Infant rotavirus vaccination may provide indirect protection to older children and adults in the United States

Following the introduction of rotavirus vaccination in the United States, rotavirus and cause-unspecified gastroenteritis discharges significantly decreased in 2008 in the 0-4, 5-14, and 15-24-year age groups, with significant reductions observed in March, the historic peak rotavirus month, in all age groups. We estimate that 15% of the total 66 000 averted hospitalizations and 20% of the $204 million in averted direct medical costs attributable to the vaccination program were among unvaccinated 5-24 year-olds. This study demonstrates a previously unrecognized burden of severe rotavirus in the population >5 years and the primacy of very young children in the transmission of rotavirus.     

Incidence and burden of rotavirus gastroenteritis in Japan, as estimated from a prospective sentinel hospital study

We assessed the burden of rotavirus infection-related disease, in terms of hospitalization and associated costs, at 3 sentinel hospitals in Akita prefecture, Japan. From January 2001 through December 2002, a total of 443 children <5 years of age were hospitalized for acute gastroenteritis. Of 422 stool specimens collected, 244 (58%) tested positive for rotavirus. Only 7.8% of the rotavirus disease-associated hospitalizations involved infants <6 months of age, whereas most cases of disease (39%) were reported in the second year of life, and 89% of cases had occurred by 36 months of age. The mean severity score for rotavirus gastroenteritis resulting in hospitalization was 16.5, according to the modified 20-point severity scoring system. The average associated direct medical cost was 136,000 yen (1236 US dollars) per case and was similar among the 3 hospitals. The estimated incidence of rotavirus disease-associated hospitalizations among children <5 years of age was 7.9-17.6 hospitalizations/1000 person-years, and the estimated cumulative incidence by 5 years of age was 6.6%. Thus, approximately 1 in 15 children will require hospitalization due to rotavirus diarrhea by their fifth year of life. In Japan, this would mean that 78,000 children <5 years of age would be hospitalized each year, resulting in a direct medical cost of 10 billion yen (96 US dollars million). The burden associated with rotavirus gastroenteritis in Japan is substantial and might be reduced through the introduction of vaccines.     

A Prospective Hospital-based Surveillance to Estimate Rotavirus Disease Burden in Bhutanese Children under 5 Years of Age

As part of efforts to develop an informed policy for rotavirus vaccination, this prospective study was conducted to estimate the burden of rotavirus diarrhea among children less than 5 years old attended to the Department of Pediatrics, Jigme Dorji Wangchuk National Referral Hospital (JDWNRH), Thimphu, Bhutan. The duration of the study was three years, extending from February 2010 through December 2012. We estimated the frequency of hospitalization in the pediatric ward and dehydration treatment unit (DTU) for diarrhea and the number of events attributable to rotavirus infection among children under 5 years of age. During the study period, a total of 284 children (1 in 45) were hospitalized in the pediatric ward, and 2,220 (1 in 6) in the DTU with diarrhea among children residing in the Thimphu district. Group A rotavirus was detected in 32.5% and 18.8% of the stool samples from children hospitalized in the pediatric ward, respectively. Overall, 22.3% of the stool samples were rotavirus-positive, and the majority (90.8%) of them was detected in children under 2 years of age. From this study, we estimated that the annual incidence of hospitalization in the pediatric ward and DTU due to rotavirus diarrhea was 2.4/1000 (95% CI 1.7–3.4) and 10.8/1000 (95% CI 9.1–12.7) children, respectively. This study revealed that rotavirus is a major cause of diarrhea in Bhutanese children in Thimphu district and since no study has been performed previously, represents an important finding for policy discussions regarding the adoption of a rotavirus vaccine in Bhutan.     

Impact of rotavirus infection at a large pediatric hospital

Information is limited about national patterns of rotavirus infection throughout the USA. Discharge records and laboratory rotavirus detection for 1979-1989 at the Texas Children's Hospital, Houston, were evaluated to determine the impact of rotavirus gastroenteritis at a large children's hospital. The availability since 1983 of diagnostic assays less expensive than electron microscopy was associated with increased rotavirus detection. Only 67% of rotavirus-positive samples came from children likely to have had community-acquired acute gastroenteritis. Combined laboratory results and ICD-9 discharge diagnosis codes (008.6, 008.8, and 558.9) measured rotavirus activity better than either alone. A case definition for hospitalization for rotavirus infection resulted in an estimate that an average of 473 children were hospitalized for rotavirus infection at Texas Children's Hospital each year over the 10-year period. These cases accounted for 3.0% of all hospital days and $1.5 million per year in bed costs at this hospital. Hospitalization rates and the impact of hospital costs for the USA were estimated by extrapolation.     

Impact of measles in France

Although measles vaccine has been licensed since 1968, immunization against measles has not met with much success in France, partly because the disease is no longer feared. The level of vaccination coverage appears to be less than 20%. Indeed, the present epidemiologic situation is similar to the natural situation in a developed country. A multicenter, retrospective hospital survey revealed that 1,157 patients with measles were hospitalized during a 30-month period in five areas (total population, 4.2 million). Analysis of the preliminary results of this survey and of available national data showed an incidence of 5.6-7.5 cases per 1,000 population; a hospitalization rate of one per 10,000; a death rate of 0.56 per 1 million; and a disability rate of 0.48 per 1 million. Encephalitis (the definition of which should be reappraised) occurred once in 2,850 cases, and subacute sclerosing panencephalitis was not rare (incidence, one case per 2.6 million people). The problem posed by measles is sufficiently grave to justify a national campaign urging the widespread vaccination of children.     

Influenza vaccination in young children reduces influenza-associated hospitalizations in older adults, 2002-2006

OBJECTIVES: To assess how influenza vaccination coverage in children is related to pneumonia and influenza (P&I) in older adults and whether sociodemographic factors modify these associations. DESIGN: Approximately 5 million hospitalization records from the Centers for Medicare and Medicaid Services for four influenza years (2002–2006) were abstracted. A single‐year age distribution of rates of P&I hospitalization was estimated according to state for each influenza season; an exponential acceleration in the P&I rates with age was observed for each influenza season. State‐ and season‐specific P&I rate accelerations were regressed against the percentage of vaccinated children, older adults, or both using mixed effects models. SETTING: U.S. population, 2002 to 2006. PARTICIPANTS: U.S. population aged 65 and older. MEASUREMENTS: State‐level influenza annual vaccination coverage data in children and older adults were obtained from the National Immunization Survey and the Behavioral Risk Factor Surveillance System, respectively. RESULTS: Child influenza vaccination coverage was negatively associated with age acceleration in P&I, whereas influenza vaccination in the older adults themselves was not significantly associated with P&I in older adults. CONCLUSION: Vaccination of children against influenza may induce herd immunity against influenza for older adults and has the potential to be more beneficial to older adults than the existing policy of preventing influenza by vaccinating older adults themselves.     

How best to estimate the global burden of pertussis?

In most countries, pertussis surveillance is inadequate for accurately estimating numbers of cases or deaths. Good estimates are needed to help set priorities for vaccination programmes. We aimed to develop a simple, reliable, and explicit method for estimating pertussis cases and deaths for children under 15 years to calculate the global disease burden in 1999. We estimated the proportion of susceptible children becoming infected in countries with poor vaccination coverage (<70%) in 1999 at 30% by 1 year, 80% by 5 years, and 100% by 15 years of age and for countries with good coverage (> or =70%) at 10% by 1 year, 60% by 5 years, and 100% by 15 years. Vaccine efficacy was estimated at 80% for preventing infection and 95% for preventing deaths. We used UN population estimates and vaccination coverage reported to WHO (adjusted for specific survey data if available). Case fatality ratios for countries with high and low child mortality were derived from published and unpublished work. For some countries with good vital events registration we used reported deaths adjusted for underascertainment. In 1999 there were an estimated 48.5 million pertussis cases in children worldwide. Deaths from pertussis were estimated at 390000 and at 295000 after adjustment for local data sources. Based on this approach, disability-adjusted life years from pertussis (12.7 million) in 2000 exceeded those of other preventable diseases such as lung cancer (11.4 million) and meningitis (5.8 million). This simple approach yields estimates that can be used for setting vaccination programme priorities. Better data are needed on the public health importance of pertussis in high mortality countries, the benefits of incomplete vaccination, and the harm from delayed vaccination.     

Rotavirus-associated acute gastroenteritis hospitalizations among Japanese children aged <5 years: active rotavirus surveillance in Mie Prefecture, Japan

Two effective vaccines for rotavirus infection will be available near future in Japan and data on the burden of rotavirus disease and the circulating rotavirus strains are urgently needed. To obtain these data, we set up active rotavirus hospitalization surveillance in three cities, Tsu, Matsusaka, and Ise in Mie Prefecture, Japan. From November 1, 2007 through October 31, 2009, we enrolled children <5 years of age who were hospitalized with a diagnosis of acute gastroenteritis (AGE) and collected information on age, sex, month of admission, city of residence, and symptoms at the time of hospitalization. Stool samples were also obtained for rotavirus testing and genotype investigation. Rotavirus infection accounted for approximately 40% to 50% of hospitalized AGE cases in each city, and approximately 63% of those hospitalized were 2 years of age or younger. Matsusaka had the highest incidence rate at 4.7 rotavirus hospitalizations per 1,000 children <5 years of age (95% confidence interval [CI]: 3.6-5.9), followed by Tsu City (4.4 per 1,000; 95% CI: 3.6-5.3), and Ise City (2.8 per 1,000; 95% CI: 2.0-4.0). The most dominant rotavirus genotype was G3P[8], which accounted for 73.1% of cases. Our findings confirm the substantial health burden of rotavirus AGE hospitalization among Japanese children <5 years of age.     

Impacto de la vacunación de las embarazadas frente a la tosferina en las hospitalizaciones de menores de un año en un hospital de tercer nivel de Cataluña

IntroductionThe recommendation for pertussis vaccination in pregnancy was established in Catalonia in February 2014. The objective of this study was to compare the hospitalization rate for pertussis in children under one year of age before and after the implementation of the vaccination program.MethodsObservational and retrospective study of patients under one year of age admitted to hospital with a diagnosis of pertussis. The hospitalization rate of patients under one year of age of the period prior to the vaccination program (2008-2013) was compared with the period with vaccination program (2014-2019) in the total of children under one year of age and in 2 subgroups: children under 3 months and between 3-11 months.ResultsHospitalization rate was significantly lower in the period with vaccination program in children under one year of age and specifically in children under 3 months (2.43 vs. 4.72 per 1,000 person-years and 6.47 vs. 13.11 per 1,000 person-years, respectively). The rate ratios were: 0.51 (95% CI 0.36-0.73) for children under one year of age; 0.49 (95% CI 0.32-0.75) for those younger than 3 months and 0.56 (95% CI 0.30-1.03) for those with 3-11 months. No statistically significant differences were observed in the clinical severity between both periods.ConclusionThe introduction of the pertussis vaccination program in pregnancy was associated with a global lower hospitalization rate for pertussis in children under one year of age and specifically in those under 3 months of age.     

Burden of Norovirus and Rotavirus in Children after Rotavirus Vaccine Introduction,Cochabamba, Bolivia

The effectiveness of rotavirus vaccine in the field may set the stage for a changing landscape of diarrheal illness affecting children worldwide. Norovirus and rotavirus are the two major viral enteropathogens of childhood. This study describes the prevalence of norovirus and rotavirus 2 years after widespread rotavirus vaccination in Cochabamba, Bolivia. Stool samples from hospitalized children with acute gastroenteritis (AGE) and outpatients aged 5–24 months without AGE were recruited from an urban hospital serving Bolivia''s third largest city. Both viruses were genotyped, and norovirus GII.4 was further sequenced. Norovirus was found much more frequently than rotavirus. Norovirus was detected in 69/201 (34.3%) of specimens from children with AGE and 13/71 (18.3%) of those without diarrhea. Rotavirus was detected in 38/201 (18.9%) of diarrheal specimens and 3/71 (4.2%) of non-diarrheal specimens. Norovirus GII was identified in 97.8% of norovirus-positive samples; GII.4 was the most common genotype (71.4% of typed specimens). Rotavirus G3P[8] was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P[4] was second most prevalent (16.0% of typed specimens). This community is likely part of a trend toward norovirus predominance over rotavirus in children after widespread vaccination against rotavirus.     

Hospitalizations and deaths from diarrhea and rotavirus among children <5 years of age in the United States, 1993-2003

Recently a new rotavirus vaccine was licensed in the United States and recommended for universal immunization of American children. The impact of the vaccine on a decrease in hospitalizations will take several years to assess and will be based on the availability of good baseline data on the disease. We used the largest US hospital discharge database available, the Healthcare Cost and Utilization Project (HCUP), to study national rates, trends, and risk factors for diarrhea- and rotavirus-associated hospitalizations and deaths among children <5 years of age, to establish a baseline against which vaccine implementation can be measured. Rotavirus remained the most important cause of pediatric diarrhea throughout the study period (1993-2003). When the data were extrapolated to the US population, rotavirus was estimated to be the cause of approximately 60,000 hospitalizations and 37 deaths annually. Black infants had a significantly higher risk of being hospitalized with and dying from rotavirus disease early in life, compared with white infants (risk ratio [RR] for hospitalization by 12 months of age was 2.4, with a 95% confidence interval [CI] of 1.2-4.7; RR for death was 2.0, with a 95% CI of 1.7-2.5). Such racial differences in age and risk of rotavirus-associated hospitalization and death highlight the importance of timely and early rotavirus immunization of minority children. The HCUP database serves as a sensitive and robust data source for monitoring the impact of a rotavirus-immunization program in the United States.     

Epidemiology and burden of rotavirus diarrhea in Thailand: results of sentinel surveillance

Diarrhea remains an important cause of morbidity and mortality among children in Thailand, with >1 million cases reported in 2002. In anticipation of the development of vaccines against rotavirus, we evaluated the disease burden associated with rotavirus infection in Thai children and evaluated the rotavirus serotypes now circulating in Thailand. Diarrhea surveillance was conducted at 6 Thai hospitals in different geographic areas. Community-based surveillance was conducted in Huaykrajao District, Kanchanaburi Province. During the 24 months of surveillance, 4057 children were admitted to the 6 participating hospitals, and 1950 stool samples were collected. Of these stool samples, 43% (838) were positive for rotavirus. All rotavirus-positive stool samples were evaluated to identify their serotypes; 54.8% of samples were of serotype G9, which was predominant each year. Other identified rotavirus serotypes included G2, G4, G1, and G3 (17.2%, 5.3%, 0.8%, and 0.1% of isolates, respectively). Approximately one-half of the children hospitalized with rotavirus diarrhea were <1 year old. Community surveillance showed the proportion of cases of rotavirus diarrhea in the community to be much lower than that in the hospitalized population (12.2% vs. 43.0%).     

Hepatitis A occurrence and outbreaks in Europe over the past two decades: A systematic review

Hepatitis A (HA) is a vaccine-preventable liver disease with >170 million new cases occurring yearly. In recent outbreaks in the USA, hospitalization and case-fatality ratios were >60% and ~1%, respectively. In Europe, endemicity persists and outbreaks continue to occur. We performed a systematic literature review to understand the changes in HA occurrence in Europe over the past two decades. PubMed and Embase were systematically searched for peer-reviewed articles published between 1 January 2001 and 14 April 2021 using terms covering HA, 11 selected European countries, outbreaks, outcomes and HA virus circulation. Here, we focus on HA occurrence and outbreaks in the five countries with the largest population and the most comprehensive vaccination recommendations: France, Germany, Italy, Spain and the UK; 118 reports included data for these five European countries. Notification rates (≤9.7/100,000 population) and percentages of men among cases (≤83.0%) peaked in 2017. The number of person-to-person-transmitted cases and outbreaks decreased in children but increased in other risk groups, such as men who have sex with men (MSM). Sexually transmitted outbreaks in MSM clustered around 2017. Travel-related outbreaks were few; the proportion of travel-related cases decreased during the past two decades, while the number of domestic cases increased. Despite the existing risk-based vaccination recommendations, HA transmission shifted in proportions from travelers and children to other risk groups, such as MSM and older age groups. Because a substantial proportion of the European population is susceptible to HA, adherence to existing recommendations should be monitored more closely, and enhanced vaccination strategies should be considered.     

Immunization status and hospitalization for vaccine-preventable and non-vaccine-preventable infections in liver-transplanted children

BACKGROUND Infections and associated morbidity and mortality may be more frequent in children who have undergone liver transplant than in healthy children.Immunization strategies to prevent vaccine-preventable infections(VPIs) can effectively minimize this infection burden.However,data on age-appropriate immunization and VPIs in children after liver transplant in Asia are limited.AIM To evaluate the immunization status,VPIs and non-VPIs requiring hospitalization in children who have undergone a liver transplant.METHODS The medical records of children who had a liver transplant between 2004 and 2018 at King Chulalongkorn Memorial Hospital(Bangkok,Thailand) were retrospectively reviewed.Immunization status was evaluated via their vaccination books.Hospitalization for infections that occurred up to 5 years after liver transplantation were evaluated,and divided into VPIs and non-VPIs.Hospitalizations for cytomegalovirus and Epstein-Barr virus were excluded.Severity of infection,length of hospital stay,ventilator support,intensive care unit requirement,and mortality were assessed.RESULTS Seventy-seven children with a mean age of 3.29±4.17 years were included in the study,of whom 41(53.2 %) were female.The mean follow-up duration was 3.68±1.45 years.Fortyeight children(62.3%) had vaccination records.There was a significant difference in the proportion of children with incomplete vaccination according to Thailand's Expanded Program on Immunization(52.0%) and accelerated vaccine from Infectious Diseases Society of America(89.5%)(P 0.001).Post-liver transplant,47.9% of the children did not catch up with ageappropriate immunizations.There were 237 infections requiring hospitalization during the 5 years of follow-up.There were no significant differences in hospitalization for VPIs or non-VPIs in children with complete and incomplete immunizations.The risk of serious infection was high in the first year after receiving a liver transplant,and two children died.Respiratory and gastrointestinal systems were common sites of infection.The most common pathogens that caused VPIs were rotavirus,influenza virus,and varicella-zoster virus.CONCLUSION Incomplete immunization was common pre-and post-transplant,and nearly all children required hospitalization for non-VPIs or VPIs within 5 years posttransplant.Infection severity was high in the first year post-transplant.     

A comparative trial of rhesus monkey (RRV-1) and bovine (RIT 4237) oral rotavirus vaccines in young children

Heterologous live, oral rotavirus vaccines of rhesus monkey (RRV-1) and bovine (RIT 4237) origin were tested for immunogenicity, excretion of virus, and clinical reactions in six- to eight-month-old infants. Antibody response, indicating infection with the vaccine virus, was detected in 21 (88%) of 24 children receiving the RRV-1 vaccine and in 18 (75%) of 24 receiving the RIT 4237 vaccine. Excretion of virus in the stools within one week after vaccination was demonstrable in 84% of the RRV-1 and in 21% of the RIT 4237 vaccinees. RRV-1 vaccination was associated with a febrile response (over 38 C) that clustered on days 3 or 4 postvaccination in 64% of the recipient children. In addition, 20% of the RRV-1 vaccinees had watery stools on days 4 or 5. Fever on days 3 and 4 and loose stools were not seen in the RIT 4237 vaccinees. We concluded that in young children the RRV-1 (rhesus monkey) rotavirus vaccine is more immunogenic than the RIT 4237 (bovine) rotavirus vaccine, but vaccination with RRV-1 is associated with significant adverse reactions.     

Epidemiology, clinical course and impact on hospitalization costs of acute diarrhea among hospitalized children in Athens, Greece.

The aim of this study was to describe the etiology, morbidity and hospitalization costs associated with acute diarrhea among hospitalized children in Greece. During 1999, 294 hospitalized children (median age 1 y) with acute diarrhea were prospectively studied. Bacterial and viral enteropathogens were detected in 100 (34%) and 37 (12.5%) patients, respectively; 17 (6%) patients had mixed infections. Isolated agents included Salmonella spp. (43 patients; 15%), rotavirus (32; 11%), Campylobacter spp. (26; 9%), enteropathogenic Escherichia coli (16; 5.5%), Shigella spp. (11; 4%), Aeromonas spp. (7; 2.5%), adenovirus (6; 2%), Yersinia enterocolitica (6; 2%), enterohemorrhagic Escherichia coli (2; 0.5%) and Giardia lamblia (1; 0.5%). Of the patients with bacterial infection, 70% were admitted between April and September 1999. A rotavirus-associated peak was noted in March. Patients with a bacterial infection were hospitalized for longer periods than those with viral infections. It is concluded that bacterial enteropathogens account for one-third of admissions due to acute diarrhea among children in Greece and are associated with significant hospitalization costs. Rotavirus is also a frequent cause of acute diarrhea necessitating hospitalization.     

Defining the Recipe for an Optimal Rotavirus Vaccine Introduction in a High-Income Country in Europe

Observational data over 15 years of rotavirus vaccine introduction in Belgium have indicated that rotavirus hospitalisations in children aged <5 years plateaued at a higher level than expected, and was followed by biennial disease peaks. The research objective was to identify factors influencing these real-world vaccine impact data. We constructed mathematical models simulating rotavirus-related hospitalisations by age group and year for those children. Two periods were defined using different model constructs. First, the vaccine uptake period encompassed the years required to cover the whole at-risk population. Second, the post-uptake period covered the years in which a new infection/disease equilibrium was reached. The models were fitted to the observational data using optimisation programmes with regression and differential equations. Modifying parameter values identified factors affecting the pattern of hospitalisations. Results indicated that starting vaccination well before the peak disease season in the first year and rapidly achieving high coverage was critical in maximising early herd effect and minimising secondary sources of infection. This, in turn, would maximise the reduction in hospitalisations and minimise the size and frequency of subsequent disease peaks. The analysis and results identified key elements to consider for countries initiating an optimal rotavirus vaccine launch programme.     

Health care costs of diarrheal disease and estimates of the cost-effectiveness of rotavirus vaccination in Vietnam

BACKGROUND: Rotavirus disease causes a significant health and economic burden worldwide. Several rotavirus vaccines may soon be available for use. A country's decision to introduce these vaccines will depend on its rotavirus disease burden, on the cost of the vaccine, and on the results of an economic assessment of the cost and effectiveness of a rotavirus vaccination program. METHODS: Data on medical and nonmedical direct costs and indirect costs were established in Khanh Hoa Province, Vietnam, and extrapolated to national estimates on the basis of the birth cohort in 2004. The main outcome measures were economic burden and cost-effectiveness ratio (United States dollars per disability-adjusted life-year averted and dollars per life saved) of vaccination. RESULTS: The disease burden is equivalent to an economic burden of an estimated 3.1 million US dollars in medical direct costs, 685,000 US dollars in nonmedical direct costs, and 1.5 million US dollars in indirect costs. From a societal perspective, treatment of rotavirus disease costs an estimated 5.3 million US dollars per year. From the health care system perspective, universal vaccination of infants at a cost of < or = 7.26 US dollars/vaccine dose would be a cost-effective public health intervention, according to the World Bank cost-effectiveness standard for low-income countries (140 US dollars/disability-adjusted life-year). CONCLUSIONS: Vaccination can effectively reduce the disease burden and health care costs of rotavirus-specific diarrhea in Vietnam.