Isabel Vives-Oñós1,2, María Gema Codina-Grau3, Antoni Noguera-Julian4,5,6,7, Daniel Blázquez-Gamero7,8, Claudia Fortuny4,5,6,7, Fernando Baquero-Artigao7,9, Marie Antoinette Frick10, Jesús Saavedra-Lozano7,11, Walter Goycochea-Valdivia9, María Teresa Rives-Ferreiro12, Abián Montesdeoca-Melián13, Olga Calavia-Garsaball10, Laura Ferreras-Antolin14, José Luís Marín-Soria15, Elena Dulín-Íñiguez16, Pere Soler-Palacín10. 1. From the Unitat de Patologia Infecciosa i Immunodeficiències de Pediatria, Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona. 2. Servicio de Pediatría, Hospital Quirónsalud Barcelona, Grupo Quirónsalud. 3. Servicio de Microbiología, Hospital Universitari Vall d'Hebron, Barcelona, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona. 4. Malalties infeccioses i resposta inflamatòria sistèmica en pediatria, Unitat d´Infeccions, Servei de Pediatria, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu. 5. Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. 6. CIBER de Epidemiología y Salud Pública (Ciberesp). 7. Spanish Translational Research Network in Pediatric Infectious Diseases (RITIP). 8. Sección de Enfermedades Infecciosas Pediátricas, Hospital Universitario 12 de Octubre, Universidad Complutense, Instituto de Investigación Hospital 12 de Octubre (imas12). 9. Servicio de Pediatría Hospitalaria y Enfermedades Infecciosas y Tropicales Pediátricas, Hospital Universitario La Paz. 10. Servicio de Pediatría, Hospital Joan XIII, Tarragona, Spain. 11. Sección de Infectología Pediátrica, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 12. Unidad de Cuidados Intensivos Pediátricos y Área Neonatal, Servicio de Pediatría, Complejo Hospitalario de Navarra, Pamplona, Spain. 13. Centro de Salud de Guanarteme, Colaborador en Unidad de Enfermedades Infecciosas, Complejo Hospitalario Universitario Insular-Materno Infantil de Las Palmas de Gran Canaria, Las Palmas, Spain. 14. Unidad de Enfermedades Infecciosas e Inmunología Pediátrica, Hospital Carlos Haya, Málaga, Spain. 15. Programa de Cribado Neonatal de Cataluña, Sección Errores Congénitos del Metabolismo, Servicio de Bioquímica y Genética Molecular, Hospital Clínic, Barcelona, Spain. 16. Laboratorio de Cribado Neonatal de la Comunidad de Madrid, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Abstract
BACKGROUND: Detection of cytomegalovirus (CMV) DNA by real-time polymerase chain reaction (rt-PCR) in dried blood spots (DBSs) collected for newborn screening has been assessed for retrospective diagnosis of congenital CMV (cCMV) infection, with variable results (sensitivities ranging from 34% to 100%). We aimed to assess the accuracy of this technique in Spain in a large patient series. METHODS: Ambispective, multicenter study including patients with confirmed cCMV from the Spanish Registry of cCMV patients. cCMV was established on the presence of CMV DNA in any body fluid, by positive culture findings or by molecular techniques during the first 2 weeks of life. Children in whom cCMV had been excluded were used as negative controls. Neonatal DBS samples were collected from both groups. The presence of CMV DNA was assessed by rt-PCR (RealStar CMV, Altona, Germany) in a central laboratory. RESULTS: One-hundred three patients and 81 controls from 10 hospitals were included. The performance of CMV DNA determination in DBS for the diagnosis of cCMV was as follows (95% confidence interval): sensitivity 0.56 (0.47-0.65), specificity 0.98 (0.91-0.99), positive likelihood ratio 22.81 (5.74-90.58) and negative likelihood ratio 0.45 (0.36-0.56). Sensitivity increased with the birth viral load (bVL) log category. In cCMV patients, lower bVL was the single variable associated with a negative DBS rt-PCR result (P = 0.017). CONCLUSIONS: The sensitivity of CMV rt-PCR in DBS in our series was low and correlated with the bVL. Thus, a negative DBS result would not rule out cCMV infection, especially in patients with a low viremia level at birth.
BACKGROUND: Detection of cytomegalovirus (CMV) DNA by real-time polymerase chain reaction (rt-PCR) in dried blood spots (DBSs) collected for newborn screening has been assessed for retrospective diagnosis of congenital CMV (cCMV) infection, with variable results (sensitivities ranging from 34% to 100%). We aimed to assess the accuracy of this technique in Spain in a large patient series. METHODS: Ambispective, multicenter study including patients with confirmed cCMV from the Spanish Registry of cCMV patients. cCMV was established on the presence of CMV DNA in any body fluid, by positive culture findings or by molecular techniques during the first 2 weeks of life. Children in whom cCMV had been excluded were used as negative controls. Neonatal DBS samples were collected from both groups. The presence of CMV DNA was assessed by rt-PCR (RealStar CMV, Altona, Germany) in a central laboratory. RESULTS: One-hundred three patients and 81 controls from 10 hospitals were included. The performance of CMV DNA determination in DBS for the diagnosis of cCMV was as follows (95% confidence interval): sensitivity 0.56 (0.47-0.65), specificity 0.98 (0.91-0.99), positive likelihood ratio 22.81 (5.74-90.58) and negative likelihood ratio 0.45 (0.36-0.56). Sensitivity increased with the birth viral load (bVL) log category. In cCMV patients, lower bVL was the single variable associated with a negative DBS rt-PCR result (P = 0.017). CONCLUSIONS: The sensitivity of CMV rt-PCR in DBS in our series was low and correlated with the bVL. Thus, a negative DBS result would not rule out cCMV infection, especially in patients with a low viremia level at birth.
Authors: Christian Berg; Martin B Friis; Mette M Rosenkilde; Thomas Benfield; Lene Nielsen; Hans R Lüttichau; Thomas Sundelin Journal: PLoS One Date: 2019-09-12 Impact factor: 3.240
Authors: Marie Antoinette Frick; Ignasi Barba; Marina Fenoy-Alejandre; Paula López-López; Fernando Baquero-Artigao; Paula Rodríguez-Molino; Antoni Noguera-Julian; Marta Nicolás-López; Asunción de la Fuente-Juárez; Maria Gemma Codina-Grau; Juliana Esperalba Esquerra; Ángeles Linde-Sillo; Pere Soler-Palacín Journal: Metabolites Date: 2019-11-25
Authors: Angela Nagel; Emmanouela Dimitrakopoulou; Norbert Teig; Peter Kern; Thomas Lücke; Dariusz Michna; Klaus Korn; Philipp Steininger; Khalid Shahada; Katrin Neumann; Klaus Überla Journal: PLoS One Date: 2020-01-09 Impact factor: 3.240
Authors: Christian Berg; Mette M Rosenkilde; Thomas Benfield; Lene Nielsen; Thomas Sundelin; Hans R Lüttichau Journal: BMC Infect Dis Date: 2021-04-26 Impact factor: 3.090