Mpox Virus - Credit CDC PHIL
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While DNA viruses (like Mpox) often evolve at a slower rate than RNA viruses (like influenza or SARS-CoV-2), they are far from static, and longer chains of infection (or infecting different host species) can help promote faster evolution (see Evolution of monkeypox virus from 2017 to 2022: In the light of point mutations).
Another study - published just 3 months before the 2022 international outbreak of Mpox Clade II - warned of the potential for Monkeypox to spread (see PLoS NTD: The Changing Epidemiology of Human Monkeypox—A potential threat?).
Just last year, in Mpox Virus: Its Molecular Evolution and Potential Impact on Viral Epidemiology by Xi Yu et al., the authors wrote:
The evolution of zoonotic infections to become more transmissible or virulent in humans is a key cause for concern. Particularly, regarding OPXVs such as MPXV, there is concern about the risk that they could evolve into infections capable of causing another smallpox-like pandemic.
Last year we also saw the emergence of a a new, and reportedly more dangerous clade Ib Mpox virus in the DRC, and more recently its spillover (along with the older clade I & clade II virus) into neighboring countries, which prompted the WHO to declare a second Mpox PHEIC last Month.
At the same time, we are seeing increasing reports of clade II outbreaks (see WHO Mpox Situation Report #37), which cited Europe and the Western Pacific region as reporting large increases in the last reporting month (August).Just as clade I continues to evolve, so do clade II viruses. And at a surprisingly brisk rate.
Which brings us to a new dispatch, published yesterday in the CDC's EID Journal, which describes a cluster of an emerging C.1 sublineage of Mpox (Clade IIb) in Vietnam, which produced particularly harsh symptoms (including several deaths) among heavily immunocompromised individuals.
This C.1 sublineage appears to have emerged in China in 2023 (see Nature Phylogeny and molecular evolution of the first local monkeypox virus cluster in Guangdong Province, China), but has since spread both regionally and internationally.
You'll find the link and some excerpts from the report below, but you'll want to read it in its entirety (warning: some graphic content). I'll have a postscript when you return.
Volume 30, Number 11—November 2024
Dispatch
Emerging Monkeypox Virus Sublineage C.1 Causing Community Transmission, Vietnam, 2023
Huynh Thi Thuy Hoa, Nguyen Thanh Dung, Le Manh Hung, Nguyen Thi Thu Hong, Vo Truong Quy, Nguyen Thi Thao, Nguyen Trong Duy, Hoang Truong, Tran Minh Hoang, Nguyen Thi Thanh, Mai Pham Hong Phuoc, Truong Ngoc Trung, Nguyen Nhut Thong, Nguyen Duc Huy, Vu Thi Kim Thoa, Vo Trong Vuong, Ngo Tan Tai, Huynh Kim Nhung, Dao Phuong Linh, Pham Thi Ngoc Thoa, Lam Minh Yen, Tran Ba Thien, Truong Hoang Chau Truc, Le Kim Thanh, Nguyen Thi Han Ny, Vo Tan Hoang, Nghiem My Ngoc, Dinh Nguyen Huy Man, Louise Thwaites, Tsublineage C.1 ran Tan Thanh, Nguyen Van Vinh Chau, Guy Thwaites, Nguyen To Anh, and Le Van Tan
Abstract
We studied a community cluster of 25 mpox cases in Vietnam caused by emerging monkeypox virus sublineage C.1 and imported into Vietnam through 2 independent events; 1 major cluster carried a novel APOBEC3-like mutation. Three patients died; all had advanced HIV co-infection. Viral evolution and its potential consequences should be closely monitored.
To date, most globally reported mpox sequences have come from Europe and North America, where sustained human-to-human transmission has resulted in explosive mpox outbreaks, especially in 2022 (1). A hallmark of the monkeypox virus (MPXV) strain responsible for the ongoing global outbreaks is its high evolution rate, which is driven by the host APOBEC3 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3) deaminases, causing a dinucleotide change from TC to TT (2).In addition, persons with advanced HIV might experience more severe outcomes (3) and delayed viral clearance, resulting in the emergence of new variants, as has been observed with SARS-CoV-2 (4). However, this possibility has not been well studied for MPXV infection (5).
Vietnam reported its first mpox cases in late 2022 in 2 female travelers returning from United Arab Emirates (6). No additional cases were reported until September 2023, when mpox was diagnosed in a 33-year-old man in Dong Nai Province in southern Vietnam (7). This case marked the start of ongoing community transmission in Vietnam, where the mpox vaccine has not been deployed.
Despite the ongoing challenges of mpox, existing literature has been dominated by reports from Europe and North America, where most cases have been reported (1). We therefore studied the longitudinal clinical, laboratory, and virological features in mpox patients admitted to a tertiary referral hospital in Ho Chi Minh City, Vietnam, in 2023. We also sought to study virus evolution in persons with advanced HIV over the course of hospitalization.
(SNIP)
Our findings emphasize that, although MPXV infections are usually self-limiting, severe clinical complications and death can occur, especially in persons with advanced HIV (3,8). Detecting MPXV in ETA and CSF samples is unusual, although it has been reported previously (3), and this finding supports further study of mpox pathogenesis.
The responsible viruses belonged to sublineage C.1, lineage B.1 of clade IIb, and were imported into Vietnam through 2 independent events, as demonstrated by their phylogenetically forming into 2 different clusters.
Sublineage C.1 has only recently emerged and caused local transmission in China (9). In addition, C.1 sequences from various countries in Asia, Europe, and the Americas have been deposited to GISAID (https://www.gisaid.orgExternal Link), demonstrating its global dispersal.
Those collective findings point to a rapid evolution of MPXV, of which the host APOBEC3 has been shown to be a main driver (2). Alternatively, immune suppression or antivirals might also enable intrahost evolution, as observed in a recent study (5). Similar findings were documented in our metagenomics datasets of longitudinal samples. However, subsequent Sanger sequencing failed to confirm those original findings, likely attributed to sequencing artifacts, emphasizing the importance subsequent Sanger sequencing–based confirmatory experiments.
The tight cluster on the global phylogenetic tree of the 13 sequences sharing 2 nonsynonymous substitutions suggested that those patients shared a transmission network, supporting findings from a recent report (10). Because direct skin-to-skin contact plays a key role in MPXV transmission, public education campaigns should raise awareness about behaviors that increase the risk for MPXV exposure (11). Vaccination remains the most effective tool to control mpox outbreaks (12).
Conclusions
We report the clinical, laboratory, and virological findings in 25 mpox patients infected with an emerging sublineage C.1 that was imported into Vietnam through 2 independent events; 1 major cluster carried a novel APOBEC3-like mutation concerning virus assembly. MPXV evolution and its potential consequences should be closely monitored. Clinicians should be aware of unusual skin lesions in patients with advanced HIV.
Dr. Hoa is a senior infectious disease specialist at the Ho Chi Minh City Hospital for Tropical Diseases. Her research interests focus on infectious diseases, including mpox.
We have a long history of underestimating viruses, thinking that the way they behaved yesterday, and the day before that, tells us how they will behave tomorrow and all the days that follow. It may be comforting, but that isn't how viruses - and disease outbreaks - work.
- Swine origin H1N1 circulated in pigs for a decade before it suddenly acquired the ability to transmit efficiently in humans, and sparked the 2009 H1N1 pandemic.
- Ebola had never sparked a regional outbreak in Africa because it was thought `too virulent to spread', until it caused a year-long 3-nation outbreak in 2014, killing tens of thousands.
- In early 2020, many `experts' predicted the end of the COVID pandemic within a matter of months', citing its `low mutation rate', and the benefits of `herd immunity'.
- Until 2022, Mpox had only rarely been exported outside of Africa, and all outbreaks were quickly contained. But over the summer of 2022, tens of thousands of cases were reported in scores of nations, and today more than 106,000 cases have now been confirmed.
- And until 6 months ago, few scientists would have guessed that HPAI H5N1 could spread across more than a dozen states in dairy cows.
With viruses, we should expect the unexpected. But somehow, we always seem to be caught flat-footed, shocked, and unprepared.
Regardless of whether Mpox has what it takes to spark a major global public health crisis, somewhere out there - in a bat, or a pig, or a bird - there is a virus that someday will accrue the right mutations to put the world at grave risk.
And when that day comes, we'd better have more prepared than just an excuse that `No one could have predicted this would happen. . . . '
