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Eric Pyrrhus

🦠
"As of 2 December 2022, over 82,000 human (or ) cases have been laboratory confirmed in 110 countries worldwide."

And sporadic reports are still coming in:
c.im/@andrew_a_lover/109673550

This may be what a very very very slow pandemic looks like.
🦠
As a step towards the development of an , (Peng et al., 2022) recently elucidated the structure of the mpox DNA polymerase:

"Structure of monkeypox DNA polymerase holoenzyme"
doi.org/10.1126/science.ade636
@virology

Picture of mpox DNA polymerase. Figures 2c and 2d from https://doi.org/10.1126/science.ade6360
Public
Eric Pyrrhus

1/3
🦠 A Few Mpox ( ) Pandemic Updates 🦠

When did the current (MPXV) pandemic start?

Although it first caught attention in 2022, some have traced the current pandemic back to 2017.

A new research letter, however, reports that "our analyses of MPXV genome sequences indicate that the virus has been circulating silently and undetected for about 2 decades."
wwwnc.cdc.gov/eid/article/29/2
h/t @travelhealthdoc

@virology

A phylogenetic tree depicting the common ancestor about 20 years ago.
Public *
Eric Pyrrhus

2/3
So, where are we now?

US CDC case reports have slowed down to "only" 47 this year so far, with a total of 30,000 reports and 23 deaths in the US:
cdc.gov/poxvirus/monkeypox/res

But the latest WHO biweekly report noted that "11 countries reported an increase in the weekly number of cases, with the highest increase reported in Mexico," along with 5 new deaths in South America:
who.int/publications/m/item/mu

Snapshots of CDC and WHO websites.
Public
Eric Pyrrhus

3/3
A big worry continues to be under-reporting of cases, especially as Mpox consciousness fades from its 2022 peak.

Some cases may not be reported due to an unusual presentation:
"A case of parotitis caused by hMPX virus"
doi.org/10.1016/S0140-6736(23)

Perhaps more accurate case numbers might be achieved by complementing clinical reports with wastewater sampling:
"We observed a positive correlation between MPXV DNA in wastewater solids and the incidence of reported cases."
nejm.org/doi/full/10.1056/NEJM

Snapshots of article titles from web sites.
Public *
Eric Pyrrhus

1/6
🦠 A Few More ( ) Pandemic Updates 🦠

"Assuming APOBEC-editing is characteristic of [mpox] infection in human hosts, we propose an APOBEC clock that – at a rate of ~6 APOBEC3 mutations per year – estimates [mpox] has been circulating in humans since 2016."
biorxiv.org/content/10.1101/20

@virology

bioRxivPutative APOBEC3 deaminase editing in MPXV as evidence for sustained human transmission since at least 2016Mpox is often described as being endemic in West and Central Africa as a zoonotic disease that transmits through contact with the reservoir rodent host, likely a species of African squirrel. In May 2022, human cases of Mpox were detected spreading internationally beyond countries with known endemic reservoirs. At time of writing, 84,700 confirmed cases have been reported in 110 countries. When the first cases from 2022 were sequenced, it was seen that they shared 42 single nucleotide differences from the closest mpox virus (MPXV) genome sampled in 2018. This number of changes within 3-4 years is unexpectedly large and points to a much greater evolutionary rate than expected for a poxvirus. Strikingly, most nucleotide changes are of a specific type – a dinucleotide change from TC->TT or its reverse complement GA->AA. This mutation type is characteristic of the action of APOBEC3 deaminases; host-enzymes with reported antiviral function. Analysis of MPXV genomes sampled from 2017 to 2022 showed further evidence of TC->TT mutation pattern enrichment, with 93% of transmitted single nucleotide mutations since 2017 consistent with APOBEC3 editing. Assuming APOBEC-editing is characteristic of MPXV infection in human hosts, we propose an APOBEC clock that – at a rate of ~6 APOBEC3 mutations per year – estimates MPXV has been circulating in humans since 2016. This evolutionary pattern of host-enzyme editing has implications for the longer-term fitness of the virus in this epidemic as such mechanisms are primarily antiviral in function, but in the context of a poxvirus also provide a source of variation that may conceivably facilitate adaptation. ### Competing Interest Statement The authors have declared no competing interest.
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Eric Pyrrhus

2/6
"The smallpox and mpox (MVA-BN), provided as a two-dose regimen, is currently the primary vaccine utilized against mpox...
We evaluated the real-world effectiveness of a single, subcutaneous dose of MVA-BN in this observational, retrospective cohort study...
The adjusted vaccine effectiveness was estimated at 86%."
nature.com/articles/s41591-023

NatureReal-world effectiveness of a single dose of mpox vaccine in males - Nature MedicineEffectiveness of one subcutaneous dose of MVA-BN, the smallpox and mpox vaccine, was estimated to be 86% in a cohort of vaccine-eligible males in Israel, supporting its use to curtail the outbreak of mpox virus.
Public *
Eric Pyrrhus

3/6
The use of the only broad-spectrum designed for DNA virus infections (brincidofovir & cidofovir) may be under-utilized for Mpox infections:

"A 48-year-old man with poorly controlled HIV presented with severe [mpox] infection, having completed 2 weeks of tecovirimat...
Despite a second, prolonged course of tecovirimat, he did not improve...
Intravenous cidofovir was given at 5 mg/kg; the patient made a noticeable improvement after the first IV dose..."
thelancet.com/journals/laninf/

The Lancet Infectious DiseasesUse of cidofovir in a patient with severe mpox and uncontrolled HIV infectionA 48-year-old man with poorly controlled HIV presented with severe human monkeypox virus (hMPXV) infection, having completed 2 weeks of tecovirimat at another hospital. He had painful, ulcerating skin lesions on most of his body and oropharyngeal cavity, with subsequent Ludwig's angina requiring repeated surgical interventions. Despite commencing a second, prolonged course of tecovirimat, he did not objectively improve, and new lesions were still noted at day 24. Discussion at the UK National Health Service England High Consequence Infectious Diseases Network recommended the use of 3% topical and then intravenous cidofovir, which was given at 5 mg/kg; the patient made a noticeable improvement after the first intravenous dose.
Public *
Eric Pyrrhus

4/6
More discussion of how the use of the only broad-spectrum designed for DNA virus infections (brincidofovir & cidofovir) may be under-utilized for Mpox infections:

"Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects"
mdpi.com/2227-9059/11/2/278

MDPIOral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and ProspectsThe monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and Drug Administration (USFDA)-approved antiviral against smallpox. This article reviews the potential of BCV for treating MPX and other Orthopoxvirus (OPXVs) diseases. The literature for this review was collected from PubMed, authentic websites (USFDA, Chimerix), and freely available patent databases (USPTO, Espacenet, and Patentscope). BCV (a lipophilic derivative of cidofovir) has been discovered and developed by Chimerix Incorporation, USA. Besides smallpox, BCV has also been tested clinically for various viral infections (adenovirus, cytomegalovirus, ebola virus, herpes simplex virus, and double-stranded DNA virus). Many health agencies and reports have recommended using BCV for MPX. However, no health agency has yet approved BCV for MPX. Accordingly, the off-label use of BCV is anticipated for MPX and various viral diseases. The patent literature revealed some important antiviral compositions of BCV. The authors believe there is a huge opportunity to create novel, inventive, and patentable BCV-based antiviral therapies (new combinations with existing antivirals) for OPXVs illnesses (MPX, smallpox, cowpox, camelpox, and vaccinia). It is also advised to conduct drug interaction (food, drug, and disease interaction) and drug resistance investigations on BCV while developing its combinations with other medications. The BCV-based drug repurposing options are also open for further exploration. BCV offers a promising opportunity for biosecurity against OPXV-based bioterrorism attacks and to control the MPX outbreak of 2022.
Public
Eric Pyrrhus

5/6
A first attempt at describing the post-acute effects of Mpox infection:

"The later consequences of the disease remain unknown. We, therefore, aimed to evaluate the medium- and long-term morbidity following the acute episode of mpox."
eurosurveillance.org/content/1

www.eurosurveillance.orgEurosurveillance | Persistent morbidity in Clade IIb mpox patients: interim results of a long-term follow-up study, Belgium, June to November 2022While mpox was well characterised during the 2022 global Clade IIb outbreak, little is known about persistent morbidity. We present interim results of a prospective cohort study of 95 mpox patients assessed 3–20 weeks post-symptom onset. Two-thirds of participants had residual morbidity, including 25 with persistent anorectal and 18 with genital symptoms. Loss of physical fitness, new-onset/worsened fatigue and mental health problems were reported in 36, 19 and 11 patients, respectively. These findings require attention by healthcare providers.
Public
Eric Pyrrhus

6/6
Besides the large impact of the Mpox pandemic on Latin America, reports continue to come in from East Asia:

Taiwan reports two locally acquired Mpox infections:
outbreaknewstoday.com/taiwan-r

Mpox acquired by a health care worker in South Korea via needle-stick injury:
wwwnc.cdc.gov/eid/article/29/5

Outbreak News TodayTaiwan reports 2 local monkeypox cases in Hsinchu County and Kaohsiung City - Outbreak News TodayNewsDesk @bactiman63 The Taiwan CDC announced Wednesday the 6th and 7th confirmed monkeypox cases in a man in his 40s in the north and a man in his 20s in the south. They live in Hsinchu County and Kaohsiung City, respectively. They developed fever, papules, and blisters in late February. Swollen lymph nodes, tongue ulcers and […]
Eric Pyrrhus

7/6
Interesting report on :
(AKA or )

"We monitored SARS-CoV-2 & MPXV genomes in the air... in Madrid nightclubs... in 2022.
...
MPXV in the air had increased considerably on Aug 8, with 57% of positive samples containing more than 100 genomes per [cubic meter]; this date coincided with the peak incidence of mpox in Spain."

The authors suggest that air sampling might be a useful surveillance method.


doi.org/10.1016/S2666-5247(23)

Mar 27, 2023, 11:04 PM·Public·Web
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