Measles

Question 1

Receptor for measles virus

Answer 1

SLAM (CD150)

Question 2

What are the two main glycoproteins in measles virus and what are their functions?

Answer 2

H = haemagluttinin - bids receptor. VNAb against H protein important in immune response

F = fusion protein - allows cell to cell spread

Question 3

Patients most at risk of measles virus?

Answer 3

Under 2 years

Pregnant women

Adults

Immunosuppressed

Question 4

R0 of measles virus

Answer 4

15-20

Question 5

What impact does measles have on the hosts immune system?

Answer 5

Suppresses adaptive immune response which can last for months/years

Blocks IFN production

Imbalance of lymphocyte populations causinng ‘immunity amnesia’

Secondary bacterial infections are common after measles infection

Question 6

Infectious period of measles

Answer 6

4 days before to 4 days after rash

Question 7

Transmission route of measles

Answer 7

Direct contact, droplet and aerosol spread

Question 8

Symptoms of measles infection

Answer 8

Three C’s - cough, coryza, conjunctivitis

Fever

Rash (starts on face, behind ears spreads to trunk - like been poured red paint on)

Question 9

Complications of acute measles

Answer 9

Mostly seen in immunocompromised, young infants and adults

Pneumoniits (highest cause of death)

Otitis media

Diarrhoea

Keratoconjunctivitis

Secondary bacterial and respiratory infection

CNS disease

Question 10

What is breakthrough measles?

Answer 10

Occurs due to incomplete immunity post vaccine or WT infection

Often from prolonged contact (HCW or household contacts who care for case)

Conjunctivitis often absent

Rash can be absent or atypical

Lower infectivity due to VNAb response in respiratory tract

Question 11

What test what you do to confirm breakthrough measles?

Answer 11

IgG avidity (this will be high) - IgM may be negative

Question 12

What is the likelihood of primary measles pneumonitis? What would a CXR show?

Answer 12

3-4% (most pneumonia caused by secondary bacterial infection)

CXR - ground-glass opacities and consolidation, bronchiolar wall thickening

Question 13

What are the four types of CNS disease occurring in measles?

Answer 13

1) Primary Measles encephalitis

2) Acute post-infectious measles encephalomyelitis (or ADEM)

3) Measles inclusion body encephalitis

3) Subacute sclerosing pan-encephalitis

Question 14

When does primary measles encephalitis occur? What would you expect to see in CSF? Is RNA detected in CSF? What is the mortality?

Answer 14

During or within 1 week of rash

Lymphocytic pleocytosis and mildly raised protein

Yes RNA is detectable

10-15% mortality

Question 15

When does ADEM occur in relation to measles infection? What would be seen in brain imaging? Is RNA detectable in CSF?

Answer 15

Weeks to months post rash

Grey and white matter lesions

No RNA as this is immune mediated (Ab reacts with myelin causing inflammation)

Question 16

When does measles inclusion body occur, and in which population? What are the symptoms? What tests can be done for diagnosis?

Answer 16

Days to months (but up to one year) post measles infection (or vaccination), only seen in immunocompromised

Altered sensorium, seizures, motor deficit, ataxia, rapidly progression to coma

Intrathecal Ab testing, PCR and IHC in brain biopsy, sequencing shows mutations in F protein

Question 17

When does SSPE occur post measles? Which population does it affect? Symptoms? What is the mortality rate? How do you diagnose?

Answer 17

5-10 years post WT infection

Much higher incidence if infection before 2 years

Slowly progressive, personality changes, mood swings, depression > jerking movements, necrotizing chorioretinitis, muscle spasms > rigidity > death

100% mortality

Intrathecal Ab

Question 18

What fluids can be tested for measles virus by PCR?

Answer 18

Urine (highly variable), oral fluid (optimal), THS/NPA

Question 19

What is oral fluid? What tests for measles are performed on this at Colindale? How is the quality of the sample assured?

Answer 19

Gingival crevicular fluid

IgM (more specific than serum), IgG and RNA

Total IgG is tested, if <1 mg/L then suggests poor quality sample

Question 20

When should a throat swab for measles testing be performed in relation to onset of rash?

Answer 20

Within 6 days

Question 21

What is the treatment for measles?

Answer 21

Supportive - antipyretics, hydration

Vitamin A for under 2 y

Ribavirin has been used in severe infection but limited data

Question 22

What are the risks of measles virus in pregnancy?

Answer 22

Risk of severe disease in pregnant women (esp pneumonitis)

Risk of preterm delivery and foetal loss

No congenital infection

Question 23

When does post-vaccine measles rash occur post MMR? What testing should be performed?

Answer 23

10-12 d post vaccine, genotyping required to confirm vaccine strain

Question 24

What would you do if a) an immunocompromised patient or B) pregnant women inadvertently received MMR?

Answer 24

a) Treat them like a measles exposure and risk assess

b) No investigation (but record in vaccine in pregnancy register)

Question 25

Regarding measles PEP, what is considered date of exposure in a) household contacts b) non-household contacts?

Answer 25

a) date of onset of rash b) date of last exposure

Question 26

When should oral fluid be collected for measles testing?

Answer 26

Up to 6 weeks post rash and regardless of any local testing results

Question 27

When contact tracing measles contacts what is the priority?

Answer 27

1) Immunosuppressed

2) Pregnant women and neonate

3) Healthcare workers

4) Healthy contacts

Question 28

Which contacts would receive PEP in a case of breakthrough measles?

Answer 28

Immunosuppressed only

Question 29

What is considered significant contact for measles exposure?

Answer 29

1) Close contact including household

2) Face to face contact

3) 15 mins in small space (eg class room 4-bedded bay)

Question 30

What PEP would an immunosuppressed patient get post measles contact, when should this occur and what testing is required?

Answer 30

IVIG - ideally within 72 h but up to 6 days (18 days for very high risk patients)

For most immunosuppressed patients (Group A - chemo, steroids, HIV <200) can use IgG result from any point on time

For those unlikely to maintain IgG (Group B(i) - ALL, SOT, >12 m HSCT, AIDS) need IgG testing at time of exposure

For highest risk (Group B(ii) - <12 m HSCT, agammaglobulinaemia) no testing required, give IVIG

In all cases after testing if IgG negative OR equivocal - give IVIG

Question 31

What testing and what PEP is given to pregnant women exposed to measles?

Answer 31

HNIG (within 6 days)

Testing depends pre-post 1990

Essentially, history of measles infection or 2 doses vaccine - assume immune
One dose or unvaccinated - test and give HNIG only if IgG NEGATIVE

Remember to offer MMR after pregnancy

Question 32

What testing and what PEP is given to infants when exposed to measles?

Answer 32

<6 m and 6-8 m household contacts = HNIG ideally within 72 h but up to 6 days

6-8 m non-household contact and >9 m = MMR ideally within 72 h

No testing required, maternal status not useful as transplacental Abs are low and wane quickly

Question 33

What would you do with a healthcare worker exposed to measles?

Answer 33

Check MMR - if 2 doses continue working

If not, check IgG within 7 days of exposure - if positive continue working (report any symptoms from d 7-21 post exposure). If negative exclude from day 5-21 post exposure

If MMR given post exposure they can return to work at 14 d post MMR (as this is not likely to prevent infection)

Question 34

Why is HNIG offered to some post measles exposure and IVIG offered to others? What is the minimum acceptable measles Ab titre in a) HNIG b) IVIG?

Answer 34

There is not sufficient Ab levels in HNIG to prevent infection, but will attenuate disease. Furthermore pregnant women and infants are usually managed in the community so IVIG not appropriate.

For immunosuppressed patients the role of PEP is to prevent rather than attenuate disease.

a) no specific level required (note that levels have declined in recent years) b) 11 IU/kg

Question 35

What is the threshold titre for protective measles IgG?

Answer 35

120 mIU/ml

Question 36

When should MMR be offered to contacts of measles?

Answer 36

Within 3 days for protection, however still offer affect 3 days for future protection

Any healthy contact who has not received 2x MMR should be offered vaccine, in outbreaks in institutional settings vaccine can be offered to those who have not had 2x MMR even without direct contact