Forgotten but not gone: Update on measles infection for hospitalists

Measles is a highly contagious acute respiratory illness that includes a characteristic rash. After exposure, up to 90% of susceptible persons develop measles.¹ Even though it is considered a childhood illness, measles can affect people of all age groups. Measles continues to be major health problem around the world, despite the availability of a safe and effective vaccine, and it remains one of the leading causes of childhood mortality, with nearly 115,000 deaths reported by the World Health Organization² in 2014. In 2000, measles was declared eliminated from the United States, but outbreaks still occasionally occur.^3-6

The disease is self-limited, but some patients develop complications that may require hospitalization for treatment. People at highest risk for complications are children younger than 5 years, adults older than 20 years, pregnant women, and immunocompromised individuals.⁷

During the licensure of live measles vaccine in 1963, an average of 549,000 measles cases and 495 measles deaths, as well as 48,000 hospitalizations and 4000 encephalitis cases, were reported annually in the United States. Almost all Americans were affected by measles by adolescence.

Implementation of the 1-dose vaccine program substantially reduced reported incidence in the United States by 1988, and led to a dramatic decline in measles-related hospitalizations and deaths.^3-6 The 2-dose MMR (measles, mumps, rubella) vaccination was introduced in 1989, and measles was declared eliminated in the United States in 2000.^3-6

National–level one-dose MMR coverage among children 19-35 months has remained above 90% during the last two decades.⁸ NIS-Teen vaccination coverage data for 13- to 17-year-olds since 2008 has been near or above 90%,⁹ and 94% of children enrolled in kindergarten had evidence of 2 MMR doses in the 2014-2015 school year.¹⁰

A large multistate measles outbreak was reported in the United States in 2014-2015.^4,11 One hundred fifty-nine cases were reported in the United States between January 4 and April 5, 2015. The majority of patients either were unvaccinated (45%) or had an unknown vaccination status (38%). Age ranged from 6 weeks to 70 years, and 22 patients (14%) were hospitalized.⁴

Measles is caused by an RNA-containing paramyxovirus that is spread by the respiratory route. Average incubation period from exposure to rash onset is 14 days (range, 7-21 days).^12,13 Peak infectivity occurs during the prodromal phase, before rash onset (Figure 1), but patients are infectious from 4 days before rash onset through 4 days after rash onset.^7,12,13

The disease prodrome consists of a high fever (39°C-40.5°C), coryza, cough, and conjunctivitis followed by Koplik spots (Figure 2A). Koplik spots are pathognomonic for measles but rarely discovered. They appear before the skin rash alongside second molars on the buccal surface of the cheeks. The spots usually disappear when the characteristic maculopapular, nonpruritic rash erupts initially at the hairline and behind the ears, and within four days progresses toward the trunk and limbs, including the palms and soles (Figures 2B, 2C).

The patient remains febrile while the rash spreads.^12,13 Usually the fever resolves while the rash fades in the same order in which it appeared. Fever that persists for more than 5 days usually indicates complications.¹³

Cellular immunity plays an important role in host defense; the virus invades T lymphocytes and triggers suppressive cytokine (interleukin 4) production. Leukopenia, expansion of mainly measles-specific T and B lymphocytes, and replacement of lymphocyte memory cell population results in further depression of cellular immunity, and predisposes patients to secondary bacterial infections for up to 2 years after measles infection.^14,15

Patients immunocompromised by congenital cellular immunity deficiency, cancer, human immunodeficiency virus (HIV) infection without effective antiretroviral therapy, or immunosuppression treatment are at higher risk for developing severe complications or dying from measles. As the rash may fail to develop in these patients, diagnosis can be challenging.¹⁶

Modified measles is milder and may occur in patients with preexisting partial immunity: those with an immunization history (2-dose vaccine effectiveness is ∼97%), and infants with minimal immunity from their mothers.^1,7 Patients may have mild respiratory symptoms with rash but little or no fever.⁷

Atypical measles is now extremely rare. It was described only among people who were vaccinated with the killed vaccine in the United States between 1963 and 1968 and subsequently exposed to measles. The disease is characterized by high fever, edema of extremities, and a rash that develops on the palms and soles and spreads centerward. It is considered noncommunicable.¹⁷

Measles infection during pregnancy is associated with increased maternal and fetal morbidity. The virus can induce neonatal low birth weight, spontaneous abortion, intrauterine fetal death, and maternal death. Pregnant women with measles are more likely to be hospitalized.^18,19