AFM update July 2019

The Centers for Disease Control and Prevention has published ‘Surveillance for Acute Flaccid Myelitis – United States, 2018’ in Morbidity and Mortality Weekly Report (click for link to article). The article summarizes AFM for 2014-2018.

There were 233 confirmed cases of AFM in 2018, which is the largest number since surveillance for this condition began in 2014. AFM is defined as a disease of the nervous system – the brain and spinal cord – in which muscles and reflexes become weak, often accompanied by paralysis. Recently the definition has been modified to include MRI evidence of spinal lesions. The number of AFM cases have increased since 2014, mainly in young children. However, AFM is a rare disease, affecting 1-2 per million children each year.

Confirmed cases of AFM reported to CDC (n=559), United States, 2014-2018.

AFM is often called a ‘polio-like’ disease due to the paralysis that is observed in children with the disease. However, poliovirus is not found in the stool of children with AFM.

AFM was first defined in 2014 after reports of limb weakness in children across the US during an outbreak of respiratory disease caused by enterovirus D-68. AFM may also be associated with infections caused by other viruses, such as enterovirus A71, Coxsackievirus A16, West Nile virus and adenovirus. Since 2014 AFM surveillance has been conducted across the US.

Of the 233 patients with confirmed AFM in 2018, EV-D68 was the most frequently detected virus, mainly in respiratory samples. Only two samples of cerebrospinal fluid were positive: one for EV-D68 and one for EV-A71.

While it seems likely that EV-D68 is an etiological agent of AFM,  additional proof is clearly needed. Such proof would include showing that EV-D68 causes similar clinical disease in animal models following respiratory infection. These experiments have not been done but are a focus of our research.

 

Update on AFM cases in the US

As of this date in 2018, CDC reports 116 confirmed cases of AFM in 31 states. These 116 confirmed cases are among the total of 286 reports that CDC is investigating.

This map illustrates the number of confirmed cases of AFM in each state, demonstrating the nationwide nature of this outbreak:

afm-state-map

This graph displays the number of confirmed cases of AFM in the US:

CDC has established an AFM task force to encourage collaborations between CDC and the scientific community so that we can better understand the cause of AFM, how to prevent it, and how to treat it. More information on the task force can be found at this link. The first meeting of the task force will be on 4 December in Atlanta, GA.

Our laboratory has joined the AFM Consortium to bring together clinicians and basic scientists working on AFM.

Acute flaccid myelitis outbreak

There is currently an increase in the number of children in the US diagnosed with acute flaccid myelitis (AFM). This condition involves weakness of the arms and legs and may include other symptoms such as inability to breathe. The CDC has a complete definition of AFM at their website.

Cases of AFM in the US and Europe began to increase in 2014. The reason for this increase is not known. It has been suggested that enterovirus D-68 was responsible for the increased AFM observed in 2014 and 2016. This conclusion is based upon detection of EV-D68 genetic material (RNA) in the respiratory tract of children with AFM.

So far in 2018 there have been 72 confirmed cases of AFM in the US out of 191 suspected in 24 states. CDC indicates that the cause of most of these cases is unknown. Certain state health departments, such as New York and Colorado, are reporting detection of EV-D68 RNA from the respiratory tract of  some children with AFM.

A second enterovirus, EV-A71, has been isolated from some of the AFM children in Colorado. This virus is different from EV-D68 and infects the intestine rather than the respiratory tract. EV-A71 causes a rash called hand, foot, and mouth disease. It is known to be shed in feces, is present in the blood (viremia) and may cause neurological disease. In contrast, EV-D68 is not found in the blood or feces. EV-D68 is very unstable in the acidic environment of the stomach and should not be found in the feces. EV-A71, like poliovirus, is stable in the stomach and can be passed in the feces where it is spread to others.

Currently news sources are reporting that some doctors claim that EV-D68 is causing the outbreak of AFM in the US. Some doctors are testing for the presence of the virus in the feces, which is incorrect because, as stated above, the virus cannot pass through the stomach without being destroyed.

EV-D68 is unusual in its apparent ability to move from the respiratory tract to the nervous system. Our laboratory is interested in understanding this mode of virus spread. One way that we are studying the virus is by using three-dimensional lung and brain cultures produced from induced stem cells.

Enterovirus D-68 has always been able to infect nerve cells

induced motor neuronsEnterovirus D68 (EV-D68) was first isolated from children with pneumonia in 1962, but an association with AFM/AFP was not observed until the 2014 outbreak.

To determine if neurotropism – the ability to infect nerve cells – of EV-D68 is shared among virus isolates, we collected isolates from 1962 through 2014.  We then used these viruses to infect cultures of human motor neurons (pictured) and human astrocytes. Six of the seven EV-D68 isolates examined replicated in human neurons, and all replicated in human astrocytes.

These observations demonstrate that EV-D68 is neurotropic independent of its genetic lineage, can infect both neurons and astrocytes, and that neurotropism is not a recently acquired characteristic as has been suggested.

These results have been submitted for publication; a preprint can be found at bioRxiv.