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NBSB Pandemic Influenza Working Group Detailed Report infected? Another key question is whether vaccinating children first will protect the rest of the population. Other mitigation options include use of antivirals to treat infection, although they are only effective in reducing disease transmission if given early—for example, within 24 hours of the first symptoms. Prophylactic use of antivirals can be very effective in reducing transmission, but supplies are insufficient in the United States. At the peak of the pandemic, school closures could reduce transmission by 40%, but they are disruptive and may not have as large an impact on the total numbers affected. Combining interventions may rise in importance if the health care system is overwhelmed. Key current issues include the severity of the pandemic, the potential health impact, and the impact on the overall health care system. Interventions must be seen as justified and tolerated by the community. The speed of disease spread and the number of people infected so far are important issues. Understanding the real-world effects of interventions is crucial. Judging the appropriate response to a pandemic requires decision-makers to balance the cost of interventions against the economic impact of the pandemic. Around the world, a wide range of policies is in place, and some countries choose to do relatively little in response. The United Kingdom has undertaken an intensive containment effort that includes prophylaxis. The challenge of assessing the severity of the disease lies in the fact that the numerator is uncertain and the denominator is not clear at all. Surveillance is worse in the United Kingdom, Mr. Ferguson said: 20 cases in which patients were hospitalized were reported by chance, not through systematic surveillance. Some U.S. States have more systematic surveillance in place, but the CDC estimate of 45–85 deaths to date is a minimum. The lag between disease onset and death can lead to underestimating the severity of disease. Very little data exists on case-fatality rates for seasonal influenza and previous pandemics. The age groups affected by seasonal influenza may be different from those affected by pandemic influenza, and while the absolute numbers for morbidity and mortality in people ages 18–50 years could be low, it could also be much higher than expected. The severity of the pandemic in the fall may differ from its current severity. On the basis of data from Mexico, transmissibility of H1N1 virus is faster than the spread of seasonal influenza but slower than seen in previous pandemics, which may reflect seasonality or suggest that the virus is not fully adapted to humans. Mr. Ferguson said it is difficult to model the spread of the disease in the United States, as the data do not account for variable case ascertainment. Household transmission data, however, may be more reliable. Secondary attack rates indicate levels of spread comparable to seasonal influenza but low for a pandemic. Mr. Ferguson projected a virus doubling time as short as two days in the fall (currently, it’s about seven days). In households, children are twofold more susceptible to the virus than adults, and children under age 5 years are even more susceptible. 12
NBSB Pandemic Influenza Working Group Detailed Report Also on the basis of data from Mexico, children appear to be at highest risk of infection but the illness is nearly always mild. U.S. and U.K. data also show that children are principally affected. The pattern of severe disease, Mr. Ferguson noted, is complex. Adults ages 20–50 years, especially those with asthma or chronic obstructive pulmonary disorder, may be at higher risk. The challenge is whether to target those with the highest rates of infection or those at the highest risk of severe disease. In the United Kingdom, everyone with a confirmed case of H1N1 influenza is treated and household contacts of people with confirmed H1N1 influenza receive prophylaxis with TamiFlu. When disease is treated within three days of onset, about 20% fewer cases occur. Households that received prophylaxis within three days of the index case had dramatically lower attack rates (no cases in 42 household contacts). Among those who received prophylaxis more than three days after the onset of disease, the index case saw an attack of 13%. Therefore, early prophylaxis appears to be very effective. The Southern Hemisphere is now entering its typical influenza season, so more rapid spread is anticipated. It is expected that the pandemic will spread more rapidly in the Northern Hemisphere when influenza season begins here. More surveillance and field data are needed to better understand what’s going on. Predictions are hampered now because of the lack of data on the total number of people affected and the real impact of seasonality on the disease. Mr. Ferguson estimated that 3 million people in the United States have been infected so far, and he suggested that may be about 5% of the number of infections expected for the year. The critical questions will be how quickly the disease will spread and how long the pandemic will last. In terms of research priorities, Mr. Ferguson said serologic surveys are key to understanding the prevalence of disease. Cohort studies are needed because they provide unique insights into transmissibility. Community cohort studies can be undertaken with intensive monitoring and biological sampling. Web cohorts can provide a sample size larger than a community. Both approaches can demonstrate the severity of disease and transmission over time. Mr. Ferguson hoped that CDC would provide surveillance reports weekly throughout the summer and fall. Finally, mechanisms are needed to monitor the effectiveness of interventions. In summary, Mr. Ferguson said to expect that about one third of the population will be sick over a concentrated period of about 8–12 weeks in the fall. Local epidemics will seem to be more “peaky” than national averages suggest, especially if sick people stay home. Combining interventions has a high impact, but consideration must be given to what interventions people will tolerate. Decisions must be made about intervention without much data, because the severity of the disease will only be well measured in retrospect. The current virus is not seasonal influenza—animal models indicate it is a different pathogen, and the virus may not be fully adapted to humans. The incubation period may be longer than seasonal influenza and may evolve over months. Precautionary efforts should seek to put mechanisms in place now for severe disease, but 13
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