DIAGNOSTICO RETROSPECTIVO DE LA INFECCION CONGENITA POR CITOMEGALOVIRUS

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El citomegalovirus congénito permanece infradiagnosticado en ausencia de clínica neonatal. Puede manifestarse con retraso de crecimiento intrauterino, microcefalia, hipoacusia neurosensorial, coriorretinitis, retardo mental y trastorno del espectro autista. El diagnóstico de certeza sólo se puede realizar pasadas las 3 primeras semanas mediante la detección de ADN de citomegalovirus a partir de sangre del papel de filtro del cribado neonatal.
Autor:
Raquel Pinillos pisón
Columnista Experta de SIIC

Institución:
Hospital Miguel Servet Zaragoza España


Artículos publicados por Raquel Pinillos pisón
Coautores
Javier Lopez-pison* Juan Pablo García Iñiguez** Victoria Caballero Perez*** Marta Callau*** Victor Rebage Moisés**** Segundo Rite Gracia* 
Hospital Miguel Servet Zaragoza España, Zaragoza, España*
Licenciado en Medicina y cirugía. Facultativo especialista en pediatría, Hospital Miguel Servet Zaragoza España, Zaragoza, España**
Licenciado en medicina y cirugía. Médico Interno Residente Pediatría, Hospital Miguel Servet Zaragoza España, Zaragoza, España***
Licenciado en medicina y cirugía. Facultativo Especialista en Pediatría. Neonatólogo, Hospital Miguel Servet Zaragoza España, Zaragoza, España****
Recepción del artículo
10 de Septiembre, 2012
Aprobación
14 de Diciembre, 2012
Primera edición
22 de Febrero, 2013
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
La infección por citomegalovirus (CMV) es la infección viral congénita más frecuente. Es causa de múltiples anomalías que involucran al sistema nervioso central. Debido a que es principalmente asintomática, dos tercios de las secuelas se producen en niños asintomáticos al nacimiento. Pasadas las primeras 2 a 3 semanas de vida, se ha propuesto como método ideal y único de certeza para el diagnóstico retrospectivo la detección del ADN viral en la muestra de sangre seca procedente de la pesquisa neonatal. La técnica se lleva a cabo mediante dilución, amplificación y extracción, con resultado en menos de 48 horas. Se han publicado en la bibliografía numerosos protocolos, que refieren variadas sensibilidades in Vitro que dependen fundamentalmente del método de extracción, desde la prueba del talón y de la amplificación, que son muy heterogéneas (entre 35% y 98%). La sensibilidad es mayor si es secundaria a primoinfección, en pacientes seleccionados, si se utiliza un buen método de extracción y amplificación, y una amplificación duplicada o, incluso, triplicada. La especificidad en todos ellos es concordante y alcanza casi el 100%. La carga viral de la prueba del talón está subestimada, pero altamente relacionada con la de sangre fresca y, aunque puede no haber viremia al nacimiento, los neonatos virémicos son los que tienen mayor riesgo de presentar secuelas neurosensoriales, por lo que los índices de detección clínica en pacientes seleccionados son altos. Se ha descrito la viabilidad de otras alternativas, como el cordón umbilical en Japón y, en los últimos años, el uso de orina seca en papel de filtro, y se comunicaron buenos resultados.

Palabras clave
infección congenita por citomegalovirus, diagnóstico retrospectivo


Artículo completo

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Abstract
Cytomegalovirus is the most common congenital viral infection. It´s cause of many abnormalities involving the central nervous system. Because of its mainly asymptomatic, two thirds of the sequelae occur in asymptomatic at birth child.

After the first 2-3 weeks of life, the viral DNA detection on dried blood sample from the neonatal screening has been proposed as an ideal and unique method of certainty for retrospective diagnosis.

The technique is carried out by dilution and extraction-amplification, resulting in less than 48 hours. It have been published a variable number of protocols in the literature that refer variables in vitro sensitivities depend mainly on the extraction method from the heel prick and amplification that are heterogeneous (between 35%-98%). The sensitivity is greater if it is secondary to primary infection, in selected patients, using a good method of extraction and amplification and amplification doubled or even tripled. The specificity is consistent in all of them reaching almost 100%. The viral load test of the voucher is underestimated but highly related to that of fresh blood and although it may not have viremia at birth, viraemic infants have higher risk of developing neurosensory sequelae, making clinical detection rates in patients selected are high.

Described the feasibility of alternatives such as the umbilical cord in Japan, and in recent years, the use of dried urine on filter paper, reported good results.

Key words
congenital citomegalovirus infection, retrospective diagnosis


Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Diagnóstico por Laboratorio, Pediatría
Relacionadas: Bioquímica, Infectología, Neurología



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Raquel Pinillos Pisón, Hospital Universitario Miguel Servet de Zaragoza, 50009, C/ Rubén Darío nº8 bajo 2ª, Zaragoza, España
Bibliografía del artículo
1. Zucca C, Binda S, Borgatti et al. Retrospective diagnosis of congenital cytomegalovirus infection and cortical maldevelopment. Neurology 61:710-712, 2003.
2. Misono S, Sie K, Weiss N, Huang M, Boeckh M, Norton S et al. Congenital Citomegalovirus Infection in Pediatric hearing Loss. Arch Otolaryngol Head Neck Surg 137:47-53, 2011.
3. Bradford R, Cloud G, lakeman A, Boppana S, Kimberlin D, Jacobs R et al. Detection of Cytomegalovirus (CMV) DNA by Polimerase chain reaction is associated with hearing loss in newborns with symptomatic congenital CMV infection involving the central nervous system. JID 191:227-233, 2005.
4. Dollard SC, Grosse SD, Ross DS. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol 17:353-63, 2007.
5. Peckham C, Tookey P,Logan S,Giaquinto C. Screening options for prevention of congenital cytomegalovirus infection. J Med Screen 8:119-24, 2001.
6. Naessens A, Casteels A,Decatte L,Foulon W. A serologic strategy for detecting neonates at risk for congenital cytomegalovirus infection. J Pediatr 146:194-7, 2005.
7. Barbi M, Binda S, Caroppo S, Calvario A, Germinario C, Bozz iA, et al. Multicity Italian study of congenital cytomegalovirus infection. Pediatr Infect Dis J 25:156-9, 2006.
8. Gaytant MA, Steegers EA, Semmekrot BA et al. Congenital cytomegalovirus infection: review of the epidemiology and outcome. Obstet Gynecol Surv 57:245-256, 2002.
9. Estripeaut D, MorenoY, Ahumada-Ruiz S et al. Seroprevalencia de la infección por citomegalovirus en puérperas y su impacto neonatal. An Pediatr (Barc) 66:135-139, 2007.
10. F. Baquero-Artigao y Grupo de estudio de la infección congénita por citomegalovirus de la Sociedad Española de Infectología Pediátrica. Documento de consenso de la Sociedad Española de Infectología Pediátrica sobre el diagnóstico y el tratamiento de la infección congénita por citomegalovirus. An Pediatr 71(6):535-547, 2009.
11. DeOry F, Castañeda R, Ramírez R, Pachón I. Estudio seroepidemiológico frente a citomegalovirus en mujeres en edad fértil de la Comunidad de Madrid. Med Clin (Barc.) 111:286-7, 1998.
12. De Ory F, Ramírez R, García-Comas L, León P, Sagües MJ, Sanz JC. Is there a change in cytomegalovirus seroepidemiology in Spain? Eur J Epidemiol 19:85-9, 2004.
13. Francoual C, Rozenberg F, Gelot A. Infection maternofoetale á cytomegalovirus. Med Mal Infect 26:441-446, 1996.
14. Pinillos R, Olloqui A, Torres y col. Citomegalovirus congénito neonatal. Comunicación de un caso y revisión. Acta Pediatr Esp 67:234-238, 2009.
15. Malm G, Engman ML. Congenital cytomegalovirus infections. Semin Fetal Neonat Med 12:154-159, 2007.
16. Lazzarotto T, Guerra B, Lanari M, Gabrielli L, Landini MP. New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol 41:192-197, 2008.
17. Fowler KB, Dahle AJ, Boppana S et al. Newborn hearing screening: will children with hearing loss caused by congenital cytomegalovirus infection be missed? J Pediatr 135:60-64, 1999.
18. Kenneson A, Canon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus infection. Rev Med Virol 17:253-276, 2007.
19. Boppana S, Fowler KB, Britt WS, Stagno S, Pass RF. Symptomatic congenital cytomegalovirus infection infants born to mother with preexisting inmunity to cytomegalovirus. Pediatrics 104:55-60, 1999.
20. Gaytant MA, Rours GI, Steegers EA, Galama Jm, Semmekrot BA. Congenital cytomegalovirus infection after recurrent infection: case report and review of the literature. Eur J pediatr 162:248-253, 2003.
21. Pass RF. Congenital cytomegalovirus infection and hearing loss. Herpes 12:50-55, 2005.
22. Haginoya K, Ohura T, Kon K et al. Abnormal white matter lesions with sensorineural hearing loss caussed by congenital cytomegalovirus infection: retrospective diagnosis by PCR using Guthrie cards. Brain Dev 24:710-714, 2002.
23. Van der Knaap MS, Vermeulen G, Barkhof F et al. Pattern of white matter abnormalities at MR imaging: Use of polimerase chain reaction testing of Guthrie cards to link pattern with congenital cytomegalovirus infection. Radiology 230:529-536, 2004.
24. Noyola D, Demler GJ, Nelson CT et al. Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection. J Pediatr 138:325-331, 2001.
25. Rivera L B , Boppana S B , Fowler K B, Britt W J , Stagno S, Pass R F. Predictors of hearing loss in children with symptomatic congenital cytomegalovirus infection. Pediatrics. 110:762-7, 2002.
26. Fowler KB, McCollister FP, Dahle AJ, et al. Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus. J Pediatr 130:624-630, 1997.
27. Dahle AJ, Fowler KB, Wright JD, et al. Longituinal investigation of hearing disorders in children with congenital CMV.J Am Acad Audiology 11:283-290, 2000.
28. Barbi M, et al. A wider role for congenital cytomegalovirus infection in sensorineural hearing loss. Pediatr Infect Dis J 22:39-42, 2003.
29. Grosse Sd, Ross DS, Dollard SC. Congenital cytomegalovirus infection as a cause of permanent bilateral hearing loss: a quantitative assesment. J Clin Virol 41:57-62, 2008.
30. Pass RF, Fowler KB, Boppana SB, Britt WJ, Stagno S. Congenital cytomegalovirus infection following first trimester maternal infection: Symptoms at birth and outcome. J Clin Virol 35:216-20, 2006. .
31. Lanari M, Lazzarotto T, Venturi V, Papa I, Gabrielli L et al. Neonatal cytomegalovirus blood load and risk of sequelae in symptomatic and asymptomatic congenitally infected new- borns. Pediatrics 117:76-83, 2006.
32. Boppana SB, Fowler KB, Pass RF, Rivera LB, Bradford RD, Lakeman FD, et al. Congenital cytomegalovirus infection: Association between virus burden ininfancy and hearing loss. J Pediatr 146:817-23, 2005.
33. Koyano S, Inoue N, Oka A,Moriuchi H, Asano K, Ito Y, et al. Screening fro congenital cytomegalovirus infection using newborn urine samples collected on filter paper: feasibility and outcomes from a multicentre study. BMJ Open 1:e000118, 2011.
34. Anderson KS, Amos CS, Boppana SB et al. Ocular abnormalities in congenital cytomegalovirus infection. J Am Optom Assoc 67:273-B, 1996.
35. Coast Dk, Demmler GJ, Paysse EA et al. Opthalmologic findings in children with congenital cytomegalovirus infection. J AAPOS 4:110-116, 2000.
36. Lazzarotto T, Gabrielli L, Lanari M, Guerra B, Belluci T, Sassi M, et al. Congenital cytomegalovirus infection: recent advances in the diagnosis of maternal infection. Hum Inmunol 65:410-415, 2004.
37. Stagno S, Pass RF, Cloud G, Britt WJ, Henderson RE, Walton OD, et al. Primaru cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. JAMA 256:1904-1908, 1986.
38. Munro SC, Hall B, Whybin LR, Leader L, Robertson P, Maine GT, et al. Diagnosis of and screening for cytomegalovirus infection in pregnant women. J Clin Microbiol 43:4713-4718, 2005.
39. Guerra B, Lazzarotto T, Quarta S, Lanari M, Bovicelli L, Nicolosi A, et al. Prenatal diagnosis of syntomatic congenital cytomegalovirus infection. Am J Obstet Gynecol 183:476-482, 2000.
40. Ville Y. The megalovirus. Ultrasound Obstet Gynecol 12:151-153.[editorial], 1998.
41. Guerra B, Simonazzi G, Puccetti C, Lanari M, Farina A, Lazzarotto T, et al. Ultrasound prediction of symptomatic congenital cytomegalovirus infection. Am J Obstet Gynecol 198:380e1-7, 2008.
42. Demmler GJ, Buffone GJ, Schimbor CM et al. Detection of cytomegalovirus in urine from newborns by using polimerase chain reaction DNA amplification. J Infect Dis 158:1177-1184, 1988.
43. Warren WP, Balcarek K, Smith R et al. Comparison of rapid methods of detection of cytomegalovirus in saliva with virus isolation in tissue culture. J Clin Microbiol 30:786-789, 1992.
44. Revello MG, Zavattoni M, Baldanti F, Sarasini A, Paolucci S, Gerna G. Diagnostic and prognostic value of human cytomegalovirus load and IgM antibody in blood of congenitally infected newborns. J Clin Virol 14:57-66, 1999.
45. Distéfano A, González C, Pardón F, Sarubi MA, Canero C. Diagnóstico de la infección congénita por citomegalovirus en muestras de sangre seca de recién nacidos en la tarjeta de Guthrie. Una técnica promisoria. Arch Argent Pediatr 106(2):132-137, 2008.
46. Ross SA, Boppana SB. Congenital cytomegalovirus infection:: outcome and diagnosis. Semin Pediatr Infect Dis 16:44-49, 2005.
47. Inoue N, Koyano S. Evaluation of screening tests for congenital cytomegalovirus infection. Pediatr Infect Dis J 27:182-4, 2008.
48. Pinillos R, Llorente M, López-Pisón J et al. Infección congénita por citomegalovirus. Revisión de nuestra experiencia diagnóstica de 18 años. Rev Neurol 48:349-353, 2009.
49. Shibata M, Takano H, Hironaka T et al. Detection of human cytomegalovirus DNA in dried newborn blood filter paper. J Virol Methods 46:279-285, 1994.
50. Barbi M, Binda S, Caroppo S. Diagnosis of congenital cytomegalovirus infection via dried blood spots. Rev Med Virol 16:385-392, 2006.
51. Barbi M, Binda S, Caroppo S et al. Neonatal screening for congenital cytomegalovirus infection and hearing loss. J Clin Virol 35:206-209, 2006.
52. Johansson PJ, Jonsson M, Ahlfors K et al. Retrospective diagnostics of congenital cytomegalovirus infections by polimerase chain reaction in blood stored on filter paper. Scan J Infect Dis 29:465-468, 1997.
53. Scanga L, Chaing S, Powell C, et al. Diagnosis of human congenital cytomegalovirus infection by amplification of viral DNA from dried blood spots on perinatal cards. J Mol Diagn 8:240-245, 2006.
54. Soetens O, Vauloup-Fellous C, Foulon I, et al. Evaluation of different cytomegalovirus (CMV) DNA PCR protocols for analysis of dried blood spots from consecutive cases of neonates with congenital CMV infections. J Clin Microbiol 46:943-946, 2008.
55. Atkinson C, Walter S, Sharland M, et al. Use of stored dried blood spots for retrospective diagnosis of congenital CMV. J Med Virol 81:1394-1398, 2009.
56. Walter S, Atkinson C, Sharland M, Rice P, Raglan E, Emery VC, et al. Congenital cytomegalovirus: association between dried blood spot viral load and hearing loss. Arch Dis Child Fetal Neonatal 93:280-285, 2008.
57. Yamamoto AY, Mussi-Pinhata MM, Pinto PC et al. Usefulness of blood and urine samples collected on filter paper in detecting cytomegalovirus infection by the polimerasa chain reaction technique. J Virol Methods 97:159-164, 2001.
58. Paixao P, Almeida S, Gouveia P, Vilarinho L, Vaz R. Prevalence of human cytomegalovirus congenital infection in Portuguese newborns. Eurosurveillance 14:1-3, 2009 (www.eurosurveillance.org).
59. Boppana B, Ross A, Novak Z et al. Dried Blood spot real-time polimerase chain reaction assays to screen newborns for congenital cytomegalovirus infection. JAMA 303:1375-1382, 2010.
60. Barbi M, Binda S, Primache V, et al. Citomegalovirus detection in guthrie cards: a powerful tool for diagnosis congenital infection. J Clin Virol 17:159-65, 2000.
61. Distefano AL, Alonso A, Martin F, Pardon H. Human cytomegalovirus: detection of congenital and perinatal infection in Argentina. BMC Pediatr 4:11, 2004.
62. Vauloup-Fellous C, Ducrox A, Couloigner V, et al. Evaluation of cytomegalovirus (CMV) DNA quantification in dried blood spots:retrospective study of CMV congenital infection. J Clin Microbiol 45:3804-3806, 2007.
63. De Vries JJ, Claas EC, Kroes AC, Vossen AC. Evaluation of DNA extraction methods for dried blood spots in the diagnosis of congenital cytomegalovirus infection. J Clin Virol 46:37-42, 2009.
64. Dollard S, Schleiss MR, Grosse SD. Public health and laboratory considerations regarding newborn screeniing for congenital cytomegalovirus. J Inherit Metabol Dis 33:5249-5254, 2010.
65. Leurez-Ville M, Vauloup-Fellous C, Couderc S, Parat S, Castel C, Avettand-fenoel V, et al. Prospective identification of congenital cytomegalovirus infection in newborns using real-time polymerase chain reaction assays in ddried blood spots. Clin Infect Dis 52:575-581, 2011.
66. Kharrazi M, Hyde T, Young S, Amin MM, Cannon MJ, Dollard SC. Use of screeening dried blood spots for estimation of prevalence, risk factors, and birth outcomes of congenital cytomegalovirus infection. J Pediatr 157:191-197, 2010.
67. Barbi M, MacKay WG, Binda S, Van Loon AM. External quality assessment of cytomegalovirus DNA detection on dried blood spots. BMC Microbiol 8:2, 2008.
68. Dollard S, Scheleiss MR. Screening newborns for congenital cytomegalovirus infection. JAMA 304:407-408, 2010.
69. Göhring K, Dietz K, Hartleif S, Jahn G, Hamprecht K. Influence of different extraction methods and PCR techniques on the sensitivity of HCMV-DNA detection in dried blood spot (DBS) filter cards. J Clin Virol 48:278-281, 2010.
70. Hallwach-Baumann G, et al. Human citomegalovirus load in various body fluids of congenitally infected newborns. J Clin Virol 25:81-87, 2002.
71. Nozawa N, et al. Real-time PCR assay using specimens on filter disk as a template for detection of cytomegalovirus in urine. J Clin Microbiol 45:1305-1307, 2007.
72. Ogawa H, Baba Y, Suzutani T, Inoue N, Fukushima E, Omori K. Congenital cytomegalovirus infection diagnosed by polimerase chain reaction with the use of preserved umbilical cord in sensorineural hearing loss children. Laryngoscope 116:1991-1994, 2006.
73. Tagawa M, Tanaka H, Moriuchi M, Moriuchi H. Rtetrospective diagnosis of congenital cytomegalovirus infection at a school for the deaf by using preserved dried umbilical cord. J Pediatr 155:749-751, 2009.
74. Pass R. Dried blood spots and universal newborn screening for congenital cytomegalovirus infection. Clin Infect Dis 52:582-584, 2011.

 
 
 
 
 
 
 
 
 
 
 
 
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