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Measles

Diagnostic Tests and Differential Diagnosis

Gary S. Marshall, MD 
Reviewed on October 18, 2024
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Key Indicators

Unless pathognomonic signs are present or symptoms consistent with measles appear during a local outbreak, diagnosing measles based on clinical signs alone is challenging. Laboratory testing thus remains essential for an accurate diagnosis. Although common in the past, diagnosis by isolation of measles morbillivirus (MeV) in cell culture is both time-consuming and costly and has now become obsolete. When faced with a patient presenting with an acute febrile rash illness (i.e., a suspected case of measles), the two best confirmatory diagnostic options are:

  • Serologic testing for measles immunoglobulin M (IgM) antibody; and
  • Molecular testing for MeV RNA by polymerase chain reaction (PCR).

Recommended tests and appropriate samples for the diagnosis of acute disease and for testing of measles immunity are shown in Figure 2-3.

Serologic testing for immunoglobulin M (IgM) is usually done by enzyme immunoassay on blood samples, which has a sensitivity of 83-89% and a specificity of…

Key Indicators

Unless pathognomonic signs are present or symptoms consistent with measles appear during a local outbreak, diagnosing measles based on clinical signs alone is challenging. Laboratory testing thus remains essential for an accurate diagnosis. Although common in the past, diagnosis by isolation of measles morbillivirus (MeV) in cell culture is both time-consuming and costly and has now become obsolete. When faced with a patient presenting with an acute febrile rash illness (i.e., a suspected case of measles), the two best confirmatory diagnostic options are:

  • Serologic testing for measles immunoglobulin M (IgM) antibody; and
  • Molecular testing for MeV RNA by polymerase chain reaction (PCR).

Recommended tests and appropriate samples for the diagnosis of acute disease and for testing of measles immunity are shown in Figure 2-3.

Serologic testing for immunoglobulin M (IgM) is usually done by enzyme immunoassay on blood samples, which has a sensitivity of 83-89% and a specificity of 95-99%. However, in up to 20-25% of measles-infected patients will not have detectable levels of IgM antibodies within 72 hours after the onset of rash. Furthermore, IgM antibodies may be absent or only transiently present in vaccinated individuals and a negative IgM test result cannot be used to rule out measles infection in these patients.

Real time PCR-based methods, which detect MeV RNA with a sensitivity of 94% and a specificity of 99%, play an increasingly important role in confirming a tentative diagnosis of measles. Adequate samples for PCR-based detection include swabs (throat, nasal, or posterior nasopharyngeal), bronchial lavage samples and urine samples. While respiratory specimens are preferred, testing the urine increases the chance of establishing a diagnosis.

Note that a positive result from any molecular or serologic test, including MeV isolation, can only be taken to indicate natural measles in the absence of vaccination for measles in the preceding 6-45 days, since measles vaccines contain live-attenuated MeV virus. Thus, a positive PCR result in the setting of mild measles-like illness may simply indicate recent vaccination.

In addition to measles, the differential diagnosis of fever and rash includes other viral infections (enterovirus, adenovirus, parvovirus, human herpesvirus-6, Epstein-Barr virus and dengue), tick-borne rickettsial disease and drug reactions.

Differentiating Kawasaki disease from measles is critical since timely treatment of the former is essential to avoiding coronary artery sequelae.

Enlarge  Figure 2-3: CDC Recommendations for Measles Test Sample Collection. Source: Adapted from: Test Types Typically Available to Clinicians and Descriptions for Measles, Mumps, Rubella and Varicella. Centers for Disease Control and Prevention. Available at: <a href=
Figure 2-3: CDC Recommendations for Measles Test Sample Collection. Source: Adapted from: Test Types Typically Available to Clinicians and Descriptions for Measles, Mumps, Rubella and Varicella. Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/chickenpox/downloads/MMRV-Testing-for-Clinicians.pdf.

References

  • Bellini WJ, Helfand RF. The challenges and strategies for laboratory diagnosis of measles in an international setting. J Infect Dis. 2003;187 Suppl 1:S283-S290.
  • Bharti N, Tatem AJ, Ferrari MJ, Grais RF, Djibo A, Grenfell BT. Explaining seasonal fluctuations of measles in Niger using nighttime lights imagery. Science. 2011;334(6061):1424-1427.
  • Carrico J, La EM, Talbird SE, et al. Value of the Immunization Program for Children in the 2017 US Birth Cohort. Pediatrics. 2022;150(3):e2021056007.
  • CDC. Measles Cases and Outbreaks. Measles (Rubeola). Published May 17, 2024. https://www.cdc.gov/measles/data-research/index.html
  • Chovatiya R, Silverberg JI. Inpatient morbidity and mortality of measles in the United States. PLoS One. 2020;15(4):e0231329.
  • Durrheim DN. Measles eradication-retreating is not an option. Lancet Infect Dis. 2020;20(6):e138-e141.
  • Ferrari MJ, Grais RF, Bharti N, et al. The dynamics of measles in sub-Saharan Africa. Nature. 2008;451(7179):679-684.
  • Fine PE, Clarkson JA. Measles in England and Wales--I: An analysis of factors underlying seasonal patterns. Int J Epidemiol. 1982;11(1):5-14.
  • Fitzgerald TL, Durrheim DN, Merritt TD, Birch C, Tran T. Measles with a possible 23 day incubation period. Commun Dis Intell Q Rep. 2012;36(3):E277-E280.
  • Flores J, Immergluck LC. Measles Update in an Era of Vaccine Hesitancy and Global Pandemic. Pediatr Rev. 2023;44(9):529-532.
  • Gastañaduy PA, Goodson JL, Panagiotakopoulos L, Rota PA, Orenstein WA, Patel M. Measles in the 21st Century: Progress Toward Achieving and Sustaining Elimination. The Journal of Infectious Diseases. 2021;224(Supplement_4):S420-S428.
  • Global progress against measles threatened amidst COVID-19 pandemic. www.who.int. Published November 10, 2021. https://www.who.int/news/item/10-11-2021-global-progress-against-measles-threatened-amidst-covid-19-pandemic
  • Guerra FM, Bolotin S, Lim G, et al. The basic reproduction number (R0) of measles: a systematic review. Lancet Infect Dis. 2017;17(12):e420-e428.
  • Hübschen JM, Gouandjika-Vasilache I, Dina J. Measles. Lancet. 2022;399(10325):678-690.
  • Jick H, Hagberg KW. Measles in the United Kingdom 1990-2008 and the effectiveness of measles vaccines. Vaccine. 2010;28(29):4588-4592.
  • Kimberlin DW, Barnett E, Lynfield R, Sawyer MH. Red Book 2024. American Academy of Pediatrics; 2024.
  • Leask J. Target the fence-sitters. Nature. 2011;473(7348):443-445.
  • Mathis AD, Raines K, Masters NB, et al. Measles - United States, January 1, 2020-March 28, 2024. MMWR Morb Mortal Wkly Rep. 2024;73(14):295-300.
  • Measles Outbreaks Strategic Response Plan 2021- 2023. World Health Organization; 2021.
  • Minta AA, Ferrari M, Antoni S, et al. Progress Toward Measles Elimination - Worldwide, 2000-2022. MMWR Morb Mortal Wkly Rep. 2023;72(46):1262-1268.
  • Moss WJ, Griffin DE. Measles. ASM Press eBooks. Published online March 7, 2016:903-928.
  • Nicolay N, Mirinaviciute G, Mollet T, Celentano LP, Bacci S. Epidemiology of measles during the COVID-19 pandemic, a description of the surveillance data, 29 EU/EEA countries and the United Kingdom, January to May 2020. Euro Surveill. 2020;25(31):2001390.
  • Portnoy A, Jit M, Ferrari M, Hanson M, Brenzel L, Verguet S. Estimates of case-fatality ratios of measles in low-income and middle-income countries: a systematic review and modelling analysis. Lancet Glob Health. 2019;7(4):e472-e481.
  • Rota PA, Moss WJ, Takeda M, de Swart RL, Thompson KM, Goodson JL. Measles. Nat Rev Dis Primers. 2016;2:16049.
  • Roy F, Mendoza L, Hiebert J, et al. Rapid Identification of Measles Virus Vaccine Genotype by Real-Time PCR. J Clin Microbiol. 2017;55(3):735-743.
  • Salama P, Assefa F, Talley L, Spiegel P, van Der Veen A, Gotway CA. Malnutrition, measles, mortality, and the humanitarian response during a famine in Ehiopia. JAMA. 2001;286(5):563-571.
  • Steichen O, Dautheville S. Koplik spots in early measles. CMAJ. 2009;180(5):583.
  • Strebel PM, Orenstein WA. Measles. N Engl J Med. 2019;381(4):349-357.
  • Talbird SE, Carrico J, La EM, et al. Impact of Routine Childhood Immunization in Reducing Vaccine-Preventable Diseases in the United States. Pediatrics. 2022;150(3):e2021056013.
  • Ten Oever J, Riza A, Sabou M, Cismaru C, Netea MG, Slavcovici A. Characterization of the Acute Inflammatory Response in Measles Infection. J Pediatric Infect Dis Soc. 2014;3(3):197-200.
  • UK measles and rubella elimination indicators and status. GOV.UK. https://www.gov.uk/government/publications/measles-and-rubella-elimination-uk/uk-measles-and-rubella-elimination#fn:2
  • Wallinga J, Heijne JC, Kretzschmar M. A measles epidemic threshold in a highly vaccinated population. PLoS Med. 2005;2(11):e316.
  • Wang R, Jing W, Liu M, Liu J. Trends of the Global, Regional, and National Incidence of Measles, Vaccine Coverage, and Risk Factors in 204 Countries From 1990 to 2019. Front Med (Lausanne). 2022;8:798031.
  • 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.
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