Measles

Etiology

The causative organism of measles is the measles virus, an enveloped, single-stranded, negative-sense ribonucleic acid (RNA) virus belonging to the genus Morbillivirus in the family Paramyxoviridae (see Image. Paramyxovirus Virion, Transmission Electron Micrograph). The genome encodes 6 structural proteins and 2 non-structural proteins, V and C. The structural proteins are nucleoprotein, phosphoprotein, matrix, fusion, haemagglutinin (HA), and large protein. The HA protein is responsible for virus attachment to the host cell.[2]

Epidemiology

The epidemiology of measles is variable globally and relates to immunization levels achieved in a particular region. Before implementing widespread vaccination programs, measles accounted for an estimated 2.6 million deaths. Despite vaccination in the present era, the World Health Organization (WHO) reported that in 2023, there were an estimated 107,500 measles deaths globally, mostly among unvaccinated or under-vaccinated children younger than 5 (WHO-Measles, 2025). Measles is resurging in the US due to vaccine hesitancy and lower vaccination rates.[4] As of May 1, 2025, the CDC has reported 935 confirmed measles cases, mostly in unvaccinated or vaccination status unknown children.[5] Texas reported most of these cases (683), with 89 hospitalizations and 2 deaths.[6]

The measles virus has no animal reservoir and occurs only in humans. The virus is highly contagious, with each case capable of causing 14 to 18 secondary cases among susceptible populations, contrasting with the SARS-CoV-2 virus, which contributes from 1 to 6 cases per infected person.[7] Respiratory droplets, small particle aerosols, and close contact transmit measles from person to person. The incubation period ranges from 6 to 21 days, with a median of 13 days; longer periods have also been documented.

Unvaccinated young children and pregnant women are at elevated risk of contracting measles; the virus is contagious from 5 days before the rash's appearance to 4 days after its appearance. To prevent widespread transmission, 95% of the population should be immune, but in 2023, only 83% of children globally were immune.[4][8] There were 16 outbreaks in the US in 2024; 40% of those were hospitalized (CDC Measles cases and outbreaks, March 21, 2025). Infants born to mothers with acquired immunity receive passive antibody protection against measles, but become susceptible as these antibodies decrease. Recent data suggest this may not be true in the current era, as vaccine-mediated passive immunity in early infancy may not be as protective.[9] Infectiousness is greatest from 4 days before to 4 days after rash onset, coinciding with peak viremia a cough, conjunctivitis, and coryza.[3]

Pathophysiology

The inhaled virus from the exposed droplets initially infects the respiratory tract’s lymphocytes, dendritic cells, and alveolar macrophages. Then the virus spreads to the adjacent lymphoid tissue and disseminates throughout the bloodstream, resulting in viremia and spreading to distant organs. The virus residing in the dendritic cells and lymphocytes transfers to the epithelial cells of the respiratory tract, which are shed and expelled as respiratory droplets during coughing and sneezing, infecting others and perpetuating the cycle. The initial inflammation leads to symptoms of coryza, conjunctivitis, and cough. The appearance of fever coincides with the development of viremia. The skin rash occurs after dissemination due to perivascular and lymphocytic infiltrates.

During the prodromal phase, the measles virus depresses host immunity by suppressing interferon production through its nonstructural proteins, V and C. The increasing viral replication then triggers both humoral and cellular immunological responses. The initial humoral response consists of immunoglobulin (Ig)M antibody production, which is detectable three to four days after the rash appears and can persist for 6 to 8 weeks. Subsequently, IgG antibodies are produced, primarily against viral nucleoprotein. Cellular immune responses are essential for recovery, as demonstrated by elevated T-helper (Th)1-dependent plasma interferon-gamma levels during the acute phase and subsequent elevation of Th2-dependent interleukin 4, interleukin 10, and interleukin 13 levels.[10] Lymph node biopsy will show the characteristic (fused lymphocytes) in a background of paracortical hyperplasia.[11]

The measles virus can induce immunosuppression that can last for weeks to years. This causes increased susceptibility to secondary bacterial and other infections. While the mechanisms causing this phenomenon are unclear, it is hypothesized that measles infection induces the proliferation of measles-specific lymphocytes that replace the previously established memory cells, causing "immune amnesia." This results in enhanced susceptibility of the host to secondary infections, leading to most of the morbidity and mortality associated with measles. Neutralizing IgG antibodies against hemagglutinin is responsible for lifelong immunity as it blocks host cell receptors from binding to the virus.

History and Physical

The WHO clinical case definition of measles is "any person with fever, generalized maculopapular rash, cough, coryza, or conjunctivitis." Measles is an acute febrile exanthema characterized by the 3 “Cs”: cough, coryza, and conjunctivitis (see Image. Koplik Spots, Measles). Small white papules on the buccal mucosa are pathognomonic for measles and appear 1 to 2 days before the rash, although they are not always seen; the fever precedes the rash. The morbilliform rash appears around the hairline and face about 2 weeks after exposure, then spreads caudally. Uncomplicated measles typically resolves a week after the rash onset in the same order it initially appeared, followed frequently by desquamation.[5][12] 

Breakthrough measles, or modified measles, is rare due to waning vaccine immunity. This condition tends to be a mild illness and can be challenging to diagnose as the rash may not follow the typical progression and can start on the trunk or extremities. The combination of cough, coryza, and conjunctivitis may appear singly or not and can present as a mild flu-like illness. Transmission of infection from cases of modified measles can occur, but is rare.[13] 

Evaluation

The diagnosis of measles hinges on a high clinical suspicion, especially when evaluating children with febrile illness and a maculopapular rash. A complete blood count may show leukopenia, particularly lymphopenia, and thrombocytopenia. Electrolyte abnormalities may occur in children with poor intake or diarrhea. Reverse transcriptase-polymerase chain reaction (RT-PCR) may detect the viral RNA in throat, nasal, nasopharyngeal secretions, peripheral blood mononuclear cells, and urine samples up to 10 days after rash appearance, but is most sensitive in the first 3 days.[5] RT-PCR is the most commonly used laboratory method to diagnose measles.[14]

Identifying measles-virus-specific IgM antibodies in serum or plasma confirms the diagnosis. However, it may be a false negative in up to 25% of cases when performed early (less than 3 days of rash onset). These antibodies usually peak within one to three weeks after the onset of a rash and become undetectable by 4 to 8 weeks. False-positive IgM test reactions can be due to the presence of rheumatoid factor or during infection with rubella, parvovirus, or human herpes virus 6.[14] See Images. Rubella Virus, Transmission Electron Micrograph and German Measles, Rubella. The gold standard test is the highly sensitive plaque reduction neutralization assay. The measles virus can be cultured from nasopharyngeal secretions, but this is labor-intensive and impractical.[14]. Both measles infection and vaccination confer lifelong immunity in most populations.

Treatment / Management

There is no specific antiviral therapy for measles; treatment is primarily supportive. The mainstay of therapy is the control of fever, prevention and correction of dehydration, and infection control measures, including appropriate isolation.[15] The WHO and American Academy of Pediatrics recommend administering daily doses of vitamin A for 2 days (or longer for malnourished children).[16][17] While vitamin A supplementation has been shown to reduce measles complications in malnourished children, it is neither a measles prevention strategy nor an antiviral agent. Vitamin A toxicity from excessive doses can cause dangerous neurologic and hepatic complications.[18] No established scientific data support using antibacterials or inhaled steroids in treating measles.(A1)

Measles Vaccine

The single best way to treat measles is to prevent it. To that end, the measles-mumps-rubella (MMR) vaccine has a well-deserved, celebrated history of being one of the safest and most effective vaccines ever produced. See StatPearls companion article, MMR Vaccine, for additional details. Before the vaccine's widespread use, measles was responsible for 7 to 8 million childhood deaths globally per year.[19] Approximately 1 in 1000 measles-infected children will develop life-threatening encephalitis as an early complication. An additional 5 to 10 in 100,000 children will develop a late-appearing measles sequela, subacute sclerosing panencephalitis. Pneumonia is the leading cause of death due to measles. Keratoconjunctivitis and otitis media due to measles can result in blindness and hearing loss, respectively.[20][21]

The measles vaccine provides 97% protection after 2 doses; it has been administered to several million recipients globally over decades, and has proven safe and effective by dramatically reducing the number of measles cases. Secondary vaccine failure rates due to waning immunity are approximately 5% at 10 to 15 years after vaccination. Breakthrough infection from waning immunity is rare and typically occurs only after intense and prolonged exposure to an active measles case.[13] Given the absence of an animal reservoir and the availability of a safe and highly effective vaccine, it is theoretically possible to eliminate measles as a cause of disease.[19] For those individuals who have not been fully vaccinated, catch-up vaccination is highly recommended.

Differential Diagnosis

The following are differential diagnoses for measles:

• Drug eruptions
• Erythema Infectiosum
• Kawasaki disease
• Meningococcemia
• Rocky Mountain Spotted Fever
• Infectious Mononucleosis
• Parvovirus B19 infection
• Pediatric enteroviral infections
• Pediatric rubella
• Pediatric sepsis
• Pediatric toxic shock syndrome
• Scarlet fever
• Multisystem inflammatory syndrome in children
• Dengue
• Zika
• Syphilis

Prognosis

Most patients will recover from measles without complications, but there is still a risk of a poor prognosis. Some common complications due to infection with measles include otitis media, keratoconjunctivitis, diarrhea, and secondary bacterial infections. Blindness and hearing loss represent potential lifelong sequelae. Those more likely to have severe complications include infants and children younger than 5, adults older than 20, pregnant women, and those who are immunocompromised. Neurological sequelae are associated with significant functional impairment and potential mortality. Measles continues to cause 100,000 to 200,000 deaths annually in the unvaccinated.[21] 

Complications

Complications of measles occur most commonly in young infants, pregnant women, and malnourished or immunocompromised children. The most common complication is pneumonia, which can be due to the measles virus itself (eg, Hecht giant cell pneumonia) or a secondary bacterial infection with organisms such as Streptococcus pneumoniae, Haemophilus influenzae, group A streptococcus, and Staphylococcus aureus. Other complications include croup, otitis media, diarrhea, and, less commonly, myocarditis, pericarditis, appendicitis, and thrombocytopenic purpura.[15]

Pregnant women with measles are at increased risk for maternal death, spontaneous abortion, intrauterine fetal death, and low birth-weight infants. Measles keratoconjunctivitis occurs mostly in children with vitamin A deficiency and can lead to blindness. Central nervous system complications include acute disseminated encephalomyelitis (ADEM), measles inclusion body encephalitis (MIBE), and subacute sclerosing panencephalitis (SSPE).[22][23] ADEM is an autoimmune demyelinating disease that occurs within days to weeks.[24][25] MIBE is thought to be a progressive brain infection in patients with impaired cellular immunity occurring within months of the initial infection. SSPE is a progressive neurological disease that presents 5 to 10 years after the acute illness and is thought to be caused by an abnormal host response to the production of mutated virions.[23][26] This condition usually occurs among children who developed measles before 2 years of age and manifests with seizures and progressive loss of cognitive and motor function.