Human rotavirus G9 and G3 as major cause of diarrhea in hospitalized children, Spain.In Spain, diarrhea remains a major cause of illness among infants and young children. To determine the prevalence of rotavirus rotavirus /ro·ta·vi·rus/ (ro´tah-vi?rus) any member of the genus Rotavirus. ro´taviral Rotavirus /Ro·ta·vi·rus/ (ro´tah-vi?rus genotypes and temporal and geographic differences in strain distribution, a structured surveillance study of hospitalized children <5 years of age with diarrhea was initiated in different regions of Spain during 2005. Rotavirus was detected alone in samples from 362 (55.2%) samples and as a coinfection with other viruses in 41 samples (6.3%). Enteropathogenic enteropathogenic having pathogenicity for the intestine. enteropathogenic Escherichia coli strains of E. coli which cause enteritis by close association with enteric cells. Includes attaching and effacing E. coli. bacterial agents were detected in 4.9% of samples; astrovirus and norovirus RNA RNA: see nucleic acid. RNA in full ribonucleic acid One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic was detected in 3.2% and 12.0% samples, respectively; and adenovirus adenovirus Any of a group of spheroidal viruses, made up of DNA wrapped in a protein coat, that cause sore throat and fever in humans, hepatitis in dogs, and several diseases in fowl, mice, cattle, pigs, and monkeys. antigen was detected in 1.8% samples. Including mixed infections, the most predominant G type was G9 (50.6%), followed by G3 (33.0%) and G1 (20.2%). Infection with multiple rotavirus strains was detected in >11.4% of the samples studied during 2005. ********** Group A rotaviruses are a major cause of severe diarrhea in infants. In developing countries, severe diarrhea caused by human rotavirus results in an estimated 500,000 to 608,000 childhood deaths annually; worldwide, it results in [approximately equal to] 2 million hospitalizations (1,2). Rotaviruses belong to the Reoviridae family. Viral particles are nonenveloped, and triple-layered protein capsids enclose the genome of 11 dsRNA segments. The major protein in the central layer of the viral capsid capsid /cap·sid/ (kap´sid) the shell of protein that protects the nucleic acid of a virus; it is composed of structural units, or capsomers. cap·sid n. is VP6, which determines 7 different groups of rotaviruses (A-G A-G Air-to-Ground ). The outer layer of the viral capsid is composed of 2 structural proteins, VP4 (encoded by gene 4) and VP7 (encoded by gene 7, 8, or 9, depending on the strain) (3). These 2 proteins carry the major antigenic determinants antigenic determinant n. Epitope. , which elicit neutralizing antibodies neu·tral·iz·ing antibody n. An antibody that reacts with an infectious agent, usually a virus, and destroys or inhibits its infectiveness and virulence. and are thought to be type specific. Group A rotaviruses are widespread in humans and animals and are subdivided into distinct genotypes, G and P (4). Epidemiologic studies epidemiologic study A study that compares 2 groups of people who are alike except for one factor, such as exposure to a chemical or the presence of a health effect; the investigators try to determine if any factor is associated with the health effect of rotavirus infections Rotavirus Infections Definition Rotavirus is the major cause of diarrhea and vomiting in young children worldwide. The infection is highly contagious and may lead to severe dehydration (loss of body fluids) and even death. are increasingly showing that a great diversity of rotavirus strains are cocirculating in the human population throughout the world. The most common genotypes of group A rotaviruses ([approximately equal to] 90%), which cause dehydrating gastroenteritis gastroenteritis: see enteritis. gastroenteritis Acute infectious syndrome of the stomach lining and intestines. Symptoms include diarrhea, vomiting, and abdominal cramps. in infants and young children worldwide, were G1P G1P Glucose 1 Phosphate [8], G2P G2P Got to Pee [4], G3P G3P Glyceraldehyde-3-Phosphate [8], and G4P[8]; G1P[8] is the most prevalent worldwide (5). However, other G genotypes are epidemiologically important, such as G5 in Brazil, (6,7), G9 and G10 in India (8,9), and G8 in Malawi (10). In Spain, diarrhea remains an important cause of illness among infants and young children. A study conducted from 1998 through 2002 detected rotavirus in 1,155 (31%) of 3,760 specimens tested. G1 was the predominant genotype genotype (jēn`ətīp'): see genetics. genotype Genetic makeup of an organism. The genotype determines the hereditary potentials and limitations of an individual. detected (53%), followed by G4 (24%), G2 (14%), G9 (6%), and G3 (2%) (11). The distribution of genotypes indicated a genotypic genotypic emanating from or pertaining to genotype. genotypic selection selection of breeding stock on the basis of known inherited characteristics. shift over time: G4 strains predominated (57%) from 1998 through 2000, whereas G1 gradually increased to account for 75% from 2000 through 2002 (11). Similar studies conducted in other regions of Spain indicated similar shifts in the prevalence of rotavirus genotypes (12,13). We conducted structured surveillance among children with diarrhea who were hospitalized in 6 hospitals in Spain This is a list of hospitals in Spain.
Materials and Methods Hospitals and Patients Stool samples were collected from children attending 6 public hospitals located in different healthcare areas throughout Spain. These hospitals intentionally represented the geographic, climatic, and ethnic diversity of Spain. Their respective catchment areas catchment area or drainage basin, area drained by a stream or other body of water. The limits of a given catchment area are the heights of land—often called drainage divides, or watersheds—separating it from neighboring drainage are shown in Table 1. The study was conducted between January 2005 and January 2006 and included children <5years of age who were hospitalized with acute gastroenteritis and from whom a stool sample was obtained. Acute gastroenteritis was defined as [greater than or equal to] 3 looser-than-normal stools within a 24-hour period or an episode of forceful vomiting vomiting, ejection of food and other matter from the stomach through the mouth, often preceded by nausea. The process is initiated by stimulation of the vomiting center of the brain by nerve impulses from the gastrointestinal tract or other part of the body. and any loose stool. To enable reporting of test results to hospitals, stool specimens were labeled with the date of collection and a unique surveillance identification number. Permission for enrollment in the study was obtained from children's legal guardians, and ethical approval was obtained from the institutional review board of the Hospital de La Ribera La Ribera ('The Shore' in Catalan) is one of quarters of Ciutat Vella ("the old city") of Barcelona. Many of the buildings date from late Medieval times. It was a well-to-do quarter during 13th-15th centuries, when it really was by the sea shore, and the area that today is . Specimen Collection and Testing Whole stool specimens were collected and transported immediately to hospital laboratories and stored at 4[degrees]C until processing. All fecal fecal /fe·cal/ (fe´k'l) pertaining to or of the nature of feces. fe·cal adj. Relating to or composed of feces. fecal pertaining to or of the nature of feces. samples were screened for enteropathogenic bacterial agents by conventional culture methods previously described (14). Each month, specimens were sent to the reference laboratory (Viral Gastroenteritis viral gastroenteritis Intestinal flu Infectious disease A generic term for GE induced by viruses Clinical presentations 1. Epidemic VGE, most often caused by the Norwalk agent or Norwalk-like viruses Clinical N&V, diarrhea, abdominal pain, anorexia, Unit, National Center for Microbiology, Instituto de Salud Carlos III Carlos III may refer to:
n. The process by which DNA is synthesized from an RNA template. (RT)-PCR for rotavirus, astrovirus, norovirus, and sapovirus (11,15,16) and by an immunochromatographic method for enteric adenoviruses enteric adenovirus Virology A serotype–eg, type 40, 41–of adenovirus which produces gastroenteritis Clinical Diarrhea; keratoconjunctivitis and nasopharyngitis–typical of infection with other adenoviruses–do not occur Management Symptomatic (14). Nucleic Acid nucleic acid, any of a group of organic substances found in the chromosomes of living cells and viruses that play a central role in the storage and replication of hereditary information and in the expression of this information through protein synthesis. Extraction and G/P Rotavirus Typing Viral RNA was extracted from 250 [micro]L of the 10% fecal suspension by using the guanidine guanidine /gua·ni·dine/ (gwah´ni-den) the compound NHdbondC(NH2)2, a strong base found in the urine as a result of protein metabolism and used in the laboratory as a protein denaturant. isothiocyanate isothiocyanate see allyl isothiocyanate. method and the Rnaid Spin Kit (BIO 101, Anachem Bioscience, Bedfordshire, UK) according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. the manufacturer's instructions, with slight modifications (16). RNA was eluted in 50 [micro]L of RNase-free distilled water Noun 1. distilled water - water that has been purified by distillation H2O, water - binary compound that occurs at room temperature as a clear colorless odorless tasteless liquid; freezes into ice below 0 degrees centigrade and boils above 100 degrees centigrade; and stored at -20[degrees]C. To determine the G/P type patterns present in children hospitalized from 2005 through 2006, a total of 98 rotavirus strains were P typed. G and P rotavirus genotyping Genotyping refers to the process of determining the genotype of an individual with a biological assay. Current methods of doing this include PCR, DNA sequencing, and hybridization to DNA microarrays or beads. were performed by using RT-PCR RT-PCR reverse transcriptase-polymerase chain reaction. See PCR1. methods as previously reported (11,17). DNA Sequencing DNA sequencing The determination of the sequence of nucleotides in a sample of DNA. and Analysis Rotavirus amplicons were genetically characterized by nucleotide sequencing of both strands of the amplified PCR PCR polymerase chain reaction. PCR abbr. polymerase chain reaction Polymerase chain reaction (PCR) products. These products were purified by using QIAquick PCR Purification kit (Qiagen, Valencia, CA, USA) and then sequenced using an ABI Abi (ā`bī) [short for Abijah], in the Bible, King Hezekiah's mother. (Application Binary Interface) A specification for a specific hardware platform combined with the operating system. PRISM BigDye Terminator (1) A character that ends a string of alphanumeric characters. (2) A hardware component that is connected to the last peripheral device in a series or the last node in a network. Cycle Sequencing Ready Reaction Kit (Applied Biosystems Applied Biosystems, Inc. (formerly NASDAQ: ABIO) is the original name of a pioneer biotechnology company founded in 1981 in Foster City, California, among the Silicon Valley cities of the southern San Francisco Bay Area. , Foster City, CA, USA) on an ABI automated sequencer See MIDI sequencer. (music) sequencer - Any system for recording and/or playback of music via a programmable memory which stores music not as audio data, but as some representation of notes. (Applied Biosystems, model 3700). Data analysis was performed by using Clustal for multiple alignments and neighbor-joining and maximum parsimony Maximum parsimony, often simply referred to as "parsimony," is a non-parametric statistical method commonly used in computational phylogenetics for estimating phylogenies. Under maximum parsimony, the preferred phylogenetic tree is the tree that requires the least number of methods for phylogenetic phy·lo·ge·net·ic adj. 1. Of or relating to phylogeny or phylogenetics. 2. Relating to or based on evolutionary development or history. analysis (Bionumerics, Kortrijk, Belgium). Spanish strains were submitted to GenBank under accession numbers DQ440613 through DQ440624. Results Microbiology A total of 656 hospitalized children were enrolled. Enteropathogenic bacterial strains were detected in 5.0% of samples (Table 2). Astrovirus and norovirus RNA was detected in 3.2% and 12.0% samples, respectively, and adenovirus antigen in 1.8% samples. A total of 403 rotavirus strains were detected. Rotavirus was found alone in 362 (55.2%) samples but was found in another 41 samples (6.3%) as a coinfection with other viruses. The percentage of children with gastroenteritis caused by rotavirus as unique agent ranged from 36.7% in Leon to 68.2% in Valencia (Table 2). Rotavirus Characterization G typing RT-PCR for rotavirus alone was performed on 362 samples positive for rotavirus but could not be determined in 10 (2.8%) samples. The G types detected, including mixed infections with multiple rotavirus strains, are shown in Table 3. Briefly, the most predominant G type was G9 (50.6%), followed by G3 (33.0%), G1 (20.2%), and G2 (7.1%); the least common G type was G4 (0.6%). G1, previously reported as the most common G type in Spain, was found in only 20.2% of rotavirus infections. With the exceptions of Valencia and Albacete, where G1 and G3, respectively, were the predominant G types, the results from all other regions showed a predominance pre·dom·i·nance also pre·dom·i·nan·cy n. The state or quality of being predominant; preponderance. Noun 1. predominance - the state of being predominant over others predomination, prepotency of G9. However, even in these 2 areas, G9 was the second most common strain detected when cases with coinfection were added (26.7% and 31.6%, respectively). Common G/P combinations, infrequent patterns, and mixed-infection combinations were all detected (Table 4). G9P[8] (40%) and G3P[8] (31%) were the most common combinations detected, but G types in combination with P[6] and P[9] were also detected. Using DNA sequencing and phylogenetic analysis of partial sequences of the gene encoding See encode. VP7, we compared 2 G3 strains from this study with 9 G3 strains isolated previously in Spain. All G3 strains from Spain shared >99.0% homology homology (hōmŏl`əjē), in biology, the correspondence between structures of different species that is attributable to their evolutionary descent from a common ancestor. and were more closely related to each other than to strains isolated in Italy, United Kingdom, India, and China. Discussion Genetically and antigenically diverse rotavirus strains cocirculate in humans. The prevalence of rotavirus genotypes varies according to location and time. Throughout the world, genotyping and serotyping studies have identified common cocirculating rotavirus types, and G1P[8], G2P[4], G3P[8], and G4P[8] are the predominant strains. However, from time to time, other less common genotypes, such as G9P[8], G5P[8], and G8P[6], have been predominant in various countries (5). In Spain, previous studies have identified G1P[8] and G4P[8] as the predominant cocirculating strains from 1996 through 2004 (11,17,18) (Table 5). However, in our study, conducted in 2005 and 2006, a major shift in the predominant strains was detected. G9P[8] and G3P[8] have become the predominant genotypes cocirculating in several regions of Spain, and infection with multiple rotavirus strains was detected in 11.4% of the cases studied. Since its widespread introduction into the human population in 1995, G9P[8] has become one of the predominant viruses worldwide. In 2 separate studies conducted in Thailand (19,20), this genotype has been reported as the predominant virus circulating from 2000 through 2002 and in Brazil from 1999 through 2002 (21). G3P[8] has recently been reported as the predominant strain circulating in the Japanese population (22). Less common G- and P-type combinations were also detected in this study. This finding may suggest either an earlier reassortment between animal and human strains, resulting in the emergence of strains such as G2P[6] and G3P[9], or zoonotic Zoonotic A disease which can be spread from animals to humans. Mentioned in: Zoonosis transmission to humans of an animal strain, as possibly occurred with G9P[6]. The VP4-genotypes P[6] and P[9] are reported to be associated with infection in pigs and cats, respectively. Although animal rotavirus strains replicate poorly in humans and person-to-person transmission is rare, the relatively high frequency of multiple infections detected in this study suggests that the opportunity for dual infection of a cell, and therefore reassortments, exists (23). The main limitations of this study are having only 1 year of data, the minimal variations in the sampling schemes in each institution (frequency of sampling, test procedures, motivations of investigators), and the small sample size collected. Although the sampling strategy enabled monitoring for rotavirus in a large number of children, future studies with hospital-based surveillance should be initiated in different areas of Spain, and even Europe, with larger samples. Morbidity rates morbidity rate n. The proportion of patients with a particular disease during a given year per given unit of population. morbidity rate Epidemiology The number of cases of a particular disease in a unit of population worldwide and morbidity and mortality Morbidity and Mortality can refer to:
n. See polyvalent vaccine. directed against G1, G2, G3, G4, and P[8] and a monovalent vaccine monovalent vaccine A vaccine containing one antigen. See Vaccine. to G1P[8] have been developed (24,25). Homotypic protection has been demonstrated for both vaccines, but the degree to which they cross-protect against less common G- and P-type combinations not included in the vaccine formulations has yet to be established, and the importance of genotype-specific protection against rotavirus disease is still under discussion (26,27). Considering that G9 rotavirus type has emerged as one of the most common rotavirus genotypes in humans around the world, and it is becoming very prevalent in some countries, future rotavirus vaccine candidates will need to provide adequate protection against disease caused by G9 viruses. Therefore, surveillance of regional networks must be maintained to document rotavirus strain distribution and prevent the appearance of new strains or new variants that could escape immune protection induced by an outdated vaccine. Acknowledgments We thank A. Potente for technical assistance and J.C. Sanz for fruitful discussions. This work was partly supported by grant no. MPY MPY Mils Per Year MPY Multiply 1176/04 from ISCIII. V. Montero mon·te·ro n. pl. mon·te·ros A hunter's cap with side flaps. [Spanish, hunter, from monte, mountain, from Latin m and S. Moreno were supported by a grant from ISCIII. References (1.) Parashar UD, Gibson CJ, Bresse JS, Glass RI. Rotavirus and severe childhood diarrhea. Emerg Infect Dis. 2006; 12:304-6. (2.) Glass RI, Bresee JS, Parashar U, Turcios R, Fischer TK, Jiang B, et al. Rotavirus vaccines: past, present, and future. Arch Pediatr. 2005;12:844-7. (3.) Kapikian AZ, Hoshino Y, Chanock RM. Rotaviruses. In: Knipe DM, Howley, PM, editors. Fields virology virology, study of viruses and their role in disease. Many viruses, such as animal RNA viruses and viruses that infect bacteria, or bacteriophages, have become useful laboratory tools in genetic studies and in work on the cellular metabolic control of gene expression . Philadelphia: Lippincott Williams and Wilkins; 2001. p. 1787-833. (4.) Desselberger U, Wolleswinkel-van den Bosch J, Mrukowicz J, Rodrigo C, Giaquinto C, Vesikari T. Rotavirus types in Europe and their significance for vaccination. Pediatr Infect Dis J. 2006;25(1 Suppl):S30-41. (5.) Santos N, Hoshino Y. Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev Med Virol. 2005;15:29-56. (6.) Gouvea V, de Castro L, Timenetsky MC, Greenberg H, Santos N. Rotavirus serotype serotype /se·ro·type/ (ser´o-tip) the type of a microorganism determined by its constituent antigens; a taxonomic subdivision based thereon. se·ro·type n. See serovar. v. G5 associated with diarrhea in Brazilian children. J Clin Microbiol. 1994;32:1408-9. (7.) Leite JP, Alfieri AA, Woods PA, Glass RI, Gentsch JR. Rotavirus G and P types circulating in Brazil: characterization by RT-PCR, probe hybridization hybridization /hy·brid·iza·tion/ (hi?brid-i-za´shun) 1. crossbreeding; the act or process of producing hybrids. 2. molecular hybridization 3. , and sequence analysis. Arch Virol. 1996; 141:2365-74. (8.) Ramachandran M, Das BK, Vij A, Kumar R, Bhambal SS, Kesari N, et al. Unusual diversity of human rotavirus G and P genotypes in India. J Clin Microbiol. 1996;34:436-9. (9.) Iturriza Gomara M, Kang G, Mammen A, Jana AK, Abraham M, Desselberger U, et al. Characterization of G10P[11] rotaviruses causing acute gastroenteritis in neonates and infants in Vellore, India. J Clin Microbiol. 2004;42:2541-7. (10.) Cunliffe NA, Gondwe JS, Broadhead RL, Molyneux ME, Woods PA, Bresee JS, et al. Rotavirus G and P types in children with acute diarrhea in Blantyre, Malawi
(11.) Sanchez-Fauquier A, Wilhelmi I, Colomina J, Cubero E, Roman E. Diversity of group A human rotavirus types circulating over a 4-year period in Madrid, Spain. J Clin Microbiol. 2004;42:1609-13. (12.) Buesa J, de Souza De Souza or D'Souza is a common Portuguese family name. Although it is still quite common outside Portugal -- especially in Brazil and India --, Souza is the old spelling of present-day Sousa. CO, Asensi M, Martinez C, Prat J, Gil MT. VP7 and VP4 genotypes among rotavirus strains recovered from children with gastroenteritis over a 3-year period in Valencia, Spain For the Valencia wine region, see . Valencia (Spanish: Valencia [ba'lenθja];[1] Valencian: València [va'ɫɛnsia]) is the capital of the Spanish autonomous community of Valencia and its province. . Eur J Epidemiol. 2000; 16:501-6. (13.) Cilia cilia /cil·ia/ (sil´e-ah) sing. cil´ium [L.] 1. the eyelids or their outer edges. 2. the eyelashes. 3. G, Perez-Trallero E, Lopez-Lopategui MC, Gilsetas A, Gomariz M. Incidence, seasonality and serotypes of rotavirus in Gipuzkoa (Basque Country Basque Country (băsk, bäsk), Basque Euzkadi, Span. País Vasco, comprising the provinces of Álava, Guipúzcoa, and Vizcaya (1990 pop. ), Spain. A 14-year study. Epidemiol Infect. 2000;125:677-83. (14.) Roman E, Wilhelmi I, Colomina J, Villar J, Cilleruelo ML, Nebreda V, et al. Acute viral gastroenteritis: proportion and clinical relevance of multiple infections in Spanish children. J Med Microbiol. 2003;52:435-40. (15.) Dalton RM, Roman ER, Negredo AA, Wilhelmi ID, Glass RI, Sachez-Fauquier A. Astrovirus acute gastroenteritis among children in Madrid, Spain. Pediatr Infect Dis J. 2002;21:1038-41. (16.) Sanchez-Fauquier A, Wilhelmi I, Roman E, Colomina J, Montero V, Negredo A. Surveillance of human calicivirus in Spain. Emerg Infect Dis. 2005;11:1327-9. (17.) Wilhelmi I, Mier C, Roman E, Colomina J, Prat J, Sanchez-Fauquier A. The molecular epidemiology molecular epidemiology Molecular medicine An evolving field that combines the tools of standard epidemiology–case studies, questionnaires and monitoring of exposure to external factors with the tools of molecular biology–eg, restriction endonucleases, of the rotavirus in Spanish children: The Rotavirus Study Group (GER GER German/Germany GER Gastroesophageal Reflux GER Geriatrics GER General Education Requirement GER Great Eastern Railway (UK) GER Gross Enrollment Ratio (education) GER Gain Electrons Reduction ). Enferm Infecc Microbiol Clin. 1999;17:509-14. (18.) Sanchez-Fauquier A. Changing epidemiology of rotavirus diarrhea in Spain. 1st European Rotavirus Biology Meeting; 2005 Apr 24-26; Paris, France. (19.) Zhou Y, Supawadee J, Khamwan C, Tonusin S, Peerakome S, Kim B, et al. Characterization of human rotavirus serotype G9 isolated in Japan and Thailand from 1995 to 1997. J Med Virol. 2001;65:619-28. (20.) Khamrin P, Peerakome S, Wongsawasdi L, Tonusin S, Sornchai P, Maneerat V, et al. Emergence of human G9 rotavirus with an exceptionally high frequency in children admitted to hospital with diarrhea in Chiang Mai Chiang Mai (jyäng` mī`) or Chiengmai (jyĕng`–), city (1990 pop. 164,902), capital of Chiang Mai prov., N Thailand, on the Ping River, near the Myanmar border. , Thailand. J Med Virol. 2006;78:273-80. (21.) Santos N, Volotao EM, Soares CC, Campos Campos (käm`p  s), city (1996 pop. 391,299), Rio de Janeiro state, SE Brazil, on the Paraíba River near its mouth. GS, Sardi SI, Hoshino
Y. Predominance of rotavirus genotype G9 during the 1999, 2000, and 2002
seasons among hospitalized children in the city of Salvador, Bahia
Salvador (in full, São Salvador da Baía de Todos os Santos , Brazil: implications for future vaccine strategies. J Clin Microbiol. 2005;43:4064-9. (22.) Zhou Y, Li L, Okitsu S, Maneekarn N, Ushijima H. Distribution of human rotaviruses, especially G9 strains, in Japan from 1996 to 2000. Microbiol Immunol. 2003;47:591-9. (23.) Iturriza-Gomara M, Kang G, Gray J. Rotavirus genotyping: keeping up with an evolving population of human rotaviruses. J Clin Virol. 2004;31:259-65. (24.) Vesikari T, Matson DO, Dennehy P, Van Damme P, Santosham M, Rodriguez Z, et al. Safety and efficacy of a pentavalent pentavalent having a valence of five. pentavalent antimony compounds see antimony. pentavalent organic arsenicals includes the pharmaceuticals arsanilic acid, roxarsone, nitarsone. See also organic arsenical. human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med. 2006;354:23-33. (25.) Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, Abate H, Breuer T, Clemens SC, et al. Safety and efficacy of an attenuated Attenuated Alive but weakened; an attenuated microorganism can no longer produce disease. Mentioned in: Tuberculin Skin Test attenuated having undergone a process of attenuation. vaccine against severe rotavirus gastroenteritis. N Engl J Med. 2006;354:11-22. (26.) Hoshino Y, Kapikian AZ. Rotavirus serotypes: classification and importance in epidemiology, immunity, and vaccine development. J Health Popul Nutr. 2000;18:5-14. (27.) Jiang B, Gentsch JR, Glass R. The role of serum antibodies in the protection against rotavirus disease: an overview. Clin Infect Dis. 2002;34:1351-61. Address for correspondence: Alicia Sanchez-Fauquier, Seccion de Gastroenteritis Virales, Centro Nacional de Microbiologia, Instituto Salud Carlos III, Ctra. Majadahonda-Pozuelo Km. 2, 28220-Majadahonda, Madrid, Spain; email: asanchez@isciii.es Alicia Sanchez-Fauquier, * Vanessa Montero, * Silvia Moreno, * Monica Sole, * Javier Colomina, ([dagger]) Miren Iturriza-Gomara, ([double dagger double dagger n. A reference mark (  ) used in printing and writing. Also called diesis.Noun 1. ]) Ana Revilla, * Isabel Wilhelmi, ([section]) Jim Gray, ([dagger]) and Gegavi/VIGESS-Net Group (1) * Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; ([dagger]) Hospital La Ribera, Alzira, Valencia Alzira (its official and Valencian name; in Spanish: Alcira) is a town and municipality of 43,253 people (2006) in eastern Spain. It is the capital of the comarca of Ribera Alta in the province of Valencia. , Spain; ([double dagger]) Centre for Infections Health Protection Agency, London, UK; and Hospital Severo Ochoa Noun 1. Severo Ochoa - United States biochemist (born in Spain) who studied the biological synthesis of nucleic acids (1905-1993) Ochoa , Majadahonda, Madrid, Spain (1) Gegavi/VIGESS-Net Group members: A. Sanchez-Fauquier, V. Montero, S. Moreno, A. Potente, F. Adam, J.C. Sanz, J. Colomina, S. Llanes, F. Gimeno, C. Gutierrez, C. Sainz de Baranda, M.J. Lopez, P. Teno, E. Roman, M. Alonso, M. Marugan, I. Fernandez, I. Wilhelmi, M.L. Cilleruelo Dr Sanchez-Fauquier is the head of the Viral Gastroenteritis Unit, National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid. Her primary research interests are the epidemiology, immunology, pathogenesis, and molecular biology molecular biology, scientific study of the molecular basis of life processes, including cellular respiration, excretion, and reproduction. The term molecular biology was coined in 1938 by Warren Weaver, then director of the natural sciences program at the Rockefeller of viral gastroenteritis. She also is coordinator of the Spanish Viral Gastroenteritis Network (VIGESS-Net).
Table 1. Description of catchment area served by each hospital in the
study *
Complejo
Hospitalario Complejo
Universitario Hospitalario San
Name Albacete Pedro Alcantara
Municipality (province) Albacete Caceres
Location within Spain Southeast West
Climate Continental, Mediterranean,
semiarid continentalized
No. habitants 159,518 89,029
Birth rate (per 1,000) 10.0 8.1
No. children <5 y of age 6,362 2,867
Complejo Hospital
Name Asistencial Leon Fuenlabrada
Municipality (province) Leon Fuenlabrada
(Madrid)
Location within Spain Northwest Center
Climate Mediterranean, Continental
continentalized
No. habitants 136,414 195,133
Birth rate (per 1,000) 6.9 11.8
No. children <5 y of age 3,776 9,210
Hospital Hospital La
Name Severo Ochoa Ribera
Municipality (province) Leganes Alzira
(Madrid) (Valencia)
Location within Spain Center East
Climate Continental Mediterranean
No. habitants 181,248 210,637
Birth rate (per 1,000) 11.9 11.3
No. children <5 y of age 8,627 9,479
* Predominant ethnic group in each area was Caucasian.
Table 2. Pathogens in children <5 years of age, hospitalized with
gastroenteritis, by region, Spain, 2005-2006
No. samples (%)
Pathogen Albacete Caceres Leon
Rotavirus 79 (55.7) 87 (54.5) 29 (36.7)
Astrovirus 0 4 (2.5) 0
Adenovirus 3 (2.1) 0 1 (1.3)
Norovirus 8 (5.6) 18 (11.3) 5 (6.3)
EB * 16 (11.3) 0 4 (5.1)
EB + adenovirus 1 (0.7) 0 0
Rotavirus + astrovirus 1 (0.7) 1 (0.6) 2 (2.5)
Rotavirus + norovirus 2 (1.4) 7 )4.4) 3 (3.8)
Norovirus + astrovirus 0 0 0
Norovirus + astrovirus + 0 0 0
rotavirus
Negative specimens 32 (22.5) 43 (26.8) 35 (44.3)
Total specimens
([dagger]) 142 (21.6) 160 (24.2) 79 (12.0)
No. samples (%)
Pathogen Fuenlabrada Leganes Valencia
Rotavirus 29 (50.9) 123 62.7) 15 (68.2)
Astrovirus 1 (1.7) 0 0
Adenovirus 0 7 (3.6) 0
Norovirus 3 (5.3) 9 (4.6) 0
EB * 3 (5.3) 9 (4.6) 0
EB + adenovirus 0 0 0
Rotavirus + astrovirus 0 5 (2.6) 1 (4.5)
Rotavirus + norovirus 2 (2.6) 16 (8.2) 0
Norovirus + astrovirus 2 (3.5) 3 (1.5) 0
Norovirus + astrovirus + 0 1 (0.5) 0
rotavirus
Negative specimens 17 (29.8) 23 (11.7) 6 (27.3)
Total specimens
([dagger]) 57 (8.7) 196 (29.9) 22 (3.4)
No. samples (%)
Pathogen Total samples (%)
Rotavirus 362 (55.2)
Astrovirus 5 (0.8)
Adenovirus 11 (1.7)
Norovirus 43 (6.5)
EB * 32 (4.9)
EB + adenovirus 1 (0.1)
Rotavirus + astrovirus 10 (1.5)
Rotavirus + norovirus 30 (4.6)
Norovirus + astrovirus 5 (0.8)
Norovirus + astrovirus + 1 (0.1)
rotavirus
Negative specimens 156 (23.8)
Total specimens
([dagger]) 656
* EB, enteropathogenic bacteria.
([dagger]) Percentages of isolations per total specimens in each region
were 77.5, 73.1, 55.7, 70.2, 88.3, 72.7, and 76.2, respectively.
Table 3. Rotavirus G genotypes in children <5 years of age
hospitalized with gastroenteritis by region, Spain, 2005-2006
No. samples (%)
Rotavirus Albacete, Caceres, Leon, Fuenlabrada,
G types n=79 n=86 n=23 n=28
G1 * 20 (25.3) 10 (11.6) 4 (17.4) 4 (14.3)
G2 * 2 (2.5) 4 (4.7) 2 (8.7) 4 (14.3)
G3 * 36 (45.6) 36 (41.9) 5 (21.7) 11 (39.3)
G4 * 0 1 (1.2) 0 0
G9 * 25 (31.6) 52 (60.5) 13 (56.5) 13 (46.4)
G1 + G2 1 (1.3) 1 (1.2) 0 2 (7.1)
G1 + G9 1 (1.3) 0 0 0
G1 + G3 0 (0.0( 0 0 0
G2 + G9 0 0 0 0
G3 + G9 2 (2.5) 16 (18.6) 1 (4.3) 2 (7.1)
No. samples (%)
Total no.
Rotavirus Leganes, Valencia, samples (%)
G types n=121 n=15 N=352 ([dagger])
G1 * 21 (17.4) 11 (73.3) 71 (20.2)
G2 * 13 (10.4) 0 25 (7.1)
G3 * 27 (22.3) 0 116 (33.0)
G4 * 1 (0.8) 0 2 (0.6)
G9 * 71 (58.7) 2 (13.3) 178 (50.6)
G1 + G2 0 0 4 (1.1)
G1 + G9 2 (1.7) 1 (6.7) 4 (1.1)
G1 + G3 1 (0.8) 0 1 (0.3)
G2 + G9 3 (2.5) 0 3 (0.9)
G3 + G9 6 (5.0) 1 (6.7) 28 (8.0)
* Includes mixed infections.
([dagger]) G typing for 10 samples could not be determined.
Table 4. G- and P-type combinations detected in 98 fully
characterized strains
Genotype No. samples Pattern
G9 P[8] 39 Common (91%)
G3 P[8] 30
G1 P[8] 15
G2 P[4] 5
G2 P[6] 1 Infrequent (3%)
G3 P[9] 1
G9 P[6] 1
G1+G9 P[8] 2 Mixed infections
G2+G9 P[8] 1 (6%)
G2+G9 P[4] 1
G2+G9 and P[4]+P[8] 1
G3+G9 and P[6]+P[8] 1
Table 5. Predominant cocirculating rotavirus strains, Spain,
1996-2006 *
Year, %
1996- 1998-
Rotavirus 1997 ([dagger]) 1999 ([double dagger])
G-type(s) (n = 322)
G1 alone 68 18
G2 alone 0 1
G3 alone 2 1
G4 alone 29 68
G9 alone 0 11
G1+G2 0 0
G1+G4 1 1
G1+G9 0 0
G1+G3 0 0
G2+G9 0 0
G3+G9 0 0
Undet. ([paragraph]) 0 0
Total 322 141
samples
Year, %
1999- 2000-
Rotavirus 2000 ([double dagger]) 2001 ([double dagger])
G-type(s) (n = 86) (n = 200)
G1 alone 27 70
G2 alone 9 23
G3 alone 12 0
G4 alone 39 3
G9 alone 13 3
G1+G2 0 0
G1+G4 0 1
G1+G9 0 0
G1+G3 0 0
G2+G9 0 0
G3+G9 0 0
Undet. ([paragraph]) 0 0
Total 86 200
samples
Year, %
2001- 2002-
Rotavirus 2002 ([double dagger]) 2003 ([section])
G-type(s) (n = 149) (n = 102)
G1 alone 79 79
G2 alone 17 16
G3 alone 0 0
G4 alone 1 0
G9 alone 2 3
G1+G2 1 0
G1+G4 0 2
G1+G9 0 0
G1+G3 0 0
G2+G9 0 0
G3+G9 0 0
Undet. ([paragraph]) 0 0
Total 149 102
samples
Year, %
2003- 2004-
Rotavirus 2004 ([section]) 2005 ([section])
G-type(s) (n = 141) (n = 105)
G1 alone 79.5 50
G2 alone 1 11
G3 alone 17 7
G4 alone 0 26
G9 alone 1 5.4
G1+G2 1.5 0.2
G1+G4 0 0.4
G1+G9 0 0
G1+G3 0 0
G2+G9 0 0
G3+G9 0 0
Undet. ([paragraph]) 0 0
Total 141 105
samples
Year, %
2005- Average
Rotavirus 2006 (%)
G-type(s) (n = 352) (n = 1,598)
G1 alone 17.1 54
G2 alone 5 9
G3 alone 24 7
G4 alone 0.6 19
G9 alone 39.5 9
G1+G2 1.1 0
G1+G4 0 1
G1+G9 1.1 0
G1+G3 0.3 0
G2+G9 0.8 0
G3+G9 7.7 1
Undet. ([paragraph]) 2.8 0
Total 362 1,608
samples
* [chi square] test showed annual variations in G1, G2, G3, G4, and G9
prevalence rotavirus types and in G3 + G9 mixed infections
([chi square] = 15.50 with 8 degrees of freedom, p>0.95).
([dagger]) Adapted from Reference 11.
([double dagger]) Adapted from Reference 17.
([section]) Adapted from Reference 18.
([paragraph]) Undet., undetermined.
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