we began an epidemiologic investigation in osaka on may 17 , 2009 , and conducted face - to - face interviews . the definition of a confirmed case - patient was a person with influenza - like illness ( ili ) and laboratory confirmation of pandemic ( h1n1 ) 2009 virus infection by real - time reverse transcription pcr . ili was defined as the presence of a fever ( > 38.0c ) and acute respiratory symptoms ( cough or sore throat ) . local public health staff also conducted face - to - face or telephone interviews , or both , with other patients and persons in close contact with the case - patients until the end of may , when the local epidemic appeared to wane ( 1,6 ) . interviews were conducted by using a standard questionnaire to collect data on patient demographics , clinical course of illness , patient behavior , and history of patient contacts . by analyzing these data and careful investigation of contact history and epidemiologic links , we found 3 clusters in which disease transmission could have occurred before symptom onset in the index case - patients ( figure ) . three clusters of pandemic ( h1n1 ) 2009 presymptomatic transmission in may 2009 in osaka , japan . all cases were confirmed as pandemic ( h1n1 ) 2009 virus infection by real - time reverse transcription pcr . colors of the squares and circles denote the similar or different schools the students attended . the first outbreak in osaka occurred in 1 high school , and no community transmission had been verified in mid - may . case - patient 1 , a student at the high school , had symptoms on may 13 . case - patient 2 , the sister of case - patient 1 , had no symptoms while she was at school , according to her answer on the self - report survey as well as face - to - face interview carried out with a classmate who sat right behind her ( case - patient 3 ) . symptoms developed in the evening of may 15 after she returned home , and the school was closed proactively the following day . for case - patient 3 , who sat immediately behind case - patient 2 in class and chatted with her , influenza - related symptoms developed on may 17 . our investigation suggested that transmission of infection from case - patient 2 to case - patient 3 occurred during the presymptomatic phase of infection in case - patient 2 . case - patients 4 , 5 , and 6 were previously healthy boys and schoolmates of case - patients 2 and 3 . they played video games together in a small room on may 18 for several hours . he may have been infected by case - patient 2 at school , but we can not confirm this . they had no opportunity to be in contact with symptomatic persons other than case - patient 4 . thus , we concluded that case - patients 5 and 6 were likely infected by case - patient 4 before symptom onset . even if transmission from case - patient 2 were the reason that case - patients 5 and 6 became ill , transmission from a presymptomatic person likely occurred because case - patient 2 would have been asymptomatic when she met case - patients 5 or 6 , or both , at school . case - patient 8 was an elementary school pupil who lived in a different region from case - patients 17 . no cases of pandemic ( h1n1 ) 2009 had been reported in the area where he lived , including at his school , in mid - may . investigation results indicate that case - patient 7 was infected by a classmate other than case - patients 18 around may 16 ; this classmate was infected by a student at the same high school that case - patient 1 attended . on may 17 , 20 persons , including case - patients 7 and 8 , went on a 1-day trip to okayama prefecture , which is 180 km west of osaka . no positive results were reported by active surveillance for ili in okayama in mid - may . case - patients 7 and 8 stayed close together during the trip . in the evening of may 18 , case - patient 7 had a sore throat and cough , and he became febrile on may 19 . case - patient 8 had symptoms on may 21 , 3 days after case - patient 7 exhibited symptoms . the trip was the only opportunity for case - patient 8 to have been exposed to the virus . this indicates that transmission from case - patient 7 to case - patient 8 occurred on the day before symptom onset . our epidemiologic investigation results indicate that pandemic influenza virus ( h1n1 ) 2009 is infectious during the presymptomatic phase . our investigation was conducted in the early phase of the outbreak in japan . during this period , almost all persons with reported cases in osaka were students and their close contacts ( 1 ) . the institute had been conducting active surveillance for patients with ili and suspected pandemic ( h1n1 ) 2009 virus infection since april 2009 ( 7 ) . since mid - june , many community - transmitted cases had been reported in japan , thereby limiting the ability to find single exposure cases . , our results are valuable in terms of collecting information before the community spread of the virus . the mode of transmission of pandemic ( h1n1 ) 2009 is considered to be similar to that of seasonal influenza . the infectious period of seasonal influenza is measured from 1 day before symptom onset to 57 days after onset or until symptoms resolve ; this period is mainly based on experimental data on viral shedding ( 4,5 ) . regarding seasonal influenza , we found only 1 report documenting that a transmission took place during the presymptomatic phase , but the index case - patient of the report could have been in a presymptomatic ,  state because this case - patient did not feel completely well when the transmission took place ( 8) . our epidemiologic results provide useful clues for understanding the transmission of pandemic ( h1n1 ) 2009 virus . this finding of presymptomatic transmission has critical implications for public health because it indicates that viral transmission in communities can not be completely prevented solely by isolating symptomatic case - patients . two possible limitations of this report are the presence of unidentified case - patients and asymptomatic infected persons because our epidemiologic investigation was based on interviews with symptomatic patients and their close contacts . however , we could not find any cases that suggested infection from these kinds of cases during the early phase of the outbreak in japan . , our epidemiologic investigation results suggest that pandemic ( h1n1 ) 2009 is probably infectious during the presymptomatic period , at least 1 day before symptom onset .
during an epidemiologic investigation of pandemic influenza ( h1n1 ) 2009 virus infection in may 2009 in osaka , japan , we found 3 clusters in which virus transmission occurred during the presymptomatic phase . 
 this finding has public health implications because it indicates that viral transmission in communities can not be prevented solely by isolating symptomatic case - patients .