Showing papers by "Paul A. Rota published in 2005"

Genetic characterization of Nipah virus, Bangladesh, 2004.

Abstract: Until 2004, identification of Nipah virus (NV)-like outbreaks in Bangladesh was based on serology. We describe the genetic characterization of a new strain of NV isolated during outbreaks in Bangladesh (NV-B) in 2004, which confirms that NV was the etiologic agent responsible for these outbreaks.

Subacute Sclerosing Panencephalitis: More Cases of This Fatal Disease Are Prevented by Measles Immunization than Was Previously Recognized

Abstract: Background. The most severe sequela of measles virus infection is subacute sclerosing panencephalitis (SSPE), a fatal disease of the central nervous system that generally develops 7-10 years after infection. From 1989 through 1991, a resurgence of measles occurred in the United States, with 55,622 cases of measles reported. The purpose of the present study was to identify cases of SSPE that were associated with the resurgence of measles and to calculate the risk of developing SSPE. Methods. Brain tissue samples obtained from 11 patients with a presumptive diagnosis of SSPE were tested for the presence of measles virus RNA. Measles virus genotypes were determined by reverse-transcriptionpolymerase chain reaction (RT-PCR) and by analysis of the sequences of the PCR products. A search of the literature was conducted to identify reports of cases of SSPE in persons residing in the United States who had measles during 1989-1991. Results. The measles virus sequences derived from brain tissue samples obtained from 11 patients with SSPE confirmed the diagnosis of SSPE. For 5 of the 11 patients with SSPE who had samples tested by RT-PCR and for 7 patients with SSPE who were identified in published case reports, it was determined that the development of SSPE was associated with the measles resurgence that occurred in the United States during 1989-1991. The estimated risk of developing SSPE was 10-fold higher than the previous estimate reported for the United States in 1982. Conclusions. Vaccination against measles prevents more cases of SSPE than was originally estimated.

Proposal for genetic characterisation of wild-type mumps strains: Preliminary standardisation of the nomenclature

Abstract: Though mumps virus (MuV) is a monotypic virus, genetic variation between strains has been described. Viruses have been placed into genotypes designated A-L based on the nucleotide sequence of the small hydrophobic (SH) gene, which is the most variable gene in the mumps genome. Molecular characterisation of MuV is an important component of mumps surveillance because it can help identify the transmission pathways of the virus as well as distinguish between wild-type and vaccine strains. Here, we propose a standardized nomenclature and an analysis protocol for the genetic characterisation of mumps strains to facilitate expansion of molecular epidemiological studies. In addition to assigning standard reference strains for the recognized genotypes of MuV, a convention is proposed for naming for strains and criteria to designate a new genotype.

Review of the temporal and geographical distribution of measles virus genotypes in the prevaccine and postvaccine eras.

Abstract: Molecular epidemiological investigation of measles outbreaks can document the interruption of endemic measles transmission and is useful for establishing and clarifying epidemiological links between cases in geographically distinct clusters. To determine the distribution of measles virus genotypes in the prevaccine and postvaccine eras, a literature search of biomedical databases, measles surveillance websites and other electronic sources was conducted for English language reports of measles outbreaks or genetic characterization of measles virus isolates. Genotype assignments based on classification systems other than the currently accepted WHO nomenclature were reassigned using the current criteria. This review gives a comprehensive overview of the distribution of MV genotypes in the prevaccine and postvaccine eras and describes the geographically diverse distribution of some measles virus genotypes and the localized distributions of other genotypes.

Nipah virus: An emergent paramyxovirus causing severe encephalitis in humans

Abstract: Nipah virus is a recently emergent paramyxovirus that is capable of causing severe disease in both humans and animals. The first outbreak of Nipah virus occurred in Malaysia and Singapore in 1999 and, more recently, outbreaks were detected in Bangladesh. In humans, Nipah virus causes febrile encephalitis with respiratory syndrome that has a high mortality rate. The reservoir for Nipah virus is believed to be fruit bats, and humans are infected by contact with infected bats or by contact with an intermediate animal host such as pigs. Person to person spread of the virus has also been described. Nipah virus retains many of the genetic and biologic properties found in other paramyxoviruses, though it also has several unique characteristics. However, the virologic characteristics that allow the virus to cause severe disease over a broad host range, and the epidemiologic, environmental and virologic features that favor transmission to humans are unknown. This review summarizes what is known about the virology, epidemiology, pathology, diagnosis and control of this novel pathogen.

Design of a Small-Molecule Entry Inhibitor with Activity against Primary Measles Virus Strains

Abstract: The incidence of measles virus (MV) infection has been significantly reduced in many nations through extensive vaccination; however, the virus still causes significant morbidity and mortality in developing countries. Measles outbreaks also occur in some developed countries that have failed to maintain high vaccine coverage rates. While vaccination is essential in preventing the spread of measles, case management would greatly benefit from the use of therapeutic agents to lower morbidity. Thus, the development of new therapeutic strategies is desirable. We previously reported the generation of a panel of small-molecule MV entry inhibitors. Here we show that our initial lead compound, although providing proof of concept for our approach, has a short half-life (<16 h) under physiological conditions. In order to combine potent antiviral activity with increased compound stability, a targeted library of candidate molecules designed on the structural basis of the first lead has been synthesized and tested against MV. We have identified an improved lead with low toxicity and high stability (half-life 16 h) that prevents viral entry and hence infection. This compound shows high MV specificity and strong activity (50% inhibitory concentration 0.6 to 3.0 M, depending on the MV genotype) against a panel of wild-type MV strains representative of viruses that are currently endemic in the field. Paramyxoviruses are nonsegmented negative-stranded RNA viruses, most of which are highly contagious airborne pathogens that spread via the respiratory route. Members of this viral family constitute major human and animal pathogens such as measles virus (MV), human parainfluenza viruses (HPIV), mumps virus, rinderpest virus, and Newcastle disease virus (12). Despite the existence of an effective live-attenuated vaccine (6), MV remains a serious threat to human health globally, accounting for approximately 0.5 million deaths annually (1). While most of these cases occur in developing countries with limited access to vaccination, measles outbreaks still occur in some developed countries that have failed to maintain high vaccine coverage rates (4, 26). Recent outbreaks, in particular in the United Kingdom, have been attributed to declining herd immunity as a result of reduced vaccination coverage due to parental concerns about vaccination safety (8). Furthermore, vaccine-induced immunity is less robust than naturally acquired protection, which may, in fully vaccinated populations, result in a progressive loss of immunity in adults due to the absence of natural boosting through circulating virus (15, 16, 27). Taken together, these facts make desirable the development of novel therapeutics that could be produced cost-effectively and that could be used for the rapid control of local outbreaks and improved case management to limit severe outcomes of infection.

New Measles Genotype, Uganda

Abstract: We report the first genetic characterization of wildtype measles viruses from Uganda. Thirty-six virus isolates from outbreaks in 6 districts were analyzed from 2000 to 2002. Analyses of sequences of the nucleoprotein (N) and hemagglutinin (H) genes showed that the Ugandan isolates were all closely related, and phylogenetic analysis indicated that these viruses were members of a unique group within clade D. Sequences of the Ugandan viruses were not closely related to any of the World Health Organization reference sequences representing the 22 currently recognized genotypes. The minimum nucleotide divergence between the Ugandan viruses and the most closely related reference strain, genotype D2, was 3.1% for the N gene and 2.6% for the H gene. Therefore, Ugandan viruses should be considered a new, proposed genotype (d10). This new sequence information will expand the utility of molecular epidemiologic techniques for describing measles transmission patterns in eastern Africa.

Genetic characterization of measles viruses isolated in Turkey during 2000 and 2001

Abstract: Background Molecular epidemiologic studies have made significant contributions to measles surveillance activities by helping to identify source and transmission pathways of the virus. This report describes the genetic characterization of wild-type measles viruses isolated in Turkey in 2000 and 2001.

Congenital and neonatal measles during an epidemic in São Paulo, Brazil in 1997.

Abstract: During a measles outbreak, 2 mothers with measles gave birth at University Hospital in Sao Paulo City, Brazil Blood, saliva and urine were collected from the mothers and newborns Measles virus genome and IgM antibodies against measles were detected In 1 infant, measles virus genome persisted in peripheral blood mononuclear cells for 157 days after birth