Lecture 7 Flashcards
Introduction to Mpox virus
Family - Poxviridae
Genus - Orthopoxvirus
Members: Variola virus-smallpox, Vaccinia virus - Smallpox vaccine, cowpox virus
Mpox is a viral zoonotic disease - occurs primarily in tropical rainforest areas
Occurs sporadically in Central and West Africa’s tropical rainforest
Symptoms similar to smallpox but less severe
Mpox virus Structure
- Largest viruses excluding giant viruses
- dsDNA genome - ~190,000bp
- More than 200 polypeptides - target immune system
- Brick shaped - ‘dumbbell’ core contains nucleic acid, lateral bodies
- Enveloped - Resistant to inactivation
- Replicate in cytoplasm
- Some explored as gene therapy vectors
History of Mpox
- Discovered in 1958
- Two outbreaks of pox like disease in crab-eating monkeys housed in Statens Serum Institut in Copenhagen
- Human Mpox cases identified in 1970 in 9 year old boy - democratic republic of congo
- Remained endemic in Central and West Africa
Two distinct clades of Mpox
Clade 1 - Congo basin or Central African clade
Morality of up to 10.6%
Clade 2, IIa, IIb - West African Clade
Sequence similarity is over 99%
Morality of up to 3.6%
Natural Reservoir of Mpox
- Unknown
- Most likely reservoir is African rodents and small mammals
- Human infection oreviously caused by handlings infected monkeys, rope and tree squirrels, gambian rats, striped mice, dormice
- Mpox virus only been isolated twice from animals in nature
First - ill African rodent (rope squirrel) IN DRC - 1958
Second - dead infant Mangabey in Tai National Park - Cote d’Ivoire - 2012
Sporadic cases
!0 African countries affected: DRC, Cameroon, Central African Republic, Nigeria, Ivory Coast, Liberia, Sierra Leone, Gabon and SOuth Sudan
Nigeria: 2017-2019:
- Largest documented outbreak
- Initial cluster of cases (two brothers, their uncle and neighbour) fell sick after eating captured monkey from neighbourhood
- 244 cases across 25 states and federal capital territory of Nigeria
- Six deaths recorded
- 3/4 cases were male and aged between 21-40
Mpox cases outside of Africa
Cases from USA in 2003:
- 53 cases
- West African clade following contact with pet prairie dogs - infected from exotic animals in Ghana
Between 2018-21:
- Handful of cases (1 in israel, 1 in Singapore, 7 in UK)
- No fatalities reported
- 5 cases were from people travelling back from Nigeria
Current number of cases of Mpox in Europe?
26703 across 29 EU/EEA countries
- Majority of EU countries have not reported a new monkeypox case in last 21 days, and 12 countries not reported one for more than 30 days.
Distribution of Mpox clades
The 2022 outbreak is caused by lineage B.1 of the West African clade
Continued evolution is being observed
Three non- synonymous single nucleotide polymorphisms (D209N, P722S and M1741I), which are found in the surface glycoprotein B21R, a key antibody target, are enhancing the transmissibility of the virus.
Life cycle of Mpox
Two infectious forms?: Extracellular Enveloped virion (EEV) and Intracellular Mature Virion (IMV) - differ in surface glycoproteins and infect cells via different mechanisms
EEV:
1. Infecting EEV attaches and enters cell
- Virus uncoats -> Leads to early gene expression or second uncoating
- Second uncoating causes intermediate gene expression (which then leads to DNA replication) or immediate DNA replication
- Viral factory activated by DNA replication
- Leads to late gene expression and assekby of progeny virions, OR forms immature virions which then form intracellular mature virions
Immune invasion of Mpox
Encodes numerous viral proteins involved in evading host immunity:
- Intrinsic immunity
- Innate immunity
- Adaptive immunity
Western African (clade II) clade does not express complement-modulating proteins
Central African (clade I) strains encode monkeypox inhibitor of complement enzyme (MOPICE) - inhibits complement activation by binding to C3 and C5 convertases
Transmission of Mpox virus
Transmission occurs via:
- bites and scratches from infected animals
- Preparation and handing of infected animal products (bushmeat) may also result in transmission
- Indirect contact with contaminated fomites e.g. bedding, clothing
- Close respiratory tract, mucous membranes, broken skin
- via placenta (congenital monkeypox)
4 stages of progression
- Stage I - incubation (5-21 days)
No symptoms
Virus present in bloodstream at end of incubation period - Stage II - Febrile stage (1-4 days)
Fever + other symptoms e.g. swollen lymph nodes, headache, chills, sore throat, fatigue, malaise
Virus in blood
Small lesions in mouth at end of stage II - Stage III - Rash stage
- Virus may be in blood early at stage
- Virus present in skin lesions
- Antibodies produced and become detectable
Stage IV - Recovery
- Patient recovered
- Specific antibodies present in blood
- Scars may remain
Smallpox vaccine for Mpox
- Mass vaccination and then targeted vaccination in conjunction with surveillance resulted in elimination of smallpox in 1977
- In 1980, after certification activates, WHO declared smallpox eradicated
- By 1985, except military personnel and lab workers exposed to orthopox virus’s smallpox vaccine was not administered to anyone
Three vaccines of Mpox
ACAM2000 - live vaccinia virus:
- SIngle dose
- Prick skin surface
- Produces lesion
- Can replicate, so not recommended for everyone e.g. pregnant women, immunocompromised people, atopic dermatitis
- Can spread from vaccinee to contacts. Post vaccination cardiac adverse events reported
Modified vaccinia Ankara (MVA) - Two doses 4 weeks apart, no lesion forms, no replication
LC16m8 (modified vaccinia virus) - liscenced in japan - Single-dose, less replication ability than ACAM2000, and safer
Mpox treatment
- No specific treatments, but outbreaks controlled
- Antivirals (Cidofovir, Brincidofovir)
- Vaccinia immune globulin can be used to control Mpox outbreak
Mpox risk groups
- People born after 1980
- Direct contact with infected people/animals
- Men who have sex with men
- Eating bush meat
Prevention
Reducing risk in people:
- Raise awareness of risk
- Educate on ways to reduce close contact
Public health educational messages should focus on the following risks:
- Reduce risk of animal-to-human transmission
- Avoid contact with rodents and primates
- Limit direct exposure to blood and meat
Thorough cooking of meat prior to consumption - PPEs should be worn while handling sick animals, infected tissues and in slaughtering procedures
