Pandemic influenza: a priority for the neurological community

Abstract

On July 24, 2009, the US Centers for Disease Control and Prevention (CDC) reported neurological complications in four previously healthy children in association with pandemic influenza A H1N1; since then, there have been further anecdotal reports from other countries of similar complications linked to the virus. Moreover, experience from an immunisation campaign against influenza H1N1 of swine origin in the USA in 1976 suggests that potential new vaccines might be associated with a raised risk of neurological disorders. As autumn approaches, preparations for the expected rise in cases of pandemic H1N1 should therefore include plans for coordinated surveillance programmes involving the neurological community to systematically monitor for neurological complications related to the virus and vaccines. The four patients, aged 7 to 17 years, were admitted to hospitals in Texas with signs of influenza-like illness and neurological complications: two had seizures and three had abnormal EEG recordings. In all cases the H1N1 virus was detected in nasopharyngeal specimens but not in the CSF. Studies of seasonal influenza suggest that neurological deficits related to pandemic H1N1 should not be surprising: influenza-associated encephalopathy (IAE) has been well described in Japan, mainly in children, and in some has led to serious neurological sequelae and death. The recent cases associated with pandemic H1N1 have been less severe than those seen with seasonal influenza and the complications seem to have resolved in all cases. Given that IAE seems to preferentially affect children during outbreaks of seasonal influenza, and that children and young adults seem to be more vulnerable to the H1N1 virus, it is likely that more neurological complications will be seen in this group as the pandemic progresses. So far, most countries that are able to monitor the complications of pandemic influenza are not specifically targeting the neurological complications. One of the major hurdles in this regard is the challenge of substantiating the diagnosis and excluding alternative causes, particularly since the virus is rarely detected in the CSF. Greater involvement of neurologists and paediatricians would therefore be invaluable in assisting with diagnosis and surveillance. Vaccines for pandemic H1N1 are currently in development, and past experience indicates the need for increased vigilance for neurological complications when immunisation programmes begin. Following the influenza outbreak in 1976 in New Jersey, USA, fears of a repeat of the devastating influenza pandemic of 1918 prompted a large-scale immunisation drive in which 40 million Americans were vaccinated. However, the campaign was halted just 3 months after it began as reports emerged of Guillain-Barré syndrome (GBS) during the 8-week period after immunisation. Although there is no agreement on the precise number of people who developed GBS in response to the vaccine, estimates suggest that there was a risk of one additional case of GBS per 100 000 people vaccinated, against a background prevalence of GBS of 1–2·3 per 100 000 in the general population. On that occasion, the fears of a pandemic were not realised, a reminder that decisions about large-scale vaccination campaigns should weigh the risks of potential complications versus the benefits of vaccinating against a strain of influenza that has so far been relatively mild in the majority of people affected. Since the number of participants in most clinical trials of vaccines against H1N1 is unlikely to exceed 1500, the chances of detecting cases of GBS during the development phase are low. Timely reporting and analysis of any neurological complications during the immunisation period will therefore be essential. WHO has recommended that health authorities in countries capable of active surveillance for GBS should collaborate to develop common protocols and share results with WHO so that other countries using similar vaccines can benefit from the information. The UK Health Protection Agency has asked the British Neurological Surveillance Unit and the British Paediatric Surveillance Unit to assist with monitoring efforts; similarly, the CDC, in collaboration with the American Academy of Neurology, is likely to call upon neurologists to play a crucial part in monitoring for GBS and other potential neurological complications of the vaccines. Coordinated surveillance will be vital to estimate the overall burden of neurological complications, to be able to provide clear and consistent diagnostic and treatment guidelines, and to understand the mechanisms that predispose some people to influenza-related and vaccine-related neurological complications. The neurological community around the world should seize this opportunity to assist with surveillance efforts and engage in issues that are of paramount importance to public health.