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Rotavirus infection: a perspective on epidemiology, genomic diversity and vaccine strategies.

ABSTRACT: For centuries, acute diarrhea has been a major cause of death in young children worldwide, and until 1973, before rotavirus was discovered; no infectious agents could be identified in about 80% of patients admitted to hospital with severe dehydrating diarrhea. Rotaviruses have now been shown to cause 40-50% of severe acute diarrhea in young children worldwide in both developing and developed countries. More than 600,000 young children die and approximately 2.4 million hospitalize annually from rotavirus disease, especially in South-East Asia and sub-Saharan Africa. Two safe and effective vaccines are now licensed in 100 countries but used in 17 countries. Rotarix (GSK) vaccine is derived from single attenuated human rotavirus G1P[8], representative of the most common serotype identified worldwide. RotaTeq (Merck) is a pentavalent mixture of naturally attenuated bovine/human rotavirus reassortants representing G1, G2, G3, G4, and P[8] serotypes. Though these vaccines have already dramatically decreased the morbidity associated with rotavirus in countries where they are widely used, the third generation of vaccines, based on inactivated viruses or recombinant virus like particle are already in pipeline. Continuous surveillance and the genetic and antigenic analysis of the various strains of rotavirus circulating worldwide will aid significantly in assessing the effectiveness of these vaccines and monitor emergence of new strains. Introduction of rotavirus vaccines in national vaccine policy along with other childhood vaccines may result in significant reduction in mortality in children in poor socioeconomic countries.

SUBMITTER: Mukherjee A

PROVIDER: S-EPMC3550723 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Rotavirus infection: a perspective on epidemiology, genomic diversity and vaccine strategies.

Mukherjee Anupam A Chawla-Sarkar Mamta M

Indian journal of virology : an official organ of Indian Virological Society 20110614 1

For centuries, acute diarrhea has been a major cause of death in young children worldwide, and until 1973, before rotavirus was discovered; no infectious agents could be identified in about 80% of patients admitted to hospital with severe dehydrating diarrhea. Rotaviruses have now been shown to cause 40-50% of severe acute diarrhea in young children worldwide in both developing and developed countries. More than 600,000 young children die and approximately 2.4 million hospitalize annually from r ...[more]

PMID: 23637497

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Project description:BackgroundThe increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We aimed to explore Treponema pallidum subspecies pallidum (TPA) molecular epidemiology essential for vaccine research by analysing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data.MethodsIn this multicentre, cross-sectional, molecular epidemiology study, we enrolled patients with primary, secondary, or early latent syphilis from clinics in China, Colombia, Malawi, and the USA between Nov 28, 2019, and May 27, 2022. Participants aged 18 years or older with laboratory confirmation of syphilis by direct detection methods or serological testing, or both, were included. Patients were excluded from enrolment if they were unwilling or unable to give informed consent, did not understand the study purpose or nature of their participation, or received antibiotics active against syphilis in the past 30 days. TPA detection and WGS were conducted on lesion swabs, skin biopsies, skin scrapings, whole blood, or rabbit-passaged isolates. We compared our WGS data to publicly available genomes and analysed TPA populations to identify mutations associated with lineage and geography.FindingsWe screened 2802 patients and enrolled 233 participants, of whom 77 (33%) had primary syphilis, 154 (66%) had secondary syphilis, and two (1%) had early latent syphilis. The median age of participants was 28 years (IQR 22-35); 154 (66%) participants were cisgender men, 77 (33%) were cisgender women, and two (1%) were transgender women. Of the cisgender men, 66 (43%) identified as gay, bisexual, or other sexuality. Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants showed a predominance of SS14-lineage strains with geographical clustering. Phylogenomic analyses confirmed that Nichols-lineage strains were more genetically diverse than SS14-lineage strains and clustered into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models showed population-specific substitutions, some in outer membrane proteins (OMPs) of interest.InterpretationOur study substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains is vital for vaccine development and understanding syphilis pathogenesis on a population level.FundingUS National Institutes of Health National Institute for Allergy and Infectious Disease, the Bill & Melinda Gates Foundation, Connecticut Children's, and the Czech Republic National Institute of Virology and Bacteriology.

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Rotavirus infection: a perspective on epidemiology, genomic diversity and vaccine strategies.

Publications

Rotavirus infection: a perspective on epidemiology, genomic diversity and vaccine strategies.

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