Do you often come across adults with fever and a rash and dismiss it as an allergy? Have you ever asked them if they were vaccinated for measles as children? Do they remember?
n 2000, the United States achieved a historic public health goal: the elimination of measles, defined by the absence of sustained transmission of the virus for more than 12 months. This achievement resulted from a concerted effort by health care practitioners and families alike, working to protect the population through widespread immunization.
Unfortunately, that momentous achievement was short-lived, and localized measles broke out in areas as people travelled to “exotic” destinations and the virus was introduced by infected persons, with subsequent spread through undervaccinated subpopulations. Remember vaccination does produce some herd immunity but people living in environments where human contact is limited and kept very sanitised may make a “herd” susceptible again.
According to the Centers for Disease Control and Prevention, 555 cases of measles in 20 states had already been confirmed from January 1 through April 11, 2019 . The increase in measles cases in the United States mirrors patterns elsewhere: several other countries that had eliminated measles are now seeing resurgences.
What is measles?
Measles is a highly contagious cause of febrile illness typically seen in young children. It is transmitted primarily by means of respiratory droplets and small-particle aerosols and can remain viable in the air for up to 2 hours. The dissemination of measles virus due to viremia, with associated infection of endothelial, epithelial, monocyte, and macrophage cells, may explain the variety of clinical manifestations and complications that can occur with measles virus infection. Exposed people who are not immune have up to a 90% chance of contracting the disease, and each person with measles may go on to infect 9 to 18 others in a susceptible population.
Measles virus infection can cause a variety of clinical syndromes, including:
- Classic measles infection in immunocompetent patients
- Modified measles infection in patients with pre-existing but incompletely protective anti-measles antibody
- Atypical measles infection in patients immunized with the killed virus vaccine. (do not transmit the disease)
- Neurologic syndromes following measles infection, including acute disseminated encephalomyelitis and subacute sclerosing panencephalitis
- Severe measles infection
- Complications of measles including secondary infection, giant cell pneumonia, and measles inclusion body encephalitis
What does measles look like?
Shown below are lesions seen in the oral cavity often referred to as Koplik spots. On the right can be seen the maculopapular rash on the back and trunk. The rash may blanch at the onset but later does not blanch, It may become hemorrhagic and include petechiae. It fades in about a week with the rash showing color changes and desquamates as it fades.
There is fever and conjunctivitis, pharyngitis and cough for 3-8 days before the rash is seen. In children the rash is often seen in the mouth first. Within 48 hours of the onset of the rash the fever settles. If the fever persists for more than 4 days after the rash a complication of measles has set in.
Why fear measles?
Most people with measles recover uneventfully after approximately 1 week of illness characterized by fever, malaise, coryza, conjunctivitis, cough, and a maculopapular rash.
However, measles is by no means a trivial disease; before widespread vaccination, the virus caused 2 million to 3 million deaths globally per year. Even today, it remains a leading cause of vaccine-preventable illness and death worldwide, claiming more than 100,000 lives each year.
Common complications include secondary infections related to measles-induced immunosuppression, diarrhea, keratoconjunctivitis (which may lead to blindness, particularly in vitamin A–deficient populations), otitis media, and pneumonia (the leading cause of measles-related deaths).
In approximately 1 in 1000 cases of measles, serious and often fatal neurologic complications such as acute disseminated encephalomyelitis and measles inclusion-body encephalitis occur, and most patients who survive these complications have long-term neurologic sequelae.
In addition, a rare neurologic complication (affecting approximately 1 in 10,000 patients) called subacute sclerosing panencephalitis (SSPE) can occur years after measles virus infection, with a severe, progressive, and fatal course.
How does measles affect immunity?
Measles virus infection can cause transient suppression of T cell responses . After measles virus infection, delayed-type hypersensitivity response is suppressed and the tuberculin test may become negative This may mean an abnormal immune response or tuberculosis reactivation in the setting of recent measles infection. Cellular and humoral responses to new antigens are restricted. Measles virus-induced immunosuppression may lead to secondary bacterial and viral illnesses including pneumonia and diarrhea, which cause the majority of measles-related morbidity and mortality.
Who is at risk of measles now?
If we continue to lose ground on measles prevention through vaccination, we face the reemergence of measles into new populations, which will pose new and varied challenges. Historically, measles has been a disease of children, with severe disease seen primarily in children younger than 5 and those with poor nutritional status, particularly if they have vitamin A deficiency. The successful implementation of measles vaccination programs is changing the epidemiology of measles from seasonal epidemics in young children to sporadic cases in older children and adults, including pregnant women. Data assessing the effects of measles infection in these latter populations are sparse but are suggestive of increased morbidity and mortality.
The greatest risk of measles-related complications occurs in immunosuppressed people. This population may have atypical presentations with severe complications that have not been documented in immunocompetent patients, such as giant-cell pneumonia and measles inclusion-body encephalitis. Exposure to measles in people with HIV infection has led to serious complications and even death.
Higher rates of measles complications and deaths have also been reported in patients with cancer, patients with solid organ transplants, people receiving high-dose glucocorticoids, and those receiving immunomodulatory therapy for rheumatologic disease. People with profound immunosuppression cannot be safely vaccinated with the live-attenuated vaccine and must rely on herd immunity to protect them from measles infection.
Exposure to measles in the community certainly represents a danger to high-risk persons during a local outbreak; however, nosocomial transmission may pose an even greater threat and has been reported throughout the world. For example, during a measles outbreak in Shanghai in 2015, a single child with measles in a pediatric oncology clinic infected 23 other children, more than 50% of whom ended up with severe complications, and the case fatality rate was 21%. When the umbrella of herd immunity is compromised, such populations are highly vulnerable.
Neurological complications of measles.
Fever, headache, vomiting, neck stiffness, seizures, obtunded consciousness leading to coma may occur. This may be encephalitis. Acute measles encephalitis may occur in the absence of rash so be on the lookout if there is an outbreak of measles in your area.
Encephalitis occurs in up to 1 per 1000 measles cases. It usually appears within a few days of the rash, typically day 5 (range 1 to 14 days). Analysis of cerebrospinal fluid is notable for pleocytosis (predominantly lymphocytes), elevated protein concentration, and normal glucose concentration. Approximately 25 percent of children have neurodevelopmental sequelae; rapidly progressive and fatal disease occurs in about 15 percent of cases.
Acute disseminated encephalomyelitis — Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that occurs in about 1 per 1000 measles cases. ADEM is thought to be a postinfectious autoimmune response; it may be triggered by a number of infectious causes . ADEM presents during the recovery phase of measles, typically within two weeks of the exanthem.Other manifestations may include ataxia, myoclonus, choreoathetosis, and signs of myelitis, such as paraplegia, quadriplegia, sensory loss, loss of bladder and bowel control, and back pain. This can occur in adults who have been in contact with children with measles.
Subacute Sclerosing Panencephalitis. SSPE.
When I was doing my postgraduate training in 1974-78 SSPE was a very real threat and diagnosed in young adults who had not received measles vaccination in childhood. The incidence slowly fell off and by the end of the 90’s the cases were very rare. This appears to have been in keeping with the measles vaccination in children which had become very active. It is seen in adolescents and young adults.
SSPE has been divided into the following stages:
- Stage I – Stage I consists of insidious development of neurologic symptoms such as personality changes, lethargy, difficulty in school, and strange behavior. Stage I may last from weeks to years.
- Stage II – Stage II is characterized by myoclonus, worsening dementia, and long-tract motor or sensory disease. The patient eventually develops a highly characteristic form of myoclonus in which massive myoclonic jerks occur approximately every 5 to 10 seconds. Stage II usually lasts 3 to 12 months.
- Stages III and IV – Stages III and IV are characterized by further neurologic deterioration with eventual flaccidity or decorticate rigidity and symptoms and signs of autonomic dysfunction. Myoclonus is absent.
- Stage IV is a vegetative state. Death usually occurs during stage IV but is possible in any of the stages .
The rate of progression is variable. Stabilization at one stage for a period of time can occur, though patients tend to progress from one stage to the next. Some patients have a remitting and relapsing course. Seizures can occur in any of the stages.
The serum anti-measles antibody concentration is elevated, and cerebrospinal fluid analysis shows elevated protein concentration and detectable anti-measles antibody.
Electroencephalogram (EEG) during stage II may demonstrate bursts of high-voltage complexes (300 to 1500 microvolts) of two- to three-per-second delta waves (slow waves) and sharp waves. These complexes last 0.5 to 3 seconds and occur every 3 to 20 seconds. Each complex is followed by a relatively flat pattern. These EEG findings are characteristic of SSPE and may be pathognomonic. The EEG may also be abnormal in the other stages of SSPE.
Computed tomography of the head may demonstrate atrophy and scarring . Magnetic resonance imaging of the brain may be normal. In one report (18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance spectroscopy revealed substantial functional abnormalities; these could be useful techniques for the early detection of SSPE and for assessing the specific brain areas affected in the early stages of SSPE (when MRI findings are likely to be normal).
The relentless and fatal course of SSPE underscores the importance of measles vaccination, not only for prevention of measles but also for prevention of the severe neurologic sequelae that can ensue.
If the potential danger posed by measles is clear, so is the solution. Live-attenuated measles vaccines are among the most highly effective vaccines available (providing 97% protection with two doses, given at 12 to 15 months and 4 to 6 years of age), with a proven safety record. The most common side effects of the measles vaccine are a sore arm and fever. A small proportion of vaccinees (about 5%) will develop a rash; an even smaller proportion will have a febrile seizure or transient decrease in platelet counts. A very rare complication, meningoencephalitis, has been described, almost always in immunocompromised vaccinees.
Measles vaccination has prevented an estimated 21 million deaths worldwide since 2000. Despite these substantial gains, global elimination goals have not been met, and previous strides are now being threatened by a 31% increase in the number of measles cases reported globally between 2016 and 2017. The World Health Organization (WHO) reported 117,075 measles cases and 1205 deaths in Madagascar between early October 2018 and early April 2019. Venezuela is also experiencing a large-scale epidemic, with endemic measles transmission now reestablished in a country where it had previously been eliminated. In Europe, the number of reported cases in 2018 was triple that in 2017 and 15 times that in 2016. In addition, it is likely that endemic measles has now been re established in several European countries where transmission had previously been interrupted.
The resurgence in measles cases is all the more frustrating since the disease is entirely preventable through vaccination. Measles has all the components of an eradicable disease: there is a safe and highly effective vaccine, it has a readily diagnosable clinical syndrome, and it has no animal reservoir to maintain circulation. But because of the highly contagious nature of the virus, near-perfect vaccination coverage (herd immunity of 93 to 95%) is needed to effectively protect against a measles resurgence. Although there are valid reasons why some people might not be vaccinated, such as a medical contraindication due to marked immunosuppression, the failure to vaccinate too often stems from misconceptions about vaccine safety, especially those resulting from a now-debunked claim that posited a connection between the vaccine and autism. The growing anti vaccination movement, based heavily on philosophical objections to vaccinations, poses a threat to public health. Vaccine hesitancy has been identified by the WHO as one of the top 10 threats to global health and is a serious hurdle to the global elimination and eradication of measles.
Unlike many infectious diseases, measles is a public health problem with a clear scientific solution. Measles vaccination is highly effective and safe. Each complication or death related to measles is a preventable tragedy that could have been avoided through vaccination. The recent upsurge in U.S. measles cases, including the worrisome number seen thus far in 2019, represents an alarming step backward. If this trend is not reversed, measles may rebound in full force in both the United States and other countries and regions where it had been eliminated.
Promoting measles vaccination is a societal responsibility, with the ultimate goal of global elimination and eradication — relegating measles to the history books.