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A7 The Severity of Pandemic H1N1 Influenza in the United States, from April to July 2009: A Bayesian Analysis
Pages 208-247

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From page 208...
... 57 Department of Community Medicine and School of Public Health, Li Ka Shing Faculty of Medi cine, The University of Hong Kong, Hong Kong SAR, China. 58 Statistics, Modelling and Bioinformatics Department, Health Protection Agency Centre for Infec tions, London, United Kingdom.
From page 209...
... Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI]
From page 210...
... has been considerably higher than in recent years (Baker et al., 2009) , and anecdotal reports in the Southern Hemisphere have indicated that some intensive care units (ICUs)
From page 211...
... In the second (Approach 2) , we use self-reported incidence of ILI in New York City, and making the assumption that these ILI cases represent the true denominator of symptomatic cases, we directly estimate the ratio between hospitalizations, ICU admissions/mechanical ventilation, and deaths (adjusting for ascertainment)
From page 212...
... . In each case, prior distributions were used to quantify information on the probability that cases at each level of severity were detected; these prior distributions reflected the limited data available on detection probabilities and associated uncertainty.
From page 213...
... Milwaukee Data Between April 6 and July 16, 2009, Milwaukee recorded 3,278 confirmed cases and four deaths due to pH1N1, reflecting sustained efforts to test patients reporting ILI and their household contacts from the start of the epidemic in April until midJuly. On April 27, Milwaukee initiated protocols including recommendations for testing persons with influenza symptoms and travel history to areas reporting novel H1N1 cases, using a reverse transcriptase polymerase chain reaction (RT-PCR)
From page 214...
... While Milwaukee data were not the main source of estimates of ICU admission or death probabilities, we did employ hospitalized cases up to an episode date of June 14 to contribute to estimates of the ratio of deaths or ICU admissions to hospitalizations, since these should not be affected by failure to test mild cases. New York Case Data New York City maintained a policy from April 26 to July 7, 2009 of testing hospitalized patients with ILI according to various criteria.
From page 215...
... These data were used to inform detection probabilities. In addition, these data were used to inform a prior distribution on the ratio between symptomatic and medically attended cases, cM|S: these surveys estimated that between 42% and 58% of symptomatic ILI patients sought medical attention (Reed et al., 2009)
From page 216...
... . The probability d for each level was informed by evidence on the probability of testing at each level of severity (which may have depended on the sensitivity of the rapid test if this was required for PCR testing)
From page 217...
... dDW Deaths PCR test sensitivity Beta (45,5) Assumption (Reed et (Milwaukee)
From page 218...
... Our prior distributions for the number of symptomatic cases in New York (overall and by age) were taken as ranging uniformly between zero and the proportion reporting ILI in the telephone survey (with the upper bound of that distribution itself having a prior distribution reflecting the confidence bounds of the survey results; details in Text S1)
From page 219...
... , which uses Markov chain Monte Carlo to sample from the posterior distribution. Results Table A7-2 shows the numbers of medically attended cases, hospitalizations, ICU admissions, and deaths in the two cities, with the Milwaukee data separated into the period (to May 20)
From page 220...
...   1 (4%) 0 Total 788 25 147 25 4 Age Group Medically Attended Hospitalized ICU-admitted Dead (total)
From page 221...
... For example, among the four age groups, the symptomatic case-fatality ratio is highest in the 18- to 64-y age group with posterior probability 62%, and in those 65 and over with probability 38%. The symptomatic case-ICU admission ratio is highest in 18- to 64-year-olds with posterior probability 51% and in those over 65 with posterior probability 38%.
From page 222...
... Discussion We have estimated, using data from two cities on tiered levels of severity and self-reported rates of seeking medical attention, that approximately 1.44% of symptomatic pH1N1 patients during the spring in the US were hospitalized; 0.239% required intensive care or mechanical ventilation; and 0.048% died. Within the assumptions made in our model, these estimates are uncertain up to a factor of about 2 in either direction, as reflected in the 95% credible intervals associated with the estimates.
From page 223...
... To date, symptomatic attack rates seem to be far lower than 25% in both the completed Southern Hemisphere winter epidemic and the autumn epidemic in progress in the US; severe outcomes seem to be considerably less numerous than those described for Approach 1 with a 25% attack rate. In New Zealand, just
From page 224...
... Worryingly, our estimates of the pro portion of symptomatic cases requiring mechanical ventilation or ICU care was approximately 4–5 × our estimate of the sCFR. It is possible that a substantial proportion of those admitted to ICUs could have died without intensive care.
From page 225...
... Third, the symptomatic CFR, CIR, and CHR are dependent upon our estimates of the true number of symptomatic cases, NiSk, and hence are sensitive to the choice of prior distribution for these, as well as to our prior assumptions on the detection probabilities. In particular, if the probability that symptomatic patients seek medical attention and are confirmed is lower than we assume in our prior distributions, then there are more cases than are inferred by our model, and severity is correspondingly lower than our estimates.
From page 226...
... However, self-reported ILI is notoriously prone to various biases, most of which suggest that true rates are probably lower than selfreported rates. A previous telephone survey conducted in New York City found that 18.5% of New Yorkers reported ILI in the 30 d prior to being surveyed in late March 2003 (Metzger et al., 2004)
From page 227...
... . Under Approach 1, and assuming a typical pandemic symptomatic attack rate of 25%, the estimated number of hospitalizations for an autumn–winter pandemic wave is considerably more than the approximately 300,000 estimated for typical seasonal influenza (Thompson et al., 2004)
From page 228...
... If attack rates in the autumn match those of prior pandemics and hospitalization rates are comparable to our estimates using Approach 1, the surge of ill individuals and subsequent burden on hospitals and intensive care units could be large. However, using Approach 2, estimates of hospitalizations and ICU admissions are considerably lower.
From page 229...
... Nair, Yuk-Wah (Fran) Ng, Trang Nguyen, Diana Nilsen, Janet Nival, Jennifer Norton, William Oleszko, Carolyn Olson, Marc Paladini, Lucille Palumbo, Peter Papadopoulos, Hilary Parton, Jacob Paternostro, Lynn Paynter, Krystal Perkins, Sharon Perlman, Haresh Persaud, Charles Peters, Melissa Pfeiffer, Roger Platt, Lindsay Pool, Amado Punsalang, Zahedur Rasul, Valerie Rawlins, Vasudha Reddy, Anne Rinchiuso, Teresa Rodriguez, Ramon Rosal, Maureen Ryan, Michael Sanderson, Allison Scaccia, Amber Levanon Seligson, Jantee Seupersad, Joanne Severe-Dildy, Asma Siddiqi, Ulirike Siemetzki, Tejinder Singh, Sally Slavinski, Meredith Slopen, Timothy Snuggs, David Starr, Catherine Stayton, Alaina Stoute, Jacqueline Terlonge, Alexandra Ternier, Lorna Thorpe, Catherine Travers, Benjamin Tsoi, Kimberly Turner, Joan Tzou, Shameeka Vines, Elizabeth Needham Waddell, Donald Walker, Connie Warner, Isaac Weisfuse, Don Weiss, Antoinette Williams-Akita, Elisha Wilson, Eliza Wilson, Marie Wong, Charles Wu, David Yang, Mohammad Younis, Sulaimon Yusuff, Christopher Zimmerman, and Jane Zucker.
From page 230...
... The New York City Swine Flu Investigation Team, who designed the surveillance for NYC, collected, cleaned, and did initial analyses of the data, is responsible for the data integrity of the NYC data and shared it with the other authors, and played a significant role in revising the paper and thinking through the analyses. Editor's Summary Background Every winter, millions of people catch influenza -- a viral infection of the airways -- and about half a million people die as a result.
From page 231...
... Similarly, the estimated burden on hospitals and intensive care facilities ranges from somewhat higher than in a normal influenza season to considerably lower. The findings of this study also suggest that, unlike seasonal influenza, which kills mainly elderly adults, a high proportion of deaths from pH1N1 infection will occur in nonelderly adults, a shift in age distribution that has been seen in previous pandemics.
From page 232...
... Virus - United States, 2009. MMWR Morb Mortal Wkly Rep 58: 826–829.
From page 233...
... Using a population-based telephone survey to estimate the ­syndromic multiplier. MMWR Morb Mortal Wkly Rep 53 Suppl: 106–111.
From page 234...
... the case-fatality ratio, defined as the ratio of the true number of H1N1pdm attributable deaths to the true number of H1N1pdm infections; we denote this cD|Inf because it is a conditional probability, Pr{death | infection}; 62 Medical Research Council Biostatistics Unit, Cambridge, UK. 63 Statistics,Modelling and Bioinformatics Department, Health Protection Agency Centre for Infections, London, UK.
From page 235...
... First, we combine data from both Milwaukee and New York on medically attended symptomatic cases, hospitalizations, ICU admissions and deaths, together with information from the Centers for Disease Control (CDC) on ascertainment probabilities and proportions of symptomatic cases seeking medical attention, to estimate the ratios cD|S, cI|S and cH|S, assuming the conditional probabilities are equal, but age-specific, across the two jurisdictions.
From page 236...
... . We consider age-group specific values for all of these conditional probabilities so all carry a subscript i for age group and we denote the actual number of people who reached a given level of severity in a given jurisdiction by Ns for symptomatic cases, NM for medically attended cases, NH for hospitalizations, NI
From page 237...
... medically attended infection)
From page 238...
... However, we do observe detected medically attended cases OiMW and detected hospitalizations OiHW in Milwaukee, and we observe detected hospitalizations OiHN, detected ICU stays OiIN, and detected deaths OiDN in New York City. We assume that these observations O are related to the true numbers N as follows: OiMk ~ Binomial (NiMk,dM)
From page 239...
... . R01627 Circles denote parameters, double circles denote parameters for which we have prior information, and squares denotebitmapped uneditable observations.
From page 240...
... Providers were advised about concerns regarding the accuracy of rapid flu tests and urged to use PCR as the preferred method for analysis. All confirmed and probable cases were entered into a line list on a rolling basis, and we used a line list dated July 21.
From page 241...
... were tested with a rapid influenza antigen test. Those patients who tested positive, and also any patient on a ventilator or in an intensive care unit (ICU)
From page 242...
... to account for imperfect PCR test sensitivity. We assume the same priors for the detection probabilities in ICU admissions.
From page 243...
... As noted above, we made no effort to account for censoring of hospitalized cases. 4e.  Detection of ICU admissions, New York Here we assume that detection is equal to the sensitivity of the PCR test, dIN ~ Uniform(.95,1)
From page 244...
... : we have not observed medically attended cases in New York, so cannot use the observation as a lower limit. We used an upper bound of symptomatic infection in New York City based on the number of persons reporting ILI in a telephone survey conducted by the New York City Department of Health and Mental Hygiene covering a 30-day period in May-June at the height of the spring epidemic (NYC DOHMH, unpublished data)
From page 245...
... However, it would not be reasonable to assume a maximum clinical attack rate of less than the telephone survey estimates for New York or less than 25% for Milwaukee, given our lack of prior knowledge on these. For this reason we do not report estimates of the total number symptomatic.
From page 246...
... (2009) Estimating the burden of pan demic influenza A/H1N1 -- United States,R01627 April-July 2009.
From page 247...
... APPENDIX A 247 FIGURE A7-6  Prior vs posterior number of symptomatic infections, by age, Approach 1. Figure A7-6 R01627 uneditable bitmapped image


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