#18,160
While much of the world expressed surprise when a clade IIb Mpox (then called Monkeypox) virus began its world tour in the spring of 2022, experts had been warning for years it was not only possible, but increasingly likely.
Cautionary reports published between 2020 and early 2022 include:
PLoS NTD: The Changing Epidemiology of Human Monkeypox—A potential threat?
EID Journal: Reemergence of Human Monkeypox and Declining Population Immunity - Nigeria, 2017–2020
WHO: Modelling Human-to-Human Transmission of Monkeypox
While largely ignored, 2 distinct clades of Mpox (I & II) had been spreading across central Africa for decades, mostly in a handful of endemic countries (clade I primarily in the DRC & CAR), with a weaker clade II virus re-emerging in Nigeria after an absence of 40 years in 2017.
Countries with endemic Mpox- Credit WHO
Mpox outbreaks in endemic African nations had been rising for years - presumably because smallpox vaccinations (which appear to provide up to 85% protection) were halted in the late 1970s (see 2010 PNAS study Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo).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:In 2013, the DRC reported a 600% increase in cases over both 2011, and 2012 (see EID Journal:Extended H-2-H Transmission during a Monkeypox Outbreak) . The authors also cited a higher attack rate, longer chains of infection, and more pronounced community spread than had earlier reports.
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.
Although the 2022 outbreak peaked quickly, and the emergency was declared over in May of 2023, cases continue to emerge around the world. As we saw in last Sunday's WHO update, surveillance and reporting are often lacking, but there are signs of increasing cases around the world.
Luckily, it has been the far less-dangerous Clade IIb that has been spreading internationally for the past 2 years. Deaths have only rarely (< 2%) been reported.
But we've seen recent increases in the spread of the more pathogenic clade I virus in the DRC, including the emergence of a new, and apparently more transmissible, clade Ib virus (see Eurosurveillance: Ongoing Mpox Outbreak in South Kivu Province, DRC Associated With a Novel Clade I Sub-lineage).
While the future course and impact of Mpox is unknowable, there are growing concerns that clade Ib might follow in the footsteps of clade IIb - or worse - clade I could evolve into an even more formidable virus before breaking out of Central Africa.
Today we've got a review article, published in the journal Biomedicines, which looks at the history of Mpox, and its potential to evolve into an even greater public health threat.
This review was submitted prior to the announcement of an emerging clade Ib in the DRC, but otherwise provides an excellent review of the Mpox threat.
I've only reproduced some excerpts from a much longer report, so follow the link to read it in its entirety.
The Re-Emergence of Mpox: Old Illness, Modern Challenges
Mohammad Ali Zinnah 1,†, Md Bashir Uddin 2,†, Tanjila Hasan 3, Shobhan Das 4, Fahima Khatun 5,
Md Hasibul Hasan 6, Ruenruetai Udonsom 7, Md Masudur Rahman 8,9,* and Hossam M. Ashour 10,*
Biomedicines 2024, 12(7), 1457; https://doi.org/10.3390/biomedicines12071457
Submission received: 12 January 2024 / Revised: 6 June 2024 / Accepted: 10 June 2024 / Published: 1 July 2024
Abstract
The Mpox virus (MPXV) is known to cause zoonotic disease in humans. The virus belongs to the genus Orthopoxvirus, of the family Poxviridae, and was first reported in monkeys in 1959 in Denmark and in humans in 1970 in the Congo. MPXV first appeared in the U.S. in 2003, re-emerged in 2017, and spread globally within a few years. Wild African rodents are thought to be the reservoir of MPXV. The exotic trade of animals and international travel can contribute to the spread of the Mpox virus. A phylogenetic analysis of MPXV revealed two distinct clades (Central African clade and West African clade).The smallpox vaccine shows cross-protection against MPXV infections in humans. Those who have not previously been exposed to Orthopoxvirus infections are more vulnerable to MPXV infections. Clinical manifestations in humans include fever, muscle pain, headache, and vesicle formation on the skin of infected individuals. Pathognomonic lesions include ballooning degenerations with Guarnieri-like inclusions in vesicular epithelial cells.Alterations in viral genome through genetic mutations might favor the re-emergence of a version of MPXV with enhanced virulence. As of November 2023, 92,783 cases and 171 deaths have been reported in 116 countries, representing a global public health concern. Here, we provide insights on the re-emergence of MPXV in humans.This review covers the origin, emergence, re-emergence, transmission, pathology, diagnosis, control measures, and immunomodulation of the virus, as well as clinical manifestations. Concerted efforts of health professionals and scientists are needed to prevent the disease and stop its transmission in vulnerable populations.
Introduction
Mpox (formerly known as monkeypox) is a transmissible disease that can impact humans and animals. The Mpox virus (MPXV) was first described in humans in the 1970s in the Democratic Republic of the Congo (DRC) causing a primarily endemic disease throughout the rainforests of Central and Western Africa with no reported outbreaks elsewhere [1]. In 2003, Mpox was reported in Wisconsin, USA [2] and was later reported in other countries outside Africa. This threat, if not contained, can potentially add to the economic losses the world has been facing since the advent of the COVID-19 pandemic era in 2019 [3].
Coinfections of MPXV and SARS-CoV-2 could enhance pathogenicity, infectivity, and/or response to vaccines in one or both cases [4]. Possible interactions between the two viruses could also trigger the emergence of new variants of SARS-CoV-2 with hosts having enhanced immune evasion capabilities [5]. Considering its characteristics and risks, MPXV has been assigned to the biosafety level 3 (BSL-3) category by the EU [6], and was similarly categorized in the Selected Agents and Toxin List in the U.S. [7].
Due to its generally reduced severity, Mpox cases suffer from underreporting and are more prone to poor case management [8]. The recent surge in case counts of Mpox is changing this. There is fear that MPXV might be the next emerging pathogen from the Poxviridae family after smallpox. Thus, prevention is both critical and timely. In this review, we summarize the latest publicly available information on the origin, evolution and emergence, transmission, pathology, diagnosis, and control of MPXV.
(SNIP)
Figure 3. Transmission of Mpox. Schematic illustration to show the different routes of transmission. In (A), the numbers correspond to the following animals: 1. rope squirrel; 2. sooty mangabey; 3. prairie dog; 4. Gambian pouched rat; 5. African dormice rodent; 6. African giant pouched rat; 7. sun squirrel; 8. rufous-nosed rat; and 9. elephant shrew. (B) represents bush meat. In (C), the numbers correspond to the following: 1. skin crust; 2. patients’ used materials; 3. contaminated saliva; and 4. fecal materials. (D) represents transplacental transmission. (E) reflects hospital-borne infection. (F) shows transmission by respiratory droplets and direct contact. (G) shows sharing of 1. bed; 2. food; 3. a glass and other utensils; and 4. hand towels.
(SNIP)
Future Recommendations
Even though Mpox infections are less severe than smallpox infections, MPXV has the potential to become highly pathogenic due to its ability to mutate and undergo the genetic recombination characteristic of the Poxviridae family [37,39]. More data are needed about the recombination of MPXV with Orthopoxviruses during coinfection or superinfection. There are also reports about the coinfection of MPXV with the Varicella-Zoster virus (VZV) [8,42] and HIV [43]. Future endeavors should cover the consequences of coinfections and superinfections in patients with MPXV.
In spite of educated guesses and speculations, the animal reservoir is yet to be identified [79,80]. Expanding research in the areas of host and tissue tropism in the context of MPXV infections can enable us to have a better understanding of the spread of the virus and the host’s immune response [70].
The re-emergence of MPXV infections could be considered a consequence of multiple factors. One factor is the decline in herd immunity in the population as a result of the cessation of the smallpox vaccination. Another main factor is the more frequent interactions between humans and potential MPXV reservoirs as a result of deforestation, urbanization, and the handling and consumption of certain food products, such as bush meat ingestion. This might have resulted in the creation of new ecological and immunological niches for the spread of MPXV.
The previous factors and recent outbreaks highlight the urgent need for consistent surveillance and the advancement of new immunoprophylactic and therapeutic strategies for MPXV. This should make us more prepared to handle potential future pandemics.
