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Biomedical subjects

P Rota

Publications and source records attributed to P Rota.

At least 19 recordsLinked to original sources

Evaluation of recombinant vaccinia virus--measles vaccines in infant rhesus macaques with preexisting measles antibody.

Immunization of newborn infants with standard measles vaccines is not effective because of the presence of maternal antibody. In this study, newborn rhesus macaques were immunized with recombinant vaccinia viruses expressing measles virus hemagglutinin (H) and fusion (F) proteins, using the replication-competent WR strain of vaccinia virus or the replication-defective MVA strain. The infants were boosted at 2 months and then challenged intranasally with measles virus at 5 months of age. Some of the newborn monkeys received measles immune globulin (MIG) prior to the first immunization, and these infants were compared to additional infants that had maternal measles-neutralizing antibody. In the absence of measles antibody, vaccination with either vector induced neutralizing antibody, cytotoxic T cell (CTL) responses to measles virus and protection from systemic measles infection and skin rash. The infants vaccinated with the MVA vector developed lower measles-neutralizing antibody titers than those vaccinated with the WR vector, and they sustained a transient measles viremia upon challenge. Either maternal antibody or passively transferred MIG blocked the humoral response to vaccination with both WR and MVA, and the frequency of positive CTL responses was reduced. Despite this inhibition of vaccine-induced immunity, there was a reduction in peak viral loads and skin rash after measles virus challenge in many of the infants with preexisting measles antibody. Therefore, vaccination using recombinant vectors such as poxviruses may be able to prevent the severe disease that often accompanies measles in infants.

Animals↗

Population biology, evolution, and immunology of vaccination and vaccination programs.

The purpose of prophylactic vaccination is to reduce morbidity and mortality in a population. Many questions related to the design of vaccines and vaccination programs require a population standpoint for their sharp formulation and laboratory and field studies to understand their immunologic background. Practical suggestions of the workshop included increased studies of age-specific immunity, better immunoepidemiologic surveillance, better design of efficacy studies, and more systematic sampling of parasite strains to study the evolutionary pressure exerted by vaccines. Theoretical immunology has much to contribute. One of the realizations of the workshop was the value of a strong interdisciplinary approach in vaccine development, utilizing relevant contributions from immunology, population biology, mathematical modeling, epidemiology, molecular biology, and virology.

Animals↗

Measles outbreaks in Micronesia, 1991 to 1994.

BACKGROUND: Several islands in Micronesia experienced large measles outbreaks, during 1991 through 1994. Except for Guam, none of the islands had reported measles outbreaks during the previous 20 years. METHODS: To characterize the outbreaks, measles surveillance data, hospital records and death certificates were reviewed. Preoutbreak vaccination coverage rates were assessed by reviewing public health vaccination records. Viral isolates were genetically sequenced to determine the source of transmission. Linear regression analysis was performed to assess the effectiveness of outbreak control measures. RESULTS: Between 1991 and 1994 more than 1300 measles cases and 16 measles-related deaths were reported in Micronesia. Preoutbreak vaccination coverage rates among 2-year-old children were 55 to 94%. Genetic sequencing of the viral isolates and epidemiologic investigations suggested transmission between islands and new importations from outside of Micronesia. The highest attack rates were among children ages < 5 years (20/1000) and 10 to 19 years (38/1000). Compared with attack rates among children ages < 1 and 10 to 19 years, attack rates were lower among those ages 5 to 9 years, in whom 2-dose vaccination coverage rates were highest (P < 0.001). Early and rapid implementation of mass vaccination campaigns was significantly associated with shorter duration of outbreaks (P = 0.049). CONCLUSION: The measles outbreaks in Micronesia show that island populations may be highly susceptible to measles. High two-dose vaccination coverage levels must be maintained to prevent such outbreaks. Early and rapidly implemented mass measles vaccination campaigns were effective in control of island outbreaks. Strengthening public health infrastructure and surveillance is necessary for early identification of outbreaks and rapid implementation of mass campaigns.

Adolescent↗

Experimental measles. II. Infection and immunity in the rhesus macaque.

Measles infection and the host immune response to measles virus was compared using naive and immunized rhesus monkeys. The monkeys were experimentally challenged with a wild-type strain of measles virus inoculated intranasally. After pathogenic virus challenge, measles virus was detected in mononuclear cells of peripheral blood, lymph node, and spleen in naive monkeys and viremia peaked on Day 7. However, only one of five vaccinated monkeys had a lower virus titer in peripheral blood mononuclear cells at one time point after challenge. No virus was detected in the lymphoid tissues from an immunized monkeys that was euthanized on Day 7 of infection. Measles-specific IgM, IgG, neutralizing antibody, and cytotoxic T lymphocytes were detected in vaccinated monkeys before challenge, but antibody titers were significantly lower in immunized monkeys than in naive monkey after challenge. Measles-specific IgG antibody and cytotoxic T cell responses were still detected more than 1 year after vaccination or infection. This animal model is useful for the further study of measles pathogenesis, immunosuppression, and immunologic memories.

Animals↗

Treatment of chronic heart failure: an expert system advisor for general practitioners.

Most decision-support systems in medicine have been developed in hospital environments, but only few are designed for being used by general practitioners. The present work aims to design an expert system for practitioners in chronic heart failure (CHF) treatment. It provides assistance in defining the therapy relying on CHF aetiology, gravity, physiopathological conditions, and discriminates if other coexistent diseases and/or drugs taken by the patient could interact with CHF management. It warns the physician about the possible interactions of the considered CHF therapy. In case of contraindications, the system suggests another alternative therapy. It also advices about the control tests to follow-up the prescribed therapy, and about the indicated hygienic-dietetic suggestions. To assess its internal consistency, we examined the behaviour of the system with 20 CHF patients, by comparing the suggested therapy with the prescriptions of cardiologists. In 9 cases the suggested therapeutic schemes contained all the "n" drugs administered by the cardiologists. In 5 cases the concordance was on at least two thirds of the prescribed medications, in 5 between one half and two thirds, while in 1 case there was no concordance at all. In none of the 10 cases with partial concordance, were there major discrepancies (i.e. potentially deleterious for the patient) between the expert system's suggestions and the cardiologists' prescriptions. In conclusion, the advices of the expert system were similar to those of the cardiologists, suggesting the feasibility of such a computer support to CHF management.

Anti-Arrhythmia Agents↗

Comparison between two peptide epitopes presented to cytotoxic T lymphocytes by HLA-A2. Evidence for discrete locations within HLA-A2.

An influenza B virus nucleoprotein (BNP) peptide, residues 82-94, defined by limited sequence homology with an HLA-A2-restricted peptide from influenza A matrix protein, was recognized by HLA-A2-restricted CTL. Reciprocal inhibition of T cell recognition by the two peptides suggest that the BNP peptide may have lower avidity for HLA-A2 molecules than the matrix peptide. The interaction between this peptide and HLA-A2 was explored by studying the CTL recognition of BNP 82-94 presented by mutant HLA-A2 molecules. Mutations at residues 9, 99, 70, 74, 152 and 156 were found to abolish T cell recognition of the BNP peptide. These results were compared with results previously obtained with the influenza A matrix peptide and suggest that the two peptides bind differently in the peptide binding site.

Amino Acid Sequence↗

Nipah virus infection in bats (order Chiroptera) in peninsular Malaysia.

Nipah virus, family Paramyxoviridae, caused disease in pigs and humans in peninsular Malaysia in 1998-99. Because Nipah virus appears closely related to Hendra virus, wildlife surveillance focused primarily on pteropid bats (suborder Megachiroptera), a natural host of Hendra virus in Australia. We collected 324 bats from 14 species on peninsular Malaysia. Neutralizing antibodies to Nipah virus were demonstrated in five species, suggesting widespread infection in bat populations in peninsular Malaysia.

Animals↗

[Features of primary structure of genes and proteins from passaged variations of measles virus].

Primary structure and proteins of measles virus variants passaged in tissue culture were studied. The findings suggest that genetic determinants responsible for measles virus attenuation are not linked with the genes coding for envelope proteins and nucleoprotein of this virus. However the detected nucleotide substitutions can be considered as the main prerequisites for the appearance of mutations in other regions of viral genome, leading to decrease of virulence for humans.

Amino Acid Sequence↗

[Genetic characterisation of wild measles strains circulating in European part of Russia in 1998-2002].

The primary structure of the N-gene COOH terminus of measles virus isolated, 1998-2000, in Russia's European part was investigated. The general analysis as well as an analysis of the primary gene structure showed the two group's isolates as belonging to the D4 genotype. A subsequent analysis of the primary structure of the N-gene COOH-terminus of Moscow/2002/61 isolated during the 2002 measles outbreak in Moscow also showed it as belonging to the D4 genotype. The obtained data are indicative of that the wild measles strains belonging to the D4 genotype have been recently circulating in Russia's territory.

Base Sequence↗