Orientador: Maria da Gloria Buzinaro / Coorientador: Samir Issa Samara / Banca: Raul José Silva Gírio / Banca: Luís Guilherme de Oliveira / Resumo: Rotavírus é uma importante causa de diarreia neonatal em humanos e em várias espécies animais, incluindo bezerros. O presente estudo teve como objetivo verificar a ocorrência de rotavírus em bezerros de rebanhos leiteiros e de corte, durante o período de março de 2010 a agosto de 2011, em propriedades rurais situadas nos Estados de São Paulo, Minas Gerais, Goiás e Mato Grosso do Sul. Foram analisadas 765 amostras de fezes de bezerros, na faixa etária entre um e 60 dias, de 56 rebanhos bovinos, sendo 53 de exploração leiteira e três de gado de corte. Pela técnica da eletroforese em gel de poliacrilamida (EGPA), observou-se a ocorrência de rotavírus em 17,8% (10/56) dos rebanhos e em 3,0% (23/765) dos animais. A proporção de rebanhos leiteiros infectados foi de 16,9% (9/53), e no gado de corte o percentual de positividade foi de 33,3% (1/3). A maior ocorrência significativa de amostras positivas foi observada em animais na faixa etária de um a 15 dias, quando comparadas com as demais (p<0,01). Foram diagnosticados bezerros infectados por rotavírus tanto em animais com sinais clínicos de diarreia (9,3%: 16/171) quanto naqueles clinicamente normais (1,1%: 7/594), existindo porém uma correlação positiva entre a presença da infecção e a manifestação clínica da diarreia (p < 0,01). Ao analisar o perfil do RNA extraído das 23 amostras positivas pelo EGPA foi possível classificá-lo em 4 eletroferotipos distintos, indicando grande diversidade genômica na região estudada. Os resultados indicaram a participação do agente na etiologia da diarreia dos bezerros. A genotipagem G e P das amostras positivas foi realizada pela técnica de RT-PCR e demonstrou que separadamente as associações de genotipos circulantes... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Rotavirus is an important cause of neonatal diarrhea in humans and several animal species, including calves. The present study aimed at verifying rotavirus occurrence in calves belonging to dairy and beef cattle herds during the period from March 2010 and August 2011, in farms located in the states of São Paulo, Minas Gerais, Goiás and Mato Grosso do Sul. It was analyzed 765 fecal samples of calves, from 1 to 60 days of age, belonging to 56 cattle herds (from which 53 were dairy and 3 were beef cattle). By the technique of electrophoresis with polyacrylamide gel (PAGE), the occurrence of rotavirus was observed in 17.8% (10 / 56) of herds and 3.0% (23/765) of the animals. The proportion of infected dairy cattle was 16.9% (9/53), and the percentage of positivity in beef cattle was 33.3% (1 / 3). The highest incidence of positive samples was observed in animals aged 1-15 days, compared to the others (p <0.01). Calves infected by rotavirus were diagnosed not only in animals with clinical signals of diarrhea (9.3%: 16/171) but also in the clinically normal ones (1.1%: 7/594), although there is a correlation between the presence of infection and the clinical manifestation of diarrhea (p < 0. 01). By analyzing the profile of RNA extracted from 23 positive samples by EGPA it was possible classify it in four distinct electropherotypes, indicating a large genomic diversity in the analyzed region. The results indicate the agent's participation in the etiology of diarrhea in calves. The polymerase chain reaction (PCR) preceded by reverse-transcription (RT) of viral RNA was employed to characterize the bovine rotavirus genotypes G and P, which indicated that the associations of genotypes circulating in herds in Brazil's southeastern region were... (Complete abstract click electronic access below) / Mestre

Rotavirus diarrhea causes a disproportionate amount of the world's childhood mortality. Approximately 611,000 children die each year due to complications of rotavirus infections. In this study we evaluate rotavirus vaccination using four different methods. We look at the epidemiological history of the disease and vaccination against the disease, then we evaluate the effectiveness of vaccination first using a cost-benefit analysis, then using an ordinary differential equations based model, and last through computer simulations in Matlab. We do a traditional cost-benefit analysis as suggested by the Public Health Service of the United States to evaluate the costs and benefits of implementing a rotavirus vaccination program in Egypt with the RotaRix vaccine. Our results show that given the current standards of care in Egypt, it would be more cost-beneficial for Egypt not to use the rotavirus vaccine. We formulate a model of the spread of rotavirus diarrhea based on a continuous time ordinary differential equations model of two viral strains of influenza. We expand this influenza model to include the case of co-infection. We further expand the original model to explore the effects of vaccination. We used computer simulations to further analyze the effect of vaccination as a control method. These simulations show that the spread of the disease is highly sensitive to the levels of cross-immunity between the strains, and the level of vaccination in the population. We found that the dynamics observed in the new model are similar to the dynamics observed in the original model. We found the minimum levels of vaccination necessary in this model to eradicate severe rotavirus disease and minimum levels of cross-immunity between the strains

Background: Gastroenteritis by rotavirus is responsible for approximately 810 annual deaths/year in children under 5 years in Peru and emerging rotavirus genotypes have led to concerns regarding cross-protection by the vaccines available. Moreover, there are no reports on the molecular-epidemiology of rotavirus diarrhea in Peru Methodology: A total of 131 stool samples were obtained from children under 5 years old hospitalized from January 2010 to December 2012 in the Hospital Regional de Cajamarca, Peru. ELISA and RT-PCR techniques were performed for rotavirus detection. G and P typing of rotavirus-positive samples were obtained by semi-nested multiplex RT-PCR and sequencing was performed to confirm the PCR results. Results: Of the 117 samples available, 18.80% (22/117) tested positive for rotavirus by ELISA and 35.90% (42/117) by RT-PCR. Among the G-genotype identified, G9 in 35.71% (15/42) and G12 in 33.33% (14/42) were the most prevalent. With the most common combination being G12/P6 in 23.81% (10/42). Conclusions: A high prevalence of the G12/P6 genotype was detected. It is know that this genotype is not covered by the current vaccines available. More in depth studies are needed to know the current rotavirus genotypes presents in Peru. / Tesis

Hajj is the annual gathering of Islam practitioners in Mecca, Saudi Arabia. During the event, gastrointestinal infections are usually experienced and outbreaks have always been a concern; nevertheless, a deep and integrative study of the etiological agents has never been carried out. Here, I describe for the first time the epidemiology of pathogenic enteric viruses during Hajj 2011, 2012 and 2013. The focus of this study was the common enteric viruses Astrovirus, Norovirus, Rotavirus and Adenovirus. An enzyme Immunoassay established their presence in 14.9%, 15.0% and 6.6% of the reported cases of acute diarrhea for 2011, 2012 and 2013, respectively. For the three years of study, Astrovirus accounted for the majority of the viral infections. To our knowledge, this is the first time an epidemiological study depicts Astrovirus as the main viral agent of gastroenteritis in a mass gathering event. Hajj is rich in strains of Astrovirus, Norovirus and Rotavirus. A first screening by RT-PCR resulted in ten different genotypes. Strains HAstV 2, HAstV 1 and HAstV 5 were identified for Astrovirus. GI.6, GII.3, GII.4 and GII.1 were described for Norovirus and G1P[8], G4P[8] and G3P[8] were found for Rotavirus. The majority of the Astrovirus isolates could not be genotyped suggesting the presence of a new variant(s). Cases like this encourage the use of metagenomics (and nextgeneration sequencing) as a state-of-the-art technology in clinical diagnosis. A sample containing Adenovirus particles is being used to standardize a process for detection directly from stool samples and results will be obtained in the near future. The overall findings of the present study support the concept of Hajj as a unique mass gathering event that potentiates the transmission of infectious diseases. The finding of Norovirus GII.4 Sydney, a variant originated from Australia, suggests that Hajj is a receptor of infectious diseases worldwide. This work is part of the Hajj project, a collaborative effort with the Ministry of Health of the Kingdom of Saudi Arabia in order to describe entirely the epidemiology of gastrointestinal diseases in Hajj. It is expected that the results of this study will serve in the refinement of public health policies.

No description available.

Rotavirus (RV) is a viral pathogen that causes severe, watery diarrhea and vomiting in the young of humans and other animals. RV infections result in over 200,000 pediatric deaths around the world each year, especially in developing nations. Within the infected host cell, RV forms inclusion bodies, called viroplasms, where many stages of viral replication occur. The RV polymerase, known as VP1, must localize to viroplasms during infection where it replicates the virus' RNA genome. The work described in this dissertation focused on identifying region(s) of VP1 essential for its viroplasmic localization and its function as a polymerase. We found that a single amino acid change in a region of the polymerase called the N-terminal domain negatively impacted its capacity to localize to viroplasms during infection as well as its enzymatic activity in a test tube. Follow up studies using VP1 proteins from divergent strains and a mutant containing only the N-terminal domain of VP1 provided more insight into polymerase localization determinants. In total, our work suggests that the VP1 N-terminal domain plays an important role in localizing the polymerase to viroplasms via interactions with other viral proteins and supporting its function as a polymerase. / Ph. D. / Rotavirus (RV) is a viral pathogen that causes severe, watery diarrhea and vomiting in the young of humans and other animals. RV infections result in over 200,000 pediatric deaths around the world each year, especially in developing nations. Within the infected host cell, RV forms inclusion bodies, called viroplasms, where many stages of viral replication occur. The RV polymerase, known as VP1, must localize to viroplasms during infection where it replicates the virus’ RNA genome. The work described in this dissertation focused on identifying region(s) of VP1 essential for its viroplasmic localization and its function as a polymerase. We found that a single amino acid change in a region of the polymerase called the N-terminal domain negatively impacted its capacity to localize to viroplasms during infection as well as its enzymatic activity in a test tube. Follow up studies using VP1 proteins from divergent strains and a mutant containing only the N-terminal domain of VP1 provided more insight into polymerase localization determinants. In total, our work suggests that the VP1 N-terminal domain plays an important role in localizing the polymerase to viroplasms via interactions with other viral proteins and supporting its function as a polymerase.

Clostridioides difficile (C. difficile) and human rotavirus (HRV) are leading causes of bacterial and viral gastroenteritis worldwide. Treatment and vaccination options for both pathogens have significant limitations. C. difficile infections are treated with antibiotics, which is paradoxical as C. difficile itself is associated with antibiotic usage. In the United States, two live oral attenuated vaccines (Rotarix and RotaTeq) are licensed for protection against HRV. Since receiving approval from the World Health Organization (WHO), Rotarix and RotaTeq have been widely implemented into global national childhood immunization schedules, with one report finding 59 countries using Rotarix and 25 using RotaTeq. However, these vaccines have much lower efficacy rates in low- and middle-income countries. Because of these caveats, there is an urgent need to generate novel prophylaxes and treatments for C. difficile and HRV. In order to address this need, animal models that replicate the nuances of each infection are imperative. We have developed gnotobiotic (Gn) pig models for each pathogen. Gn pigs infected with spores of the hypervirulent UK1 strain of C. difficile develop classical signs of infection, including watery diarrhea and weight loss. Gross necropsy reveals colonic distention and discoloration, and histopathological evaluation shows volcano lesions, pseudo membrane formation, and epithelial cell erosion. Gn pigs infected with a G4P[6] strain of HRV also display pathogen specific signs of infection, including diarrhea, fecal rotavirus shedding, and damaged intestinal villi. A dose response study of the G4P[6] strain revealed diarrhea and virus shedding occurred at all tested doses, however the most severe diarrhea and virus shedding, measured by cumulative diarrhea score, area under the curve (AUC) of diarrhea, peak virus titer, and AUC of virus shedding, were all detected in the highest dose group. Based on the presentation of clinical signs of infection, 105 fluorescent focus units was selected as the optimal challenge dose for future studies. These models enable us to test candidate therapeutics, but also elucidate unique replicative features of the pathogens. For example, we found that HRV can replicate in the salivary glands and nasal cavity of Gn pigs in addition to the small intestine. HRV infection primed immune responses in the ileum, tonsils, and facial lymph nodes; infection also induced high levels of systemic and mucosal rotavirus specific antibody responses. Moving forward, we hope to expand upon this replication study to identify what cell types within the glands are infected as well as look at local cellular immune responses to HRV infection. Additional future directions include determining the protective efficacy of next generation HRV vaccines and evaluating effectiveness of an engineered probiotic yeast in reducing severity of C. difficile infection and disease. The Gn pig models of C. difficile and G4P[6] HRV are clinically relevant, and they will continue to serve as useful tools to better our understanding of pathogenesis, infection, and prevention of these pathogens. / Doctor of Philosophy / Clostridioides difficile (C. difficile) and human rotavirus (HRV) both cause gastrointestinal related symptoms when they infect humans. Treatments available for C. difficile and HRV all have significant drawbacks. This represents a gap in knowledge which we aimed to fill by developing germ-free (gnotobiotic [Gn]) pig models of C. difficile and HRV infection and disease. Animal models that mimic the outcomes of disease seen in humans are essential for evaluating protectiveness of new therapeutics. The more similar the disease presentation, the more likely the treatment results will be translational to humans. We began with C. difficile; pigs were orally fed C. difficile and monitored for a week post infection for development of signs of infection. Inoculated pigs lost weight and developed diarrhea. Bacterial cells and toxins were isolated from fecal samples collected on various days post infection. Multiple changes were observed in infected pigs’ large intestinal tissues, including severe bleeding, tissue distension, and fluid buildup. Infected pigs also had significant upregulation of pro-inflammatory cytokines, indicating activation of the immune response. We performed a similar procedure for the establishment of the HRV model. Gn pigs were orally challenged with differing doses of G4P[6] HRV and followed for several days post infection. Consistent with HRV infection in children, the pigs developed watery diarrhea that lasted for multiple days. Small intestinal tissues collected at necropsy had several signs of damage, including blunted villi, fluid buildup, and immune cell invasion. These lesions were also consistent with HRV infection in humans. Taken all together, these results indicated successful establishment of both C. difficile and HRV models. While the primary goal of generating these models was to evaluate new treatments, a secondary goal was to use them to better our understanding of pathogen replication dynamics. For example, the small intestine was thought to be the primary site of HRV infection. Using a pig model of HRV, we expanded on this knowledge to show that HRV can replicate in the nose and salivary glands as well. Additionally, we found HRV infection to induce immune responses near the sites of infection, including the intestine, the tonsils, and the facial lymph nodes. Overall, these studies demonstrate the utility of germ-free pig models and are an important first step in generating more effective treatments for bacterial and viral infections.

No presente estudo foi analisado o perfil eletroforético de 15 amostras de rotavírus, sendo 11 de bezerros, 02 de leitões e 02 de criança, que foram cultivadas até a sexta passagem em células da linhagem MA104, com o monitoramento realizado pela técnica de eletroforese em gel de poliacrilamida (PAGE). O objetivo foi comparar o perfil eletroforético de amostras fecais e após o isolamento As amostras leitões não revelaram mudanças de migração aparente, mas uma amostra apresentou um segmento adicional entre os segmentos 5 e 6, tanto no material anterior ao cultivo, quanto na amostra isolada. Em relação as amostras de crianças, uma apresentou diferença na velocidade de migração eletroforética. Além disso, uma amostra de bezerro apresentou um segmento adicional entre os segmentos 5 e 6. Estes dados ressaltam a importância da PAGE como uma técnica de triagem de amostras, que podem, posteriormente serem analisadas por técnicas moleculares mais especificas. As mudanças de comportamento na migração eletroforética dos segmentos genômicos do RNA viral podem ser sugestivas de alteração nas propriedades antigênicas, além do fato de que mudanças que ocorreram in vitro poderão, também, ocorrer in vivo. / In the present work, we have analyzed the electrophoretic profile of 15 samples of rotavírus, 11 of calves, 02 of pigs and 02 of children, that have been cultivated on MA,104 cell up to the sixth passage. The polyacrilamide gel electrophoresis(PAGE) was used to confirm the viral isolation. The aim of the work was to compare the electropherotic profile of fecal samples before and after isolation in MA104 cells. The samples from pigs did not reveal apparent changes in bands migration. However, an additional segment, betweem segments 5 and 6 was detected, in one fecal sample and after isolation. Furthermore, one child sample showed differences in the electrophoretic mobility and also an additional segment was detected between segments 5 - 6 in one sample from a calf. The results emphasize the importance of PAGE as a technique to screen samples that could be analyzed posteriorly by more specific molecular techniques. The changes in the electrophoretic profiles of genomic segments of viral RNA might be suggestive of changes in the antigenic properties, besides the fact that changes that occurred in vitro may also happen in vivo.

Rotavírus (RV) é um importante patógeno viral que causa diarreia em leitões e indivíduos jovens de várias outras espécies animais. RV dos grupos A, B, C e E foram descritos como causa de diarreia em suínos. Este estudo reúne achados histopatológicos, imunohistoquímicos e de reação em cadeia da polimerase com transcriptase reversa (RT-PCR) presentes em quatro surtos de diarreia causados por RV de um e de múltiplos grupos na região sul do Brasil. Vacinação para RV não era aplicada em nenhuma das granjas estudadas. Necropsia, exames histológicos e imuni-histoquímicos foram realizados em 34 suínos de maternidade que apresentavam diarreia severa, além disso, realizou-se cultivo bacteriano e RT-PCR para RV dos grupos A, B e C, vírus da gastroenterite transmissível (TGEV), vírus da diarreia epidêmica dos suínos (PEDV), sapovírus (SaV), norovírus (NoV) e kobuvírus (Aichi vírus C) em 30 dessas amostras. Desidratação e conteúdo pastoso a líquido no cólon foram observados em todos os suínos. Exame histológico revelou atrofia de vilosidades em 29 casos, vacuolização de enterócitos em 27 casos e debris celulares na lâmina própria em 20 casos. Houve marcação imunohistoquímica positiva em 21 casos. RT-PCR foi positiva para RV em 20 casos e RV do grupo C foi o mais frequentemente detectado, presente em 17 amostras. Cultivo e isolamento de Escherichia coli ocorreu em todos os casos e quatro destes foram de E. coli α-hemolítica. Em 15 amostras houve isolamento de Clostridium sp. Sapovirus foi detectado em oito amostras, duas amostras foram positivas para norovírus e detectou-se kobuvírus em 11 animais. Os achados histológicos foram consistentes com infecção por RV e a imuno-histoquímica revelou dois padrões de marcação para o agente no intestino delgado. Os resultados de RT-PCR mostraram que o RV do grupo C foi o principal agente detectado neste estudo. O isolamento de E. coli e a detecção de SaV os destacou como agentes associados à infecção por RV. A detecção de kobuvírus o enfatiza como um novo candidato em associação com RV. / Rotavirus is an important viral pathogen causing diarrhea in piglets and other animal species worldwide. Groups A, B, C and E have been described causing diarrhea in swine. This study reunites histopathological, immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR) findings present in four outbreaks of diarrhea caused by single and multiple groups of rotavirus in the south of Brazil. None of the herds studied applied vaccination against rotavirus. Necropsy, histological examination and immunohistochemistry were performed in 34 nursing piglets that presented severe diarrhea, bacterial culture and reverse transcriptase polymerase chain reaction (RT-PCR) for rotavirus from groups A, B and C, transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), sapovirus (SaV), norovirus (NoV) and kobuvirus (Aichi virus C) were carried out in 30 of the animals necropsied. Additionally, RT-PCR was performed in fecal pools from two outbreaks. Dehydration and fluid to pasty contents were observed in the colon of all 34 swine examined. Histological examination revealed villus atrophy in 29 cases, vacuolation of enterocytes in 27 cases and necrotic debris in the lamina propria of 20 cases. IHC was positive in 21 samples. RT-PCR was positive for rotavirus in 20 samples and group C rotavirus was the most frequently detected, present in 17 samples. Escherichia coli was isolated from all cases, and in four cases, it was α-hemolytic. Clostridium sp. was isolated from 15 samples. Sapovirus was detected in eight samples, samples from two animals were positive for norovirus and kobuvirus was detected from 11 samples. Histological findings were consistent with rotavirus infection and immunohistochemistry revealed two patterns of staining for rotavirus in the small intestine. RT-PCR results have shown group C rotavirus as the main agent detected in this study. The isolation of Escherichia coli and the detection of sapovirus highlighted them as possible agents associated to rotavirus infection. Kobuvirus detection has emphasized it as a new candidate in the association with rotavirus.

La vaccination représente l'un des grands succès des stratégies de santé publique. Cependant, depuis leur introduction, les vaccins ont fait l’objet de controverses. Des polémiques médiatiques ont contribué à ébranler la confiance que les citoyens portent dans la vaccination et les autorités sanitaires. Une communication transparente et fondée sur une démonstration robuste du rapport bénéfice-risque des vaccins est donc nécessaire afin d’éclairer les décisions des autorités de santé et rétablir la confiance du grand public et des professionnels de santé.Les modèles quantitatifs pour l’évaluation du rapport bénéfice-risque (qBRm) sont de plus en plus utilisés par les parties prenantes comme outils d’aide à la décision. Ces modèles fournissent une structure permettant d’incorporer des données provenant de plusieurs sources afin de quantifier et de mettre en perspective les bénéfices et les risques d’une intervention. Cependant, les autorités de santé et les laboratoires pharmaceutiques se préoccupent du manque de cadre explicite et systématique. Des initiatives se développent afin d’optimiser l’évaluation quantitative du rapport bénéfice-risque des produits de santé. Néanmoins, peu d’entre elles sont spécifiques aux vaccins.Au vu de ce contexte, ce travail de recherche avait pour vocation de proposer et de tester de nouveaux outils permettant de structurer l’évaluation quantitative du bénéfice-risque des vaccins afin d’optimiser son utilisation dans l’aide à la décision des différentes parties prenantes.Pour cela, l’objectif de la première partie de ce travail était de synthétiser les données disponibles sur les qBRm appliqués aux vaccins afin de les analyser. L’état de l’art effectué a confirmé que les qBRm étaient de plus en plus utilisés pour aider à l’évaluation du bénéfice-risque des vaccins. Les chiffres montrent une nette augmentation du nombre de publications dans ce domaine depuis le début des années 2000. Un tiers des qBRm identifiés concernait la vaccination contre le rotavirus. Cependant aucune de ces études sur le rotavirus n’avait été développée spécifiquement pour la France. L’analyse des études sélectionnées a mis en évidence des divergences en termes d’approches méthodologiques utilisées et des lacunes concernant la qualité de l’information renseignée dans les études, rendant l’interprétation et la comparaison des modèles complexes.Au cours de la deuxième partie de ce travail nous nous sommes donc attachés à proposer des axes d’amélioration. Tout d’abord nous avons conçu un guide pour améliorer la description des analyses afin d’apporter plus de transparence et de garantir ainsi une meilleure interprétation des résultats sur les qBRm appliqués aux vaccins. Puis, en l’absence d’évaluation quantitative du rapport bénéfice-risque de la vaccination contre le rotavirus en France et compte tenu des interrogations existantes autour de son intérêt, nous avons réalisé un qBRm évaluant la vaccination contre le rotavirus en France. Enfin, nous avons souhaité explorer l’utilisation d’un nouvel outil de modélisation pour le développement de qBRm appliqués aux vaccins : le Discretely Integrated Condition Event (DICE). Le DICE constitue un outil standardisé qui pourrait être utilisé par toutes les parties prenantes. L’application d’une telle interface commune à tous les qBRm pourrait faciliter leur conception, leur analyse et leur comparaison.Cependant, ces axes d’amélioration ne constituent qu’un point de départ des efforts nécessaires à réaliser pour l’évaluation du rapport bénéfice-risque des vaccins. De nouvelles initiatives sont essentielles afin de poursuivre la généralisation des qBRm appliqués aux vaccins, tout en les rendant plus performants et assortis de résultats robustes et transparents. Ces étapes semblent nécessaires pour rétablir la confiance en la vaccination et améliorer les couvertures vaccinales, assurant ainsi une protection optimale des populations face à des maladies infectieuses. / Vaccination is one of the most successful public health achievements in disease prevention. However, since their introduction, vaccines have been relatively contentious. Health controversies have contributed to erode the population’s confidence in vaccination and health authorities. A transparent communication based on a robust demonstration of the benefit-risk assessment (BRA) of vaccines could be therefore necessary to inform decision-makers and restore the public’s confidence.Quantitative benefit-risk models (qBRm) applied on vaccines is an important, and increasingly used, tool to support the BRA from decision-makers. These models provide a structure for incorporating evidence from multiple sources to quantify and put into perspective the benefits and risks of an intervention. However, health authorities and pharmaceutical companies are concerned about the lack of an explicit and systematic framework. While some initiatives that aims at optimising the BRA of health products are emerging, few of them are specific to vaccines. In this context, our research aimed to propose and test new tools to structure qBRm applied on vaccines in order to optimise them use in the decision-making process from different stakeholders. The first part of this work aimed at identifying publications reporting on qBRm for vaccines through a systematic literature review and describing their study characteristics according to specific classification criteria. The analyses confirmed that the number of qBRm of vaccines publications has been increasing since 2000. One-third of the qBRm publications were related to rotavirus vaccination. However, none of these studies on rotavirus vaccination had been performed to specifically address the French context. The analysis of the selected studies revealed divergences in terms of the methodological approaches used and gaps in the granularity of information reported, making complex the interpretation and comparison of the models. In the second part of this research, we therefore endeavoured to propose areas for improvement. To start with, we designed an operational checklist to improve the reporting of qBRm applied on vaccines. Indeed, an adequate reporting is key to ensure a transparent disclosure of the analysis and its reproducibility, thereby facilitating study result interpretation and comparability. Then, to palliate for the absence of qBRm applied on rotavirus vaccination and given the historical context in France, we developed our own qBRm. Finally, we tested a new alternative for designing and structuring qBRm applied on vaccines: the Discretely Integrated Condition Event (DICE) simulation. DICE is a standardised tool that could be used by every stakeholder. The systematic use of such common interface to qBRm could facilitate their design, analysis and comparison. Nevertheless, these areas for improvement are only a starting point, further initiatives are essential to continue the uptake of qBRm applied on vaccines, while making them more efficient, with robust and transparent results. These steps, although not exclusive, seem necessary to enhance public confidence in vaccination and improve vaccine coverage, ensuring as a result an optimal protection of population against infectious diseases.