Health

Mysterious illness that paralyzes healthy kids prompts plea from CDC – Ars Technica


Enlarge / 13-year-old boy recovering in a Denver hospital from a suspected case of human enterovirus 68 during a 2014 outbreak.

After a record number of cases in 2018 of a rare, puzzling illness that causes paralysis in otherwise healthy kids, officials at the Centers for Disease Control and Prevention are urging doctors to hasten reporting and boost data collection before the next big wave of illness hits—which is expected in 2020.

The illness is called acute flaccid myelitis, or AFM, and is marked by the sudden onset of limb weakness (usually upper limb), paralysis, and spinal lesions seen on MRI scans. It most often occurs in children. It’s unclear what causes it and why instances are increasing—though officials suspect that a relative of poliovirus is involved. There is no specific treatment, and doctors can’t predict how affected patients will fare; some regain muscle strength and recover full use of paralyzed limbs over time, some don’t. In rare cases, AFM can cause respiratory failure and death.

AFM first gained attention in 2014, when health officials noted a spike in the polio-like condition nationwide and began carefully documenting cases. Since then, health officials have seen a distinct every-other-year pattern to the illness.

There were 120 recorded cases across 34 states that first year in 2014, followed by just 22 in 2015. Then 149 cases across 39 states and Washington, DC, in 2016, and a drop to 35 cases in 2017. In 2018, the CDC confirmed 233 cases in 41 states, the largest number yet. Of those, nearly all affected people ended up hospitalized, with 60% admitted to intensive care and 27% needing respiratory support. The average age of the patients was 5 years old.

So far, 2019 is looking like a typical off-year, with just 11 cases in eight states halfway through. That said, in each peak year, AFM cases tend to cluster in late summer to fall, generally between August and November.

Viral suspect

The first burst of AFM cases in 2014 coincided with a nationwide outbreak of Enterovirus D68 (EV-D68), which typically causes only respiratory illnesses. Experts immediately suspected a connection between AFM and EV-D68. For one thing, enteroviruses were already linked to paralytic illnesses—poliovirus is a type of enterovirus. Enterovirus type 71 (EV-A71), which is a main cause of hand-foot-and-mouth disease, has also been linked to a polio-like illness.

Moreover, researchers in California found evidence of EV-D68 infections in some of the 2014 AFM cases they closely examined. And they reported that the damage they saw in some AFM patients’ spinal cords was “consistent with spinal motor neuron injury from direct viral invasion of tissue, which is characteristic of poliovirus and enterovirus A71 infections.”

To date, more than 90% of those with AFM report having a mild respiratory infection or fever right before the onset of limb weakness. In the 2018 cases, limb weakness first appeared an average of just five days after the start of a mild viral illness. And enteroviruses—like some other viral respiratory infections—often peak when AFM does, in late summer to fall.

Collectively, the circumstantial evidence points to the idea that in some children, respiratory infections from enteroviruses spill over into motor neurons in the spinal cord and cause devastating damage.

Feeble data

But while that hypothesis seems like a slam-dunk, the evidence to back up the connection between EV-D68 and AFM has been maddeningly hard to get. From the 233 confirmed AFM cases in 2018, health officials were able to collect just 123 respiratory samples. Of those, only 30 tested positive for EV-D68, while ten others were positive for EV-A71 and 14 were positive for other enterovirus infections. Likewise, officials collected 74 samples of cerebrospinal fluid from the 233 cases, and only one tested positive for EV-D68. One other sample tested positive for EV-A71.

Researchers at the CDC suspect that the problem is either that the viruses simply aren’t shedding into spinal fluid or that doctors are collecting spinal fluid samples too late, days after the viral culprit is gone and the damage is done. That’s in part why the CDC is calling on doctors to notify health departments of suspected cases as soon as they can. The main purpose of the call to action is to prompt doctors to speed up their reporting, Dr. Tom Clark tells Ars. Clark is the deputy director of the CDC’s Division of Viral Diseases. Faster reporting could help officials collect more samples faster, as well as try out additional tests.

Beyond fingering a specific virus behind AFM cases, there are still plenty of other questions to answer. Namely, why are cases suddenly popping up now, or in these two-year cycles, or in certain, otherwise healthy children, and how is AFM best treated? Investigators have found evidence of EV-D68 infections in sets of siblings, while only one sibling develops AFM, hinting at some unknown, individual-specific risk factors. Doctors have come up with interim treatment recommendations, including physical therapy, steroids, and antiviral medications, but it’s unclear if they work.

Remaining riddles

Answers to these questions are far more speculative. For instance, though Clark tells Ars that the current thinking is that AFM is caused by a virus directly infecting and damaging spinal cord tissue—in part because it seems that damage occurs so quickly after the onset of a viral infection—there’s also the possibility that the damage is caused by a berserk immune response.

This is thought to be the cause of other paralytic conditions linked to viral infections, namely Guillain-Barré Syndrome (GBS). As in AFM, GBS usually strikes after a viral infection, either a respiratory or gastrointestinal illness. Upticks in GBS cases were noted in the wake of recent Zika outbreaks, for instance. Unlike AFM, GBS tends to start with weakness in the legs and back and progress toward paralysis relatively slowly, over weeks rather than days.

Intriguingly, a report from 2006 suggested that a single virus—West Nile virus—was associated with both AFM cases and a GBS-like syndrome in a cluster of 32 patients in Colorado. (West Nile virus infects birds in the US and spreads to humans via mosquito bites, typically causing asymptomatic infections or ones with vague viral symptoms, such as fever and body aches.)

Another odd ripple comes from a 2003 report from an international team of researchers who noted that a cluster of eight cases of AFM during an outbreak of hand-foot-and-mouth disease (caused by EV-A71) in Malaysia also seemed to be associated with a second virus, an unusual adenovirus. This led them to wonder if the overlap or interactions of the viruses had something to do with the severe illness. “Whether the epidemic of EV71-associated HFMD was coincidental or whether the severe presentation was due to an interaction between the 2 viruses is not certain… Clearly, more detailed prospective clinical, virological, and pathophysiological studies are needed to investigate the possible interaction between enteroviruses and adenoviruses and the patterns of disease that they cause,” they concluded.

For now, Clark tells Ars that it’s too early to speculate on all the factors that may be behind the current trend in AFM cases in the US. Cases are simply too few, with too little data to say much for certain. He and others at the CDC are hopeful that speedier reporting and closer surveillance from doctors will yield insight soon.

In the meantime, Clark recommends that parents be vigilant as well. “Colds are common and AFM is rare,” he says. But if a child suddenly develops weakness in a limb, take it seriously and get it checked by a doctor, he says.

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