Mpox
Mpox (formerly known as Monkeypox) is a viral zoonosis with symptoms similar to but less severe than smallpox. Mpox was first discovered in 1958 when two outbreaks of a pox-like disease occurred in colonies of monkeys kept for research, hence the name "monkeypox."
All edits by Meredith Hanel
November 28, 2022
November 28, 2022
Jynneos, produced by Bavarian Nordic, is approved in Canada and the US for monkeypox and used off-label in Europe for monkeypox. The Jynneos vaccine is derived from Modified Vaccinia Ankara (MVA) and is a live virus that does not replicate in humans. WHO recommended MVA to be given up to 14 days after exposure with the ideal time being within 4 days. Jynneos is sold as Imvanex in the EU.
Since the May 2022 monkeypox outbreak three distinct clades of monkeypox virus are recognized. Clade 2 and clade 3 fall within the “West African” clade which causes less severe disease. Clade 1 is formerly known as the “Central African” or “Congo Basin” clade which is associated with higher fatality. The May 2022 outbreak is thought to have a single origin because all sequenced outbreak strains of the MPXV cluster together with similar sequence. The 2022 outbreak cluster is called B.1 which branches off from lineage A.1 in clade 3. The A.1 lineage was associated with the exportation of MPXV from Nigeria to the United Kingdom, Israel and Singapore in 2018 and 2019 and a large outbreak in Nigeria in 2017-2018.
Cepheid announced plans to develop a PCR test specifically for monkeypox in partnership with BioGX, a reagents company. Monkeypox PCR tests will be designed to run on the Cepheid's GeneXpert hardware.
On June 17, 2022 WHO removed the distinction between endemic and non-endemic countries when reporting on monkeypox. As of June 15, 2103 laboratory confirmed cases and one probable case, including one death were reported to WHO. 84% of confirmed cases were from the WHO European Region.
On June 17 WHO removed the distinction between endemic and non-endemic countries when reporting on monkeypox. As of June 15, 2103 laboratory confirmed cases and one probable case, including one death were reported to WHO. 84% of confirmed cases were from the WHO European Region.
Officials for the CDC and the WHO stated that many transmissions of monkeypox are not detected because the disease does not match descriptions in medical textbooks. Whereas textbooks show pox lesions covering a person from head to toe, people with monkeypox in the 2022 outbreak have presented with only a few localized lesions. Monkeypox may be misdiagnosed for common sexually transmitted diseases such as herpes or syphilis. Epidemiologist Jennifer McQuiston at the CDC said that doctors should suspect monkeypox in anyone with a new rash. Common presenting symptoms of monkeypox in the 2022 outbreak include genital and peri-anal lesions, fever, swollen lymph nodes and pain when swallowing. Guidance for clinicians on signs, symptoms and testing for monkeypox was distributed by the CDC Health Alert Network.
On June 22, 2022 the Department of Heath and Human Services through the CDC began shipping orthopoxvirus tests to five commercial laboratory companies which are Aegis Science, Labcorp, Mayo Clinic Laboratories, Quest Diagnostics and Sonic Healthcare, to increase monkeypox testing capacity and access.
- S105L mutation in the C23L(S105L) mutationgene occursencoding ina chemokine binding protein, which when deleted from rabbitpox virus increases disease severity in rabbits
- S54F mutation occurs in the C22L(S54F) mutationgene, occursencoding ina tumour necrosis factor (TNF) receptor-like protein. and deletionDeletion of a similar gene from ectromelia virus increases lung pathology in mice
- D266N mutation occurs in the C19L(D266N) mutation occursgene, inencoding an ankyrin repeat protein which has unknown function but may have a role in host range or virulence
- F13L(E353K) mutation in the F13L gene occurs in a target of the antiviral drug tecovirimat and tecovirimat resistance was conferred by a F13L protein mutation corresponding to the single F13L amino acid mutation corresponding to the nucleotide sequence change G277C. The F13L gene is involved in the production of enveloped orthopoxvirus virions.
- R48C mutation occurs in the C9L(R48C) mutation occursgene, inencoding an antagonist of gene products stimulated by interferon that when deleted from vaccinia virus causes the virus to replicate worse in the presence of interferon
- H221Y mutation occurs in the A46L(H221Y) mutation occursgene, inencoding a virulence factor gene that when deleted in vaccinia virus reduces virulence in mice
Tecovirimat (Tpoxx), produced by Siga Technologies, is approved in Europe to treat monkeypox and approved by FDA for smallpox. The 2022 monkeypox virus has a mutation in the F13L gene and mutations in this gene are associated with resistance to tecovirimat.
The 2022 version of monkeypox virus has on average 50 nucleotide base changes, also called small nucleotide polymorphisms (SNPs), from the 2018-2019 monkeypox virus sequences. A research group from Portugal suggested that this branch may represent accelerated evolution since the rate of nucleotide changes is about 6-12 times more than expected for Orthopoxviruses, expected to have 1-2 substitutions per year. It was suggested that accelerated evolution of monkeypox virus could be driven by the action of APOBEC3, an enzyme that mutates viruses as a defense tactic. APOBEC3 forces mutations to occur during virus replication by deaminase and deaminase-independent mechanisms.
The differences between the 2018 MPXV reference sequence and the 2022 MPXV outbreak virus include 3 amino acid changes (D209N, P722S, M1741I) in the immunogenic surface glycoprotein B21, a previously suggested antibody target. The UK government classified these three mutations as high priority. Inserting this version of the protein into non-virulent cowpox strains increased disease severity and mortality in rats.
The differences between the 2018 MPXV reference sequence and the 2022 MPXV outbreak virus include 3 amino acid changes (D209N, P722S, M1741I) in the immunogenic surface glycoprotein B21, a previously suggested antibody target. It was suggested that accelerated evolution of monkeypox virus could be driven by the action of APOBEC3, an enzyme that mutates viruses as a defense tactic. APOBEC3 forces mutations to occur during virus replication by deaminase and deaminase-independent mechanisms.
The UK classified 4 mutations as medium priority:
- C23L(S105L) mutation occurs in chemokine binding protein, which when deleted from rabbitpox virus increases disease severity in rabbits
- C22L(S54F) mutation occurs in tumour necrosis factor (TNF) receptor-like protein and deletion of a similar gene from ectromelia virus increases lung pathology in mice
- C19L(D266N) mutation occurs in an ankyrin repeat protein which has unknown function but may have a role in host range or virulence
- F13L(E353K) mutation occurs in a target of the antiviral drug tecovirimat and tecovirimat resistance was conferred by a single F13L amino acid mutation corresponding to the nucleotide sequence change G277C
The UK classified 2 mutations as low priority:
- C9L(R48C) mutation occurs in an antagonist of gene products stimulated by interferon that when deleted from vaccinia virus causes the virus to replicate worse in the presence of interferon
- A46L(H221Y) mutation occurs in a virulence factor gene that when deleted in vaccinia virus reduces virulence in mice
Monkeypox virus was initially divided into two clades: The Central African strain/clade, also known as the Congo Basin strain/clade of monkeypox virus spreads more easily and cause more severe disease than the West African strain/clade. The West African clade of monkeypox has been reported to have a case fatality ratios of 1% and less than 1%. The Congo Basin/Central African clade has been reported to have case fatality ratios between 3-10% and more than 10%. Case fatality rate/case fatality risk/case fatality ratio/CFR refers to the proportion of people who die from a disease among those diagnosed over a certain period of time.
Since the May 2022 monkeypox outbreak there are three distinct clades of monkeypox virus. Clade 2 and clade 3 fall within the “West African” clade which causes less severe disease. Clade 1 is formerly known as the “Central African” or “Congo Basin” clade which is associated with higher fatality. The May 2022 outbreak is thought to have a single origin because all sequenced outbreak strains of the MPXV cluster together with similar sequence. The 2022 outbreak cluster is called B.1 which branches off from lineage A.1. The A.1 lineage was associated with the exportation of MPXV from Nigeria to the United Kingdom, Israel and Singapore in 2018 and 2019 and a large outbreak in Nigeria in 2017-2018.
The 2022 version of monkeypox virus has on average 50 nucleotide base changes, also called small nucleotide polymorphisms (SNPs), from the 2018-2019 monkeypox virus sequences. A research group from Portugal suggested that this branch may represent accelerated evolution since the rate of nucleotide changes is about 6-12 times more than expected for Orthopoxviruses, expected to have 1-2 substitutions per year.
The differences between the 2018 MPXV reference sequence and the 2022 MPXV outbreak virus include 3 amino acid changes (D209N, P722S, M1741I) in the immunogenic surface glycoprotein B21, a previously suggested antibody target. It was suggested that accelerated evolution of monkeypox virus could be driven by the action of APOBEC3, an enzyme that mutates viruses as a defense tactic. APOBEC3 forces mutations to occur during virus replication by deaminase and deaminase-independent mechanisms.
The milder lesions reported in the 2022 monkeypox outbreak are thought to reflect an incomplete picture of the spectrum of monkeypox illness, in which mild cases are not easily recognized. There is no evidence to suggest that a recent mutation in monkeypox, lead to a change in symptoms or mode of spread. Monkeypox is a DNA virus, which mutates and changes more slowly than RNA viruses such as SARS-CoV-2 which causes COVID-19. This is because DNA viruses are better at detecting and repairing mutations.
Monkeypox virus was initially divided into two clades: The Central African strain/clade, also known as the Congo Basin strain/clade of monkeypox virus spreads more easily and cause more severe disease than the West African strain/clade. The West African clade of monkeypox has been reported to have a case fatality ratios of 1% and less than 1%. The Congo Basin/Central African clade has been reported to have case fatality ratios between 3-10% and more than 10%. Case fatality rate/case fatality risk/case fatality ratio/CFR refers to the proportion of people who die from a disease among those diagnosed over a certain period of time.
The milder lesions reported in the 2022 monkeypox outbreak are thought to reflect an incomplete picture of the spectrum of monkeypox illness, in which mild cases are not easily recognized. There is no evidence to suggest that a recent mutation in monkeypox, lead to a change in symptoms or mode of spread. Monkeypox is a DNA virus, which mutates and changes more slowly than RNA viruses such as SARS-CoV-2 which causes COVID-19. This is because DNA viruses are better at detecting and repairing mutations.
Since the May 2022 monkeypox outbreak three distinct clades of monkeypox virus are recognized. Clade 2 and clade 3 fall within the “West African” clade which causes less severe disease. Clade 1 is formerly known as the “Central African” or “Congo Basin” clade which is associated with higher fatality. The May 2022 outbreak is thought to have a single origin because all sequenced outbreak strains of the MPXV cluster together with similar sequence. The 2022 outbreak cluster is called B.1 which branches off from lineage A.1. The A.1 lineage was associated with the exportation of MPXV from Nigeria to the United Kingdom, Israel and Singapore in 2018 and 2019 and a large outbreak in Nigeria in 2017-2018.
The 2022 version of monkeypox virus has on average 50 nucleotide base changes, also called small nucleotide polymorphisms (SNPs), from the 2018-2019 monkeypox virus sequences. A research group from Portugal suggested that this branch may represent accelerated evolution since the rate of nucleotide changes is about 6-12 times more than expected for Orthopoxviruses, expected to have 1-2 substitutions per year.
The differences between the 2018 MPXV reference sequence and the 2022 MPXV outbreak virus include 3 amino acid changes (D209N, P722S, M1741I) in the immunogenic surface glycoprotein B21, a previously suggested antibody target. It was suggested that accelerated evolution of monkeypox virus could be driven by the action of APOBEC3, an enzyme that mutates viruses as a defense tactic. APOBEC3 forces mutations to occur during virus replication by deaminase and deaminase-independent mechanisms.
Brincidofovir (Tembexa) is FDA approved for smallpox and considered safer than the smallpox drug cidofovir. Brincidofovir inhibits viral DNA polymerase and prevents DNA replication. Emergent BioSolutions bought the rights to Tembexa from Chimerix for $225 million in May 2022.
Chimerix for $225 million in May 2022.
Monkeypox virus was initially divided into two clades: The Central African strain/clade, also known as the Congo Basin strain/clade of monkeypox virus is thought to spreadspreads more easily and cause more severe disease than the West African strain/clade. The West African clade of monkeypox has been reported to have a case fatality ratioratios of 1% and less thethan 1%. The Congo Basin/Central African clade has been reported to have case fatality ratioratios between 3-10% and more than 10%. Case fatality rate/case fatality risk/case fatality ratio/CFR refers to the proportion of people who die from a disease among those diagnosed over a certain period of time.
Since the May 2022 monkeypox outbreak there are three distinct clades of monkeypox virus. Clade 2 and clade 3 fall within the “West African” clade which causes less severe disease. Clade 1 is formerly known as the “Central African” or “Congo Basin” clade which is associated with higher fatality. The May 2022 outbreak is thought to have a single origin because all sequenced outbreak strains of the MPXV cluster together with similar sequence. The 2022 outbreak cluster is called B.1 which branches off from lineage A.1. The A.1 lineage was associated with the exportation of MPXV from Nigeria to the United Kingdom, Israel and Singapore in 2018 and 2019 and a large outbreak in Nigeria in 2017-2018.
The 2022 version of monkeypox virus has on average 50 nucleotide base changes, also called small nucleotide polymorphisms (SNPs), from the 2018-2019 monkeypox virus sequences. A research group from Portugal suggested that this branch may represent accelerated evolution since the rate of nucleotide changes is about 6-12 times more than expected for Orthopoxviruses, expected to have 1-2 substitutions per year.
The differences between the 2018 MPXV reference sequence and the 2022 MPXV outbreak virus include 3 amino acid changes (D209N, P722S, M1741I) in the immunogenic surface glycoprotein B21, a previously suggested antibody target. It was suggested that accelerated evolution of monkeypox virus could be driven by the action of APOBEC3, an enzyme that mutates viruses as a defense tactic. APOBEC3 forces mutations to occur during virus replication by deaminase and deaminase-independent mechanisms.
Creative Biogene has a Monkeypox Virus Real Time PCR kit.
As of June 5, 2022 the US has capability to process about 7000 orthopoxvirus diagnostic tests per week through about 70 labs in 46 states. Many diagnositic tests do not specifically test for monkeypox, but the family orthopoxvirus, of which monkeypox virus is a member. A positive orthopoxvirus molecular test may be assumed to be monkeypox during a monkeypox outbreak.
Tetracore is developing a rapid antigen test for monkeypox point-of-care testing. Results were published in 2013 on its test called Orthopox BioThreat Alert assay, which can be used outside the laboratory. The test is an antibody-based lateral-flow assay which labels and captures orthopox virus.
Trivitron Healthcare, a medical device company in India, developed a four-color fluorescence-based kit, reported to take an hour to complete.
Becton Dickinson partnered with CerTest Biotec to produce the monkeypox virus molecular diagnostic test called VIASURE Monkeypox CE/IVD test. The test will use and be validated on the BD MAX system, an automated platform for nucleic acid extraction and real-time PCR. The test is reported to give results for up to 24 samples within three hours.
Monkeypox is a viral zoonosis with symptoms similar to, but less severe than smallpox. This disease, caused by Monkeypox virus infection, has two periods. The first period, is characterized by fever, headache, lymphadenopathy, myalgia and intense asthenia. The second period is characterized by skin rash that appears within 1-3 days of fever. Most people recover from monkeypox within a few weeks without the need for treatment but the disease can be more sever in young children, pregnant women and immunocompromised individuals. The incubation period for monkeypox is reported to be up to 21 days. Public health institutes recommend active monitoring and isolation/quarantine of close contacts for a minimum of 21 days after the last day of exposure.
Monkeypox primarily occursoccurred in central and west Africa until an atypical monkeypox outbreak began in May 2022. Monkeypox endemic countries include Benin, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Gabon, Ghana (animals only), Ivory Coast, Liberia, Nigeria, the Republic of the Congo, Sierra Leone and South Sudan. Animal hosts include rodents and non-human primates. The first monkeypox outbreak outside of Africa infected 70 cases in the United States in 2003. This outbreak was linked to contact with infected pet prairie dogs that had been housed with animals that were imported from Ghana.
Abbott Laboratories stated it is developing a test for monkeypox.
BGI Group, based in Shenzhen, developed PCR-based monkeypox virus detection kit.
Daan Gene, based in Guangzhou, has a CE certified PCR-based detection kit for monkeypox virus.
Sansure Biotech developed a monkepox virus nucleic acid diagnostic kit that has CE certification. The kits is compatible with fluorescence PCR and their iPonatic Molecular Diagnostic System for point-of-care testing (POCT) and COVID-19 molecular diagnostics platforms.
Shanghai Zhijiang Bio has a CE registered monkeypox virus nucleic acid detection kit which uses fluorescent PCR.
Roche and subsidiary TIB Molbiol, developed three PCR tests for diagnosis of monkeypox. The three LightMix Modular Virus test kits use quantitative PCR technology and run on the company’s PCR analyzers. One test detects orthopoxvirus which includes smallpox, cowpox, horsepox and monkeypox. The second test detects the West African and Central African clades of virus. The third test identifies the presence of orthopoxvirus and whether it is either of the two monkeypox forms.
Inovio Pharmeuticals has a DNA medicines platform and worked on a smallpox vaccine with published results in 2010. The experimental DNA-based smallpox vaccine protected nonhuman primates against monkeypox in a challenge trial.
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