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Rotavirus Antigenemia in Children Is Associated with Viremia  [PDF]
Sarah E Blutt,David O Matson,Sue E Crawford,Mary Allen Staat,Parvin Azimi,Berkeley L Bennett,Pedro A Piedra,Margaret E Conner
PLOS Medicine , 2007, DOI: 10.1371/journal.pmed.0040121
Abstract: Background Antigenemia is commonly detected in rotavirus-infected children. Although rotavirus RNA has been detected in serum, definitive proof of rotavirus viremia has not been shown. We aimed to analyze a defined patient population to determine if infectious virus could be detected in sera from children with rotavirus antigenemia. Methods and Findings Serum samples obtained upon hospitalization from children with gastroenteritis (57 stool rotavirus-positive and 41 rotavirus-negative), children with diagnosed bronchiolitis of known (n = 58) or unknown (n = 17) viral etiology, children with noninfectious, nonchronic conditions (n = 17), and healthy adults (n = 28) were tested for rotavirus antigen by enzyme immunoassay (EIA). Results of serum antigen testing were assessed for association with clinical and immunological attributes of the children. Rotavirus antigenemia was detected in 90% (51/57) of children with rotavirus-positive stools, in 89% (8/9) of children without diarrhea but with rotavirus-positive stools, in 12% (2/17) of children with bronchiolitis of unknown etiology without gastroenteritis, and in 12% (5/41) of children with gastroenteritis but with rotavirus-negative stools. Antigenemia was not detected in sera from children with noninfectious nonchronic conditions, children with bronchiolitis of known etiology and no gastroenteritis, or healthy adults. Neither age nor timing of serum collection within eight days after onset of gastroenteritis significantly affected levels of antigenemia, and there was no correlation between antigenemia and viral genotype. However, there was a negative correlation between serum rotavirus antigen and acute rotavirus-specific serum IgA (r = ?0.44, p = 0.025) and IgG (r = ?0.40, p = 0.01) titers. We examined 11 antigen-positive and nine antigen-negative sera for infectious virus after three blind serial passages in HT-29 cells using immunofluorescence staining for rotavirus structural and nonstructural proteins. Infectious virus was detected in 11/11 (100%) sera from serum antigen-positive children and in two out of nine (22%) sera samples from antigen-negative children (p = 0.002). Conclusions Most children infected with rotavirus are viremic. The presence of viremia is directly related to the detection of antigenemia and is independent of the presence of diarrhea. Antigenemia load is inversely related to the titer of antirotavirus antibody in the serum. The finding of infectious rotavirus in the blood suggests extraintestinal involvement in rotavirus pathogenesis; however, the impact of rotavirus viremia on
Anti-rotaviral effects of Glycyrrhiza uralensis extract in piglets with rotavirus diarrhea
Alfajaro Mia Madel,Kim Hyun-Jeong,Park Jun-Gyu,Ryu Eun-Hye
Virology Journal , 2012, DOI: 10.1186/1743-422x-9-310
Abstract: Background Since rotavirus is one of the leading pathogens that cause severe gastroenteritis and represents a serious threat to human and animal health, researchers have been searching for cheap, safe, and effective anti-rotaviral drugs. There is a widespread of interest in using natural products as antiviral agents, and among them, licorice derived from Glycyrrhiza spp. has exerted antiviral properties against several viruses. In this study, anti-rotaviral efficacy of Glycyrrhiza uralensis extract (GUE) as an effective and cheaper remedy without side-effects was evaluated in colostrums-deprived piglets after induction of rotavirus diarrhea. Methods Colostrums-deprived piglets were inoculated with porcine rotavirus K85 (G5P[7]) strain. On the onset of diarrhea, piglets were treated with different concentration of GUE. To evaluate the antiviral efficacy of GUE, fecal consistency score, fecal virus shedding and histological changes of the small intestine, mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α), signaling molecules (p38 and JNK), and transcription factor (NFκB) in the small intestine and spleen were determined. Results Among the dosages (100-400 mg/ml) administrated to animals, 400 mg/ml of GUE cured diarrhea, and markedly improved small intestinal lesion score and fecal virus shedding. mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α), signaling molecules (p38 and JNK), and transcription factor (NFκB) in the small intestine and spleen were markedly increased in animals with RVA-induced diarrhea, but dose- dependently decreased in GUE treated animals after RVA-induced diarrhea. Conclusions GUE cures rotaviral enteritis by coordinating antiviral and anti-inflammatory effects. Therapy of this herbal medicine can be a viable medication for curing rotaviral enteritis in animals and humans.
Human rotavirus genotypes circulating in Brazil before and after a nationwide rotavirus vaccination program established in 2006
Caruzo TAR
Research and Reports in Tropical Medicine , 2011, DOI: http://dx.doi.org/10.2147/RRTM.S13650
Abstract: man rotavirus genotypes circulating in Brazil before and after a nationwide rotavirus vaccination program established in 2006 Review (1967) Total Article Views Authors: Caruzo TAR Published Date April 2011 Volume 2011:2 Pages 57 - 64 DOI: http://dx.doi.org/10.2147/RRTM.S13650 Thabata AR Caruzo Genetics, Evolution and Bioagents Department, Institute of Biology, State University of Campinas, Campinas, S o Paulo, Brazil Abstract: Accounting for an estimated 600,000 deaths worldwide each year, rotaviruses are recognized as the most important etiologic agents causing severe acute gastroenteritis among children under the age of five years. In Brazil, until rotavirus vaccination was established in the public health system in 2006, acute gastroenteritis striking children under five years and caused by these viruses was clearly associated with 3.5 million episodes of diarrhea, 650,000 visits to outpatient health care facilities, 92,000 hospitalizations, and 850 deaths each year. After the introduction of the rotavirus vaccine in Brazil in March 2006, studies all over the country have been comparing rotavirus genotypes circulating in the recent pre- and postvaccination era. Most of these studies have reported a high prevalence of the G2P[4] genotype and also a decrease in rotavirus detection all over Brazil after the introduction of the vaccine. So far, these are preliminary studies, as a longer period of time is necessary to establish if this high prevalence of G2P[4] is due to selective pressure by the vaccine on the circulating viruses or to a normal genotype fluctuation, and if it will have any impact on vaccine efficacy in the future. This review describes results from the most recent studies addressing this issue and on rotavirus genotypic variability in Brazil.
Molecular Characterization of Rotavirus Strains Circulating in Enugu Nigeria: 2011 to 2016  [PDF]
B. N. Tagbo, C. Chukwubike, J. M. Mwenda, M. L. Seheri, G. Armah, J. M. Mphahlele, U. C. Ozumba, C. Benjamin-Puja, C. Azubuike, H. U. Okafor, R. O. Nnani, V. Okafor, B. O. Edelu, C. B. Eke, O. Udemba, A. Isiaka, L. Namadi, N. Umezinne, R. Njoku, C. Odume, V. Osaro, N. Ogude, M. U. Okwesili, S. K. Ezebilo, K. M. Yusuf, E. O. Obidike, ICH UNTH Enugu Rotavirus Group
World Journal of Vaccines (WJV) , 2019, DOI: 10.4236/wjv.2019.91002
Abstract: Rotavirus gastroenteritis is a major public health concern globally, estimated to cause 215,000 deaths among children < 5 years of age in 2013; with majority of mortality occurring in developing countries. In 2013, it was estimated that Nigeria was the second country with the highest number of rotavirus deaths. Monitoring of circulating rotavirus strains in Enugu, Nigeria is part of on-going rotavirus surveillance before the introduction of rotavirus vaccination. A total of 2694 stool samples were collected from enrolled under 5 years old children with diarrhoea between January 2011 and December 2016 and tested the virus using an antigen enzyme immunoassay. Randomly selected rotavirus positive samples were further characterized by rotavirus genotype methods to identify the G and P types circulating during the study period. Rotavirus was detected in 1242 (46%) of the 2694 samples collected over the six years period. Of these, 867 were randomly selected for genotyping. G and P types could be assigned for 832 samples (96%), while 31 (3.6%) could only be assigned either genotype G or P (partially typed) and 4 (0.4%) could not be assigned genotype G and P (untypeable). The most common G-genotypes detected during the entire study period were G12, G1 and G3 accounting for 27.6%, 21.0% and 16.3% respectively. Mixed G and P-genotypes were commonly detected. Ninety-one of the samples, representing 10.8% (91/839) had mixed G-genotype whilst 130 of the samples representing 15.2% (130/852) had mixed P-genotype. The most common P-genotypes detected were P[8], P[6] and P[4] representing 38.3%, 35.4% and 9.1% respectively. The predominant strain detected was G12P[8] (22.3%) followed by G3P[6] (14.5%), G1P[8] (9.2%) and G1P[6] (8.0%). These data are useful for making an informed decision about the introduction of rotavirus vaccine into the national routine immunization program and to monitor the impact of the vaccine post licensure.
Genetic Diversity of Circulating Rotavirus Strains in Tanzania Prior to the Introduction of Vaccination  [PDF]
Sabrina J. Moyo, Bj?rn Blomberg, Kurt Hanevik, Oyvind Kommedal, Kirsti Vainio, Samuel Y. Maselle, Nina Langeland
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097562
Abstract: Background Tanzania currently rolls out vaccination against rotavirus-diarrhea, a major cause of child illness and death. As the vaccine covers a limited number of rotavirus variants, this study describes the molecular epidemiology of rotavirus among children under two years in Dar es Salaam, Tanzania, prior to implementation of vaccination. Methods Stool specimens, demographic and clinical information, were collected from 690 children admitted to hospital due to diarrhea (cases) and 545 children without diarrhea (controls) during one year. Controls were inpatient or children attending child health clinics. Rotavirus antigen was detected using ELISA and positive samples were typed by multiplex semi-nested PCR and sequencing. Results The prevalence of rotavirus was higher in cases (32.5%) than in controls (7.7%, P<0.001). The most common G genotypes were G1 followed by G8, G12, and G4 in cases and G1, G12 and G8 in controls. The Tanzanian G1 variants displayed 94% similarity with the Rotarix vaccine G1 variant. The commonest P genotypes were P[8], P[4] and P[6], and the commonest G/P combination G1 P[8] (n = 123), G8 P[4] and G12 P[6]. Overall, rotavirus prevalence was higher in cool (23.9%) than hot months (17.1%) of the year (P = 0.012). We also observed significant seasonal variation of G genotypes. Rotavirus was most frequently found in the age group of four to six months. The prevalence of rotavirus in cases was lower in stunted children (28.9%) than in non-stunted children (40.1%, P = 0.003) and lower in HIV-infected (15.4%, 4/26) than in HIV-uninfected children (55.3%, 42/76, P<0.001). Conclusion This pre-vaccination study shows predominance of genotype G1 in Tanzania, which is phylogenetically distantly related to the vaccine strains. We confirm the emergence of genotype G8 and G12. Rotavirus infection and circulating genotypes showed seasonal variation. This study also suggests that rotavirus may not be an opportunistic pathogen in children infected with HIV.
Human rotavirus genotypes circulating in Brazil before and after a nationwide rotavirus vaccination program established in 2006  [cached]
Caruzo TAR
Research and Reports in Tropical Medicine , 2011,
Abstract: Thabata AR CaruzoGenetics, Evolution and Bioagents Department, Institute of Biology, State University of Campinas, Campinas, S o Paulo, BrazilAbstract: Accounting for an estimated 600,000 deaths worldwide each year, rotaviruses are recognized as the most important etiologic agents causing severe acute gastroenteritis among children under the age of five years. In Brazil, until rotavirus vaccination was established in the public health system in 2006, acute gastroenteritis striking children under five years and caused by these viruses was clearly associated with 3.5 million episodes of diarrhea, 650,000 visits to outpatient health care facilities, 92,000 hospitalizations, and 850 deaths each year. After the introduction of the rotavirus vaccine in Brazil in March 2006, studies all over the country have been comparing rotavirus genotypes circulating in the recent pre- and postvaccination era. Most of these studies have reported a high prevalence of the G2P[4] genotype and also a decrease in rotavirus detection all over Brazil after the introduction of the vaccine. So far, these are preliminary studies, as a longer period of time is necessary to establish if this high prevalence of G2P[4] is due to selective pressure by the vaccine on the circulating viruses or to a normal genotype fluctuation, and if it will have any impact on vaccine efficacy in the future. This review describes results from the most recent studies addressing this issue and on rotavirus genotypic variability in Brazil.Keywords: human rotavirus, vaccine, genotypes, prevalence, Brazil
Human rotavirus vaccine Rotarix provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial  [cached]
Steele Andrew,Neuzil Kathleen M,Cunliffe Nigel A,Madhi Shabir A
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-213
Abstract: Background Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children <5 years of age. The human, G1P[8] rotavirus vaccine Rotarix significantly reduced severe rotavirus gastroenteritis episodes in a Phase III clinical trial conducted in infants in South Africa and Malawi. This paper examines rotavirus vaccine efficacy in preventing severe rotavirus gastroenteritis, during infancy, caused by the various G and P rotavirus types encountered during the first rotavirus-season. Methods Healthy infants aged 5–10 weeks were enrolled and randomized into three groups to receive either two (10 and 14 weeks) or three doses of Rotarix (together forming the pooled Rotarix group) or three doses of placebo at a 6,10,14-week schedule. Weekly home visits were conducted to identify gastroenteritis episodes. Rotaviruses were detected by ELISA and genotyped by RT-PCR and nucleotide sequencing. The percentage of infants with severe rotavirus gastroenteritis caused by the circulating G and P types from 2 weeks post-last dose until one year of age and the corresponding vaccine efficacy was calculated with 95% CI. Results Overall, 4939 infants were vaccinated and 4417 (pooled Rotarix = 2974; placebo = 1443) were included in the per protocol efficacy cohort. G1 wild-type was detected in 23 (1.6%) severe rotavirus gastroenteritis episodes from the placebo group. This was followed in order of detection by G12 (15 [1%] in placebo) and G8 types (15 [1%] in placebo). Vaccine efficacy against G1 wild-type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%), 51.5% (95% CI:-6.5%; 77.9%) and 64.4% (95% CI: 17.1%; 85.2%), respectively. Genotype P[8] was the predominant circulating P type and was detected in 38 (2.6%) severe rotavirus gastroenteritis cases in placebo group. The remaining circulating P types comprised of P[4] (20 [1.4%] in placebo) and P[6] (13 [0.9%] in placebo). Vaccine efficacy against P[8] was 59.1% (95% CI: 32.8%; 75.3%), P[4] was 70.9% (95% CI: 37.5%; 87.0%) and P[6] was 55.2% (95% CI: -6.5%; 81.3%) Conclusions Rotarix vaccine demonstrated efficacy against severe gastroenteritis caused by diverse circulating rotavirus types. These data add to a growing body of evidence supporting heterotypic protection provided by Rotarix . Trial registration number NCT00241644
Molecular Epidemiology of Rotavirus Strains Circulating Among Children with Gastroenteritis in Iran
Mohammad Kargar,Maryam Zare,Akram Najafi
Iranian Journal of Pediatrics , 2012,
Abstract: Objective: This study was conducted to evaluate the prevalence of rotavirus disease and to investigate the genotypes of rotavirus strains causing acute gastroenteritis among children aged <5 years old in Marvdasht, Iran.Methods: One hundred and forty-one children, aged 1 month to 5 years, afflicted with severe diarrhea wereenrolled during January 2007 to December 2008. Their stool samples were studied with enzyme immunoassays (EIA) for group A rotaviruses. Rotavirus-positive specimens were genotyped by the NestedRT-PCR using different types of specific primers.Findings: Out of total collected samples rotavirus infection was detected in 40 (28.37%). Of the rotavirus episodes, 72.91% occurred during the first 2 years of life (P=0.038). The highest prevalence of infection was identified in summer (52.50%) and the lowest in winter (7.50%). The most common clinical features includeddiarrhea (96.25%), vomiting (82.50%) and fever (45.0%). Mixed genotypes were the predominant G type (60.0%), followed by non-typeable (12.50%), G2 (12.50%), G4 (10.0%) and G1 (5.0%) genotypes. G3/G8 mixed infection is the first of these rotavirus genotypes to be reported in Iran.Conclusion: Regarding high frequency of rotavirus infection, continuous surveillance is needed to inform diarrhea prevention programs as well as to provide information about the occurrence of new rotavirus strains. This will assist policy makers in decision making on rotavirus vaccine introduction.
EPIDEMIOLOGY OF ROTAVIRUS AND ASTROVIRUS INFECTIONS IN CHILDREN IN NORTHWESTERN NIGERIA
M Aminu, MD Esona, A Geyer, AD Steele
Annals of African Medicine , 2008,
Abstract: Background: Recent estimates attribute 527 000 deaths in children less than five years of age to rotavirus diarrhea annually, with 145 000 occurring in sub-Saharan Africa. Human astroviruses have been identified as one of the most frequent causes of infantile diarrhea, second in incidence only to rotavirus. This study was conducted to determine the prevalence of rotavirus and astrovirus and also to establish the circulating strains of rotavirus in a community in Nigeria where most diarrheic patients do not visit clinics or health care centers. Methods: A total of 154 stool samples (134 diarrheic and 20 non-diarrheic) were collected from infants and young children less than 5 years of age from January-March 2002. Samples were obtained by house-to-house visit in randomly selected districts in Zaria, Northwestern Nigeria. The samples were screened for rotavirus and astrovirus antigens using commercially available Enzyme Linked Immunosorbent Assay (ELISA) kits. All positive group A rotavirus samples were further subjected to VP6 sub-group ELISA, Polyacrylamide gel electrophoresis (PAGE) to determine their RNA electropherotypes and Reverse transcription polymerase chain reaction (RT-PCR) to determine their VP7 and VP4 genotypes. Results: Rotavirus and astrovirus antigens were detected in 9% (12) and 5% (7) of the 134 diarrheic stool samples respectively. No viral antigen was detected in the non-diarrheic stools. Rotavirus infection was more common in younger children than astrovirus infection. VP6 sub-group II specificity (58.3%), long RNA electropherotypes (41.6%), VP7 genotype G1 (33.3%) and VP4 genotype P [6] (33.3%) were the most common strains in circulation at that time in the community. Of significance is the fact that a large proportion of the rotavirus strains in circulation could not be assigned either a VP6 subgroup or RNA electrophoretic pattern probably as a result of low viral load. Conclusion: In this community-based study, rotavirus and astrovirus were significantly associated with diarrhea. However, the prevalence of rotavirus infection among children appears to be low while that of astrovirus falls in the range seen in hospital-based studies around the continent.
Epidemiology of rotavirus and astrovirus infections in children in Northwestern Nigeria  [cached]
Aminu M,Esona M,Geyer A,Steele A
Annals of African Medicine , 2008,
Abstract: Background: Recent estimates attribute 527 000 deaths in children less than five years of age to rotavirus diarrhea annually, with 145 000 occurring in sub-Saharan Africa. Human astroviruses have been identified as one of the most frequent causes of infantile diarrhea, second in incidence only to rotavirus. This study was conducted to determine the prevalence of rotavirus and astrovirus and also to establish the circulating strains of rotavirus in a community in Nigeria where most diarrheic patients do not visit clinics or health care centers. Methods: A total of 154 stool samples (134 diarrheic and 20 non-diarrheic) were collected from infants and young children less than 5 years of age from January-March 2002. Samples were obtained by house-to-house visit in randomly selected districts in Zaria, Northwestern Nigeria. The samples were screened for rotavirus and astrovirus antigens using commercially available Enzyme Linked Immunosorbent Assay (ELISA) kits. All positive group A rotavirus samples were further subjected to VP6 sub-group ELISA, Polyacrylamide gel electrophoresis (PAGE) to determine their RNA electropherotypes and Reverse transcription polymerase chain reaction (RT-PCR) to determine their VP7 and VP4 genotypes. Results: Rotavirus and astrovirus antigens were detected in 9% (12) and 5% (7) of the 134 diarrheic stool samples respectively. No viral antigen was detected in the non-diarrheic stools. Rotavirus infection was more common in younger children than astrovirus infection. VP6 sub-group II specificity (58.3%), long RNA electropherotypes (41.6%), VP7 genotype G1 (33.3%) and VP4 genotype P [6] (33.3%) were the most common strains in circulation at that time in the community. Of significance is the fact that a large proportion of the rotavirus strains in circulation could not be assigned either a VP6 sub-group or RNA electrophoretic pattern probably as a result of low viral load. Conclusion: In this community-based study, rotavirus and astrovirus were significantly associated with diarrhea. However, the prevalence of rotavirus infection among children appears to be low while that of astrovirus falls in the range seen in hospital-based studies around the continent.
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