Whole-genome analysis of human group A rotaviruses in 1980s Japan and evolutionary assessment of global Wa-like strains across half a century.

Historically, the Wa-like strains of human group A rotavirus (RVA) have been major causes of gastroenteritis. However, since the 2010s, the circulation of non-Wa-like strains has been increasingly reported, indicating a shift in the molecular epidemiology of RVA. Although understanding RVA evolution requires the analysis of both current and historical strains, comprehensive pre-1980's sequencing data are scarce globally. We determined the whole-genome sequences of representative strains from six RVA gastroenteritis outbreaks observed at an infant home in Sapporo, Japan, between 1981 and 1989. These outbreaks were mainly caused by G1 or G3 Wa-like strains, resembling strains from the United States in the 1970s-1980s and from Malawi in the 1990s. Phylogenetic analysis of these infant home strains, together with Wa-like strains collected worldwide from the 1970s to 2020, revealed a notable trend: pre-2010 strains diverged into multiple lineages in many genomic segments, whereas post-2010 strains tended to converge into a single lineage. However, Bayesian skyline plot indicated near-constant effective population sizes from the 1970s to 2020, and selection pressure analysis identified positive selection only at amino acid 75 of NSP2. These results suggest that evidence supporting the influence of rotavirus vaccines, introduced globally since 2006, on Wa-like RVA molecular evolution is lacking at present, and phylogenetic analysis may simply reflect natural fluctuations in RVA molecular evolution. Evaluating the long-term impact of RV vaccines on the molecular evolution of RVA requires sustained surveillance.

The impact of rotavirus vaccination in the prevalence of gastroenteritis and comorbidities among children after suboptimal rotavirus vaccines implementation in Taiwan: A population-based study.

ABSTRACT: In Taiwan, rotavirus vaccination was implemented in 2006 in the private sector. The population-based impact of rotavirus vaccination on gastroenteritis and comorbidities of children remains under-investigated.We analyzed the annual prevalence of rotavirus-related disease, including gastroenteritis, convulsions, epilepsy, type I diabetes mellitus, intussusception, and biliary atresia among children under 5 years of age. Data were collected from Taiwan's National Health Insurance Research Database, a nationwide population-based database. A 16-year retrospective cohort study was conducted between 2000 and 2015.Among children <5 years of age, the prevalence of gastroenteritis decreased after 2012 (44,259.69 per 100 thousands) and remained lower through 2015 (39,931.11per 100 thousands, P < .001). The prevalence of convulsions rose steadily and significantly from 2007 (775.90 per 100 thousands) to 2015 (962.17 per 100 thousands, P < .001). The prevalence of epilepsy decreased significantly until reaching a nadir in 2013 (from 501.56 to 293.53 per 100 thousands, P < .001). The prevalence of biliary atresia tended upward, and surged suddenly in 2007 with a peak in 2013 (18.74 per 100 thousands). Among infants (<1 year of age) from 2000 to 2015, the prevalence of gastroenteritis declined steadily, and more rapidly after 2007 (22,513 to 17,285 per 100 thousands).In Taiwan, after introducing rotavirus vaccination, gastroenteritis in young children decreased, especially in infancy. However, gastroenteritis is still common in children, given other emerging pathogens. Our results highlight the impact of rotavirus vaccines on children's health in Taiwan and provide indications for future preventive medicine and healthcare strategies in children.

Gastroenteric Viruses Detection in a Drinking Water Distribution-to-Consumption System in a Low-Income Community in Rio de Janeiro.

The availability of drinking water is one of the main determinants of quality of life, disease prevention and the promotion of health. Viruses are important agents of waterborne diseases and have been described as important markers of human faecal contamination. This study aimed to investigate viruses' presence as an indicator of drinking water quality in low-income communities in the Manguinhos area, Rio de Janeiro, Brazil. Three hundred and four drinking water samples (2L/each) were collected along the drinking water distribution-to-consumption pathway in households, as well as healthcare and school units. Water samples were collected both directly from the water supply prior to distribution and after storage in tanks and filtration units. Using qPCR, viruses were detected 50 times in 45 water samples (15%), 19 of these being human adenovirus, 17 rotavirus A and 14 norovirus GII. Viral loads recovered ranged from 5E+10 to 8.7E+106 genome copies/Liter. Co-detection was observed in five household water samples and there was no difference regarding virus detection across sampling sites. Precarious and inadequate environmental conditions characterized by the lack of local infrastructure regarding basic sanitation and waste collection in the territory, as well as negligent hygiene habits, could explain viral detection in drinking water in regions with a water supply system.

Detection, Quantification, and Microbial Risk Assessment of Group A Rotavirus in Rivers from Uruguay.

The aim of this study was to detect, quantify, and assess the risk of infection and illness for Group A Rotavirus (RVA) in the watersheds of the Santa Lucia and Uruguay rivers in Uruguay. Monthly sampling was carried out for one year in six sites in the watershed of the Santa Lucía River and four in the Uruguay River. All the collection sites are used for recreational activities. Viral concentration was performed with the adsorption-elution method, and detection and quantification of RVA was carried out by TaqMan quantitative PCR (qPCR). Quantitative microbial risk assessment was applied to estimate the daily and annual risk of RVA infection, as well as the daily risk of illness considering direct exposure through recreational activity. RVA was detected in 42% (20/48) of the analyzed samples in the Uruguay River and 40% (29/72) in the Santa Lucía River. The virus was present in all the analyzed points in both watersheds. A pattern of seasonality, characterized by a higher detection frequency of the virus during coldest month of the year, was observed in both basins. The mean concentration for RVA was 1.3 × 105 genomic copies/L. The microbiological risk assessment shows that Santa Lucía watershed presented the highest daily risk of infection (6.41E-01) and illness (3.20E-01) estimated for the point downstream of Florida City; meanwhile for Uruguay River, the highest probabilities of infection (6.82E-01) and illness (3.41E-01) were estimated for the collection site for drinking water intake in Salto city. These results suggest that RVA contamination of these important rivers negatively impact on their microbiological quality since they are used for recreation and drinking water intake, demonstrating that the disposal of waste from cities located in their riverside confers a constant threat of infection for the general population, especially for children.

Evidence for Household Transmission of Rotavirus in the United States, 2011-2016.

BACKGROUND: Rotavirus is a leading cause of acute gastroenteritis (AGE) in children and is highly transmissible. In this study, we assessed the presence of AGE in household contacts (HHCs) of pediatric patients with laboratory-confirmed rotavirus. METHODS: Between December 2011 and June 2016, children aged 14 days to 11 years with AGE were enrolled at 1 of 7 hospitals or emergency departments as part of the New Vaccine Surveillance Network. Parental interviews, medical and vaccination records, and stool specimens were collected at enrollment. Stool was tested for rotavirus by an enzyme immunoassay and confirmed by real-time or conventional reverse transcription-polymerase chain reaction assay or repeated enzyme immunoassay. Follow-up telephone interviews were conducted to assess AGE in HHCs the week after the enrolled child's illness. A mixed-effects multivariate model was used to calculate odds ratios. RESULTS: Overall, 829 rotavirus-positive subjects and 8858 rotavirus-negative subjects were enrolled. Households of rotavirus-positive subjects were more likely to report AGE illness in ≥1 HHC than were rotavirus-negative households (35% vs 20%, respectively; P < .0001). A total of 466 (16%) HHCs of rotavirus-positive subjects reported AGE illness. Of the 466 ill HHCs, 107 (23%) sought healthcare; 6 (6%) of these encounters resulted in hospitalization. HHCs who were <5 years old (odds ratio, 2.2 [P = .004]) were more likely to report AGE illness than those in other age groups. In addition, 144 households reported out-of-pocket expenses (median, $20; range, $2-$640) necessary to care for an ill HHC. CONCLUSIONS: Rotavirus-associated AGE in children can lead to significant disease burden in HHCs, especially in children aged <5 years. Prevention of pediatric rotavirus illness, notably through vaccination, can prevent additional illnesses in HHCs.

Burden of rotavirus infection in hospitalized elderly individuals prior to the introduction of rotavirus vaccination in Sweden.

BACKGROUND: Rotavirus gastroenteritis (GE) in the elderly has been much less studied than in children. OBJECTIVES: The aim of this study was to determine the morbidity and mortality for elderly hospitalized patients with rotavirus GE prior to the introduction of rotavirus vaccination in Sweden, and to investigate the epidemiology of rotavirus genotypes in these patients. STUDY DESIGN: All patients 60 years or older who were hospitalized at Sahlgrenska University Hospital, Gothenburg, Sweden, and were rotavirus positive in a clinical diagnostic test from 2009 to 2016, were included. Medical records were reviewed and rotavirus genotyping real-time PCR was performed. RESULTS: One hundred and fifty-nine patients were included, corresponding to an annual incidence of hospitalization due to rotavirus GE of 16/100 000 inhabitants aged 60 years or older. G2P[4] was the most common genotype, followed by G1P[8] and G4P[8]. The majority of patients had community-onset of symptoms and no or few pre-existing health disorders. Four patients (2.5%) died within 30 days of sampling. Patients with hospital-onset rotavirus GE had a longer median length of stay following diagnosis compared with patients with community-onset of symptoms (19 vs. 5 days, p = 0.001) and higher 30-day mortality (8.6% (3/35) vs. < 1% (1/124), p = 0.03). CONCLUSIONS: Hospitalization due to rotavirus GE among the elderly seems to mainly affect otherwise healthy individuals and is associated with low 30-day mortality.

Microbial risk assessment in recreational freshwaters from southern Brazil.

In this study, total coliforms (TC), Escherichia coli, enterovirus (EV), rotavirus (RV), and human mastadenovirus species C and F (HAdV-C and HAdV-F) were evaluated in water samples from Belo Stream. For HAdV-C and F, the infectivity was assessed by integrated cell culture quantitative real-time polymerase chain reaction (ICC-qPCR). Samples were collected monthly (May/2015 to April/2016) at four sites. Viral analyses were performed for both ultracentrifuge-concentrated and unconcentrated samples. For site P4 (used for recreational purposes), QMRA was applied to estimate health risks associated with exposure to E. coli and HAdV-C and F. TC and E. coli were present throughout the collection period. EV and RV were not detected. HAdV-C were present in 8.51% (1.89E + 06 to 2.28E + 07 GC (Genomic Copies)/L) and 21.27% (2.36E + 05 to 1.29E + 07 GC/L) for unconcentrated and concentrated samples, respectively. For HAdV-F were 12.76% (2.77E + 07 to 3.31E + 08 GC/L) and 48.93% (1.10E + 05 to 4.50E + 08 GC/L) for unconcentrated and concentrated samples, respectively. For unconcentrated samples, infectivity for HAdV-C was detected in 37.20% (1st ICC-qPCR) and 25.58% (2nd ICC-qPCR). For HAdV-F, infectivity was detected in 6.97% (1st ICC-qPCR) and 6.97% (2nd ICC-qPCR). For concentrated samples, HAdV-C infectious was observed in 17.02% (1st ICC-qPCR) and in 8.51% (2nd ICC-qPCR). For HAdV-F, were present in 8.51% for both 1st and 2nd ICC-qPCR. Statistical analyzes showed significant difference between the collection sites when analyzed the molecular data of HAdV-F, data of TC and E. coli. Correlation tests showed direct correlation between HAdV-F with E. coli and TC. E. coli concentrations translated to the lowest estimates of infection risks (8.58E-05 to 2.17E-03). HAdV-F concentrations were associated with the highest infection risks at 9.99E-01 and for group C, 1.29E-01 to 9.99E-01. These results show that commonly used bacterial indicators for water quality may not infer health risks associated with viruses in recreational freshwaters.

Hospital based surveillance and molecular characterization of rotavirus in children less than 5 years of age with acute gastroenteritis in Nepal.

BACKGROUND: Rotavirus remains a significant causative agent of childhood acute gastroenteritis, particularly among children less than 5 years of age. Although precise data on childhood mortality associated with diarrheal disease in Nepal is not available, it is estimated that22% of all rotavirus deaths globally occurs in neighboring country of India. In spite of the substantial burden of rotavirus gastroenteritis in the Indian subcontinent, rotavirus vaccine has not been introduced in Nepal. Continuous surveillance for monitoring rotavirus disease burden and molecular characterization is needed prior to rotavirus vaccine introduction in Nepal. METHODS: A total of 3310 stool samples (2849 hospitalized cases and 461 non-hospitalized cases), were collected from patients <5 years of age from January 2013 to December 2016 and tested for rotavirus antigen by ELISA (ProSpecT, USA). A subset of ELISA positive stool samples was genotyped. Demographic data were collected. RESULTS: During the four-year surveillance period, the overall burden of rotavirus infection was 24% among hospitalized children which was much higher than among non-hospitalized children (12%). The majority of children hospitalized with rotavirus gastroenteritis were less than 2 years of age (86%). Rotavirus-associated gastroenteritis hospitalizations occur year-round in Nepal, but a distinct peak in winter (up to 40% among hospitalized) was observed. Of 735 ELISA positive samples, 492 were genotyped by RT-PCR. The most prevalent genotype was G12P[6] (45.3%), followed byG2P[4](12.2%), G1P[8] (9.6%), G9P[4](7.3%), and G9P[8](4.5%). Mixed infection accounted for 4.4% of cases, 6.2% were partially typed and 10.5% of the samples were G and P untypable. CONCLUSIONS: A high burden of rotavirus gastroenteritis and a diversity of circulating rotavirus strains in Nepal were observed. Recommendation to introduce a rotavirus vaccine with known vaccine effectiveness would help in reducing the severity of Rotavirus diarrheal disease in children less than 5 years of age.

First assessment of all-cause acute diarrhoea and rotavirus-confirmed cases following massive vaccination in Argentina.

Argentina incorporated rotavirus massive vaccination in 2015. No specific strategy has been designed to accurately measure the impact of this recent introduction on the diarrhoeal disease burden in our country. We assessed post-vaccine introduction data (all-cause acute diarrhoea and rotavirus laboratory-confirmed cases, and genotype distribution), compared with pre-vaccination period in children under 5 years of age in Argentina. Cross-sectional ecologic analysis was conducted with data from the Argentine Surveillance Health System. Endemic channel and global and seasonal incidence rates of pre- and post-vaccination periods were calculated and further compared. Conventional binary genotypification on rotavirus-positive samples was also performed. In post-vaccination period, a global decrease of 20.8% in the rate of all-cause acute diarrhoea cases was found. The endemic channel showed that declination was more significant in the autumn/winter season. Rotavirus laboratory-confirmed cases showed 61.7% of reduction and the weekly distribution analyses indicated a significant flattening of the expected seasonal peak. G2P[4] was the most prevalent circulating genotype (57.2%). This study represents the first assessment of diarrhoeal disease burden since rotavirus massive vaccination strategy was implemented in Argentina. This introduction represented a successful intervention due to the significant decrease in all-cause acute diarrhoea cases and rotavirus laboratory-confirmed cases.

Rotavirus gastroenteritis surveillance in Azerbaijan, 2011-2016.

INTRODUCTION: Rotavirus is a leading cause of acute gastroenteritis and mortality among children worldwide but data describing rotavirus disease in Azerbaijan are lacking. This analysis describes the rotavirus disease burden in Baku, the largest city in Azerbaijan. METHODS: We conducted active, prospective, sentinel hospital surveillance with laboratory confirmation for rotavirus among children under 5 years of age hospitalized at a large pediatric hospital in Baku during 2011-2016. Children with bloody diarrhea, or prior use of antibiotics or intravenous fluids were excluded. The guardians of enrolled children completed a questionnaire documenting clinical and demographic information. A stool specimen was collected from each enrolled child. We report the number and proportion of rotavirus positive hospitalizations during the surveillance period and a clinical description of rotavirus-positive and rotavirus-negative children. RESULTS: From July 2011 through June 2016, 3139 children <5 years of age were enrolled into the surveillance system. Of these, 523 (17%) were positive for rotavirus, varying from 13% to 21% by surveillance year, with a median of 16% over the surveillance period. Increase in rotavirus detections occurred during December-May. Most rotavirus infections (303/523; 58%) occurred in children aged 6-23 months. CONCLUSION: Rotavirus is responsible for approximately 16% of annual hospital admissions for acute gastroenteritis in children <5 years of age in Baku. This is lower than regional estimates. Exclusion of children with a history of antibiotic use or intravenous fluids may be accounting for this lower prevalence, and expansion of surveillance to include these groups could provide a more comprehensive picture of acute rotavirus gastroenteritis in Baku.

The economic burden of rotavirus infection in South Korea from 2009 to 2012.

Rotavirus is a common cause of diarrhea worldwide, and vaccination prevents rotaviral gastroenteritis. Since the rotavirus vaccine was introduced in Korea in 2007, the prevalence of rotaviral gastroenteritis has decreased. However, little is known on the economic burden of rotavirus infection and its variations in Korea. Here, we estimated the economic costs of rotavirus infection from 2009 to 2012 using nationwide data from the National Health Insurance Service (NHIS) claims. Socioeconomic costs were subdivided into direct and indirect and measured with a prevalence-based approach. Costs were converted from Won to United States dollars (US$). The number of children <5 years old infected with rotavirus decreased from 21,437 to 10,295 during the study period, representing a decrease in prevalence from 947 to 443 per 100,000. The sum of direct and indirect costs also decreased, from $17.3 million to $9.6 million, and the days of admission decreased from 76,000 to 38,000. However, per capita expenditures slightly increased, from $809 to $934. Thus, the economic burden of rotavirus infection decreased after implementation of rotavirus vaccination. Including the vaccine as part of the national essential vaccination program could reduce the prevalence of and economic loss from rotavirus infection in Korea.

Pediatric hospitalizations attributable to rotavirus gastroenteritis among Cambodian children: Seven years of active surveillance, 2010-2016.

BACKGROUND: Each year, approximately 1,066 Cambodian children under five years old die of diarrhea, and 51% of these deaths are due to rotavirus gastroenteritis. Quantifying childhood hospitalizations caused by severe rotavirus infections is also important in demonstrating disease burden caused by this virus. The objective of this study is to update and confirm the current burden of pediatric hospitalizations attributable to rotavirus gastroenteritis among Cambodian children using seven years of continuous active, prospective surveillance from 2010 to 2016. We also characterize the circulating rotavirus genotypic strains during this period. METHODS: Active surveillance for rotavirus gastroenteritis was conducted from January 2010 through December 2016 at a national hospital in Phnom Penh, Cambodia. Children <60 months of age who were hospitalized for acute gastroenteritis (AGE) were consented and enrolled. Information on gender, age, clinical characteristics, and month of onset were collected. Stool specimens were collected and tested by enzyme immunoassay for the presence of rotavirus antigen, and genotyping was performed on rotavirus test-positive specimens to characterize predominant rotavirus strains during the surveillance period. RESULTS: Of 7007 children enrolled with AGE and having specimens collected, 3473 (50%) were attributed to rotavirus gastroenteritis. The majority of rotavirus hospitalizations occurred in children younger than two years old (92%). Year-round rotavirus transmission was observed, with seasonal peaks during the cooler, dry months between November and May. Genotypic trends in rotavirus were observed over the surveillance period; the predominant rotavirus strains changed from G1P[8] (2010-2012), to G2P[4] (2013-2014), the emergence of genotype G8P[8] in 2015, and G3P[8] in 2016. CONCLUSIONS: Rotavirus is the leading cause of severe acute gastroenteritis hospitalizations in Cambodian children under five years old, with 50% of such hospitalizations attributable to rotavirus. Over 90% of rotavirus hospitalizations occurred in children under 2 years of age. Changes in the predominant rotavirus strains occurred over time among these unvaccinated children. This information is important to understand and prioritize the current potential impacts upon child health that could be achieved through the introduction of rotavirus vaccines in Cambodia.

Impact on affected families and society of severe rotavirus infections in Swedish children assessed in a prospective cohort study.

BACKGROUND: Few prospective cohort studies have estimated the overall impact of severe rotavirus gastroenteritis (RVGE) leading to hospitalization on families and society. We assessed human and economic resources needed to care for an affected average child aged <5 years in Sweden. METHODS: The study was conducted in Astrid Lindgren Children's Hospital which serves approximately 14% of all Swedish children <5 years of age. All children admitted with acute gastroenteritis in the study period were tested for rotavirus. Health care consumption was collected prospectively and publically available unit costs used to calculate direct costs. Non-medical and indirect costs were collected in interviews with families using a standardized questionnaire during the hospital stay and approximately 14 days post-discharge. RESULTS: 144/206 children (70%) with laboratory-confirmed RVGE were included. The median age was 14 months. The average total cost per hospitalized child was €3894, of which €2169 (56%) was due to direct healthcare-related costs (including Emergency Department visits and in-patient care), €104 (2%) to non-medical direct costs and €1621 (42%) to indirect costs due to productivity loss. Carers of children with severe RVGE were absent from work on average five days per study child: four days during hospitalization of affected child and one day due to gastroenteritis in the carer. CONCLUSIONS: Costs for RVGE are dominated by direct costs which are similar to some other countries in Europe, but indirect costs due to productivity loss are also important, and should be considered in decisions to introduce rotavirus vaccines into national vaccination programmes.

Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger.

BACKGROUND: Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa. METHODS: We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. RESULTS: Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception. CONCLUSIONS: Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).

Burden of Rotavirus and Enteric Bacterial Pathogens among Children under 5 Years of Age Hospitalized with Diarrhea in Suburban and Rural Areas in Kenya.

This cross-sectional descriptive study aimed to investigate the incidence of rotavirus and enteric bacterial infections among children up to 5 years old with diarrhea living in suburban and rural areas of Kenya. Between August 2011 and December 2013, a total of 1,060 diarrheal fecal specimens were obtained from 722 children at Kiambu County Hospital (KCH), located in a suburban area, and from 338 children from Mbita District Hospital (MDH), located in a rural part of western Kenya. Of the 1,060 isolates, group A rotavirus was detected in 29.6% (214/722) and 11.2% (38/338) fecal specimens from KCH and MDH, respectively. Diarrheagenic Escherichia coli (DEC) was found to be the most frequently isolated bacterial pathogens in both study areas (32.8% at KCH and 44.1% at MDH). Two different mixed infection patterns (virus/bacteria and bacteria/bacteria) were observed among patients. A significantly higher infection rate of rotavirus (17.6%, p = 0.001) and DEC (10.5%, p = 0.007) were observed during the dry season. Our study found that in both suburban and rural settings in Kenya, rotavirus and DEC are the principal cause of pediatric diarrhea and exhibit higher incidence during the dry season.

Burden of Childhood Rotavirus Disease in the Outpatient Setting of the Russian Federation.

BACKGROUND: This is a prospective, multicentered study conducted in 9 large urban areas in Russia, in order to determine the burden of rotavirus gastroenteritis in children <5 years of age and the genotypes circulating during 1 rotavirus season. METHODS: From November 2012 to May 2013, surveillance was conducted in Moscow, Saint-Petersburg, Vologda, Krasnodar, Krasnoyarsk, Novosibirsk, Yaroslavl, Khanty-Mansiysk and Vladivostok. Children <5 years of age presenting at outpatient clinics with acute gastroenteritis (AGE) of less than 72 hours duration were enrolled in the study. Stool samples were tested for rotavirus and positive samples were P- and G-typed. Clinical symptoms were captured by physicians and parents on Day 1. Symptom severity was analyzed by Vesikari scoring system. The direct expenses of parents caused by AGE were obtained from questionnaires provided to parents by phone. RESULTS: A total of 501 were children enrolled. Stool samples were analyzed for 487 (97%) children, and 151 (31%) of those were rotavirus positive. Rotavirus gastroenteritis was associated with more severe clinical course (Vesikari score 11.4 ± 2.2) versus non-rotavirus gastroenteritis (Vesikari score 9 ± 3). The identified serotypes were G4P[8] 38.9%, G1P[8] 34.2%, G3P[8] 6%, G9P[8] 6%, G2P[4] 2% and G4P[4] 0.7%. The mean overall expenses of parents caused by rotavirus and non-rotavirus gastroenteritis were 143.7 USD and 128.8 USD, respectively. CONCLUSIONS: Rotavirus accounted for 31% of all AGE-related outpatient visits. The major rotavirus genotypes were G1P[8] and G4P[8]. Rotavirus gastroenteritis was associated with significantly more severe clinical symptoms than non-rotavirus gastroenteritis. The average costs of rotavirus cases for parents of children were elevated against the same indications for non-rotavirus. These findings underscore the need for a safe and effective rotavirus vaccine in Russia.

Economic evaluation of routine infant rotavirus immunisation program in Japan.

Two rotavirus vaccines are currently available in Japan. We estimated the incremental cost-effectiveness ratio (ICER) of routine infant rotavirus immunisation program without defining which vaccine to be evaluated, which reflects the current deliberation at the Health Science Council in charge of Immunisation and Vaccine established by the Ministry of Health, Labor and Welfare of Japan. Three ICERs were estimated, one from payers' perspective and 2 from societal perspective depending on the scenarios to uptake vaccines. The health statuses following the birth cohort were as follows: not infected by rotavirus, asymptomatic infection, outpatients after infection, hospitalised after infection, developing encephalitis/encephalopathy followed by recovery, sequelae, and death. Costs of per course of vaccination was ¥30,000 (US$283; US$1 = ¥106). The model runs for 60 months with one month cycle. From payers' perspective, estimated ICERs were ¥6,877,000 (US$64,877) per QALY. From societal perspective, immunisation program turns out to be cost-saving for 75% simultaneous vaccination scenario, while it is at ¥337,000 (US$3,179) per QALY gained with vaccine alone scenario. The probability of rotavirus immunisation program to be under ¥5,000,000 (US$47,170) per QALY was at 19.8%, 40.7%, and 75.6% when costs per course of vaccination were set at ¥30,000 (US$283), ¥25,000 (US$236), and ¥20,000 (US$189), respectively. Rotavirus immunisation program has a potential to be cost-effective from payers' perspective and even cost-saving from societal perspective in Japan, however, caution should be taken with regard to the interpretation of the results as cost-effectiveness is critically dependent on vaccination costs.

Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study.

BACKGROUND: Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). METHODS: GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen-specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children. FINDINGS: We analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni o C coli (around two times), and heat-stable enterotoxin-producing E coli ([ST-ETEC] around 1·5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen-attributable diarrhoeal burden was 89·3% (95% CI 83·2-96·0) at the population level, compared with 51·5% (48·0-55·0) in the original GEMS analysis. The top six pathogens accounted for 77·8% (74·6-80·9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42·5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38·9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. INTERPRETATION: A quantitative molecular diagnostic approach improved population-level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised. FUNDING: Bill & Melinda Gates Foundation.

Quality of greywater treated in biochar filter and risk assessment of gastroenteritis due to household exposure during maintenance and irrigation.

AIM: This study evaluated treatment of greywater (GW) by a biochar filter in Jordan and assessed the annual risks of infection (Pi-annual ), annual risk of disease (Pd-annual ) and disease burden (in disability-adjusted life years; DALYs) of gastroenteritis caused by Salmonella spp. and rotavirus due to ingestion of GW during system maintenance and consumption of green onions irrigated with treated and nontreated GW. METHODS AND RESULTS: The biochar filter efficiently removed 93% of biochemical oxygen demand (BOD5 ) and 85% of solids, while removal of Escherichia coli was insignificant. Treatment of GW decreased the median Pd-annual due to ingestion of GW from 1·39 × 10-2 to 6·0 × 10-3 for Salmonella spp. but did not affect Pd-annual caused by rotavirus (9·73 × 10-1 to 1·0). Consumption of onions irrigated with treated GW had a median Pd-annual of 1·25 × 10-9 to 1·2 × 10-8 for Salmonella spp. and 4·96 × 10-4 to 4·37 × 10-3 for rotavirus infection, which was 99·9 and 90% lower, respectively, than the risk when consuming onions irrigated with nontreated GW. The highest risks of gastrointestinal disease were thus associated mainly with direct ingestion of GW when maintaining the system. CONCLUSIONS: Garden produce irrigated with GW treated in biochar filter did not display intolerable risks of rotavirus-based gastroenteritis during summer season in the study area given that the produce is harvested 1 to 2 days, and washed, before consumption. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributes to scientific-based knowledge on the suitability of biochar filters for onsite greywater treatment and confirms the microbial safety of recycling treated greywater for garden irrigation.

Use of Patients With Diarrhea Who Test Negative for Rotavirus as Controls to Estimate Rotavirus Vaccine Effectiveness Through Case-Control Studies.

BACKGROUND: Case-control studies are often performed to estimate postlicensure vaccine effectiveness (VE), but the enrollment of controls can be challenging, time-consuming, and costly. We evaluated whether children enrolled in the same hospital-based diarrheal surveillance used to identify rotavirus cases but who test negative for rotavirus (test-negative controls) can be considered a suitable alternative to nondiarrheal hospital or community-based control groups (traditional controls). METHODS: We compared calculated VE estimates as a function of varying values of true VE, attack rates of rotavirus and nonrotavirus diarrhea in the population, and sensitivity and specificity of the rotavirus enzyme immunoasssay. We also searched the literature to identify rotavirus VE studies that used traditional and test-negative control groups and compared VE estimates obtained using the different control groups. RESULTS: Assuming a 1% attack rate for severe rotavirus diarrhea, a 3% attack rate for severe nonrotavirus diarrhea in the population, a test sensitivity of 96%, and a specificity of 100%, the calculated VE estimates using both the traditional and test-negative control groups closely approximated the true VE for all values from 30% to 100%. As true VE decreased, the traditional case-control approach slightly overestimated the true VE and the test-negative case-control approach slightly underestimated this estimate, but the absolute difference was only ±0.2 percentage points. Field VE estimates from 10 evaluations that used both traditional and test-negative control groups were similar regardless of control group used. CONCLUSIONS: The use of rotavirus test-negative controls offers an efficient and cost-effective approach to estimating rotavirus VE through case-control studies.