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Wild-type measles virus in brain tissue of children with subacute sclerosing panencephalitis, Argentina.

Article Excerpt
We studied eight children who had measles at 6 to 10 months of age during the 1998 Argentine measles outbreak and in whom subacute sclerosing panencephalitis developed 4 years later. We report the genetic characterization of brain tissue-associated measles virus samples from three patients. Phylogenetic relationships clustered these viruses with the wild-type D6 genotype isolated during the 1998 outbreak. The children received measles vaccine; however, vaccinal strains were not found.

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Measles is often incorrectly regarded as a mild disease, and priority is not given to measles elimination programs in some countries (1). Nevertheless, substantial progress has been made in eliminating measles virus from the Americas through massive vaccination campaigns and maintaining high measles population immunity over time. From 1990 to 1996, measles cases declined from 250,000 to 2,109; however, in 1997, measles reemerged in the Americas, with 70,983 confirmed cases. From the last Argentine outbreak (July 1997-May 1999), 10,354 confirmed measles cases were reported, most of them in unvaccinated preschool-aged children in the greater Buenos Aires metropolitan area (2).

Although measles virus (Morbillivirus genus, Paramyxovirus family) is not highly neurotropic, it can establish long-term persistent infection in brain cells. Three different neurologic complications result from interactions of measles virus with neural tissue. Acute postinfectious encephalitis, usually appearing 5-14 days after the rash, is thought to be a virus-induced autoimmune disease. Measles inclusion body encephalitis, which occurs in immunocompromised patients after a latent period of 3-6 months, is believed to be a direct measles virus infection of neural tissue. The third form, subacute sclerosing panencephalitis (SSPE), manifests 2-10 years after primary measles infection as a progressive and fatal chronic neurodegenerative disease caused by persistent defective measles virus in neurons and oligodendrocytes. SSPE develops with high titers of anti-measles antibodies both in cerebrospinal fluid (CSF) and serum, which seem unable to eliminate measles virus from the brain (3).

Although measles virus is serologically monotypic, genetic variability has defined eight clades, including 20 genotypes and a putative new genotype that are geographically and temporally restricted (4). Evidence does not indicate that wild-type measles virus strains differ in terms of either pathogenesis or neurovirulence. Measles virus recovered from patients with SSPE differs from wild-type viruses in a number of mutations that mainly affect the matrix, hemagglutinin (H), nucleocapsid (N), and fusion genes. The matrix accumulates the highest level of mutations in the entire open reading frame; by contrast, the N is modified in the carboxyl terminus, and the H has biased hypermutation in a limited region (5,6). Despite the paucity of studies in molecular epidemiology of SSPE, measles virus sequences obtained from brain tissues are homologous to the genotype circulating at the time of primary exposure to measles virus (7).

We studied eight children who had measles as infants during the 1998 measles outbreak in Argentina and...