#17,238
For more than a decade we've been following reports (see below) from researchers warning that the Monkeypox virus (aka Mpox) - endemic in central Africa - was evolving and expanding its geographic range.
A 2016 study (see EID Journal:Extended H-2-H Transmission during a Monkeypox Outbreak) looked at a large 2013 outbreak of Monkeypox in the DRC and suggested that the virus's epidemiological characteristics may be changing (possibly due to the waning smallpox vaccine derived immunity in the community).
In 2017, Monkeypox - which had been endemic in central Africa - turned up in Nigeria for the first time in 40 years (see EID Journal: Reemergence of Human Monkeypox and Declining Population Immunity - Nigeria, 2017–2020).
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.
In 2019's CDC: 8 Zoonotic Diseases Of Most Concern In The United States, Monkeypox ranked 29th; about halfway down their list. Similarly, in 2018's WHO List Of Blueprint Priority Diseases - while Monkeypox did not make the final list (n=8) - it was mentioned as a disease to watch.
Luckily, there were some who viewed the threat as seriously enough to work on, and approve (in 2019), a new live, Non-replicating Vaccine to Prevent Smallpox & Monkeypox.
Despite ongoing outbreaks in the DRC and Nigeria, a report from the WHO in 2020 (see WHO: Modelling Human-to-Human Transmission of Monkeypox), and occasional exported cases to other countries (see here, here, and here), Monkeypox has remained a low priority concern.
That perception abruptly changed in May of last year when the UK reported 2 Monkeypox Cases In London, whose source of infection was unknown and under investigation. Both belonged to the same household, and while travel-related Monkeypox has been previously reported in the UK, neither had recent travel history out of the country.
Within 48 hours, the UK had Reported 4 More Monkeypox Cases (3 in London, 1 linked case in the Northeast of the country), all without recent travel history to West or Central Africa. Two days later, Portugal & Spain were reporting suspected cases.
Fast forward roughly 8 months and the global case count exceeds 80,000, while more than 29,000 cases have been identified in the United States. Both numbers are likely serious under counts, and both are expected to continue to rise in the weeks and months to come.
While Monkeypox continues to simmer more than boil - and has been largely dropped from the headlines in favor of newer, more clickable stories - today's report from the EID Journal suggests that the virus has not only stealthily established a firm foothold in humans over a period of years, it continues to adapt and evolve.
Meaning that it may have more surprises in store for us in the years to come.
Follow the link to read the report, and its supporting files, in their entirety. I'll have a postscript after the break.
Monkeypox Virus Evolution before 2022 Outbreak
Eric Dumonteil, Claudia Herrera, and Gilberto Sabino-Santos
Abstract
Phylogenetic analysis of monkeypox virus genomes showed statistically significant divergence and nascent subclades during the 2022 outbreak. Frequency of G>A/C>T transitions has increased in recent years, probably resulting from apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) deaminase editing. This microevolutionary pattern most likely reflects community spread of the virus and adaptation to humans.
Monkeypox virus (MPXV) is a double-stranded DNA virus mostly associated with rodents and occasionally spilling over to humans, causing outbreaks that have been relatively short-lived and self-limiting because of ineffective transmission among humans (1). However, this view is challenged by reports that, since the start of the ongoing outbreak, in early April 2022, a total of 49,482 cases in 94 countries had been confirmed (https://ourworldindata.org/monkeypoxExternal Link).Initial epidemiologic studies provided evidence of sustained human-to-human transmission in some non–MPXV-endemic countries in Europe, through close contacts, including in sexual networks (2). The first MPXV genome sequences from the outbreak were reported from Portugal on May 19, 2022 (3), and multiple additional sequences, which can shed light on virus circulation, are now available.
Initial phylogenetic analyses indicated that the virus causing the 2022 outbreak belonged to MPXV clade II (formerly West African clade), which is less severe than clade I (formerly Congo Basin clade) (4), suggesting that the current outbreak was caused by the recent introduction of the virus into communities in non–MPXV-endemic countries (2). However, further analysis including additional MPXV genome sequences indicates a different scenario.
Figure. Origin of the 2022 monkeypox virus (MPXV) outbreak and substitution profiles. A) MPXV phylogeny of the 2022 outbreak, created by using 87 sequences from the 2022 outbreak together with sequences...
Indeed, phylogenetic analysis of 105 MPXV genomes (Appendix Table 1) revealed that viruses from 2022 belong to 2 clades that can be traced back to the previous 2017–2018 outbreak (Figure). One of those subclades, so far only identified in the United States (5), seems to have limited circulation (only 3 cases). All other 2022 viral genomes form a large monophyletic group, although a substantial level of sequence divergence among strains can already be detected, with several nascent subclades (Figure).Such divergence is not compatible with a recent diversification of the virus during the past few months of the outbreak. Rather, it reflects a continuous microevolution since the previous outbreak in 2017–2018. The most recent common ancestor for the 2022 outbreak can be traced back to around 20 years ago, at a rather similar time as the most recent common ancestor for the 2017–2018 outbreak.Furthermore, MPXVs from the 2022 outbreak are more closely related to strains that had been exported from Africa during the previous outbreak, rather than with strains circulating in Nigeria at that time. A strain from a person who traveled from Nigeria to Maryland, USA, in 2021 (5) can also be traced back to the root of the 2022 outbreak. Thus, the most likely scenario is that there has been silent and undetected circulation of MPXV, possibly including multiple non–MPXV-endemic countries outside Africa, since the 2017–2018 outbreak.
Our observations raise the question of potentially increased adaptation of current virus strains to humans. Variations in genomic content may shape the evolution of orthopoxviruses, and gene gain/loss may correlate with pathogenicity and host adaptation (6). We found multiple genomic changes in the MPXVs from 2022; at least 51 single-nucleotide polymorphisms (SNPs) differentiated the first 18 viral genomes from the 2022 outbreak from those from 2017–2018 (Appendix Table 2) and a few larger insertions/deletions. Of the 51 SNPs, 26 caused amino acid changes and 21 were synonymous substitutions. Additional SNPs can be detected among genome sequences from 2022, underlying the established divergence within the outbreak (Appendix Table 2). Those changes may be associated with mutational pressure and adaptation (7,8), and future studies should help assess their phenotypic effects.
(SNIP)
In conclusion, our analyses of MPXV genome sequences indicate that the virus has been circulating silently and undetected for about 2 decades, probably in multiple non–MPXV-endemic countries outside of Africa. Also, a clear genomic signature of a recent change in hosts is evidenced by major changes in its nucleotide substitution pattern. Our observations have major public health implications; the changing epidemiology of MPXV infections and human circulation of the virus in non–MPXV-endemic countries call for increased surveillance (1). The public health crisis caused by the COVID-19 pandemic may have favored the spread of MPXV under the radar in the past few years; however, the existence of asymptomatic carriers cannot be ruled out and may have contributed to the undetected spread of MPXV.
Dr. Dumonteil is an associate professor at the Tulane School of Public Health and Tropical Medicine, New Orleans, LA, USA. His main research interests are neglected infectious diseases and interdisciplinary studies for their surveillance and control.
It is worth noting that the early signs of the ascension of Monkeypox to an international threat - the sporadic spillovers into humans, the rarely detected exported cases, and the (largely ignored) studies showing it was becoming more transmissible - are nearly identical to what we've seen unfold with Avian and Swine flu, MERS-CoV, SARS-CoV, Ebola, Lassa, and at least a dozen other zoonotic diseases.
And while not all of those will make the same leap - given enough time - a few probably will.
And when it happens, you can be sure that no matter how many warning signs were ignored, we'll be told by those in charge that no one could have seen it coming.
Again.
