Measles 2025

Between 10 and 14 days (range, 7 to 23) after exposure, illness starts with a prodromal phase that includes fever and any of three symptoms — cough, coryza, and conjunctivitis (the “three Cs”). The prodromal phase lasts for 2 to 4 days. Koplik spots, small white spots on the buccal mucosa, are pathognomonic for measles but are not always present (Figure 1A). The spots may appear 1 to 2 days before the onset of rash and last for an additional 1 to 2 days after rash onset. A typical measles rash is an erythematous maculopapular exanthem that appears 2 to 4 days after the onset of fever, starting with the face and proceeding to the head, trunk, arms, and legs Figure 1B. Persons with the infection typically can transmit the virus 4 days before and 4 days after the eruption of the rash (Figure 1D). Diarrhea can appear early in the acute phase and may last for a month.⁴ Prodromal symptoms, rash, and diarrhea in any child should arouse suspicion for measles infection.

Because measles is a systemic infection, it can affect the skin, eyes, gut, and respiratory system. Complications that occur in approximately 30% of measles cases⁴ — and frequently occur up to 1 month after infection — include diarrhea, pneumonia, otitis media, and conjunctivitis (Table 1 and Figure 1C).^5-14 Pneumonitis and giant-cell pneumonia are rare but severe and potentially fatal complications of measles. These conditions are reported mainly in persons who are immunosuppressed and in young children.

Even after recovery, children who have had measles are at high risk for late complications such as pneumonia, malnutrition, and blindness. Blindness is usually due to severe corneal ulceration, and sometimes corneal perforation, in children who are deficient in vitamin A.⁴ Temporary immune amnesia caused by depletion of B-cell and T-cell memory by the measles virus has recently been shown to be a mechanism for longer-term susceptibility to secondary infections in persons who have had measles (see the Supplementary Appendix, available with the full text of this article at NEJM.org). Children recovering from measles are at elevated relative risk for serious secondary infection, particularly pneumonia. Even in a high-resource area of Germany, the risk of pneumonia among children with measles was elevated as compared with that among children who had noninfectious diseases (risk ratio, 1.6; 95% confidence interval [CI], 1.4 to 2.0).¹⁵ In low- and middle-income countries, the risk is greater than in countries with higher incomes, and measles is associated with substantial mortality.¹⁶

Measles-associated encephalitis is a rare but serious, and potentially fatal, complication. It can occur during the first 7 days of infection (acute postinfectious measles encephalitis), 1 to 6 months after infection (measles-inclusion body encephalitis), or even years after full recovery (subacute sclerosing panencephalitis).¹⁴

Atypical measles syndrome was first reported in the 1960s among children who received the inactivated (killed) measles vaccine that was in use during the period 1963–1967. After these children were exposed to measles virus in the community, they became ill with a severe form of measles disease marked by high fever, an unusual type of rash (a petechial or morbilliform rash that began on the arms and legs), and severe pneumonia.¹⁷ This atypical measles syndrome has been reported rarely since the inactivated measles vaccine was withdrawn in 1967.¹⁴

Measles can occur in persons who are fully vaccinated (i.e., have received two doses) or who are undervaccinated. These breakthrough infections can result from primary vaccine failure, lack of seroconversion after immunization, or secondary vaccine failure due to waning of the measles-antibody level (waning immunity), which can occur 6 or more years after vaccination.¹⁸

Persons with primary vaccine failure may have the classic measles syndrome, but persons with secondary vaccine failure tend to have milder symptoms — often only a rash with little or no fever, nonspecific respiratory symptoms, and a lower viral load. Persons with secondary vaccine failure are at lower risk for transmission than unvaccinated persons who have measles infection.¹⁸

When measles outbreaks occur, persons with compromised immunity, such as malnourished children, immunocompromised persons (e.g., persons who have human immunodeficiency virus [HIV] or are receiving cancer treatment), and pregnant persons are particularly vulnerable. Persons with HIV who are not immune to measles are at increased risk for more severe measles infection with pneumonia or encephalitis.

In a series of 23 pediatric cancer patients in China who had measles infection, 5 underwent ventilation, 1 had liver failure, and 4 died. These outcomes occurred even though 20 of the 23 patients had been vaccinated (including the 4 who died) and 21 had been treated with intravenous immune globulin.¹⁹

Malnutrition and measles have a historical link, particularly in the context of humanitarian relief efforts. The bidirectional relationship between measles and malnutrition was described decades ago.²⁰ Malnutrition is a primary contributor to death in 45% of fatal measles cases.²¹ Measles is worse in children who are already malnourished, and postmeasles effects can lead to malnutrition in children who were not malnourished before they were infected with measles.¹³ Measles can lead to or exacerbate vitamin A deficiency²² or a persistent nutritional deficit.²³ Malnourished children have a poor response to measles vaccine and other vaccines.^24,25

Measles vaccine has a long history. Various attenuated measles vaccine strains were developed and are in active use worldwide (see the Supplementary Appendix) either as a monovalent vaccine or combined with mumps and rubella vaccines, with or without varicella vaccine.

The recommended age for the first dose of measles-containing vaccine depends on the waning of maternal antibodies in the patient and the risk of measles exposure.⁴ In countries where measles is in elimination status (i.e., continuous transmission has been absent for more than 12 months), the first dose may be given at 12 to 18 months of age for maximum immunogenicity, although this schedule leaves most infants in the country susceptible to infection. In countries where measles is endemic — mainly low- and middle-income countries — the first dose of measles vaccine is usually given at 9 months of age. China and South Africa are exceptions, with the routine first dose given at 8 months and 6 months of age, respectively.² Given that 10 to 15% of infants who receive the first dose at 9 months of age do not have seroconversion and to ensure protection for children who either do not have a response to the first dose or miss the first dose entirely, the WHO recommends a second dose for all children globally.⁴ The recommended shortest time between the two doses is 4 weeks. The timing of the first and second doses of measles vaccine in each country depends on the epidemiologic context and the recommendations of the immunization program of the country. The WHO also recommends an additional dose for infants 6 to 11 months of age during measles outbreaks in regions where measles is endemic.⁴

In the United States, the first dose is given at 12 to 15 months of age and the second dose at 4 to 6 years. Infants 6 to 11 months of age may also be given an additional dose in regions where there are outbreaks or before international travel (Table 2).²⁸

Because the measles virus has a high reproduction number, high coverage of both doses of measles vaccine (≥95%) at the population level is required to maintain effective herd immunity against measles transmission.²⁹ In reality, this goal is a very difficult one to attain for most countries owing to growing global vaccine hesitancy and other challenges, such as financial barriers, poor access to health care, and inappropriate contraindications in certain cases. Even when high vaccination coverage is achieved, small, poorly vaccinated communities may still have outbreaks.^30,31

In unvaccinated or undervaccinated persons, measles vaccine is recommended within 72 hours after exposure. When there are contraindications to the measles vaccine, such as in immunocompromised or pregnant persons or infants younger than 6 months of age, human immune globulin is recommended to be given within 6 days after exposure.⁴

Recommendations for postexposure prophylaxis and the availability of immune globulin products vary among countries.³² In many low- and middle-income countries, access to immune globulin is very limited owing to its high cost and low availability.

A recent meta-analysis showed that the estimated effectiveness of postexposure prophylaxis for the prevention of measles ranged from 76% (95% CI, 0 to 94) to 100% (95% CI, 56 to 100) with immune globulin and from 83% (95% CI, 34 to 96) to 100% (95% CI, not evaluable) with the measles vaccine.³³ Postexposure prophylaxis with immune globulin offers greater short-term protection than postexposure prophylaxis with the measles vaccine but at greater cost and use of resources.

The effectiveness of postexposure prophylaxis may be affected by the concentration of measles antibodies in immune globulin products,³⁴ the nature and intensity of measles exposure events, and the timing of postexposure prophylaxis.³⁵ The timing of postexposure prophylaxis reported in the studies included in the meta-analysis was recommended mainly on the basis of the duration of measles incubation; there are very limited data on the effect of delayed postexposure prophylaxis.^33,36

Because levels of measles antibodies in the immune globulin donor population have decreased over time,³⁷ measles antibody concentration in immune globulin products is also decreasing. This change highlights the need for periodic review of the recommended dose.^38,39 Although the correlates of protection for measles have been recently debated,⁴⁰ the previously published threshold (i.e., >120 mIU per milliliter) has been widely accepted and used as the target serum concentration for measles antibodies after postexposure passive immunization, thereby guiding the recommended dose.^38,39

There is no approved antiviral medication for measles. Management of measles infection involves early detection and treatment of complications as well as patient isolation to prevent nosocomial and community transmission.

Vitamin A deficiency has been associated with measles severity and mortality among children in low- and middle-income countries. In large-scale, community-based, randomized trials in many Asian and African countries between 1983 and 1992, administration of vitamin A reduced measles mortality by 34 to 50% among children 1 to 5 years of age in low- and middle-income countries.⁴¹ Vitamin A deficiency (serum retinol level, <10 μg per deciliter) is a major public health issue affecting preschool-age children in low- and middle-income countries.⁴¹ Since 1993, the WHO has recommended vitamin A, with specific doses according to age groups, to all persons who have acute measles infection, irrespective of the timing of previous doses of vitamin A (Table 3).⁴ This recommendation is based on data from studies conducted in low- and middle-income countries,⁴³ and there has been no report of toxic effects from vitamin A in patients with measles who have received vitamin A according to WHO recommendations.^41,43 The benefit of routine vitamin A supplementation outside of treating measles or other specific diseases remains debated, particularly when the vitamin A–deficiency status is unknown.⁴⁴ In addition, routine vitamin A supplementation in excess of the recommended dietary allowance can cause acute and chronic toxic effects in well-nourished children and adults.⁴⁵ Children are particularly sensitive; daily intakes of more than 1500 IU per kilogram of body weight have been associated with toxic effects in children.⁴⁵

In the only known study of the use of vitamin A in measles management in the United States, only 39% of patients received vitamin A and received a much lower dose than that recommended by the WHO.⁴¹ In contrast, recent cases of toxic effects of vitamin A intake associated with measles outbreaks in the United States (notably in West Texas) were linked to excessive or unsupervised intake of vitamin A outside medical guidance owing to misinformation. These data point to a need for clarity regarding vitamin A supplementation in the treatment of measles to inform health care workers and the public in the United States.

Data are limited regarding the benefit of vitamin A in the context of the United States, where vitamin A deficiency is rare. Measles depresses serum levels of vitamin A in well-nourished children to below the levels observed in malnourished children without measles.⁴⁶ In the United States, hospitalized children with measles frequently have low serum vitamin A levels, correlating with measles severity.⁴¹ Because vitamin A is critical in enhancing immune responses against infections,⁴¹ supplementation with vitamin A is recommended in children with measles. A meeting on the subject led by the National Foundation for Infectious Diseases in November 2019 provided suggestions on vitamin A doses (Table 3).

In 2023 and 2024, more than 90% of the measles cases worldwide were among children in low- and middle-income countries.²⁹ Most of those infected were children younger than 5 years of age, with the highest mortality among those younger than 1 year.¹² No systematic analysis has been conducted over the past decade to confirm the observed trend of increasing proportions of measles cases and deaths among young infants. Vietnam, which was among the top 10 countries in terms of number of measles cases in March 2025, had reported a rising number of cases among children 6 to 8 months of age; that age group represented 25% of measles cases in some areas.⁵² Young infants are at heightened risk for severe measles-related complications such as pneumonia, encephalitis, and death.^53,54 Children in this group are also at increased risk for subacute sclerosing panencephalitis, a rare but fatal condition.^55,56

In recognition of the potential vulnerability of young infants, discussions on the timing of the first dose of measles vaccine have been under way for decades and more recently at the WHO.^4,57–60 An early dose of measles vaccine given at 3 to 4 months of age could provide protection throughout infancy. Three studies conducted more than a decade ago provided some data regarding the safety, efficacy, and potential blunting effect (i.e., reducing the immunogenicity, both short term and long term, of subsequent doses) of an early dose of measles vaccine given at 4 to 4.5 months of age.^61-63 This dose could be either the early administration of the first recommended dose of the vaccine or an additional dose to the current two-dose schedule.^61-63 Both approaches have shown acceptable safety and immunogenicity.^61,62 The first dose, when given at 4.5 months of age, provided 94% efficacy against measles infection and 100% efficacy against hospitalization for measles.⁶² Determining the appropriate timing of an early dose requires a balance between the age-stratified infection risk (the age at which maternal antibodies would no longer inhibit measles vaccine immunogenicity) and the duration of vaccine effectiveness over time.^57,58 A trade-off of administering an early dose is the reportedly more rapid reduction of measles antibody in children who are vaccinated early in infancy.^64,65 Whether this antibody reduction would translate to reduced vaccine efficacy in later childhood is still an open question.

Because the two-dose measles vaccine schedule was not introduced in the United States until 1989, persons who received the vaccine between 1967 and 1989 may consider receiving a second dose if they are in a high-risk group, such as health care workers or international travelers.²⁸ An extra dose of measles vaccine may be also considered in persons who received the vaccine between 1963 and 1967, because the inactivated (killed) vaccine that was used was less effective than the current live attenuated vaccine.²⁸ Of note, persons who received measles vaccine between 1967 and 1989 or who received the inactivated measles vaccine may have immunity that is “boosted” over time by natural measles exposure, because measles was still endemic in the United States until 2000.

The primary cause of the resurgence in measles cases is failure to vaccinate, not failure of the vaccine. Neither the Centers for Disease Control and Prevention nor the WHO recommend routine boosters in persons who are fully vaccinated. Studies regarding serologic events conducted in the past 5 years in areas where measles is endemic and in ones where measles has been eliminated have reported immunity gaps in persons who received the vaccine on the two-dose schedule during childhood.^48,66,67 Most of these persons are 13 to 30 years of age, with some older than 40 years of age. Adults who have likely secondary vaccine failure account for some of the measles cases in outbreaks in well-vaccinated countries, as was the case recently in Mongolia.⁶⁸ A third dose of measles vaccine has been offered, mainly to health care workers, with similar safety and rates of adverse events as those seen with the recommended two doses. However, high antibody levels induced by the third dose waned quickly over a period of 1 to 3 years after the third dose.⁶⁹

Worldwide, reported measles cases saw a dramatic increase in recent years, from a historic low of 132,490 in 2016 to 869,770 in 2019.⁷⁰ The global increase in measles cases in 2019 was driven by large outbreaks in several countries. The Democratic Republic of the Congo, Madagascar, Samoa, Ukraine, and Brazil were the countries most affected. Vaccine hesitancy was an important cause in each of the affected countries.⁷⁰ This factor also contributed to the more than 100,000 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 had been eliminated in 2000.⁷¹ In 2019, vaccine hesitancy was recognized by the WHO as one of the top 10 challenges to global health.¹ Since 2019, no WHO region has achieved and sustained elimination of measles.

The Covid-19 pandemic worsened the situation by interrupting routine immunization and catch-up campaigns. During the pandemic, global coverage of first measles vaccines decreased to 81%, the lowest level since 2008. Coverage has improved slightly, to 83% in 2022 and 2023.²⁹ Low- and middle-income countries have the lowest coverage of first measles vaccines — 64% in low-income countries and 86% in middle-income countries.²⁹ A recent analysis of county-level rates of measles–mumps–rubella (MMR) vaccinations in 37 U.S. states shows that coverage was below 95% in 990 of 1501 counties and below 74% in 70 counties.⁷²

This poor coverage has sparked large measles outbreaks in several countries since early 2024, and measles is now spreading widely. In 2024, the European region reported the highest number of measles cases in more than 25 years, accounting for 20% of the total measles cases worldwide.² In the United States, as of May 30, 2025, 1088 confirmed measles cases and 3 deaths have been reported; 96% of those measles cases involved persons who were unvaccinated or whose vaccination status was unknown. In approximately 12% of reported cases, the infected persons were hospitalized.⁷³ The current number of cases is already approximately four times as high as the total reported in 2024. If measles outbreaks continue to spread through the United States for more than 12 months, the country will lose its elimination status.

Misinformation suggesting that measles vaccine causes autism and that vitamin A prevents measles has been a serious threat to effective measles control and management in the United States and worldwide. More than 25 years ago, a campaign of misinformation suggesting that measles vaccine causes autism led to loss of confidence in MMR vaccines, especially in the United Kingdom.⁷⁴ This misinformation has been thoroughly investigated and proved to be incorrect. In the United States, the recent decrease in childhood vaccinations has been associated with vaccine hesitancy. Estimates suggest that a 10% decrease in MMR vaccination in the United States may lead to 11.1 million measles cases over a period of 25 years.⁷⁵

The withdrawal of the United States from global public health initiatives and from support of global immunization programs is having a profound effect on measles control worldwide. Specifically, removal of support for the WHO, for which the United States contributes 19% of the budget, and Gavi, the Vaccine Alliance, for which it contributes 13% of the budget, will probably affect measles control and contribute to a large number of deaths from measles and other vaccine-preventable diseases in the poorest countries.⁷⁶ As a result, the outlook for measles control in the coming years is bleak. This situation puts U.S. domestic health security at high risk, because infectious diseases do not respect geographic borders.

In the context of increased international travel, rapid identification of measles cases and genotyping of measles virus are crucial for early detection of outbreaks, tracking of transmission chains, and effective outbreak control. Updates on measles diagnostic and molecular genotypes are provided in the Supplementary Appendix.