Poxviruses

Question 1

Mpox structure & classification

Answer 1

Family: Poxviridae
Genus: Orthopox

Enveloped dsDNA

2 clades: Ia(Central African) & Ib (South Kivu) - HCID
II (West-African) with subclades IIa & IIb

Baltimore: I

Question 2

Mpox reservoir

Answer 2

Animal to human - rope squirrels, tree squirrels, Gambian pouched rats, monkeys (incidental host).

Humans (incidental hosts).

Question 3

Mpox incubation & infectious period

Answer 3

4 to 21 days

Infectious period - unclear but likely beginning of prodrome to when lesions scab over

Question 4

Mpox mortality

Answer 4

Clade 1: 10%
Clade 2: 0.1%

Question 5

Mpox diagnostics

Answer 5

1. RT-PCR - for orthopox & mpox. Done locally and offered by RIPL with melting curves to identify clades.

Novel variant of Clade 1 in early 2024 in DRC - deletions causing false negative Clade 1 PCR & false positive Clade 2 PCR.

Question 6

Mpox IPC

Answer 6

Clade 1: HCID
Clade 2: NOT HCID - self isolate until asymptomatic (all lesions crusted, fallen off and repithelialised)
If hospitalised - Resp isolation room with en-suite and PPV lobby

Question 7

Mpox management

Answer 7

1. Tecovirimat - inhibits viral envelope protein p37 highly conserved in all orthopox viruses. Prevents formation and egress of virions.

No published trial data - given authorisation under ‘exceptional circumstances’

Ongoing RCT -

PALM trial - DRC - Tecovirimat RCT - PRELIM results - no mortality benefit.

PLATINUM. Various observational trials show benefit.

Eligibility:

Confirmed Mpox &
Symptomatic &
Meeting criteria for severe disease - ocular, pain, critical illness, >100 lesions, CNS disease etc

Dosing:
600mg BD for 2 weeks

2. Cidofovir/Brincidofovir with probenecid - no data but in vitro activity

EYE disease - trufluridine eye drops in addition

3. Vaccinia immune globulin (VIG)

Question 8

Mpox/smallpox vaccines

Answer 8

1st gen - calf skin & purified from calf lymph
2nd gen - tissue cell culture

Both live replicating vaccinia - Lister & NYCBH/ACAM2000

3rd gen - Imvanex - modified vaccinia ankara- replication defective virus which is attenuated by serial passages through chicken embryo fibroblast cells - cannot replicate in mammalian cells.

2 doses - 28 days apart

Question 9

Imvanex & PEP

Answer 9

Regular dosing: JCVI endorse 0.1ml Intradermal 2 doses 28 days apart (1 dose if previous smallpox immunisation).

PEP: offer single dose 0.1 ml ID preferably within 4 days of exposure or max 14 days after exposure.

MAY be given with other live vaccines and can be given in HIV with CD4>100.

Question 10

Mpox tecovirimat resistance

Answer 10

F13 protein mutations - T289A mutation resulted in 8 fold increase in 50% effective concentration.

Question 11

Poxviridae subgroups

Answer 11

Orthopox - Mpox, Vaccinia, Cowpox, Variola

Parapox - Orf

Molluscipox - Molluscum contagiosum

Yatapox - Tanapox, Yana Monkey Tumour virus

Question 12

Tanapox

Answer 12

Family: Poxviridae
Genus: Yatapoxvirus

NHPs in Africa are natural host

Somalia to Senegal

Likely vector: Mansonia mosquito

5 human cases - nodular umbilicated skin lesions. Self limiting.

Diagnosis by EM/sequencing.

Question 13

Molluscum contagiosum

Answer 13

Family: Poxviridae
Genus: Molluscipox

Linear, dsDNA enveloped

Baltimore: I

Diagnostics: EM at VRD colindale. RT-PCR at RIPL.

Therapeutics: Canthadirin (beetle juice) & Berdazimer FDA approved.

Question 14

Orf

Answer 14

Family: Poxviridae
Genus: Parapoxvirus

dsDNA enveloped

Baltimore: I

Diagnostics: RT-PCR at RIPL, EM at VRD.

Therapeutics: Imiquomod, liquid nitrogen

Question 15

Mpox PEP

Answer 15

Vaccine within 4 days but up to 14 days

One dose of Imvanex booster if previous smallpox vaccination or previous course of Imvanex > 2 years go.