Impact of self-financed rotavirus vaccines on hospital stays and costs in Spain after a 3-year introductory period.

Vaccination has reduced rotavirus hospitalizations by 25% in European regions with low-moderate vaccine availability. We aimed to quantify the reduction in hospital costs after the longest period in which Rotarix® and Rotateq® were simultaneously commercially available in Spain. Cases, length of stay (LOS), and diagnosis-related groups (DRGs) were retrieved from the Minimum Basic Data Set. Healthcare expenditure was estimated through the cost accounting system Gescot®. DRGs were clustered: I, non-bacterial gastroenteritis with complications; II, without complications; III, requiring surgical/other procedures or neonatal cases (highest DRG weights). Comparisons between pre (2003-2005)- and post-vaccine (2007-2009) hospital stays and costs by DRG group were made. Rotaviruses were the most common agents of specific-coded gastroenteritis (N = 1657/5012). LOS and extended LOS of rotaviruses fell significantly in 2007-2009 (ß-coefficient = -0·43, 95% confidence intervals (95% CI) -0·68 to -0·17; and odds ratio 0·62, 95% CI 0·50-0·76, respectively). Overall, costs attributable to rotavirus hospitalizations fell approximately €244 per patient (95% CI -365 to -123); the decrease in DRG group III was €2269 per patient (95% CI -4098 to -380). We concluded modest savings in hospital costs, largely attributable to cases with higher DRG weights, and a faster recovery. A universal rotavirus vaccination program deserves being re-evaluated, regarding its potential high impact on both at-risk children and societal costs.

Trends of rotavirus in Nepal.

BACKGROUND: Rotavirus gastroenteritis is the major cause of morbidity and mortality in infants and young children worldwide. Safe and effective rotavirus vaccine is needed to have significant impact on severe rotavirus gastroenteritis. Currently, two live oral rotavirus vaccines have been licensed in many countries. Knowledge on distribution of human rotavirus of G and P types are essential before rotavirus vaccines are introduced in the target populations. OBJECTIVE: To observe the trends of rotavirus strains in children below five years of age, during the years, 2003-2005 in Nepal. METHODS: Stool specimen collected from children with acute diarrhea who were referred to observation unit or hospitalized in Kanti Children Hospital between 2003 and 2005 were examined. Meteorological data was obtained from Ministry of Environment, Nepal to examine the possibility on the impact of weather on rotavirus infection. RESULTS: Of 1250 stool specimens, 271(22%) were positive for rotavirus by Rotaclone ELISA. G1 was the most common serotype in the first year of study, and G2 in the following year. G12 serotype emerged and remained predominant in two consecutive years. In addition, G9 and G3 emerged in the second year of the study. Children less than three years of age were commonly affected. The records reveal that rotavirus infection is related to the climate, and is commonly seen in the dry season, peaking in January. CONCLUSIONS: Continued surveillance of different regions is needed to monitor the trend of rotavirus strains and to establish rotavirus disease burden, which will help policy makers to make a decision in introducing rotavirus vaccine in Nepal.

[Prospective epidemiological study of rotavirus gastroenteritis in Europe (REVEAL study). Results in the French area of the study]. / Etude épidémiologique prospective de la gastroentérite à rotavirus en Europe (étude REVEAL). Résultats de la zone d'étude française.

PRIMARY OBJECTIVE: To estimate the incidence of acute gastroenteritis (AGE) and rotavirus acute gastroenteritis (RVAGE) in children less than 5 years of age seeking medical care in primary care, emergency department, and hospital settings. SECONDARY OBJECTIVES: To compare the clinical profile of RVAGE and non-RVAGE and to describe the distribution of RV serotypes among RVAGE cases. METHODS: A prospective primary care, emergency ward and hospital-based observational study was conducted during 1 year in a selected city of France with 250,000 inhabitants. Children less than 5 years of age presenting with symptoms of AGE were included. Rotavirus was identified using an Elisa test in stools. RESULTS: The estimated annual incidence of RVAGE was 1.56% for AGE and 0.87% for RVAGE in hospital, 5.87% for AGE and 2.65% for RVAGE in emergency-wards, 7.39% for AGE and 1.45% for RVAGE in primary care. Total incidence was 14.82% for AGE and 4.96% for RVAGE among children less than 5 years of age. RVAGE were more clinically severe than the AGE: dehydration (26.8% vs. 14.7%, p<0.0001), vomiting 84.9% vs. 60.9%, p<0.0001), fever (74.3% vs. 44.4%, p<0.0001), lethargy (84.9% vs. 70.2%, p<0.0001). G9 serotype was the most frequent serotype encountered (54.7%) during the study period followed by G3 serotype (33.6%) and G2 serotype (7.9%). CONCLUSION: In this study, RVAGE, caused by serotypes G9 and G3, represented about 1/3 of AGE and were more severe than non-RV AGE with twice as high dehydration rate. These results underline the need for continued promotion on the use of oral rehydration fluids and provide some arguments on the benefits of vaccination against rotavirus and also permanent virological monitoring of circulating serotypes.

Characterisation of rotavirus strains among hospitalised and non-hospitalised children in Guinea-Bissau, 2002 A high frequency of mixed infections with serotype G8.

BACKGROUND: In a previous community-based cohort study in Guinea-Bissau from 1996 to 1998, characterisation of rotavirus strains showed a high frequency of less common genotypes such as G8 and G9 and a high proportion of mixed infections. OBJECTIVES AND STUDY DESIGN: In the present study, we examined the prevalence of rotavirus genotypes among 81 hospitalised and 23 non-hospitalised Guinean children with rotavirus associated diarrhoea during the 2002 seasonal rotavirus outbreak. G- and P-types were determined in a two-step procedure using reverse transcription followed by a standard multiplex PCR. The multiplex PCR for G-types was furthermore supplemented with a single locus PCR including the MW8 primer for the G8-genotype. RESULTS: The dual infection G2/P[4]P[6] (24%) appeared to be the most frequent cause of rotavirus infections followed by G2P[4] (19%), G2P[6] (16%) and G8P[6] (13%). Overall 38% of the infections were mixed and 18% of the samples had the genotype G8. However, by subjecting all samples and not only the strains, which according to the standard multiplex PCR procedure were non-typeable, to a single locus G8-PCR, we found that the genotype G8 appeared in 62% of the infections, either as a single G-strain or in combination with other G-types, especially G2. Including these results, more than 63% of infections emerged as mixed. Neither genotype (including the presence of G8) nor the presence of mixed infections, seem to influence the severity of the rotavirus infection. CONCLUSION: We found a high frequency of mixed infections especially due to G8-genotypes, which might have implications for development of rotavirus vaccine candidates for use in Africa. Our results do not suggest that a single genotype is associated with severity, but the present study is based on a modest number of samples and results should be interpreted with caution.

Comparison of Vesikari and Clark scales regarding the definition of severe rotavirus gastroenteritis in children.

BACKGROUND: Two clinical severity scales, the Vesikari scale and the Clark scale, are commonly used to assess the efficacy of rotavirus vaccines. The results obtained using the two severity scales differ significantly and hamper comparisons. The aim of this study was to compare the Clark and Vesikari scales and to determine whether modified classifications would provide a better correlation between the two scales. METHODS: The severity of rotavirus gastroenteritis was assessed for each child using both the Vesikari and Clark scales. To make a statistical comparison between the two scales, the classifications were modified. RESULTS: In total, 200 children with rotavirus gastroenteritis were evaluated. Of these, 57% were classified as severe by the Vesikari scale, and only 1.5% by the Clark scale (p < 0.001). When the Clark three-category scale was transformed into a two-category scale by merging mild and moderate categories as non-severe, a good correlation with the Vesikari scale still could not be found. Using the median of the severity scores as the severity threshold did not provide a better correlation between the two scales. Transforming the Vesikari two-category scale into a three-category scale by further subdividing the severe category into two parts, as moderate and severe (≥ 16), provided a better correlation between the two severity scales, but still did not achieve a good level of agreement. CONCLUSIONS: The Clark and Vesikari scales differ significantly in the definition of severe gastroenteritis. Even the attempts at reclassifying the scales did not achieve a good correlation.

Conocimiento vaccinal en madres con hijos menores de 5 años / Vaccinal knowledge, in mothers with children under 5 years old

La inmunización, es un mecanismo de defensa que asegura la inmunidad humoral para prevenir enfermedades infantiles graves, y es responsabilidad de los padres. Objetivo: Se plantea indagar el conocimiento vaccinal, en madres con hijos menores de 5 años. Métodos: el estudio se orienta bajo el paradigma cualitativo, enfoque fenomenológico; Los participantes del estudio fueron madres que vacunaron a sus hijos en el centro de salud 20 de febrero, distrito 12D03 Quevedo-Mocache, Ecuador. Para el análisis de los datos se utilizó el soware Atlas ti, vinculando 18 preguntas de reflexión. Resultados: Las categorías emergentes fueron: 1) Las vacunas son muy importantes y necesarias. 2. Vacunaron porque sus hijos crecen sanos y fuertes. 3. para algunas el vacunatorio es agradable y para otras no. 4. Algunas reciben buen trato y atención, otras no. 5. Es insuficiente la información sobre las vacunas. 6. Piden cambios de enfermeras y horarios. Conclusión: el conocimiento vaccinal de las madres, esdeterminante para la protección y la no propagación de enfermedades en sus hijos(AU)

Immunization is a defense mechanism that ensures humoral immunity to prevent serious childhood diseases, and is the responsibility of the parents. Objective: to investigate the vaccine knowledge in mothers with children under 5 years. Methods: the study is oriented under the qualitative paradigm, hermeneutic approach; e study participants were mothers who vaccinated their children in the health center February 20, district 12D03 Quevedo-Mocache, Ecuador. The Atlas ti soware was used to analyze the data, linking 18 reflection questions. Results: The emerging categories were: 1) Vaccines are very important and necessary. 2. They vaccinated because their children grow up healthy and strong. 3. For some the vaccine is nice and for others it is not. 4. Some receive good treatment and attention, others do not. 5. Insufficient information about vaccines. 6. Ask for changes of nurses and schedules. Conclusion: the vaccinal knowledge of the mothers, is decisive for the protection and non-propagation of diseases in their children(AU)

Molecular and immunological methods to detect rotavirus in formalin-fixed tissue.

In 1999, a tetravalent rhesus-based rotavirus vaccine was withdrawn from the market after reports of intussusception cases among vaccinated infants. Methods to detect rotavirus in formalin-fixed pathology specimens from such patients will be important in examining the possible associations between the vaccine and intussusception, in investigating fatalities caused by natural rotavirus infection, and in furthering our understanding of the pathogenesis of rotavirus disease. Three different methods, reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and in situ hybridization (ISH), were developed to detect rotavirus in infected cell lines that were fixed in formalin and embedded in paraffin. Using specific primer pairs to identify the VP4 gene with a one-step RT-PCR method, we detected simian rotavirus strains RRV and YK-1 in the liver of an RRV-infected SCID mouse and in the small intestine of an YK-1 infected macaque, respectively. Using a two-step indirect immunoalkaline phosphatase technique, we found RRV antigens in the liver of an infected SCID mouse with a rabbit polyclonal anti-group A rotavirus antibody and a murine monoclonal anti-rotavirus VP2 antibody. Using riboprobes designed to detect RRV genes, VP4 and NSP4, we obtained a positive hybridization signal in the same area of the infected SCID mouse liver as the area in which rotavirus antigens were localized. These techniques should prove valuable to detect rotavirus antigens and nucleic acids in tissues from patients infected naturally with rotavirus or with intussususception associated with rotavirus vaccine.

Rotavirus gastroenteritis among children under five years of age in Izmir, Turkey.

Little is known about the epidemiology of rotavirus infection in Turkey. The aim of the study was to determine the incidence and clinical significance of rotavirus gastroenteritis, in view of the potentially available prevention by rotavirus vaccination. The study also sought to determine possible risk factors for rotavirus gastroenteritis. Therefore, 920 children under five years of age with acute gastroenteritis admitted to three pediatric hospitals in Izmir were studied. Rotavirus was identified in 39.8% of the children. Most children with rotavirus gastroenteritis (80.7%) were younger than two years of age. Marked seasonality of rotavirus gastroenteritis was observed, with a peak incidence from January to March. A total of 91% of rotavirus strains that were typed were of serotypes G 1-4. There was no significant difference among rotavirus-positive and rotavirus-negative patients with regard to family income. Compared with children who were exclusively breast-fed, those who were not exclusively breast-fed were at a two-fold greater risk of rotavirus diarrhea. Rotavirus gastroenteritis was significantly more severe than non-rotavirus gastroenteritis; 69% of children with rotavirus infection had severe gastroenteritis (score > or = 11). In conclusion, rotavirus is the most common cause of severe gastroenteritis among children under five years of age in Izmir. A new potent rotavirus vaccine, when available, will provide effective protection against severe rotavirus infection. Promotion of breast-feeding would augment the impact of rotavirus vaccines in preventing severe childhood diarrhea.

Predominant human rotavirus genotype G1P[8] infection in infants and children in Bangkok, Thailand.

Human rotavirus is the major etiologic agent of infantile diarrhea on a worldwide scale. In this study, rotaviruses were detected by reverse-transcription PCR in 42 of 83 stool specimens from children below the age of 3 years with acute diarrhea in Bangkok, Thailand, between November 1998 and August 1999. G and P types of all samples were characterized by restriction endonuclease analysis (REA) and multiplex PCR typing assay, respectively. Strain G1P[8] (76.1%) was the predominant type, followed by G1P[6] (2.4%). Strain G1 combined with mixed P[8]/P[6] was identified in 2 specimens (4.8%) and 7 untypeable G strains (16.7%) were observed. This information on the circulating G and P combinations should be useful for understanding the epidemiology of human rotavirus in Bangkok, Thailand.

Rotavirus and not age determines gastroenteritis severity in children: a hospital-based study.

BACKGROUND: The severity of childhood gastroenteritis is generally believed to be age-related rather than aetiology-related. Rotavirus-induced gastroenteritis is more severe than gastroenteritis caused by other enteric pathogens and is also age-related. We thus addressed the question of whether the increased severity of rotavirus-induced gastroenteritis is related to age or to features intrinsic to the agent. STUDY DESIGN: In this multicentre, hospital-based, prospective survey, we evaluated the severity of diarrhoea in rotavirus-positive and rotavirus-negative children up to 4 years of age. Severity was assessed with a score in four groups of age-matched children. RESULTS: Rotavirus was detected in 381 of 911 children. Disease severity was evaluated in 589 cases for which clinical data were complete. The rotavirus-positive and rotavirus-negative groups differed with regards to diarrhoea duration, hospital stay, degree of dehydration and the number of episodes of vomiting. Gastroenteritis was more severe in rotavirus-positive than in rotavirus-negative children. In contrast, none of the main severity parameters differed in the four age groups, irrespective of the presence of rotavirus. CONCLUSIONS: These data provide the evidence that aetiology and not age determines diarrhoeal severity. The demonstration that diarrhoea was more severe in rotavirus-positive children supports the need for a rotavirus vaccine and for studies that address the duration of vaccine protection.

Extraintestinal spread and replication of a homologous EC rotavirus strain and a heterologous rhesus rotavirus in BALB/c mice.

Although rotavirus infection has generally been felt to be restricted to the gastrointestinal tract, over the last two decades there have been sporadic reports of children with acute or fatal cases of rotavirus gastroenteritis testing positive for rotavirus antigen and/or nucleic acid in various extraintestinal locations such as serum, liver, kidney, bladder, testes, nasal secretions, cerebrospinal fluid, and the central nervous system. Recently, studies in animals and people have demonstrated that rotavirus antigenemia is a common event during natural infection. In this study, we extend these observations and compare the intestinal and extraintestinal spread of wild-type homologous murine rotavirus EC and a heterologous strain, rhesus rotavirus (RRV), in newborn mice. A strand-specific quantitative reverse transcription-PCR (ssQRT-PCR) assay was used to quantify the ability of different rotavirus strains to spread and replicate extraintestinally. Both strain EC and RRV were detected extraintestinally in the mesenteric lymph nodes (MLN), livers, lungs, blood, and kidneys. Extraintestinal replication, as measured by ssQRT-PCR, was most prominent in the MLN and occurred to a lesser degree in the livers, kidneys, and lungs. In the MLN, strain EC and RRV had similar (P < 0.05) RNA copy numbers, although EC was present at a 10,000-fold excess over RRV in the small intestine. Rotavirus nonstructural protein 4 (NSP4) and/or assembled triple-layered particles, indicated by immunostaining with the VP7 conformation-dependent monoclonal antibody 159, were detected in the MLN, lungs, and livers of EC- and RRV-inoculated mice, confirming the ssQRT-PCR findings. Infectious RRV was detected in the MLN in quantities exceeding the amount present in the small intestines or blood. The cells in the MLN that supported rotavirus replication included dendritic cells and potentially B cells and macrophages. These data indicate that extraintestinal spread and replication occurs commonly during homologous and some heterologous rotaviral infections; that the substantial host range restrictions for rhesus rotavirus, a heterologous strain present in the intestine, are not necessarily apparent at systemic sites; that the level and location of extraintestinal replication varies between strains; that replication can occur in several leukocytes subsets; and that extraintestinal replication is likely a part of the normal pathogenic sequence of homologous rotavirus infection.

G and P genotyping of human rotavirus isolated in a university hospital in Korea: implications for nosocomial infections.

To characterize rotavirus G and P genotypes circulating among infants and young children hospitalized with severe diarrhea in a university hospital in Gyeonggi province, Korea, and to examine any association of the genotypes and nosocomial infections, we genotyped 103 isolates of rotavirus by multiplex RT-PCR. In July 2001-June 2002, we found that globally common strains constituted 64.2% (G2P[4] 28.3%, G3P[8] 28.3%, G4P[8] 5.7%, and G1P[8] 1.9%), and the uncommon strain, G4P[6], constituted 26.4%. During July 2002-June 2003, the percentage of common strains decreased to 44.0% (G3P[8] 18.0%, G2P[4] 16.8%, and G1P[8] 10.0%), but G4P[6] increased to 36.0%. G9P[8] was identified in 10.0% of cases, and thus can be considered an emerging strain in Korea. Eight-eight percent of G4P[6] was isolated from newborn babies. Among the 103 patients, there was an evidence of nosocomial rotavirus infection in 23 children (22.3%). Of these, 19 (82.6%) were newborns infected with G4P[6] strains of rotavirus. Most of the children who acquired rotavirus infection nosocomially showed symptoms of diarrhea, vomiting, fever, poor sucking, or dehydration, regardless of the genotype. This study revealed that G4P[6] has been the major genotype causing nosocomial rotavirus infection in our hospital.

Use of active surveillance to validate international classification of diseases code estimates of rotavirus hospitalizations in children.

OBJECTIVE: National estimates of hospitalizations for rotavirus, the leading cause of acute gastroenteritis (AGE) in children, have been used to establish the need for rotavirus vaccines. A previous method directly estimated discharges by using the rotavirus-specific International Classification of Diseases (ICD) code, but this method has not been validated. Our study evaluated the sensitivity of the rotavirus ICD code among children hospitalized for AGE by using active surveillance for rotavirus at a tertiary children's hospital. DESIGN: We compared data for rotavirus-coded hospital discharges in 2000-2001 at Cincinnati Children's Hospital Medical Center with data on laboratory-confirmed cases of rotavirus obtained from active surveillance. We estimated additional rotavirus hospitalizations by extrapolating the proportion of rotavirus-positive results from active-surveillance cases to those with an unknown rotavirus status. RESULTS: Of 767 cases of AGE-related discharge codes, 103 (13%) were coded as rotavirus, 91% (94 of 103) of which were laboratory-confirmed diagnoses. Among all children discharged with an AGE-related illness, 260 (34%) were enrolled in active surveillance, of whom 155 (60%) tested positive for rotavirus. An additional 47 laboratory-confirmed rotavirus-case patients not enrolled in active surveillance yielded a total of 202 rotavirus cases and a maximum sensitivity of the rotavirus code of 47%. Extrapolation indicated that an additional 170 untested children might be rotavirus-positive, yielding a total of 372 rotavirus hospitalizations and a minimum sensitivity of the rotavirus code of 25%. CONCLUSIONS: Measurement of rotavirus-coded hospital discharges alone seems to greatly underestimate the true burden of rotavirus-associated hospitalizations. The numbers of national rotavirus hospitalization discharges may be substantially greater than previously estimated.

Rotavirus disease, but not infection and development of intestinal histopathological lesions, is age restricted in rabbits.

The rabbit model of rotavirus infection has proved to be useful for assessing active immunity and protection after infection or vaccination with virus or virus-like particles. One limitation of the rabbit model is that after experimental infection of rabbits, clinical diarrhea is not routinely induced. Lack of diarrhea in the rabbit model has been proposed to be due to the fluid absorptive capability of the cecum or attenuation of virus strains through tissue culture adaptation. To test whether a wild-type lapine rotavirus strain BAP (BAPwt) isolated from diarrheic rabbits would cause disease on passage in rabbits, 1-, 2-, 10-, and 16-week-old rabbits were orally inoculated with BAPwt, its tissue culture-adapted counterpart strain (BAP-2), tissue culture-adapted lapine strain ALA, or PBS. Lapine rotavirus infection in 1-week-old, but not >/=2-week-old, rabbits resulted in the development of disease characterized by soft, wet, yellow-to-brownish-green partially formed-to-liquid stools observed only at the time of virus antigen shedding. The level and duration of virus shedding after infection were prolonged in 1-week-old rabbits compared with rabbits >/=2 weeks of age. Although diarrhea was not observed beyond the first 2 weeks of life, histopathological changes, including villus shortening and fusion, increased vacuolation of epithelial cells, and mononuclear infiltration of the lamina propria, were observed throughout the small intestine between 12 and 120 h after ALA infection in 1-week-old, 1- to 2-month-old, and 11-month-old rabbits. In 11-month-old rabbits, onset of intestinal damage appeared to be slightly delayed, was less severe, and was not observed in the duodenum. There were no differences in the immune responses to rotavirus infection in rabbits of different age groups (1 week to 5 years of age). All lapine rotavirus-inoculated rabbits seroconverted and were protected from virus challenge at 28 days postinoculation. Like in mice, rotavirus disease is age restricted in rabbits.

VP4 genotyping of human rotavirus in the United States.

The VP4 (P) and VP7 (G) types of 171 rotavirus isolates obtained from children with diarrhea in the United States were characterized by PCR typing assays. Strains P1G1 predominated (71%); this was followed by strains P1G3 (20%) and P2G2 and P1G4 (2% each). Mixed types were identified in five (3%) specimens. Two (1%) strains bearing the P3 genotype (P3G1 and P3G2) were found in children with severe dehydrating diarrhea, although the P3 genotype has been regarded as a possible marker for virus attenuation.

Hospitalizations associated with rotavirus diarrhea in the United States, 1993 through 1995: surveillance based on the new ICD-9-CM rotavirus-specific diagnostic code.

The introduction of a specific International Classification of Diseases code for rotavirus diarrhea in 1992 prompted examination of the National Hospital Discharge Survey (NHDS) for trends in rotavirus-associated hospitalizations among US children aged 1 month through 4 years. During 1993-1995, 13.5% of hospitalizations were associated with diarrhea (n = 162,478/year). Rotavirus was the most common pathogen identified, coded in 16.5% of diarrhea cases (n = 26,798/year), and increased from 13.3% in 1993 to 18.9% in 1995. The age distribution and seasonality of hospitalizations of presumed noninfectious and viral etiology resembled those associated with rotavirus. Rotavirus was reported as a cause of diarrhea more frequently by hospitals that were large (> or =100 beds), proprietary-owned, or in the West/Midwest. Although these findings suggest incomplete detection of rotavirus diarrhea cases, the large number of rotavirus-associated hospitalizations underscores the need for vaccines and indicates that NHDS data could be used to monitor the impact of a US rotavirus immunization program.