Significance of Seasonal Influenza Viruses in the Stool of Pediatric Patients (2010)

To the Editors: Seasonal influenza patients occasionally exhibit gastrointestinal symptoms (e.g. diarrhea, vomiting, and abdominal pain).1,2 The RNA of these viruses has been detected in the fecal excretion of infected pediatric patients3,4; however, these studies did not attempt to detect infectious viruses in the specimens. Accordingly, the significance of fecal excretion of seasonal influenza viruses to public health remains unknown. We investigated the presence of influenza viral genes and infectious virus in stool specimens collected from 18 pediatric influenza patients who presented to the pediatric services at Tokyo Saiseikai Central Hospital (Tokyo, Japan) during the August 2007 and September 2008 influenza seasons. None of the patients was immunocompromised or receiving corticosteroids or immunosuppressive drugs. Informed written consent was obtained for each child. All patients exhibited fever (>37.5°C) and upper respiratory symptoms and were diagnosed by using an influenza rapid diagnosis kit. In total, 28 stool specimens were collected from 18 pediatric influenza patients within 6 days of onset of illness for each case (Table, Supplemental Digital Content 1, https://links.lww.com/INF/A436). To detect influenza viral genes in the stool specimens, we used a 1-step reverse transcription-polymerase chain reaction method with hemagglutinin gene-specific primers. The limit of our system for detecting A/Aichi/2/1968 (H3N2) virus in control stool was 2.6 × 102 plaque-forming units per milliliter. By using this method, we detected viral genes in 15 stool samples collected from 11 patients: 9 of whom were infected with H1N1 and 2 with H3N2 viruses (Table, Supplemental Digital Content 1, https://links.lww.com/INF/A436). We detected no viral genes in swabs of hand, neck, and groin skin collected from the patients with viral gene-positive stool samples. Among the 7 children exhibiting gastrointestinal symptoms, 5 (71%) had viral gene-positive stool samples, whereas viral genes were detected in 6 (54%) of 11 patients without gastrointestinal symptoms. Further, 2 (29%) of 7 patients exhibiting gastrointestinal symptoms tested negative for viral genes in their stool specimens. To isolate infectious virus from stool samples, the specimens were inoculated into Madin-Darby canine kidney cells; infectious influenza virus was isolated from only 1 stool specimen. These results suggest that the presence of viral genes, as detected by reverse transcription-polymerase chain reaction, in stool samples may not be associated with virus infection in intestinal organs. It may be that the viral genes in stool specimens are derived from respiratory secretions that are swallowed. While we were preparing this article, Dilantika et al5 reported detection of an infectious influenza B virus in the stool of a seasonal influenza patient. Although they concluded that viable influenza virus from stool could be a potential mode of transmission of seasonal influenza viruses, the prevalence of infectious virus-positive stool samples was limited: an infectious virus was detected in the stool sample of only 1 of 13 patients who were viral gene-positive. Collectively, these results indicate that fecal excretion of seasonal influenza viruses is unlikely to be a major public health concern. Daisuke Tamura, MD Division of Virology Department of Microbiology and Immunology Institute of Medical Science University of Tokyo Motoko Fujino, MD Department of Pediatrics Tokyo Saiseikai Central Hospital Tokyo, Japan Makoto Ozawa, DVM, PhD International Research Center for Infectious Diseases Institute of Medical Science University of Tokyo Tokyo, Japan Influenza Research Institute School of Veterinary Medicine University of Wisconsin-Madison Madison, WI Kiyoko Iwatsuki-Horimoto, DVM, PhD Hideo Goto, DVM, PhD Yuko Sakai-Tagawa, PhD Taisuke Horimoto, DVM, PhD Division of Virology Department of Microbiology and Immunology Institute of Medical Science University of Tokyo Mari Nirasawa, MD Department of Pediatrics Tokyo Saiseikai Central Hospital Tokyo, Japan Yoshihiro Kawaoka, DVM, PhD Division of Virology Department of Microbiology and Immunology International Research Center for Infectious Diseases Institute of Medical Science University of Tokyo Tokyo, Japan Influenza Research Institute School of Veterinary Medicine University of Wisconsin-Madison Madison, WI ERATO Infection-Induced Host Responses Project Japan Science and Technology Agency Saitama, Japan [email protected]