EXPEDITO JOSE DE ALBUQUERQUE LUNA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Medicina Preventiva, Faculdade de Medicina - Docente
LIM/38 - Laboratório de Epidemiologia e Imunobiologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/38 - Laboratório de Epidemiologia e Imunobiologia, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease(2013) WEG, Cornelia A. M. van de; PANNUTI, Claudio S.; ARAUJO, Evaldo S. A. de; HAM, Henk-Jan van den; ANDEWEG, Arno C.; BOAS, Lucy S. V.; FELIX, Alvina C.; CARVALHO, Karina I.; MATOS, Andreia M. de; LEVI, Jose E.; ROMANO, Camila M.; CENTRONE, Cristiane C.; RODRIGUES, Celia L. de Lima; LUNA, Expedito; GORP, Eric C. M. van; OSTERHAUS, Albert D. M. E.; MARTINA, Byron E. E.; KALLAS, Esper G.Background: Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection. Methods: Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of Sao Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles. Results: Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease. Conclusions: The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis.
- Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma Is genotype B associated with better prognosis of AIDS-KS?(2016) TOZETTO-MENDOZA, Tania Regina; IBRAHIM, Karim Yaqub; TATENO, Adriana Fumie; OLIVEIRA, Cristiane Mendes de; SUMITA, Laura Massami; SANCHEZ, Maria Carmem Arroyo; LUNA, Expedito Jose; PIERROTTI, Ligia Camara; DREXLER, Jan Felix; BRAZ-SILVA, Paulo Henrique; PANNUTI, Claudio Sergio; ROMANO, Camila MaltaAIDS-associated Kaposi's sarcoma (AIDS-KS) caused by human herpes virus 8 (HHV-8) is the most severe and resistant form of KS tumor. Our aim was to verify whether there is an association between HHV-8 variability and development of AIDS-KS in Brazil by comparing the HHV-8 variability between individuals without and with KS. Saliva samples and blood, when available, were analyzed by PCR techniques for detection of the fragments of ORF K1 of HHV-8, which were then genotyped and analyzed regarding the genetic variability. Our study described 106 positive cases for HHV-8 in the saliva from 751 AIDS patients without previous KS. In addition, we performed a phylogenetic analysis of HHV-8 in 34 of the 106 AIDS patients without KS and in 33 of the 37 patients with active KS. The distribution of HHV-8 genotypes A, B, C, and F in AIDS individuals was indistinguishable by comparing non-KS and KS groups, as well as regarding ethnicity. Considering the KS group, genotype B was associated with better prognosis of KS tumor. Interestingly. we found a particular profile of diversity within Glade C and 2 recombinant patterns of HHV-8 in the saliva of AIDS individuals without KS. We emphasize the need to achieve standard genotyping protocol for ORF K1 amplification, thus allowing for substantial detection of HHV-8 variants. Our findings can shed light on the role of HHV-8 variability in the pathogenesis of AIDS-KS.
conferenceObject A COHORT STUDY TO DETERMINE THE INCIDENCE OF ZIKA VIRUS INFECTION AMONG NEWBORNS, SANTOS, BRAZIL, 2016-2017(2017) LUNA, Expedito J.; ROMANO, Camila M.; ARAUJO, Evaldo S.; LEVI, Jose E.; OLIVEIRA, Olimpia N.; FERNANDES, Luis R.; FELIX, Alvina C.; SOUZA, Nathalia S.; FERNANDES, Joao H.; CAMPOS, Sergio R.; FRAGOSO, Danielli B.; PANNUTI, Claudio S.- Phylogenetics, Epidemiology and Temporal Patterns of Dengue Virus in Araraquara, São Paulo State(2024) SOUZA, Caio Santos de; CALEIRO, Giovana Santos; CLARO, Ingra Morales; JESUS, Jaqueline Goes de; COLETTI, Thais Moura; SILVA, Camila Alves Maia da; COSTA, Angela Aparecida; INENAMI, Marta; RIBEIRO, Andreia C.; FELIX, Alvina Clara; PAULA, Anderson Vicente de; FIGUEIREDO, Walter M.; LUNA, Expedito Jose de Albuquerque; SABINO, Ester C.; ROMANO, Camila M.Dengue virus (DENV) is a prominent arbovirus with global spread, causing approximately 390 million infections each year. In Brazil, yearly epidemics follow a well-documented pattern of serotype replacement every three to four years on average. Araraquara, located in the state of Sao Paulo, has faced significant impacts from DENV epidemics since the emergence of DENV-1 in 2010. The municipality then transitioned from low to moderate endemicity in less than 10 years. Yet, there remains an insufficient understanding of virus circulation dynamics, particularly concerning DENV-1, in the region, as well as the genetic characteristics of the virus. To address this, we sequenced 37 complete or partial DENV-1 genomes sampled from 2015 to 2022 in Araraquara. Then, using also Brazilian and worldwide DENV-1 sequences we reconstructed the evolutionary history of DENV-1 in Araraquara and estimated the time to the most recent common ancestor (tMRCA) for serotype 1, for genotype V and its main lineages. Within the last ten years, there have been at least three introductions of genotype V in Araraquara, distributed in two main lineages (L Ia and L Ib, and L II). The tMRCA for the first sampled lineage (2015/2016 epidemics) was approximately 15 years ago (in 2008). Crucially, our analysis challenges existing assumptions regarding the emergence time of the DENV-1 genotypes, suggesting that genotype V might have diverged more recently than previously described. The presence of the two lineages of genotype V in the municipality might have contributed to the extended persistence of DENV-1 in the region.
- Low prevalence after the first Zika virus epidemic wave in Southeastern Brazil(2018) LUNA, E.; ROMANO, C.; ARAUJO, E.; FELIX, A. C.; NAKASONE, O.; CAMPOS, S.; FERNANDES, L.; LEVI, J. E.; SANTIAGO, N.; FERNANDES, J.; FRAGOSO, D.; KALLAS, E.; PANNUTI, C.
- Serum angiopoietin-2 and soluble VEGF receptor 2 are surrogate markers for plasma leakage in patients with acute dengue virus infection(2014) WEG, Cornella A. M. van de; PANNUTI, Claudio S.; HAM, Henk-Jan van den; ARAUJO, Evaldo S. A. de; BOAS, Lucy S. V.; FELIX, Alvina C.; CARVALHO, Karina I.; LEVI, Jose E.; ROMANO, Camila M.; CENTRONE, Cristiane C.; RODRIGUES, Celia L. de Lima; LUNA, Expedito; GORP, Eric C. M. van; OSTERHAUS, Albert D. M. E.; KALLAS, Esper G.; MARTINA, Byron E. E.Background: Endothelial cell dysfunction is believed to play an important role in the pathogenesis of plasma leakage in patients with acute dengue virus (DENV) infection. Several factors, produced by activated endothelial cells, have been associated with plasma leakage or severe disease in patients with infectious diseases. Objectives: The aim of this study was to investigate which of these markers could serve as a surrogate marker for the occurrence of plasma leakage in patients with acute DENV infection. Study design: A case-control study was performed in patients with acute DENV infection in Santos, Brazil. Plasma leakage was detected with X-ray and/or ultrasound examination at admission. Serum levels of soluble endoglin, endothelin-1, angiopoietin-2, VEGF, soluble VEGFR-2, MMP-2, MMP-9, TIMP-1 and TIMP2 were determined using commercially available ELISAs. Results: Increased levels of angiopoietin-2, endothelin-1 and MMP-2 and decreased levels of soluble VEGFR2 were significantly associated with the occurrence of plasma leakage. An unsupervised cluster analysis confirmed that angiopoietin-2 and soluble VEGFR-2 were strongly associated with clinical apparent vascular leakage. Conclusion: Angiopoietin-2 and soluble VEGFR-2 can serve as surrogate markers for the occurrence of plasma leakage in patients with acute DENV infection.
- Pre-transplant shedding of BK virus in urine is unrelated to post-transplant viruria and viremia in kidney transplant recipients(2016) BICALHO, C. S.; OLIVEIRA, R. R.; PIERROTTI, L. C.; FINK, M. C. D. S.; URBANO, P. R. P.; NALI, L. H. S.; LUNA, E. J. A.; ROMANO, C. M.; DAVID, D. R.; DAVID-NETO, E.; PANNUTI, C. S.BK virus-(BKV) associated nephropathy (BKVN) is a major cause of allograft injury in kidney transplant recipients. In such patients, subclinical reactivation of latent BKV infection can occur in the pre-transplant period. The purpose of this study was to determine whether urinary BKV shedding in the immediate pre-transplant period is associated with a higher incidence of viruria and viremia during the first year after kidney transplantation. We examined urine samples from 34 kidney transplant recipients, using real-time quantitative polymerase chain reaction to detect BKV. Urine samples were obtained in the immediate pre-transplant period and during the first year after transplant on a monthly basis. If BKV viruria was detected, blood samples were collected and screened for BKV viremia. In the immediate pre-transplant period, we detected BKV viruria in 11 (32.3%) of the 34 recipients. During the first year after transplantation, we detected BKV viruria in all 34 patients and viremia in eight (23.5%). We found no correlation between pre-transplant viruria and post-transplant viruria or viremia (p = 0.2). Although reactivation of latent BKV infection in the pre-transplant period is fairly common among kidney transplant recipients, it is not a risk factor for post-transplant BKV viruria or viremia.
- Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons(2020) MACHADO, Clarisse M.; SOUZA, Ana Carolina Mamana Fernandes de; ROMANO, Camila Malta; FREIRE, Wilton dos Santos; COSTA, Angela Aparecida; FIGUEIREDO, Walter Manso; PANNUTI, Claudio S.; LUNA, Expedito J. A.Introduction: Influenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. Objectives: Determine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). Methods: A cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. Results: 179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. Conclusions: Influenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population. (C) 2020 Sociedade Brasileira de Infectologia.