Rotavirus is a leading cause of diarrhoeal mortality in children but there is considerable disagreement about how many deaths occur each year.
We compared CHERG, GBD and WHO/CDC estimates of age ...under 5 years (U5) rotavirus deaths at the global, regional and national level using a standard year (2013) and standard list of 186 countries. The global estimates were 157,398 (CHERG), 122,322 (GBD) and 215,757 (WHO/CDC). The three groups used different methods: (i) to select data points for rotavirus-positive proportions; (ii) to extrapolate data points to individual countries; (iii) to account for rotavirus vaccine coverage; (iv) to convert rotavirus-positive proportions to rotavirus attributable fractions; and (v) to calculate uncertainty ranges. We conducted new analyses to inform future estimates. We found that acute watery diarrhoea was associated with 87% (95% CI 83-90%) of U5 diarrhoea hospitalisations based on data from 84 hospital sites in 9 countries, and 65% (95% CI 57-74%) of U5 diarrhoea deaths based on verbal autopsy reports from 9 country sites. We reanalysed data from the Global Enteric Multicenter Study (GEMS) and found 44% (55% in Asia, and 32% in Africa) rotavirus-positivity among U5 acute watery diarrhoea hospitalisations, and 28% rotavirus-positivity among U5 acute watery diarrhoea deaths. 97% (95% CI 95-98%) of the U5 diarrhoea hospitalisations that tested positive for rotavirus were entirely attributable to rotavirus. For all clinical syndromes combined the rotavirus attributable fraction was 34% (95% CI 31-36%). This increased by a factor of 1.08 (95% CI 1.02-1.14) when the GEMS results were reanalysed using a more sensitive molecular test.
We developed consensus on seven proposals for improving the quality and transparency of future rotavirus mortality estimates.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Type I and type III IFNs bind to different cell-surface receptors but induce identical signal transduction pathways, leading to the expression of antiviral host effector molecules. Despite the fact ...that type III IFN (IFN-λ) has been shown to predominantly act on mucosal organs, in vivo infection studies have failed to attribute a specific, nonredundant function. Instead, a predominant role of type I IFN was observed, which was explained by the ubiquitous expression of the type I IFN receptor. Here we comparatively analyzed the role of functional IFN-λ and type I IFN receptor signaling in the innate immune response to intestinal rotavirus infection in vivo, and determined viral replication and antiviral gene expression on the cellular level. We observed that both suckling and adult mice lacking functional receptors for IFN-λ were impaired in the control of oral rotavirus infection, whereas animals lacking functional receptors for type I IFN were similar to wild-type mice. Using Mx1 protein accumulation as marker for IFN responsiveness of individual cells, we demonstrate that intestinal epithelial cells, which are the prime target cells of rotavirus, strongly responded to IFN-λ but only marginally to type I IFN in vivo. Systemic treatment of suckling mice with IFN-λ repressed rotavirus replication in the gut, whereas treatment with type I IFN was not effective. These results are unique in identifying a critical role of IFN-λ in the epithelial antiviral host defense.
Summary Background WHO recommends routine use of rotavirus vaccines in all countries, particularly in those with high mortality attributable to diarrhoeal diseases. To establish the burden of ...life-threatening rotavirus disease before the introduction of a rotavirus vaccine, we aimed to update the estimated number of deaths worldwide in children younger than 5 years due to diarrhoea attributable to rotavirus infection. Methods We used PubMed to identify studies of at least 100 children younger than 5 years who had been admitted to hospital with diarrhoea. Additionally, we required the studies to have a data collection midpoint of the year 2000 or later, to be done in full-year increments, and to assesses diarrhoea attributable to rotavirus with EIAs or polyacrylamide gel electrophoresis. We also included data from countries that participated in the WHO-coordinated Global Rotavirus Surveillance Network (consisting of participating member states during 2009) and that met study criteria. For countries that have introduced a rotavirus vaccine into their national immunisation programmes, we excluded data subsequent to the introduction. We classified studies into one of five groups on the basis of region and the level of child mortality in the country in which the study was done. For each group, to obtain estimates of rotavirus-associated mortality, we multiplied the random-effect mean rotavirus detection rate by the 2008 diarrhoea-related mortality figures for countries in that group. We derived the worldwide mortality estimate by summing our regional estimates. Findings Worldwide in 2008, diarrhoea attributable to rotavirus infection resulted in 453 000 deaths (95% CI 420 000–494 000) in children younger than 5 years—37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than 5 years. Five countries accounted for more than half of all deaths attributable to rotavirus infection: Democratic Republic of the Congo, Ethiopia, India, Nigeria, and Pakistan; India alone accounted for 22% of deaths (98 621 deaths). Interpretation Introduction of effective and available rotavirus vaccines could substantially affect worldwide deaths attributable to diarrhoea. Our new estimates can be used to advocate for rotavirus vaccine introduction and to monitor the effect of vaccination on mortality once introduced. Funding None.
Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. ...We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. Methods. We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip. Results. We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009). Conclusions. The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries.
Rotavirus and severe childhood diarrhea Parashar, Umesh D; Gibson, Christopher J; Bresee, Joseph S ...
Emerging infectious diseases,
02/2006, Letnik:
12, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Studies published between 1986 and 1999 indicated that rotavirus causes approximately 22% (range 17%-28%) of childhood diarrhea hospitalizations. From 2000 to 2004, this proportion increased to 39% ...(range 29%-45%). Application of this proportion to the recent World Health Organization estimates of diarrhea-related childhood deaths gave an estimated 611,000 (range 454,000-705,000) rotavirus-related deaths.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. Rotavirus vaccine is recommended for routine use in all countries globally. To facilitate decision making on rotavirus vaccine adoption by countries, help donors prioritize investments in ...health interventions, and monitor vaccine impact, we estimated rotavirus mortality for children <5 years of age from 2000 to 2013. Methods. We searched PubMed using the keyword "rotavirus" to identify studies that met each of the following criteria: data collection midpoint in year 1998 or later, study period of a 12-month increment, and detection of rotavirus infection by enzyme immunoassay in at least 100 children <5 years of age who were hospitalized with diarrhea and systematically enrolled through active surveillance. We also included data from countries that participated in the World Health Organization (WHO)-coordinated rotavirus surveillance network between 2008 and 2013 that met these criteria. To predict the proportion of diarrhea due to rotavirus, we constructed a multiple linear regression model. To determine the number of rotavirus deaths in children <5 years of age from 2000 to 2013, we multiplied annual, country-specific estimates of the proportion of diarrhea due to rotavirus from the regression model by the annual number of WHO-estimated child deaths caused by diarrhea in each country. Results. Globally, we estimated that the number of rotavirus deaths in children <5 years of age declined from 528 000 (range, 465 000–591 000) in 2000 to 215 000 (range, 197 000–233 000) in 2013. The predicted annual rotavirus detection rate from these studies declined slightly over time from 42.5% (95% confidence interval CI, 37.4%–47.5%) in 2000 to 37.3% (95% CI, 34.2%–40.5%) in 2013 globally. In 2013, an estimated 47 100 rotavirus deaths occurred in India, 22% of all rotavirus deaths that occurred globally. Four countries (India, Nigeria, Pakistan, and Democratic Republic of Congo) accounted for approximately half (49%) of all estimated rotavirus deaths in 2013. Discussion. While rotavirus vaccine had been introduced in >60 countries worldwide by the end of 2013, the majority of countries using rotavirus vaccine during the review period were low-mortality countries and the impact of rotavirus vaccine on global estimates of rotavirus mortality has been limited. Continued monitoring of rotavirus mortality rates and deaths through rotavirus surveillance will aid in monitoring the impact of vaccination.
Highlights ► Prevalence data on ∼110,000 rotavirus strains identified from 100 countries worldwide during a 12-year period preceding introduction of rotavirus vaccines were collected and presented in ...this systematic review ► The paper summarizes (i) baseline strain prevalence data for the pre-vaccine era, (ii) analyzes spatiotemporal trends in distribution of circulating strains, and (iii) provides a weighted model to describe a more reliable estimate on the medical importance of individual rotavirus strains.
The epithelium is the main entry point for many viruses, but the processes that protect barrier surfaces against viral infections are incompletely understood. Here we identified interleukin 22 ...(IL-22) produced by innate lymphoid cell group 3 (ILC3) as an amplifier of signaling via interferon-λ (IFN-λ), a synergism needed to curtail the replication of rotavirus, the leading cause of childhood gastroenteritis. Cooperation between the receptor for IL-22 and the receptor for IFN-λ, both of which were 'preferentially' expressed by intestinal epithelial cells (IECs), was required for optimal activation of the transcription factor STAT1 and expression of interferon-stimulated genes (ISGs). These data suggested that epithelial cells are protected against viral replication by co-option of two evolutionarily related cytokine networks. These data may inform the design of novel immunotherapy for viral infections that are sensitive to interferons.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Rotaviruses are important enteric pathogens of humans and animals. Group A rotaviruses (GARVs) account for up to 1 million children deaths each year, chiefly in developing countries and human ...vaccines are now available in many countries. Rotavirus-associated enteritis is a major problem in livestock animals, notably in young calves and piglets. Early in the epidemiological GARV studies in humans, either sporadic cases or epidemics by atypical, animal-like GARV strains were described. Complete genome sequencing of human and animal GARV strains has revealed a striking genetic heterogeneity in the 11 double stranded RNA segments across different rotavirus strains and has provided evidence for frequent intersections between the evolution of human and animal rotaviruses, as a result of multiple, repeated events of interspecies transmission and subsequent adaptation.
Background. The live oral rotavirus (RV) vaccines have shown a reduced efficacy in Africa. Recent in vitro studies have shown binding of the RV surface protein (VP4) to histo–blood group antigens ...(HBGAs) in an RV genotype–dependent manner, suggesting them to be putative receptors for RV. The diversity of HBGA phenotypes in different ethnic populations, combined with prevalence/absence of specific RV genotypes, led us to hypothesize whether the genetic variations in HBGAs in a population limit susceptibility to certain RV genotypes, plausibly leading to reduced vaccine efficacy. Methods. Association between HBGAs status and susceptibility to RV P genotypes was investigated in children in Burkina Faso and Nicaragua. In total, 242 children with diarrhea in Burkina Faso and Nicaragua were investigated, 93 of whom were RV positive. Results. In Burkina Faso, the P8 RV strains (n = 27) infected only Lewis- and secretor-positive children (27/27; P < .0001), but no Lewis-negative children. In contrast, the P6 strains (n = 27) infected predominantly Lewis-negative children (n = 18; P < .0001) but also Lewis-positive children, irrespective of their secretor status. The results from Nicaragua confirmed that all P8-infected children (n = 22) were secretor Lewis positive. Conclusions. As VP4 of genotype P8 is a component of current RV vaccines, our finding that Lewis-negative children are resistant to P8 strains provides a plausible explanation for the reduced vaccine efficacy in populations with a high percentage of Lewis-negative individuals, such as in Africa. Furthermore, our findings provide a plausible explanation as to why P6 RV strains are more common in Africa.
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