Perspectives on the pandemic: Lessons learned

For the past decade my colleagues and I have been working with the CDC to track influenza infections in children through active surveillance in our community. One day this past April I was talking with a colleague at the CDC, when she related that they had just isolated novel swine H1N1 influenza viruses from two children in California during similar surveillance activities. Neither of us would have predicted that these strains would be the origin of the next global pandemic or the impact that this new virus would have on children in the United States and globally.

As the next few weeks evolved, scientists molecularly characterized the H1N1 strain and discovered genetic elements derived from avian, human and both Eurasian and North American swine strains. The novel influenza strain was identified as a result of enhanced respiratory surveillance in children and the rapid referral of the influenza isolate to the CDC for further study.

This new strain was also responsible for a widespread outbreak in Mexico and global dissemination of the virus occurred rapidly.

Most influenza epidemiologists believe that this H1N1 strain had been circulating in the swine population for some time, but had gone undetected. Active surveillance in the swine population would have likely identified its evolution more rapidly and might have provided an isolate that could have been more quickly adapted to vaccine production. The first lesson to be learned from this pandemic is that enhanced national and international surveillance is needed in both the human and animal populations and that the rapid identification of new and evolving strains spreading from animals to humans, or from humans to humans, is needed to generate stock viruses for accelerated vaccine development.

When local pediatricians reported influenza-like illnesses in children returning from Mexico, we identified the first cases of the novel H1N1 virus in our community. Although only one child was hospitalized with respiratory symptoms early in the outbreak; most children were only seen in the clinic, presenting with clinical manifestations similar to yearly seasonal influenza. Based on early CDC guidelines, we promptly treated these children with neuraminidase inhibitors and soon the H1N1 influenza activity waned.

However, mindful that the usual influenza season was just beginning in the southern hemisphere, we worked closely with colleagues in Buenos Aires to chart the affect of the novel strain on pediatric hospitalizations in that region.

We conducted a retrospective case series enrolling children with acute respiratory infections or fever who were diagnosed to have novel H1N1 infection by reverse transcriptase polymerase chain reaction (RT-PCR) and admitted to one of six public hospitals in Buenos Aires. We compared numbers of admissions and deaths associated with the new H1N1 strain with age-matched children admitted with seasonal influenza in previous years.

Between May and July of 2009, 251 children were hospitalized in these six hospitals, doubling the number of admissions for influenza compared with previous influenza seasons. Of the hospitalized children, 19% were admitted to intensive care units, 17% required mechanical ventilation, and 5% died. The overall number of children that died was 10-fold higher than those seen in previous seasons. Most of the deaths were due to refractory hypoxia and many occurred in children younger than 1 year. Nine of the 13 children who died had underlying high risk medical conditions, such as asthma, chronic pulmonary disease and neurologic conditions.

When school resumed in the United States in September, H1N1 returned to our community, and subsequently spread to other regions of the country. Nearly identical to our findings in Buenos Aires, children were particularly affected with marked increases in clinic and emergency department visits and hospitalizations. Overall, the CDC has projected that nationally, through Jan. 16, 2010, there have been 57 million cases of novel H1N1 infections, more than 250,000 hospitalizations, and 11,670 deaths. The burden of the pandemic has been particularly great for those with underlying high risk medical conditions such as asthma, cardiopulmonary disease and immunosuppression.

The second lesson to be learned from this pandemic is that both the pandemic strain and the usual seasonal strains are formidable pediatric pathogens, particularly in high risk children.

Vaccine development

Vaccine development was a high priority from the onset of the pandemic and once the viral seed strain was available to the manufacturers, vaccine production began. Capacity had been enhanced over the past several years through pandemic preparedness funding. However, the seed strains were difficult to derive and reached the manufacturers later than desired.

When the first vaccine strains were available, we began safety and immunogenicity studies through our NIH-funded Vaccine Treatment and Evaluation unit (VTEU), first in adults and then rapidly moving to children aged 6 months to 18 years in August. Several hundred trial participants were enrolled at each of the VTEU study sites and the vaccines were shown to be associated with few local or systemic adverse events. The reaction profiles were comparable to those of the seasonal vaccines, as would be expected since both the novel H1N1 and the seasonal vaccines are produced in exactly the same manner.

The third lesson of the pandemic was that pandemic preplanning had increased the capacity to produce influenza vaccine, but that the process needed to be further streamlined.

One of the most distressing aspects of the pandemic has been the lack of public acceptance of the safety of the vaccine. One potential reason for this distrust might have been the association with Guillain-Barre syndrome with the earlier swine vaccination program in 1976. Another reason could be media and Internet reports of adverse events temporally related to, but not causally related to the vaccine. The fourth lesson of the pandemic is that we need to better understand the reasons for vaccine refusal and how we might overcome these concerns.

The pandemic has reaffirmed that influenza is a serious disease and that the virus has an amazing ability to evolve. It has also shown us that influenza vaccines are safe and effective and that they should be used, while simultaneously working to improve surveillance and the speed of vaccine manufacture. Finally, the novel H1N1 will likely be incorporated into the seasonal vaccine for next season and recommended by the ACIP and AAP for universal administration to all children.

Kathryn M. Edwards, MD, is a Sarah H. Sell Professor of Pediatrics at Vanderbilt University Medical School in Nashville.