National sentinel hospital-based surveillance for influenza-like illness (ILI) was launched in China in 2005. This type of surveillance is primarily dedicated to virologic surveillance with a goal of providing information for annual WHO influenza vaccine selection (Technical Appendix). Each week, 193 sentinel hospitals in 30 provinces report the total number of outpatient visits and the number of those patients with ILI by age group to a centralized online system maintained by the Chinese Center for Disease Control and Prevention (China CDC). In addition, respiratory specimens are collected each day from the first or second ILI case-patient who visits each hospital’s outpatient clinic. This collection results in virologic samples from 10–15 respiratory tract specimens per hospital each week. Specimens are sent to 1 of the 62 province- or prefecture-level disease control centers for testing. Laboratory results are reported weekly online to China CDC. These data are collected systematically throughout the year and are an unbiased sample of the timing of influenza activity.

During the early containment phase of the 2009 pandemic (until mid-July 2009), an individual case–based surveillance system was implemented. A(H1N1)pdm09 virus infection was added to China’s list of notifiable communicable diseases on April 30, 2009. Persons with suspected A(H1N1)pdm09 infection were identified through active surveillance with border entry screening and medical monitoring of close contacts exposed to confirmed case-patients or through passive reporting by clinicians when those patients sought health care. Any person entering China was required to undergo screening at the border (any point of entry into China from another country or from a neighboring region, such as Hong Kong Special Administrative Region), regardless of border type or travel mode. All patients with suspected A(H1N1)pdm09 virus infection, regardless of its clinical severity, were admitted to designated hospitals for containment (13,14). Upper respiratory specimens were collected and sent to the national sentinel ILI surveillance network of 62 laboratories for A(H1N1)pdm09 testing by real-time reverse transcription PCR (rRT-PCR) (Technical Appendix). All suspected and laboratory-confirmed cases were reported online within 24 hours to China CDC by public health officers in county-, prefecture-, and province-level disease control centers and clinicians nationwide. Data posted on a standardized reporting card included sex, age, place, overseas travel history, and date of symptom onset.

In accordance with recommendations from the Ministry of Health of China, local disease control centers were asked to investigate all institutional or community outbreaks (e.g., associated with particular schools or shared public transport vehicles) by using the case definition for acute respiratory illness (ARI). Data on all suspected cases, probable cases, and confirmed cases were reported online to China CDC.

In addition, through July 31, a joint team from local disease control centers and China CDC investigated confirmed international travel–related cases (Technical Appendix) to collect detailed epidemiologic information. A standardized questionnaire was used to collect data about international travel histories, date of symptom onset, and reported symptoms on arrival in China. Data on contacts were also obtained. In accordance with Ministry of Health recommendations, all close contacts of confirmed case-patients were quarantined at home or in designated hotels and monitored daily for fever and respiratory symptoms for 7 days after their last exposure to a confirmed case-patient.

We also learned whether the case was detected at the border. Data were not available on how these case-patients entered mainland China (e.g., by air, sea, or land).

A case-patient with ARI had fever (temperature >37.3°C), and/or recent onset of >1 of the following: rhinorrhea, nasal congestion, sore throat, or cough. A case-patient with ILI had a body temperature >38°C with either cough or sore throat in the absence of an alternative diagnosis. A person with a suspected case of A(H1N1)pdm09 virus infection had ARI and 1 of the following: illness onset within 7 days after travel to an area with >1 confirmed A(H1N1)pdm09 cases or within 7 days after close contact with a confirmed case-patient. A person with a confirmed case had ARI and laboratory evidence of A(H1N1)pdm09 virus infection diagnosed by rRT-PCR of respiratory specimens. A person with a probable case had ARI that was epidemiologically linked to a patient with a confirmed case. On the basis of information about overseas travel and any identified links to other known case-patients, all reported confirmed cases were classified as international travel–related cases, individual domestic cases, and institutional or community outbreaks.

By mid-August 2009, as A(H1N1)pdm09 activity expanded, the national surveillance strategy changed from individual case-based surveillance to identification of hospitalized patients who required medical treatment for complications, identification of outbreaks, and ongoing routine sentinel ILI surveillance. Only patients who required hospital care were admitted; patients with milder infection were cared for at home.

The serial interval of an infectious disease is defined as the time between onset of symptoms in an index patient and onset of symptoms in an infected contact. We analyzed data on transmission among the first 47 identified clusters we investigated, each with a single index case, to estimate the serial intervals associated with 60 infected contacts.

We estimated the incubation period distribution using data from the 22 persons with identified single-day exposures and the 35 persons with identified multiple-day exposure intervals (Technical Appendix Table 2), excluding 3 persons with exposures implying incubation periods of >20 days (Technical Appendix). We report the posterior median and 95% credible interval (CrI) of the mean and SD of the incubation period.

Doubling times in case numbers were estimated from the epidemic curve of weekly ILI incidence attributable to A(H1N1)pdm09 virus infection, obtained by multiplying raw ILI data by the weekly proportion of ILI case-patients who tested positive for A(H1N1)pdm09 virus. Those estimates, along with the evidence-based assumption that the generation time of influenza A(H1N1)pdm09 had a mean of 2.6 days and an SD of 1.3 days (3,5,6,15,16) (consistent with data analyzed on the serial interval), were used to estimate the effective reproduction number of A(H1N1)pdm09 virus infections in China. A simple epidemic model was fitted to the A(H1N1)pdm09 virus–attributable ILI case curve on the calendar weeks before and after the National Day Holiday (October 1–8) to estimate the effect of holidays on effective reproduction numbers and reporting rates. The model is based on the observation that numbers of cases increase at a rate that is a function of the reproduction number and the generation time of the disease (17). From the rate of growth of case numbers observed in the epidemic and the generation time of influenza A(H1N1)pdm09, the model can be used to derive the reproduction number of the disease for different intervals. In the past, this approach has been used to estimate the reproduction number of 1918 pandemic influenza in US cities (18).

International travel–related case-patients who had symptoms on arrival were classified as either “having fever” or “without fever but having respiratory symptoms” (Technical Appendix). Frequency tables (with χ² tests) were constructed to examine the univariate associations between the probability of detection at the border and patients’ characteristics. Univariable and multivariable logistic regression models were used to examine potential predictors of the probability of detection at the border (fever on arrival, time between onset and arrival, age group, and province) individually and simultaneously (i.e., using univariable and multivariable regression models, respectively) and to quantify their effects.

During May 7–November 30, 2009, a total of 71,665 persons with confirmed A(H1N1)pdm09 virus infection were reported to China CDC. Of those, 932 (1%) were related to international travel; 27,806 (39%) cases were detected during domestic outbreak investigations; and 42,917 (60%) were domestic nonoutbreak cases (Figure 1, panel A). The first case-patient was a traveler who returned from the United States with illness onset on May 7; the first domestic case-patient had symptom onset on May 10 (Figure 1, panels C, D). The origin of reported cases slowly shifted: most cases were international travel related until early June; in June, roughly half were international travel related and the other half were domestic; in July, most cases were domestic (Figure 1, panel C; Technical Appendix Figure 2). The last known international travel–related case was reported on July 31, after which intensive border entry screening was gradually reduced. Irrespective of the type of case, persons 5–24 years of age were most affected, with the proportion of cases ranging from 64% in international travelers to 94% in outbreak cases (Figure 1, panel B). The proportion of persons 25–49 years was <12% in all categories, except international travel–related cases, for which it was 28% (likely because persons 25–49 years were overrepresented among international travelers).

The infection spread rapidly throughout China; 11 provinces (containing many of the most globally connected cities) reported confirmed cases in May, and all but 5 western provinces reported cases in July (Figure 2). By September, all provinces reported confirmed cases. Geographic variation occurred in the incidence of confirmed cases per 1 million persons throughout the epidemic, but how much this variation was caused by surveillance system variation (e.g., differences in access, use of health care, in laboratory capacity) is difficult to determine.

The percentage of visits for ILI from sentinel surveillance increased slowly from May 2009 through the end of August 2009, although the percentage was lower than that observed during the same months in 2007 and 2008 (Figure 3, panel A). In September 2009, ILI activity increased substantially and was higher than in the 2 previous seasons. ILI activity decreased sharply during the National Day Holiday, then rebounded at the end of the holiday period. Similar fluctuations were observed for other influenza viruses (Figure 3, panel B). The number and proportion of influenza-positive cases from sentinel ILI surveillance increased stably from May 2009 onward; A(H1N1)pdm09 became the predominant strain at the end of September and subsequently declined after early December.

In the household setting, the average serial interval was 2.6 days (95% CI 2.2–3.0 days; Figure 4, panel A). Similar results were obtained in the analysis restricted to data from the 38 clusters in which the single index case-patient transmitted infection to a single contact. The incubation period had a mean of 2.2 days (95% CrI 1.9–2.5 days) and an SD of 1.0 days (95% CrI 0.8–1.2 days) (Figure 4, panel B).

We estimated that the effective reproduction number changed from 1.25 (95% CrI 1.22–1.28) before the National Day Holiday (August 31–September 30) to <1 during that holiday (0.79; 95% CrI 0.69–0.90) and back to 1.23 (95% CrI 1.15–1.32) after that holiday (October 7–October 25) (Figure 5, panel A; Table 1; Technical Appendix Table 1). The National Day Holiday was therefore found to reduce the effective reproduction number by 37% (95% CrI 28%–45%). Our model also predicted that underreporting had increased by 19% (95% CrI 6%–31%) and 32% (95% CrI 11%–48%), respectively during the first and second calendar weeks of the National Day Holiday. However, the 8-week summer school holiday appeared to have had a limited effect on transmission as measured by A(H1N1)pdm09 virus–attributable ILI incidence, in contrast to what was observed in other countries, such as the United Kingdom (19). The doubling time during the summer school holiday (8.7 days during July 13–August 30) was similar to that observed in the month after schools reopened in September (7.1 days) (Figure 5, panel B). Using the rate of growth observed during July–August (Figure 5, panel B), we extrapolated the A(H1N1)pdm09 virus–attributable ILI case curve back in time and inferred that the first sentinel-detected ILI case caused by A(H1N1)pdm09 virus occurred in China in week 19 (May 11–17), near the date when the first imported case was detected (May 11).

International travel–related cases were detected either at the border or later by contact tracing and passive case finding within the country. Overall, 37% of international travel–related cases ever detected were detected at the border. The timing of onset of symptoms affected the probability of detection by symptom screening at the border. Half (468/932) of international travel–related case-patients ever detected had onset of symptoms >1 days after arrival (Figure 5, panel C).

Among international travel–related case-patients who had symptoms on arrival, those with fever were significantly more likely to be detected at the border. The percentage of patients detected at the border was as follows: 76% for those with fever, 63% for those without fever but with respiratory symptoms (χ² 4.41; df 1; p = 0.036; n = 464). Overall, 74% of persons ever detected with symptom onset on or before the day of arrival were identified at the border. Multiple logistic regression modeling showed a significant interaction (p = 0.023) between whether a case-patient had a fever on arrival and the time between symptom onset and arrival (stratified by those with onsets 0 or 1 day before arrival and those with onsets >1 day before arrival; Table 2, Table 3). Thus, if a case-patient had a fever on arrival, then the time since onset was irrelevant. Similarly, the odds ratios (ORs) were similar for those with fever on arrival and onset 0 or 1 day before arrival (OR 1.80) relative to those with no fever and onset 0 or 1 day before arrival) and those with fever on arrival and onset >1 day before arrival (OR 1.91 relative to those with no fever and onset 0 or 1 day before arrival) (Table 3). However, among persons who did not have a fever on arrival, those who had been ill longer before arrival (>1 day) were more likely to be detected at the border (the percentage of detection = 83%, Table 2; OR 2.36, Table 3). After adjusting for these effects, neither age group nor province affected the probability of a case being detected at the border.