Posts Tagged ‘Rotavirus’

Rotavirus Roundup

Monday, March 18th, 2013

Rotaviruses There have been several interesting papers recently on responses to rotavirus infection, so I thought I’d round them up in one place:


The Battle between Rotavirus and Its Host for Control of the Interferon Signaling Pathway. (2013) PLoS Pathog 9(1): e1003064
Viral pathogens must overcome innate antiviral responses to replicate successfully in the host organism. Some of the mechanisms viruses use to interfere with antiviral responses in the infected cell include preventing detection of viral components, perturbing the function of transcription factors that initiate antiviral responses, and inhibiting downstream signal transduction. RNA viruses with small genomes and limited coding space often express multifunctional proteins that modulate several aspects of the normal host response to infection. One such virus, rotavirus, is an important pediatric pathogen that causes severe gastroenteritis, leading to ~450,000 deaths globally each year. This review discusses the nature of the innate antiviral responses triggered by rotavirus infection and the viral mechanisms for inhibiting these responses.


The impact of Rotavirus mass vaccination on hospitalization rates, nosocomial Rotavirus gastroenteritis and secondary blood stream infections. (2013) BMC Infect Dis. 13(1): 112
The aim of this study was to evaluate the effects of universal mass vaccination (UMV) against rotavirus (RV) on the hospitalization rates, nosocomial RV infections and RV-gastroenteritis (GE)-associated secondary blood stream infections (BSI).
Retrospective evaluation (2002-2009) by chart analysis included all clinically diagnosed and microbiologically confirmed RV-GE cases in a large tertiary care hospital in Austria. The pre-vaccination period (2002-2005) was compared with the recommended and early funded (2006–2007) and the funded (2008–2009) vaccination periods. Primary outcomes were RV-GE-associated hospitalizations, secondary outcomes nosocomial RV disease, secondary BSI and direct hospitalization costs for children and their accompanying persons.
In 1,532 children with RV-GE, a significant reduction by 73.9% of hospitalized RV-GE cases per year could be observed between the pre-vaccination and the funded vaccination period, which was most pronounced in the age groups 0-11 months (by 87.8%), 6-10 years (by 84.2%) and 11-18 years (88.9%). In the funded vaccination period, a reduction by 71.9% of nosocomial RV-GE cases per year was found compared to the pre-vaccination period. Fatalities due to nosocomial RV-GE were only observed in the pre-vaccination period (3 cases). Direct costs of hospitalized, community-acquired RV-GE cases per year were reduced by 72.7% in the funded vaccination period. The reduction of direct costs for patients (by 86.9%) and accompanying persons (86.2%) was most pronounced in the age group 0-11 months.
UMV may have contributed to the significant decrease of RV-GE-associated hospitalizations, to a reduction in nosocomial RV infections and RV-associated morbidity due to secondary BSI and reduced direct hospitalization costs. The reduction in nosocomial cases is an important aspect considering severe disease courses in hospitalized patients with co-morbidities and death due to nosocomial RV-GE.


Innate cellular responses to rotavirus infection. J Gen Virol. 13 Mar 2013
Rotavirus is a leading cause of severe dehydrating diarrhoea in infants and young children. Following rotavirus infection in the intestine an innate immune response is rapidly triggered. This response leads to the induction of type I and type III interferons (IFNs) and other cytokines, resulting in a reduction in viral replication. Here we review the current literature describing the detection of rotavirus infection by pattern recognition receptors within host cells, the subsequent molecular mechanisms leading to IFN and cytokine production, and the processes leading to reduced rotavirus replication and the development of protective immunity. Rotavirus countermeasures against innate responses, and their roles in modulating rotavirus replication in mice, also are discussed. By linking these different aspects of innate immunity we provide a comprehensive overview of the host’s first line of defence against rotavirus infection. Understanding these processes is expected to be of benefit in improving strategies to combat rotavirus disease.


Rotavirus vaccine for UK babies 

Saturday, November 10th, 2012

Rotavirus vaccine, Rotarix, will be added to the UK routine childhood vaccination schedule next year. It is estimated that the vaccine will halve the number of vomiting and diarrhoea cases caused by rotavirus and there could be 70% fewer hospital stays as a result. In the USA, rotavirus-related hospital admissions have fallen by as much as 86% since the Rotarix vaccine was introduced:


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Routine rotavirus vaccination in Brazil has reduced diarrheoa deaths in children

Wednesday, April 20th, 2011

Rotavirus Diarrhoeal disease, usually caused by infectious agents, is the second major cause of death in children aged under five years. Access to clean water and improved sanitation is the key to the primary prevention of diarrheal illnesses. Yet despite the targets of Millennium Development Goal 7 to half the number of people without access to clean water or improved sanitation by 2015, over one billion people worldwide do not currently have access to clean water and over two billion do not currently have access to improved sanitation. Since enteric viruses are primarily transmitted directly from one person to another, they cannot be controlled completely by improvements in sanitation. Therefore, although not replacing the urgent need to provide access to clean water and improved sanitation for all, vaccination programs that protect young children against some infections that cause diarrhea, such as rotavirus, which accounts for one-third of all child deaths caused by diarrhoea, are a pragmatic way forward. As large clinical trials have shown the safety and efficacy of rotavirus vaccines in population settings, in July 2009, the World Health Organization recommended including rotavirus vaccines into every country’s national immunization programs.

Rotavirus vaccination in all areas of Brazil is associated with reduced diarrheoa-related deaths and hospital admissions in children aged under five years. New research has shown that these real-world impact data – what actually happens in reality rather than in strictly controlled clinical trial settings – are consistent with the clinical trials and conclude that their study strengthens the evidence base for use of rotavirus vaccination as an effective measure for controlling severe and fatal childhood diarrheoa.

Brazil has a high incidence of diarrhea-related deaths and hospital admissions in young children and, in July 2006, the Brazilian Ministry of Health introduced rotavirus vaccination simultaneously in all 27 states, allowing the authors to conduct a ‘‘before’’ and ‘‘after’’ intervention analysis. Using routinely collected national data, the authors found that in 2007 an estimated 80% of infants received two doses of rotavirus vaccine, and by 2009 that this proportion rose to 84% of children younger than one year of age. In the three years following the introduction of rotavirus vaccination, diarrhea-related mortality rates and admissions among children aged under five years were, respectively, 22% and 17% lower than expected, with a cumulative total of 1,500 fewer diarrheoa deaths and 130,000 fewer hospital admissions. Furthermore, the largest reductions in deaths and admissions were among children who had the highest rates of vaccination (less than two years of age), and the lowest reductions were among children who were not age-eligible for vaccination during the study period (aged 2–4 years).

This time-series analysis provides evidence of substantial reductions following the introduction of rotavirus vaccination of both diarrheoa-related deaths and diarrheoa-related hospital admissions from a large middle-income country in the Americas with both developing and developed regions. In middle-income countries that are not eligible for financial support from donors, the potential reductions in diarrheoa-related hospital admissions and other health-care costs will be important for cost-effectiveness considerations to justify the purchase of these relatively expensive vaccines.

Decline in Diarrhea Mortality and Admissions after Routine Childhood Rotavirus Immunization in Brazil: A Time-Series Analysis. 2011 PLoS Med 8(4): e1001024. doi:10.1371/journal.pmed.1001024
Background: In 2006, Brazil began routine immunization of infants ,15 wk of age with a single-strain rotavirus vaccine. We evaluated whether the rotavirus vaccination program was associated with declines in childhood diarrhea deaths and hospital admissions by monitoring disease trends before and after vaccine introduction in all five regions of Brazil with varying disease burden and distinct socioeconomic and health indicators.
Methods and Findings: National data were analyzed with an interrupted time-series analysis that used diarrhea-related mortality or hospitalization rates as the main outcomes. Monthly mortality and admission rates estimated for the years after rotavirus vaccination (2007–2009) were compared with expected rates calculated from pre-vaccine years (2002–2005), adjusting for secular and seasonal trends. During the three years following rotavirus vaccination in Brazil, rates for diarrhea- related mortality and admissions among children ,5 y of age were 22% (95% confidence interval 6%–44%) and 17% (95% confidence interval 5%–27%) lower than expected, respectively. A cumulative total of ,1,500 fewer diarrhea deaths and 130,000 fewer admissions were observed among children ,5 y during the three years after rotavirus vaccination. The largest reductions in deaths (22%–28%) and admissions (21%–25%) were among children younger than 2 y, who had the highest rates of vaccination. In contrast, lower reductions in deaths (4%) and admissions (7%) were noted among children two years of age and older, who were not age-eligible for vaccination during the study period.
Conclusions: After the introduction of rotavirus vaccination for infants, significant declines for three full years were observed in under-5-y diarrhea-related mortality and hospital admissions for diarrhea in Brazil. The largest reductions in diarrhea-related mortality and hospital admissions for diarrhea were among children younger than 2 y, who were eligible for vaccination as infants, which suggests that the reduced diarrhea burden in this age group was associated with introduction of the rotavirus vaccine. These real-world data are consistent with evidence obtained from clinical trials and strengthen the evidence base for the introduction of rotavirus vaccination as an effective measure for controlling severe and fatal childhood diarrhea.

Assortment and packaging of the rotavirus genome

Wednesday, February 9th, 2011

Rotavirus The rotavirus (RV) genome comprises 11 segments of double-stranded RNA (dsRNA) and is contained within a non-enveloped, icosahedral particle. During assembly, a highly coordinated selective packaging mechanism ensures that progeny RV virions contain one of each genome segment. Cis-acting signals thought to mediate assortment and packaging are associated with putative panhandle structures formed by base-pairing of the ends of RV plus-strand RNAs (+RNAs). Viral polymerases within assembling core particles convert the 11 distinct +RNAs to dsRNA genome segments. It remains unclear whether RV +RNAs are assorted before or during encapsidation, and the functions of viral proteins during these processes are not resolved. However, as reviewed in this article, recent insights gained from the study of RV and two other segmented RNA viruses, influenza A virus and bacteriophage Φ6, reveal potential mechanisms of RV assortment and packaging.

Assortment and packaging of the segmented rotavirus genome. Trends Microbiol. Dec 30 2010


How to make a rotavirus vaccine

Tuesday, July 6th, 2010

Rotavirus Group A rotaviruses (RVs) are important pathogens that cause acute, dehydrating gastroenteritis in infants and young children. The burden of disease is severe, particularly in developing countries where RV infections lead to more than 500,000 deaths annually. RVs are non-enveloped, triple-layered icosahedral particles that enclose an eleven-segmented, double-stranded (ds) RNA genome. The genome encodes six structural proteins (VP1–VP4, VP6, and VP7) and five or six non-structural proteins (NSP1–NSP5, and sometimes NSP6). Individual RV strains have traditionally been classified into serotypes based on the antibody responses generated against the outermost structural proteins VP7 (G-serotypes) and VP4 (P-serotypes). Due to the ease of sequencing, RVs are now classified into G/P-genotypes based on the relatedness of the genes encoding VP7 and VP4.

Although the mechanism by which RV infection leads to immunological protection is not fully understood, G/P-type-specific neutralizing antibodies have been shown to play an important role. Strains with particular G/P-type combinations are the most prevalent causes of disease in humans worldwide, and these are the targets of the two currently licensed RV vaccines. RotaTeq (Merck) contains five live-attenuated, reassortant viruses with human VP7 genes in a predominantly bovine RV background. In contrast, Rotarix (GlaxoSmithKline) is a live-attenuated, human RV containing genotype 1 internal genes. Both vaccines have proven safe and effective at protecting against severe diarrheal disease in industrialized countries and Latin America. However, the efficacy of RotaTeq and Rotarix in developing countries is expected to be reduced, which may be related to viral serotype diversity among other factors. Additionally, the high monetary cost of these current vaccines may limit their availability in regions of the world where they are most needed. As a result, there is a global health initiative to develop new RV vaccines that can be manufactured on-site at a lower cost. Two vaccine candidates being considered are the live-attenuated human strains RV3 and 116E.

Complete genome sequence analysis of candidate human rotavirus vaccine strains RV3 and 116E. Virology. Jun 25 2010
Rotaviruses (RVs) cause severe gastroenteritis in infants and young children; yet, several strains have been isolated from newborns showing no signs of clinical illness. Two of these neonatal strains, RV3 (G3P[6]) and 116E (G9P[11]), are currently being developed as live-attenuated vaccines. In this study, we sequenced the eleven-segmented double-stranded RNA genomes of cell culture-adapted RV3 and 116E and compared their genes and protein products to those of other RVs. Using amino acid alignments and structural predictions, we identified residues of RV3 or 116E that may contribute to attenuation or influence vaccine efficacy. We also discovered residues of the VP4 attachment protein that correlate with the capacity of some P[6] strains, including RV3, to infect newborns versus older infants. The results of this study enhance our understanding of the molecular determinants of RV3 and 116E attenuation and are expected to aid in the ongoing development of these vaccine candidates.


Rotavirus vaccines for the developing world

Thursday, October 8th, 2009

Rotavirus Rotaviruses were discovered in 1972 when the virus was seen by direct electron microscopy visualization in the intestinal biopsies of children with acute diarrhoea. The authors of a new review discuss the most relevant information in the field of rotavirus vaccines published from October 2007 to June 2009; new information on the virus, host response and disease burden that relate to our understanding of vaccine mechanisms and impact are discussed. The review focusses on the role of the vaccines for the developing world but this does not preclude the relevance of these vaccines for children living in the industrialized world.

Immune mechanisms involved in rotavirus-associated immunity potentially relevant for vaccine-associated immunity continue to be identified including anti-NSP4 antibodies, cellular and mucosal mechanisms. Rotavirus-associated disease burden is high, causing approximately 40% of diarrhea-associated hospitalizations in children less than 5 years of age worldwide; G12, G8 and P[6] antigenic types emerging in developing countries are increasing in prevalence and may share worldwide circulation with the other five more common serotypes. The two currently available vaccines, based on different immune concepts, (VP7/VP4 homotypic specificity for RotaTeq vs. homotypic and heterotypic specificity for Rotarix) have demonstrated high and sustained efficacy in middle and high-income countries. Recent efficacy and effectiveness studies demonstrate acceptable protection levels in the poorest countries of the world against most antigenic types, leading to universal vaccine recommendation. Postlicensure surveillance has not detected any signal of increased risk for intussusception in children vaccinated with any of the two vaccines.

Rotavirus vaccines are well tolerated and provide adequate protection against moderate to severe disease in high, middle and low-income regions. Partnerships between governments, industry, and funding agencies will now be urgently needed to promote vaccine use, especially in the less privileged countries of the world.

Rotavirus vaccines for the developing world. 2009 Current Opinion in Infectious Diseases 22 (5): 483-489