Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.
机构:
Univ Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Harvey, Soriah M.
Murphy, Vanessa E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Murphy, Vanessa E.
Gibson, Peter G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Newcastle, Prior Res Ctr Hlth Lungs, Resp Dept, Newcastle, NSW, Australia
Hunter Med Res Inst, Newcastle, NSW, Australia
John Hunter Hosp, Dept Resp & Sleep Med, Newcastle, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Gibson, Peter G.
论文数: 引用数:
h-index:
机构:
Collison, Adam
Robinson, Paul
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Westmead, Woolcock Institue Med Res, Dept Resp Med, Sydney, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Robinson, Paul
Sly, Peter D.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Queensland, Child Hlth Res Ctr, Childrens Hlth & Environm, South Brisbane, Qld, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Sly, Peter D.
Mattes, Joerg
论文数: 0引用数: 0
h-index: 0
机构:
Univ Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
John Hunter Childrens Hosp, Dept Paediat Resp & Sleep Med, Newcastle, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Mattes, Joerg
Jensen, Megan E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX1 2JD, England
Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, AustraliaUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Anders, Katherine L.
Nguyen, Hoa L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen, Hoa L.
Nguyet Minh Nguyen
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Hosp Trop Dis, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyet Minh Nguyen
Nguyen Thi Van Thuy
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen Thi Van Thuy
Nguyen Thi Hong Van
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen Thi Hong Van
Nguyen Trong Hieu
论文数: 0引用数: 0
h-index: 0
机构:
Hung Vuong Hosp, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen Trong Hieu
Nguyen Thi Hong Tham
论文数: 0引用数: 0
h-index: 0
机构:
Dong Thap Hosp, Cao Lanh, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen Thi Hong Tham
Phan Thi Thanh Ha
论文数: 0引用数: 0
h-index: 0
机构:
Dist 8 Hosp, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Phan Thi Thanh Ha
Le Bich Lien
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp 1, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Le Bich Lien
Nguyen Van Vinh Chau
论文数: 0引用数: 0
h-index: 0
机构:
Hosp Trop Dis, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen Van Vinh Chau
Vu Thi Ty Hang
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Vu Thi Ty Hang
van Doorn, H. Rogier
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX1 2JD, EnglandUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
van Doorn, H. Rogier
Simmons, Cameron P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX1 2JD, England
Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, AustraliaUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
机构:
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Ahmadi, Sara
Patel, Sanket
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Patel, Sanket
Gibson, Molly K.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Gibson, Molly K.
Wang, Bin
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Wang, Bin
Ndao, I. Malick
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Ndao, I. Malick
Deych, Elena
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Biostat, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Deych, Elena
Shannon, William
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Biostat, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Shannon, William
Tarr, Phillip I.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Tarr, Phillip I.
Warner, Barbara B.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Warner, Barbara B.
Dantas, Gautam
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA
Washington Univ, Dept Biomed Engn, St Louis, MO 63130 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
机构:
Univ Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Harvey, Soriah M.
Murphy, Vanessa E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Murphy, Vanessa E.
Gibson, Peter G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Newcastle, Prior Res Ctr Hlth Lungs, Resp Dept, Newcastle, NSW, Australia
Hunter Med Res Inst, Newcastle, NSW, Australia
John Hunter Hosp, Dept Resp & Sleep Med, Newcastle, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Gibson, Peter G.
论文数: 引用数:
h-index:
机构:
Collison, Adam
Robinson, Paul
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Westmead, Woolcock Institue Med Res, Dept Resp Med, Sydney, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Robinson, Paul
Sly, Peter D.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Queensland, Child Hlth Res Ctr, Childrens Hlth & Environm, South Brisbane, Qld, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Sly, Peter D.
Mattes, Joerg
论文数: 0引用数: 0
h-index: 0
机构:
Univ Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
John Hunter Childrens Hosp, Dept Paediat Resp & Sleep Med, Newcastle, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
Mattes, Joerg
Jensen, Megan E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, AustraliaUniv Newcastle, Hunter Med Res Inst, Sch Med & Publ Hlth, Resp Dept,Prior Res Ctr Grow Well, Newcastle, NSW, Australia
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX1 2JD, England
Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, AustraliaUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Anders, Katherine L.
Nguyen, Hoa L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen, Hoa L.
Nguyet Minh Nguyen
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Hosp Trop Dis, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyet Minh Nguyen
Nguyen Thi Van Thuy
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen Thi Van Thuy
Nguyen Thi Hong Van
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen Thi Hong Van
Nguyen Trong Hieu
论文数: 0引用数: 0
h-index: 0
机构:
Hung Vuong Hosp, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen Trong Hieu
Nguyen Thi Hong Tham
论文数: 0引用数: 0
h-index: 0
机构:
Dong Thap Hosp, Cao Lanh, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen Thi Hong Tham
Phan Thi Thanh Ha
论文数: 0引用数: 0
h-index: 0
机构:
Dist 8 Hosp, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Phan Thi Thanh Ha
Le Bich Lien
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp 1, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Le Bich Lien
Nguyen Van Vinh Chau
论文数: 0引用数: 0
h-index: 0
机构:
Hosp Trop Dis, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Nguyen Van Vinh Chau
Vu Thi Ty Hang
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, VietnamUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Vu Thi Ty Hang
van Doorn, H. Rogier
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX1 2JD, EnglandUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
van Doorn, H. Rogier
Simmons, Cameron P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX1 2JD, England
Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, AustraliaUniv Oxford, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam
机构:
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Ahmadi, Sara
Patel, Sanket
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Patel, Sanket
Gibson, Molly K.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Gibson, Molly K.
Wang, Bin
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Wang, Bin
Ndao, I. Malick
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Ndao, I. Malick
Deych, Elena
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Biostat, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Deych, Elena
Shannon, William
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Biostat, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Shannon, William
Tarr, Phillip I.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Tarr, Phillip I.
Warner, Barbara B.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
Warner, Barbara B.
Dantas, Gautam
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA
Washington Univ, Dept Biomed Engn, St Louis, MO 63130 USAWashington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA