In the wake of the third nationwide outbreak of acute flaccid myelitis (AFM) since 2014, the CDC is calling on frontline providers to act quickly to report suspected cases and to collect specimens. In a media briefing on the subject on July 9, Anne Schuchat, MD, the CDC’s principal deputy director, noted that a heightened awareness of AFM symptoms and immediate reporting to the health department is needed for investigators to make headway against the illness.

“When specimens are collected as soon as possible after symptom onset, we have a better chance of understanding the causes of AFM and these recurrent outbreaks and for developing a diagnostic test,” Schuchat noted. “Rapid reporting also helps us to identify and respond to outbreaks early and to alert clinicians and the public.”

The frightening illness causes limb weakness, mostly in children, and can be devastating to patients and their families, Schuchat said. “We have seen a seasonal pattern to this illness. Most patients develop AFM between August and October,” she stated. “Most [of the identified patients] had a mild respiratory illness or fever less than a week before they developed arm or leg weakness. These are important pieces of evidence that point to viruses, including enteroviruses in particular, playing a role in AFM.”

The CDC began tracking AFM after the outbreak of the illness that occurred in 2014. Since then, the agency has been working with local and state public health departments to investigate the illness by reviewing each case and testing every specimen received. Further, the agency is collaborating with universities and the National Institutes of Health to conduct research on AFM.

“Our sustained work will help lead to more answers about this serious illness, such as why some children develop AFM and why these outbreaks are occurring,” she said. “The CDC’s AFM task force of national experts is also playing a critical role in the AFM investigation by evaluating the current understanding of the causes of AFM and strengthening the knowledge base about the best ways to support patients through treatment and rehabilitation.”

Eliminate Delays

Tom Clark, MD, MPH, deputy director of the CDC’s Division of Viral Diseases, is leading the agency’s investigation into AFM. “The CDC confirmed that 233 patients in 41 states had AFM. This was the third and largest outbreak since we started our surveillance of AFM in 2014,” he said of the 2018 AFM outbreak during the July 9 media briefing. “Similar to the outbreaks in 2014 and 2016, most AFM cases were in young children; the average age was 5 years.”

Clark noted that children identified with AFM in 2018 were severely affected by the disease, with 98% hospitalized, 60% admitted to the ICU, and 27% requiring machines to help them breathe.

While all stool samples tested were negative for the poliovirus, roughly half of the stool and respiratory samples tested were positive for an enterovirus or rhinovirus, including EVA-71 and EVD-68. “The spinal fluid [from these patients] tested positive in two cases. One had evidence of EVA-71 and one had evidence of EVD-68,” Clark explained.

Since 2014, Clark noted the spinal fluid from patients has been tested in most AFM cases, but investigators have identified a pathogen in only a few cases. However, when a pathogen is found in the spinal fluid, that is good evidence that it was the cause of the patient’s illness, he said. Data from 2018 indicate that patients identified with AFM that year received prompt medical care. “On average, patients were hospitalized within one day after they started experiencing limb weakness, and an MRI was performed within two days,” Clark shared.

However, he observed that specimen collection from these patients for virus testing occurred within two to seven days, on average, and suspected cases were not reported to the CDC until 18 to 36 days after the onset of limb weakness. “This delay hampers our ability to understand the causes of AFM,” Clark advised. “The CDC urges healthcare providers to recognize AFM symptoms, collect specimens early, and immediately report all suspected cases to their health department.”

Boost Awareness

As of June 24, 11 cases of AFM have been reported this year to the CDC from eight different states. While an uptick in cases typically occurs from August through October, the illness can occur year-round. Schuchat noted that the every-other-year pattern of the outbreaks of AFM observed since 2014 is intriguing, but she cautioned clinicians against assuming that this will be a long-term pattern. “We want clinicians and parents to be ready for a possible significant outbreak this year,” she said. “We really need to be ready to rapidly detect, report, and investigate each case this year and to be ready for a possibly bad year.”

Nonetheless, the biannual pattern of the outbreaks of AFM is pointing investigators toward viruses as a likely cause of the illness. “We really do suspect viruses play a role, and enterovirus is among the leading suspects,” Clark observed. “These are really ubiquitous infections common in childhood. As you age, you’ve had many of them, so it may be that adults are less susceptible ... but we have a lot to learn through the research we’ve proposed in understanding what triggers AFM in some children.” Roughly 93% to 95% of AFM cases occur in children, but a handful occur in adults, Clark added.

While the CDC has published some interim considerations for clinicians on how to manage cases of AFM, there is not enough evidence to support any specific treatments (http://bit.ly/2YlkENh). Investigators are collaborating with the National Institutes of Health on a prospective study to better understand the treatments used and what steps might improve outcomes, Clark observed.

“We really do think that early and aggressive physical therapy and rehabilitation holds good promise to help kids strengthen the function that they have after AFM and regain as much strength and function as possible,” he shared.

Unfortunately, the experiences published from some of the cases that have occurred since 2014 indicate that 70% to 80% or more of the patients have experienced ongoing limb weakness, lasting several months after the onset of AFM, reported Clark, although he acknowledged there are some gaps in the investigators’ understanding in this area. “We’re going back to all of the cases that occurred in 2018 to assess muscle function, strength, and ability to perform activities of daily living up to six and 12 months after the illness onset,” he said. “We will learn a lot more about the persistence of limb weakness after AFM.”

Investigators also will be conducting structured interviews with patients and families to try to identify any potential risk factors for the illness, although most patients diagnosed with AFM thus far have been healthy children with no unusual patterns or exposures that have come to light.

Although diagnosing AFM is a challenge, CDC investigators are working with clinicians on the frontlines, such as those in EDs or in urgent care centers, to make sure they are aware of AFM and that they move to quickly report any suspected cases.