Klaus Hamprecht1, Alfred Lennart Bissinger2, Jose Arellano-Galindo3, Katrin Schweinzer3, Xioajing Jiang3, Katharina Göhring3, Elfriede Mikeler3, Gerhard Jahn3. 1. Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tuebingen, D-72076 Tuebingen, Germany. Electronic address: klaus.hamprecht@med.uni-tuebingen.de. 2. 1st Medical Department, University Hospital of Tuebingen, 72076 Tuebingen, Germany. 3. Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital of Tuebingen, D-72076 Tuebingen, Germany.
Abstract
BACKGROUND: The role of a special early family formation (PEKiP), which is popular in Germany, as a potential origin of HCMV-transmission to seronegative mothers is not documented. OBJECTIVES: To describe the clinical courses, to identify the virological origin and to evaluate a new tool for diagnosis of a cascade of intrafamilial HCMV primary infections. STUDY DESIGN: This prospectively analyzed long-term course of HCMV primary infection leading to hospitalization of two family members, included the evaluation of different IgG/IgM/IgG avidity-assays with an epitope-specific recombinant immunoblot-assay. Additionally, neutralization (NT) assays using fibroblast-and epithelial-target cells were performed to correlate NT₅₀ values to avidity maturation. HCMV gN/gO/gB-RFLP-genotyping and phylogenetic analyses were performed using urine viral isolates. RESULTS: The clinical courses of the sequentially occurring intrafamilial HCMV primary infections were unusual, leading to hospitalization. Long-term-serology of the mother revealed concordant results for an unimodal IgG-course and a rapid decrease of IgM-indices from week 7 to week 21 p.i. Interestingly, the cut-off definitions for low and high avidity ranged discordantly from 15 to 25 weeks, and from 18 to 42 weeks p.i., respectively. A good correlation was found between the increase of fibroblast-adapted NT50 values and the appearance of high avidity using the epitope-specific immunoblot (>18 weeks p.i.). RFLP-genotyping and sequencing could identify the index patient as member of PEKiP-meetings. CONCLUSIONS: PEKiP-meetings with naked babies may be an important source of horizontal HCMV-transmission to seronegative pregnant mothers in Germany. Using epitope-specific immunoblots, persisting HCMVp150-IgM-reactivities and good concordance between high IgG-avidity and increase of fibroblast adapted neutralization capacity were found.
BACKGROUND: The role of a special early family formation (PEKiP), which is popular in Germany, as a potential origin of HCMV-transmission to seronegative mothers is not documented. OBJECTIVES: To describe the clinical courses, to identify the virological origin and to evaluate a new tool for diagnosis of a cascade of intrafamilial HCMV primary infections. STUDY DESIGN: This prospectively analyzed long-term course of HCMV primary infection leading to hospitalization of two family members, included the evaluation of different IgG/IgM/IgG avidity-assays with an epitope-specific recombinant immunoblot-assay. Additionally, neutralization (NT) assays using fibroblast-and epithelial-target cells were performed to correlate NT₅₀ values to avidity maturation. HCMV gN/gO/gB-RFLP-genotyping and phylogenetic analyses were performed using urine viral isolates. RESULTS: The clinical courses of the sequentially occurring intrafamilial HCMV primary infections were unusual, leading to hospitalization. Long-term-serology of the mother revealed concordant results for an unimodal IgG-course and a rapid decrease of IgM-indices from week 7 to week 21 p.i. Interestingly, the cut-off definitions for low and high avidity ranged discordantly from 15 to 25 weeks, and from 18 to 42 weeks p.i., respectively. A good correlation was found between the increase of fibroblast-adapted NT50 values and the appearance of high avidity using the epitope-specific immunoblot (>18 weeks p.i.). RFLP-genotyping and sequencing could identify the index patient as member of PEKiP-meetings. CONCLUSIONS: PEKiP-meetings with naked babies may be an important source of horizontal HCMV-transmission to seronegative pregnant mothers in Germany. Using epitope-specific immunoblots, persisting HCMVp150-IgM-reactivities and good concordance between high IgG-avidity and increase of fibroblast adapted neutralization capacity were found.
Authors: Niklas F Müller; Matthias Schampera; Gerhard Jahn; Nisar P Malek; Christoph P Berg; Klaus Hamprecht Journal: BMC Infect Dis Date: 2016-01-19 Impact factor: 3.090