Measles Flashcards
Is clinical diagnosis of Measles reliable during low measles incidence?
The reliability of a clinical diagnosis declines
This necessitates laboratory methods for investigation (EVERY suspected case is Ix and excluded/confirmed by lab methods)
What is the definition of Measles elimination?
the absence of endemic measles circulation for at least 12M in a country with a high-quality surveillance system.
Family?genus?
Paramyxovirirdae
Morbilivirus
How many genotypes? currently circulating?
24 Genotypes (many eliminated) —> 2021: 3 genotypes globally
B3: Africa, some countries ME
D8: South Asia, Europe (UK) and the America (USA)
H1: East Asia (China)
When do you use WARN and INFORM?
Where a large group of people have been exposed, BUT the level of contact cannot be defined at individuals basis
What are the aims of WARN and INFORM?
Encourage rapid self-ID of those who may be vulnerable,
To ensure any linked cases are ID and diagnosed promptly
To provide re-assurance to those who are likely to already be protected.
What are the complications of Measles?
The most common:
-OM
-Pneumonitis (most frequent), within 2W of symptoms onset.
-Diarrhea
-Temporary reduction in immune response —> increase risk of severe secondary bacterial and viral infection
-Tracheo-bronchitis/Measles Croup
-Convulsions
Rare:
Encephalitis (0.05%-0.1%- 1/1000 cases of measles)
Very rare: very severe—> SSPE (0.01%)
What are Measles complication in pregnancy?
Severe maternal morbidity (Pneumonitis 10-52%)
Increased risk of Prematurity/pre-term delivery and fetal loss.
No evidence of congenital defects
Neonatal Measles associated with SSPE (short latency)
Infants <1Y at high risk of complications: Pneumonia, OM, SSPE, death.
What is an important element for Measles control?
Good epidemiological and virological surveillance
This helps identify chains of transmission early to effective intervention are started promptly to limit further spread.
Given the limited effectiveness of most PEP, accurate surveillance to inform this pro-active strategy is a high priority
When shud management of suspected cases AND contacts start?
On the basis of risk assessment:
Age,
Vaccination history,
CF,
EPI features.
What should clinicians do upon suspecting a Measles case?
Notify all suspected Measles cases ASAP to their local HPT
This is crucial for surveillance and timely public health actions.
What are the symptoms of Measles?
Prodrome illness; 2-4D
High fever, Conjunctivitis, Cough, Cold symptoms
CONJUNCTIVITIS is a more specific symptom.
Symptoms typically PEAK on the 1st day of the rash.
Where does the Measles rash typically start?
Start in the face behind the ear.
Lesions can become confluent, particularly on the face and the trunk.
The rash is red, blotchy,
MP, not itchy,
Generally lasts for 3-7D, fading gradually
What does ‘breakthrough Measles’ refer to?
A confirmed case of Measles in someone who developed immunity from natural Measles OR prior vaccination
Usually as a result of intense &/or prolonged exposure toinfected pt (HCW/HH)
Typically occurs 6-30 years after infection/immunization.
What are common features of breakthrough Measles?
*Generally mild,
*Conjunctivitis absent,
*Atypical rash,
*Shorter duration,
*Infectivity much lower & transient (Although PCR positive, the presence of nAb in respiratory secretions greatly reduces the infectiveness of the virus).
Represents <10% of total infections in endemic areas (expected to incraese with increase vaccine coverage and availability of PCR testing)
What is post MMR rash?
Usually occur D10-12 post MMR
May hv mild fever BUT otherwise well.
Measles virus can be detected in OF/Mouth/Throat swabs.
Sample should be sent to VRD for Measles-Specific PCR assay/Genotyping.
What are the types of Measles surveillance?
Lab surveillance
National immunisation and VPD division follow ALL positive cases to obtain epi/clinical/vaccination history
International surveillance:
When did Measles lab surveillance started?
and what did include?
How its arranged?
What tests are done?
Started Nov/1994
Included OFT of ALL notified and suspected cases which is sent to VRD
HPT send OFT kit to GP/Pt
Sample shud b taken asap and up-to 6W after rash onset
Tested for Measles IgM, IgG and/or RNA and reported back to GP/local HPT
If RNA positive –> genotyping–>
To differ WT from vaccine
ID imported cases
To monitor progress towards elimination
What are the international surveillance standards? and what is their aim?
-Laboratory testing of ALL suspected measles cases is undertaken at VRD which enables systematic testing, using reference methods -highly sensitive and specific.
-Measles virus sequences are entered on the WHO global Measles Nucleotide Sequence (MeaNS) database hosted by UKHSA.
-VRD report monthly data on the number of samples tested for measles to the WHO laboratory network.
To monitor progress towards elimination
For WHO purposes, what is required to exclude Measles?
Measles Ab test
What is the optimal sample for lab surveillance?
Why?
What is the alternative?
Can not be used for?
OFT
*Minimally invasive
*Acceptable > serum in infants/children
*More S&S > serum esp if taken few D after onset of rash.
*Can be tested for:
IgM (pos>50% on D1 and >90% on D3 of rash)
IgG (EIA) and
RNA (if taken within 7D of onset) therefore –> Reliably exclude/confirm Measles diagnosis
*Indicate wether 1ry of BT infection (The relative level of Measles IgG)
*Genotype confirmed cases
If not available: send SERUM + TS to VRD
Can NOT be used to asses immune status (use serum)
IgG avidity test not done in OF
For how long is RNA expected to be detected in OF samples?
RNA can b detected from b4 onset of rash -2W after onset of symptoms
What is the most appropriate sample to check immune status?
What test are done in this sample type?
What test can NOT be done?
Serum
IgM/G by EIA (preferably using a mu-capture assay for IgM)
IgG avidity if high confirm BT infection
Not suitable for PCR/GP.
What should be collected within 6 days of the onset of rash for PCR testing?
Mouth swabs and throat swabs
They must be collected by a healthcare worker.
Negative dose not exclude esp if no test for cellular RNA
Can the following sample be tested for Measles PCR:
1)Urine?
2)Dry swab
1)Highly variable
Not advised in the UK
2)Yes for PCR
What indicates a poor quality OF sample?
Total IgG < 1mg/L
The test needs to be repeated
What can be used to indicate/confirm whether a case is primary or breakthrough infection?
The relative level of Measles IgG in OF sample may indicate
High avidity Measles IgG in SERUM sample confirms breakthrough infection
What is the significance of detecting Measles virus sequences?
They are entered on the WHO global Measles Nucleotide Sequence (MeaNS) database
This helps in monitoring global Measles elimination efforts.
What defines a lab confirmed case of Measles?
Suspected case + lab evidence of ACUTE Measles:
-IgM in serum/OF with no recent vaccination OR
-Confirmed WT-Measles RNA in any clinical sample
What characterizes a presumed primary infection of Measles?
Lab confirmed with NO evidence of 2 doses of Measles containing vaccine
What is presumed BT Measles?
Detection of Measles virus RNA in a suspected case + Mild/atypical symptoms + reliable history of 2 doses of vaccine
*Measles IgM in serum may be negative.
Confirmation can be established by high avidity IgG in serum OR high levels of MS-IgG in OF,
What types of assays are used for Measles IgG testing of contacts?
Qualitative (pos/neg/equ) OR
Quantitative (defined measure)
Usually EIA is used
Highly specific BUT less sensitive
What sample should ALWAYS be requested for accurate exclusion of Measles?
Oral fluid (OF) sample sent to VRD REGARDLESS of any local test results,
When should the OF sample be taken after the onset of rash?
As soon as possible and up to 6 weeks after the onset of rash
What should be done with samples from cases testing positive at local labs?
All samples should be forwarded to VRD for
Confirmation and Genotyping
What affects the likelihood of Measles in non-endemic areas in the absence of lab results?
Assessment of the epidemiological features
When should case management start ?
Start based on Clinical + epidemiological features (EPI) without waiting for lab results
What should public health advise regarding lab samples for testing?
Use appropriate lab samples for testing at the right time to reduce the risk of false negative results
What is the purpose of a PH risk assessment for every suspected Measles cases?
To decide on PH management and actions
What are the classifications for Measles case definitions?
Lab confirmed,
EPI confirmed,
Likely/probable,
Likely breakthrough,
Unlikely/possible
*Classification may change
*Likely and unlikely are qualitative judgment
What defines an EPI confirmed case?
Clinically classical case + Direct EPI link to:
A confirmed case (onset of symptoms occurred within 7-21D of exposure)
OR
Related to another EPI confirmed case (eg in an OB)
This term is used for SURVEILLANCE purposes to define confirmed cases in the absence of a lab test to confirm measles.
What defines Likely/probable Measles case?
Clinically classical case + EPI features*
*Either increase the likelihood of the patient having been exposed
AND/OR
*Favour the diagnosis of measles relative to other causes of rash illness.
What is considered a likely breakthrough case?
Suspected case in a patient who had:
2 doses of Measles containing vaccine (usually at least 6Y after vaccination)
OR
Previous confirmed Measles infection (IgG positive)
**The case will usually have mild symptoms AND epidemiological information that suggest exposure to Measles (RARE)
What defines unlikely/Possible Measles case?
Suspected case does NOT meet definition of Likely case
*NOT CCC
OR
*No EPI=No recent conformed case and has not visited an area with OB during InP
What factors to consider in risk assessment?
Factors increasing the risk of exposure
Factors favoring the diagnosis of 1ry Measles infection
What factors increase the risk of exposure to Measles?
- Members of community known to be more susceptible
- Visited an area where Measles is circulating during the incubation period
- Attendance to large gatherings
What factors favor the diagnosis of primary Measles infection?
- Age: higher among adolescents/young adults
- Lack of immunity/incomplete vaccination + No prior infection
Who should be risk assessed and managed WITHOUT OFT RESULT in the index case?
ALL Contacts of EPI/Lab confirmed cases
AND
IS Contacts of Likely cases (including BT)
When should contacts assessment and management delayed until OFT result in index case?
Contacts of unlikely cases should await the results of OFT
Unlikely cases are defined as having NO EPI OR not being CCC.
In which scenarios is URGENT Measles testing required for index and contact?
If the index is Unlikely Measles with IS contact within 6D of exposure.
If the index is Likely Measles with IC contact within 6D of exposure.
**IS contact of likely and ALL contacts of confirmed cases are assessed and managed without waiting for results.
What are the reasons for urgent testing in a likely case?
To avoid significant public health actions if diagnosis is excluded (eg administering MMR/HNIG to exposed infants in nursery settings).
To inform use of HNIG/IVIG for vulnerable contacts, during periods of low level transmission.
What are the reasons for urgent testing of an UN-likely case with EPI features?
To inform the risk assessment of an IS contacts.
With whom testing should be discussed?What should be documented on the request form for measles testing?
With HPT
Date of onset of symptoms,
Date of onset of rash, and
History/dates of MMR vaccine
True or False: A negative local result excludes measles.
False
Exclusion depends on
Timing and adequacy of the sample and Tests undertaken.
What factors should be considered in risk assessment?
CF,
EPI features,
Vaccination history, and
Lab results
What Advice should be given to Confirmed and Likely cases regarding IPC?
Should stay at home (No work/school/nursery) and
Avoid contact with vulnerable ppl for the entire InP (4d b4 rash 4d after)
GIVEN HIGH INFECTIVITY > return ONLY after full recovery.
What is the infectious status of IS cases?
IS may be infectious for longer and may not display typical symptoms
Fill in the blank: A negative local result does not exclude _______.
Measles
It’s important to consider testing timing and adequacy.
What is the best way to achieve Measles elimination?
High vaccination coverage with 2 doses of MMR vaccine (=/>95%)
What should all contacts of a reported Measles case be provided with?
Information on symptoms and instructions to exclude themselves if symptoms develop
True or False: PEP is highly effective for all contacts.
False
PEP is of limited effectiveness.
Who should be prioritized for PEP?
- Immunosuppressed contacts
- Pregnant women and infants <12 months
- Healthcare workers
- Healthy contacts
How should a HCW contact be managed?
Can be source of transmission —> need urgent assessment +/-Exclusion from work
Vaccination of un-immunised contacts should confer benefit against FUTURE exposures and will protect against Rubella & Mumps.
What is the likelihood of susceptible healthy contacts benefiting from PE-vaccination?
Unlikely to benefit unless offered rapidly following exposure
In outbreak settings like schools, what strategy should be considered? and why?
Mass vaccination of susceptible people
To prevent tertiary transmission
What factors determine the management of each Measles contact?
- Exposure risk (is index case 1ry or BT)
- Vaccination status/susceptibility to Measles
**For IS contacts asses the level of IS
Within ‘defined contacts’ of Measles case, who shud contact tracing focus on?
Contact tracing should identify close contacts within the InP
CC including HH
F2F contact of any length
>15 minutes in a small, confined area (eg room in a house, classroom, 4-bed hospital bay (including HCW)
What type of exposure should trigger a risk assessment (susceptibility & PEP) for IS contacts of a Measles case?
Consider even limited exposure; as are more likely to develop severe Measles disease —> Hence ANY LEVEL OF CONTACT shud trigger assessment
Even if the index case has BT infection
Without waiting for lab results
***IC contacts of BT infection does not need Risk assesmnet/PEP
What is poorly defined contacts? How do you manage?
PPL exposed in a shared setting (ED/GP waiting area) where level of contact in unclear.
*If there are known IS involved —> manage as CC (rapid assess + PEP)
*If there is a List (not known IS status) —> WARN and INFORM LETTER/MSGS
*If there is no list —> writing to local HC providers/info leaflets/posters
What should immunosuppressed patients be considered for following any exposure?
IVIG (Intravenous Immunoglobulin)
At risk of severe Measles
What factors influence whether PEP is provided to immunosuppressed patients?
- Level of immunosuppression
- Likelihood of retaining pre-existing Measles immunity
If contact is from the USA/Canada, when can you assume they are immune?
ONLY if fully vaccinated
OR
Born before 1957
What is the recommendation for individuals with severe defects in CMI on regular IVIG replacement?
Do not require additional IVIG if the most recent dose was administered =/<3 weeks before exposure.
*Their IVIG requirement will be advised by their immunologist.
How is IS contacts divided? based on what?
Group A and B
Based on their ability to maintain adequate Ab from past exposure/vaccination.
Who are included in Group A and B?
and how are they managed?
Group A: able to develop and maintain adequate Ab from any prior vaccination/infection.
Can be managed based on evidence of protection at any time (b4/since diagnosis/ttt end)
Group B: Unlikely to hv developed/maintained adequate Ab levels from past
B(I): Managed based on Measles IgG test at time of exposure/at any point since the end of TTT/Diagnosis.
B(ii): Require IVIG post exposure WITHOUT testing
What assessment needs to be urgently undertaken for immunosuppressed individuals?
Assessment of susceptibility based on: Age /History of Measles infection/Vaccine status –> Group A only
Measles IgG result since diagnosis/ttt (Group B /1)
What are the 2 clinical scenarios where you would give PEP (IVIG):
1)If you can not test for Measles IgG within 6 days (Group A)?
2) Without testing?
If born b/w 1970-1990 with NO history of infection/Vaccination.
If born after 1990 and had ONE dose of MMR vaccine
If born after 1990 and UNvaccinated
What is the specificity and sensitivity of most qualitative EIAs?
Specificity is high; sensitivity remains low.
Hence recommendations about PEP for equivocal results will differ by age and type of vulnerability.
What is cut-off duration after exposure can IS contact get IVIG?
For IS patients where exposure is recognised late
OR
Found to be Ab negative/equivocal b/w 6-18D after exposure»_space;
d/w the specialist caring for the individual should take place, and
IVIG may be considered in order to attenuate infection.
What is required if a second exposure occurs
<3W from a dose of IVIG?
>3W after dose of IVIG?
No further IVIG dose required
Consider a further dose of IVIG.
What is the seroprevalence of individuals born before 1970 regarding measles Ab negativity?
<1% are Ab negative.
What is the seroprevalence of individuals born between 1970-1989 regarding measles Ab negativity?
<10% are Ab negative.
What do individuals who tested IgG positive/equivocal for measles Ab on standard assays show when tested in VRD?
Detectable measles Ab by Neutralisation assays.
Why should routine Ab tests be avoided in older women born before 1990 with a reliable history of Measles infection?
Routine Ab test lack sensitivity > A high proportion of those found to be Equivocal/Negative are likely to be truly immune.
What percentage of individuals respond to a single dose of MC-vaccine?
~90% respond.
What percentage of individuals are protected following 2 doses of the MC-vaccine?
~95% will be protected.
What PEP is used for pregnant women and infants? and what is the main aim of PEP?
HNIG
Attenuation of disaese.
What is the likelihood of UK mothers having been exposed to natural measles infection?
UNLIKELY
Most UK mothers are born after Measles vaccination was introduced (1968).
What happens to the level of trans-placental antibodies in vaccinated mothers?
Low and wanes rapidly (Few Weeks)
This contrasts with mothers who had previous infections, where antibodies wane after a few months.
What PEP is given to:
All infants <6
6-8M
=/>9M
*HNIG regardless of mum status (Maternal Ab can interfere with the MMR response).
*HH C HNIG/ non-HH C MMR
*MMR
HNIG within 72H but up-to 6D
MMR only 72H
When should MMR be ideally given following exposure?
Within 3 days
Would MMR PEP <12M counted in immunisation schedule?
NO
Doses offered <1Y should be discounted and children should be offered 2 doses of MMR vaccine according to the national schedule
The efficacy of a dose of vaccine b/w 6-11M < that at 12-13M, due to interference from maternal Ab.
***All additional immunisations should be recorded in the red book and should be notified to the local Child Health Information System (CHIS).
What is recommended for neonates born to mothers who develop a measles rash 6D b4 OR 6D after delivery?
PEP with HNIG or IVIG
D/W UKHSA duty dr case by case
What risks are associated with maternal measles?
Pre-term delivery,
HIGH RISK for premature/low birth weight infants
What is the efficacy of HNIG in preventing secondary cases?
69%
Efficacy increases with dose.
What is less well established as PEP for measles?
The use of MMR vaccine
Limited evidence suggests it may prevent disease/reduce severity if given within 72H –> beyond future protection
IN OB settings, when given to those who has not significantly exposed yet can prevent tertiary transmission.
What are the D/D of rash that appears within 21D following exposre in a contact who received MMR as PEP?
Either WT Measles and Vaccine rash
OFT can be used to type the virus (vaccine vs WT) if taken within 1W of onset.
When is the maximum time of infectiousness?
4D b4 rash onset
How should the time window for receiving PEP be calculated for:
HH/continuous contacts?
Other contacts?
From the onset of rash in the index case.
From the last day of exposure to the index case
What should be done following inadvertent vaccination with a measles-containing vaccine?
IS: risk assess as a potential exposure to measles
Pregnant women: No PEP, Report to Inadvertent vaccination during pregnancy.
What is the recommended dose of IVIG for IS?
0.15 g/kg
~11 IU/Kg Measles Ab
What is the recommended dosage of HNIG for pregnant women and infant?
For pregnant: ~3g
For infants: 0.6 ml/kg up to a maximum of 1g
What should HCWs do if they are exposed to a confirmed/Likely case without evidence of protection?
Be excluded from work from the 5th day after the first exposure to 21 days after the final exposure
If tested rapidly and are IgG positive within 7Dof exposure, can continue to work BUT report to OH if developed symptoms b/w 7D after 1st exposure and 21D after last exposure.
They can return if they remain symptom-free for at least 14 days after receiving the MMR vaccine.
How should exposed HCWs who develop fever/rash managed?
Exclude until 4 full days after onset of the rash
They should be treated as epidemiologically confirmed cases –> send lab test and notify HPT
What are Measles complication in IS?
At risk of developing prolonged/severe Measles & complications.
Pneumonitis is the most common cause of death.
Most at highest risk: Severely CMI (recent BMT, 1ry T-cell dysfunction, AIDS, ALL)
What are the types of Measles Encephalitis?
1)Post-infectious encephalomyelitis
1W after onset of rash
AI-demyelination (virus rarely found in the brain)
2)Measles inclusion body encephalitis
(Acute encephalitis of the delayed type):
IS ONLY
Might occur without measles-like illness (exposure history possible W/M)
Acute neurological compromise/decreased consciousness/Seizure/progressive N
Measles RNA can normally be detected from clinical specimens for several D/W
3)SSPE
VERY RARE (0.01%),
kids infected <1Y: 1/8000 (16X > infected >5Y).
FATAL.
LATE complication (median 7Y -up to 2-3 decades later)
May follow unrecognized Measles infection (WT virus found in brain)
Progressive neuro-cognitive symptoms —> Coma —> Death.
What is Measles vaccine effectiveness?
Once dose of MMR is at least
95% effective in preventing clinical Measles
92% effective in preventing 2ry cases among HH contacts.
What are the types of vaccine failures?
Primary failure: when an individual fails to make an initial immunological response to the vaccine.
RARE. particular after a SINGLE dose.
Secondary failure: when an individual responds initially BUT then protection wanes over time.
