Rotavirus Disease Research Articles

Rotavirus vaccination effectiveness: A case–case study in the EDICS project, Castellón (Spain)

In Spain, in 2006, two oral live-attenuated vaccines against rotavirus disease were licensed for infants up to 6 months. Recent data suggest that vaccine efficacy may vary by region. This makes the real-life postmarketing monitoring of rotavirus vaccination effectiveness an important aspect of rotavirus epidemiologic surveillance. We carried out a case–case study to assess the rotavirus vaccination effectiveness in children from 2 to 35 months of age during the year 2009 in Castellón. As a second- and counterfactual objective to evaluate the possible selection bias and the specificity of the association, we evaluated the “effectiveness” of pneumococcal vaccination against rotavirus diarrhea. Cases were 71 children with confirmed rotavirus gastroenteritis, and controls were 261 children with positive results to any other organism that was not rotavirus. The immunization status of each child, the number of doses and dates of vaccination were assessed by consulting the Regional Immunization Registry. The lowest proportion of vaccinated cases was observed among rotavirus diarrhea (2.8%). The proportion of vaccinated children among the control group was 21.8%. The effectiveness of vaccination with at least one dose of vaccine against rotavirus was 87.7% (45.5–99.7%). If we restrict the analysis to non-hospitalized children, this figure was slightly lower, 83.5% (25.4–96.3%). As expected, pneumococcal vaccination was not protective against rotavirus infection showing the specificity of the association found. The immunization information systems in combination with population-based studies of the incidence of infectious gastroenteritis, such as EDICS offer appropriate conditions for postmarketing monitoring of vaccine effectiveness.

A Cost Effectiveness and Capacity Analysis for the Introduction of Universal Rotavirus Vaccination in Kenya: Comparison between Rotarix and RotaTeq Vaccines

BackgroundDiarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination.MethodsCost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain.ResultsThe median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix.ConclusionVaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability.

Rotavirus genotype distribution in Kyrgyzstan and Kazakhstan, 2007–2009

This is the first study to present rotavirus genotype distribution in children admitted to a hospital with acute gastroenteritis in Kyrgyzstan and Kazakhstan from January 2007 through December 2009. In total, 858 rotavirus ELISA-positive samples were characterized by RT-PCR, with a considerable geographical and seasonal variation in genotype distribution observed during the study. The globally common genotypes (G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], G12P[8] and G12P[6]) accounted for 81.5-88.2% of the infections in Kyrgyzstan and 72.3-79.3% of the infections in Kazakhstan. The predominant genotypes were G1P[8], G2P[4] and G3P[8]. G1P[8] was the dominating genotype in Kyrgyzstan, detected in 51-64.7% of the samples. A similar predominance was not seen for G1P[8] in Kazakhstan, with a shift to G2P[4] predominance being seen in 2008. G9P[8] was a rare genotype in both countries, whereas G12 was detected in between 2.2% and 7.6% of the samples. The surveillance period was characterized by many co-circulating genotypes, and eight unusual combinations (G1P[4], G2P[8], G2P[6], G3P[4], G9P[4], G12P[4], G9P[9] and G10P[4]) were detected. This study provides important baseline data on rotavirus genotypes in Kyrgyzstan and Kazakhstan in the pre-vaccine era, and the results may indicate that the two licensed vaccines can be expected to prevent rotavirus disease in these countries.

Diversity of rotavirus strains circulating in children under 5 years of age admitted to hospital for acute gastroenteritis in morocco, june 2006 to may 2009

Rotavirus vaccine was introduced in Morocco during 2010. In anticipation of introducing rotavirus vaccines, the Ministry of Health in Morocco established a rotavirus surveillance network in June 2006 at four hospitals in Morocco to obtain baseline data on rotavirus disease burden and prevalent strains. From June 2006 to May 2009, stool samples were collected from children under 5 years of age admitted for diarrhea to four sentinel hospitals serving different regions of Morocco. Rotaviruses were detected in stools using enzyme immunoassay, then genotyped by reverse-transcriptase polymerase chain reaction. Samples with adequate stool in which the P or G types could not be determined by RT-PCR were subjected to nucleotide sequence analysis. Overall, 42% (579 of 1,388) of the stools samples tested were positive for rotavirus. Genotyping of 548 (95%) samples demonstrated that G1P[8] (55%) was the most prevalent strain, followed by G9P[8] (11.3%), G2P[4] (9.1%), G4P[8] (0.9%), and G3P[8] (0.4%). Several other strains were identified including G1P[4] (0.2%), G1P[6] (0.9%), G2P[6] (4.3%), G2P[8] (0.2%), G3P[6] (0.4%), G3P[4] (0.2%), and G9P[6] (0.2%). A high prevalence of mixed infections was found (15% of all samples) of which G1G2P[8] (4%) and G1G3P[8] (3.6%) accounted for the majority. Considerable diversity of rotavirus genotypes was present among strains circulating in Morocco prior to the introduction of the vaccine. This study highlighted the need for maintaining active surveillance to monitor changes in rotavirus disease burden and strain dynamics and to detect changes over time that could impact the effectiveness of the vaccination program.

Changes in hospitalisations for acute gastroenteritis in Australia after the national rotavirus vaccination program

To evaluate the impact of the Australian rotavirus vaccination program on both rotavirus and all-cause acute gastroenteritis (AGE) hospitalisations and to compare outcomes in Indigenous and non-Indigenous people. Retrospective analysis of the Australian Institute of Health and Welfare National Hospital Morbidity database for hospitalisations coded as rotavirus and all-cause AGE, between 1 July 2001 and 30 June 2010. Age-specific hospitalisation rates in Indigenous and non-Indigenous people, before and after the introduction of the vaccine program in July 2007. There was a 71% decline in rotavirus-coded hospitalisations of children aged < 5 years between periods before and after rotavirus vaccination (from 261 per 100,000 to 75 per 100,000). There was also a 38% decline in non-rotavirus coded AGE hospitalisations (from 1419 per 100,000 to 880 per 100,000). This represented more than 7700 hospitalisations of children aged < 5 years being averted in the financial year 2009-10. Reductions were also observed in the 5-19-years age group, suggesting that transmission of virus was reduced at a population level. Decreases in hospitalisations of Indigenous children were smaller than those for the general population, and fluctuated by location and year. These data show a sustained and substantial decline in severe rotavirus disease and all-cause AGE since the introduction of rotavirus vaccination, most pronounced in the target age group, but with evidence of herd immunity. The impact of rotavirus vaccination in Indigenous children in hyperendemic settings was less remarkable.

Monitoring of rotavirus vaccination in Morocco: Establishing the baseline burden of rotavirus disease

BackgroundRotavirus is a leading cause of childhood morbidity and mortality worldwide. Clinical trials for two rotavirus vaccines recommended by the WHO for global use since 2009 have successfully demonstrated the safety and efficacy of these vaccines in a wide range of countries. To control the burden of severe and fatal diarrheal disease, the Ministry of Health of Morocco introduced the single strain rotavirus vaccine into their national immunization program in 2010. MethodsWe employed a standard WHO case definition to identify children under 5 hospitalized with AGE at four hospitals from June 2006 to May 2010 to establish baseline burden of rotavirus disease before introduction of vaccine. Stool samples were collected and tested for rotavirus using a standard enzyme immunoassay. ResultsOverall, 40% (741 of 1841) of the children hospitalized with AGE tested positive for rotavirus, making it the single most common cause of severe gastroenteritis among children in Morocco. Applying this prevalence to the estimates of diarrheal hospitalizations and deaths in Morocco, we estimate that rotavirus annually causes 19,646 hospitalizations and 1604 deaths in children under 5 years of age. DiscussionOn the basis of these surveillance data, we estimate that 1 in 389 Moroccan children died and 1 in 32 was hospitalized due to rotavirus before their fifth birthday. A considerable proportion of these deaths and hospitalizations should be preventable through vaccination, and the 4 years of stable prevaccine surveillance in Morocco will be a tremendously useful platform for assessing potential changes in the epidemiology of rotavirus disease and measuring impact of the new rotavirus vaccine program in Morocco.

Bridging the gap from knowledge to delivery in the control of childhood diarrhoea

Despite its low profile on the child survival agenda, diarrhoea is the second leading killer of children under 5 years of age and accounts for 10% of child deaths every year.1 But although diarrhoeal disease is preventable and can be managed with low-cost interventions, progress in reducing its incidence in children has been slow in recent years.2 In 2009, the United Nations Children’s Fund (UNICEF) and the World Health Organization (WHO) jointly published Diarrhoea: why children are still dying and what can be done, a report intended to raise awareness of the issue and to lay out a comprehensive plan of action for reducing the incidence of childhood diarrhoea and its associated mortality.3 In June 2012, UNICEF issued another call to action in Pneumonia and diarrhoea: tackling the deadliest diseases for the world's poorest children and urged a refocusing of efforts to reduce preventable deaths caused by diarrhoea.4 This most recent UNICEF report underscores the need to intensify global commitment and funding for the fight against childhood diarrhoea and argues that scaling up key interventions among the poorest children would save lives. Key preventive interventions include an improved water supply and the promotion of community-wide sanitation and hand washing with soap, as well as vaccination against rotavirus infection and measles, promotion of breastfeeding and vitamin A supplementation.3 Key therapeutic interventions for children with diarrhoea include continued feeding, the use of zinc tablets and fluid replacement therapy with low-osmolarity oral rehydration salts (ORS). With the approach of the deadline for attaining the health-related Millennium Development Goals, the point has been repeatedly made that we know what interventions work.3,5 This message is simple and strategic, but it fails to make clear that although proven preventive and therapeutic interventions do exist, we are not always able to deliver them. If further reductions in the burden of childhood diarrhoea and its associated mortality are to be realized, we need more than a catalogue of proven interventions. We need strategies for delivering them with high acceptability and coverage. Our experience with the treatment of childhood diarrhoea illustrates the difficulty of translating knowledge into effective interventions. The use of ORS, which cost a mere US$ 0.10 per sachet, has been widely promoted since the 1970s and endorsed by national health programmes across the developing world, yet today only 34% of children under 5 years of age with diarrhoea receive ORS.4 Many factors account for this disappointing coverage, including ORS’ unpleasant taste and inconvenient one-litre packaging, which have made traditional formulations unpopular with children and caregivers alike. After years of stagnating ORS coverage, innovative delivery strategies are emerging. Flavoured varieties, smaller sachets for children and new distribution mechanisms are being promoted to at last improve the acceptability and uptake of this life-saving product. Vaccination against rotavirus infection is another promising new component of diarrhoea prevention. Rotavirus is the leading cause of severe diarrhoea in young children and vaccination against rotavirus disease could play a crucial role in the control of childhood diarrhoea throughout the world. WHO now recommends including rotavirus vaccination in all national routine immunization programmes. Furthermore, the GAVI Alliance plans to support the vaccine’s introduction in more than 40 countries by 2015. Despite this high-level support, the product’s presentation could make widespread vaccine delivery difficult. The available rotavirus vaccines require a cold chain capacity much greater than that needed for Expanded Programme on Immunization (EPI) vaccines6 and beyond what the public health infrastructure can sustain in some resource-limited settings. In fact, early experiences in Latin America and computational models for the Niger suggest that introducing the rotavirus vaccine where refrigeration and transport are inadequate could create bottlenecks that would reduce the flow of all vaccines.7 Vaccination against rotavirus infection certainly holds promise for reducing diarrhoea incidence and mortality, but without innovations in vaccine delivery, including the development of more EPI-friendly presentations, vaccination may become so difficult that its potential impact may be undercut. We echo the call of others for greater attention to delivery strategies3,8and take UNICEF’s appeal for stronger global commitment in the fight against childhood diarrhoea as an opportunity to underscore the necessity to bridge the gap between knowing what interventions work and delivering them to all those in need. Progress in the fight against diarrhoeal disease will stagnate unless better intervention delivery strategies are developed. We commit ourselves and call upon our partners to critically assess the delivery strategies currently in place, identify local barriers to intervention uptake and respond with appropriate measures for improving outcomes in children with diarrhoea. Only by delivering what we know to be effective can we further reduce childhood diarrhoea throughout the world.

Determinants of parents' decision to vaccinate their children against rotavirus: results of a longitudinal study

Rotavirus disease is a common cause of health care utilization and almost all children are affected by the age of 5 years. In Canada, at the time of this survey (2008-09), immunization rates for rotavirus were <20%. We assessed the determinants of a parent's acceptance to have their child immunized against rotavirus. The survey instruments were based on the Theory of Planned Behavior. Data were collected in two phases. In all, 413 and 394 parents completed the first and second interviews, respectively (retention rate 95%). Most parents (67%) intended to immunize their child against rotavirus. Factors significantly associated with parental intentions (Phase 1) were as follows: perception of the moral correctness of having their child immunized (personal normative belief) and perception that significant others will approve of the immunization behavior (subjective norm), perceived capability of having their child immunized (perceived behavioral control) and household income. At Phase 2, 165 parents (42%) reported that their child was immunized against rotavirus. The main determinant of vaccination behavior was parental intention to have their child vaccinated, whereas personal normative beliefs influenced both intention and behavior. The acceptability of the rotavirus vaccine will be higher if health promotion addresses parental knowledge, attitudes and beliefs regarding the disease and the vaccine.

Duration of Protection of Pentavalent Rotavirus Vaccination in Nicaragua

To evaluate the duration of protection of pentavaent rotavirus vaccine (RV5) against rotavirus hospitalizations in Nicaragua, a developing country in Central America. We conducted a case-control study at 4 hospitals from 2007 through 2010, including 1016 children hospitalized with laboratory-confirmed rotavirus diarrhea, 4930 controls with nonrotavirus diarrhea (ie, "test-negative"), and 5627 controls without diarrhea. All cases and controls were aged ≥ 6 months and born after August 2006. Outcomes included odds of antecedent vaccination between case-patients and controls, and effectiveness of vaccination (1 - adjusted odds ratio [OR] × 100). Duration of protection was assessed by comparing effectiveness among children aged <1 year compared with ≥ 1 year. Indicators of socioeconomic conditions and nonrotavirus vaccination (oral polio vaccine and diphtheria/tetanus/pertussis/hepatitis A/hepatitis B) for test-negative controls were more comparable to the rotavirus case-patients than nondiarrhea controls. RV5 vaccination was associated with a significantly lower risk of rotavirus hospitalization by using test-negative controls (OR: 0.55; 95% confidence interval [CI]: 0.41-0.74) and nondiarrhea controls (OR: 0.30; 95% CI: 0.22-0.40). Risk of rotavirus hospitalization was twofold lower among RV5 vaccinated children aged <1 year (OR: 0.36; 95% CI: 0.22-0.57) compared with RV5 vaccinated children aged ≥ 1 year (OR: 0.70; 95% CI: 0.47-1.05). RV5 provided good protection against severe rotavirus disease in Nicaragua during the first year of life, when most severe and fatal rotavirus disease in developing countries occurs. However, the decline in protection with age warrants monitoring of disease among older children and consideration of a booster dose evaluation at the end of infancy.

Risk Factors Associated With Rotavirus Gastroenteritis During a Community Outbreak in Chiapas, Mexico During the Postvaccination Era.

In January 2010, surveillance detected a rotavirus gastroenteritis outbreak in Chiapas, Mexico. We aimed to identify risk and protective factors for developing rotavirus gastroenteritis of any severity among children in the epidemic setting. A case-control study was conducted, comparing case patients (defined as children <36 months of age with acute gastroenteritis of any severity whose stool tested positive for rotavirus by enzyme immunoassay) with age- and municipality-matched controls. Information was obtained through face-to-face interviews on clinical outcome, demographics, breastfeeding history, rotavirus immunization status, and indicators of socioeconomic status. Eighty-five case patients and 170 controls were enrolled. Factors associated with lower risk of rotavirus gastroenteritis included current breastfeeding, owning a refrigerator, and being immunized with 1 or 2 doses of a live-attenuated monovalent rotavirus vaccine. History of previous diarrheal episodes and living with 7 or more people in the same household were associated with higher risk of developing rotavirus gastroenteritis. During this outbreak, dietary, socioeconomic, and environmental factors were independently associated with risk of developing rotavirus disease. Rotavirus vaccine also offered significant protection against rotavirus disease of any severity, emphasizing the value of vaccination as a simple and highly effective public health strategy for prevention of rotavirus illness.

An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts

BackgroundRotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease.Methods150 plant extracts with nutritional applications were screened in vitro on MA-104 cells for their antiviral activity against rhesus rotavirus (RRV). One extract (Aspalathus linearis (Burm.f.) R.Dahlgren) was also tested for its effect on the loss of transepithelial resistance (TER) of Caco-2 cells caused by simian rotavirus (SA-11) infection.ResultsAqueous extracts of Nelumbo nucifera Gaertn. fruit, Urtica dioica L. root, Aspalathus linearis (Burm.f.) R.Dahlgren leaves, Glycyrrhiza glabra L. root and Olea europaea L. leaves were found to have strong significant antiviral activity with a 50% inhibitory concentration (IC50) < 300 μg/ml. The pure compound 18ß-glycyrrhetinic acid from Glycyrrhiza glabra was found to have the strongest antiviral activity (IC50 46 μM), followed by luteolin and vitexin from Aspalathus linearis (IC50 respectively 116 μM and 129 μM) and apigenin-7-O-glucoside from Melissa officinalis (IC50 150 μM). A combination of Glycyrrhiza glabra L. + Nelumbo nucifera Gaertn. and Urtica dioica L. + Nelumbo nucifera Gaertn. showed synergy in their anti-viral activities. Aspalathus linearis (Burm.f.) R.Dahlgren showed no positive effect on the maintenance of the TER.ConclusionsThese results indicate that nutritional intervention with extracts of Nelumbo nucifera Gaertn., Aspalathus linearis (Burm.f.) R.Dahlgren, Urtica dioica L., Glycyrrhiza glabra L. and Olea europaea L. might be useful in the treatment of diarrhea caused by rotavirus infection.

Inhibition of rotavirus infection in cultured cells by N-acetyl-cysteine, PPARγ agonists and NSAIDs

Although the current rotavirus vaccines have shown good tolerance and significant efficacy, it would be useful to develop alternative or complementary strategies aimed at preventing or treating acute diarrhoeal disease caused by this viral agent. A variety of antiviral strategies other than vaccines have been assayed for rotavirus infection management. The recently demonstrated sensitivity of rotavirus infectivity to thiol/disulfide reagents prompted assays for screening drugs that potentially affect cellular redox reactions. MA104 or Caco-2 cells were inoculated with the rotavirus strains RRV, Wa, Wi or M69 and then incubated with different concentrations of drugs belonging to a selected group of 60 drugs that are currently used in humans for purposes other than rotavirus infection treatment. Eighteen of these drugs were able to inhibit rotavirus infectivity to different extents. A more systematic evaluation was performed with drugs that could be used in children such as N-acetylcysteine and ascorbic acid, in addition to ibuprofen, pioglitazone and rosiglitazone, all of which affecting cellular pathways potentially needed by the rotavirus infection process. Evidence is provided here that rotavirus infectivity is significantly inhibited by NAC in different cell-culture systems. These findings suggest that NAC has the potential to be used as a therapeutic tool for treatment and prevention of rotavirus disease in children.

Distribution of rotavirus genotypes after vaccine introduction in the Triângulo Mineiro region of Brazil: 4-Year follow-up study

BackgroundRotaviruses are the major cause of diarrhea in children for which a monovalent G1P[8] vaccine has been provided free for all Brazilian infants since March 2006. ObjectivesTo investigate prevalence and genotypes of rotavirus strains causing diarrhea in children in Triângulo Mineiro, Minas Gerais, during 2007–2010, and to assess local vaccine impact. Study designFecal specimens were analyzed for rotavirus detection and characterization by PAGE, RT-PCR and PCR-genotyping assays. ResultsOverall, rotavirus was diagnosed in 12.1% (76/630) cases, accounting for 35.8% of the hospitalizations and 6.5% of outpatient attendance due to diarrhea. A trend in rotavirus disease reduction occurred in both cities (71.8% and 83.4% in Uberaba; 95.3% in Uberlândia) up to 2009, but it reversed in 2010 with increased rotavirus cases in Uberlândia. Short pattern G2P[4] strains were detected in all but three (96%) cases of mixed/P[NT] infections with long electropherotypes. ConclusionsThis 4-year follow-up study showed a reduction in rotavirus-related diarrhea and even skipped a rotavirus season, which is consistent with vaccine mediated protection. The 2007–2010 rotavirus epidemic curve reflected the natural cyclic fluctuation of the single G2P[4] genotype, with sharp reduction of cases in 2008 leading to lack of a rotavirus 2009 season (both cases and hospitalizations) followed by its come back in 2010. Diarrhea cases related to either vaccine serotype/genotype (G1 or P[8]) were not detected. Thus, a new scenario emerged with a single epidemic genotype replacing the cocirculation of great diversity of genotypes, thus far, a hallmark of the epidemiology of rotavirus in Brazil.

EPIDEMIOLOGICAL, CLINICAL AND LABORATORY FEATURES OF ROTAVIRUS GASTROENTERITIS AMONG HOSPITALIZED CHILDREN LESS THAN FIVE YEARS OLD IN SELECTED HOSPITALS IN JORDAN, 2007-2008

Background: Acute gastroenteritis continues to be a significant cause of morbidity and mortality worldwide. Rotavirus causes more than 130 million episodes of severe diarrhea in children less than five years throughout the world and is considered as main problem in many countries. Few data are available about gastroenteritis attributable to rotavirus in Jordan. Objectives: The primary purpose of this study is to determine epidemiological, clinical and laboratory characteristics of hospitalized cases attributable to rotavirus gastroenteritis in children less than five years old in selected hospitals during the period May 2007-April 2008 to provide Ministry of Health with evidence upon which to base its futuristic decision in regard to development of more suitable preventive measures. This study will improve the existing diarrhea surveillance system in MoH, facilitate and support the decision of introducing rotavirus vaccine in national immunization programme. Methods: Descriptive Cross-sectional study was performed on the hospitalized children less than five years old with acute gastroenteritis in three selected hospitals in three governorates (north, middle and south regions) with population about 45.3% of Jordan population for the period May 2007 to April 2008. Standard case definition was adopted. Analysis was performed using SPSS and Epi Info statistical packages. Results: 377 cases were enrolled with 171 positive for rotavirus. Results showed that Incidence rate of rotavirus disease is 5.2/ 10000 children less than five years old per year; male: female ratio is 1.8:1 with largest proportion of cases among children 6-11 months old. Southern region has the highest incidence rate. Vomiting is an outstanding symptom for rotavirus cases (P< 0.01) in addition to diarrhea and fever which require admission to hospital for fluid replacement. Majority of rotavirus cases were with some dehydration (30%). Mean stay duration is 3 days. Predominant genotypes are G1P8.G2P4 and G9P untypeable. Conclusions: Although mortality of gastroenteritis is no longer a problem in Jordan due to accessibility to health services, morbidity is still high and rotavirus is a relevant cause for gastroenteritis in children less than five years old; which require hospitalization most of the time (45.4% of admitted gastroenteritis).

Fulfilling the promise of rotavirus vaccines: how far have we come since licensure?

Rotavirus is the most common cause of fatal and severe childhood diarrhoea worldwide. Two new rotavirus vaccines have shown efficacy against severe rotavirus disease in large clinical trials. Between 2006 and 2010, 27 countries introduced rotavirus vaccination into national immunisation programmes and, subsequently, the burden of severe rotavirus disease in these countries has decreased substantially in both vaccinated and unvaccinated children. Rotavirus vaccination has led to large, sustained declines in childhood deaths from diarrhoea in Brazil and Mexico, which supports estimates that rotavirus was the leading cause of diarrhoeal deaths in these countries. Studies after licensing have provided new insights into these vaccines, such as the duration of protection, relative effectiveness in poor populations, and strain evolution after vaccine introduction. The challenge for policy makers worldwide is to analyse the effect of vaccination in early adopter countries and to assess whether the benefits outweigh the costs and encourage wider dissemination of these vaccines.

Laboratory-Confirmed Rotavirus Disease in Utah Children: Clinical and Economic Impact of Rotavirus Vaccination

Rotavirus is the most common cause of infectious diarrhea in children worldwide. Recent studies have described changes in the burden of all-cause gastroenteritis; however, there are limited data on the clinical and economic impact of rotavirus vaccine on cases of laboratory-confirmed rotavirus disease. We performed a retrospective study of laboratory-confirmed rotavirus disease from July 2003 through June 2010 at a children's hospital and a community hospital in Utah. Demographics and hospital costs for children <5 years with rotavirus symptoms and a positive rotavirus enzyme immunoassay test on a stool specimen were abstracted from electronic medical records. We compared the prevaccine period (2003-2007) with the postvaccine period (2008-2010). The overall incidence of rotavirus gastroenteritis declined in the postvaccine period, from 26.6 to 5.2 cases per 10 000 person-years for Salt Lake County residents. The largest decrease in the incidence of rotavirus gastroenteritis was among children <12 months (-87%; 95% confidence interval [CI], 79-93). Older children (12-23 months) also experienced significant decreases (-81%; 95% CI, 72-88), as did those 24-59 months (-61%; 95% CI, 51-71). In 2009, 3 years after rotavirus vaccine introduction, there was a 79% decrease in emergency department visits and a 78% decrease in hospitalizations across both hospitals. The cost of emergency department visits and hospitalizations for rotavirus gastroenteritis decreased by 79% and 72%, respectively, resulting in annual savings of $790 000 at a children's hospital and $140 000 at a community hospital. Rotavirus vaccination in infants has dramatically decreased the clinical burden and direct medical costs of rotavirus gastroenteritis in both infants and young children.

Projected health impact and cost-effectiveness of rotavirus vaccination among children

IntroductionTwo rotavirus vaccines have been licensed globally since 2006. In China, only a lamb rotavirus vaccine is licensed and several new rotavirus vaccines are in development. Data regarding the projected health impact and cost-effectiveness of vaccination of children in China against rotavirus will assist policy makers in developing recommendations for vaccination. MethodsUsing a Microsoft Excel model, we compared the national health and economic burden of rotavirus disease in China with and without a vaccination program. Model inputs included 2007 data on burden and cost of rotavirus outcomes (deaths, hospitalizations, outpatient visits), projected vaccine efficacy, coverage, and cost. Cost-effectiveness was measured in US dollars per disability-adjusted life-year (DALY) and US dollars per life saved. ResultsA 2-dose rotavirus vaccination program could annually avert 3013 (62%) deaths, 194,794 (59%) hospitalizations and 1,333,356 (51%) outpatient visits associated with rotavirus disease in China. The medical break-even price of the vaccine is $1.19 per dose. From a societal perspective, a vaccination program would be highly cost-effective in China at the vaccine price of $2.50 to $5 per dose, and be cost-effective at the price of $10 to $20 per dose. ConclusionsA national rotavirus vaccination program could be a cost-effective measure to effectively reduce deaths, hospitalizations, and outpatient visits due to rotavirus disease in China.

Trends of Rotavirus in Nepal

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. To observe the trends of rotavirus strains in children below five years of age, during the years, 2003-2005 in Nepal. 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. 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. 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.

Epidemiology and prospects for prevention of rotavirus disease in India

With rotavirus vaccines now available globally, it will be useful to assemble the available evidence on the epidemiology and burden of rotavirus gastroenteritis in India, in order to weigh the urgency of introducing a vaccine to help control rotavirus disease. We reviewed published studies on rotavirus infection and genotype distribution in India, as well as safety and immunogenicity studies of currently available vaccines. PubMed was searched for papers published after 1990, and several authors who are experts in the field recommended papers of known significance. Rotavirus accounts for close to 40% of hospitalizations for diarrhea in India, with more recent studies showing an increased proportion compared with older studies. There is substantial serotype diversity in India, although there is less intra-country variation than previously thought. Two genotypes, G1P[8] and G2P[4], account for roughly 50% of symptomatic infections in non-neonates. Currently licensed vaccines are safe, and although the efficacy appears lower in developing countries, given the extremely high incidence of diarrhea these could still be cost-effective interventions. The epidemiology and burden of rotavirus diarrhea is fairly well characterized in India. Introducing rotavirus vaccine into the UIP, along with adequate surveillance, should be an important part of efforts to reduce diarrhea mortality, the third leading cause of death among Indian children, and achieve the country's MDG goals.

Rotavirus vaccination and herd immunity: an evidence-based review

Correspondence: Lorna M Seybolt Children’s Hospital, Infectious Diseases, ACC #2316, 200 Henry Clay Avenue, New Orleans, LA 70118, USA Tel +1 504 896 9820 Fax +1 504 894 5137 Email lseybo@lsuhsc.edu Abstract: Until recently, rotavirus was the most common cause of diarrhea in infants and young children with over 100 million cases and 400,000 deaths every year worldwide. Yet, its epidemiology is changing rapidly with the introduction of two rotavirus vaccines in the mid 2000s. Both vaccines were shown to be highly efficacious in prelicensure studies to reduce severe rotavirus disease; the efficacy being more pronounced in highand middle-income countries than in low-income countries. Herd immunity – the indirect protection of unimmunized individuals as a result of others being immunized – was not expected to be a benefit of rotavirus vaccination programs since the vaccines were thought to reduce severe disease but not to decrease virus transmission significantly. Postlicensure studies, however, have suggested that this assumption may need reassessment. Studies in a variety of settings have shown evidence of greater than expected declines in rotavirus disease. While these studies were not designed specifically to detect herd immunity – and few failed to detect this phenomenon – the consistency of the evidence is compelling. These studies are reviewed and described here. While further work is needed, clarifying the presence of herd immunity is not just an academic exercise but an important issue for rotavirus control, especially in lower income countries where the incidence of the disease is highest and the direct protection of the vaccines is lower.