Mpox 2024 - Contemporary Issues in Biology - PDF

2Y Contemporary Issues in Biology How we lost control of Mpox Dr Claire Donald 21st November 2024  Aims After this session you should be able to: Explain the biology of Mpox virus disease Understa...

2Y Contemporary Issues in Biology How we lost control of Mpox Dr Claire Donald 21st November 2024  Aims After this session you should be able to: Explain the biology of Mpox virus disease Understand that mpox virus is a zoonotic infection and explain how it spreads Understand the molecular technologies used to diagnose the infection and describe the clinical symptoms Appreciate the vaccine and treatment options available  Credit: NIAID/SCIENCE PHOTO LIBRARY Mpox Disease Previously called monkeypox virus First discovered in 1958 Two outbreaks of a pox-like disease in monkeys kept in research colonies First human case documented in 1970 In what is now the Democratic Republic of Congo (DRC)  MPXV Linear double-stranded DNA Genus: Orthopoxvirus Family: Poxviridae Brick-shaped virion Enveloped Host cell-derived membrane Li, Heng et al. eBioMedicine, 2023 Ebolavirus Poxvirus Replication Cycle 1. Binding / Attachment 2. Fusion / Entry 3. Nucleocapsid Release 4. Transcription 5. Translation 6. Replication 7. Lysis or budding 8. Release / Egress ViralZone  MPXV Clade I Responsible for the current rise of cases in Central and Eastern Africa Incidence (2024): 16,000 Fatality rate of 3.6% Clade II Caused the global https://www.cdc.gov/mpox/about/? CDC_AAref_Val=https://www.cdc.gov/ outbreak that began in 2022 poxvirus/mpox/about/index.html Incidence (2022): 92,167 Fatality rate 0.03% Clade I is endemic to Central Africa whereas Clade II is endemic to West Africa Historically, Clade I causes more severe disease than Clade II  Outbreaks Discovered in 1958 Initial cases of mpox were misdiagnosed as chickenpox WHO began actively monitoring human mpox cases in Congo in the 1980’s Cases remained largely endemic to Africa with some cases exported internationally In 2022, over 60,000 cases of mpox had been reported in over 105 countries WHO declares mpox a public health emergency of international concern Lu et al, Signal Transduction and Targeted Therapy, 2023 Outbreaks May 2023 Aug 2024 The spread of clade II mpox had reduced by The more deadly Clade Ib began to spread 90% between Feb-May 2023 in comparison to across borders. the previous 3 months Concerns are heightened by increasing Therefore, after more than 87,000 cases and evidence of mpox-HIV co-infection 140 dealths reported in 111 countries the PHEIC was ended Mirroring the historical spread of HIV on the continent via transport corridors and sexual networks, raising the risk of infection among women and children. Outbreaks  Transmission First spreads to people from animals Zoonotic infection Mpox virus can infect various mammalian species Rodents, gazelles, hedgehogs, prairie dogs, non-human primates, and humans Animal reservoir species Unknown Problem for eradication Duarte et al., 2024 Transmission Lu et al., 2023 The specified method by which MPXV spreads to humans is unknown Direct transmission (touch, bite, scratch) Indirect transmission (blood, body fluids, cutaneous lesions, or mucosal lesions) The virus enters the body through: Skin breaks (some of which are not apparent) Eyes, mouth, nose, and other regions of the respiratory tract Symptoms Usually begin within 7 days but can take up to 21 days Typically, last 2-4 weeks May last longer in those with weakened immune systems Symptoms Adapted from: https://my.clevelandclinic.org/health/diseases/22371-monkeypox Diagnosis da Silva et al., 2023  Diagnosis The gold standard for MPXV diagnostics Highly sensitive and fast diagnostics Multiple different targets available Important for determining which clade is present  Diagnosis Highly important techniques for determining seroprevalence of MPXV within a population Integral to vaccine efficacy studies Limited use for MPXV diagnostics Potential cross-reactivity with other circulating orthopoxviruses IgM maybe more informative than IgG tests da Silva et al., 2023  Diagnosis Used in addition to traditional diagnosis Due to high reagent and infrastructure costs as well as the requirement for specialist training makes this unsuitable for clinical use Therefore, only a small proportion of clinical samples are being sequenced To combat this, new approaches such as MinION sequencers are being used to increase the number of sequences available Like COVID-19, these sequences are crucial to public health decision making da Silva et al., 2023  Treatment No proven effective antiviral therapies for mpox Three drugs commonly used in clinic ⚬ Tecovirimat ⚬ Cidofovir ⚬ Brincidofovir Often prescribed as combination therapy to avoid drug resistance Lu et al., 2023 Supportive Care: ⚬ Oral or intravenous fluids ⚬ Treat the symptoms ⚬ Treat other infections as necessary  Vaccination Smallpox vaccination protects against MPXV Two approved vaccines against MPXV ⚬ Third-generation smallpox vaccines ⚬ Both vaccines are live-attenuated ⚬ MVA-BN and LC16m8 Effective against both clades: I & II People born after 1971 are at higher risk of infection Preparedness Community engagement is key Similarities to the COVID-19 pandemic community prevention Large emphasis on getting vaccinated where possible Strong advocacy presence from MSM community  Conclusions Mpox Zoonotic Community engagement is key Formally monkeypox and related Transmitted from animals Outbreak control relies on suitable to smallpox - a persistent public - but reservoir is still unknown prevention and control methods health threat worldwide - vaccination is key Than You k Questions? [email protected]