Measles

MICROBIOLOGY

  • Morbillivirus, a negative sense, single-strand RNA virus of the Paramyxoviridae group.
    • Related to other morbilliviruses infecting animals, including rinderpest virus, peste des petitis ruminants virus, canine distemper virus and dolphin morbillivirus.
  • Measles virus (MV), also known as rubeola, is a respiratory agent with subsequent viremia.
  • Others in the paramyxovirus family:

CLINICAL

  • Until routine measles immunization, the rubeola virus was the most common and highly contagious of childhood diseases.
  • Remains a worldwide problem with 140,000 measles-related deaths (2018, WHO). Eradication is difficult despite WHO efforts due to problems in lower-resource countries, maintaining cold-chain for the vaccine.
    • U.S. (2022 data): 121 cases in six jurisdictions.
      • Outbreaks continue to occur in the U.S. due to an under-immunized population in many locales and imported infections.
      • In 2019, 1,274 individual cases of measles were confirmed in 31 states, the highest number in the US since 1992.
        • Factors driving the persistence of outbreaks include:
          • More travelers who acquire measles overseas and remain infectious upon returning to the U.S. →
          • Further transmission in communities, especially those with higher rates of unvaccinated people.
    • For outbreak reports, see CDC: Measles Cases and Outbreaks.
  • Risks:
    • Non-immunized or poor response to the vaccine.
      • Most cases in the U.S. are in non-immunized children/adolescents or adults.
      • Exposure risk typically from travelers visiting the U.S. or just returning from visiting overseas in a country with active measles
      • See the WHO map for countries with active cases; most cases (2020, latest data) are seen in Africa (especially DRC), Khazikstan, Philippines; however, many countries report positive cases annually.
  • Typical signs and symptoms are fever, coryza, and cough followed by a rash [Fig 1].
    • Incubation: typically 10-12 days following exposure; first symptom typically high fever and flu-like symptoms along with cough and coryza.
    • Koplik spots: appear 2-3d after the onset of symptoms, and occur on the inside of the mouth as tiny, bluish-white spots surrounded by erythema on the buccal mucosa [Fig 2]. May precede the onset of rash and are pathognomonic of measles.
    • Rash: typically 3-5d after illness onset as a macular rash that begins on the face and spreads downward to become large confluent blotches over the entire body [Fig 3]. Fever may spike and then abate with the onset of rash with the disappearance of viremia.
    • Patients may also experience diarrhea, vomiting, lymphadenopathy, abdominal pain, pharyngitis, splenomegaly, leukopenia, and thrombocytopenia.
  • The entire illness lasts up to 10-14d. Patients usually become afebrile following the onset of the rash.
    • If fever persists, suspect a secondary bacterial infection.
  • Diagnosis:
    • Clinical: usually a clinically based dx based on acute febrile illness, characteristic rash and/or Koplik spots (irregular red spots w/tiny blue-white specks on buccal/lingual mucosa) in a patient with residence or travel within an endemic country or recent exposure to an index or secondary case.
    • Serology: measles EIA
      • IgM is helpful for acute infection. It can be negative before the rash but typically becomes positive at the rash onset.
      • IgG is used to assess immune status.
    • Culture: tissue/secretions may be cultured for viruses and/or identified by IFA.
      • Nasopharyngeal aspirate IFA offers rapid dx.
    • RT-PCR: respiratory or urine samples.
    • In the U.S.: contact the local or state health department first.
      • The CDC Infectious Diseases Laboratories offers diagnostic assistance (culture, PCR): T: 404-639-1156; E-Mail: jrota@cdc.gov
  • Secondary complications: otitis media, bronchopneumonia, croup, diarrhea, bronchitis.
    • Most common in children < 5 yrs, adults > 20 yrs.
    • Many deaths from measles occur in malnourished children succumbing to pneumonia or diarrhea.
    • Pregnancy: miscarriage, pre-term delivery
    • Direct measles complications are less common
      • Encephalomyelitis: 100/100,000 infections
      • Subacute sclerosing panencephalitis (SSPE): 10/100,000

SITES OF INFECTION

  • Mucocutaneous/systemic: characteristic disease progression starts with a prodrome of fever, cough, coryza, and conjunctivitis followed by flat macular rash fusing to form blotches first over the chest/trunk and then to limbs.
  • Pulmonary: pneumonitis (giant-cell pneumonia) during primary measles virus infection.
    • Atypical measles: now rare or nonexistent, pneumonitis as hallmark w/ hypersensitivity-like reaction in recipients of killed-measles vaccine (given in the 1960s-1970s) exposed to native measles.
  • CNS:
    • Acute encephalomyelitis occurs 1:1000 w/ 15% mortality.
      • The most frequently seen neurological complication of measles.
      • Two types:
        • Primary acute measles encephalitis
          • Direct viral CNS infection, mortality 10-25%, with 25% suffering permanent neurologic sequelae.
          • May recover MV in CSF.
        • Acute, post-measles encephalitis (immune-mediated)
          • More common than primary measles encephalitis.
          • Frequent symptoms include visual disturbances, difficulty with micturition, reduced reflexes.
          • Relapses may occur in one-third.
    • Measles inclusion body encephalitis (MIBE)
      • Occurs typically in immunodeficient children ~ 1 year after measles or measles immunization.
      • Native MV >> vaccine strains may cause.
      • CSF is usually normal.
      • High anti-measles IgG in CSF.
      • MV RNA may be detected in brain biopsies.
      • Mortality: 75%
    • Subacute sclerosing panencephalitis (SSPE): very rare, < 1:300,000 cases usually occurring 7-10 years or more after measles.
      • Due to defective, persistent measles virions.
      • Progressive brain inflammation leads to gradually progressive cognitive impairment, behavioral disturbances, myoclonus/spasms, seizures, and subsequently, gait abnormalities and speech impairment that result in mutism, a vegetative state before coma and death.
        • Diagnostic findings:
          • MRI: white matter changes in the cerebral cortex and brain stem
          • CSF: elevated measles IgG
          • EEG: characteristic periodic spikes (Rademecker complex)
          • Brain biopsy: eosinophilic inclusion bodies

TREATMENT

General

  • Report suspected measles cases ASAP to the local or state health department--do not wait for diagnostic confirmation.
  • Hospitalized patients should be in respiratory isolation with airborne precautions (N95, PAPR).
    • Specific CDC guidance here.
  • If at home, isolation is necessary:
    • Consider patients infectious from 4 days before rash onset until 4 days after onset of rash.

Children

  • Most well children may be observed without intervention.
  • Supplementation: vitamin A recommended by the American Academy of Pediatrics for children ill enough to be hospitalized (6mos-2yrs) or if suffering from neurological/ophthalmological complication, malnutrition or immunodeficiency (>2yrs). Data in developing countries suggest it may help lower mortality
    • Consider vitamin A supplementation:
      • ≥ 12 mos: 200,000IU PO
      • 6-12 mos: 100,000IU PO
      • < 6 mos: 50,000IU PO
      • Duration: daily x 2 doses
        • Repeat vitamin A dosing at four weeks if suffering from eye disease.

Adults

  • Supportive care.
    • The infection tends to be more severe than in pediatric populations.
  • Some experience w/ ribavirin used parenterally (20-35mg/kg/d x 7d) in adults w/ severe pneumonitis[29].
    • Also available by aerosol, and oral routes--but little clinical data for measles.
    • IV formulation may not be available in the U.S.

Neurological disease

  • Acute post-measles encephalitis: corticosteroids and/or gammaglobulin.
    • It may be difficult to distinguish from primary measles virus encephalitis, wherein only supportive care is recommended.
  • MIBE: ribavirin has been employed, and variable results.
  • SSPE: ribavirin and alpha-interferon (intrathecal) have been used, but no robust data to support them.

Prevention

  • Detailed information regarding primary and secondary measles (and mumps, rubella) prevention, the need for serologic testing, HCW recommendations and outbreak investigation techniques are available in the CDC 2013 guidance document[4].
    • Also, see the measles vaccine module for details.
    • Acceptable presumptive evidence of immunity includes having at least one of the following (CDC):
      • 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
  • Vaccine effectiveness: public health goal is to create herd immunity. Vaccine effectiveness is probably life-long in most.
    • If immunized > 12 mos of age
      • One dose: 93% protective
      • Two doses: 97%
  • Primary prophylaxis: since the vaccine is a live, attenuated virus, it should not be given to individuals with severe immunosuppression.
    • Vaccine contraindications: hypersensitivity to neomycin or prior measles vaccine, pregnancy, immunodeficiency states, lymphoma/leukemia, AIDS.
    • Children use the two-dose schedule in the U.S.: routine vaccine w/ MMR at 12- 15 mos (once maternal antibody lost) with a booster at ages 4-6 years.
      • MMR may be administered before age 4-6 years, provided more than 4 weeks have elapsed since the first dose, and both doses are administered at age 12mos or beyond.
      • Measles vaccine is NOT linked with the development of autism, multiple sclerosis, inflammatory bowel disease, etc.
      • MMRV vaccine: may be used instead of the MMR + varicella vaccine (separately), but providers should discuss risks/benefits with parents.
        • First dose: CDC recommends separate administration of MMR + varicella vaccinations instead of MMRV at age 12-47 mos.
        • Second dose (15 mos--12 yrs) or first dose ≥ 48mos: MMRV preferred over separate injections.
    • Adults born > 1957 should receive at least one dose of measles vaccine (MMR) unless they already have measles and are immune.
      • Other risk groups: healthcare workers without documented immunity, non-pregnant women of childbearing age without evidence of immunity.
      • Second dose MMR recommended: students in secondary education, healthcare workers, international travelers, measles outbreak exposure, prior immunization with killed measles vaccine or vaccination with unknown measles vaccine between 1963-1967.
      • Healthcare workers born after 1957 should have documented evidence of immunity (seropositive or 2 documented MMR doses).
      • Second dose rationale: 2-5% don’t respond to the initial vaccine.
    • International travel:
        • Infants 6 through 11 months of age should receive one dose of the MMR vaccine
          • Children 12 months of age or older should have documentation of two doses of MMR vaccine (the first dose of MMR vaccine should be administered at age 12 months or older; the second dose no earlier than 28 days after the first dose)
          • Teenagers and adults born during or after 1957 without evidence of immunity against measles should have documentation of two doses of MMR vaccine, with the second dose administered no earlier than 28 days after the first dose.
          • People 6 months or older who travel internationally should be protected against measles. Before traveling internationally,
          • Infants who get one dose of MMR vaccine before their first birthday should get two more doses according to the routinely recommended schedule (one dose at 12 through 15 months of age and another dose at 4 through 6 years of age or at least 28 days later).
    • Birth before 1957, believed immune because of native acquired infection.
    • HIV: immunization is now recommended for HIV-infected persons without evidence of severe immunosuppression (as scheduled above)
      • Definition of severe immunodeficiency: CD4+ < 15% at any age or CD4 count < 200 ages >5 years.
      • No serious ADRs were reported in children on ART with histories of immunosuppression.
      • MMRV vaccine is not approved for use in any persons with HIV infection.
  • Post-exposure prophylaxis: recommendations suggest all, even infants from birth, should receive if non-immune with significant exposure to measles (significant exposure = if age < 1yr, pregnant, immunocompromised or susceptible)
    • Immunization: preferred if contact w/ known case in a susceptible individual without MMR contraindication within 72h of exposure.
      • Consider any potentially exposed person in the household, classroom, etc., who otherwise doesn’t have an MMR contraindication.
      • ~90% effective in preventing the onset of measles.
    • Immunoglobulin: if administered within 6d of exposure, it may help prevent. Especially needed for infants < 12 mos of age, pregnant women or if severely immunocompromised.
      • If received ≥1 dose of MMR in the past, only administer to those with severe immunocompromising states.
      • Intramuscular: 0.5 mL/kg of body weight (maximum dose = 15 mL)
        • Use the IM route only if < 30 kilograms.
      • Intravenous: 400 mg/kg
        • Use the IV route if > 30 kg.
      • Efficacy ~ 95%
    • If receiving gammaglobulin, still need MMR immunization later.
      • Immunize ~ 6mos after receiving immunoglobulin to avoid antibody neutralization of vaccine.

OTHER INFORMATION

  • Measles had been considered eradicated in the U.S. (2000) as few cases were imported; however, two-plus decades have seen numerous outbreaks in the non-immune that appear to be the consequence of < 90-92% community immunization rates.
  • Koplik spots may help differentiate febrile illness (like influenza) as they can be seen in prodrome before the rash.
  • HIV, immune suppression, pregnancy, cancer or vitamin A deficiency/malnutrition are all risks for severe measles.
  • Measles cases (suspected or confirmed) should be reported promptly to local public health authorities.
  • Vaccine immunity may wane, but 95% protection is commonly quoted; however, since 1989 two-dose vaccine schedule has been used to decrease the risk of infection with 2-5% who fail to seroconvert after one dose.
    • Conversion failure may also be linked to inadequate vaccine refrigeration, leading to potency loss.
    • In mumps outbreaks, the third dose of MMR vaccine is now recommended for those at increased risk.
  • Multiple extensive studies have not been able to link the MMR vaccine to autism, asthma, etc. The famous Wakefield Lancet paper that started the fracas has been withdrawn, the researcher’s physician censured, and his medical license pulled.
  • Global statistics (WHO):
    • Measles immunization has reduced the number of cases, but there is still substantial morbidity, with 140,000 deaths globally (2018, WHO).
    • Estimated 95% of measles now occur in low-income countries.
    • According to WHO data, global immunization in children receiving at least one dose of measles vaccine has risen to 86% receiving at least one dose (2018) from 72% (2000).

Basis for recommendation

  1. Hübschen JM, Gouandjika-Vasilache I, Dina J. Measles. Lancet. 2022;399(10325):678-690.  [PMID:35093206]

    Comment: The review article includes diagnostic issues, management and issues regarding immunization and needs yet to be realized.

  2. Strebel PM, Orenstein WA. Measles. N Engl J Med. 2019;381(4):349-357.  [PMID:31184814]

    Comment: A comprehensive review also addresses measles (MMR) vaccine safety and efficacy.

  3. Moss WJ. Measles. Lancet. 2017;390(10111):2490-2502.  [PMID:28673424]

    Comment: A thorough review includes clinical principles, pathogenesis, immunity, and prevention/eradication discussion.

  4. McLean HQ, Fiebelkorn AP, Temte JL, et al. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62(RR-04):1-34.  [PMID:23760231]

    Comment: Report summarizes all recommendations since 1998. New recommendations in this version include:


    1) For acceptable evidence of immunity, removing documentation of physician diagnosed disease as an acceptable criterion for evidence of immunity for measles and mumps, and including laboratory confirmation of disease as a criterion for acceptable evidence of immunity for measles, rubella, and mumps.


    2) For persons with human immunodeficiency virus (HIV) infection, expanding recommendations for vaccination to all persons aged ≥12 months with HIV infection who do not have evidence of current severe immunosuppression; recommending revaccination of persons with perinatal HIV infection who were vaccinated before establishment of effective antiretroviral therapy (ART) with 2 appropriately spaced doses of MMR vaccine once effective ART has been established; and changing the recommended timing of the 2 doses of MMR vaccine for HIV-infected persons to age 12 through 15 months and 4 through 6 years.


    3) For measles postexposure prophylaxis, expanding recommendations for use of immune globulin administered intramuscularly (IGIM) to include infants aged birth to 6 months exposed to measles; increasing the recommended dose of IGIM for immunocompetent persons; and recommending use of immune globulin administered intravenously (IGIV) for severely immunocompromised persons and pregnant women without evidence of measles immunity who are exposed to measles.

  5. American Academy of Pediatrics Committee on Infectious Diseases: Vitamin A treatment of measles. Pediatrics. 1993;91(5):1014-5.  [PMID:8474793]

    Comment: Guidelines based on studies suggesting treatment for very sick children or those suffering from malnutrition, immunodeficiency, or complication of infection all do better with measles infection. Note high dose of Vitamin A may cause temporary headaches or nausea.

References

  1. Krow-Lucal E, Marin M, Shepersky L, et al. Measles, Mumps, Rubella Vaccine (PRIORIX): Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(46):1465-1470.  [PMID:36395065]

    Comment: A new formulation of the MMR vaccine is available and can be used interchangeably with the existing vaccine; therefore, previous ACIP recommendations are unchanged.

  2. Lo Vecchio A, Krzysztofiak A, Montagnani C, et al. Complications and risk factors for severe outcome in children with measles. Arch Dis Child. 2020;105(9):896-899.  [PMID:30636224]

    Comment: Somewhat surprisingly, this study from Italy did not find an age relationship but rather CRP as a risk factor for complications. This may well contrast with what is seen in children in low-resource settings, especially if malnourished.

  3. Choisy M, Trinh ST, Nguyen TND, et al. Sero-Prevalence Surveillance to Predict Vaccine-Preventable Disease Outbreaks; A Lesson from the 2014 Measles Epidemic in Northern Vietnam. Open Forum Infect Dis. 2019;6(3):ofz030.  [PMID:30863786]

    Comment: The study used banked sera from Vietnamese cohorts suggesting that routine serosurviellance in populations may help understand when to institute preventative immunization measures beyond the routine to prevent outbreaks.

  4. Marin M, Marlow M, Moore KL, et al. Recommendation of the Advisory Committee on Immunization Practices for Use of a Third Dose of Mumps Virus-Containing Vaccine in Persons at Increased Risk for Mumps During an Outbreak. MMWR Morb Mortal Wkly Rep. 2018;67(1):33-38.  [PMID:29324728]

    Comment: Although this notice is directed at mumps, a third dose of MMR is advocated for people at risk/exposure with outbreaks.

  5. Guerra FM, Crowcroft NS, Friedman L, et al. Waning of measles maternal antibody in infants in measles elimination settings - A systematic literature review. Vaccine. 2018;36(10):1248-1255.  [PMID:29398276]

    Comment: Eight studies of antibody levels in cord blood and then followed in infants suggest that insufficient maternal immunization is present in some infants well before customary immunization age.

  6. Orenstein WA, Hinman A, Nkowane B, et al. Measles and Rubella Global Strategic Plan 2012-2020 midterm review. Vaccine. 2018;36 Suppl 1:A1-A34.  [PMID:29307367]

    Comment: Update with barriers including children infected with HIV, cold-chain issues for the vaccine, high contagiousness and dynamic travel, the fact that much MV eradication has been tied to polio elimination, and those grant dollars (Gates, others) may decline soon. The potential breakthrough would be a new vaccine delivery system that does not require refrigeration and can immunize effectively at younger ages safely.

  7. Hall V, Banerjee E, Kenyon C, et al. Measles Outbreak - Minnesota April-May 2017. MMWR Morb Mortal Wkly Rep. 2017;66(27):713-717.  [PMID:28704350]

    Comment: Report of cases traced to unvaccinated people (65 total cases), many in a Somali-American community with the misunderstanding that autism was tied to MMR immunization. Though multiple studies have shown no such link, this linkage remains factual in some communities.

  8. Wendorf KA, Winter K, Zipprich J, et al. Subacute Sclerosing Panencephalitis: The Devastating Measles Complication That Might Be More Common Than Previously Estimated. Clin Infect Dis. 2017;65(2):226-232.  [PMID:28387784]

    Comment: Report from California of 17 SSPE cases, particularly in unvaccinated children who acquired native infection in infancy. The median age of diagnosis = is 12 years, with a latency period estimated at 9.5 years (range 2.5 to 34 years). Authors argue not to allow infants, especially before immunization travel to regions endemic for measles or consider early immunization during months 6-11.

  9. Liko J, Guzman-Cottrill JA, Cieslak PR. Notes from the Field: Subacute Sclerosing Panencephalitis Death - Oregon, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(1):10-1.  [PMID:26765654]

    Comment: Fourteen-year-old succumbed to SSPE who was thought to have been vaccinated at age 8 mos in the Phillipines (probably too young to engender good immunity) and acquired native measles at age 1 year. Thought to be an extraordinarily rare complicated (due to defective structural protein in the virus), analysis of SSPE among persons who had measles during the 1989–1991 U.S. measles resurgence indicated an incidence of 4–11 SSPE cases per 100,000 measles cases, approximately 10 times higher than earlier estimates.

  10. Fisher DL, Defres S, Solomon T. Measles-induced encephalitis. QJM. 2015;108(3):177-82.  [PMID:24865261]

    Comment: Helpful survey article reviewing the four major types of encephalitis related to the measles virus.

  11. Clemmons NS, Gastanaduy PA, Fiebelkorn AP, et al. Measles - United States, January 4-April 2, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(14):373-6.  [PMID:25879894]

    Comment: Imported cases continue to trigger outbreaks in the US, especially in populations where parents have not immunized their children at fairly high rates, such as California. Over 80% of US-based measles are in those unvaccinated or had unknown vaccination status. Four outbreaks were described this year, but 70% accounted for one more significant outbreak. These circumstances certainly highlight why continued immunization rates should be high and universal.

  12. Perry RT, Murray JS, Gacic-Dobo M, et al. Progress toward regional measles elimination - worldwide, 2000-2014. MMWR Morb Mortal Wkly Rep. 2015;64(44):1246-51.  [PMID:26562349]

    Comment: Measles cases globally are slowly decreasing, but challenging to reach eradication goals. Currently, 63% of countries have > 90% vaccine coverage.

  13. Centers for Disease Control and Prevention (CDC). Notes from the field: measles outbreak among members of a religious community - Brooklyn, New York, March-June 2013. MMWR Morb Mortal Wkly Rep. 2013;62(36):752-3.  [PMID:24025758]

    Comment: The story of intentionally non-immunized 17yr who acquired measles in the UK led to the largest outbreak in the US since 2000 with 58 cases. Over 3500 contacts had to be assessed receiving post-exposure MMR or IVIG. This points to two key facts: the highly infectious nature without protective immunity and the significant costs driven by a single case.

  14. Rafat C, Klouche K, Ricard JD, et al. Severe Measles Infection: The Spectrum of Disease in 36 Critically Ill Adult Patients. Medicine (Baltimore). 2013;92(5):257-272.  [PMID:23982057]

    Comment: Review from France, where recent measles outbreaks have been more common. In this case series, none of the patients had received two doses of MMR--hence at risk. Measles pneumonitis was the primary driver of ICU care, although the viral infection had protean manifestations. Post-infectious encephalomyelitis is also seen, but less commonly.

  15. Keegan R, Dabbagh A, Strebel PM, et al. Comparing measles with previous eradication programs: enabling and constraining factors. J Infect Dis. 2011;204 Suppl 1:S54-61.  [PMID:21666211]

    Comment: Attempts at eradicating measles have not been achieved; authors review that success likely lies in societal factors in a few endemic countries compared to biological factors. Current estimates place costs of measles eradication at $5-8 billion, but factors such as concurrent polio eradication, anti-vaccine lobbyists, civil wars/terrorism and lack of perceived problems in industrialized countries as reasons slowing or preventing progress.

  16. Scott P, Moss WJ, Gilani Z, et al. Measles vaccination in HIV-infected children: systematic review and meta-analysis of safety and immunogenicity. J Infect Dis. 2011;204 Suppl 1:S164-78.  [PMID:21666158]

    Comment: Immunization appears generally safe in HIV-infected children upon review of 39 studies, but authors cite the data as limited.

  17. Martins CL, Garly ML, Balé C, et al. Protective efficacy of standard Edmonston-Zagreb measles vaccination in infants aged 4.5 months: interim analysis of a randomised clinical trial. BMJ. 2008;337:a661.  [PMID:18653640]

    Comment: Safety and efficacy of immunization as early as 4 and 1/2 months compared to the usual approach at 9 months during a measles outbreak in Guinea-Bissau. Infants had 92% seroconversion, and only 0.7% of immunized infants at this earlier timeframe developed measles. There was a trend toward lower mortality, but this was not significant.

  18. Greenaway C, Dongier P, Boivin JF, et al. Susceptibility to measles, mumps, and rubella in newly arrived adult immigrants and refugees. Ann Intern Med. 2007;146(1):20-4.  [PMID:17200218]

    Comment: Immigrants to Canada, found that about one-third (36%) were non-immune to either measles, mumps or rubella.

  19. Tierney LM, Wang KC. Images in clinical medicine. Koplik's spots. N Engl J Med. 2006;354(7):740.  [PMID:16481641]

    Comment: View of Koplik spots.

  20. Parker AA, Staggs W, Dayan GH, et al. Implications of a 2005 measles outbreak in Indiana for sustained elimination of measles in the United States. N Engl J Med. 2006;355(5):447-55.  [PMID:16885548]

    Comment: A large outbreak of measles in the US was attributed to a case imported from Romania that spread in a population of children in whom routine vaccination was refused. The epidemic reinforces the need to maintain high rates of immunization.
    Rating: Important

  21. Dine MS, Hutchins SS, Thomas A, et al. Persistence of vaccine-induced antibody to measles 26-33 years after vaccination. J Infect Dis. 2004;189 Suppl 1:S123-30.  [PMID:15106101]

    Comment: Addressing concerns about the longevity of measles immunization protection, 56 participants (77% were 2-dose recipients) all had antibodies detected by the plaque reduction neutralization (PRN) antibody assay an average of 26-33 years after the first or second dose of measles vaccine; 92% had a PRN titer considered protective (>1:120). These data support routine two-dose immunization.
    Rating: Important

  22. van den Hof S, Conyn-van Spaendonck MA, van Steenbergen JE. Measles epidemic in the Netherlands, 1999-2000. J Infect Dis. 2002;186(10):1483-6.  [PMID:12404165]

    Comment: A large outbreak in an industrialized country, with 3292 reported cases, 94% of affected patients were unvaccinated. Only 1 patient had received 2 doses of the vaccine. Three patients died, and 16% had complications. Herd immunity outside unvaccinated clusters was high enough to prevent further transmission. This jives with a measles-associated mortality rate in the United States, generally quoted as 0.3%. By contrast, in some developing countries, the mortality rate of measles is as high as 10%

  23. Centers for Disease Control and Prevention (CDC). Measles outbreak among internationally adopted children arriving in the United States, February-March 2001. MMWR Morb Mortal Wkly Rep. 2002;51(49):1115-6.  [PMID:12530709]

    Comment: Report of case of child aged 10 months adopted from orphanage A in China who was taken to a Texas hospital with fever, conjunctivitis, coryza, Koplik spots, and a maculopapular rash. Measles was confirmed by serologic testing. Public health authorities in Texas notified CDC, which then collaborated with health officials in other states to contact recently adopted children from China and their adoptive families. Contact investigations that identified 14 U.S. measles cases. Most cases in the US arise from importation.

  24. Forni AL, Schluger NW, Roberts RB. Severe measles pneumonitis in adults: evaluation of clinical characteristics and therapy with intravenous ribavirin. Clin Infect Dis. 1994;19(3):454-62.  [PMID:7811865]

    Comment: Small series from Cornell of six patients with severe measles pneumonitis. One pt. died. However, the other five were thought to improve respiratory status with the early administration of parenteral ribavirin significantly.
    Rating: Important

  25. Sprauer MA, Markowitz LE, Nicholson JK, et al. Response of human immunodeficiency virus-infected adults to measles-rubella vaccination. J Acquir Immune Defic Syndr (1988). 1993;6(9):1013-6.  [PMID:8340890]

    Comment: Report of one HIV-infected adult who developed fever, rash, coryza and conjunctivitis 12 days after measles immunization. A retrospective survey by the New York City Department of Health found no complications following measles immunization of HIV-infected children.

  26. Kaplan LJ, Daum RS, Smaron M, et al. Severe measles in immunocompromised patients. JAMA. 1992;267(9):1237-41.  [PMID:1538561]

    Comment: The disease is more severe in patients with HIV, cancer or immunosuppression. The characteristic rash may be absent (27-40%) and hence delay diagnosis consideration. These patients commonly have fever and pneumonitis (58-80%) as the most common features. Giant-cell (Hecht’s Giant Cell) pneumonia with syncytia may be tip-off with culture or IFA confirming since antibody production may not be reliable in this patient population.

  27. Rahmathullah L, Underwood BA, Thulasiraj RD, et al. Reduced mortality among children in southern India receiving a small weekly dose of vitamin A. N Engl J Med. 1990;323(14):929-35.  [PMID:2205798]

    Comment: A large study suggested that prevention of vitamin A deficiency decreased mortality, probably by reducing diarrheal and pulmonary disease due to childhood illnesses such as measles.

  28. Gremillion DH, Crawford GE. Measles pneumonia in young adults. An analysis of 106 cases. Am J Med. 1981;71(4):539-42.  [PMID:7282741]

    Comment: Atypical measles occurred in recipients of the formalin-inactivated measles vaccine [1963-1967] and subsequently exposed to wild-type measles virus. Sx severity is worse in atypical measles. Instead of starting at the head and spreading down the body, the rash of atypical measles spreads centripetally, not only maculopapular but also hemorrhagic, vesicular, or urticarial. Coryza, conjunctivitis, and Koplik spots were unusual in atypical measles. However, interstitial pneumonia is a prominent feature of atypical measles, pleural effusions, extremity edema, hepatitis, and hyperesthesia. Has been confused with RMSF

Media

Measles rash

Descriptive text is not available for this image

Source: CDC

Koplik spots

Descriptive text is not available for this image

Source: CDC

Measles d3 rash

Descriptive text is not available for this image

Source: CDC

Last updated: March 20, 2023