LUIZ VICENTE RIBEIRO FERREIRA DA SILVA FILHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject MARKED CFTR GENOTYPING DIFFERENCES BETWEEN BRAZILIAN REGIONS(2018) SILVA FILHO, L. R.; REIS, F. C.; MAROSTICA, P.; ATHANAZIO, R. A.; DAMACENO, N.; PAES, A. T.; HIRA, A. Y.bookPart Crise asmática(2023) SEVERINI, Rafael da Silva Giannasi; SILVA FILHO, Luiz Vicente Ribeiro Ferreira da- Evidence for an Ancestral Association of Human Coronavirus 229E with Bats(2015) CORMAN, Victor Max; BALDWIN, Heather J.; TATENO, Adriana Fumie; ZERBINATI, Rodrigo Melim; ANNAN, Augustina; OWUSU, Michael; NKRUMAH, Evans Ewald; MAGANGA, Gael Darren; OPPONG, Samuel; ADU-SARKODIE, Yaw; VALLO, Peter; SILVA FILHO, Luiz Vicente Ribeiro Ferreira da; LEROY, Eric M.; THIEL, Volker; HOEK, Lia van der; POON, Leo L. M.; TSCHAPKA, Marco; DROSTEN, Christian; DREXLER, Jan FelixWe previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related viruses by reverse transcription-PCR (RT-PCR). Only hipposiderid bats tested positive. To compare the genetic diversity of bat viruses and HCoV-229E, we tested historical isolates and diagnostic specimens sampled globally over 10 years. Bat viruses were 5- and 6-fold more diversified than HCoV-229E in the RNA-dependent RNA polymerase (RdRp) and spike genes. In phylogenetic analyses, HCoV-229E strains were monophyletic and not intermixed with animal viruses. Bat viruses formed three large clades in close and more distant sister relationships. A recently described 229E-related alpaca virus occupied an intermediate phylogenetic position between bat and human viruses. According to taxonomic criteria, human, alpaca, and bat viruses form a single CoV species showing evidence for multiple recombination events. HCoV-229E and the alpaca virus showed a major deletion in the spike S1 region compared to all bat viruses. Analyses of four full genomes from 229E-related bat CoVs revealed an eighth open reading frame (ORF8) located at the genomic 3' end. ORF8 also existed in the 229E-related alpaca virus. Reanalysis of HCoV-229E sequences showed a conserved transcription regulatory sequence preceding remnants of this ORF, suggesting its loss after acquisition of a 229E-related CoV by humans. These data suggested an evolutionary origin of 229E-related CoVs in hipposiderid bats, hypothetically with camelids as intermediate hosts preceding the establishment of HCoV-229E. IMPORTANCE The ancestral origins of major human coronaviruses (HCoVs) likely involve bat hosts. Here, we provide conclusive genetic evidence for an evolutionary origin of the common cold virus HCoV-229E in hipposiderid bats by analyzing a large sample of African bats and characterizing several bat viruses on a full-genome level. Our evolutionary analyses show that animal and human viruses are genetically closely related, can exchange genetic material, and form a single viral species. We show that the putative host switches leading to the formation of HCoV-229E were accompanied by major genomic changes, including deletions in the viral spike glycoprotein gene and loss of an open reading frame. We reanalyze a previously described genetically related alpaca virus and discuss the role of camelids as potential intermediate hosts between bat and human viruses. The evolutionary history of HCoV-229E likely shares important characteristics with that of the recently emerged highly pathogenic Middle East respiratory syndrome (MERS) coronavirus.
conferenceObject Early CF Lung Disease: The Brazilian Experience(2017) SILVA FILHO, Luiz Vicente Ribeiro F. da- Use of elexacaftor plus tezacaftor plus ivacaftor in individuals with cystic fibrosis and at least one F508del allele: a systematic review and meta-analysis(2023) SILVA FILHO, Luiz Vicente Ribeiro Ferreira da; ATHANAZIO, Rodrigo Abensur; TONON, Carolina Rodrigues; FERREIRA, Juliana Carvalho; TANNI, Suzana EricoObjective: To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezac aftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis. Methods: This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV 1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, -0.16; 95% CI, -0.28 to -0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m(2); 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, -0.03; 95% CI, -0.08 to 0.01), and none of the studies reported deaths. Conclusions: Our findings demonstrate that ETI treatment substantially improves clinically significant, patientcentered outcomes.
- Cystic fibrosis carriership and tuberculosis: hints toward an evolutionary selective advantage based on data from the Brazilian territory(2017) BOSCH, Lander; BOSCH, Barbara; BOECK, Kris De; NAWROT, Tim; MEYTS, Isabelle; VANNESTE, Dominique; BOURLEGAT, Cleonice Alexandre Le; CRODA, Julio; SILVA FILHO, Luiz Vicente Ribeiro Ferreira daBackground: The reason why Cystic Fibrosis (CF) is the most common fatal genetic disease among Caucasians has been incompletely studied. We aimed at deepening the hypothesis that CF carriers have a relative protection against Mycobacterium tuberculosis(Mtb) infection. Methods: Applying spatial epidemiology, we studied the link between CF carriership rate and tuberculosis ( TB) incidence in Brazil. We corrected for 5 potential environmental and 2 immunological confounders in this relation: monthly income, sanitary provisions, literacy rates, racial composition and population density along with AIDS incidence rates and diabetes mellitus type 2. Smoking data were incomplete and not available for analysis. Results: A significant, negative correlation between CF carriership rate and TB incidence, independent of any of the seven confounders was found. Conclusion: We provide exploratory support for the hypothesis that carrying a single CFTR mutation arms against Mtb infections.
- Cystic fibrosis in low and middle-income countries (LMIC): A view from four different regions of the world(2021) SILVA FILHO, Luiz Vicente Ribeiro Ferreira da; ZAMPOLI, Marco; COHEN-CYMBERKNOH, Malena; KABRA, Sushil K.Cystic fibrosis (CF) has been shown to affect people all over the world. While life expectancy for people with CF has increased substantially, CF is still associated with death in infants and young children in many regions, particularly in low and middle-income countries (LMIC). These countries face significant challenges to promote CF diagnosis and improvements to CF care due to financial constraints and a significant burden of other diseases. In this review, we describe the status of CF diagnosis and care in different LMIC settings, from four different parts of the world (Brazil, South Africa, Israel and India). We highlight challenges and opportunities for CF practitioners in LMIC to improve CF care and outcomes. While early CF diagnosis is the key to optimising outcomes, newborn screening may not be feasible for countries with lower CF incidence and higher birth rates, such as India or South Africa. CF therapies and care in LMIC need to be adapted to available resources of these countries. Collaboration initiatives of the global CF community with LMIC may improve CF care in these countries. Most individuals with CF in LMIC are not benefiting from CFTR modulator treatments due to the prohibitive cost of these drugs.
- Systematic Review of Probiotics for Cystic Fibrosis Patients: Moving Forward(2019) NERI, Lenycia de Cassya Lopes; TAMINATO, Monica; SILVA FILHO, Luiz Vicente Ribeiro Ferreira daBackground: Cystic fibrosis (CF) is associated with chronic respiratory disease and pancreatic insufficiency and results in the malabsorption of nutrients and intestinal inflammation. There is evidence that probiotic supplementation may impact the gastrointestinal and respiratory microbiota. This study aimed to categorize current evidence regarding the effects of supplementing with probiotics in CF patients on gastrointestinal and respiratory outcomes according to the type of intervention. Methods: The initial database search included all identified studies according to the recommendations of the Cochrane Collaboration, regardless of language, publication date or design. Studies were categorized by probiotic strain (Lactobacillus reuteri; Lactobacillus rhamnosus GG or a mix of strains); dosage (low dosage if <10(9) CFU [ colony forming units] or high dosage if >10(9) CFU); and duration of intervention (1, 3, 6, or 12 months). Assessment of quality was performed based on the Cochrane risk of bias criteria and the Downs & Black checklist. Results: A total of 205 studies were identified; however, only 9 met the criteria for inclusion. The studies were considered to have a high risk of bias, hampering the possibility of performing a meta-analysis. Eighty percent of the studies (4 of 5) reported a positive result for intestinal inflammation, and another 4 studies (4 of 5) reported a positive result for pulmonary exacerbation frequency, regardless of the treatment approach. Conclusions: The present data indicate a promising future for probiotic use in cystic fibrosis, which has an impact on exacerbations and intestinal inflammation; however, further studies of standardized therapeutic interventions are required.
conferenceObject A NEW INSIGHT ON CFTR ALLELE FREQUENCY IN BRAZIL THROUGH NEXT GENERATION SEQUENCING(2016) NUNES, Luisa Mesquita; RIBEIRO, Roberto; SABINO, Ester; NIEWIANDONSKI, Vivian D. T.; YAMAMOTO, Guilherme Lopes; SILVA FILHO, Luiz Vicente Ribeiro F. daconferenceObject ALBUTEROL VIA METERED-DOSE INHALER FOR ACUTE ASTHMA IN CHILDREN: LOWER DOSES ARE SUFFICIENT AND HIGHER DOSES ARE SAFE(2015) MUCHAO, F. P.; SOUZA, J. M.; TORRES, H. C.; LALIBERA, I. B.; SCHVARTSMAN, C.; RODRIGUES, J. C.; V, L. Silva Filho