measles, not just your grandmother’s diseasemeasles, not just your grandmother’s disease steven...

Measles, Not Just Your

Grandmother’s Disease

Steven Pergam, MD, MPHDirector, Infection Prevention SCCA

Associate Member, VIDD & CRD, FHCRC

@pergamic

Goals

• Review measles disease

• Measles complications

• Measles vaccine history

• Measles outbreaks worldwide

• Anti-vaccine movement

• Measles in high risk patients

• What can you do?

©2014 Fred Hutchinson Cancer Research Center 2

Measles basics

• Is a single-stranded, enveloped

RNA virus with only 1 serotype

• It is classified as a member of

the genus Morbillivirus in the


Paramyxoviridae family

• Humans are the only natural hosts of measles

virus

• Transmission is through respiratory

droplets

Measles pathogenesis after infection


Initial symptoms after exposure

• NONE – the virus incubates for 10-14 days

before you develop symptoms

• Makes tracking patients after exposure very

difficult and requires lots of people to be

quarantined if exposed and not protected


Early symptoms – Prodromal Phase

• Like most respiratory viruses

• Cough, Coryza and Conjunctivitis (3 “C”s)

• Common symptoms:

• Cough

• Runny nose *1 in 10 will have diarrhea

• Sore throat – Koplik Spots

• Eye inflammation*

• NO RASH

• Contagious at this time 3-4 days prior to the rash


Rash phase

• Ongoing symptoms but now associated with fever and

rash

• Start out as small raised bumps may also appear on top

of the flat red spots. The spots may become joined

together as they spread from the head to the rest of

the body.

• “Poured on” – head to toe pattern


Measles


Contagious?

• 4 days prior to rash to 4 days after the rash


Diagnosis

• Clinical presentation after high-risk exposure?

• Serology – IgM (can be false positive)

• Molecular testing – PCR from blood, urine, CSF

• Pathology – e.g. giant cell pneumonia


Complications of Measles

• Ear infections occur in about one out of every 10 children

with measles and can result in permanent hearing loss

• As many as 1 in 20 children with measles gets

pneumonia, the most common cause of death from

measles in young children

• About 1 in 1,000 children will develop encephalitis

(swelling of the brain) that can lead to seizures, deafness

or long term intellectual disability


Subacute sclerosing panencephalitis

• Starts with mild mental deterioration (such as memory

loss)

• Changes in behavior (such as irritability)

• Followed by disturbances in motor function, including

uncontrollable involuntary jerking movements of the

head, trunk or limbs called myoclonic jerks – seizures

• Inability to walk, blindness may occur

• Progressive disease which leads to death within 1-3

years from diagnosis – no treatment


Immune dysfunction

• Patients with measles develop weakened immune systems

following infection:

1) lymphopenia

2) a prolonged cytokine imbalance consistent with

suppression of cellular immunity to 2ndary infections

3) silencing of peripheral blood lymphocytes, which

cannot expand in response to ex-vivo stimulation

• Population data shows that non-measles infectious disease

mortality is linked to measles incidence in both the pre- and

post-vaccine eras (but prevented by vaccination!!)

• Up to 2-3 years post-illness


Schneider-Schaulies Curr Top Microbiology Immunol 2009

Mina Science 2015

Treatment for measles

• Antipyretics for fever (don’t give aspirin)

• Ribavirin (IV and inhaled) has been tried but unclear if

efficacious

• Vitamin A – low levels associated with increased risk of

death, so recommended for some young children with

measles

• IVIG doesn’t work for acute illness


Measles vaccination

• Developed by in early in 1960’s using a

weakened form of the virus

• Eventually combined in a triple vaccine (MMR)

for measles mumps and rubella in 1971


Measles rates after introduction of the vaccine


Vaccine

licensed

Eliminated but not gone

• In 2000 Measles was declared eliminated from

the US – i.e. no cases originating from the US

• All current outbreaks are related to imported

measles cases into large unvaccinated (at-risk)

populations

• This continues to be a problem because

vaccination rates in the US have declined


International Measles

• Canada (Vancouver)

• Israel

• Brazil

• Venezuela

• Georgia

• Poland

• Philippines (>30,000, >300 deaths), Ukraine

(>3000 cases)

• Congo (>155,000, 1000’s dead)

• Madagascar (>127,000 cases, 1000’s dead)

• Thailand, etc.©2014 Fred Hutchinson Cancer Research Center 19

Measles in US


Antivaccine movement


Antivaccine / “Vaccine Hesitancy” Movement

• Has been present since first vaccines, including smallpox

• Often related to personal choice vs. government

mandated, concerns about contents of vaccines, interest

in getting “real immunity”, vaccine side effects, etc.

• Expanded with now-debunked “Measles vaccine and

autism” pseudo-”study” in the Lancet in 1998

• Events that happen to kids that occur around timing of

vaccines – scapegoat

• Issues have occurred (no medicine is perfect) with

vaccines – e.g. vaccine related polio cases from live polio

vaccine (rare)


Pockets of risk?

Traditional tight-knit communities – believed to be

75% of recent measles cases currently and related

to recent vaccine outbreaks – targets of antivaccine

movement

• WA Measles – Ukrainian/Russian community

• MN Measles – Somali Americans

• OH Measles – Amish populations

• NY Measles – Ultra-orthodox Jewish community

• IN Mumps – Mennonite community


US Non-medical exemptions

©2014 Fred Hutchinson Cancer Research Center 24Hotez PLOSMed 2016

Hot spots for Measles/Antivaccine movement in US

©2014 Fred Hutchinson Cancer Research Center 25Olive PLOSMed 2018

Hot spots for Measles/Antivaccine movement in US


Costs for Measles to Public?

• Washington State over 3 million to control

outbreak

• NY – over 500 Department of Health Staff

working on Measles, preliminary costs over 8

million because over 20,000 exposures had to be

followed

• Costs to healthcare – hospital and ICU

admissions


Myths and Concerns about Vaccines?


Vaccine concerns – They make you sick

• I got the “flu” from the vaccine (No)

• Worse than the disease (No)

• Neurologic complications

• Movement disorders

• Depression

• Cancer

• etc, etc, etc…..


MMR and Autism? - NO

• A study suggested possible links between MMR and

autism in 1998

• Study based on 12 patients

• Work by Brain Deer (journalist) found that study was

organized for financial gain of main author

• Numerous studies which have refuted these claims – but

remains part of anti-vaccine movement arguments

• Paper retracted and main author lost medical license

• Recommend reading How the case against the MMR

vaccine was fixed – BMJ 2011

• ©2014 Fred Hutchinson Cancer Research Center 30


• NUMEROUS studies show no association

• Largest study to date – of 657,451 children born

in Denmark between 1999 and 2010 – with

5,025,754 person-years of follow-up

• Using Danish registries to identify vaccines

given, autism, and other behavioral disorders

• Comparison over time between those who

received MMR and those who did not


Vaccine concerns – “Contaminants/Products”

• Mercury and heavy metals (Thimerosal)

• Live viruses

• Formaldehyde

• Fetal DNA

• “Chemicals”


Media representations matter


Stock images of vaccination


Self Magazine and AAP


Combating anti-vaccine movement

• California SB 276 and SB277

• Washington HB 1638 - 2019-20 Promoting immunity

against vaccine preventable diseases

• Removed personal belief exemption for school mandated MMR

• Social media….


Combating anti-vaccine movement

• California

• Washington

• Social media


Why is vaccination so important?

Why do singular measles cases scare

cancer patients and providers?


Risk of Transmission?

• R0 – the basic reproduction rate is the transmission

potential of a disease. Estimates the number of

secondary transmission that happen when population is

totally susceptible

• Influenza = 1.5

• Ebola = 1.86

• Smallpox = 3.5-6

• Measles = 12-18


95% vaccination rate needed to limit spread

• 4/30 EU countries had reached 95% fully

vaccinated

• Median per county in WA (median 88.5% (IQR =

84.9-91.6%) – King County (88.8%)

• Only 3 counties >95%, 13/39 (33%) of counties

>90%

• Lowest rates in San Juan county (56%

vaccinated)


Simulations of Measles to Demonstrate


Low & High rates of

vaccination uptake

https://fred.publichealth.pitt.edu/measles

https://www.theguardian.com/society/ng-interactive/2015/feb/05/-sp-watch-how-measles-outbreak-spreads-when-kids-get-vaccinated

Cancer/Immunosuppression and Measles?

• Chinese outbreak 23 children with malignancies and

HCT – 13 (56.5%) had pneumonia/acute liver failure, 5

deaths (21.7%)1

• 5 Liver transplant patients, 1 died of respiratory failure2

• 8 measles cases in HCT patients in Sao Paulo, 7 were

mild, 1 with measles pneumonia (nearly all after 1 year

post-HCT)3

• 15 children in a Hem/Onc ward in India, 2 deaths4


1. Ge Chin Med 2017

2. Liu Clin Transp 2015

3. Marchado Blood 2003

4. Moulik Ped Blood Cancer 2013

Cancer patients present differently

More likely to present with:

• Symptoms similar to an other URI

• No rash

• Atypical rash

• No fever

• Presentation with tissue invasive disease (e.g. hepatitis,

encephalitis or pneumonia)

*Last death in US of measles was an immunosuppressed

woman found to have measles pneumonia at autopsy


Decline in measles immunity after HCT in the absence of posttransplant vaccination

© Fred Hutchinson Cancer Research Center 46

Ljungman et al, Blood 1994;2:657-63

Pro

babili

ty

What can happen?

• Transplant patient came to clinic with 5 children

• 2 (youngest) were noted by nurse to have “full body

rashes” and so were put in isolation

• Discharged from clinic after approval from SKC public

health

• To ER in Pierce county due to development of fever and

rash – tested for measles

• Delays in testing – results finally at nearly 5 days after

exposure


Scenario


46

known pt

contacts

in clinic

IVIG

prophylaxis

Developed National Guidelines


Check your immunity/vaccine status

• Written documentation of adequate vaccination: • one or more doses of a measles-containing vaccine administered on or

after the first birthday for preschool-age children and adults not at high risk

• two doses of measles-containing vaccine for school-age children and

adults at high risk, including college students, healthcare personnel, and

international travelers

• Laboratory evidence of immunity

• Laboratory confirmation of measles

• Birth before 1957

Ask your Healthcare provider/Employee Health to

see your status!©2014 Fred Hutchinson Cancer Research Center 50

Increase your awareness

• BE MEASLES AWARE

• Learn signs and symptoms of the illness

• Get educated about vaccine-preventable illness


Talk about the importance of vaccines

• Everyone in healthcare has an important role

• The community listens

• All of us must be advocates for vaccination in the

community to help protect our patients

• Talk to your communities, preschool parents,

church groups, or others to promote the

importance of vaccination – we all need to

contribute

• Post a #flushotselfie©2014 Fred Hutchinson Cancer Research Center 52

#Flushotselfie


#WhyIVaccinate


Protecting yourself helps to improve herd immunity

“Community Immunity”


Questions?

Steven Pergam, MD, MPH

Seattle Cancer Care Alliance

University of Washington

Fred Hutchinson Cancer Research Center

Email: [email protected]

@PergamIC

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