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Biomedicines: The Re-Emergence of Mpox - PAHO Epi Alert On Mpox Clade I (Aug 8th)

Michael Coston

Editor, Senior Moderator
Biomedicines: The Re-Emergence of Mpox - Old Illness, Modern Challenges



2022-2024 Mpox - Credit CDC




#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:


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.


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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).

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.​


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.


Although the 2022 outbreak peaked quickly, and the emergency was declared overin 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.


(Continue . . . )

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https://afludiary.blogspot.com/2024/07/biomedicines-re-emergence-of-mpox-old.html
 
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PAHO Epidemiological Alert On MPXV Clade I




#18,237

Over the weekend the Director General of the WHO Dr. Tedros announced (see below) that he would be convening an Emergency Committee Meeting of the IHR this week to consider whether the new emerging Mpox Clade Ib virus in central Africa constitutes a public health emergency of international concern (PHEIC).



We've been following this upsurge since last November, and saw the identification of a new clade (Ib) last March (see Preprint: Sustained Human Outbreak of a New MPXV Clade I Lineage in Eastern Democratic Republic of the Congo).

Unlike the clade II Mpox virus, which began its world tour in the spring of 2022, clade I & Ib Mpox cause far more severe illness, and carry a significantly higher fatality rate.​

So far, Clade I has not been identified outside of Africa, but current laboratory tests have encountered challenges identifying the new clade Ib virus (see Predicted failure of common Mpox PCR testing on a recent DRC clade I variant).

Clade Ib appears to be spreading far more efficiently in the DRC than previous strains, and is disproportionately affecting (and killing) children. In recent weeks clade Ib has been detected in three new countries (Rwanda, Uganda and Kenya), and testing is ongoing in a 4th (Burundi).​

Add in the fact that many countries are lax in looking for, or reporting cases (see WHO statement below), and it becomes difficult to say with absolute certainty how widespread clade I has become.

WHO continues to encourage all countries to ensure that mpox is a notifiable disease and to report mpox cases, including reporting when no cases have been detected (known as ‘zero-reporting’, as outlined in the Standing Recommendations on mpox issued by the WHO Director General).

This report does not highlight non-reporting countries. Therefore, it should be noted that an absence of reported cases from a country may be due to the country not reporting, rather than having no cases. Reporting to WHO has been declining, therefore, the decline in reported cases should be interpreted with caution.

Clade II Mpox was obviously spreading internationally - but under the radar - for months before the first cases were identified in the UK & Portugal in May of 2022 (see EID Journal: Monkeypox Virus Evolution before 2022 Outbreak).

Within 30 days, the United States was detecting 50-60 new cases a day, climbing to > 440 a day by August 1st, 2022. While cases began to decline after that, clade II cases are rising once again (see NYC HAN Advisory: `Substantial' Increases In Mpox Infections Over Past Few Months).

Between that, and the potential spread of clade I outside of Africa, and we've seen a sudden surge of risk assessments and epidemiological alerts on Mpox. Late last week, PAHO (the Pan American Health Organization) issued their own epidemiological alert, calling for enhanced surveillance.

First excerpts from the PAHO News release, followed by a link and some excerpts, from the PAHO Alert.

Countries of the Americas should strengthen Mpox surveillance in light of potential spread of new variant detected in African region, PAHO says

Washington D.C. 9 August 2024 (PAHO/WHO) – In an epidemiological alert released on 8 August, the Pan American Health Organization (PAHO) has called on countries of the Americas to strengthen surveillance, including laboratory detection and genomic sequencing of confirmed cases, following the identification of a new variant of mpox virus, Clade I (Clade Ib), in the sub-Saharan African Region. While the new variant has not been reported in the Americas, countries should remain alert to possible imported cases.

The new variant is associated with sustained transmission, as well as the occurrence of cases in a wider range of age groups than during previous outbreaks, including children. It is estimated to have emerged in the Democratic Republic of the Congo in September 2023 and is associated with a significant increase of cases in the country.

Mpox is a viral illness caused by the monkeypox virus, a species of the genus Orthopoxvirus. Two different clades exist: clade I and clade II. Symptoms include fever, intense headache, muscle aches, back pain, low energy, swollen lymph nodes, and a skin rash or mucosal lesions. The rash tends to be concentrated on the face, palms of the hands, and soles of the feet, but can also be found on the mouth, anogenital region, and eyes. Symptoms typically last between 2 to 4 weeks and go away on their own without treatment.

Since the beginning of 2024 (to 26 July 2024), the Democratic Republic of Congo Ministry of Health reported 14,479 cases of mpox, and 455 deaths. According to the report, “the number of cases reported in the first six months of this year match the number reported in all of last year.” Children under the age of 15 accounted for 66% of cases and 82% of deaths. Cases of the new variant have also been reported in Rwanda, Uganda and Kenya. Testing is also underway in Burundi to determine whether reported cases in that country are also due to the new variant.

As a result of the hike in cases, on 7 August the World Health Organization (WHO) Director General, Dr. Tedros Adhanom Ghebreyesus announced that he will convene a panel of experts to advise him on whether the expanding outbreak constitutes a global health emergency.


(Continue . . . )


Epidemiological Alert Mpox (MPXV clade I) - 8 August 2024
148695-2024-aug-8-phe-epi-alert-mpox-eng.png

DOWNLOAD (285.78 KB)

Given the circulation of the variant of clade I of mpox virus (MPXV) in the African Region, which is associated in the African Region with sustained transmission and the occurrence of cases in a wider range of age groups, including children, the Pan American Health Organization/World Health Organization (PAHO/WHO) encourages Member States to remain vigilant to the possibility of introduction of this variant in the Americas, and to continue their surveillance efforts, including genomic sequencing of detected cases, with special emphasis on high-risk groups.

(Excerpt)

In December 2022, the Democratic Republic of the Congo declared a nationwide outbreak of mpox and since September 2023 the outbreak that affected South Kivu province has spread and affected several provinces. As part of the outbreak investigation, a new variant of mpox virus clade I (MPXV) was identified and is estimated to have emerged around mid- September. The variant was associated with the significant increase in cases of mpox in that country, and sexual transmission was the main mode of infection in most of the reported cases (8).

The clade I variant contains predominantly APOBEC3-type mutations, indicating an adaptation of the virus due to intense circulation in humans (8). Person-to-person transmission has been continuous since its detection, and this is the first time that sustained community transmission of the virus has been described in the country (8).
Since the beginning of 2024, as of the last report on 26 July 2024, the Democratic Republic of the Congo Ministry of Health reported 14,479 cases of mpox (2,715 confirmed; 11,764 suspected) and 455 deaths (case fatality rate: 3.1%), affecting 25 of the country's 26 provinces. Children under 15 years of age accounted for 66% of cases and 82% of deaths. Of the confirmed cases, 73% were males (9).


(Continue . . . )


Globally, our community immunity to poxviruses has waned dramatically, as smallpox vaccinations were halted in most countries more than 50 years ago. An emerging Mpox virus would presumably find a plethora of susceptible hosts.

Exactly what that would look like is impossible to say, since the virus continues to evolve. Past performance has never been a reliable guarantee of future results.​

About the only thing we can say is, the longer we wait to acknowledge a problem, the harder is becomes to effectively deal with it.

And the warning lights have been flashing with Mpox for quite some time.

https://afludiary.blogspot.com/2024/08/paho-epidemiological-alert-on-mpxv.html
 
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