Predominance of zoonotic transmission of the mpox virus in the Democratic Republic of the Congo

Last updated on 25 November 2024

In brief

Central Africa, especially the Democratic Republic of the Congo (DRC), is highly affected by successive mpox outbreaks. Until now, the extent of genetic diversity of the virus had not been well characterised in this region of the world. For the first time, as part of the AFROSCREEN project[1] and the PANAFPOX project[2], teams from the Institut National de Recherche Biomédicale (INRB) in DRC, IRD and Inserm have provided important new information on the genetic diversity of mpox virus circulating in DRC and on the predominant route of transmission. Results of this work have just been published on the Cell website on 24 October 2024.

 

[1] Project coordinated by ANRS MIE in partnership with IRD and the Institut Pasteur, and financed by the French Development Agency (AFD)

[2] Multidisciplinary project with a “One Health” approach, funded by ANRS MIE

The background: An alarming expansion

Mpox is a viral zoonosis most likely transmitted from rodents to humans. The first case was reported in the Democratic Republic of the Congo (DRC) in 1970. This disease, which had been endemic mainly in rural and forested areas of West and Central Africa for several decades, spread around the world in 2022, including cases in European countries. For the first time, the disease has spread rapidly between individuals through sexual contact, a mode of transmission rarely observed before. This growing mpox outbreak has led to a declaration of a public health emergency of international concern.

The mpox virus can be divided into two major clades*. Clade I, the ‘historical’ strain of the virus, found in the Congo Basin and Central Africa, and clade II, present in West Africa, with clade IIb, found in Nigeria and responsible for the 2022 mpox outbreak.

The most affected country is DRC, where the number of cases has doubled in recent years, rising from around 3,000 in 2021 to 5,600 in 2022, and from over 14,000 in 2023 to over 20,000 by 1st September 2024. This increase is accompanied by an alarming expansion of the geographical spread, first in eastern DRC but also in urban areas including the capital city Kinshasa, and in neighbouring countries (Rwanda, Burundi, Kenya and Uganda) previously unaffected by mpox. On 14 August 2024, the substantial rise in mpox cases led the World Health Organisation to declare the mpox outbreak a public health emergency of international concern for the second time. These new infections have been attributed to clade Ib, a new variant of clade I with increased numbers of APOBEC3** mutations, which indicate that the virus has adapted to human hosts.

* a group of organisms, including a particular organism and all of its descendants.

** APOBEC3 (Apolipoprotein B Editing Complex) are proteins that help protect against viral infections.

The study

The study, conducted in DRC between February 2018 and March 2024, aimed to investigate whether the rising numbers of mpox infections in the country were due to zoonotic spillovers or viral evolution linked to human adaptation and sustained human-to-human transmission. A total of of 337 viral genomes from 14 out of 26 provinces were successfully sequenced.

Results

All new sequences from the South Kivu province, in eastern DRC, corresponded to the recently described clade Ib. This variant is associated with sexual contact and sustained human-to-human transmission, and the limited genetic diversity is compatible with its emergence in 2023.

All other genomes from other provinces (i.e. 95% of cases) belonged to clade Ia, which is characterised by high genetic diversity and a low number of APOBEC3 mutations compared with clade Ib. The study results therefore suggest a predominance of zoonotic transmission of mpox in the human population. The co-circulation of genetically diverse viral lineages in small geographical areas even suggests multiple zoonotic introductions over a short period from one or more reservoir species.

Conclusion

For the first time, a large number of clade I mpox sequences have been analysed. This study has provided important new information about the genetic diversity of mpox viruses circulating in DRC, and shows that there are two modes of transmission: zoonotic transmission (clade Ia), which predominates, and human-to-human transmission, which is emerging (clade Ib) in South Kivu and is spreading rapidly to other regions in DRC and neighbouring countries.

The presence of several clade I variants in urban areas, particularly Kinshasa, also highlights the need to continue monitoring the evolution and diversity of the virus in DRC as well as its modes of transmission. It is also urgent to better document the animal reservoirs involved in zoonotic transmission.

Reference

Clade I Monkeypox virus genomic diversity in the Democratic Republic of the Congo, 2018 – 2024: Predominance of Zoonotic Transmission.

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

Cell

  1. Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo
  2. Service de Microbiologie, Département de Biologie Médicale, Cliniques Universitaires de Kinshasa, Université de Kinshasa, Kinshasa, Democratic Republic of the Congo
  3. TransVIHMI, Université de Montpellier, INSERM, IRD, 34394 Montpellier, France
  4. Graduate School of Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland
  5. Biosurv International, Salisbury, SP4 0DQ, England, United Kingdom
  6. Department of Epidemiology, Jonathan and Karin Fielding School of Public Health, University of California, Los Angeles, CA 90095, USA
  7. Rodolphe Merieux INRB-Goma Laboratory, Goma, Democratic Republic of the Congo
  8. Institute of Ecology and Evolution, University of Edinburgh, Edinburgh, UK.
  9. Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
  10. PNLFHMPX, Hemorrhagic Fever and Mpox Program, Ministry of Health, Kinshasa, Democratic Republic of the Congo
  11. Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
  12. World Health Organization, Geneva, Switzerland
  13. Department of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, MB R3E 0J9, Canada
  14. Africa Centers for Disease Control and Prevention (Africa CDC), Addis Abeba, Ethiopia
  15. ANRS Emerging Infectious Diseases (ANRS MIE), Inserm, 75015 Paris, France.
  16. US Department of Agriculture, Manhattan, KS 66502, USA
  17. these authors contributed equally
  18. senior author
  19. lead contact

Press contact

ANRS MIE: presse@anrs.fr
IRD: presse@ird.fr

About ANRS MIE

ANRS Emerging Infectious Diseases is an autonomous agency of Inserm (the French National Institute for Health and Medical Research). Its mission is to facilitate, evaluate, coordinate and fund research into HIV/AIDS, viral hepatitis, sexually transmitted infections, tuberculosis and emerging and re-emerging infectious diseases.

About the Institut de recherche pour le développement (IRD)

As a French institute for international scientific research, IRD contributes to strengthening the resilience of societies to the challenges of global change.
It operates in over 50 countries across Africa, Latin America, Asia, the Pacific, as well as in mainland France and the overseas territories. Its research activities address priority needs in practical ways: mitigating and adapting to climate change, combating poverty and inequality, preserving biodiversity, improving access to healthcare, and understanding social dynamics. Research projects are developed in collaboration with stakeholders on the field and local communities. Teams integrate different perspectives, disciplines, and knowledge through long-term partnerships to build robust, high-impact solutions. IRD advocates for research that benefits the broadest population possible. It openly shares research results and leverages science for action. In this way, it supports the transformation of societies towards more just and sustainable, social, economic, and ecological models.

For more information: https://en.ird.fr/

About the Institut National de Recherche Biomédicale (INRB)

Founded in 1984, as a result of Franco-Congolese collaboration (inaugurated in the presence of President François Mitterrand), INRB is a multidisciplinary institute specialised in the identification, treatment and prevention of diseases in the DRC. Its core activities include medical and biological analyses, applied and translational research, the surveillance of communicable diseases and the promotion of professional growth and development. It has been a WHO collaborating centre since 2018, an Africa CDC collaborating centre, and serves as the national biomedical research laboratory for the DRC’s Ministry of Health.

For more information: https://inrb.net/

About Inserm

Founded in 1964, Inserm is a public scientific and technological institute dedicated to biomedical research and human health, and is involved in the entire range of activities from the laboratory to the patient’s bedside. It also partners with the most prestigious research institutions in the world that are committed to scientific challenges and progress in these fields.

For more information: https://www.inserm.fr/en/home/