Measles Flashcards
Receptor for measles virus
SLAM (CD150)
What are the two main glycoproteins in measles virus and what are their functions?
H = haemagluttinin - bids receptor. VNAb against H protein important in immune response
F = fusion protein - allows cell to cell spread
Patients most at risk of measles virus?
Under 2 years
Pregnant women
Adults
Immunosuppressed
R0 of measles virus
15-20
What impact does measles have on the hosts immune system?
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
Infectious period of measles
4 days before to 4 days after rash
Transmission route of measles
Direct contact, droplet and aerosol spread
Symptoms of measles infection
Three C’s - cough, coryza, conjunctivitis
Fever
Rash (starts on face, behind ears spreads to trunk - like been poured red paint on)
Complications of acute measles
Mostly seen in immunocompromised, young infants and adults
Pneumoniits (highest cause of death)
Otitis media
Diarrhoea
Keratoconjunctivitis
Secondary bacterial and respiratory infection
CNS disease
What is breakthrough measles?
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
What test what you do to confirm breakthrough measles?
IgG avidity (this will be high) - IgM may be negative
What is the likelihood of primary measles pneumonitis? What would a CXR show?
3-4% (most pneumonia caused by secondary bacterial infection)
CXR - ground-glass opacities and consolidation, bronchiolar wall thickening
What are the four types of CNS disease occurring in measles?
1) Primary Measles encephalitis
2) Acute post-infectious measles encephalomyelitis (or ADEM)
3) Measles inclusion body encephalitis
3) Subacute sclerosing pan-encephalitis
When does primary measles encephalitis occur? What would you expect to see in CSF? Is RNA detected in CSF? What is the mortality?
During or within 1 week of rash
Lymphocytic pleocytosis and mildly raised protein
Yes RNA is detectable
10-15% mortality
When does ADEM occur in relation to measles infection? What would be seen in brain imaging? Is RNA detectable in CSF?
Weeks to months post rash
Grey and white matter lesions
No RNA as this is immune mediated (Ab reacts with myelin causing inflammation)
When does measles inclusion body occur, and in which population? What are the symptoms? What tests can be done for diagnosis?
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
When does SSPE occur post measles? Which population does it affect? Symptoms? What is the mortality rate? How do you diagnose?
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
What fluids can be tested for measles virus by PCR?
Urine (highly variable), oral fluid (optimal), THS/NPA
What is oral fluid? What tests for measles are performed on this at Colindale? How is the quality of the sample assured?
Gingival crevicular fluid
IgM (more specific than serum), IgG and RNA
Total IgG is tested, if <1 mg/L then suggests poor quality sample
When should a throat swab for measles testing be performed in relation to onset of rash?
Within 6 days
What is the treatment for measles?
Supportive - antipyretics, hydration
Vitamin A for under 2 y
Ribavirin has been used in severe infection but limited data
What are the risks of measles virus in pregnancy?
Risk of severe disease in pregnant women (esp pneumonitis)
Risk of preterm delivery and foetal loss
No congenital infection
When does post-vaccine measles rash occur post MMR? What testing should be performed?
10-12 d post vaccine, genotyping required to confirm vaccine strain
What would you do if a) an immunocompromised patient or B) pregnant women inadvertently received MMR?
a) Treat them like a measles exposure and risk assess
b) No investigation (but record in vaccine in pregnancy register)
Regarding measles PEP, what is considered date of exposure in a) household contacts b) non-household contacts?
a) date of onset of rash b) date of last exposure
When should oral fluid be collected for measles testing?
Up to 6 weeks post rash and regardless of any local testing results
When contact tracing measles contacts what is the priority?
1) Immunosuppressed
2) Pregnant women and neonate
3) Healthcare workers
4) Healthy contacts
Which contacts would receive PEP in a case of breakthrough measles?
Immunosuppressed only
What is considered significant contact for measles exposure?
1) Close contact including household
2) Face to face contact
3) 15 mins in small space (eg class room 4-bedded bay)
What PEP would an immunosuppressed patient get post measles contact, when should this occur and what testing is required?
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
What testing and what PEP is given to pregnant women exposed to measles?
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
What testing and what PEP is given to infants when exposed to measles?
<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
What would you do with a healthcare worker exposed to measles?
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)
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?
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
What is the threshold titre for protective measles IgG?
120 mIU/ml
When should MMR be offered to contacts of measles?
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
Spread of Measles?
Airborne or droplet
Natural course of measles infection?
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)
Complications of measles infections?
- Secondary bacterial infections (typically OM or pneumonia)
- Viral pneumonitis (esp immunocompromised)
- Encephalitis
– SSPE
– Post infectious encephalitis
– Inclusion body (immunocompromised)
Effectiveness of one and two doses of MMR?
One dose
- Measles 90%
- Mumps 61-91%
- Rubella c100%
Two doses
- Measles > 95%
- Mumps - >61-91%*
- Rubella c100%
Green book unclear on this
What type of vaccine is MMR?
Live attenuated
Who gets MMR and when?
Childhood - one dose at 1 year and second dose from 18/12 onwards
Occupational exposure (if not vaccinated as child)
Why don’t children <1 year routinely get MMR vaccine and what should happen if they do receive this vaccine?
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.
How long after immunoglobulins can the MMR vaccine be given?
3 months. Any earlier and the immunoglobulin may attenuate response
How do you identify vaccine derived measles infection?
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)
Incubation period of measles?
10 days (7-21)
Infectious period for measles?
4 days before to 4 days after rash onset
Measles exposure - definition of group A and actions, if any?
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.
Measles exposure - definition of group B-i and actions, if any?
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.
Measles exposure - definition of group B-ii and actions, if any?
Individuals who are unlikely to have maintained a immune response from previous immunisation/infection. - Individuals who will require IVIG regardless of potential previous immunity.
Measles exposure - Who gets IVIG and who gets HNIG?
Group A and B immunocompromised patients get IVIG
Infants and pregnant women (antibody negative) get HNIG
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
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.)
Patient comes to GP with 10 month old asking for early MMR due to outbreak in community
Offer MMR but will require 2 further doses after 1 year of life.
Renal tx patient measles IgG neg, inadvertently given 1x MMR.
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.
Who falls into group A contacts?
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.
Who falls into group Bi for contacts?
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)
Who falls into Group Bii for contacts?
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)
MMR/Vaccine for pre 1 year old children. ?Age cutoffs?
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
