S E Luck1, V C Emery2, C Atkinson3, M Sharland4, P D Griffiths5. 1. Centre for Virology, University College London Medical School, London, UK; Paediatric Infectious Diseases Research Group, St George's University of London, London, UK. Electronic address: Suzanne.luck@ucl.ac.uk. 2. Centre for Virology, University College London Medical School, London, UK; Department of Microbial and Cellular Sciences, University of Surrey, Guildford, UK. Electronic address: v.emery@surrey.ac.uk. 3. Centre for Virology, University College London Medical School, London, UK. Electronic address: claire.atkinson1@nhs.net. 4. Paediatric Infectious Diseases Research Group, St George's University of London, London, UK. Electronic address: Mike.sharland@stgeorges.nhs.uk. 5. Centre for Virology, University College London Medical School, London, UK. Electronic address: p.griffiths@ucl.ac.uk.
Abstract
BACKGROUND: Cytomegalovirus (CMV) is the most prevalent congenital infection in developed countries. A significant number of infected infants develop long-term neurodevelopmental and hearing impairment irrespective of whether disease is detectable at birth. Studies of viral load and replication dynamics have informed the treatment of CMV in adult populations but no similar data exist in neonates. OBJECTIVES: To study CMV virus kinetics in different body fluids of babies treated for congenital infection. STUDY DESIGN: CMV virus load was sequentially analyzed in blood, urine and saliva in 17 babies treated for symptomatic congenital CMV infection. RESULTS: Virus was detectable in the urine and saliva of all babies at baseline but in only 15/17 in blood. At the end of 6 weeks of antiviral treatment CMV remained detectable in 9/14 blood samples, 9/12 urine samples and 4/7 salivary swabs. Median half-life (T1/2) of virus decline in blood was 2.4 days (IQR 1.9-3.3) and basic reproductive number (Ro) was 2.3. Although T1/2 values were similar in urine and saliva to those observed in blood, virus dynamics differed both during and after treatment. CONCLUSIONS: T1/2 and Ro in blood in this group of neonates were similar to values derived from studies of immunocompromised adults. The persistent viremia observed in treated neonates cannot therefore be adequately explained by the virus dynamics early in treatment. The different dynamics exhibited in blood and urine suggests that studying changes in distinct body compartments may assist in further understanding long-term manifestations of disease. Crown
BACKGROUND: Cytomegalovirus (CMV) is the most prevalent congenital infection in developed countries. A significant number of infected infants develop long-term neurodevelopmental and hearing impairment irrespective of whether disease is detectable at birth. Studies of viral load and replication dynamics have informed the treatment of CMV in adult populations but no similar data exist in neonates. OBJECTIVES: To study CMV virus kinetics in different body fluids of babies treated for congenital infection. STUDY DESIGN: CMV virus load was sequentially analyzed in blood, urine and saliva in 17 babies treated for symptomatic congenital CMV infection. RESULTS: Virus was detectable in the urine and saliva of all babies at baseline but in only 15/17 in blood. At the end of 6 weeks of antiviral treatment CMV remained detectable in 9/14 blood samples, 9/12 urine samples and 4/7 salivary swabs. Median half-life (T1/2) of virus decline in blood was 2.4 days (IQR 1.9-3.3) and basic reproductive number (Ro) was 2.3. Although T1/2 values were similar in urine and saliva to those observed in blood, virus dynamics differed both during and after treatment. CONCLUSIONS: T1/2 and Ro in blood in this group of neonates were similar to values derived from studies of immunocompromised adults. The persistent viremia observed in treated neonates cannot therefore be adequately explained by the virus dynamics early in treatment. The different dynamics exhibited in blood and urine suggests that studying changes in distinct body compartments may assist in further understanding long-term manifestations of disease. Crown
Authors: Concetta Marsico; Immaculada Aban; Huichien Kuo; Scott H James; Pablo J Sanchez; Amina Ahmed; Ravit Arav-Boger; Marian G Michaels; Negar Ashouri; Janet A Englund; Benjamin Estrada; Richard F Jacobs; José R Romero; Sunil K Sood; Suzanne Whitworth; Penelope M Jester; Richard J Whitley; David W Kimberlin Journal: J Infect Dis Date: 2019-04-16 Impact factor: 5.226
Authors: James A Hutchinson; Katharina Kronenberg; Paloma Riquelme; Jürgen J Wenzel; Gunther Glehr; Hannah-Lou Schilling; Florian Zeman; Katja Evert; Martin Schmiedel; Marion Mickler; Konstantin Drexler; Florian Bitterer; Laura Cordero; Lukas Beyer; Christian Bach; Josef Koestler; Ralph Burkhardt; Hans J Schlitt; Dirk Hellwig; Jens M Werner; Rainer Spang; Barbara Schmidt; Edward K Geissler; Sebastian Haferkamp Journal: Nat Commun Date: 2021-03-04 Impact factor: 14.919