Prediction of promiscuous multiepitope-based peptide vaccine against RdRp of rotavirus using immunoinformatics studies.

Rotavirus, a dsRNA virus in the Reoviridae family, shows a segmented genome. The VP1 gene encodes the RNA-dependent RNA polymerase (RdRp). This study aims to develop a multiepitope-based vaccine targeting RdRp using immunoinformatic approaches. In this study, 100 available nucleotide sequences of VP1-Rotavirus belonging to different strains across the world were retrieved from NCBI database. The selected sequences were aligned, and a global consensus sequence was developed by using CLC work bench. The study involved immunoinformatic approaches and molecular docking studies to reveal the promiscuous epitopes that can be eventually used as active vaccine candidates for Rotavirus. In total, 27 highly immunogenic, antigenic, and non-allergenic T-cell and B-cell epitopes were predicted for the Multiepitope vaccine (MEV) against rotavirus. It was also observed that MEV can prove to be effective worldwide due to its high population coverage, demonstrating the consistency of this vaccine. Moreover, there is a high docking interaction and immunological response with a binding score of -50.2 kcal/mol, suggesting the vaccine's efficacy. Toll-like receptors (TLRs) also suggest that the vaccine is physiologically and immunologically effective. Collectively, our data point to an effective MEV against rotavirus that can effectively reduce viral infections and improve the health status worldwide.

Zero-dose children and the extended immunisation cascade: Understanding the path to full immunisation with six childhood vaccines in 43 countries.

Background: As part of the Immunisation Agenda 2030, the World Health Organization set a goal to reduce the number of children who did not receive any routine vaccine by 50% by 2030. We aimed to describe the patterns of vaccines received for children with zero, one, and up to full vaccination, while considering newly deployed vaccines (pneumococcal conjugate vaccine (PCV) and rotavirus (ROTA) vaccine) alongside longstanding ones such as the Bacille Calmete-Guérin (BCG), diphtheria, tetanus, and pertussis (DPT), and poliomyelitis vaccines, and measles-containing vaccines (MCVs). Methods: We used data from national household surveys (Demographic and Health Surveys and Multiple Indicator Cluster Surveys) carried out in 43 low- and middle-income countries since 2014. We calculated the immunisation cascade as a score ranging from zero to six, considering BCG, polio, DPT, and ROTA vaccines, and the MCV and PCV. We also described the most prevalent combination of vaccines. The analyses were pooled across countries and stratified by household wealth quintiles. Results: In the pooled analyses with all countries combined, 9.0% of children failed to receive any vaccines, 58.6% received at least one dose of each of the six vaccines, and 47.2% were fully vaccinated with all doses. Among the few children receiving 1-5 vaccines, the most frequent were BCG vaccines, polio vaccines, DPT vaccines, PCV, ROTA vaccines, and MCV. Conclusions: Targeting children with their initial vaccine is crucial, as those who receive a first vaccine are more likely to undergo subsequent vaccinations. Finding zero-dose children and starting their immunisation is essential to leaving no one behind during the era of Sustainable Development Goals.

Update on Early-Life T Cells: Impact on Oral Rotavirus Vaccines.

Rotavirus infection continues to be a significant public health problem in developing countries, despite the availability of several vaccines. The efficacy of oral rotavirus vaccines in young children may be affected by significant immunological differences between individuals in early life and adults. Therefore, understanding the dynamics of early-life systemic and mucosal immune responses and the factors that affect them is essential to improve the current rotavirus vaccines and develop the next generation of mucosal vaccines. This review focuses on the advances in T-cell development during early life in mice and humans, discussing how immune homeostasis and response to pathogens is established in this period compared to adults. Finally, the review explores how this knowledge of early-life T-cell immunity could be utilized to enhance current and novel rotavirus vaccines.

Impact of rotavirus vaccination on diarrheal disease burden of children in South America.

INTRODUCTION: Rotavirus is a leading cause of severe diarrheal disease and death in children under five years of age worldwide. Vaccination is one of the most important public health interventions to reduce this significant burden. AREAS COVERED: This literature review examined vaccination coverage, hospitalization rate, mortality, genotypic distribution, immunogenicity, cost-effectiveness, and risk versus benefit of rotavirus vaccination in children in South America. Nine out of twelve countries in South America currently include a rotavirus vaccine in their national immunization program with coverage rates in 2022 above 90%. EXPERT OPINION: Introduction of the rotavirus vaccination has led to a marked reduction in hospitalizations and deaths from diarrheal diseases in children under 5 years, particularly infants under 1 year, in several South American countries. In Brazil, hospitalizations decreased by 59% and deaths by 21% (30-38% in infants). In Peru, hospitalizations in infants fell by 46% and deaths by 37% (56% in infants). Overall, data suggest that rotavirus vaccination has reduced rotavirus deaths by 15-50% in various South American countries. There is some evidence that immunity wanes after the age of 1-year old. Ongoing surveillance of vaccine coverage and changes in morbidity and mortality is important to maximize protection against this disease.

Immunogenicity of RV1 and RV5 vaccines administered in standard and interchangeable mixed schedules: a randomized, double-blind, non-inferiority clinical trial in Mexican infants.

Introduction: Rotavirus-associated diarrheal diseases significantly burden healthcare systems, particularly affecting infants under five years. Both Rotarix™ (RV1) and RotaTeq™ (RV5) vaccines have been effective but have distinct application schedules and limited interchangeability data. This study aims to provide evidence on the immunogenicity, reactogenicity, and safety of mixed RV1-RV5 schedules compared to their standard counterparts. Methods: This randomized, double-blind study evaluated the non-inferiority in terms of immunogenicity of mixed rotavirus vaccine schedules compared to standard RV1 and RV5 schedules in a cohort of 1,498 healthy infants aged 6 to 10 weeks. Participants were randomly assigned to one of seven groups receiving various combinations of RV1, and RV5. Standard RV1 and RV5 schedules served as controls of immunogenicity, reactogenicity, and safety analysis. IgA antibody levels were measured from blood samples collected before the first dose and one month after the third dose. Non-inferiority was concluded if the reduction in seroresponse rate in the mixed schemes, compared to the standard highest responding scheme, did not exceed the non-inferiority margin of -0.10. Reactogenicity traits and adverse events were monitored for 30 days after each vaccination and analyzed on the entire cohort. Results: Out of the initial cohort, 1,365 infants completed the study. Immunogenicity analysis included 1,014 infants, considering IgA antibody titers ≥20 U/mL as seropositive. Mixed vaccine schedules demonstrated non-inferiority to standard schedules, with no significant differences in immunogenic response. Safety profiles were comparable across all groups, with no increased incidence of serious adverse events or intussusception. Conclusion: The study confirms that mixed rotavirus vaccine schedules are non-inferior to standard RV1 and RV5 regimens in terms of immunogenicity and safety. This finding supports the flexibility of rotavirus vaccination strategies, particularly in contexts of vaccine shortage or logistic constraints. These results contribute to the global effort to optimize rotavirus vaccination programs for broader and more effective pediatric coverage.Clinical trial registration: ClinicalTrials.gov, NCT02193061.

Etiologies of Mild and Moderate Diarrheal Illness among Children in Consuelo, Dominican Republic.

Since the rotavirus vaccine was included in the Dominican Republic's national immunization schedule in 2012, the microbiologic etiologies of acute gastroenteritis have not been described. This study aimed to determine the contribution of rotavirus as an etiology of acute gastroenteritis over a 12-month period in children under 5 years of age in both an inpatient and an outpatient setting in Consuelo, Dominican Republic. All children who were seen at Niños Primeros en Salud clinic or admitted to Hospital Municipal Dr. Angel Ponce Pinedo for acute gastroenteritis during January 2021-April 2022 were enrolled in the study. Stools were evaluated for rotavirus, enteric parasites, and pathogenic bacteria. Pathogen detection was compared between outpatients and inpatients and on the basis of child's vaccination status. From 181 children enrolled, 170 stool samples were collected, 28 (16.5%) from inpatients and 142 (83.5%) from outpatients. Rotavirus was the most commonly detected pathogen and was proportionately more common among hospitalized children, with nine (32.1%) cases among hospitalized children and 16 (11.3%) among outpatient children. (Pearson χ2 = 8.1, P = 0.004). Among patients with a positive rotavirus result, vaccination rate was lower among moderate (hospitalized) (three of six; 50%) compared with mild (outpatient) diarrhea patients (12 of 15; 80%). Giardia lamblia (10%) was the next most prevalent pathogen detected in both inpatients and outpatients using standard laboratory measures. Despite the availability of rotavirus vaccination, rotavirus remains a common cause of gastrointestinal illness among children under 5 years of age in our cohort. Incomplete vaccination status was associated with hospitalization for gastrointestinal illness.

Rotavirus del grupo A circulantes en el Gran Buenos Aires durante los períodos pre- y post-vacunales / Vaccines against rotavirus and impact of their introduction in Argentina

[RESUMEN]. Hacia 2022, más de 100 países habían introducido una de las cuatro vacunas autorizadas para uso mundial contra rotavirus, sin embargo, según modelos matemáticos se estima que es poco probable que la reducción en mortalidad con vacunas orales supere el 40%. Esto se debe a que la mayoría de las muertes asociadas a RVA ocurren en países de ingresos bajos y medianos, donde la efectividad de estas vacunas es menor. Este problema de desempeño en medios de bajo nivel socio-económico, se verifica también en menor efectividad sobre morbilidad y duración de la protección. En este trabajo se discuten los posible factores involucrados en este bajo rendimiento relacionados al patógeno, el huésped y factores ambientales. En Argentina, la vacuna monovalente Rotarix® (GSK) ha sido incorporada en el Calendario Nacional en 2015, sin embargo, aún no existen estudios completos de efectividad. Las observaciones iniciales de nuestro grupo registran una disminución en el número de casos de gastroenteritis aguda requi- riendo hospitalización en el Hospital de Niños Ricardo Gutiérrez (HNRG) a partir del 2015. Para los casos con diagnóstico específico de RVA la diferencia fue cada vez más significativa para los años 2016, 2017 y 2018 (p<<0,05). Comparando las medias anuales en los períodos pre y post vacunales se hallan valores de 104,7 para los años 2008-2014 y de 40,2 para los años 2015-2018 (p<0,05) lo que implica una disminución del 61,6%. También se hallaron diferencias a la baja en el número medio de internaciones por GEA por todas las causas del 19,6%.

[ABSTRACT]. By 2022, more than 100 countries had introduced one of the four vaccines authorized for global use against rotavirus; however, according to mathematical models, it is estimated that the reduction in mortality with oral vaccines is unlikely to exceed 40%. This is because the majority of RVA-associated deaths occur in low- and middle-income countries, where the effectiveness of these vaccines is lower. This performance problem in low socioeconomic environments is also verified in lower effectiveness on morbidity and duration of protection. In this work, the possible factors involved in this low performance related to the pathogen, the host and environmental factors are discussed. In Argentina, the monovalent Rotarix® (GSK) vaccine has been incorporated into the National Schedule in 2015, however, there are still no complete effectiveness studies. The initial observations of our group record a decrease in the number of cases of acute gastroenteritis requiring hospitalization at the Ricardo Gutiérrez Children's Hospital (HNRG) starting in 2015. For cases with a specific diagnosis of RVA, the difference was increasingly significant for the years 2016, 2017 and 2018 (p<<0.05). Comparing the annual averages in the pre- and post-vac- cine periods, values of 104.7 are found for the years 2008-2014 and 40.2 for the years 2015-2018 (p<0.05), which implies a decrease of 61. 6%. Downward differences were also found in the average number of hospitalizations for AGE due to all causes of 19.6%.

Molecular characterization of human adenovirus causing infantile acute gastroenteritis in Venezuela before and after rotavirus vaccine implementation.

Human adenoviruses (HAdV) of species F are commonly involved in pediatric acute gastroenteritis (AGE). The real impact on Venezuelan health is unknown. To investigate the prevalence and molecular diversity of HAdV in Venezuela, 630 fecal samples collected from children with AGE in 3 cities, from 2001 to 2013, were tested by PCR. Species F and types F40/41 were identified by REA. HAdV was detected in 123 cases (19.5%), most from outpatient females under 24 months old. A progressive and substantial increase in the detection rate was observed over time, significantly higher in rotavirus vaccinated than unvaccinated children (28.4% vs. 9.5%, P = 0.00019). Phylogenetic analysis of 28 randomly selected genomes showed high similarity among HAdV-F40/41 and those worldwide. HAdV-F of type 41 prevailed (79.8%) and clustered into 2 intratypic major clades. The significant involvement of HAdV-F41 in AGE suggests the importance of actively monitoring viral agents other than rotavirus, especially after vaccine introduction.

Cost-effectiveness analysis measuring the total costs against the health benefits of three different rotavirus vaccines for Mexico.

Rotavirus (RV) infection causes acute rotavirus gastroenteritis (RVGE) in infants. Safe and effective RV vaccines are available, of which Mexico has included one in its national immunization program (NIP) since 2007. Health outcome gains, expressed in quality-adjusted life years (QALYs), and cost improvements are important additional factors for the selection of a NIP vaccine. These two factors were analyzed here for Mexico over one year implementing three RV vaccines: 2-dose Rotarix (HRV), versus 3-dose RotaTeq (HBRV), and 3-dose Rotasiil (BRV-PV), presented in a 1-dose or 2-dose vial). HRV would annually result in discounted QALY gains of 263 extra years compared with the other vaccines by averting an extra 24,022 homecare cases, 10,779 medical visits, 392 hospitalizations, and 12 deaths. From a payer's perspective and compared with HRV, BRV-PV 2-dose vial and BRV-PV 1-dose vial would annually result in $13,548,179 and $4,633,957 net savings, respectively, while HBRV would result in $3,403,309 extra costs. The societal perspective may also show savings compared with HRV for BRV-PV 2-dose vial of $4,875,860, while BRV-PV 1-dose vial and HBRV may show extra costs of $4,038,363 and $12,075,629 respectively. HRV and HBRV were both approved in Mexico, with HRV requiring less investment than HBRV with higher QALY gains and cost savings. The HRV vaccine produced those higher health gains due to its earlier protection and greater coverage achieved after its schedule completion with two doses only, providing full protection at four months of age instead of longer periods for the other vaccines.

Rotavirus (RV) infection causes acute diarrhea in infants and can be life-threatening. Several safe and effective vaccines against RV and its complications exist. For many governments choosing vaccines for national immunization programs, total costs or savings and health gains are important factors in the selection process. We compared the costs and health benefits of three RV vaccines for Mexico: HRV, HBRV, and BRV-PV, that have different dosing schedules: two doses for HRV and three doses for HBRV and BRV-PV. HRV is currently part of the national immunization program in Mexico. HRV would result in more health benefits as it incurs fewer RV-related cases, medical visits, hospitalizations, and infant deaths than the other vaccines due to its early protection achieved after only two doses to complete its schedule. However, from a payer's perspective, the least expensive vaccine was BRV-PV, while HRV was less expensive than HBRV. From a societal perspective, also accounting for families' costs and loss in income due to an infant's RV disease, and the families' costs and loss in income when accompanying the infant to the vaccination center, the HRV vaccine was less expensive than HBRV and BRV-PV presented in a 1-dose vial, while more expensive than BRV-PV presented in a 2-dose vial. HRV and HBRV are both approved in Mexico, although HBRV requires a greater investment at lower health benefits than HRV, from both a payer's and a societal perspective. A 2-dose vaccination scheme is an important asset for the economic value of this vaccination program.

A Comparison of Pathogen Detection and Risk Factors among Symptomatic Children with Gastroenteritis Compared with Asymptomatic Children in the Post-rotavirus Vaccine Era.

OBJECTIVE: To describe demographics, pathogen distribution/seasonality, and risk factors in children seeking care for acute gastroenteritis (AGE) at a midwestern US emergency department during 5 postrotavirus vaccine years (2011-2016), and further, to compare the same data with matched healthy controls (HC). STUDY DESIGN: AGE and HC participants <11 years old enrolled in the New Vaccine Surveillance Network study between December 2011 to June 2016 were included. AGE was defined as ≥3 diarrhea episodes or ≥1 vomiting episode. Each HC's age was similar to an AGE participant's age. Pathogens were analyzed for seasonality effects. Participant risk factors for AGE illness and pathogen detections were compared between HC and a matched subset of AGE cases. RESULTS: One or more organisms was detected in 1159 of 2503 children (46.3%) with AGE compared with 99 of 537 HC (17.3%). Norovirus was detected most frequently among AGE (n = 568 [22.7%]) and second-most frequently in HC (n = 39 [6.8%]). Rotavirus was the second most frequently detected pathogen among AGE (n = 196 [7.8%]). Children with AGE were significantly more likely to have reported a sick contact compared with HC, both outside the home (15.6% vs 1.4%; P < .001) and inside the home (18.6% vs 2.1%; P < .001). Daycare attendance was higher among children with AGE (41.4%) compared with HC (29.5%; P < .001). The Clostridium difficile detection rate was slightly higher among HC (7.0%) than AGE (5.3%). CONCLUSIONS: Norovirus was the most prevalent pathogen among children with AGE. Norovirus was detected in some HC, suggesting potential asymptomatic shedding among HC. The proportion of AGE participants with a sick contact was approximately 10 times greater than that of HC.

Nonsecretor Phenotype Is Associated With Less Risk of Rotavirus-Associated Acute Gastroenteritis in a Vaccinated Nicaraguan Birth Cohort.

BACKGROUND: Histo-blood group antigens (HBGAs) have been associated with rotavirus vaccine take; but the effect of these HBGAs on rotavirus incidence and risk remains poorly explored in vaccinated populations. METHODS: Rotavirus-associated acute gastroenteritis (AGE) was assessed in 444 Nicaraguan children followed from birth until 3 years of age. AGE episodes were tested for rotavirus by reverse-transcription quantitative polymerase chain reaction, and saliva or blood was used to determine HBGA phenotypes. Cox proportional hazards models were used to estimate the relative hazard of rotavirus AGE by HBGA phenotypes. RESULTS: Rotavirus was detected in 109 (7%) stool samples from 1689 AGE episodes over 36 months of observation between June 2017 and July 2021. Forty-six samples were successfully genotyped. Of these, 15 (35%) were rotavirus vaccine strain G1P[8], followed by G8P[8] or G8P[nt] (11 [24%]) and equine-like G3P[8] (11 [24%]). The overall incidence of rotavirus-associated AGE was 9.2 per 100 child-years, and was significantly higher in secretor than nonsecretor children (9.8 vs 3.5/100 child-years, P = .002). CONCLUSIONS: The nonsecretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure in a vaccinated Nicaraguan birth cohort. These results show the importance of secretor status on rotavirus risk, even in vaccinated children.

Effectiveness of Pentavalent Rotavirus Vaccine in Shanghai, China: A Test-Negative Design Study.

OBJECTIVE: To evaluate vaccine effectiveness (VE) of a live oral pentavalent rotavirus vaccine (RotaTeq, RV5) among young children in Shanghai, China, via a test-negative design study. STUDY DESIGN: We consecutively recruited children visiting a tertiary children's hospital for acute diarrhea from November 2021 to February 2022. Information on clinical data and rotavirus vaccination was collected. Fresh fecal samples were obtained for rotavirus detection and genotyping. To evaluate VE of RV5 against rotavirus gastroenteritis among young children, unconditional logistic regression models were conducted to compare ORs for vaccination between rotavirus-positive cases and test-negative controls. RESULTS: A total of 390 eligible children with acute diarrhea were enrolled, including 45 (11.54%) rotavirus-positive cases and 345 (88.46%) test-negative controls. After excluding 4 cases (8.89%) and 55 controls (15.94%) who had received the Lanzhou lamb rotavirus vaccine, 41 cases (12.39%) and 290 controls (87.61%) were included for the evaluation of RV5 VE. After adjustment for potential confounders, the 3-dose RV5 vaccination showed 85% (95% CI, 50%-95%) VE against mild to moderate rotavirus gastroenteritis among children aged 14 weeks to ≤4 years and 97% (95% CI, 83%-100%) VE among children aged 14 weeks to ≤2 years with genotypes G8P8, G9P8, and G2P4 represented 78.95%, 18.42%, and 2.63% of circulation strains, respectively. CONCLUSIONS: A 3-dose vaccination of RV5 is highly protective against rotavirus gastroenteritis among young children in Shanghai. The G8P8 genotype prevailled in Shanghai after RV5 introduction.

Circulation of Vaccine-derived Rotavirus G1P[8] in a Vulnerable Child Cohort in Rio de Janeiro.

BACKGROUND: The expansion of rotavirus (RV) immunization in several countries reduced the burden of acute diarrheal disease (ADD) and diarrhea-associated mortality. Although community transmission of live attenuated monovalent rotavirus vaccine (G1P[8] RV1) virus has been demonstrated in children and household contacts, fecal shedding of these strains in neonates and infants under six weeks of age has never been demonstrated. The objective of the study was to assess ADD and rotavirus vaccine strain shedding before and after immunization through 24 months of age. METHODS: This was a prospective cohort study in a low-resource community in which stool samples were collected from neonates from 15 to 45 days of age every 2 weeks, after both doses of G1P[8] RV1, and in subsequent ADD episodes until 2 years of age. RV was detected and genotyped in stool samples by RT-PCR. RESULTS: We enrolled 242 participants who were followed for an average of 23 months. The specific prevalence of G1P[8] RV1 virus was 3.3% in neonates and infants less than six weeks of age, 50% after the first dose, and 25.6% after the second dose. Among the 70 participants with ADD, G1P[8] RV1 virus was identified in only one participant (1.4% prevalence). CONCLUSIONS: In vaccinated children, there were no breakthrough infections with G1P[8] RV1 and ADD was rare supporting high vaccine effectiveness. We observed G1P[8] RV1 virus shedding among neonates and infants before the first vaccine dose, providing evidence of transmission of the vaccine strain from immunized children to those who are not yet vaccinated.

Change in Rotavirus Vaccine Coverage in Brazil from before (2015-2019) through the COVID-19 Pandemic Period (2020-2021).

During the COVID-19 pandemic, a reduction in vaccination coverage of children and adolescents was observed in several countries. The aim of this study was to assess the impact of the pandemic, in the first two years, on human rotavirus vaccine (HRV) coverage in Brazil compared with previous years. The number of doses of HRV administered in the period from January 2015 to December 2021 and its annual vaccination coverage were analyzed. The vaccination coverage decreased to 77.3% in 2020 and to 70.4% in 2021, substantially lower than the minimum that would be expected (89.2%); the decline was more pronounced in the second year of the pandemic despite the fact that in this period, the circulation restrictions were already less tight. Of the five Brazilian macro-regions, the northeast had the largest decline, and the south had the smallest impact on coverage. At the municipal level, less than half of the Brazilian municipalities managed to achieve vaccination coverage above 90% in either pandemic year. Although there was already a downward trend in coverage in the pre-pandemic years, the present study shows that the values recorded in 2020 and 2021 were significantly lower. Monitoring of vaccination coverage in the coming years should be carried out continuously in order to avoid a possible resurgence of rotavirus-induced diarrhea.

Genomic constellations of RVA detected in Brazil from 1986 to 2016: a temporal and geographical distribution and occurrence of reassortments / Constelações genômicas de RVA detectadas no Brasil de 1986 a 2016: uma distribuição temporal e geográfica e ocorrência de rearranjos

INTRODUCTION: Species A rotavirus (RVA) infections are a major cause of severe gastroenteritis in children of <5 years worldwide. In Brazil, before vaccination, RVA was associated with 3.5 million episodes of acute diarrheal disease per year. Due to the segmented nature of their genomes, rotaviruses can exchange genes during co-infections, and generate new virus strains and new reinfections. OBJECTIVE: To evaluate the genomic diversity of RVA isolated in Brazil in 30 years, between 1986 to 2016, to investigate possible changes in the frequency of genotype constellations before and after the implementation of the vaccine. METHODS: In total, 4,474 nucleotide sequences were obtained from the Virus Variation Database. Genomic constellation was compared, and the proportion of rotavirus genotypes was analyzed by time and geographic region. RESULTS: Our results showed that major known genotypes were circulating in the country during the period under analysis, with a prevalence of the G1P[8] Wa-like genotype, decreasing only in the period immediately after the introduction of the vaccine. Regarding the geographical distribution, most of our constellations, 62 (39.2%), and 50 (31.6%) were concentrated in the North and Northeast regions. Our analysis also showed the circulation of multiple strains during the periods when the DS-1-like and AU-1-like genotypes were co-circulating with the Wa-like genotype. CONCLUSION: Therefore, it is likely that inter-genogroup reassortments are still occurring in Brazil and so it is important to establish an efficient surveillance system to follow the emergence of novel reassorted strains that might not be targeted by the vaccine.

INTRODUÇÃO: As infecções por rotavírus A (RVA) são uma das principais causas de gastroenterite grave em crianças <5 anos em todo o mundo. No Brasil, antes da vacinação, o RVA estava associado a 3,5 milhões de episódios de diarreia aguda por ano. Devido à natureza segmentada de seus genomas, os rotavírus podem trocar genes durante as coinfecções, gerar novas cepas de vírus e novas reinfecções. OBJETIVO: Avaliar a diversidade genômica de RVA isolados no Brasil entre 1986 a 2016 para investigar possíveis alterações na frequência das constelações de genótipos antes e após a implantação da vacina. MÉTODOS: No total, 4.474 sequências de nucleotídeos foram obtidas do Banco de Dados de Variação de Vírus. A constelação genômica foi comparada e a proporção dos genótipos de rotavírus foi analisada por tempo e região geográfica. RESULTADOS: Nossos resultados mostraram que os principais genótipos conhecidos circulavam no país no período em análise, com prevalência do genótipo G1P[8] Wa-like, diminuindo apenas no período imediatamente após a introdução da vacina. Em relação à distribuição geográfica, a maioria das nossas constelações, 62 (39,2%) e 50 (31,6%), concentrava-se nas regiões Norte e Nordeste. Nossa análise também mostrou a circulação de cepas múltiplas durante os períodos em que os genótipos DS-1-like e AU-1-like estavam co-circulando com o genótipo Wa-like. CONCLUSÃO: Portanto, é provável que rearranjos inter-genogrupos ainda estejam ocorrendo no Brasil e por isso é importante estabelecer um sistema de vigilância eficiente para acompanhar o surgimento de novas cepas rearranjadas que podem não ser protegidas pela vacina.

Vaccination strategies for people living with inborn errors of metabolism in Brazil.

OBJECTIVE: Through a literature review, make recommendations regarding immunizations in people living with Inborn Error of Metabolism (IEM) in Brazil, assess the possible impact on metabolic decompensations after immunization, and if this specific population may have an impaired immune response to vaccines. SOURCE OF DATA: The MeSH Terms vaccination OR vaccine OR immunization associated with the term inborn error of metabolism AND recommendation were used in combination with search databases. Only articles published after 1990, in the languages English, Spanish, French or Portuguese, human-related were included. SYNTHESIS OF DATA: A total of 44 articles were included to make the following recommendations. Individuals with IEMs need to be up to date with their immunizations. Regarding which vaccines should be offered, children and adults should follow the routine immunization schedules locally available, including the COVID-19 vaccines. The only exception is the rotavirus vaccine for hereditary fructose intolerance. The benefit of immunization outweighs the very low risk of metabolic decompensation. Since not all patients will have an adequate immune response, measuring antibody conversion and titers is recommended CONCLUSIONS: All patients should receive age-appropriate immunizations in their respective schedules without delays. The only situation when vaccination may be contraindicated is with oral rotavirus vaccine in hereditary fructose intolerance. Monitoring the levels of antibodies should be done to detect any immune dysfunction or the necessity for boosters. A personalized immunization schedule is ideal for patients with IEMs. The reference organizations could improve their recommendations to address all IEMs, not only some of them.

The COVID-19 pandemic and vaccination abandonment in children: spatial heterogeneity maps.

OBJECTIVE: to identify spatial clusters corresponding to abandonment of routine vaccines in children. METHOD: an ecological study, according to data from the 853 municipalities of a Brazilian state. The records analyzed were those of the multidose pentavalent, pneumococcal 10-valent, inactivated poliomyelitis and oral human rotavirus vaccines of 781,489 children aged less than one year old. The spatial scan statistics was used to identify spatial clusters and assess the relative risk based on the vaccination abandonment indicator. RESULTS: the spatial scan statistics detected the presence of statistically significant clusters for abandonment regarding the four vaccines in all the years analyzed. However, the highest number of clusters with high relative risk estimates was identified in 2020. The Vale do Aço and West, North and West, and Southwest regions stand out for the pentavalent, poliomyelitis and rotavirus vaccines, respectively. CONCLUSION: in an attempt to mitigate the devastating impact of the COVID-19 pandemic, the immunization program experienced setbacks. The presence of clusters points to the need to implement integrated strategies that may involve different sectors for an active search for children and prevent outbreaks of vaccine-preventable diseases in the near future.

Impact of polio vaccines (oral polio vaccine - OPV or inactivated polio vaccine - IPV) on rotavirus vaccine-associated intussusception.

Although safe, rotavirus vaccines have been associated with increased intussusception risk. In Brazil, after the oral human rotavirus vaccine (OHRV) introduction in the childhood immunization, in 2006, increased intussusception risk was identified after the second OHRV dose, whereas in other countries, higher risk was associated to the first vaccine dose. It was hypothesized that the concomitant use of oral poliovirus vaccine (OPV) in Brazil might explain this difference. In 2012, the inactivated polio vaccine (IPV) was adopted in the first two doses of Brazilian childhood immunization schedule, creating an opportunity to study the subject. Our objective was analyzing the impact of polio vaccines on rotavirus-associated intussusception. We used surveillance data on intussusception in infants living in São Paulo State. Two periods were considered: an OPV-period (March 2006 to June 2012) and an IPV-period (October 2012 to December 2017). The period from June to September 2012 were considered as transition. Self-controlled case series analysis with event-dependent exposure was performed, considering two risk periods (7 and 21 days post-vaccination). We identified 325 intussusception cases in infants reported to the surveillance systems during the study period. The statistical analysis included 221 cases that occurred within 60 days after vaccination. Overall, a higher intussusception risk was observed in the first week after vaccination for both the first (Relative Incidence [RI] = 4.3, 95%CI 2.8-6.5, p < .001) and second vaccine doses (RI = 4.2, 95%CI 2.7-6.4; p < .001). There were no statistically significant differences in intussusception risk according to the rotavirus vaccine dose and the polio vaccine (OPV or IPV) administered concomitantly.