Sat, 08/13/2022 - 22:16
Episode 281 Monkeypox update
Epidemiology
Ep 281-1 Recent WHO data:
Ep 281-2: Sciensano Belgium
Dutch https://epidemio.wiv-isp.be/ID/Documents/Monkeypox/Info%20HCW_NL.pdf
French: https://epidemio.wiv-isp.be/ID/Pages/MonkeyPox.aspx
Sorry, not in English
Are we “over the top” or will Amsterdam and Antwerp pride give a “boost”?
Ep 281-3: Christophe Van Dijck medRxiv Modeling of Belgian epidemic
A network model to simulate a monkeypox epidemic among men who have sex with men suggest
- that unrecognized infections have an important impact on the epidemic,
- that vaccination of individuals at highest risk of infection reduces epidemic size more than post-exposure prophylaxis of sexual partners
Ep 281-4: Technical briefing from UK Health Service Agency
Route of transmission
Whilst the primary reported route is through close or sexual contact, monkeypoxvirus has been detected in air and environmental samples in the hospital room of infected patients. There are no confirmed instances of airborne transmission. Limited household transmission has been described in the UK. Detailed investigations of some cases have found small numbers with no known route of acquisition, due to reporting no sex or other potential exposures during their incubation. Assessment (confidence): transmitting primarily through close or sexual contact(moderate).
CASES RELATIVE TO POPULATION
While new cases tend to drop in European countries, they increase in the US.
THERAPY
Ep 281-5: Gaelle Frenois-Veyrat bioRxiv 20 July : Tecovirmat has nanomolar activity, while cidofovir has only micromolar activity in vitro against MPX
According to https://pubmed.ncbi.nlm.nih.gov/19195323/ resistance to Tecovirimat is associated with particular mutations in the FL13L or VP37 protein: positions F25V, H194N, G277C, I372N and insertion SVK at 303-305
Conclusions:
These results support the use of tecovirimat in the clinical response to the 2022 MPXV
outbreak, in particular for immunosuppressed patients. Of note, tecovirimat is not
recommended for pregnant women due the absence of safety data.
Considering that resistance mutations to tecovirimat under artificial culture pressure have
been described for various orthopoxviruses 17 (Figure S2), attention to adherence to
treatment will be needed, especially in the context of milder clinical forms, and it will be
important to monitor of the evolution of the virus during its outbreak circulation.
VACCINATION
Ep 281-6: Patrick Smits collected info on various strategy throughout Europe
Ep 281-7: Michael Thy medRxiv 4 August 2022 Breakthrough infections after post-exposure MPX vaccination
From 276 post-exposure vaccinated individuals, 12 (4%) had a MPX breakthrough infection with no severe infection.
10/12 patients developed MPX in the five days and 2 had a BTI at 22 and 25 days after vaccination
Ep 281-8: Flavia Chiuppesi medRxiv 11 August 2022 Synthetic modified vaccinia Ankara vaccines confer potent monkeypox immunity in non- human primates and healthy adults
A vaccine carrier, Modified Vaccinie Ankara (non-replication competent), developed as (experimental) SARS-CoV-2 vaccine, also induces high neutralizing Ab and T cells in non-human primates
Human data
Intesting data, but still a long way to go with clinical trials
GENOMIC INFORMATION
Ep 281-4:
Most UK genomes fall in the known outbreak lineage B.1, but 2 are designated as lineage A.2, which may be co-circulating internationally.
B1 contains 105 distinct point mutations when compared to reference ON563414.3.
79 of the mutations (75.24%) are consistent with the action of human apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) (also known to produce hypermutation in HIV, and copunteracted by HIV Vif).
Remarkably: evidence of genetic variation within individual lesion samples, which could be either acquired (by APOBEC3) or transmitted diversity
Ep 281-9: Tery Jones medRxiv 11 August 2022: Important genetic variability in first European isolates
- Identical non-synonymous amino acid changes in six genes and the signature of APOBEC editing match other sequences from the European outbreak.
- Non-synonymous changes that were present in one to three sequences were found in 34 other genes.
Conclusion: The relatively sustained and widespread human-to-human transmission is new and may lead to a new viral evolution. The consequence of changes in poxvirus genes in a new host … is unpredictable.
Ep 281-10: WHO on renaming MPX
Consensus was reached to now refer to the former Congo Basin (Central African) clade as Clade one (I) and the former West African clade as Clade two (II). Additionally, it was agreed that the Clade II consists of two subclades clade II A and II B, the latter referring to the group of variants circulating in the 2022 global outbreak.