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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor-In-Chief: Joseph Nasr, M.D.[2]

## Overview

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Measles is a highly contagious viral disease caused by the Morbillivirus, a member of the Paramyxoviridae family. The virus is transmitted primarily by respiratory droplets and aerosols from infected individuals.

The incubation period is typically 10–14 days (range, 7–23), during which patients are asymptomatic. Illness begins with a prodrome of fever plus cough, coryza, or conjunctivitis (the “three Cs”). Koplik spots on the buccal mucosa may appear 1–2 days before rash onset. The rash is an erythematous maculopapular exanthem that starts on the face and spreads to the trunk and extremities[1].

Infected persons are contagious from approximately 4 days before rash onset until 4 days after[1].

Measles remains a major global health concern. Since 2024, all WHO regions have reported rising numbers of measles cases. In 2024, there were 395,521 laboratory-confirmed cases worldwide, and in just the first two months of 2025, 16,147 cases were reported. Hospitalization occurred in more than half of reported cases, suggesting the true burden is much higher[2].

## Historical Perspective

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The measles virus was first isolated in cell culture in 1954 by John F. Enders and Thomas C. Peebles, leading to the development of measles-containing vaccines. The first vaccine was licensed in 1963, based on the Edmonston prototype strain. An inactivated (killed) vaccine, used between 1963 and 1967, was later withdrawn because it predisposed recipients to a severe form of disease called atypical measles syndrome when they were exposed to wild-type measles virus[3].

Subsequent development of live attenuated vaccine strains, including Edmonston B, Edmonston-Enders, and Moraten strains, provided effective durable protection. The first combined measles-mumps-rubella (MMR) vaccine was licensed in 1971[4].

In 1977, the World Health Organization (WHO) introduced the Expanded Programme on Immunization, initially recommending a one-dose measles schedule. By 2000, WHO and UNICEF endorsed a two-dose schedule globally[5].

Despite large gains, measles resurgence has been a recurring theme. In 2019, global cases surged to 869,770, driven by outbreaks in the Democratic Republic of Congo, Madagascar, Samoa, Ukraine, and Brazil, largely due to vaccine hesitancy[6]. This factor also contributed to the more than 100,00 measles cases in Europe in 2019 and the increased number of measles cases in the United States almost 20 years after the declaration that the disease head been eliminated in 2000[7].

Since 2024, measles cases have been rising sharply again, with major outbreaks in Europe and the United States. If the United States experiences uninterrupted transmission for more than 12 months, it risks losing its measles elimination status[4].

## Pathophysiology

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Measles is caused by a nonsegmented, negative-stranded RNA virus of the Paramyxoviridae family, genus Morbillivirus. The virus initially infects the respiratory epithelium of the nasopharynx and then spreads systemically.

Cellular receptors:

* CD46 – used primarily by vaccine strains[8][9].
* SLAM (CD150⁺) – expressed on B and T lymphocytes, the main receptor for wild-type measles virus[10].
* Nectin-4 – an epithelial cell receptor identified in 2010-2011[11].

The Virus induces a viremia that disseminates widely, causing systemic infection involving the skin, eyes, respiratory tract, and gastrointestinal tract[12].

A central feature of measles pathogenesis is immune amnesia. The virus depletes memory B and T lymphocytes (CD150⁺ cells), leading to loss of preexisting immunity to other pathogens. This results in increased susceptibility to secondary infections, particularly bacterial pneumonia, for up to a year after recovery[13][14].

Severe disease is more likely in malnourished children, immunocompromised patients (including those with HIV or undergoing cancer treatment), and pregnant women[15][16][17].

## Differentiating Measles from other Diseases

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The clinical features of measles, fever, cough, coryza, conjunctivitis, and a maculopapular rash, can overlap with several other infectious exanthems.

Conditions that may resemble measles include[18]:

* Dengue fever
* Zika virus infection
* Parvovirus infection

Therefore, because of this overlap, laboratory confirmation is essential, particularly in the early stages of an outbreak or in areas with low measles incidence. Confirmation relies on[19]:

* Detection of measles-specific IgM antibodies (enzyme immunoassays).
* Detection of measles RNA by real-time reverse transcriptase polymerase chain reaction (RT-PCR).

These methods are especially important in immunocompromised patients, who may not mount a detectable antibody response.

## Epidemiology and Demographics

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Measles is one of the most contagious infectious diseases, with a primary case reproduction number (R₀) of 12 to 18[20]. According to the WHO, it remains a leading cause of vaccine-preventable childhood mortality worldwide.

### Global Trends

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According to the World Health Organization (WHO), measles deaths had fallen substantially with the expansion of immunization programs. Between 1999 and 2005, global measles deaths decreased by approximately 60%, from an estimated 873,000 deaths to 345,000 deaths, with Africa experiencing a 75% reduction (from 506,000 to 126,000 deaths). This progress was largely driven by international partnerships such as the Measles Initiative (American Red Cross, CDC, UNICEF, UN Foundation, and WHO).

However, these gains have been eroded in recent years

* 2019: Global cases rose to 869,770, the highest number in decades, with large outbreaks in the Democratic Republic of Congo, Madagascar, Samoa, Ukraine, and Brazil[6].
* Covid-19 pandemic (2020): Caused major disruptions in routine immunization and catch-up campaigns. Global coverage with the first measles vaccine dose fell to 81% — the lowest since 2008 — before recovering slightly to 83% in 2022–2023[21].
* 2024: WHO regions reported widespread resurgence, with 395,521 laboratory-confirmed measles cases worldwide[2].
* Early 2025: In just the first two months, 16,147 cases were reported globally. More than half of confirmed cases required hospitalization, indicating that the true burden is likely higher[2].

### Regional Burden

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* Low- and middle-income countries (LMICs): Account for the vast majority of measles cases. In 2023–2024, more than 90% of global cases occurred in LMICs, mostly in children under 5 years of age. Mortality is highest in infants younger than 1 year[21].
* Vietnam (2025): Among the top 10 countries for reported measles cases; children 6–8 months old accounted for up to 25% of cases in some areas[22].
* Europe: In 2024, Europe reported its highest number of measles cases in more than 25 years, representing 20% of global cases[2].

* United States: By May 30, 2025, there were 1,088 confirmed measles cases and 3 deaths. About 96% of these cases were in unvaccinated persons or those with unknown vaccination status, and 12% required hospitalization. This represents nearly four times the total reported in 2024. If uninterrupted transmission continues for 12 months, the United States will lose its elimination status[23].

### Drivers of the resurgence

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* Vaccine hesitancy, fueled by misinformation (e.g., false claims linking MMR vaccine to autism, unfounded belief that vitamin A prevents measles)[24].
* Disruptions during Covid-19, which delayed or canceled mass immunization campaigns[25].

* Political and funding changes, including U.S. withdrawal of support from WHO and Gavi, the Vaccine Alliance, reducing resources for global measles control[4].

## Risk Factors

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Measles has very low incidence in many developed countries, but outbreaks continue to occur worldwide, especially in areas with low vaccination coverage.

### Classic Risk Factors

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* Lack of vaccination: The strongest risk factor for measles. In the U.S. and other developed countries, most cases are attributed to unvaccinated or incompletely vaccinated travelers or residents.
* Vaccine hesitancy: A growing contributor to outbreaks worldwide. False claims linking the MMR vaccine to autism and misinformation about vitamin A as a preventive measure have lowered vaccine uptake.
* Primary vaccine failure: Occurs in about 5% of individuals vaccinated with a single dose at 12 months of age or older, leaving them susceptible.
* Infants under 6 months of age: Maternal antibodies are waning earlier than in past decades. By 3–4 months of age, most infants no longer have protective levels, leaving them vulnerable until vaccination[26]. Outbreak data from Vietnam in 2025 showed up to 25% of cases in infants aged 6–8 months[22].
* Immunocompromised individuals: People with HIV, those undergoing cancer treatment, or those on immunosuppressive therapy are at higher risk of severe disease (e.g., giant-cell pneumonia, encephalitis) and poorer outcomes[27].
* Pregnancy: Measles in pregnant women is associated with higher case fatality (5–30%, depending on context), as well as fetal loss, intrauterine growth restriction, and preterm birth[28].
* Poor access to healthcare: Financial and logistical barriers to vaccination and postexposure prophylaxis increase risk in low- and middle-income countries.
* Malnutrition: A major factor in measles mortality. Malnutrition worsens measles severity and measles itself can lead to nutritional deficits, including vitamin A deficiency. About 45% of measles-related deaths are associated with malnutrition[29].
* Outbreak settings: Crowding (e.g., refugee camps, humanitarian crises) can raise attack rates and case fatality, sometimes exceeding 10–18%[28].

## Natural History, Complications and Prognosis

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* Transmission: Measles spreads via breathing, coughing, or sneezing; the virus can survive in the air or on surfaces for up to 2 hours. Nearly all susceptible children exposed will become infected.
* Incubation: 7–23 days (typically 10–14); patients are asymptomatic.
* Prodrome: Fever, cough, coryza, conjunctivitis; Koplik spots may appear before rash.
* Rash: Maculopapular, starting on the face → trunk → extremities.
* Contagious period: From ~4 days before rash onset to ~4 days after.
* Immune amnesia: Depletion of B- and T-cell memory causes increased risk of secondary infections for 5–12 months after illness.

### Complications (≈30% of cases):

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* Mild: Diarrhea (8–10%), otitis media (7–9%).
* Serious: Pneumonia (1–6%; leading cause of death), keratitis/corneal ulceration → blindness (esp. with vitamin A deficiency).
* Neurologic: Encephalitis (subacute sclerosing panencephalitis \- SSPE) (1/1000; ~20% mortality), measles-inclusion body encephalitis (1/1000; nearly 100% fatal), SSPE (7–11 per 100,000; universally fatal).
* High risk: Malnourished children (~45% of measles deaths linked to malnutrition), immunocompromised patients (giant-cell pneumonia, severe encephalitis), and pregnant women (maternal mortality 5–30%, fetal loss, prematurity).

### Prognosis:

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* Case fatality: 1–3/1000 in high-income countries; 9–16/1000 in LMICs; up to 180/1000 in humanitarian crises.
* Worst outcomes: infants <1 year, malnourished, immunocompromised, and pregnant women.

## Diagnosis

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### Clinical criteria:

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* Fever ≥3 days plus one or more of: cough, coryza, conjunctivitis[30][31].
* Koplik spots: pathognomonic but not always present.
* Rash: erythematous, maculopapular, face → trunk → extremities.

### Differentiation from other diseases:

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* Early clinical features may overlap with dengue, Zika, and parvovirus B19.
* Laboratory confirmation is therefore essential, especially in early outbreak detection or low-incidence settings.

### Laboratory confirmation:

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* IgM antibody detection (enzyme immunoassays).
* RT-PCR for measles RNA from throat or nasopharyngeal swabs, and sometimes urine[31].
* Genotyping of measles virus (currently B3, D8, and H1 circulating worldwide, 2024–2025)[32].
* In immunocompromised patients, RT-PCR is preferred since they may not mount an antibody response.

### Other tools:

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* Chest X-ray: may show pneumonia as a complication, but not specific for measles[33].
* Vero/hSLAM cell culture methods are historical; no longer frontline diagnostics.

### Emerging diagnostics:

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* Rapid diagnostic tests (RDTs) for measles IgM detection in capillary blood or oral fluid are under evaluation and may allow point-of-care confirmation and outbreak surveillance[18][19].

## Prevention and Treatment

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### Primary Prevention[34]

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* Vaccination (2-dose schedule; >95% coverage needed for herd immunity).
* Public health measures: isolation, surveillance.
* Cost-effective: vaccination prevents >99% of cases.
* Future: microneedle patches, earlier infant vaccination (3–4 months).

### Secondary Prevention[35]

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* Postexposure prophylaxis:
* MMR vaccine within 72h.
* Immune globulin within 6 days for infants, pregnant women, immunocompromised.
* Diagnostic confirmation: IgM serology, RT-PCR, emerging rapid tests.

### Tertiary Prevention

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* Supportive care: hydration, fever control, treat bacterial complications.
* Vitamin A supplementation (all cases; reduces mortality/complications).
* Manage complications: pneumonia, otitis media, encephalitis.

### Quaternary Prevention

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* Avoid misuse: vitamin A overdosing, unnecessary antivirals.
* Counter misinformation: vaccine safety, vitamin A not preventive.

### Future/Investigational

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* Microneedle vaccine patches.
* Early infant vaccination.
* Pneumococcal booster post-measles (to counter immune amnesia).
* Trained immunity benefits from MMR.

## References

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1. ↑ 1.0 1.1 (No date) Iris home. Available at: https://iris.who.int/handle/10665/365133 (Accessed: 17 September 2025).
2. ↑ 2.0 2.1 2.2 2.3 World Health Organization. Immunization data: provisional measles and rubella data. 2024 (https://immunizationdata .who.int/global?topic=Provisional
3. ↑ Polack, F.P. (2007) ‘Atypical measles and enhanced respiratory syncytial virus disease (ERD) made simple’, Pediatric Research, 62(1), pp. 111–115. doi:10.1203/pdr.0b013e3180686ce0.
4. ↑ 4.0 4.1 4.2 Do, L.A. and Mulholland, K. (2025) ‘Measles 2025’, New England Journal of Medicine [Preprint]. doi:10.1056/nejmra2504516.
5. ↑ MMR vaccine vis (no date) Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/vaccines/hcp/current-vis/mmr.html (Accessed: 17 September 2025).
6. ↑ 6.0 6.1 Patel, M.K. et al. (2020) ‘Progress toward regional measles elimination — worldwide, 2000–2019’, MMWR. Morbidity and Mortality Weekly Report, 69(45), pp. 1700–1705. doi:10.15585/mmwr.mm6945a6.
7. ↑ Hotez, P.J., Nuzhath, T. and Colwell, B. (2020) ‘Combating vaccine hesitancy and other 21st century social determinants in the global fight against measles’, Current Opinion in Virology, 41, pp. 1–7. doi:10.1016/j.coviro.2020.01.001.
8. ↑ Dorig RE, Marcil A, Chopra A, Richardson CD. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell. 1993;75(2):295-305
9. ↑ Naniche D, Varior-Krishnan G, Cervoni F, Wild TF, Rossi B, Rabourdin-Combe C, et al. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol. 1993;67(10):6025-32
10. ↑ Tatsuo H, Ono N, Tanaka K, Yanagi Y. SLAM (CDw150) is a cellular receptor for measles virus. Nature. 2000;406(6798):893-7
11. ↑ Muhlebach MD, Mateo M, Sinn PL, Prufer S, Uhlig KM, Leonard VH, et al. Adherens junction protein nectin-4 is the epithelial receptor for measles virus. Nature. 2011;480(7378):530-3
12. ↑ World Health Organization. Immunization data: provisional measles and rubella data. 2024 (https://immunizationdata.who.int/global?topic=Provisional-measles-and-rubella-data&location=)
13. ↑ Mina MJ, Kula T, Leng Y, Li M, de Vries RD, Knip M, et al. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens. Science. 2019;366(6465):599- 606
14. ↑ Petrova VN, Sawatsky B, Han AX, Laksono BM, Walz L, Parker E, et al. Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles. Sci Immunol. 2019;4(41)
15. ↑ Routine MMR vaccination recommendations: For Providers (2021) Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/vaccines/vpd/mmr/hcp/recommendations.html (Accessed: 17 September 2025).
16. ↑ e Y-L, Zhai X-W, Zhu Y-F, et al. Mea�sles outbreak in pediatric hematology and oncology patients in Shanghai, 2015. Chin Med J (Engl) 2017;130:1320-6
17. ↑ Khalil A, Samara A, Campbell C, Lad�hani SN. Pregnant women and measles: we need to be vigilant during outbreaks. EClinicalMedicine 2024;72:102594
18. ↑ 18.0 18.1 Brown DW, Warrener L, Scobie HM, Donadel M, Waku-Kouomou D, Mulders MN, et al. Rapid diagnostic tests to address challenges for global measles surveillance. Curr Opin Virol. 2020;41:77-84
19. ↑ 19.0 19.1 Warrener L, Andrews N, Koroma H, Alessandrini I, Haque M, Garcia CC, et al. Evaluation of a rapid diagnostic test for measles IgM detection; accuracy and the reliability of visual reading using sera from the measles surveillance programme in Brazil, 2015. Epidemiol Infect. 2023;151:e151.
20. ↑ Larson, H.J., Gakidou, E. and Murray, C.J.L. (2022) ‘The vaccine-hesitant moment’, New England Journal of Medicine, 387(1), pp. 58–65. doi:10.1056/nejmra2106441.
21. ↑ 21.0 21.1 Minta, A.A. et al. (2023) ‘Progress toward measles elimination — worldwide, 2000–2022’, MMWR. Morbidity and Mortality Weekly Report, 72(46), pp. 1262–1268. doi:10.15585/mmwr.mm7246a3.
22. ↑ 22.0 22.1 ProMed. Measles — Viet Nam (03): WHO assessment, alert 2025 (https:// promedmail.org/promed-post/?id=8721943)\
23. ↑ Centers for Disease Control and Prevention. Measles cases and outbreaks. June 6, 2025 (https://www.cdc.gov/measles/ data-research/index.html)
24. ↑ DeStefano, F. and Shimabukuro, T.T. (2019) ‘The MMR vaccine and autism’, Annual Review of Virology, 6(1), pp. 585–600. doi:10.1146/annurev-virology-092818-015515.
25. ↑ Centers for Disease Control and Prevention. ACIP recommendations: measles, mumps and rubella (MMR) vaccine. July 29, 2024 (https://www.cdc.gov/acip -recs/hcp/vaccine-specific/mmr.html)
26. ↑ Guerra, F.M. et al. (2018) ‘Waning of measles maternal antibody in infants in measles elimination settings – a systematic literature review’, Vaccine, 36(10), pp. 1248–1255. doi:10.1016/j.vaccine.2018.01.002.
27. ↑ Ferren, M., Horvat, B. and Mathieu, C. (2019) “Measles encephalitis: Towards new therapeutics,” Viruses, 11(11), p. 1017. Available at: https://doi.org/10.3390/v11111017.
28. ↑ 28.0 28.1 Congera, P. et al. (2020) “Measles in pregnant women: A systematic review of clinical outcomes and a meta-analysis of antibodies seroprevalence,” The Journal of infection, 80(2), pp. 152–160. Available at: https://doi.org/10.1016/j.jinf.2019.12.012.
29. ↑ Bryce, J. et al. (2005) “WHO estimates of the causes of death in children,” Lancet, 365(9465), pp. 1147–1152. Available at: https://doi.org/10.1016/S0140-6736(05)71877-8.
30. ↑ "WHO GUIDELINES FOR EPIDEMIC PREPAREDNESS AND RESPONSE TO MEASLES OUTBREAKS".
31. ↑ 31.0 31.1 "CDC Measles".
32. ↑ CDC (2024) Genetic Analysis of Measles Viruses, Measles (Rubeola). Available at: https://www.cdc.gov/measles/php/laboratories/genetic-analysis.html (Accessed: September 18, 2025).
33. ↑ Kim, Eun A; Lee, Kyung Soo; Primack, Steven L.; Yoon, Hye Kyung; Byun, Hong Sik; Kim, Tae Sung; Suh, Gee Young; Kwon, O Jung; Han, Joungho (2002). "Viral Pneumonias in Adults: Radiologic and Pathologic Findings1". RadioGraphics. 22 (suppl_1): S137–S149. doi:10.1148/radiographics.22.suppl_1.g02oc15s137. ISSN 0271-5333.
34. ↑ Moss, William J; Griffin, Diane E (2012). "Measles". The Lancet. 379 (9811): 153–164. doi:10.1016/S0140-6736(10)62352-5. ISSN 0140-6736.
35. ↑ Huiming Y, Chaomin W, Meng M (2005). "Vitamin A for treating measles in children". Cochrane Database Syst Rev (4): CD001479. doi:10.1002/14651858.CD001479.pub3. PMID 16235283.CS1 maint: Multiple names: authors list (link)

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