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

Question 38

Spread of Measles?

Answer 38

Airborne or droplet

Question 39

Natural course of measles infection?

Answer 39

Prodromal period of 2 - 4 days with fever, coryza, conjunctivitis and cough, followed by mac-pap rash which starts behind the ear and spreads to face a trunk. Generally lasts 3-7 days. Koplik spots can sometimes be seen but are unreliable. Constellation of conjunctivitis or coryza or cough, rash for 3 days and fever for at least one day are strongly suggestive of measles (according to green book)

Question 40

Complications of measles infections?

Answer 40

- Secondary bacterial infections (typically OM or pneumonia) - Viral pneumonitis (esp immunocompromised) - Encephalitis -- SSPE -- Post infectious encephalitis -- Inclusion body (immunocompromised)

Question 41

Effectiveness of one and two doses of MMR?

Answer 41

One dose - Measles 90% - Mumps 61-91% - Rubella c100% Two doses - Measles > 95% - Mumps - >61-91%* - Rubella c100% Green book unclear on this

Question 42

What type of vaccine is MMR?

Answer 42

Live attenuated

Question 43

Who gets MMR and when?

Answer 43

Childhood - one dose at 1 year and second dose from 18/12 onwards Occupational exposure (if not vaccinated as child)

Question 44

Why don't children <1 year routinely get MMR vaccine and what should happen if they do receive this vaccine?

Answer 44

Concern that maternal antibody will attenuate the response to live vaccine. If given a dose pre 1 years then they should go on to receive two further doses.

Question 45

How long after immunoglobulins can the MMR vaccine be given?

Answer 45

3 months. Any earlier and the immunoglobulin may attenuate response

Question 46

How do you identify vaccine derived measles infection?

Answer 46

Sample should be sent to Virus Reference Department for either their measles vaccine-specific PCR assay or formal genotyping. ??Genotype A is the vaccine strain which doesn't circulate (can't find a reference for this but Emily says from ref lab reports)

Question 47

Incubation period of measles?

Answer 47

10 days (7-21)

Question 48

Infectious period for measles?

Answer 48

4 days before to 4 days after rash onset

Question 49

Measles exposure - definition of group A and actions, if any?

Answer 49

Individuals who should be able to maintain an adequate antibody response from prior infection but unlike pregnant contacts this should be checked by presence of Measles IgG (at any time) If negative they should get IVIG following a significant exposure.

Question 50

Measles exposure - definition of group B-i and actions, if any?

Answer 50

Individuals who are unlikely to have maintained a immune response from previous immunisation/infection. B-i patients can be managed based on measles IgG following completion of their treatment or at time of exposure. If negative they should get IVIG following a significant exposure.

Question 51

Measles exposure - definition of group B-ii and actions, if any?

Answer 51

Individuals who are unlikely to have maintained a immune response from previous immunisation/infection. - Individuals who will require IVIG regardless of potential previous immunity.

Question 52

Measles exposure - Who gets IVIG and who gets HNIG?

Answer 52

Group A and B immunocompromised patients get IVIG Infants and pregnant women (antibody negative) get HNIG

Question 53

Paediatric patient admitted to ward, 24 h later comes out with rash, PCR positive for measles, unvaccinated. What prophylaxis: A 5 m old sibling, mum 2x MMR B 1 y in 4 bedded bay with bronchiolitis C 24 y nurse 18 weeks pregnant, 1 dose MMR, IgG equivocal D 11 y on infliximab, IgG pos pre-treatment. E Uncle 3 m post BMT, 2x MMR pre BMT. Face to face 4 days prior to symptom onset

Answer 53

Infection period for measles 4 days before to 4 days after rash. A - Sibling - HNIG within 72h ideally, Mum - none B - MMR vaccine (incl 2nd dose at 18 months onwards) C - Equivocal in pregnant women has been shown to equate to good measles neutralisation so are actually immune. Not considered for IVIG. D -Manage on the basis of IgG at the time of exposure (Group B1) E -VZIG (group B2) (assuming symptoms onset means rash onset and not coryza. If not unlikely to be in infectious period as prodrome exists for a few days before rash and infectivity = rash +- 4 days.)

Question 54

Patient comes to GP with 10 month old asking for early MMR due to outbreak in community

Answer 54

Offer MMR but will require 2 further doses after 1 year of life.

Question 55

Renal tx patient measles IgG neg, inadvertently given 1x MMR.

Answer 55

Inadvertent administration of MMR should be treated as potential exposure and managed as per guidelines. (NB this doesn't apply to pregnant women). This patient falls into group Bi - should have immunity checked following rx/at time of exposure, so urgent measles IgG + IVIG if neg.

Question 56

Who falls into group A contacts?

Answer 56

Group A. Individuals who should develop and maintain adequate antibody from past exposure or vaccination Manage on basis of evidence of protection at any time (prior to or since the diagnosis or treatment end): Patients receiving or within 6 months of completing immunosuppressive chemotherapy or radiotherapy for malignant disease (other than those with all, a lymphoproliferative disorder or who have had haematopoietic stem cell transplantation, HSCT). Patients with human immunodeficiency virus (HIV) infection: i) over 5 years of age and with a CD4 count less than 200 cells/μl (but without a diagnosis of AIDS) or ii) aged 5 years or less, with a CD4 count less than 500 cells/μl Patients with chronic immune mediated inflammatory disease who are receiving or have received immunosuppressive therapy: * moderate to high dose corticosteroids (equivalent ≥20mg prednisolone per day; children one mg/kg/day) for more than 10 days in the previous month * long term moderate dose corticosteroids (equivalent to ≥10mg prednisolone per day or children 0.5 mg/kg/day for more than 4 weeks) in the previous 3 months * adults on non-biological oral immune modulating drugs, for example, methotrexate >20mg per week (oral and subcutaneous), azathioprine >3.0mg/kg/day; 6mercaptopurine >1.5mg/kg/day, mycophenolate >1g/day, in the previous 3 months * children on any dose of non-biological oral immune modulating drugs * certain combination therapies at individual doses lower than stated above, including those on ≥7.5mg prednisolone per day in combination with other immunosuppressants (other than hydroxychloroquine or sulfasalazine) and those receiving methotrexate (any dose) with leflunomide in the previous 3 months Individuals who have received a short course of high dose steroids (equivalent >40mg prednisolone per day or children 2 mg/kg/day for more than a week) for any reason in the previous month.

Question 57

Who falls into group Bi for contacts?

Answer 57

Manage on basis of IgG obtained at the time of exposure (or since the diagnosis or treatment end): * patients on or after completion of immunosuppressive chemotherapy for acute lymphoblastic leukaemia (all) * patients with lymphoproliferative disorders (including haematological malignancies such as indolent lymphoma, leukaemia and plasma cell lymphoma) * patients who have received a solid organ transplant * patients more than 12 months after receiving a haematopoietic stem cell transplant (HSCT) patients receiving or within 6 months of completing biological therapies (alone or in combination with steroids); these include: o monoclonal antibodies, for example, alemtuzumab, o fatumumab o rituximab cytokine inhibitors, for example, etanercept * patients with a diagnosis of acquired immunodeficiency syndrome (AIDs)

Question 58

Who falls into Group Bii for contacts?

Answer 58

Offer PEP regardless of status: * patients who have received a haematopoietic stem cell transplant (HSCT) within the past 12 months * patients with persistent agammglobulinaemia (IgG less than 3g/L) due to primary immunodeficiency (for example, common variable immunodeficiency) or secondary to disease or therapy (this group may already be on long term IVIG replacement, which should provide equivalent protection to post exposure immunoglobulin)

Question 59

MMR/Vaccine for pre 1 year old children. ?Age cutoffs?

Answer 59

Infants under 6 months - Assume susceptible and administer HNIG, ideally within 72 hours but up to 6 days, regardless of maternal status. Infants aged 6 to 8 months - For household exposure, administer HNIG, ideally within 72 hours but up to 6 days if necessary. - For exposures outside of the household, administer MMR, ideally within 72 hours. Infants 9 months and older - Administer MMR vaccine, ideally within 72 hours of exposure. Vaccines given pre 1 year should be followed by full course after 1 year