Through July 23, 2009, a total of 43,677 laboratory-confirmed infections with pandemic (H1N1) 2009 had been reported in the United States by the 50 states and the District of Columbia, including 5,009 hospitalizations and 302 deaths. To estimate the total number of cases of pandemic (H1N1) 2009, we built a probabilistic multiplier model that adjusts the count of laboratory-confirmed cases for each of the following steps: medical care seeking (A), specimen collection (B), submission of specimens for confirmation (C), laboratory detection of pandemic (H1N1) 2009 (D), and reporting of confirmed cases (E) (). This approach has been used to calculate the underrecognized impact of foodborne illness in the United States (3
Schematic of the steps involved in adjusting counts of reported cases of pandemic (H1N1) 2009 to estimate total cases.
At each step, we identified a range of proportions observed in prior published studies and recent surveys and investigations of pandemic (H1N1) 2009. These include 2 unpublished community surveys on influenza-like illness (ILI) and health-seeking behavior, the 2007 Behavioral Risk Factor Surveillance Survey conducted in 10 states and repeated in the same states during May 2009, and field investigations conducted during early outbreaks of pandemic (H1N1) 2009 in Chicago and Delaware (Technical Appendix
]). We theorized that, given recommendations for testing, patients hospitalized with pandemic (H1N1) 2009 would more likely have been tested and their cases reported than would outpatients. We therefore stratified our model between hospitalized and nonhospitalized cases (). For hospitalized patients, we used larger estimates of the proportion of specimens collected, tested, and reported, which resulted in smaller multiplier values (). We also adjusted for the fact that early in the epidemic physicians and health departments were encouraged to collect clinical specimens from all suspect case-patients with ILI and forward them for confirmatory testing with RT-PCR. By May 12, due to the increasing number of cases and the demands on public health laboratories, guidance for confirmatory testing was revised to focus on hospitalized patients. We therefore used a lower estimate for the proportion of specimens collected from patients with mild illness after that date, effectively increasing the multiplier for those patients ().
Model parameters and sources of data included in the model estimating prevalence of pandemic (H1N1) 2009, United States, April–July 2009*
Multipliers were calculated as the simple inverses of the proportions at each step. We accounted for variability and uncertainty in model parameters by using a probabilistic (Monte Carlo) approach (built by using SAS version 9.2; SAS Institute, Cary, NC, USA). For each parameter included in the model, we used uniform probability distributions that covered a range of minimum to maximum values, from which the model randomly sampled 10,000 iterations (Technical Appendix
). We generated median, upper, and lower 90% values for the number of total illnesses and hospitalizations.
To further divide estimated cases into age groups, we applied the age distribution of confirmed cases and hospitalizations as reported to the US Centers for Disease Control and Prevention through July 23, 2009 (Technical Appendix
), and calculated overall and age-specific incidence of illness and hospitalization, based on the US Census monthly population estimates for May 2009. We did not have age-specific parameter estimates, and thus did not stratify by age group within the model. This approach may not fully capture differences in the probability of ascertainment by age.
Using this approach, between April and July 2009, we estimate that the median multiplier of reported to estimated cases was 79; that is, every reported case of pandemic (H1N1) 2009 may represent 79 total cases, with a 90% probability range of 47–148, for a median estimate of 3.0 million (range 1.8–5.7 million) symptomatic cases of pandemic (H1N1) 2009 in the United States. Likewise, we estimate that every hospitalized case of pandemic (H1N1) 2009 that was reported may represent a median of 2.7 total hospitalized persons (90% range 1.9–4.3). This represents a median estimate of 14,000 (range 9,000–21,000) hospitalizations () and thus an estimated ratio of hospitalizations to total symptomatic cases of 0.45% (range 0.16%–1.2%).
Estimates of pandemic (H1N1) 2009–related cases and rates of illness and hospitalization by age distribution of confirmed case-patients, United States, April–July 2009
We also estimate that incidence of pandemic (H1N1) 2009 over the first 4 months of the pandemic in the United States ranged from a median of 107/100,000 in persons >65 years of age, to 2,196/100,000 in persons 5–24 years of age (). The incidence of hospitalization was estimated to be highest in young children <5 years of age (median 13.0/100,000, 90% range 8.8–20.2).