April 18, 2019
5 min read

Q&A: Is the CDC’s delay in linking AFM to EV-D68 warranted?

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Amesh Adalja
Amesh A. Adalja

The United States witnessed an uptick in the number of children experiencing weakness and paralysis of unknown origin in 2014. The CDC began investigating cases of the condition, known as acute flaccid myelitis, or AFM, and since then, surveillance data have shown a spike in cases occurring every 2 years.

The CDC said it has tested patients with AFM for a wide range of pathogens that could be potentially responsible for the condition. Coxsackievirus A16, enterovirus A71 and enterovirus D68 (EV-D68) were detected in spinal fluid samples from four of 558 confirmed cases since 2014, “which points to the cause of their AFM,” the CDC said, but no other pathogens have been detected in patients’ spinal fluid. The agency has set up a task force to further study the cause of AFM and improve treatment for patients.

However, some physicians have spoken out against the CDC’s slow progress in linking the most likely culprit — EV-D68 — with AFM. In an October 2018 interview with NBC News, Ali S. Khan, MD, MPH, dean of the College of Public Health at the University of Nebraska Medical Center, said it was “puzzling” that the CDC had not yet confirmed the etiology of AFM cases.

Infectious Diseases in Children spoke with Amesh A. Adalja, MD, FIDSA, an infectious disease physician and senior scholar at the Johns Hopkins Center for Health Security and member of the Infectious Diseases Society of America, to better understand what the CDC has done to investigate AFM cases and why the delay in naming its cause may be warranted. – by Katherine Bortz

Q: Have there been any developments regarding the link between AFM and EV-D68, and has the CDC moved fast enough to establish this link?

A: There are going to be scientists and physicians who are frustrated when establishing a complex causal chain for a complication of an infection or a syndrome, which is not something that is very easily done. AFM is an after-effect of infection, so it is going to take time.

I agree that EV-D68 is probably the prime suspect, and the evidence is getting clearer and clearer, but it may be very difficult to prove because of the nature of AFM.

AFM occurs after respiratory illness, and the actual virus is often not found in the patient when they are diagnosed with AFM. There are a lot of hypotheses for how EV-D68 is related to AFM that need to be sorted out before we can prove a causal, fully conceptualized model of the relationship.


When people hesitate to make a full claim, it’s probably out of experience and respect for trying to get the whole picture right before they announce it. For all intents and purposes, I think that people in the field are assuming that EV-D68 is the most important piece of the AFM puzzle.

The last report from the CDC really shows a correlation between spikes of EV-D68 activity in years in which AFM cases spiked as well. I think this is the strongest case that we’ve seen that years when EV-D68 is prevalent are years when you have seen AFM, and years where you have not seen EV-D68, you have not seen AFM.

Q: Has the CDC’s reluctance to designate EV-D68 as a likely cause of AFM delayed the development of improved surveillance, diagnostic and therapeutic measures?

A: I don’t believe the lack of an official label from the CDC has caused a major delay with respect to AFM diagnostic and surveillance measures. From the start in 2014, it has been generally accepted that EV-D68 was somehow linked to AFM, but the nature of the relationship was not — and still is not — completely clear. EV-D68-related research began in earnest around that time and has already led to increased knowledge about this viral strain, including its development of neurotropic features.

Q: How has the CDC responded to the spike in cases ?

A: The CDC has tracked AFM since its first appearance in 2014. Most of that work has largely included defining cases, trying to identify cases and keeping track of the number of cases. That may not seem like a very important role, but it is huge because you have to delineate who has AFM and who does not to get an idea of what the true burden of infection is.

There is enterovirus surveillance work being done, and what we saw in the most recent CDC report were the results of that surveillance showing an EV-D68 spike in AFM years and the absence of EV-D68 cases in non-AFM years. That is an important piece of knowledge that they discovered that helps link EV-D68 to AFM. There has been a network set up to look at patients who developed AFM, to track their prognosis and try and understand best practices for the treatment of those patients.


The CDC has also done a lot of work in public relations and explaining what AFM is. It is something that can grab a lot of headlines, especially when it is described as a polio-like condition. What gets lost in those headlines is the rarity of it, and you can get a lot of people who are panicked. I have seen patients in my own personal practice with upper respiratory symptoms who are scared that they are going to develop AFM. I think that the CDC statistics on how rare this is — like a one in a million type of thing — is useful.

There are a lot of things that the CDC has done, but when you are in the middle of a mysterious outbreak that is paralyzing children, there is always going to be a call for what more can be done, how quickly can this be figured out and when will we have all the answers to all the questions that people have. I think that the CDC has taken AFM very seriously.

Q: What does the CDC need to do to ease experts’ concerns about the delay in labeling EV-D68 as the cause of AFM ?

A: It’s going to be really hard to reduce concerns because of the nature of AFM. When people are becoming paralyzed, there are going to be experts who want to move faster. It’s important to remember that the CDC must be adequately resourced to do all this. They also have a lot of competing priorities, but examining infectious diseases is a core founding mission of the CDC. It is hoped that they will not let up, because I suspect we won’t see as many cases in 2019, and things are going to fade from the headlines soon if AFM follows this 2-year pattern.

A priority for the CDC is disseminating information as studies are completed to help clinicians understand, as well as dispute, myths about AFM. The longer that this remains unsolved, the more these myths and conspiracy theories start to crop up.

I also think the task force will go a long way toward solving the puzzle of AFM sooner rather than later.


CDC. Acute flaccid myelitis: About acute flaccid myelitis. https://www.cdc.gov/acute-flaccid-myelitis/about-afm.html. Accessed April 9, 2019.

CDC. Acute flaccid myelitis: AFM surveillance. https://www.cdc.gov/acute-flaccid-myelitis/afm-surveillance.html. Accessed April 9, 2019.

Disclosure: Adalja reports no relevant financial disclosures.