AAN.com Talks with CDC Neuroepidemiologist James J. Sejvar About Influenza Monitoring

Neurologists Must Play an Active Public Health Role in the H1N1 Pandemic

October 16, 2009

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Over one million people in the United States have been infected with the novel influenza A (H1N1) virus, and as the winter approaches, there will be increased influenza activity from pandemic H1N1 and seasonal influenza viruses. In most people, the H1N1 virus causes mild symptoms, but in some it leads to severe complications and can be life threatening. A predicted second wave of the pandemic will have a particular impact on neurologists, because the virus can have neurologic complications: individuals with neurologic disorders may be at higher risk of severe illness and death, and surveillance for neurologic adverse events—including Guillain-Barré syndrome (GBS) following the H1N1 vaccine—will be critically important.

To discuss the neurologic implications of the H1N1 virus and to highlight how the neurologic community can impact public health, José G. Merino, MD, MPhil, Science Editor of AAN.com, spoke with James J. Sejvar, MD, neuroepidemiologist in the Division of Viral and Ricketsial Diseases and the Division of the Vector-Borne Infectious Diseases at the Centers for Disease Control and Prevention (CDC).

AAN.com: What are the neurologic complications of influenza, and are there differences between seasonal and pandemic H1N1 infection?

Sejvar: Influenza associated encephalopathy (IAE) is an infrequent but well-known complication of seasonal influenza in children. It leads to changes in mental status, seizures, and focal neurologic deficits, but is not due to inflammation of the CNS. While most cases have been reported in Japan, IAE is also seen in other countries, including the United States. This summer, the CDC was notified of four children (aged seven to 17 years) who developed neurologic complications—encephalopathy, seizures, and EEG abnormalities—within a couple of days of onset of an influenza-like illness. In all of them, novel influenza A (H1N1) viral RNA was detected in the nasopharynx but not in the cerebrospinal fluid. They all recovered without short-term sequelae. Since then, several additional cases have come to the attention of the CDC, but it does not appear that neurologic complications are occurring at a greater rate than in seasonal influenza. It is not known whether adults are also at an increased risk of neurologic complications.

AAN.com: How is the CDC monitoring for H1N1-associated IAE, and what is the role of neurologists?

Sejvar: The CDC is monitoring severe illnesses associated with H1N1 infection, including neurologic complications. Neurologists should be aware of these complications and consider seasonal and novel influenza A (H1N1) in the differential diagnosis of children with encephalopathy or seizures that start within a few days of the onset of an influenza-like illness. These children should have a Rapid Influenza Diagnostic Test and, if positive, a confirmatory test. If a diagnosis of influenza is suspected and the child is at risk for complications, prompt antiviral therapy is indicated. Neurologists, as clinicians on the front line, should report cases of encephalopathy in persons with flu-like illnesses to local and state health departments.

AAN.com: What is the risk of complications and death from the novel influenza A (H1N1) virus among patients with neurologic disorders?

Sejvar: Children with neuromuscular and neurocognitive disorders may have a higher risk of neurologic complications and death. Preliminary reports suggest that children with pre-existing neurologic illnesses have an increased risk for severe illness and for a bad outcome. As of August 8, 2009, the CDC had received reports of 36 deaths of children associated with the 2009 pandemic influenza A (H1N1) in the US; 22 of these children had neurodevelopmental disorders (developmental delay or cerebral palsy), and 13 had more than one neurodevelopmental disorder. A CDC task force is looking into this issue, to identify what specific conditions increase risk and to develop direct vaccination and treatment and prevention measures. CDC continues to look at data from spring and summer. Adults with these conditions are also a focus of active surveillance. Neurologists should ensure that their patients with these conditions get vaccinated as soon as the vaccine becomes available.

AAN.com: Can you tell me about the H1N1 vaccine and its potential neurologic complications?

Sejvar: The FDA approved the vaccine for novel influenza A (H1N1) on September 15, 2009, after clinical trials to determine the optimal dose were completed. More recent studies suggest that the vaccine generates a strong immunological response in children. The vaccine will be administered to high-risk groups initially: pregnant woman, household contacts and caregivers for children younger than six months of age, health care and emergency medical services personnel, all people from six months to 24 years of age, and persons aged 25 through 64 years who have health conditions associated with higher risk of medical complications from influenza. People who are at higher risk for seasonal influenza should also get the seasonal flu vaccine.

In 1976 there was fear of a large outbreak of swine flu. Over 40 million people were vaccinated with the A/New Jersey/8/76 H1N1 swine flu vaccine, but the vaccination program was stopped after three months when the CDC identified, through a surveillance system, that there was a small but significant risk of developing Guillain-Barré syndrome six to eight weeks after vaccination (there was one additional case for every 100,000 people vaccinated). The reasons for the increased risk are not clear, but robust epidemiological data supports the vaccine–GBS association. Since then, there has been heightened surveillance for GBS, but there does not seem to be an increased risk with the use of seasonal flu vaccines. There is concern about GBS with the novel influenza A (H1N1) vaccine, however, because, as in 1976, the virus is partly of swine origin. Since 1976 there have been improvements in manufacturing methods and quality control. Without a clear idea of what led to the increased risk of GBS in 1976, however, it is hard to estimate the impact of these manufacturing changes.

AAN.com: How is CDC monitoring the situation, and what can neurologists do?

Sejvar: The CDC will actively monitor for the appearance of cases of post-vaccination GBS. CDC conducts active surveillance in several states which participate in CDC's Emerging Infections Program (EIP), observing over 40 million people in 10 regions of the country (California, Connecticut, Maryland, Minnesota, New Mexico, New York, Colorado, Oregon, Georgia, and Tennessee). In addition, CDC is partnering with professional organizations, including the AAN, to encourage reporting of suspected cases by its members. Neurologists play a critical public health role in our effort to understand the relationship between the vaccine and GBS, if any exists. We encourage them to report all cases of GBS that are temporally related to vaccine administration through the Vaccine Adverse Events Reporting System (VAERS). This is a passive surveillance system, co-managed by the CDC and the FDA to collect reports about possible vaccine side effects. CDC and FDA scientists review all reports and investigate severe events to determine whether they are associated with the vaccine.

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Author disclosures

Dr. Sejvar has nothing to disclose.

Dr. Merino performed a one-time consultation with staff from Bell, Falla and Associates.