Clinical and Epidemiologic Characteristics of 3 Early Cases of Influenza A Pandemic (H1N1) 2009 Virus Infection, People’s Republic of China, 2009

A national network is essential for controlling this infection.

and Mexico (3) and spread rapidly to other regions of the world (4,5). Pandemic (H1N1) 2009 virus has been reported to be a triple reassortant influenza virus (containing genes from human, porcine, and avian influenza viruses) that has circulated among swine in the United States since 1999 (6)(7)(8). Sporadic human infections by influenza virus of swine origin had been described, mostly in young persons in contact with pigs (9). The current outbreak indicates that the new pandemic (H1N1) 2009 virus can be transmitted from human to human. As of June 17, 2009, a total of 88 countries officially reported a cumulative total of 39,620 laboratory-confirmed pandemic (H1N1) 2009 cases; these cases occurred in Mexico ( A confirmed case of human infection with pandemic (H1N1) 2009 virus was defined as laboratory confirmation of infection from a human sample at the Chinese CDC or the Chinese Academy of Medical Sciences (CAMS) (see the Laboratory Confirmation section below). A suspected case was defined as 1) an influenza-like illness (ILI; fever >37.5°C with at least 1 symptom or sign, including sore throat, cough, rhinorrhea, nasal congestion) in a person who has traveled to a country where >1 confirmed pandemic (H1N1) 2009 cases had been found in the past 7 days, or 2) clinical symptoms or signs of ILI in a person with an epidemiologic link to a patient found to have confirmed or suspected pandemic (H1N1) 2009 in the previous 7 days.
Close contacts were defined as persons who had lived with a person with probable or confirmed pandemic (H1N1) 2009 or who had had direct contact with the respiratory secretions or body fluids of such persons. All close contacts were quarantined for medical observation for 7 days; during this time, pharyngeal swabs were collected for identification of pandemic (H1N1) 2009 virus (once if results were negative; serial repeat tests if results were positive).
All suspected cases were required to be reported to the Chinese CDC and to the MOH within 24 hours of diagnosis. Pharyngeal swabs were forwarded to a local branch of the Chinese CDC for detection of influenza A pandemic (H1N1) 2009 virus by real-time reverse transcription-PCR (RT-PCR). All patients with a positive RT-PCR result for pandemic (H1N1) 2009 virus were admitted to the local infectious disease hospital where the patient was placed in isolation. Additional specimens were sent to the State Reference Influenza Laboratories at the Chinese CDC or CAMS for further characterization and nucleic acid sequencing.
A standardized surveillance reporting form was used to collect clinical, epidemiologic, or demographic data. We included information about the patient's demographic characteristics, underlying medical conditions, status with respect to seasonal influenza vaccination, exposures to swine and other animals, travel to a country with confirmed pandemic (H1N1) 2009 infection, clinical signs and symptoms, chest radiograph results, laboratory findings, results of diagnostic testing for influenza, antiviral treatment, clinical complications, and clinical outcome.

Laboratory Confirmation
Pharyngeal swabs were collected from all patients and their close contacts, which were submitted to local branch of the Chinese CDC and reference laboratories in the Chinese CDC or CAMS for investigation. We used the protocol of the US Centers for Disease Control and Prevention of realtime RT-PCR for pandemic (H1N1) 2009 as recommended by the World Health Organization (11). The PCR products were sequenced for further confirmation by standard highthroughput sequencing system with the use of BigDye Terminator, version 3.1 (Applied Biosystems, Foster City, CA, USA) with 1 mm 3 of double-stranded template.

Results
The demographic and epidemiologic characteristics of the 3 patients with confirmed pandemic (H1N1) 2009, including the estimated disease incubation period and their travel histories, are listed in Table 1. Their clinical characteristics are shown in Table 2. All 3 patients were Chinese students who had been studying abroad (2 in United States and 1 in Canada  Table 3). The dynamic virologic monitoring of pharyngeal swab samples from the 3 case-patients showed that realtime RT-PCR results for influenza A pandemic (H1N1) 2009 virus were negative on day 5, day 7, and day 6, respectively (Table 3).
Only 1 sample from a total of 186 close contacts tested positive for pandemic (H1N1) 2009 virus by real-time RT-PCR. This sample came from the 48-year-old mother of patient 3, who had lived with patient 3 for 2 days before her illness and had taken care of her for 2 days after her illness began. On the fifth day (May 16) after exposure to patient 3, the woman's sample became positive ( Table 3). As with all the other close contacts, this woman had no fever or ILI symptoms.

Discussion
The 3 cases were mild, and the patients were young, which is consistent with the profile of other pandemic (H1N1) 2009 infections reported around the world (6). The most frequent signs and symptoms in the patients were fever and other manifestations that were nonspecific for pandemic (H1N1) 2009 and indistinguishable from those of seasonal influenza. None of them had evidence of severe lower respiratory tract illness or unusual symptoms of influenza, such as diarrhea. All patients recovered quickly, with a median duration of fever of 3 days. All 3 patients had complete blood counts performed during the course of their disease, but none had leukopenia (leukocyte count <4,000/ mm 3 ), or lymphopenia (total lymphocyte count <800/mm 3 ), or thrombocytopenia (total platelet count <100,000/mm 3 ).
The transmissibility of influenza A pandemic (H1N1) 2009 virus is uncertain. One study assumed that its transmissibility (R 0 ) is substantially higher than that of seasonal influenza and comparable with the viruses in previous influenza pandemics (12). Our study demonstrates, on the basis of PCR testing, that the average time of pandemic (H1N1) 2009 virus shedding is 4-6 days. Positive RT-PCR results do not necessarily confirm virus shedding, but the PCR-based method is more sensitive than culture methods for detecting virus shedding (13). Our study also shows that the risk for person-to-person transmission is greatest in households. Among 186 close contacts, only the mother of patient 3, who lived with her, had a positive result for pandemic (H1N1) 2009 virus by real-time RT-PCR, although she had no symptoms of influenza. All other close contacts, including taxi drivers, passengers in an airplane or the same car of a train, were negative for pandemic (H1N1) 2009 virus at screening, and illness did not develop subsequently while they were being observed. Asymptomatic infections appear to be possible among household members, as demonstrated by case-patient 3 and her mother.
Our study has several limitations. First, numbers in this series were low. Second, the exact date of exposure to a known infectious source was difficult to trace. Third, pharyngeal swab samples may have a lower sensitivity (than nasopharyngeal), and thus some false-negative results might have occurred, which could lead to underestimation of viral shedding.
A national network for the surveillance and control of pandemic (H1N1) 2009 was quickly organized in China, and the response was quick and thorough. The Chinese government is moving swiftly to contain the new influenza, drawing on lessons from the severe acute respiratory syndrome and bird influenza outbreaks in recent years. In all airports, thermal scanners have been installed, and all asymptomatic contacts of case-patients were quarantined for 7 days as part of the early response. As the number of imported cases has increased, the quarantine policy is changing. During the past 4 weeks, only symptomatic travelers at ports of entry and passengers sitting within a short distance (<2 m) to a person with a suspected or confirmed case were quarantined. As local transmission has been documented, more efforts have been paid to communities. Since June 22, hand temperature monitors were used in all schools in Beijing. All students with body temperatures >37.2°C were asked to stay at home until their temperature returned to normal. Further evaluation is needed to continue to clarify the nature of pandemic (H1N1) 2009, including its clinical features, severity, incubation period, and transmission patterns (14).
Dr Cao is the director of the Department of Infectious Diseases and Clinical Microbiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing. His research interests focus on the diagnosis and treatment of respiratory tract infections. - Discharged --10 Discharged -