MEASLES Clinical review and Up-date · Clinical review and Up-date: A vaccine Preventable Disease...
Transcript of MEASLES Clinical review and Up-date · Clinical review and Up-date: A vaccine Preventable Disease...
ANTHONY OGNJAN DO FACPMetro Infectious Disease Consultants43134 Dequindere RdSterling Heights, Michigan, 48314Phone: 586 446-8688Fax: 586 446-9994
Clinical review and Up-dateA vaccine Preventable Disease
MEASLES
Michigan Osteopathic Association120th Annual Spring
Scientific ConventionSouthfield Michigan
May 16-19, 2019
MeaslesClinical review and Up-date: A vaccine Preventable Disease
SUMMARY
Epidemic Measles In the United States eliminated 2000 v Airport Measles
Sporadic Measles Still a threat among Groups of Unvaccinated / non-immune
Measles is a highly contagious disease among the susceptible : 90% attack rate
ComplicationsCan be Serious
v Immunosuppressionv Diarrheav Pneumonia
v Neurological
Symptomatic treatment: Fever control (No aspirin) : Hydration: NO ANTIVIRALS
Suspect v Incubation 5-21 days Febrile illness: Koplik Spots
v Out break with groups non-immune Morbilliform rash: Head- toe
Vaccinev Is safe and effective for protectionv 2 Shot series: Adults & Childrenv MMR® Is Preferred vaccine (MMR-V)
ENCOURAGE VACCINATIONS
Michigan Osteopathic Association120th Annual Spring
Scientific ConventionSouthfield Michigan
May 16-19, 2019
MeaslesMeasles Re-emerges5 things to remember
Measles Re-emerges: 5 things to remember
#1
Certain Patient Groups Are Most Vulnerablev Children < 5 years of agev Especially infantsv Adults older >20 yearsv Pregnant women
v Malnourished children
v People with severely compromised immune systems
- Cancer chemotherapy, leukemia- Organ transplantation- HIV infections- Immunosuppressive drugs
#2
People Who Think They Are Immune : May Not Be…v Born before 1957 v Are considered Immune
v Born 1957-1988 v Vaccinated: 1963-1963 Less effective vaccinev Vaccinated: 1962- 1989 Only single vaccine
v Check vaccine records for administration of 2 doses of vaccine as evidence of immunityv Alternatively, measuring measles IgG titers can demonstrate immunity v Proof of immunity should be documented for all people working in the healthcare field. v Proof of immunity is recommended for people living in or traveling to areas with ongoing
measles transmission.
Andrew T. Pavia, MD Never Seen Measles? 5 Things to Know May 02, 2019. Perspective/ Medscape/ Infectious Disease https://www.medscape.com/viewarticle/912500_
MeaslesMeasles Re-emerging5 things to remember
Measles Re-emerges: 5 things to remember
#3
The Most Important Diagnostic Tool Is Your H&P
Diagnose measles quickly
v Allows for quarantinev Important for contact tracingv vaccination of susceptible contactsv Other public health interventions
Historyv Patients vaccination statusv Possible exposure to measlesv Travel to areas of ongoing transmission.
PhysicalA careful history of disease progression & symptoms is critical.
v After an incubation period of 8-12 (“3Cs”)v Prodromal symptoms: Fever, Cough, Coryza, Conjunctivitis v During this period, Koplik spots
#4 LabsHighly contagious. (Aerosols). If patients need to go to a lab to have blood drawn, you should
notify the lab and infection control to help prevent exposing other patients.
Serum IGM v 1-2 day : after rashv Poor Specificity
PCR v Not generally availablev Throat and nasopharynx are the preferred
Andrew T. Pavia, MD Never Seen Measles? 5 Things to Know May 02, 2019. Perspective/ Medscape/ Infectious Disease https://www.medscape.com/viewarticle/912500_
Measles Re-emerges: 5 things to remember
#5
Infants an Children: MMR Vaccine Doses Can Be Given EarlierRoutine Childhood vaccinations v 1st 12-15 months
v 2nd dose before school entry at age 4-6 years.
During outbreaks or before travel v 2nd dose can be given 28 days after the first dose
High risk : 6-11 months
v MMR vaccine can be givenv Providing reasonable short-term protection. v However not considered a valid first dose:
Another dose must be given after the child's first birthday.
Outbreak situation:v Second dose aged 12 months or olderv An early dose to children aged 6-11 months living in
areas where transmission is ongoing or who will be traveling.
MeaslesMeasles Re-emerging5 things to remember
Andrew T. Pavia, MD Never Seen Measles? 5 Things to Know May 02, 2019. Perspective/ Medscape/ Infectious Disease https://www.medscape.com/viewarticle/912500_
Measles
EpidemiologyComparison Of Morbidity-Mortality
Historical Comparison Morbidity-Mortality For Vaccine Preventable Disease before 1980. (Measles-Mumps-Rubella)
Estimated Annual Cases (Average) PEAKDiseases Cases Deaths Cases Deaths
Measles 530,217 440 763,094 552
Years 1953-1962 1953-1962 1958 1958
Mumps 162,334 39 212,932 50
Years 1963-1968 1963-1968 1964 1964
Rubella 47,745 17 448,796 24
Years 1966-1968 1966-1968 1964 1968
JAMA, November, 14,2007. Vol.298, No 18 (2156)
EcologyMeaslesDefined: Epidemics Impact
• People born before 1957 lived through several years of epidemic measles before the first measles vaccine was licensed in 1963.
• Surveys suggest 95% - 98% of those born before 1957 are immune to measles.
US: How does being born before 1957 confer immunity to measles?
Therefore:Persons born before 1957 can be presumed to be immune.
ECOLOGY*
Measles …Defined
“Measles is one of the most important infectious diseases of humans….
Has caused millions of deaths since its emergence as a zoonotic disease thousands of years ago…..
For infectious disease epidemiologists…measles has served as a model of an acute infectious disease, particularly for understanding the nature of epidemics””
-Kenneth MaxcyJohns Hopkins University School of Public Health, 1948
*Ecology is the branch of biology which studies the interactions among organisms and their environment
EcologyMeaslesDefined: Clinical
“What is Measles?”
“Highly contagious” viral illness characterized by Fever, Malaise, Rash, Cough, Coryza, and Conjunctivitis
that occurs worldwide….
Natural measles infection is thought to confer lifelong immunity.
Immunity due to Measles vaccination is also highly protective against clinical infection.
Measles
Viral Human Ecology
Exposure
Prodrome*v FEVER 1040 f (400C)v COUGHv RHINORHEAv CONJUNCTIVITIS
VIRA
L LO
ADMeasles MorbidityHospitalized 1 : 4Encephalitis 1 :1,000 (0.1%)Death 1-2 :1,000
Contagious ~4 days before 4 days after the rash appears
TIMEPRODOROME*2-4 days
EXANTHEM~3-5 days After fever
Resolves 5-6 days
RECOVERYCough may persist
1-2 weeksKoplik Spots
INCUBATION5-21 days Median(Asymptomatic)
Immune Response
MeaslesClinical Exanthems
Development and distribution of measles rash. Reproduced from Perry RT and Halsey NA. The clinical significance of measles. J Infect Dis 2004;189(Suppl 1):S5
DiscreteMaculopapules
ConfluentMaculopapules
MeaslesFirst day Third day
of rash of rash
Koplik’s spotsOn Buccal mucosa
RashDiscrete
Search carefully for Koplik spots in patients with suspected measles, since they can improve the accuracy of clinical diagnosis …..However, this enanthem does not appear in all patients with measles.
Measles Exanthem:v Arises approximately 2- 4 days after onset of feverv Erythematous, Maculopapular, Blanching rash v Classically begins face
- And spreads cephalocaudally and centrifugally- To involve the neck, upper trunk, lower trunk, and extremities
v Early on, the lesions are blanching; v Later stages….they are not v May include petechiaev Severe cases, may appear hemorrhagic Children:
the extent of the rash and degree of confluence generallycorrelate with the severity of the illness.
v The palms and soles are rarely involved.
Respiratory Infections*v Otitis Mediav Mastoiditisv Bronchopneumoniav Laryngotracheobronchitis (croup)v Bronchiolitisv Giant cell pneumonia
CENTRAL NERVOUS SYSTEMv Febrile Convulsionsv Guillain-Bare syndromev Reye’s Syndromev Transverse myelitisv Encephalitisv Acute Disseminated Encephalomyelitisv Subacute Sclerosing Panencephalitis
S
Gastrointestinalv Diarrhea (Most common)v Mesenteric Enteritisv Appendicitisv Hepatitisv Pancreatitisv Stomatitisv Cancrun Oris)
MEASLESCOMPLICATIONS
*Bacterial Superinfections ~5%S. pneumoniaeS pyogenes
H influenzaeS. aureus
v Corneal Ulceration v Corneal Perforationsv Central Vein Occlusion
Symptomsv severity ranges from mild and less serious v First 4–6 wks. after an acute phase (and upon the immune functions are disturbance)v Complications are usually more severe in adults CASES v And malnourished and immune compromised individuals.
IMMUNE SYSTEMReticuloendothelial or Macrophage system:
v Dysfunctionv Suppression
v TTPv DIC
v Myocarditisv Pericarditis
Measles
VirologyMeasles morbillivirusPathology IMMUNOSUPRESSION
Measles Virus:IMMUNOSUPRESSION Multiple organ systems
Targets v Epithelial tissuesv Reticuloendothelial tissues*
Mononuclear phagocytev Monocytesv Macrophagesv T-Lymphocytes
Pathological studies of children dying during acute measles
Multinucleated giant cells (typical of measles virus infection)
Throughoutv Respiratoryv Gastrointestinal tract
v Most Lymphoid tissues
In immunology, the mononuclear phagocyte system (also known as the reticuloendothelial system or macrophage system) is a part of the immune system that consists of the phagocytic cells located in reticular connective tissue.
Measles Mump Rubella VaccineVaccine OptionsIMPACT OF : “MMR VACCINE”
MEASLESVACCINATION INPACT United states
Post MMR VACCINE 1969:v Measles : Endemic Disease Elimination: 2000v Rubella : Endemic Disease Elimination: 2004v Mumps : 99% Endemic Disease Elimination
Measles
VirologyMeasles morbillivirus
Virus Classification
Unranked Virus
Realm Ribovira
Phylum Negarnaviricota
Class Monjivicetes
Order Mononegavirales
Family Paramyxoviridas
Genus Morbillivirus
Species Measles Morbillivirus
synonyms
Measles virus
Classic measles infection in immunocompetent patients
●Modified measles infection in patients with pre-existing but incompletely protective anti-measles antibody
●Atypical measles infection in patients immunized with the killed virus vaccine
●Neurologic syndromes following measles infection, including acute disseminated encephalomyelitis and subacute sclerosing panencephalitis
●Severe measles infection
●Complications of measles including secondary infection, giant cell pneumonia, and measles inclusion body encephalitis
Measles virus: v Single-strandedv Negative-sensev Envelopedv Non-segmented RNA virus
MEASLESVaccine : MMR(Measles, Mumps Rubella)Measles Immunosupression
Measles Vaccination
Long-term benefits of Measles Vaccination: By preventing measles-associated immune memory loss:
v Vaccination protects polymicrobial herd immunity:Measle Infections; Secondary Infection Complications
v There-by preventing all-cause infectious disease
MEASLES
Recovery and ComplicationsNeurological Complications : Encephalitis
EncephalitisAcute measles encephalitis may also occur in the absence of rash
CLINICALIncidence 1:1,000 Measles casesPresentation Appears within a few days of the rash typically day 5 (range 1 - 14 days)
Signs &Symptoms
v Feverv Headachev Vomitingv Stiff neck
v Meningeal irritation v Drowsinessv Convulsionsv Coma
CSFv Lymphocyte Pleocytosisv Protein Elevationv Glucose Normal
Pognisis v Neuro developmental sequelae v ~25% of casesv Rapidly progressive and fatal disease v ~15% of cases
MEASLES
Recovery and ComplicationsNeurological Complications : Acute Disseminated Encephalomyelitis
Acute Disseminated Encephalomyelitis DEMYELINATING NEUROPATHY
CLINICAL Symptoms: Thought to be a postinfectious autoimmune responseIncidence ~1 per 1,000 measles cases.
Presentation Develops during the Recovery phase of Acute Disease : typically within 2 weeks of the exanthem
Signs &Symptoms
GENERAL Mental status changes:
Neurological Myelitis
v Feverv Headachev Neck stiffnessv Seizures
v Confusionv Somnolencev Coma
v Ataxiav Myoclonusv Choreoathetosis
v Paraplegia / Quadriplegiav Sensory lossv Loss of bladder & Bowel
control
CSF v Lymphocytic pleocytosis Elevated protein concentration.
Prognisisv MORTALITY v 10-20%v Common Residual neurologic
abnormalities among survivorsv Behavior disordersv Mental retardationv Epilepsy
MEASLES
Recovery and ComplicationsNeurological Complications : Subacute Sclerosing Panencephalitis I
Subacute Sclerosing PanencephalitisProgressive Fatal degenerative disease of the Central Nervous System
Occurs 7 -10 years after natural measles virus infectionMay involve persistent infection with a genetic variant of measles virus within the CNS
CLINICAL Symptoms
Incidence Natural Measel Infection : 8.5 cases per million casesPost Vaccination : 0.06 cases per million (Decrease Cases)
Presentationv Age : onset : ≤20 yearsv Onset 7 -10 years after natural measles infection v ~50% had measles Infection before the age of 2 years
Stages
v Stage one v last fweeks - years
v Personality changesv Lethargy
v Strange behavior
v Stage twolasts 3 - 12 months
v Myoclonusv Worsening dementia
Stage three & fourv Further neurologic deteriorationv Flaccidity or decorticate rigidity
v Symptoms & signs of Autonomic dysfunction.
v Myoclonus is absent
v Stage four v Vegetative state. : Death
MEASLES
Recovery and ComplicationsNeurological Complications : Subacute Sclerosing Panencephalitis II
Subacute Sclerosing PanencephalitisProgressive Fatal degenerative disease of the Central Nervous System
DIAGNOSTIC STUDIES AND FINDINGSSERUM v Serum anti-measles antibody concentration is elevated
CSF v Detectable anti-measles antibodies v Elevated protein
EEGv EEG findings are characteristic of SSPE and may be pathognomonic
v Bursts of high-voltage complexes v Delta waves (slow waves) and sharp wavesv Each complex is followed by a relatively flat pattern
Brain Imaging v CT BRAIN v Demonstrate atrophy and scarring v MRI BRAIN v Brain may be normal.
The relentless and fatal course of SSPE underscores the importance of measles vaccination, not only for prevention of measles but also for
prevention of the severe neurologic sequelae that can ensue
1920’sThe Measles death rate in the
was around 30%
Pre-antibiotics : Post-antibioticsMeasles can lead to serious complications and death
even with modern medical care
Measles Morbidity Mortality has declined in developed countries
in association with economic development, improved nutritional status, and supportive care…. And Vaccines
Particularly antibiotic therapy to control secondary bacterial pneumonia….
VIRAL ECOLOGY:Measles has been targeted for eradicationgiven the favorable biologic characteristic that Humans are the only virus reservoir. …
Global Vaccine Action Plan*
Measles and rubella Targeted for elimination in five WHO Regions by 2020
However:Due to social and political factors
high transmissibility, Local, Regional, and Global elimination of measles has been achieved in very few areas of the world…
And…Measles remains “Endemic” in areas with low vaccination rates, particularly in the developing world…….
*Attack rate: is the biostatistical measure of frequency of morbidity, or speed of spread, in an at risk population. It is used in hypothetical predictions and during actual outbreaks of disease.
MeaslesAttack Rates*
90%Susceptible Non-immune
Individuals
Infectious droplets from the respiratory secretions of a patient with measles can remain airborne for up to two hours …
Therefore, the illness may be transmitted in public spaces, even in the absence of person-to-person contact.
AIRPORT MEASLES
MeaslesEpidemiology : Persons at risk
*PERSONS At RISK FOR MEASLESPerson RISK
v All Susceptible: Unvaccinated : And/or : No history of clinical disease
vInfants: Who lose passive antibody before the age of routine immunization
vChildren: Immunodeficiency due to HIV or AIDS, leukemia, or malnourished regardless of immunization status.
v SusceptibleIndividuals
Travelers v Areas where measles is endemic….v Contact with travelers infected…
from travel to endemic areas
*High risk person not vaccine eligible can be treated within six days of exposure withimmune globulin.
U.S. MEASLES : Since 2000*The majority of U.S measles cases v Occur among “unvaccinated” travelers including citizens and visitors who Acquire infections
while visiting endemic or epidemic outbreak areas of other countries
v Measles is more likely to spread and cause out breaks in U.S. communities where there are communities and groups of unvaccinated individuals
* The year 2000 Endemic Measles declared eliminated from the U.S ( “Endemic” end of endemic transmission for 12 months or more)
v College campuses (Dormitories)v Close-knit religious communities
Measles
Epidemic 2019U.S. Measles Statistics
2019 The states that have reported cases to CDC are Arizona, California, Colorado, Connecticut, Florida, Georgia, Illinois, Indiana, Kentucky, Maryland, Massachusetts, Michigan, Missouri, Nevada, New Hampshire, New Jersey, New York, Oregon, Texas, and Washington.
NUMBER OF MEASLES CASES REPORTED BY YEAR2010-2019 (January 1 - April 26, 2019)
MeaslesMeasles EpidemiologyAmerica’s biggest recent measles outbreaks: 2010-2109
v Orthodox Jewish Community: New Yorkv Amish Communities: Ohiov Somali American Community: Minnesota
2019v *Orthodox Jewish Community:
Metro-Detroit
*Under-vaccinated community
MICHIGANMEASLES 2019
Michigan is one of 17 states that allows parents to opt out of vaccinating their children for religious or philosophical reasons. Although as of 2014, parents are required to “receive education regarding the benefits of vaccination and the risks of disease” before claiming a nonmedical waiver for their child.
“Scientists had predicted that Oakland County Mi, would be at high risk for a measles outbreak...
Scientists from Baylor College of Medicine Found that Oakland County had the 5th largest number of vaccination exemptions in the country….
So this outbreak was, sadly, predicted.”- Abram Wagner
Professor Epidemiology University of Michigan
5
2017 Vaccination Ratesv Wayne County: 92.4% v Macomb County: 91.7%v Oakland County: 90.3%
MeaslesEpidemiologyMichigan Measles 2019
April 26, 2019 (Since March 13, 2019) 43 casesLocation CASES Demographics
Oakland County 40
Age 8 months - 63 yearsWayne County 1
Detroit 1
Washtenaw County 1
CDC has confirmed measles 704 Cases
v Arizonav Coloradov Connecticut v Georgiav Kentucky
v Michiganv Missouriv New Hampshirev New Jerseyv Oregon
2018: 17 measles outbreaks : TOTAL 349 cases2019 MEASLES OUTBREAKS319 CASES REPORTED NATIONWIDE 2018
Measles
Cracks in the Wall
Control of Vaccine Preventable Diseases
“Science and factsVs.
Superstition and Ignorance”*
*Ollie MaceCivil EngineerEuchre Master & Scotch aficionado
Vaccination
Is the societies' Admission price to prevent human suffering and death by controlling pestilence and disease…Vaccine preventable Disease… To be shared by all?
OrShould “some” be allowed free admission (No vaccines) …
placing the rest of society risk for vaccine preventable diseases?
Philosophically: Measles Attack rate 90%
Humans are social creaturesWhat is the admission charge to belong to
Society?
MeaslesVaccinesControl of Vaccine Preventable DiseasesVaccination Exemptions by State
VACCINATION EXEMPTIONS BY STATE ALL 50 STATES ALLOW FOR MEDICAL EXEMPTION FROM VACCINES. 3 STATES HAVE OTHER EXEMPTIONS
*Virginia an Missouri haveCertain specific Exemptions
Medical Exemption Only
Religious Exemptions
Religious and PersonBelief Exemptions
Measles
VaccinesControl of Vaccine Preventable DiseasesVaccination Exemptions by State
2017 Oakland county population1.251 million
PRE - VACCINE ERA Antiquity to 1963
Rhazes' book A Treatise on Smallpox and Measles
9th CenturyTwo forms of “Smallpox”:
v Variola major : Mortality rate ~30%v Variola minor : Mortality rate ~1%.
v Valuable information about diagnosis, therapy, and concepts of diseases during the Middle Ages.
Measles
HistoryTime Line : Landmark
Rhazes, Avicenna* (Ibn Sina, 980-1037)*
Modanlou HD A tribute to Zakariya Razi (865 - 925 AD), an Iranian pioneer scholar. Arch Iran Med. 2008 Nov; 11(6):673-7
*1970 His accurate description of measles was recognized by the World Health Organization is the first written account of the condition.
PRE - VACCINE ERA Antiquity to 1963
Francis Home Scottish physician
Measles
HistoryTime Line: Landmark
“1757… attempted to produce mild measles by mimicking the variolation process….
This process involved taking blood from an infected patient and inoculating it through the skin of an uninfected person….
In this way he was able to transfer measles to 10 of 12 patients….
This experiment clearly demonstrated the presence of measles virus in human blood”…Francis Home
1719 - 1813
Measles
HistoryTime Line: LandmarkKoplik Spots: 1896
“Koplik's spots“* 1896The spots, which are considered pathognomonic
for measles, occur in the mouth a few days before the skin rash appears, and before infectivity reaches its maximum.
This allows individuals incubating the disease to be isolated and helps to control epidemics.
Henry Koplik*1858 – 1927
*Some authors ascribe the first written description of these spots to Russian Nil Filatov (1847-1902) in 1895,who had observed equivalent phenomena. Koplik was aware of Filatov's work, thought his evidence insufficient and rejected his claim for priority.
Measles
Koplik Spots
“The first twenty-four to forty-eight hours of the invasion of measlesis marked by a suffusion, slight or marked, of the eyes, and the
conjunctiva at the nasal canthus is not only reddened but also slightly redundant. There is, at this stage, a slight febrile movement; there may be a cough or some little sneezing; the mother has noticed nothing except that the infant or child has a slight fever. At this period the eruption on the skin has not made its appearance. In the majority of cases there is no suspicion of any exanthema. In a few cases there is an indistinct spotting around the lips and alae nasi, but no eruption.
The mouth — If we look in the mouth at this period we see a redness of the faces; perhaps, not in all cases, a few spots on the soft palate. On the buccal mucous membrane and the inside of the lips, we invariably see a distinct eruption. It consists of small, irregular spots, of a bright red colour. In the centre of each spot, there is noted, in strong daylight, a minute bluish white speck. These red spots, with accompanying specks of a bluish colour, are absolutely pathognomonic of beginning measles, and when seen can be relied upon as the forerunner of the skin eruption”
- Dr Henry Koplik, MD
Koplik H. The diagnosis of the invasion of measles from a study of the exanthema as it appears on the buccal mucous membrane. Arch Pediatr 1896;13:918-22
Measles
HISTORY TIME LINE
Prior to the introduction of the measles vaccine in 1963, the CDC admits there was massive underreporting of
measles cases…
“because virtually all children acquired measles… The number of measles cases
probably approached 3.5 million per year”
An entire birth cohort!
MeaslesMeasles casesVaccine impact: Measles : MMR : Booster
Data are from the US Centers for Disease Control.
Measles cases in the United States: 1944-2007
MEASLES Vaccine 1963 MMR 1969
Second dose recommended
*2% - 5% of people do not develop measles immunity after the first dose of vaccine. The second dose is not a booster, but rather is intended to produce immunity in the small number of people who fail to respond to the first dose.
Measles
HistoryTimeline : Ecology Pre-vaccines
MEASLES HISTORICAL TIME LINE
PRE-VACCINE ERA Antiquity to 1963
1921 Measles became a nationally notifiable disease in the United States
First decade of reporting, an average of 6,000 measles-related deaths were reported each year.
.
Measles
HistoryTimeline : Ecology : Pre-vaccines
MEASLES HISTORICAL TIME LINE
Epidemiology
Before 1912 No accurate data
1920 United States
469,924 cases 7,575 deaths
1958- 1962 ANNUAL 503,282 cases 432 deaths1960 3 years before the first measles vaccine marketed 1960
442,000 cases Reported
1960380 Deaths
Likely 3.5 – 5 million infected
1969 Measles deaths were estimated at 1 in 10,000 cases.
PRE VACCINE ERA Antiquity to 1963John Enders &Thomas Peoples Edmonston “Measles” Virus
1954Thomas Peebles, following a measles outbreak at a local
school, succeeded in isolating a measles virus throat swab from an 11-year-old pupil,
David Edmonston.
Enders had been skeptical about Peebles’s work, but once the virus had been isolated he and other researchers set
about developing a vaccine.
v The virus continuously cultured until a live attenuated less virulent strain was isolated dubbed
Edmonston B vaccine virusv Licensed by the US Food & Drug Administration 1963.
Measles
HistoryTime Line Landmark : Isolation Measles Vaccine Virus
John Enders* 1897 - 1985
Thomas Peoples**1921 - 2010
*Children’s Medical Center at Boston. In this laboratory much outstanding work on the viral diseases of man has been done under his direction and it was here that the work was done on the cultivation of the poliomyelitis viruses for which Enders was awarded, together with T. H. Weller and F. C. Robbins, the Nobel Prize for Physiology or Medicine in 1954
** Early Dr Peoples 1950’s, worked at the side of Dr John Enders whose “breakout” work on virus andtissue cultures led to the development of polio vaccines and a Nobel Prize in 1954
Measles
HistoryTime Line: Hallmark Vaccine Development : 1963-1967
MEASLES HISTORICAL TIME LINE 1963 - 1967
VACCINE DEVELOPMENT 1953 - 2005
1963To1967
Two Vaccines MarketedMerck
Rubeovax®Attenuated (“Live”) vaccine
Pfizer
Pfizer-Vax Measles-K®Inactivated (“killed”) virus vaccine
v 95% effective at preventing measlesv Protection ~ 3 years
However:v 30-40%:children: fever of +1030 f:
~6th day (Lasting 2- 5 days)v 30-60%: developed “modified measles rash”
v Due to the high number of side effectsv recommended co-administration measles
immune globulin
v No detectable levels of measles antibodies one year later
v 1965: new and abnormal measles-like illnessv Among children previously vaccinated with
inactivated measles virus vaccine and exposed to measles.
v Pfizer’s inactivated vaccine was taken off the market in 1968
.
Measles
HistoryTime Line: Hall mark: Vaccine Development
MEASLES HISTORICAL TIME LINE
VACCINE DEVELOPMENT 1953 - 2005
1967Live attenuated measles vaccine introduced in the United States in 1967
Attenuvax®Merck further attenuated
Edmonston B strain
PRESENTLY
Edmonston-Enders Measles Virus (Formerly Moraten Vaccine Strain)
Approved for Vaccine use in 1969 Edmonston – Ender Measles strain
1969 Incorporated: Measles; Mump; Rubella (MMR®) Vaccine
2018 Incorporated: Measles; Mumps; Rubella & Varicella Vaccine (Proquad®)
.
Vaccine ControversyCan Vaccines Cause Autism?
Science and Facts Vs. Superstition and Ignorance
VaccinesMyths and perceptions What is Autism
Autism, or autism spectrum disorder (ASD):Refers to a broad range of conditions characterized by
challenges with social skills, repetitive behaviors, speech and nonverbal communication.
We now know that there is not one autism :but many subtypes,
and each person with autism can have unique strengths and challenges….
What is Autism. There is no one type of Autism, but many. https://www.autismspeaks.org/what-autism
Autism
Vaccines
Myths and perceptions perceptionsAndrew Jeremy Wakesfield 1998
Andrew Jeremy Wakefield• Discredited former British doctor who became an anti-vaccine activist. • Gastroenterologist until he was struck off the UK medical register for
unethical behaviour, misconduct and fraud.
1998 Authored a fraudulent “research paper” claiming that there was a link between the measles, mumps and rubella (MMR) vaccine, and autism and bowel disease.
- "Profile: Dr Andrew Wakefield". BBC. 27 January 2010.- Smith, Rebecca (29 January 2010). "Andrew Wakefield – the man behind the MMR controversy". The Daily Telegraph. London.- Godlee F, Smith J, Marcovitch H (2011). "Wakefield's article linking MMR vaccine and autism was fraudulent". BMJ. 342: c7452. doi:10.1136/bmj.c7452.- Fang FC; Steen RG; Casadevall A (October 2012). "Misconduct accounts for the majority of retracted scientific publications". Proceedings of the National Academy of
Sciences. 109: 17028–17033. doi:10.1073/pnas.1212247109. PMC 3479492. PMID 23027971.-- "Great Science Frauds". Time Magazine, 13 January 2012- *Robin Birch, (Australia )· Andrew Wakefield Is Not A Fraud April 12, 2017. Vax Info Start Here For researching alternative information about vaccines.
http://vaxinfostarthere.com/wakefield-not-fraud/
AUTISMLack of evidence Vaccination
for association:
No causal association between MMR vaccine and ASD is established
v Drutz JE, Duryea TK, Torchia MM. Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor. UpToDate® March 20,2019
v DeStefano F, Bodenstab HM, Offit PA . Principal Controversies in Vaccine Safety in the United States. Clin Infect Dis. 2019;
v Immunization Safety Review: Vaccines and Autism. A report of the Institute of Medicine, National Academies Press, Washington, DC 2004
Unlike most other medical interventions, vaccines are given to healthy people, and people are far less willing to tolerate vaccines adverse effects ….….than adverse effects of other treatments.
Random thoughts
VACCINES WORK
SAFTETY FIRST
Measles Mump Rubella VaccineVaccine Options
MEASLESVACCINATION
Post MMR VACCINE 1969:v Measles : Endemic Disease Elimination: 2000v Rubella : Endemic Disease Elimination: 2004v Mumps : 99% Endemic Disease Elimination
Measles Mump Rubella VaccineVaccine Options
MMR®)MMRV* (Proquad®): with Varicella: “Chicken Pox”)Live Vaccines
Unless the parent expresses a preference for MMRV vaccine:
Centers for Disease Control and Prevention recommends
MMR® vaccine and varicella vaccine should be administered as separate injections for the first
dose in children 12-47 months of age.
Measles Mump Rubella VaccineHistorically: Vaccine availability
MMRVACCINE Characteristics : Available
IndividualVaccines
Year Vaccine1963 Measles1967 Mump1969 Rubella
IncorporatedVaccines
1969 Measles; Mump; Rubella (MMR) 1985 Measles; Mumps; Rubella & Varicella (MMRV)
Measles Mump Rubella Vaccine
Immune Response
MMRVACINATION:
Immune response
Induces both humoral and cellular immune responses……v Induces measles virus-specific T lymphocytesv Antibodies First appear between 12 -15 days v Antibodies Peak at 21 to 28 days.
• IgM antibodies appear transiently in blood • IgA antibodies are predominant in mucosal secretions• IgG antibodies persist in blood for years
Both humoral and cellular responses can be induced by measles vaccine, Lower magnitude and shorted duration compared to those following wild-type
measles virus infection.
MEASLESVaccine : MMRVaccine Effectivness I
MMR Vaccine Effectiveness and Duration of Protection
MMR U.S. vaccination schedule: considered protected for life against Measles & Rubella. Mumps immunity may decrease over time: and may not be protected later in life.
v MEASLES v Both serologic / epidemiologic evidence indicate : vaccine-induced measles immunity appears to be long-term and probably lifelong in most persons.
v MUMPS v A third dose of MMR can provide added short term protection to a close contact with a mumps patient during an outbreak.
v RUBELLA v Studies indicate one dose of confers long-term, probably lifelong, protection against rubella
MEASLESVaccine : MMRVaccine Effectivness II
MMR Vaccine Effectiveness and Duration of Protection
One Dose
Virus Effective RangeMeasles 93% (39-100%)Mumps 78% (49-92%)Rubella 97% (94-100%)
Two Doses
Measles 97% (67-100%)Mumps 88% (31%-95%)
MEASLESVaccine : MMR(Measles, Mumps Rubella)Indications Children
MMR VACCINES: 2 Vaccinations
Childrenv Starting with the first dose at 12 - 15 months of agev Second dose at 4 through 6 years of age.
v At least 1 month should elapse between a dose of a measles-containing vaccine such as M-M-R® and a dose of ProQuad®
v At least 3 months should elapse between a dose of varicella-containing vaccine and ProQuad®
VACCINE Birth 1month
2month
4month
6month
12Month
15month
18month
19-23month
2-3years
4-6years
Hepatitis B 1st 2nd 3rd
Rotovirus 1st 2nd 3rd
Diphtheria, Tetanus,Pertussis
1st 2nd 3rd 4th
Haemophilus Influenza B
1st 2nd At risk 3rd or 4th
PneumococcusConjugate PCV 13
1st 2nd 3rd 4th PPSV 23Inactivated Polio 1st 2nd 3rd 4th
Influenza Influenza Yearly : (Killed virus : IM Vaccine Live Attenuated Virus : Intranasal
Measles, MumpsRubella
1st 2nd
Varicella 1st 3rd
Hepatitis A HEP A 2 doses HepA seriesMeningococcal CERTAIN HIGH RISK GROUPS
Range of Recommended ages
Certain High Risk Groups
Measles Vaccine ScheduleRecommended Immunization Schedule for Persons Age 0 through 18 years, United States, 2014 Immunization Schedules, Centers for Disease Control and Prevention http://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html (Accessed 5/15/2014)
1st live (VIRAL) Vaccine *2nd Dose MMR / MMRV
*2% - 5% of people do not develop measles immunity after the first dose of vaccine. The second dose is not a booster, but rather is intended to produce immunity in the small number of people who fail to respond to the first dose.
MMR VACCINES: 2 Vaccinations
Adults*v No Evidence of Immunity* v One Dose
v High Risk
High-risk people need 2 dosesv Healthcare personnelv International travelers v Students at post-high school educational institutions, v people exposed to measles in an outbreak setting
* Previously vaccinated with killed measles vaccine or th an unknown type of measles vaccineduring 1963 – 1967*.
** The killed vaccine was found to be not effective and people who received it should be revaccinated with live vaccine
*No evidence of immunity: “Defined”:- Having Historically documented receipt of 1 dose [ or 2 doses: 4 weeks apart if high risk] of live measles virus- containing vaccine,
- OR laboratory evidence of immunity or laboratory confirmation of disease,- OR No Evidence of immunity having been born birth before 1957
MEASLESVaccine : MMR(Measles, Mumps Rubella)
MEASLESVaccine : MMR(Measles, Mumps Rubella)
VACCINE SAFETYv The MMRV vaccine is very safe, and it is effective at preventing measles,
mumps, rubella, and varicella.
Vaccines, like any medicine, can have side effects.
v Most people who get MMRV vaccine do not have any serious problemsGetting MMR or MMR-V vaccine is much safer than getting measles, mumps,
rubella, or varicella
MEASLESVaccine : MMR(Measles, Mumps RubellaMMR Vs MMR(V)
MMR Vs. MMRV Varicella
MMR®MMRV (Proquad®) First dose 12 months to 23 Month
Fewer Vaccine Injections
Fever* v Higher risks of fever within the 42 days after vaccinationv Highest risk occurs during the 5-12 days after vaccinationv Febrile seizures during the 5-12 days after vaccination.
v * Important to discuss febrile seizure risk with parents when considering using MMRV vaccine for the first dose in a child aged 12-47 months.
v A personal history of febrile seizures or a family history of either febrile seizures or epilepsy increases a child’s risk of having a febrile seizure.
v These children should generally be vaccinated with MMR and varicella vaccines instead of MMRV vaccine
MEASLESVaccine : MMR(Measles, Mumps RubellaVaccine Side effects)
Three systems used to monitor vaccine safety
VARES Vaccine Adverse Event Reporting System v An early warning system that helps CDC and FDA monitor problems following
vaccination. Anyone can report possible vaccine side effects to VAERS.
VSD Vaccine Safety Datalinkv Collaboration between CDC and nine health care organizations which allows
ongoing monitoring and proactive searches of vaccine-related data.
CISA The Clinical Immunization Safety Assessment Project:v Partnership between CDC and several medical centers that conducts clinical
research on vaccine-associated health risks
Post Exposureprophylaxis
MEASLES
MEASLESPOST EXPOSURENon-immune Exposure2013 MMR ACIP post-exposure IG prophylaxis for measles.
2013 MMR ACIP post-exposure IG prophylaxis for measles.
Is there anything that can be done for unvaccinated people who have already been exposed to measles, mumps, or rubella?
v MMR v Measles vaccine, given as MMR, may be effective if given within the first 3 days (72 hours) after exposure to measles
v Immune Globulin v May be effective for as long as 6 days after exposure.
v Postexposure prophylaxis with MMR vaccine does not prevent or alter the clinical severity of mumps or rubella.
v If the exposed person does not have evidence of mumps or rubella immunity they should be vaccinated since not all exposures result in infection
Ask the experts: Measles mumps Rubella. Immunization Action Coalition. http://www.immunize.org/askexperts/experts_mmr.asp
MEASLESPOST EXPOSURENon-immune Exposure2013 MMR ACIP post-exposure IG prophylaxis for measles.
Ask the experts: Measles mumps Rubella. Immunization Action Coalition. http://www.immunize.org/askexperts/experts_mmr.asp
2013 MMR ACIP post-exposure IG prophylaxis for measles. NON Immune
Age Recommendations
All infants <12 months: v IGIM : 0.5 mL/kg of body weight: the maximum dose is 15 mL.
Infants age 6 -11 months:Alternatively:v MMR vaccine (instead of IGIM) if it can be given within 72 hours
of exposure.
>12 monthsPost 1 dose MMR:
v IG is NOT indicated for these individualsv UNLESS they are severely immunocompromised.
Pregnant (Non-immune) v Intravenous IGIV) dose of 400 mg/kg of body weight.
Severe Immunosuppressed v Intaveneous IGIV dose of 400 mg/kg of body weight.
Immune Globulin should not be used to control measles outbreaks
Vaccines:Staying current with vaccines
Admittedly, some physicians aren’t well versed in the science or technology of vaccines….
This opens the attacks, and fuels the controversy upon vaccine medicine by opponents of vaccinations…
“Celebrity scientists”, “Free choice advocates”, Alternate Medical, and certain Religious groups…
But Vaccine technology does not function in a vacuum…
Vaccine science has come a long way since Edward Jenner and others first immunized people with the Cowpox virus to protect against Smallpox…
Random thoughts
Vaccines:Staying current with vaccines
Today‘s vaccines are created using modern technology, and involve many scientific disciplines including : Microbiology, Microbial Genetics, Biochemistry, Pharmacology, Pathophysiology, Computer Science, Epidemiology, Immunology Statistics and on and on….
AND…..The safety and effectiveness of vaccines are “time tested” and “clinically” validated by the Millions of vaccine recipients….Vaccinations are scrutinized on a continuous basis (“VAERS”*) … and, I might add… by the most modern and most sophisticated system of statistical analysis ever developed….
*Vaccine Adverse Event Reporting System
Random thoughts
Vaccines:Staying current with vaccines
Our patients and their families should feel confident that the“How to, and Wherefores” of vaccine administration is greatly understood….
...And the techniques involved, for safe and effectivevaccination delivery, have been simplified for the average physician by consensus, of multiple, and an incredibly large, and diverse groups of Scientists, Physicians and Clinical Practitioners
- Anthony F. Ognjan, D.O., FACPYou are in good hands
Random thoughts
Measles
Lecture Bibliography
Measles
Bibliography I SIX RASHES OF CHILDHOOD• Bialecki C, Feder HM, Grant-Kels JM (November 1989). "The six classic childhood exanthems: a review and
update". J Am Acad Dermatol. 21 (5 Pt 1): 891–903• Chamberlain N. Skin Rashes: Diseases 1-6* A. T. Still University of Health Sciences/Kirksville College of Osteopathic
Medicin © 1996-2013• Morens DM, Katz AR. The "fourth disease" of childhood: reevaluation of a nonexistent disease. Am J Epidemiol.
1991 Sep 15;134(6):628-40.• Powell KR. Filatow-Dukes' disease. Epidermolytic toxin-producing staphylococci as the etiologic agent of the
fourth childhood exanthem. Am J Dis Child. 1979 Jan;133(1):88-911• Weisse ME. The fourth disease, 1900-2000. Lancet. 2001 Jan 27;357(9252):299-301.
MEASLES• Maldonad YA, Kaplan SL, Sullivan M. Measles: Clinical manifestations, diagnosis, treatment, and prevention.
UpToDate® Feb 2019.updated: Oct 26, 2018• Orenstein WA, Robert T. Perry RT, Neal A. Halsey NA. The Clinical Significance of Measles: A ReviewThe Journal
of Infectious Diseases, Volume 189, Issue Supplement_1, 1 May 2004, Pages S4–S16, https://doi.org/10.1086/377712
• Maldonad YA, Kaplan SL, Sullivan M. Measles: Clinical manifestations, diagnosis, treatment, and prevention. UpToDate® Feb 2019.updated: Oct 26, 2018
Measles
Bibliography II
TRANSMISSION• SIMPSON RE. Infectiousness of communicable diseases in the household (measles, chickenpox, and mumps).
Lancet. 1952;2(6734):549.• Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases, 12th
ed, second printing, Atkinson W, Wolfe C, Hamborsky J (Eds), Public Health Foundation, Washington, DC 2012• Bloch AB, Orenstein WA, Ewing WM, Spain WH, Mallison GF, Herrmann KL, Hinman AR Measles outbreak in a
pediatric practice: airborne transmission in an office setting. Pediatrics. 1985;75(4):676• Notes from the field: Multiple cases of measles after exposure during air travel--Australia and New Zealand,
January 2011.Centers for Disease Control and Prevention (CDC) MMWR Morb Mortal Wkly Rep. 2011;60(25):851• Vega JS, Escobedo M, Schulte CR, Rosen JB, Schauer S, Wiseman R, Lippold SA, Regan JJ, Notes from the field:
measles transmission at a domestic terminal gate in an international airport - United States, January 2014.Centers for Disease Control and Prevention (CDC) MMWR Morb Mortal Wkly Rep. 2014;63(50):1211.
• Banerjee E, Hickman C, Engels K, Kenyon C Notes from the Field: Measles Transmission in an International Airport at a Domestic Terminal Gate--April-May 2014. Centers for Disease Control and Prevention (CDC) MMWR Morb Mortal Wkly Rep. 2015;64(24):679.
Measles
Bibliography IIIMEASLES HISTORICAL TIME LINE
• What is the History of Measles in America and Other Countries? National Vaccine Information Center. https://www.nvic.org/vaccines-and-diseases/measles/measles-history-in-america.aspx#_edn2
• Lois N Manger The Medical Influence of Rhazes Overview. Science and it’s times. Understanting Social Significance of Scientific Discovery. Gale group inc. Copyright 201. Encyclopedia.comhttps://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/medical-influence-rhaze
• Measles Pre vaccine History. Center for Disease Control and Prevention (CDC) Atlanta, Georgia. https://www.cdc.gov/measles/about/history.htm
• Measles Vaccine Development. Center for Disease Control and Prevention. CDC Atlanta, Georgia https://www.cdc.gov/measles/about/history.htm
• Measles Elimination. Center for Disease Control and Prevention. CDC Atlanta, Georgia https://www.cdc.gov/measles/about/history.htm
• Immunization, Vaccines and Biologicals: Measles World Health Organizaion. (WHO) https://www.who.int/immunization/diseases/measles/en/
THOMAS PEOPLES & JOHN ENDERS• Douglas Martin Dr. Thomas C Peoples, who Identified measles Virus, dies at 89. New York Times Aug 4 2010.
https://www.nytimes.com/2010/08/05/health/05peebles.html• Thomas Peoples The telegraphhttps://www.telegraph.co.uk/news/obituaries/medicine-obituaries/7937398/Thomas-Peebles.html
10 August 2010
Measles
Bibliography III MEASLES HISTORICAL TIME LINE
Francis Home:• Plotkin SA. Vaccination against measles in the 18th century. Clin Pediatr (Phila). 1967 May;6(5):312-5
EPIDEMIOLOGY• CDC: Achievements in Public Health, 1900-1999 Impact of Vaccines Universally Recommended for Children -- United States, 1990-
1998 MMWR April 02, 1999 / 48(12);243-248• CDC. Measles, Mumps and Rubella – Vaccine Use and Strategies for Elimination of Measles, Rubella and Congenital Rubella
Syndrome and Control of Mumps: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR May 22, 1998; 47(RR-8): 1-57.
• CDC SUPPLEMENT – Collected Recommendations of the Public Health Service Advisory Committee on Immunization Practices MMWR Oct. 25, 1969; 18(43) : 1-31
• Durrheim DN, Crowcroft NS, Strebel PM Measles - The epidemiology of elimination Vaccine. 2014;32(51):6880. Epub 2014 Nov 4• Global Vaccine Action Plan. Decade of vaccine collaboration. Vaccine. 2013;31 Suppl 2:B5
Measles
Bibliography IV COMPLICATIONS
MEASLES IMMUNOSUPRESSION• C. L. Karp, M. Wysocka, L. M. Wahl, J. M. Ahearn, P. J. Cuomo, B. Sherry, G. Trinchieri, D. E. Griffin Mechanism of
suppression of cell-mediated immunity by measles virus. Science 273, 228–231 (1996). doi:10.1126/science.273.5272.228 pmid:8662504
• B. Hahm, Hostile communication of measles virus with host innate immunity and dendritic cells. Curr. Top. Microbiol. Immunol. 330, 271–287 (2009). doi:10.1007/978-3-540-70617-5_13 pmid:19203114
• . Schneider-Schaulies, J. Schneider-Schaulies, Measles virus-induced immunosuppression. Curr. Top. Microbiol. Immunol. 330, 243–269 (2009). doi:10.1007/978-3-540-70617-5_12 pmid:1920311
• R. D. de Vries, S. McQuaid, G. van Amerongen, S. Yüksel, R. J. Verburgh, A. D. Osterhaus, W. P. Duprex, R. L. de Swart, Measles immune suppression: Lessons from the macaque model. PLOS Pathog. 8, e1002885 (2012). doi:10.1371/journal.ppat.1002885 pmid:22952446
• Laksono BM, de Vries RD, McQuaid S, Duprex WP Measles Virus Host Invasion and Pathogenesis Viruses. 2016 Aug; 8(8): 210. Published online 2016 Jul 28. doi: 10.3390/v8080210 PMCID: PMC4997572PMID: 27483301
• Mina M.J., Metcalf C.J., de Swart R.L., Osterhaus A.D., Grenfell B.T. Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Science. 2015;348:694–699. doi: 10.1126/science.aaa3662.
Measles
Bibliography VComplications
PNEUMONIA
• Maldonad YA, Kaplan SL, Sullivan M. Measles: Clinical manifestations, diagnosis, treatment, and prevention. UpToDate® Feb 2019.updated: Oct 26, 2018
• Rupp ME, Schwartz ML, Bechard DE. Measles Pneumonia: Treatment of a Near-Fatal Case With Corticosteroids and Vitamin A. https://doi.org/10.1378/chest.103.5.1625
• Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book), 12th ed, Atkinson W, Wolfe C, Hamborsky J (Eds), The Public Health Foundation, Washington, DC 2011.
• Bernstein DI, Schiff GM. Measles. In: Infectious Diseases, Gorbach SL, Bartlett JG, Blacklow NR (Eds), WB Saunders, Philadelphia 1998. p.1296.
• Beckford AP, Kaschula RO, Stephen C Factors associated with fatal cases of measles. A retrospective autopsy study. S Afr Med J. 1985;68(12):858
• Quiambao BP, Gatchalian SR, Halonen P, Lucero M, Sombrero L, Paladin FJ, Meurman O, Merin J, Ruutu P. Coinfection is common in measles-associated pneumonia. Pediatr Infect Dis J. 1998;17(2):89
• Olson RW. Hodge GR. Measles Pneumonia Bacterial Suprainfection as a Complicating Factor JAMA. 1975;232(4):363-365.doi:10.1001/jama.1975.03250040017018
NEUROLOGIC COMPLICATIONSENCEPHALITIS• Maldonad YA, Kaplan SL, Sullivan M. Measles: Clinical manifestations, diagnosis, treatment, and prevention.
UpToDate® Feb 2019.updated: Oct 26, 2018• Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book), 12th ed, Atkinson W, Wolfe C,
Hamborsky J (Eds), The Public Health Foundation, Washington, DC 2011.• Zeng SZ, Zhang B, Zhang Y, Xie LY, Xiong J, Yu T, Xie ZP, Gao HC, Duan ZJ Identification of 12 Cases of Acute Measles
Encephalitis Without Rash. Clin Infect Dis. 2016;63(12):1630
Measles
Bibliography VIComplications
NEUROLOGIC COMPLICATIONSENCEPHALITIS• Maldonad YA, Kaplan SL, Sullivan M. Measles: Clinical manifestations, diagnosis, treatment, and prevention.
UpToDate® Feb 2019.updated: Oct 26, 2018• Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book), 12th ed, Atkinson W, Wolfe C,
Hamborsky J (Eds), The Public Health Foundation, Washington, DC 2011.• Zeng SZ, Zhang B, Zhang Y, Xie LY, Xiong J, Yu T, Xie ZP, Gao HC, Duan ZJ Identification of 12 Cases of Acute Measles
Encephalitis Without Rash. Clin Infect Dis. 2016;63(12):1630• Cherry JD. Measles virus. In: Textbook of Pediatric Infectious Diseases, 6th ed, Feigin RD, Cherry JD, Demmler-Harrison
GJ, et al (Eds), Saunders, Philadelphia 2009. p.242
ACUTE DISSEMINATED ENCEPHALOMYELITIS• Maldonad YA, Kaplan SL, Sullivan M. Measles: Clinical manifestations, diagnosis, treatment, and prevention.
UpToDate® Feb 2019.updated: Oct 26, 2018• Bernstein DI, Schiff GM. Measles. In: Infectious Diseases, Gorbach SL, Bartlett JG, Blacklow NR (Eds), WB Saunders,
Philadelphia 1998. p.1296• Johnson RT, Griffin DE, Hirsch RL, Wolinsky JS, Roedenbeck S, Lindo de Soriano I, Vaisberg A. Measles
encephalomyelitis--clinical and immunologic studies. N Engl J Med. 1984;310(3):137• Tenembaum S, Chamoles N, Fejerman N Acute disseminated encephalomyelitis: a long-term follow-up study of 84
pediatric patients. Neurology. 2002;59(8):1224
Measles
Bibliography VIIComplications
NEUROLOGIC COMPLICATIONS
SUBUBACUTE SCLEROSING PANENCEPHALITIS • Maldonad YA, Kaplan SL, Sullivan M. Measles: Clinical manifestations, diagnosis, treatment, and prevention.
UpToDate® Feb 2019.updated: Oct 26, 2018• Dyken PR. Viral diseases of the central nervous system. In: Pediatric Neurology: Principles and Practice, Mosby, St.
Louis 1994. p.670• Subacute sclerosing panencephalitis surveillance - United States. Centers for Disease Control (CDC) MMWR Morb
Mortal Wkly Rep. 1982;31(43):585• Bellini WJ, Rota JS, Lowe LE, Katz RS, Dyken PR, Zaki SR, Shieh WJ, Rota PA Subacute sclerosing panencephalitis: more
cases of this fatal disease are prevented by measles immunization than was previously recognized. J Infect Dis. 2005;192(10):1686.
• Bernstein DI, Reuman PD, Schiff GM. Rubeola (measles) and subacute sclerosing panencephalitis virus. In: Infectious Diseases, Gorbach SL, Bartlett JG, Blacklow NR (Eds), WB Saunders, Philadelphia 1998. p.2135
• Garg RK Subacute sclerosing panencephalitis. J Neurol. 2008;255(12):1861. Epub 2008 Oct 14• Adams RD, Victor M, Ropper AH. Viral infections of the central nervous system. In: Principles of Neurology, McGraw-
Hill, New York City 1997. p.767.• Seo YS, Kim HS, Jung DE 18F-FDG PET and MRS of the early stages of subacute sclerosing panencephalitis in a child
with a normal initial MRI. Pediatr Radiol. 2010 Nov;40(11):1822-5. Epub 2010 Mar 1
Measles
Bibliography VIIIEpidemiology§ Naim Y. Measles virus A pathogen, vaccine, and a vector. Hum Vaccin Immunother. 2015 Jan; 11(1): 21–26. Published
online 2014 Aug 5. doi: 10.4161/hv.34298PMCID: PMC4514292PMID: 25483511§ Measles, World Health Organization Fact sheet Updated February 2014 § Millennium Development Goals. United Nations. 18 March 2013§ Briefed V, Hashed Y, Sherman FE, Odagiri K, Yunis EJ. Fatal measles infection in children with leukemia. Lab Invest 1973;
28:279 - 91; PMID: 4348408 [PubMed] [Google Scholar]§ Polonsky JA, Ronsse A, Ciglenecki I, Rull M, Porten K.High levels of mortality, malnutrition, and measles, among recently-
displaced Somali refugees in Dagahaley camp, Dadaab refugee camp complex, Kenya, 2011. Confl Health 2013; 7:1; http://dx.doi.org/10.1186/1752-1505-7-1; PMID: 23339463
§ Clements CJ, Cutts FT. The epidemiology of measles: thirty years of vaccination. Curr Top Microbiol Immunol 1995; 191:13 - 33; http://dx.doi.org/10.1007/978-3-642-78621-1_2; PMID: 7789156
§ Ask the experts: Measles mumps Rubella. Immunization Action Coalition. http://www.immunize.org/askexperts/experts_mmr.asp
MEALSES OUTBREAKS§ Cultural Perspectives on Vaccination. History of Vaccines: History and Society: Vaccine Science. The History of Vaccines.
https://www.historyofvaccines.org/index.php/content/articles/cultural-perspectives-vaccination§ Julia Belluz New York’s Orthodox Jewish community is battling measles outbreaks. Vaccine deniers are to blame. March 27, 2019.
Vox Media. https://www.vox.com/science-and-health/2018/11/9/18068036/measles-new-york-orthodox-jewish-community-vaccines• Measles outbreak sickens dozens of Minnesota Somalis. ASSOCIATED PRESS. SC Times. Published 2:12 p.m. CT May 3,
2017. https://www.sctimes.com/story/news/local/minnesota/2017/05/03/measles-outbreak-sickens-dozens-minnesota-somalis/101252532/
• Melissa Jenco. Study: Low vaccination rate in Amish children linked to hospitalization. AAP news August 2, 2017. AAP news and Journals, Gateway https://www.aappublications.org/news/2017/08/02/AmishVaccines080217
• Williamson G, Ahmed B,Kumar PS, et.al. Vaccine-Preventable Diseases Requiring Hospitalization. Pediatrics. September 2017 Vol 130/issue 3
Measles
Bibliography IX EpidemiologyMICHIGAN MEASLES § 2019 Michigan Measles Outbreak Information. Michigan Department of Health & Human Services.
https://www.michigan.gov/mdhhs/0,5885,7-339-73971_4911_4914_68359-492981--,00.html§ Mike Martindale and Shawn D. Lewis With 5th most vaccine exemptions, Oakland measles outbreak 'sadly, predicted’, The Detroit
News. Published 10:31 p.m. ET April 3, 2019 | Updated 10:19 a.m. ET April 4, 2019 https://www.detroitnews.com/story/news/local/oakland-county/2019/04/04/measles-outbreak-puts-detroit-area-high-alert/3304068002/
§ Tracy Samilton & Kate Wells. Orthodox Jewish community in Oakland County gets word out on measles case. March 14, 2019. Michigan Radio (“NPR”) https://www.michiganradio.org/post/orthodox-jewish-community-oakland-county-gets-word-out-measles-case
§ CDC: Michigan Vaccination Among the Worst in Country, Preventable Illnesses Poised To Make Comeback. https://forum.facepunch.com/f/pd/beapr/CDC-Michigan-Vaccination-Among-the-Worst-in-Country-Preventable-Illnesses-Poised-To-Make-Comeback/1/
§ Kristen Jordan Shamus. How Oakland Co.'s Orthodox Jewish enclave became the epicenter for Michigan measles outbreak, Detroit Free Press. Published 6:01 a.m. ET April 14, 2019 | Updated 2:12 p.m. ET April 29, 2019. https://www.freep.com/story/news/local/michigan/2019/04/14/michigan-measles-outbreak-orthodox-jewish-community-oakland-county/3411582002/
§ (Michigan) School Immunization Data MDHHS Adult & Children's Services Children & Families Immunization Info for Families & Providers. https://www.michigan.gov/mdhhs/0,5885,7-339-73971_4911_4914_68361-335711--,00.html
§ Julie Mack The 49 Michigan schools with vaccine waiver rates of 30 percent or more. [email protected] | Posted February 10, 2019 at 08:45 AM | Updated March 10, 2019 at 12:58 PM https://expo.mlive.com/news/g66l-2019/02/0a8a2145747498/the-49-michigan-schools-with-vaccine-waiver-rates-of-30-percent-or-more.html
Measles
Bibliography X
VIROLOGY
• Enders JF, Peebles TC.Propagation in tissue cultures of cytopathogenic agents from patients with measles. Proc Soc Exp Biol Med 1954; 86:277 - 86; http://dx.doi.org/10.3181/00379727-86-21073; PMID: 13177653
• Naim Y. Measles virus A pathogen, vaccine, and a vector. Hum Vaccin Immunother. 2015 Jan; 11(1): 21–26. Published online 2014 Aug 5. doi: 10.4161/hv.34298PMCID: PMC4514292PMID: 25483511
• Katz SL John F. Enders and measles virus vaccine--a reminiscence. Curr Top Microbiol Immunol. 2009;329:3-11. https://www.ncbi.nlm.nih.gov/pubmed/19198559
Measles
Bibliography XIClinical Disease• Measles (Rubeola) Measles: It Isn’t Just a Little Rash Infographic. Center for Disease Control and Prevention, Atlanta Georgia.
https://www.cdc.gov/measles/parent-infographic.html• Measles home: About Measles: Transmission of Measles. Centers For Disease Control and prevention.(CDC) Atlanta,
Georgiahttps://www.cdc.gov/measles/about/transmission.html• Maldonad YA, Kaplan SL, Sullivan M. Measles: Clinical manifestations, diagnosis, treatment, and prevention. UpToDate® Feb
2019.updated: Oct 26, 2018
KOPLIK SPOTS• Koplik's spots: Related people Henry Koplik, Nikolaj Flindt, Nil Feodorovich Filatov. Whonamedit? A dictionary of
medical eponyms. http://www.whonamedit.com/synd.cfm/1437.html• Henry Koplik From Wikipedia, the free encyclopedia. https://en.wikipedia.org/wiki/Henry_Koplik• Koplik spots © 2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved (Photo)• Koplik H. The diagnosis of the invasion of measles from a study of the exanthema as it appears on the buccal
mucous membrane. Arch Pediatr 1896;13:918-22• Bixby, Derrick (July 1997). "Classic Paper: The diagnosis of the invasion of measles from a study of the exanthema
as it appears on the buccal mucous membrane". Reviews in Medical Virology. 7 (2): 71–74. doi:10.1002/(SICI)1099-1654(199707)7:2<71::AID-RMV185>3.0.CO;2-S. PMID 10398471.
• Enders, J.F.; Peebles, T.C. (1954). "Propagation in tissue culture of cytopathogenic agents from patients with measles". Proc. Soc. Exp. Biol. Med. 86 (2): 277–86. doi:10.3181/00379727-86-21073. PMID 13177653.
• Koplik, H (1896). "The diagnosis of the invasion of measles from a study of the exanthema as it appears on the buccal mucous membrane". Arch Pediatr. 13: 918–22.
• Koplik, Henry (1899). "the new diagnostic spots of measles on the buccal and labial mucous membranes". Med. News, (NY). 74: 673–6.
• Anon (1903). "Review; The Diseases of Infancy and Childhood, by Henry Koplik". Lancet. 162 (4171): 389–390.
Measles
Bibliography XIIClinical DiseaseKOPLIK SPOTS Continued• Zenner D, Nakul L .Predictive power of Koplik's spots for the diagnosis of measles.J Infect Dev Ctries. 2012;6(3):271. Epub 2012 Mar 12• Falkener, L (1901). "Fitalow's spots in morbilli". Lancet. 157 (4040): 315–7.
EXANTHAMS• Hudson JB, Weinstein L. Chang TW. Thrombocytopenic purpura in measles. J Pediatr. 1956;48(1):48• Abramson O, Dagan R, Tal A, Sofer S. Severe complications of measles requiring intensive care in infants and young children. Arch
Pediatr Adolesc Med. 1995;149(11):1237• Suringa DW, Bank LJ, Ackerman AB .Role of measles virus in skin lesions and Koplik's spots. N Engl J Med. 1970;283(21):1139.• Bernstein DI, Schiff GM. Measles. In: Infectious Diseases, Gorbach SL, Bartlett JG, Blacklow NR (Eds), WB Saunders, Philadelphia 1998.
p.1296• Koplik, Henry (1899). "the new diagnostic spots of measles on the buccal and labial mucous membranes". Med. News, (NY). 74: 673–6
DIFFEIRENTAL DIAGNOSIS• Measles Rash Differential. Epocrates on line. https://online.epocrates.com/diseases/21735/Measles-infection/Differential-Diagnosis• Maldonad YA, Kaplan SL, Sullivan M. Measles: Clinical manifestations, diagnosis, treatment, and prevention. UpToDate® Feb
2019.updated: Oct 26, 2018
Measles
Bibliography XIII
MMR VACCINE CONTROVERSY
• Brian Deer. Huge sums paid to Andrew Wakefield :MMR doctor given legal aid thousands. The Sunday Times, December 31 2006. http://briandeer.com/mmr/st-dec-2006.htm
• Lisa A. Rickard. The Anti-Vaccine Movement And A Trial Lawyer-Funded Climate Of Fear. Forbeshttps://www.forbes.com/sites/theapothecary/2014/04/28/the-anti-vaccine-movement-and-a-trial-lawyer-funded-climate-of-fear/#307fd76762bd
• Andrew Wakefield’s Harmful Myth of Vaccine-induced “Autistic Entercolitis”: How the MMR Vaccine Scare Began. GI Society: The Canadian Society of Intestional research. https://www.badgut.org/information-centre/a-z-digestive-topics/andrew-wakefield-vaccine-myth/
• Alice Park. Doctor behind vaccine-autism link loses license. TIME MAGAZINE May 24, 2010. http://healthland.time.com/2010/05/24/doctor-behind-vaccine-autism-link-loses-license
• Burgess DC1, Burgess MA, Leask J The MMR vaccination and autism controversy in United Kingdom 1998-2005: inevitable community outrage or a failure of risk communication? Vaccine. 2006 May 1;24(18):3921-8. Epub 2006 Mar 3.
• Do Vaccines Cause Autism?. Common Questions. The History of Vaccines. An educational resource by the College of Physicians of Philadelphia. https://www.historyofvaccines.org/content/articles/do-vaccines-cause-autism
• Vaccines Do Not Cause Autism. Common concerns. Vaccine Safety. Centers of Disease Control and Prevention, Atlanta Georgia. https://www.cdc.gov/vaccinesafety/concerns/autism.html
Measles
Bibliography XIVVACCINES
VACCINE• Polio and Swimming Pools: Historical Connections. History of Vaccines June 28, 2012 Project Direction. History of Vaccines
https://www.historyofvaccines.org/content/blog/polio-and-swimming-pools-historical-connections• John Enders: the Father of Modern Vaccines. Tag Achives: David Edmonston. Virology Molecular Biology and Pathogenesis
August 4, 2016. https://norkinvirology.wordpress.com/tag/david-edmonston/• ProQuad® (MMR) Mark Vaccines.com. Product Information https://www.merckvaccines.com/products/proquad• CDC. Use of Combination Measles, Mumps, Rubella, and Varicella Vaccine: Recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR. 2010 May 07;59(RR03):1-12.• Hornig M, Briese T, Buie T, Bauman ML, Lauwers G, et al. Lack of association between measles virus vaccine and autism with
enteropathy: A case-control study. PLoS One. 2008 Sep 4;3(9):e3140.• Klein NP, Fireman B, Yih WK, Lewis E, Kulldorff M. Measles-mumps-rubella-varicella combination vaccine and the risk of
febrile seizures. Pediatrics. 2010 Jul;126(1):e1-8.• Klein NP, Lewis E, Baxter R, et al. Measles-containing vaccines and febrile seizures in children age 4 to 6 years Pediatrics. 2012
May;129(5):809 -814.• Rowhani-Rahbar A, Fireman B, Lewis E, Nordin J, Naleway A, et al. Effect of age on the risk of Fever and seizures following
immunization with measles-containing vaccines in children JAMA Pediatr. 2013 Dec;167(12):1111-7.• Low vaccination rates a big factor in ongoing measles outbreak. By ABC Radio | @ABCRadioJanuary 27, 2019 6:22 pm
https://wtop.com/health-fitness/2019/01/low-vaccination-rates-a-big-factor-in-ongoing-measles-outbreak/• Mike Martindale and Shawn D. Lewis With 5th most vaccine exemptions, Oakland measles outbreak 'sadly, predicted’, The
Detroit News. Published 10:31 p.m. ET April 3, 2019 | Updated 10:19 a.m. ET April 4, 2019 https://www.detroitnews.com/story/news/local/oakland-county/2019/04/04/measles-outbreak-puts-detroit-area-high-alert/3304068002/
Measles
Bibliography XV VACCINESHISTORY• What is the History of Measles Vaccine in America and Other Countries? National Vaccine Infeormation Center: Your
Health, Your Family. Your Choice. https://www.nvic.org/vaccines-and-diseases/measles/history-measles-vaccine.aspx• Hendriks J, Blume S Measles Vaccination Before the Measles-Mumps-Rubella Vaccine Am J Public Health. 2013
Aug;103(8):1393-401• Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Events Associated with Childhood
Vaccines (Evidence Bearing on Causality). Washington, DC: The National Academies Press. 1994 Chap. 6. P. 118• FDA Measles, Mumps, Rubella and Varicella Virus Vaccine Live. Oct 23, 2018
VACCINE EFFECTIVNESS & DURATION• One of the Recommended Vaccines: MMR and MMRV Vaccine Composition and Dosage: About the vaccine. Vaccine and
Preventable Disease. Centers for Disease Control and prevention (CDC) Atlanta, Georgia. MMR and MMRV Vaccine Composition and Dosage. MMR and MMRV Vaccine Composition and Dosage
VACCINE SAFETY• Vaccine Adverse Event Reporting System: Vaccine Safety Monitoring – VAER. Centers for Disease Control and Prevention. Atlanta Georga.
https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vaers/index.html• Vaccine Safety Datalink (VSD) Vaccine Safety Monitoring – VSD. Centers for Disease Control and Prevention. Atlanta Georga.
https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vsd/index.html• Clinical Immunization Safety Assessment (CISA) Project. Vaccine Safety Monitoring – CISA. Centers for Disease Control and Prevention. Atlanta
Georga. https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/cisa/index.htm