Wednesday, April 17, 2024

Preprint: Sustained Human Outbreak of a New MPXV Clade I Lineage in Eastern Democratic Republic of the Congo



#18,011

While the global health emergency for the international spread of a new clade (IIb) of Mpox (formerly Monkeypox) ended nearly a year ago, we continue to see sporadic infections around the globe, while a more dangerous clade I mpox virus continues to rage (>12,000 cases in 2023) in the DRC.

Last month we looked at a report in Eurosurveillance: Ongoing Mpox Outbreak in South Kivu Province, DRC Associated With a Novel Clade I Sub-lineage, which contained the first genomic analysis of samples from a previously unaffected region of the DRC (the city of Kamituga). 

That study revealed a novel clade I sub-linage had emerged - most likely from a zoonotic introduction - with changes that may render current CDC tests unreliable.

The changing epidemiology and genetic evolution of mpox clade I in central Africa has sparked a number of risks assessments over the past few months, including:

Today we have a preprint which further describes the outbreak of Mpox in the city of Kamituga. The authors warn in this 30-page PDF that the potential exists for this novel MPXV clade to eventually spread beyond the DRC, and potentially spark another global mpox outbreak. 

Due to its length I've only posted some excerpts, I'll have a postscript after the break. 
Emmanuel H. Vakaniaki, Cris Kaciat, Eddy Kinganda-Lusamaki, Aine O'Toole, Tony Wawina-Bokalanga, Daniel Mukadi-Bamuleka, Adrienne Amuri Aziza, Nadine Malyamungu-Bubala, Francklin Mweshi-Kumbana, Leandre Mutimbwa-Mambo, Freddy Belesi-Siangoli, Yves Mujula, Edyth Parker, Pauline-Chloe Muswamba-Kayembe, Sabin S. Nundu, Robert S. Lushima, Jean Claude Makangara Cigolo, Noella Mulopo-Mukanya, Elisabeth Pukuta Simbu, Prince Akil-Bandali, Hugo Kavunga, Koen Vercauteren, Nadia A. Sam-Agudu, Edward J Mills, Olivier Tshiani-Mbaya, Nicole A. Hoff, View ORCID ProfileAnne W Rimoin, Lisa E. Hensley, View ORCID ProfileJason Kindrachuk, Ahidjo Ayouba, Martine Peeters, Eric Delaporte, Steve Ahuka-Mundeke, Jean B. Nachega, Jean-Jacques Tamfum Muyembe, Andrew Rambaut, View ORCID ProfileLaurens Liesenborghs, Placide Mbala-Kingebeni
doi: https://doi.org/10.1101/2024.04.12.24305195
ABSTRACT
Background: Monkeypox virus (MPXV) attracted global attention in 2022 during a widespread outbreak linked primarily to sexual contact. Clade I MPXV is prevalent in Central Africa and characterized by severe disease and high mortality, while Clade II is confined to West Africa and associated with milder illness. A Clade IIb MPXV emerged in Nigeria in 2017, with protracted human-to-human transmission a forerunner of the global Clade II B.1 lineage outbreak in 2022. In October 2023, a large mpox outbreak emerged in the Kamituga mining region of the Democratic Republic of the Congo (DRC), of which we conducted an outbreak investigation. 
Methods: Surveillance data and hospital records were collected between October 2023 and January 2024. Blood samples and skin/oropharyngeal swabs were obtained for molecular diagnosis at the National Institute of Biomedical Research, Kinshasa. MPXV genomes were sequenced and analyzed using Illumina NextSeq 2000 and bioinformatic tools. 
Results: The Kamituga mpox outbreak spread rapidly, with 241 suspected cases reported within 5 months of the first reported case. Of 108 confirmed cases, 29% were sex workers, highlighting sexual contact as a key mode of infection. Genomic analysis revealed a distinct MPXV Clade Ib lineage, divergent from previously sequenced Clade I strains in DRC. Predominance of APOBEC3-type mutations and estimated time of emergence around mid-September 2023 suggest recent human-to-human transmission. 
Conclusions: Urgent measures, including reinforced, expanded surveillance, contact tracing, case management support, and targeted vaccination are needed to contain this new pandemic-potential Clade Ib outbreak.

          (SNIP)

DISCUSSION This report describes a novel Clade I MPXV lineage associated with sustained human-to-human transmission in an ongoing outbreak in eastern DRC. Identification of APOBEC3-related mutations – the hallmark of efficient MPXV spread via human-to-human transmission – bolsters this assertion. 
Due to its distinct geographical location and divergent phylogenetic relationship, we propose to name this new Clade Ib, with the previously described Clade I renamed Clade Ia. The previous distinction between Clades IIa and IIb was borne out of a similar rationale, with the diversity within Clades IIa and IIb more than half the divergence between them. 16
(SNIP)
The situation in Kamituga echoes the 2017-2018 outbreak of Clade IIb MPXV in Nigeria. Without intervention, this localized Kamituga outbreak harbors the potential to spread nationally and internationally. Urgent measures must be implemented, including intensifying local surveillance, enhancing referral systems and case management, and implementing targeted mpox vaccination for individuals at high-risk, such as contacts of index cases, HCWs, sex workers, and men who have sex with men. 20 Given the recent history of mpox outbreaks in DRC, we advocate for swift action by endemic countries and the international community to avert another global mpox outbreak.       

Like all viruses, Monkeypox continues to evolve and diversify, as discussed in the 2014 EID Journal article Genomic Variability of Monkeypox Virus among Humans, Democratic Republic of the Congo, where the authors cautioned:

Small genetic changes could favor adaptation to a human host, and this potential is greatest for pathogens with moderate transmission rates (such as MPXV) (40). The ability to spread rapidly and efficiently from human to human could enhance spread by travelers to new regions.

Which means we shouldn't be surprised if new variants, or subclades, of Mpox appear over time. Especially when very little has been done to curb the spread of the virus in endemic regions like the DRC. 

Complicating matters, recent studies suggest that the protective effects of the JYNNEOS vaccine - at least in those who had not received a smallpox vaccination - wanes over a period of months (see ECCMID 2024 Study: Mpox (monkeypox) Antibodies Wane Within A Year of Vaccination).

While there are no confirmed cases of this new clade outside of the DRC, borders and oceans no longer provide the barrier against the spread of infectious diseases they once did.  

A reminder that an infectious disease threat anywhere in the world is potentially a threat everywhere. 


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