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Mysterious disease paralyzes healthy children calls for CDC appeal

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

After a record number of cases in 2018 of a rare and confusing illness that causes paralysis of healthy children, officials at the Centers for Disease Control and Prevention urge doctors to hasten reporting and to speed up the data collection before the next wave of disease … which is expected in 2020.

The disease is called acute flaccid myelitis or MAF. It is characterized by the sudden onset of weakness of the limbs (usually the upper limb), paralysis and spinal injuries observed during an MRI examination. It occurs most often in children. It is unclear what causes it and why the number of cases increases – although officials suspect the presence of a poliovirus parent. There is no specific treatment, and doctors can not predict how patients will be treated. Some regain muscle strength and recover full use of paralyzed limbs over time, others do not. In rare cases, AFM can cause respiratory failure and death.

The AFM drew attention for the first time in 2014, when health officials saw a spike in the state of polio nationwide and began documenting carefully the cases. Since then, health officials have seen a change in the disease every two years.

There were 120 cases registered in 34 states this first year in 2014, followed by only 22 in 2015. Then, 149 cases in 39 states and Washington, DC, in 2016, and 35 cases in 2017. In 2018, the CDC has confirmed 233 cases in 41 states, the largest number so far. Almost all those affected were hospitalized: 60% were admitted to intensive care and 27% needed a respirator. The average age of the patients was 5 years old.

Until now, 2019 seems to be a typical year, with only 11 cases in eight states at mid-term. That said, at each peak year, MFA cases tend to cluster around the end of the summer, usually between August and November.

Viral Suspect

The first outbreak of MFA cases in 2014 coincided with a national outbreak of enterovirus D68 (EV-D68), which usually causes only respiratory diseases. Experts immediately suspected a connection between AFM and EV-D68. On the one hand, enteroviruses were already linked to paralytic diseases – poliovirus is a type of enterovirus. The enterovirus type 71 (EV-A71), which is a leading cause of hand-foot-mouth-mouth disease, has also been associated with a polio-like illness.

In addition, California researchers have found evidence of EV-D68 infections in some of the 2014 MFA cases that they have closely examined. They also indicated that the damage they found in the spinal cord of some patients with CFD was "consistent with spinal motor neuron injury resulting from direct viral invasion of tissue, characteristic of poliovirus infections." and enterovirus A71 ".

To date, more than 90% of people with AFM have reported mild respiratory infection or fever just before the appearance of limb weakness. In the 2018 cases, limb weakness appeared on average five days only after the onset of a benign viral disease. And enteroviruses – like some other viral respiratory infections – often reach their peak when the AFM does so, in the late summer or until the fall.

Together, circumstantial evidence suggests that in some children, enterovirus respiratory infections spread into motor neurons in the spinal cord and cause devastating lesions.

Low data

But while this hypothesis seems to be a slam-dunk, the evidence to confirm the connection between EV-D68 and AFM has been terribly difficult to obtain. Of the 233 confirmed AFM cases in 2018, health officials were able to collect only 123 respiratory specimens. Of these, only 30 were positive for EV-D68, another 10 for EV-A71 and 14 for other enterovirus infections. Similarly, officials took 74 cerebrospinal fluid samples out of 233 cases, only one of which was positive for EV-D68. Another sample was positive for EV-A71.

CDC researchers suspect that the problem is either that the viruses simply do not spread in the cerebrospinal fluid, or that doctors take cerebrospinal fluid samples too late, a few days after the responsible virus has disappeared and the damage has been done. are caused. This is partly why the CDC calls on physicians to inform health services of suspected cases as soon as possible. The main goal of the call to action is to encourage doctors to speed up their statements, said Dr. Tom Clark in Ars. Clark is the Deputy Director of the CDC's Viral Diseases Division. Faster reporting could help officials collect more samples more quickly and perform additional tests.

Beyond looking for a specific virus behind MFA cases, there are still many questions to answer. Namely, why do cases suddenly arise now, or in these two-year cycles, or in some healthy children, and how is the AFM best treated? Investigators found evidence of EV-D68 infections in siblings, while only one of the siblings developed AFM, alluding to certain unknown risk factors specific to each individual. Doctors have made recommendations on interim treatment, including physical therapy, steroids and antiviral drugs, but their effectiveness is uncertain.

Remaining riddles

The answers to these questions are much more speculative. For example, although Clark tells Ars that, according to the current idea, AFM is caused by a virus that directly infects and damages the tissue of the spinal cord – partly because it appears that the damage occurs if soon after the start of a viral infection – it is also possible that the damage is caused by a crazy immune response.

This would be at the origin of other paralytic conditions related to viral infections, namely Guillain-Barre Syndrome (GBS). As in the AFM, the SGB usually breaks down after a viral infection, that it is a respiratory or gastrointestinal disease. For example, GBS declines have been observed following recent Zika outbreaks. Unlike the AFM, GBS tends to start with leg and back weakness and progressively progress to paralysis over several weeks rather than days.

Surprisingly, a 2006 report suggested that only one virus – West Nile virus – was associated with both MFA cases and GBS syndrome in a group of 32 patients in Colorado. (West Nile virus infects birds in the United States and is transmitted to humans through mosquito bites, usually causing asymptomatic infections or having vague viral symptoms, such as fever and body aches.)

Another strange reaction comes from a 2003 report from an international team of researchers who reported that a group of eight cases of MFA during an outbreak of 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 whether the overlap or the interactions of the viruses had anything to do with serious illness. "There is no certainty that the outbreak of MMPB associated with EV71 is coincidental or that the severe presentation is due to an interaction between the two viruses … It is clear that more clinical, virological and pathophysiological studies are needed. detailed and in-depth studies to study possible interactions between enteroviruses and adenoviruses and the types of diseases they cause, "they concluded.

For the moment, Clark tells Ars that it is too early to speculate on all the factors that can explain the current trend of MFA cases in the United States. The cases are simply too few, with too little data to say much. He and other members of the CDC hope that faster reports and closer monitoring of doctors will soon provide insight.

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

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