Measles: An Update on the Outbreak, Laboratory Testing, and Diagnosis [Hot Topic]

Elitza Theel, Ph.D.
Elitza Theel, Ph.D.

The United States is currently experiencing a large, multi-state outbreak of measles linked to an amusement park in California. The outbreak started in December 2014 and has spread to more than a dozen other states. When evaluating patients with a febrile rash, health care professionals are urged to consider measles and ask about a patient's vaccine status, recent travel history, and contact with individuals who have febrile rash illness. Measles starts with fever, runny nose, cough, red eyes, and sore throat. It’s followed by a rash that spreads over the body. Measles virus is a highly contagious virus and spreads through the air through coughing and sneezing. Measles can be prevented with the measles, mumps, and rubella (MMR) vaccine.

Presenter and Credentials:
Elitza Theel, Ph.D., Director of the Infectious Disease Serology Laboratory at Mayo Clinic.

Transcript

Our speaker for this program is Dr. Elli Theel, Director of the Infectious Disease Serology Laboratory at Mayo Clinic, Rochester, Minnesota.Welcome to Mayo Medical Laboratories Hot Topics. These presentations provide short discussion of current topics and may be helpful to you in your practice. Today our topic is a discussion of the measles outbreak in the United States.

Dr. Theel, thank you for presenting today.

Thank you for the introduction and to the viewers for joining us today.

Before I begin, I should note that I have nothing to disclose.

During this presentation I will provide an overview of measles virus, discuss how it is transmitted, and provide a status update on the ongoing multistate outbreak that we are currently experiencing in the US.  I will also review the clinical manifestations of infection, proper test utilization and finally, prevention strategies.

Measles virus, also referred to as rubeola in reference to the reddish color of the classic measles rash, was first officially documented during the tenth century by a Persian physician, who interestingly described it as ”more dreaded than smallpox.”

Measles is an enveloped, single-stranded negative-sense RNA virus which is categorized in the family Paramyxoviridae and in the genus Morbillivirus.  There is a single measles virus serotype, and though some genetic heterogeneity has been documented in the hemagglutinin or H protein of the virus, these changes are epidemiologically insignificant and importantly, there has not been any effect on vaccine efficacy.

Regarding measles transmission, it is important to note that humans are the only reservoirs for this virus.

Measles is a highly contagious virus, as approximately 90% of nonimmune individuals who come into close contact with a measles patient will develop the infection.

Measles transmission is primarily person-to-person through direct contact with infectious droplets or secretions, for example after an infected individual coughs or sneezes.  Less commonly, airborne transmission can occur through contact with smaller, aerosolized droplet nuclei which remain infectious in the air and on solid surfaces for up to 2 hours after a measles patient leaves the area.

And finally, individuals with measles are infectious for a prolonged period of time, typically from 4 days before to 4 days after rash onset.

The first vaccines against measles were introduced in 1963.  Prior to this time, there were approximately 3 to 4 million cases of measles annually in the United States, which resulted in 48,000 hospitalizations and approximately 500 deaths per year.  Since introduction of the vaccine, measles incidence has decreased by 98%, but it wasn’t until the year 2000 that measles was declared eliminated, defined as the absence of continuous disease transmission for greater than 12 months, in the United States.

Measles does however remain endemic in many parts of Asia, the Pacific, Africa and in some areas of Europe and it is largely due to travelers with measles coming into the United States from these regions that have led to significant outbreaks among unvaccinated individuals and contributed to the recent increase in measles incidence as indicated in the table on this slide.

Regarding the most recent outbreak in the United States, the index case was likely a traveler who became infected overseas and subsequently visited an amusement park in California during the infectious period.  As of February 6, 2015, 121 measles cases have been reported to the CDC, of which 103 or 85% have been directly linked to the implicated amusement park in California.  The states directly affected and have reported outbreak-associated measles cases are indicated in the pink on the map below.

The incubation period for measles from exposure to onset of the prodromal phase ranges from 8 to 12 days.

Clinically, the prodrome lasts from 3 to 4 days and is characterized by high fever, cough, coryza, or a runny nose, and conjunctivitis, classically referred to as the ‘3 C’s’.  Koplik spots, which appear as blue-white spots on the buccal mucosa appear 1 to 2 days before to 1 to 2 days after rash onset and are show in the top picture by the black arrows. While pathognomonic for measles, Koplik spots are not always observed by clinicians at the time of patient presentation.

Following the prodrome and approximately 10 to 14 days after exposure, susceptible patients will develop the classic morbilliform rash which begins on the head and spreads downward towards the trunk and out to the extremities, as well as on the palms and soles.  The rash subsequently recedes in the same directions and the vast majority of individuals will recover completely within 1 to 2 weeks.

Serious complications from measles infection can occur however.  At-risk patients may develop pneumonia, which is the most common cause of death among children with measles, and approximately 1 in 1000 children will develop encephalitis which can result in permanent hearing loss and neurologic damage.

Additionally, some individuals may recover entirely from an acute measles infection, but 7 to 10 years later may develop subacute sclerosing panencephalitis or SSPE.  While SSPE is exceedingly rare, it’s a fatal degenerative disease of the central nervous system characterized by behavioral and intellectual deterioration as well as seizures.

Finally, as mentioned before, measles infection can result in death and between 1987 and 2000 every 3 measles cases out of 1000 resulted in death, most often among young, unvaccinated children.

Regarding diagnosis, measles should be considered in patients with compatible symptoms as outlined on the previous slide and a significant exposure history, for example in patients with recent international travel to a measles endemic area or an outbreak setting.  Also, it should be considered in nonimmune individuals with known exposure to patients with measles.

Other infections which may present with a similar generalized rash and should be considered by clinicians include infection with coxsackievirus, HIV, Rocky Mountain spotted fever, syphilis, and echovirus among others.

Finally, patients at increased risk for complications due to measles include infants and children less than 5 years of age, pregnant women, and immunosuppressed individuals.

The preferred laboratory method for diagnosis of acute or ongoing measles infection is by detection of measles RNA using a reverse-transcriptase PCR assay and/or culture.

Recommended specimens to submit include throat, oropharyngeal, nasal or nasopharyngeal swabs which ideally, are collected within 5 days of rash onset to maximize sensitivity.  Specimens collected more than 9 days after rash onset may be negative by PCR and culture

Urine collected 5 to 9 days following rash onset is an alternative source that can be tested by RT-PCR for measles RNA.

Currently, both RT-PCR and culture for measles are primarily offered through the CDC, select public health laboratories and public health laboratories that are part of the Vaccine Preventable Diseases Reference Lab Testing Network.  Providers are asked to contact their local hospital infection prevention and control team or the state health laboratory for additional sample submission information.

Serologic detection of antibodies to measles is also commonly used to support a recent measles infection, however a number of caveats to such testing must be considered.

First, serum should be collected at least 72 hours after rash onset, as samples collected prior to that may not have detectable levels of anti-measles IgM antibodies.  Additionally, a single negative result should not be used to rule out infection.

Secondly, while a positive IgM result suggests recent infection, false-positive result may occur due to prior infection with parvovirus, EBV, CMV, or due to elevated rheumatoid factor.  Also, recently vaccinated individuals may still have detectable, vaccine-induced IgM levels.

Finally, IgM antibodies will remain detectable for at least 28 days after rash onset.

Detection of anti-measles IgG-class antibodies can be used to document recent infection if providers observe a 4-fold or higher rise in titers between samples collected in the acute setting and convalescent samples collected at least 10 days later.  A single IgG positive result in a patient without symptoms is typically reflective of protective immunity against measles.

With regards to treatment, there is no specific antiviral therapy for measles.

Postexposure prophylaxis through vaccination is recommended however for individuals who have been exposed to measles and have close contact with children less than 1 year of age, pregnant woman, or immunocompromised hosts.  Postexposure vaccination may prevent infection in susceptible individuals if given within 72 hours of exposure.

The key to prevention of future measles outbreaks is vaccination.  As has been well documented, a single dose of the measles-mumps-rubella or measles-mumps-rubella-varicella vaccine administered to children 12 months or older provides protective immunity in approximately 95% of individuals.  A second dose of the vaccine induces immunity in an additional 95% of the remaining individuals who did not respond to the first dose.

Both MMR and MMRV are composed of live, attenuated viruses, and as such, approximately 5 to 15% of individuals will develop fever and approximately 5% of individuals may experience a rash around the injection site.  Despite these more common reactions, the MMR and MMRV vaccines have been proven to be a safe and effective means to limit the spread of measles and other preventable infections and are recommended by all medical authorities.

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