Aseptic meningitis in a large MMR vaccine campaign (590,609 people) in Curitiba, Paraná, Brazil, 1998

Abstract

The aseptic meningitis after Measles-Mumps-Rubella vaccine (MMR) is a well recognized complication, and different incidences have been observed in several studies. We retrospectively analyzed forty cases of aseptic meningitis, during a large public immunization campaign (1998) in Curitiba, Southern Brazil (590,609 people), admitted in our Service. The vaccine utilized was Leningrad-3-Zagreb mumps strain, Edmonston-Zagreb measles strain, and RA 27#3 rubella strain. In all county, a total number of 87 cases were reported, resulting in a incidence of 1.7 cases per 10,000 given doses. The mean age was 23.7 +/- 12.8 years. The female:male ratio was 1.35:1. Severe headache with meningismus (92.5%), fever (87.5%), nausea/vomiting (82.5%) were the most common clinical findings. Three cases (7.5%) developed mild mumps. All patients underwent cerebrospinal fluid (CSF) tap with the following findings: mononuclear pleocytosis from 100 to 500 cells/mm(3) in 17 cases (42.5%; 257.5 +/- 260.6 cells/mm3); increased protein 28 cases (67.5%; 92.1 +/- 76.9 mg/dL); glucose was normal in all cases (56.8 +/- 11.2 mg/dL) except in 4 (10%) cases, which presented less than 44 mg/dL. All serological tests (latex to bacterial meningitis, Cryptococcus, cysticercosis, VDRL) and bacteriological cultures were negative. Virus identification were also negative in 8 samples. None of the patients had neurological deficits or related symptoms after one year of onset. We believe the benefit of vaccination clearly outweighs the incidence of benign vaccine-associated meningitis.

The Rat‐Based Neurovirulence Safety Test for the Assessment of Mumps Virus Neurovirulence in Humans: An International Collaborative Study

“…Such testing has historically been performed in monkeys [4,5], but results obtained from these tests have raised questions as to whether this assay can reliably discriminate neurovirulent from nonneurovirulent mumps virus strains [6][7][8][9]. The difficulty in evaluating the neurovirulence potential of mumps viruses by use of the monkey-based assay is suggested further by reports of causal links between mumps virus CNS infections and immunization with selected mumps virus vaccines [10][11][12][13][14]. This has resulted in the withdrawal from the market of some mumps vaccines, public resistance to vaccination, and, in some countries, complete cessation of national vaccination programs.…”

“…Additional modifications are needed, such as the establishment of reference viruses and testing of other mumps vaccinessuch as the Leningrad-3-based vaccine strains, which have been associated with reports of meningitis in vaccine recipients [10]. Further validation of the rat-based neurovirulence safety test through larger studies by additional independent laboratories are required to provide a basis for the adoption of this assay by regulatory authorities and vaccine manufacturers as a replacement for the monkey-based test for the assessment of the neurovirulence potential of candidate mumps vaccine virus strains in humans.…”

Two clones obtained from Urabe AM9 mumps virus vaccine differ in their replicative efficiency in neuroblastoma cells

“…Rubini strain) [4,6], or as a result of inoculation by a relatively neurovirulent vaccine (e.g. Urabe AM9, Leningrad-3 and L-Zagreb strains) [4,[7][8][9][10][11][12][13][14][15]. A high incidence of post-vaccinal aseptic meningitis has been associated with the Urabe AM9 strain [4,7,10,11,14].…”

MMR mass vaccination campaigns, vaccine-related adverse events, and the limits of the decision making process, in Brazil

“…A report on an investigation supported by the PNI was conducted in two states and available in 1998/1999 (published in 2002 [13]). The results pointed to an association between meningitis and mumps outbreaks and MMR MIC, and again the authors suggested the interruption of MMR MIC with LZ strains (another investigation regarding campaign in 1998 in a third state was published in 2001, not available until then [14], and their authors supported such a vaccination). After these outbreaks MMR vaccines containing LZ strain were no longer used in mass campaigns by the PNI.…”