Measles' Deadliest Sequelae
— How much do you know about its most dire consequences?
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| KAMENETSKY - KOTLER - SALOMON |
In the late 1990s, my long-time colleague, Pam Nagami, MD, met a petite, Indian-American student she later called "Manju" when writing a terrific bookopens in a new tab or window about patients with infectious diseases. Some of the stories by Nagami end happily, but Manju's did not -- and all because of a case of measles she contracted early in life.
So, now that WHO experts are predicting that more than half the world could face serious measles outbreaksopens in a new tab or window by the end of this year, I've begun to wonder: just how many modern-day doctors, much less vaccine-hesitant parents, know the virus's most calamitous blows?
Mind you, I'm not just talking about classic complicationsopens in a new tab or window -- pneumonia in one in 20 infected children, acute encephalitis in one in 1,000, death in as many as three in 1,000 children -- but stealthy assaults that are sometimes far deadlier.
In the case of Manju, who was adopted by a single mom in Chicago when she was not yet 2 years old, 20 years had passed before the girl from Calcutta with big, brown eyes showed early, non-specific signs of subacute sclerosing panencephalitisopens in a new tab or window (SSPE), a rare but fatal condition in which measles lies dormant, then goes rogue in a person's brain. Soon Manju was losing her vision and started to stutter, stumble, and twitch. Her diagnosis was confirmed by an EEG and measles-specific antibodies in her spinal fluid. Finally, 10 months after Nagami started administering twice-per-week, intrathecal injections of alpha-interferonopens in a new tab or window in a last-ditch effort to prolong Manju's life, her patient was dead.
I'll return to Manju soon. But first let's review additional facts about SSPE, then segue to one more murderous blow by the illness once described by Rhazesopens in a new tab or window (Abu Bakr al-Razi), a 10th century Persian physician, as "more dreaded than smallpoxopens in a new tab or window."
My closing message will come as no surprise. Anti-vaxxers, take note: Down the road, if the world doesn't aggressively immunize youngsters, future healthcare professionals will definitely see more measles-maimed children, including some like Manju with a ticking time bomb in their brain.
An Expert Weighs In on SSPE
Not far from my university lives a 93-year-old medical icon whose publisher will soon release the 9th edition of his weighty 2-volume textbookopens in a new tab or window on pediatric infectious diseases. So, today -- after decades spent caring for children injured by vaccine-preventable infections -- it's natural that UCLA's distinguished professor James Cherry, MD, MSc, is speaking out about measles.
Our currentopens in a new tab or window global resurgence of measlesopens in a new tab or window -- mainly linked to pandemic-related declines in immunizationsopens in a new tab or window and rising vaccine hesitancyopens in a new tab or window among parents -- raises the risk of serious complications and deaths, Cherry told NBC Newsopens in a new tab or window just last week.
Cherry is also worried about SSPE based on research in collaboration with the California Department of Public Health. In a 2017 paperopens in a new tab or window ominously sub-titled "The Devastating Measles Complication That Might Be More Common Than Previously Estimated," he and his co-authors reviewed all SSPE cases reported to the California Department of Public Health between 1998 and 2015, ultimately concluding that SSPE was 10 times more common than once assumed. Their research also showed that the age when children contract measles is an important SSPE predictor. Actual numbers? A deep dive into 18,000 cases of measles diagnosed in California between 1988 and 1991 revealed that SSPE later struck one in 609 youngsters under 12 months of age when first infected and one in 1,367 who were under 5 years old.
Finally, what exactly causes SSPE? A wild-type measles virus in the brain develops one or more point mutationsopens in a new tab or window in its genome that initially halt the virus's replication and spread, but later cause chronic encephalitis, inflammation, and demyelination. In a typical SSPE patient, the latent period preceding symptoms is 7 to 10 years, but sometimes exceeds two decades. Final clinical findings include a poignant constellation of visual abnormalities, convulsions, myoclonic jerks, and cognitive decline eventually culminating in mutism, spasticity, coma, and death.
Lessons Learned in London
I'm old enough to have seen plenty of patients with measles, both here and abroad, but my true awakening to its final furtive harm began while attending lectures at the London School of Hygiene and Tropical Medicine (LSHTM).
Back in 1979, when I was a student at LSHTM, annual global deaths due to measles were still shockingly high -- an estimated 2.6 million per year. But what was also drummed into our heads by researchers and clinicians who had worked for years in Africa and Asia, were the secondary woes that could follow it like evil dominoes.
For example, in a marginally-nourished child, an acute case of measles could infect the gut, cause diarrhea, and tip its sufferer into life-threatening protein-calorie malnutrition, also known as kwashiorkoropens in a new tab or window. In a child severely deficient in vitamin A, measles could suddenly produce blindness. Finally, a so-called "simple case of measles," we learned in that venerable lecture hall, could initiate a one-two immune punch leading to a subsequent death from malaria, typhoid, or another common infection.
Today, far more is known about the mechanisms by which measles paralyzes pre-existing human defenses against many infectious pathogens in a process called "immune amnesiaopens in a new tab or window" that sometimes lasts not just for months but years, as demonstrated in a seminal studyopens in a new tab or window published in Science in 2015.
Why these facts are not better known and shared with vaccine-hesitant parents is, in my view, both mystifying and concerning, since the simple antidote to all of the above ills are two doses of measles vaccine, which -- according to Cherry -- should ideally be given before the age of 2 years.
A Death With Dignity
One day, as Manju lay on a metal gurney in an outpatient exam room, my other writer-colleague asked her patient: "Are you afraid?" As Nagami's book attests, the deeply-loved, former orphan from India -- whose speech was now so slow and slurred it was difficult to understand -- sadly smiled and shook her head no.
In fact, Manju and her mother had already discussed what they would do when Manju's SSPE finally progressed to an irreversible, vegetative state. In short: no intubation, no ventilator, no resuscitation.
Six days after she was finally hospitalized and lost consciousness, Manju developed pneumonia, received morphine for comfort, and passed away.
Claire Panosian Dunavan is a professor of medicine and infectious diseases at the David Geffen School of Medicine at UCLA and a past-president of the American Society of Tropical Medicine and Hygiene.
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