Measles

Summary

Measles is an extremely contagious viral disease caused by the measles virus, primarily affecting children. Pneumonia is most common cause of death in patients with measles. It is prevalent in areas with low vaccination rates and involves transmission through airborne respiratory droplets thus airborne precautions are required. The course of the illness typically begins with a prodrome of high fever, cough, coryza, and conjunctivitis, followed by the appearance of Koplik spots (4Cs) and a characteristic maculopapular rash that starts on the face and spreads downward. Koplik spots are pathognomonic for measles. Diagnosis requires laboratory testing with CDC recommendations to obtain both RT-PCR and serum IgM antibodies. Prevention with MMR or MMRV vaccine. Treatment is mainly supportive, including hydration, antipyretics, and vitamin A supplementation. Airbourne isolation precautions should be performed. Ideally use negative pressure room. Infected persons contagious from 4 days before to 4 days after rash onset. Close contacts should be evaluated for post exposure prophylaxis. Consider inpatient services for severe complications such as pneumonia, encephalitis, or if pt is immunocompromised. During post infectious period, SSPE can occur 7-10 years after measles infection which is universally fatal.

Key Terms

Measles: aka Rubeola or "10 Day" Measles or Regular Measles
German Measles: aka Rubella or “3-day” measles
Koplik Spots: Pathognomonic sign of measles and typically appear 1-2 days before the characteristic measles rash. Small, white lesions with a red base that appear on the buccal mucosa (inside the mouth) opposite the molars.
Enanthem: mucous membrane rash INSIDE the body. Example is koplik spots.
Exanthem: mucous membrane rash OUTISDE the body
MMR: measles, mumps, and rubella
MMRV: measles, mumps, rubella, and varicella
MCV: Measles Containing Vaccine
SSPE: Subacute sclerosing panencephalitis. Rare but universially fatal complication of measles that occurs 7-10 years after measles infection.
Atypical Measles Syndrome: Most cases occured in 1960s. Extremely rare complication since 1980s. Occured in pts who received the original killed virus vaccine.

Mnemonics

"MEASLES" (Stages of Measles Progression):

M - Maculopapular rash
E - Enanthem (Koplik spots)
A - Airborne transmission
S - Subacute sclerosing panencephalitis (SSPE)
L - Lymphadenopathy
E - Erythematous rash
S - Supportive care

"Rubeola (Measles) vs. Rubella (German Measles)"

Rubella - "The Friendly 🐶German Shepherd🐶"
- Gentle & Short illness (mild symptoms, lasts ~3 days)
- Extra danger for pregnant women (Congenital Rubella Syndrome)
- Rapid rash (spreads fast, disappears quickly)
- Mild fever, less severe than measles
- Adenopathy (swollen lymph nodes, especially behind ears)
- No Koplik spots
Rubeola - "The Dangerous 🔻Ruby Stone🔻"
- Red rash
- Unrelenting rash (spreads slower, lasts longer ~7+ days)
- Breathing issues (Cough, Coryza, Conjunctivitis)
- Yucky white Koplik spots in the mouth
- Severe symptoms (fever, pneumonia, encephalitis risk)
- Transmission is highly contagious (Airborne)
- Ongoing complications (can cause SSPE years later)
- Never mild—can be deadly
- Eyes (Conjunctivitis)

Microbiology

Taxonomy: Paramyxoviridae -> Morbillivirus -> Measles Virus
Genetics: RNA, single-stranded, negative sense, enveloped virus
Serotype: Only one serotype
Hosts: Humans are the only natural host
Virulence: Highly contagious. "A large infective dose of virus may occasionally overcome the protection afforded by maternal antibodies, and measles has been observed in neonates and infants whose mothers escaped wild-type virus infection and had never been vaccinated against measles." - WHO
Disinfection: Can be inactivated by heat, UV light, and disinfectants.
Transmission: Can survive in the environment for up to 2 hours

Epidemiology

Mortality
- 1-2 deaths per 1000 cases
- Most common cause of death in pts w/ measles is pneumonia
- Risk Factors
  - Immunocompromised: HIV/AIDS
  - Malnourished
  - Vitamin A Deficiency
Complications
- Most to Least Common:
  - Otitis Media > Croup > Diarrhea > PNA > Encephalitis > SSPE
- MCC Death: Pneumonia
- Encephalitis
  - 1:1000 cases
  - Occurs 1-3 weeks after rash onset
  - Can cause permanent brain damage
- Atypical Measles Syndrome
  - Most cases occured in 1960s after administration of an inactivated virus vaccine which was subsequently taken off market and never reintroduced.
  - Extremely rare complication since 1980s
  - Occured in pts who received the original killed virus vaccine
- Post Infectious Measles Encephalitis
- Subacute sclerosing panencephalitis (SSPE)
  - 1:10,000 to 100,000
  - Universally fatal complication of measles
  - Occurs 7-10 years after measles infection
- Bacterial superinfection, including pneumonia
- Acute Thrombocytopenic purpura
- Transient Hepatitis
Transmission
- Airborne (resp dropslets can suspend for 2 hours in air)
- Spread through respiratory droplets
- Highly contagious
- late winter / spring
- Contagious 4 days before and 4 days after rash onset
Prevention
- Vaccination
- Good hygiene practices
Outbreaks
- CDC Measles Cases and Outbreaks
- Year 2000: considered eliminated in USA
- Year 2004: 37 cases
- Year 2019: 1200 cases (majority not vaccinated)
- Year 2024: 114 of 285 cases (40%) hospitalized
- Common in areas with low vaccination rates
- Can occur in densely populated areas
Incubation period
- Typically 10-14 days
- Time from exposure to symptom onset
Contagious period
- 4 days before rash onset
- 4 days after rash onset

Highly contagious viral disease

Prevalent in areas with low vaccination rates

Primarily affects children

Etiology

Caused by the measles virus
Transmission through respiratory droplets from an infected person
Humans are only the only natural host

Pathophysiology

***

HPI

Incubation Period:11-14 days
Exposure to Rash:14 days (7-21 days)
Prodrome Period:2-4 days
Exposure Recent contact with individuals who are not vaccinated against MMR
Fever High fever (as high as 105°F range 103°F to 105°F)
4Cs: cough, coryza, conjunctivitis, and Koplik spots (not a c but sounds like)
Rash Starts on head at hairline with face and upper neck involvement. Rash proceeds to spread down to hands and feet. Maculopapular in appearance. Lesions blanch initially then by days 3-4 do not blanch. Lasts 5 -6 days. Rash recedes in the order it presents.
Story: 4 year old child presents to clinic, accompanied by mother, with high fever for 2 days, cough, eye watering, and conjunctivitis. When asked about vaccination history, mother reports they do not vaccinate but rely on "getting the virus" to "have better antibodies", and "the MMR vaccine causes autism because of heavy metals".

Physical Exam

Temperature: as high as 105°F
HEENT: Conjunctivitis, runny nose (coryza), koplik spots on buccal mucosa (pathognomonic)
Lungs: dry, hacking cough
Skin: maculopapular initially blanching rash spreads from head to trunk to lower extremities

Diagnostics

CDC Diagnostics Summary Table Link
**Measles is a mandatory, immediately notifiable infectious disease**
Most Ideal: RT-PCR nasopharngeal swab AND serum IgM collected at same time
Active Infection
- RT-PCR:
  - RT-PCR can be performed on respiratory (nasopharyngeal or throat) swabs and on urine but nasopharynx is ideal.
  - RT-PCR is most sensitive within 3 days of rash onset but can be positive up to 10 days after rash onset.
  - Ideally, specimens should be collected at first patient contact once measles is suspected and should be paired with serology testing (IgM) for evaluation of all suspect measles cases.
  - For many jurisdictions, RT-PCR is primarily available through the state/local health department.
- Serum IgM:
  - Detection of measles IgM can confirm measles.
  - Timing: IgM is most sensitive 3 or more days after rash onset, so a negative IgM within 3 days of rash onset should be interpreted with caution.
  - False Positives: can occur due to cross-reactivity with other causes of febrile rashes (e.g., Parvovirus).
  - Synergistic Testing: Ideally, RT-PCR and serology should be performed together for all suspect measles cases.
  - DON'T: use to evaluate for immunity rather use Serum IgG
Testing for Immunity
- THIS ONE: Measles Serum IgG antibody
- NOT THIS ONE: Measles Serum IgM antibody
- "The presence of measles-specific IgG indicates a recent or prior exposure to measles virus or measles vaccine and is appropriate to test for evidence of immunity." - CDC

Differential Diagnosis

Parvovirus B19
Enteroviruses
HHV-6 (Roseola) Human Herpesvirus 6

Treatment

***Patient Isolation***
- Negative Pressure Room
- N95 Mask
Supportive Therapy: hydration, antipyretics, abx for bacterial infections.
Vitamin A Supplementation
- Administer to all cases of measles
- Data shows higher risk of complications and mortality in pts w/ vit A deficiency
- Interval: immediately on diagnosis, irrespective of previous doses of vitamin A, and repeated the next day. Consider 3rd dose, if the child has clinical ophthalmic signs of vitamin A deficiency such as Bitot’s spots, a third dose should be given 4–6 weeks later.
- Dose:
  - < 6 months: 50,000 IU
  - 6 to 11 months: 100,000 IU
  - ≥ 12 months: 200,000 IU
Post Exposure Prophylaxis
- Unimmunized or Insufficiently Immunized: Administered w/in 72 hrs of exposure to measles virus to protect against disease. If disease does develop, symptoms are usually not severe and the duration of illness is shortened.
- Pregnancy/Immunocompromised: If live vaccine is contraindicated, human immune globulin may be given after measles virus exposure, particularly to pregnant women, infants aged less than 6 months, and individuals with impaired immune systems. If administered within 6 days of exposure, this method of passive immunization can prevent illness or reduce its severity.

Prevention

Currently Available Vaccines
- M-M-R II
  - Trade Name: M-M-R II
  - Proper Name: Measles, Mumps and Rubella Virus Vaccine Live
  - Manufacturer: Merck Sharp & Dohme LLC
  - FDA Page
- PRIORIX
  - Proper Name: Measles, Mumps and Rubella Vaccine, Live
  - Tradename: PRIORIX
  - Manufacturer: GlaxoSmithKline Biologicals SA
  - FDA Page
- PROQUAD
  - Proper Name: Measles, Mumps, Rubella and Varicella Virus Vaccine Live
  - Tradename: ProQuad
  - Manufacturer: Merck Sharpe & Dohme LLC
  - FDA Page
Vaccine Schedule
- Routine Schedule
  - CDC Vaccine Schedule
  - 2 dose series
  - Minimum Age: 12 months
  - First: 12 to 15 months old
  - Second: 4 to 6 years old
  - Either MMR or MMRV but MMR is recommneded as first dose
- Catch Up
  - Unvaccinated Children and Adolescents: 2 dose series at least 4 weeks apart
  - MMRV max age is 12 years old
  - MMRV interval is 3 months

Vaccine History

Vaccine Development Timeline
- 1963 Both inactivated and live attenuated measles (Edmonston B strain) vaccine were licensed by FDA
- 1967 Inactivated vaccine was withdrawn because it did not protect well against measles and occurences of atypical measles syndrome with this vaccine
- 1968 Edmonston-Enders strain live attenuated vaccine was licensed (fewer reactions than Edmonston B)
- 1971 Combined MMR first licensed for use in the United States
- 1975 Original Edmonston B vaccine was withdrawn d/t high frequency of fever and rash
- 1989 2nd dose of MMR recommended.
- 2005 MMRV combination vaccine was licensed

Vaccine Hesitancy

1998 Andrew Wakefield and colleagues publish case series in Lancet suggesting MMR vaccine linked to Autism.
- Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998;351:637–41. doi: 10.1016/s0140-6736(97)11096-0.
Dramatic drop in MMR vaccination worldwide
Further published studies disprove link between autism and MMR vaccine
2010 Lancet fully retracts original 1998 Wakefield paper from publishing record due to judgement by UK General Medical Council's Fitness to Practice Panel.
- Anonymous. Retraction-Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorder in children. Lancet. 2010;375:445. doi: 10.1016/S0140-6736(10)60175-4.
Read more here from Children's Hospital of Philadelphia.

Referrals

Hospitalization: occurs in 50% of children < 5 years old d/t complications of pneumonia.

Compare and Contrast

**Comparrison of German Measles (Rubella) vs. Measles (Rubeola)**
Feature	Rubella (German Measles)	Rubeola (Measles)
Causative Agent	Rubella virus	Measles virus
Incubation Period	14-21 days	10-14 days
Prodromal Symptoms (Early Symptoms)	Mild fever (often low-grade) Headache Mild cold symptoms Swollen lymph nodes (especially behind ears and neck)	High fever (as high as 105°F) Cough Runny nose (coryza) Conjunctivitis (red, watery eyes) Koplik spots (small white spots inside the mouth)
Rash Characteristics	Pink or light red maculopapular rash Starts on the face and spreads down the body Usually fades within 3 days Not as pronounced or intense as measles rash	Red-brown maculopapular rash Starts on the face (around hairline) and spreads downward Rash may become confluent (spots merge) Can last 5-7 days
Complications	Generally mild Arthritis (especially in women) Rare: Encephalitis Serious risk of Congenital Rubella Syndrome (CRS) in pregnant women, affecting the fetus.	Pneumonia Ear infections Diarrhea Encephalitis (brain inflammation) Subacute sclerosing panencephalitis (SSPE) a rare but fatal disease.
Contagious Period	7 days before and after rash onset	4 days before and 4 days after rash onset
Vaccine	MMR vaccine (Measles, Mumps, Rubella)	MMR vaccine (Measles, Mumps, Rubella)
Severity	Generally mild in children and adults. Severe danger to pregnant women	More severe and can be deadly, especially in young children.

Knowledge Assessment

Q: What are Koplik spots, and when do they typically appear in the course of measles?
A: Koplik spots are small, white lesions with a red base that appear on the buccal mucosa (inside the mouth) opposite the molars. They typically appear 1-2 days before the characteristic measles rash.

Q: Which measles is most dangerous to pregnant women?
Q: Which measles is longer in duration? shorter?
Q: What is the characteristic rash seen in measles, and how does it typically progress?
Q: What are the key differences between rubeola and rubella?
Q: How is measles diagnosed, and what are the key findings on physical exam?
Q: In addition to PCR testing, what other test should be paired?
Q: What area of body is most ideal to swap for PCR?
Q: When is serum IgM a reliable test of measles? When should it be interpreted with caution?
Q: Which test is used to detect immunity against measles?
Q: What is the treatment for measles, and when should patients be referred to a healthcare provider?
Q: How long after measles infection can SSPE occur?

Case Study

Related Diseases

German Measles (Rubella)