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Influenza RNA viral detection in cerebrospinal fluid by PCR in pediatric patients: first report from Cuba

2010; Elsevier BV; Volume: 14; Linguagem: Inglês

10.1016/j.ijid.2010.01.002

1878-3511

Alexander Piñón Ramos, Belsy Acosta Herrera, Odalys Valdés Ramírez, Clara Savón Valdés, Ángel Goyenechea Hernández, Grehete González, Guelsys González Baez,

Respiratory viral infections research

Influenza central nervous system (CNS) disorders are a serious complication of influenza infection, mostly affecting young children.1Amin R. Ford-Jones E. Richardson S.E. MacGregor D. Tellier R. Heurter H. et al.Acute childhood encephalitis and encephalopathy associated with influenza: a prospective 11-year review.Pediatr Infect Dis J. 2008; 27: 390-395Crossref PubMed Scopus (99) Google Scholar In Cuba, the majority of viral CNS disorders are diagnosed as being caused by enterovirus or herpesvirus infections,2Bello M. Más P. Palomera R. Morier L. Avalos I. Acosta B. et al.Meningoencefalitis virales por enterovirus en Cuba en el período de 1990-1995.Rev Arg Med Trop. 1997; 29: 176-183Google Scholar, 3Martínez P.A. Díaz R. González D. Oropesa L. González R. Pérez L. et al.The effect of highly active antiretroviral therapy on outcome of central nervous system herpesviruses infection in Cuban human immunodeficiency virus-infected individuals.J Neurovirol. 2007; 13: 446-451Crossref PubMed Scopus (12) Google Scholar however the remainder of cases, having predominant early acute respiratory infection symptoms, remain undiagnosed. In July and August 2005, in the city of Havana, Cuba, eight children died of adenovirus myocarditis during an atypical outbreak of an acute febrile syndrome.4Valdés O. Acosta B. Piñón A. Savón C. Goyenechea Hernandez A. Gonzales G. First report on fatal myocarditis associated with adenovirus infection in Cuba.J Med Virol. 2008; 80: 1756-1761Crossref PubMed Scopus (21) Google Scholar In the same period, primary care services detected a spectrum of syndromes, mainly in children – CNS disorders, fever, vomiting and diarrhea, and flu-like illness symptoms – extending the diagnosis of viruses capable of producing them. The National Influenza Center is involved in investigating CNS disorders in patients with a history of predominant early acute respiratory infection symptoms and cerebrospinal fluid (CSF) samples negative for the genome detection of enteroviruses, herpesviruses, and flaviviruses. Accordingly, 22 pediatric patients were investigated and included in our study; CSF samples and nasopharyngeal swabs were collected. Viral RNA was extracted from clinical samples using a method described by Casas et al.5Casas I. Powell L. Klapper P.E. Cleator G.M. New method for the extraction of viral RNA and DNA from cerebrospinal fluid for use in the polymerase chain reaction assay.J Virol Methods. 1995; 53: 25-36Crossref PubMed Scopus (198) Google Scholar and tested for respiratory viruses using a previously described multiplex nested reverse transcription polymerase chain reaction (RT-PCR).6Coiras M.T. Perez-Brena P. Garcia M.L. Casas I. Simultaneous detection of influenza A, B, and C viruses, respiratory syncytial virus, and adenoviruses in clinical samples by multiplex reverse transcription nested-PCR assay.J Med Virol. 2003; 69: 132-144Crossref PubMed Scopus (213) Google Scholar Isolation was performed in MDCK cell culture, as described in the literature.7Youil R. Su Q. Toner T.J. Szymkowiak C. Kwan W.S. Rubin B. et al.Comparative study of influenza virus replication in Vero and MDCK cell lines.J Virol Methods. 2004; 120: 23-31Crossref PubMed Scopus (77) Google Scholar The average age of the patients was 5 years, ranging between 5 months and 15 years. Clinical records showed fever (90%), cough (85%), and headache (60%) as the most common symptoms. Other symptoms were vomiting and weakness (45%) and diarrhea (37%). The most important finding was the detection of three CSF samples positive for influenza virus – one for type A and two for type C; only the patient with CSF positive for influenza A was positive for the virus in the nasopharyngeal swab. The isolation of influenza A from the nasopharyngeal swab was successful; however the virus could not be isolated from any of the CSF samples. Virus isolation from positive CSF is rarely reported,8Okabe N. Yamashita K. Taniguchi K. Inouye S. Influenza surveillance system of Japan and acute encephalitis and encephalopathy in the influenza season.Pediatr Int. 2000; 42: 187-191Crossref PubMed Google Scholar possibly because the virus has disappeared by the time of sampling or because of the low viral load. A report in the literature has demonstrated that PCR in CSF for other viruses is accurate enough for the diagnosis of viral CNS disorders.9Jeffery K.J. Read S.J. Peto T.E. Mayon-White R.T. Bangham C.R. Diagnosis of viral infections of the central nervous system: clinical interpretation of PCR results.Lancet. 1997; 349: 313-317Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar It is not surprising to encounter influenza viruses circulating in Cuba during July and August – the time period of our study – since in tropical zones, seasonal patterns appear to be less pronounced, with year-round detection and isolation of virus.10Girard M. Cherian T. Pervikov Y. Kieny M.P. A review of vaccine research and development: human acute respiratory infections.Vaccine. 2005; 23: 5708-5724Crossref PubMed Scopus (137) Google Scholar The two hurricanes that hit the island only a few weeks before this situation occurred would also have had an impact. We could not find any earlier reports of influenza C detection in CSF in the international literature and hence this is the first report from Cuba of the detection of influenza virus genome in CSF. An increased awareness of influenza A, B and C viruses as causes of viral encephalitis is necessary, and studies to determine the incidence, especially during yearly epidemics, should be undertaken. We have no competing interests to declare.