mpox cases in Kinshasa shows that multiple lineages circulate in a large urban center, indicating separate introduction events.

Conclusion

The mpox epidemic in the DRC exhibits two distinct patterns. In traditional endemic regions, the epidemic is predominated by zoonotic spill-over events involving clade Ia. Conversely, in the eastern part of the country, the clade Ib outbreak is driven by human-to-human transmission highlighting the need for a coordinated response effort at the national, regional and international levels.

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