Artigos e Materiais de Revistas Científicas - IMT

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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.

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Core Promoter and Pre-Core Variants of the Hepatitis B Virus (HBV) Are Frequent in Chronic Hepatitis B HBeAg-Negative Patients Infected by Genotypes A and D
(2023) REUTER, Tania; GOMES-GOUVEA, Michele Soares; CHUFFI, Samira; DUQUE, Ulisses Horst; PERINI, Waltesia; AZEVEDO, Raymundo Soares; PINHO, Joao Renato Rebello; LEWIS-XIMENEZ, Lia L.; VILLAR, Livia Melo; ESPUL, Carlos Alberto; PUJOL, Flor H.; ROMAN, Sonia
In Brazil, hepatitis B virus endemicity is low, moderate, or high in some areas, such as Espirito Santo State in the southeast region. In this study, we intend to characterize the basal core promoter (BCP) and pre-core region (PC) variants and their association with clinical/epidemiological disease patterns in patients infected with genotypes A and D. The study included 116 chronic hepatitis B patients from Espirito Santo State, Southeast Brazil, infected with genotypes A and D. Basal core promoter (BCP) and pre-core mutations were analyzed in these patients. The frequency of BCP and PC mutations was compared with age, HBeAg status, HBV genotype and subgenotype, HBV-DNA level, clinical classification, and transmission route. HBeAg-negative status was found in 101 (87.1%) patients: 87 (75.0%) were infected with genotype A (A1 = 85; A2 = 2) and 29 (25.0%) were infected with genotype D (D3 = 24; D4 = 3; D2 = 2). BCP + PC variants altogether were more frequent (48.1%) in genotype D than in genotype A strains (6.0%) (p < 0.001). When this evaluation was performed considering the cases that presented only the A1762T and/or G1764A (BCP) mutations, it was observed that the frequency was higher in genotype A (67.5%) compared to genotype D (7.4%) (p < 0.001). On the other hand, considering the samples with mutations only in positions G1896A and/or G1899A (PC), the frequency was higher in genotype D (75.8%) than in genotype A (6.9%) (p < 0.001). Interestingly, HBV DNA was lower than 2000 IU/mL especially when both BCP/PC mutations were present (p < 0.001) or when only PC mutations were detected (p = 0.047), reinforcing their role in viral replication.
Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection
(2023) RUSSO, Momtchilo; MENDES-CORREA, Maria Cassia; LINS, Bruna B.; KERSTEN, Victor; PERNAMBUCO, Paulo C. A.; MARTINS, Toni Ricardo; TOZETTO-MENDOZA, Tania Regina; BOAS, Lucy Santos Vilas; GOMES, Brisa Moreira; DATI, Livia Mendonca Munhoz; DUARTE-NETO, Amaro Nunes; REIGADO, Gustavo Roncoli; FREDERICO, Ana Beatriz T.; CUNHA, Danielle R. de A.; PAULA, Anderson Vicente de; SILVA, Jose Igor G. da; VASCONCELOS, Carlos F. Moreira; CHAMBERGO, Felipe S.; NUNES, Viviane Abreu; BOM, Ana Paula Dinis Ano; CASTILHO, Leda R.; MARTINS, Rodrigo A. P.; HIRATA, Mario Hiroyuki; MIROTTI, Luciana; TRIPP, Ralph A.
Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.
Encephalopathy Caused by Human Parvovirus B19 Genotype 1 Associated with Haemophilus influenzae Meningitis in a Newborn
(2023) FERREIRA, Noely Evangelista; COSTA, Antonio C. da; KALLAS, Esper G.; SILVEIRA, Cassia G. T.; OLIVEIRA, Ana Carolina S. de; HONORATO, Layla; PAIAO, Heuder G. O.; LIMA, Silvia H.; VASCONCELOS, Dewton de M.; CORTES, Marina F.; COSTA, Silvia F.; MENDOZA, Tania R. T.; GOMES, Helio R.; WITKIN, Steven S.; MENDES-CORREA, Maria C.
Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact of B19 on public health remains unclear. We report the case of a 38-day old girl admitted to Sao Paulo Clinical Hospital, Brazil, with an initial diagnosis of bacterial meningitis, seizures, and acute hydrocephalus. Antibiotic therapy was maintained for one week after admission and discontinued after negative laboratory results were obtained. Nine days after symptoms onset, a cerebral spinal fluid (CSF) sample revealed persistent pleocytosis. The complete B19 complete genome was subsequently identified in her CSF by a metagenomic next-generation sequencing approach. This report highlights the possible involvement of B19 in the occurrence of acute neurological manifestations and emphasizes that its possible involvement might be better revealed by the use of metagenomic technology to detect viral agents in clinical situations of unknown or uncertain etiology.
Imiquimod chemoprophylaxis for field cancerization in xeroderma pigmentosum patients-A prospective study
(2023) ROCHA, Lilian Kelly Faria Licariao; FERREIRA, Paula; GIANOTTI, Marcelo A.; AVANCINI, Joao; MENCK, Carlos F. M.; CASTRO, Ligia P.; OLIVEIRA, Zilda Najjar Prado de; RIVITTI, Maria C.; SAMORANO, Luciana P.; PEREIRA, Naiura Vieira; FESTA NETO, Cyro
Coronary Inflammation by Computed Tomography Pericoronary Fat Attenuation and Increased Cytokines in Young Male Anabolic Androgenic Steroid Users
(2023) SOUZA, Francis Ribeiro de; ROCHITTE, Carlos E.; SILVA, Douglas Carli; SAMPAIO, Barbara; PASSARELLI, Marisa; SANTOS, Marcelo R. dos; FONSECA, Guilherme W.; BATTAGLIA-FILHO, Antonio Carlos; CORREA, Kelly; VAL, Renata Margarida do; YONAMINE, Mauricio; PEREIRA, Rosa Maria R.; NEGRAO, Carlos Eduardo; KALIL-FILHO, Roberto; ALVES, Maria Janieire de Nazare Nunes
Background: Anabolic androgenic steroid (AAS) abuse has been associated with coronary artery disease (CAD). Pericoronary fat attenuation (pFA) is a marker of coronary inflammation, which is key in the atherosclerotic process.Objective: To evaluate pFA and inflammatory profile in AAS users.Methods: Twenty strength-trained AAS users (AASU), 20 AAS nonusers (AASNU), and 10 sedentary controls (SC) were evaluated. Coronary inflammation was evaluated by mean pericoronary fat attenuation (mPFA) in the right coronary artery (RCA), left anterior descending coronary artery (LAD), and left circumflex (LCx). Interleukin (IL)-1 (IL-1), IL-6, IL-10, and TNF-alpha were evaluated by optical density (OD) in a spectrophotometer with a 450 nm filter. P<0.05 indicated statistical significance.Results: AASU had higher mPFA in the RCA (-65.87 [70.51-60.70] vs.-78.07 [83.66-72.87] vs.-78.46 [85.41-71.99] Hounsfield Units (HU), respectively, p<0.001) and mPFA in the LAD (-71.47 [76.40-66.61] vs.-79.32 [84.37-74.59] vs.-82.52 [88.44-75.81] HU, respectively, p=0.006) compared with AASNU and SC. mPFA in the LCx was not different between AASU, AASNU, and SC (-72.41 [77.17-70.37] vs.-80.13 [86.22-72.23] vs.-78.29 [80.63-72.29] HU, respectively, p=0.163). AASU compared with AASNU and SC, had higher IL-1, (0.975 [0.847-1.250] vs. 0.437 [0.311-0.565] vs. 0.530 [0.402-0.780] OD, respectively, p=0.002), IL-6 (1.195 [0.947-1.405] vs. 0.427 [0.377-0.577] vs. 0.605 [0.332-0.950] OD, p=0.005) and IL-10 (1.145 [0.920-1.292] vs. 0.477 [0.382-0.591] vs. 0.340 [0.316-0.560] OD, p<0.001). TNF-alpha was not different between the AASU, AASNU, and SC groups (0.520 [0.250-0.610] vs. 0.377 [0.261-0.548] vs. 0.350 [0.182-430]), respectively.Conclusion: Compared with ASSNU and controls, AASU have higher mPFA and higher systemic inflammatory cytokines profile suggesting that AAS may induce coronary atherosclerosis through coronary and systemic inflammation.
Complexity of malaria transmission dynamics in the Brazilian Atlantic Forest
(2021) DUARTE, Ana Maria Ribeiro de Castro; FERNANDES, Licia Natal; SILVA, Fabiana Santos; SICCHI, Igor Lucoves; MUCCI, Luis Filipe; CURADO, Izilda; FERNANDES, Aristides; MEDEIROS-SOUSA, Antonio Ralph; CERETTI-JUNIOR, Walter; MARRELLI, Mauro Toledo; EVANGELISTA, Eduardo; TEIXEIRA, Renildo; SUMMA, Juliana Laurito; NARDI, Marcello Schiavo; GARNICA, Margoth Ramos; LOSS, Ana Carolina; BUERY, Julyana Cerqueira; CERUTT, Crispim; PACHECO, M. Andreina; ESCALANTE, Ananias A.; SALLUM, Maria Anice Mureb; LAPORTA, Gabriel Zorello
Plasmodium malariae and Plasmodium vivax are protozoan parasites that can cause malaria in humans. They are genetically indistinguishable from, respectively, Plasmodium brasilianum and Plasmodium simium, i.e. parasites infecting New World non-human primates in South America. In the tropical rainforests of the Brazilian Atlantic coast, it has long been hypothesized that P. brasilianum and P. simium in platyrrhine primates originated from P. malariae and P. vivax in humans. A recent hypothesis proposed the inclusion of Plasmodium falciparum into the transmission dynamics between humans and non-human primates in the Brazilian Atlantic tropical rainforest. Herein, we assess the occurrence of human malaria in simians and sylvatic anophelines using field-collected samples in the Capivari-Monos Environmental Protection Area from 2015 to 2017. We first tested simian blood and anopheline samples. Two simian (Aloutta) blood samples (18%, n = 11) showed Plasmodium cytb DNA sequences, one for P. vivax and another for P. malariae. From a total of 9,416 anopheline females, we found 17 pools positive for Plasmodium species with a 18S qPCR assay. Only three showed P. cytb DNA sequence, one for P. vivax and the others for rodent malaria species (similar to Plasmodium chabaudi and Plasmodium berghei). Based on these results, we tested 25 rodent liver samples for the presence of Plasmodium and obtained P. falciparum cytb DNA sequence in a rodent (Oligoryzomys sp.) liver. The findings of this study indicate complex malaria transmission dynamics composed by parallel spillover-spillback of human malaria parasites, i.e. P. malariae, P. vivax, and P. falciparum, in the Brazilian Atlantic forest.
New Allele-Specific Oligonucleotide (ASO) amplifications for Toxoplasma gondii rop18 allele typing: Analysis of 86 human congenital infections in Brazil
(2023) SANTOS, Emilly Henrique dos; BARREIRA, Gabriel Acca; YAMAMOTO, Lidia; ROCHA, Mussya Cisotto; RODRIGUES, Karen Alessandra; CRUZ, Maria Carolina Pires; KANUNFRE, Kelly Aparecida; OKAY, Thelma Suely
This study aimed to detect and differentiate Toxoplasma gondii by the allele typing of its polymorphic rop18 gene. For this purpose, a novel genotyping system using allele-specific oligonucleotides (ASOs) was designed, consisting of three ASO pairs. The first and third pairs specifically amplify rop18 allele I and allele III, while the second pair amplify both allele I and II. Genomic DNA from 86 congenital infections was analyzed by ASO-PCRs, successfully typing 82 (95.35%) samples. The remaining 4 samples (4.65%) required sequencing and single nucleotide polymorphism (SNP) analysis of the amplification products. The distribution of samples according to rop18 alleles was: 39.5% of allele III, 38.4% of allele II, 19.8% of mixed rop18 alleles (I/III or II/III), and 2.3% of allele I. The six severely compromised infants exhibited the highest parasite load levels and were infected during the first and early second trimesters of pregnancy. Among these cases, two were associated with rop18 allele I parasites, two with mixed rop18 alleles (I/III), one with allele II, and one with allele III parasites. In conclusion, all severe cases of congenital toxoplasmosis were infected during early pregnancy, but they were not exclusively associated with rop18 allele I parasites, as observed in murine toxoplasmosis. Furthermore, nearly one-fifth of parasites were non-archetypal, exhibiting more than one rop18 allele, indicating a higher genetic diversity of Toxoplasma gondii in this South American sample. Overall, a robust T. gondii rop18 allele typing was developed and suggested that congenital toxoplasmosis in humans involves complex mechanisms beyond the parasite genotype.
Technical comparison of MinIon and Illumina technologies for genotyping Chikungunya virus in clinical samples
(2023) SOUZA, Leandro Menezes de; OLIVEIRA, Isabelle Dias de; SALES, Flavia Cristina Silva; COSTA, Antonio Charlys da; CAMPOS, Karoline Rodrigues; ABBUD, Adriano; GUERRA, Juliana Mariotti; BORGES, Cinthya dos Santos Cirqueira; TAKAHASHI, Carlos Pires Fernandes Junior; ARAUJO, Leonardo Jose Tadeu de
New-generation sequencing (NGS) techniques have brought the opportunity for genomic monitoring of several microorganisms potentially relevant to public health. The establishment of different methods with different mechanisms provides a wide choice, taking into account several aspects. With that in mind, the present aim of the study was to compare basic genomic sequencing metrics that could potentially impact genotyping by nanopores from Oxford Nanopore Technologies and by synthesis from Illumina in clinical samples positive for Chikungunya (CHIKV). Among the metrics studied, running time, read production, and Q score were better represented in Illumina sequencing, while the MinIOn platform showed better response time and greater diversity of generated files. That said, it was possible to establish differences between the studied metrics in addition to verifying that the distinctions in the methods did not impact the identification of the CHIKV virus genotype.
Deep serological profiling of the Trypanosoma cruzi TSSA antigen reveals different epitopes and modes of recognition by Chagas disease patients
(2023) ROMER, Guadalupe; BRACCO, Leonel C.; RICCI, Alejandro M.; BALOUZ, Virginia S.; BERNA, Luisa; VILLAR, Juan; RAMSEY, Janine; NOLAN, Melissa; TORRICO, Faustino A.; KESPER, Norival; ALTCHEH, Jaime L.; ROBELLO, Carlos L.; BUSCAGLIA, Carlos L.; AGUERO, Fernan L.
BackgroundTrypanosoma cruzi, the agent of Chagas disease, displays a highly structured population, with multiple strains that can be grouped into 6-7 evolutionary lineages showing variable eco-epidemiological traits and likely also distinct disease-associated features. Previous works have shown that antibody responses to 'isoforms' of the polymorphic parasite antigen TSSA enable robust and sensitive identification of the infecting strain with near lineage-level resolution. To optimize the serotyping performance of this molecule, we herein used a combination of immunosignaturing approaches based on peptide microarrays and serum samples from Chagas disease patients to establish a deep linear B-cell epitope profiling of TSSA. Methods/Principle findingsOur assays revealed variations in the seroprevalence of TSSA isoforms among Chagas disease populations from different settings, hence strongly supporting the differential distribution of parasite lineages in domestic cycles across the Americas. Alanine scanning mutagenesis and the use of peptides of different lengths allowed us to identify key residues involved in antibody pairing and the presence of three discrete B-cell linear epitopes in TSSAII, the isoform with highest seroprevalence in human infections. Comprehensive screening of parasite genomic repositories led to the discovery of 9 novel T. cruzi TSSA variants and one TSSA sequence from the phylogenetically related bat parasite T. cruzi marinkellei. Further residue permutation analyses enabled the identification of diagnostically relevant or non-relevant substitutions among TSSA natural polymorphisms. Interestingly, T. cruzi marinkellei TSSA displayed specific serorecognition by one chronic Chagas disease patient from Colombia, which warrant further investigations on the diagnostic impact of such atypical TSSA. Conclusions/SignificanceOverall, our findings shed new light into TSSA evolution, epitope landscape and modes of recognition by Chagas disease patients; and have practical implications for the design and/or evaluation of T. cruzi serotyping strategies. Author summaryChagas disease, caused by the protozoan Trypanosoma cruzi, is a chronic, debilitating illness of major significance in Latin America. Due to the extensive genetic and phenotypic variability of this parasite, methods able to reliably assign the infecting strain type are expected to have a positive effect on epidemiologic surveillance, prevention of transmission, and clinical management of Chagas disease. Herein we describe the diversity of human antibody specificities directed to a polymorphic T. cruzi antigen, TSSA, using a combination of bioinformatics and state of the art immunoassays based on peptide arrays. Our results led to the identification of novel variants of the antigen, distinct epitopes, and their key residues for antibody binding across diverse human populations and have practical implications for the design and/or evaluation of T. cruzi serotyping strategies.
Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America
(2023) IBRAHIM, Amy; MANKO, Emilia; DOMBROWSKI, Jamille G.; CAMPOS, Monica; BENAVENTE, Ernest Diez; NOLDER, Debbie; SUTHERLAND, Colin J.; NOSTEN, Francois; FERNANDEZ, Diana; VELEZ-TOBON, Gabriel; CASTANO, Alberto Tobon; AGUIAR, Anna Caroline C.; PEREIRA, Dhelio Batista; SANTOS, Simone da Silva; SUAREZ-MUTIS, Martha; SANTI, Silvia Maria Di; BAPTISTA, Andrea Regina de Souza; MACHADO, Ricardo Luiz Dantas; MARINHO, Claudio R. F.; CLARK, Taane G.; CAMPINO, Susana
Background Brazil is a unique and understudied setting for malaria, with complex foci of transmission associated with human and environmental conditions. An understanding of the population genomic diversity of P. vivax parasites across Brazil can support malaria control strategies.Methods Through whole genome sequencing of P. vivax isolates across 7 Brazilian states, we use population genomic approaches to compare genetic diversity within country (n = 123), continent (6 countries, n = 315) and globally (26 countries, n = 885).Findings We confirm that South American isolates are distinct, have more ancestral populations than the other global regions, with differentiating mutations in genes under selective pressure linked to antimalarial drugs (pvmdr1, pvdhfr-ts) and mosquito vectors (pvcrmp3, pvP45/48, pvP47). We demonstrate Brazil as a distinct parasite population, with signals of selection including ABC transporter (PvABCI3) and PHIST exported proteins.Interpretation Brazil has a complex population structure, with evidence of P. simium infections and Amazonian parasites separating into multiple clusters. Overall, our work provides the first Brazil-wide analysis of P. vivax population structure and identifies important mutations, which can inform future research and control measures.Funding AI is funded by an MRC LiD PhD studentship. TGC is funded by the Medical Research Council (Grant no. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1). SC is funded by Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1) and Blooms-bury SET (ref. CCF17-7779). FN is funded by The Shloklo Malaria Research Unit -part of the Mahidol Oxford Research Unit, supported by the Wellcome Trust (Grant no. 220211). ARSB is funded by Sao Paulo Research Foundation -FAPESP (Grant no. 2002/09546-1). RLDM is funded by Brazilian National Council for Scientific and Technological Development -CNPq (Grant no. 302353/2003-8 and 471605/2011-5); CRFM is funded by FAPESP (Grant no. 2020/06747-4) and CNPq (Grant no. 302917/2019-5 and 408636/2018-1); JGD is funded by FAPESP fellowships (2016/13465-0 and 2019/12068-5) and CNPq (Grant no. 409216/2018-6).Copyright & COPY; 2022 The Author(s).
Characterization of Torquetenovirus in amniotic fluid at the time of in utero fetal surgery: correlation with early premature delivery and respiratory distress
(2023) TOZETTO-MENDOZA, Tania Regina; DA-COSTA, A. Charlys; MORON, Antonio F.; LEAL, Elcio; LIMA, Silvia Helena; FERREIRA, Noely Evangelista; HONORATO, Layla; PAIAO, Heuder Gustavo Oliveira; FREIRE, Wilton Santos; MENDES-CORREA, Maria Cassia; WITKIN, Steven S.
Torquetenovirus (TTV) is a commensal virus present in many healthy individuals. Although considered to be non-pathogenic, its presence and titer have been shown to be indicative of altered immune status in individuals with chronic infections or following allogeneic transplantations. We evaluated if TTV was present in amniotic fluid (AF) at the time of in utero surgery to correct a fetal neurological defect, and whether its detection was predictive of adverse post-surgical parameters. AF was collected from 27 women by needle aspiration prior to a uterine incision. TTV titer in the AF was measured by isolation of viral DNA followed by gene amplification and analysis. The TTV genomes were further characterized and sequenced by metagenomics. Pregnancy outcome parameters were subsequently obtained by chart review. Three of the AFs (11.1%) were positive for TTV at 3.36, 4.16, and 4.19 log(10) copies/mL. Analysis of their genomes revealed DNA sequences similar to previously identified TTV isolates. Mean gestational age at delivery was >2 weeks earlier (32.5 vs. 34.6 weeks) and the prevalence of respiratory distress was greater (100% vs. 20.8%) in the TTV-positive pregnancies. TTV detection in AF prior to intrauterine surgery may indicate elevated post-surgical risk for earlier delivery and newborn respiratory distress.
Association between development of severe COVID-19 and a polymorphism in the CIAS1 gene that codes for an inflammasome component
(2023) TOZETTO-MENDOZA, Tania R. R.; MENDES-CORREA, Maria Cassia; LINHARES, Iara Moreno; RAYMUNDI, Vanessa de Cassia; PAIAO, Heuder Gustavo de Oliveira; BARBOSA, Erick Matheus Garcia; LUNA-MUSCHI, Alessandra; HONORATO, Layla; CORREA, Giovanna Francisco; COSTA, Antonio Charlys da; COSTA, Silvia Figueiredo; WITKIN, Steven S. S.
An elevated pro-inflammatory cytokine response is associated with severe life-threatening symptoms in individuals with Coronavirus Disease-2019 (COVID). The inflammasome is an intracellular structure responsible for generation of interleukin (IL)-1 & beta; and IL-18. NALP3, a product of the CIAS1 gene, is the rate-limiting component for inflammasome activity. We evaluated if a CIAS1 42 base pair length polymorphism (rs74163773) was associated with severe COVID. DNA from 93 individuals with severe COVID, 38 with mild COVID, and 98 controls were analyzed for this polymorphism. The 12 unit repeat allele is associated with the highest inflammasome activity. Five alleles, corresponding to 6, 7, 9, 12 or 13 repeat units, divided into 12 genotypes were identified. The frequency of the 12 unit repeat allele was 45.3% in those with severe disease as opposed to 30.0% in those with mild disease and 26.0% in controls (p < 0.0001, severe vs. controls). In contrast, the 7 unit repeat allele frequency was 30.1% in controls as opposed to 14.0% and 12.5% in those with severe or mild disease, respectively (p & LE; 0.0017). We conclude that individuals positive for the CIAS1 12 allele may be at elevated risk for development of severe COVID due to an increased level of induced pro-inflammatory cytokine production.
Detailed characterization of Redondovirus in saliva of SARS-CoV-2-infected individuals in Sao Paulo, Brazil
(2023) COSTA, Antonio Charlys da; MENDES-CORREA, Maria C.; TOZETTO-MENDOZA, Tania Regina; VILLAS-BOAS, Lucy S.; PAULA, Anderson Vicente de; PAIAO, Heuder Gustavo Oliveira; LEAL, Fabio E.; FERREIRA, Noely E.; HONORATO, Layla; LEAL, Elcio; GRANDI, Giuliano; MORAIS, Vanessa dos Santos; MANULI, Erika R.; SABINO, Ester C.; WITKIN, Steven S.
BackgroundRedondovirus (ReDoV) is a DNA virus present in the respiratory tract of many healthy individuals. Since SARS-CoV-2, the virus responsible for COVID-19, also primarily infects the same site, we evaluated whether ReDoV was present at increased frequency in patients with COVID-19 and influenced infection parameters.MethodsSaliva samples were collected weekly from 59 individuals with COVID-19 and from 132 controls. ReDoV was detected by polymerase chain reaction and the genotypes were identified by metagenomics. Torque Teno Virus (TTV) in these samples were previously reported.ResultsReDoV was detected in saliva more frequently from COVID-19 patients (72.9%) than from controls (50.0%) (p = 0.0015). There were no associations between ReDoV detection and either continuous or intermittent SARS-CoV-2 shedding, the duration of SARS-CoV-2 detection in saliva, patients' sex or if infection was by the B1 or Gamma strain. The two ReDoV strains, Brisavirus and Vientovirus, were present in equivalent frequencies in ReDoV-positive COVID-19 patients and controls. Phylogenetic analysis suggested that the two ReDoV strains in Brazil were similar to strains previously detected on other continents.ConclusionReDoV expression in saliva is increased in males and females in Brazil with mild COVID-19 but its presence does not appear to influence properties of the SARS-CoV-2 infection.
Histopathological characteristics of cutaneous lesions caused by Leishmania Viannia panamensis in Panama
(2018) GONZÁLEZ, Kadir; DIAZ, Rosendo; FERREIRA, Aurea F.; GARCÍA, Víctor; PAZ, Héctor; CALZADA, José E.; RUÍZ, Michelle; LAURENTI, Márcia; SALDAñA, Azael
ABSTRACT Cutaneous leishmaniasis (CL) is an endemic disease in the Republic of Panama, caused by Leishmania (Viannia) parasites, whose most common clinical manifestation is the presence of ulcerated lesions on the skin. These lesions usually present a chronic inflammatory reaction, sometimes granulomatous, with the presence of lymphocytes, plasma cells and macrophages. This study describes the histopathological characteristics found in the skin lesions of patients with CL caused by Leishmania (V.) panamensis in Panama. We analyzed 49 skin biopsy samples from patients with clinical suspicion of CL, by molecular tests (PCR for subgenus Viannia and HSP-70) and by Hematoxylin-Eosin staining. Samples were characterized at the species level by PCR-HSP-70/RFLP. From the 49 samples studied, 46 (94%) were positive by PCR and were characterized as Leishmania (V.) panamensis. Of these, 48% were positive by Hematoxylin-Eosin staining with alterations being observed both, in the epidermis (85%) and in the dermis (100%) of skin biopsies. The inflammatory infiltrate was characterized according to histopathological patterns: lymphohistiocytic (50%), lymphoplasmacytic (61%) and granulomatous (46%) infiltration, being the combination of these patterns frequently found. The predominant histopathological characteristics observed in CL lesions caused by L. (V.) panamensis in Panama were: an intense inflammatory reaction in the dermis with a combination of lymphohistiocytic, lymphoplasmacytic and granulomatous presentation patterns and the presence of ulcers, acanthosis, exocytosis and spongiosis in the epidermis.
The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas
(2023) RICCI, Alejandro D.; BRACCO, Leonel; SALAS-SARDUY, Emir; RAMSEY, Janine M.; NOLAN, Melissa S.; LYNN, M. Katie; ALTCHEH, Jaime; BALLERING, Griselda E.; TORRICO, Faustino; KESPER, Norival; VILLAR, Juan C.; MARCIPAR, Ivan S.; MARCO, Jorge D.; AGUERO, Fernan
During an infection the immune system produces pathogen-specific antibodies. These antibody repertoires become specific to the history of infections and represent a rich source of diagnostic markers. However, the specificities of these antibodies are mostly unknown. Here, using high-density peptide arrays we examined the human antibody repertoires of Chagas disease patients. Chagas disease is a neglected disease caused by Trypanosoma cruzi, a protozoan parasite that evades immune mediated elimination and mounts long-lasting chronic infections. We describe a proteome-wide search for antigens, characterised their linear epitopes, and show their reactivity on 71 individuals from diverse human populations. Using single-residue mutagenesis we revealed the core functional residues for 232 of these epitopes. Finally, we show the diagnostic performance of identified antigens on challenging samples. These datasets enable the study of the Chagas antibody repertoire at an unprecedented depth and granularity, while also providing a rich source of serological biomarkers. This work reveals the diversity and extent of human antibody specificities in Chagas disease and provides a wealth of well-defined antigenic markers for diagnosis and development of serological applications for this neglected infectious disease.
SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains
(2023) MENDES-CORREA, Maria Cassia; SALOMAO, Matias Chiarastelli; GHILARDI, Fabio; TOZETTO-MENDOZA, Tania Regina; VILLAS-BOAS, Lucy Santos; PAULA, Anderson Vicente de; PAIAO, Heuder Gustavo Oliveira; COSTA, Antonio Charlys da; LEAL, Fabio E.; FERRAZ, Andrea de Barros Coscelli; SALES, Flavia C. S.; CLARO, Ingra M.; FERREIRA, Noely E.; PEREIRA, Geovana M.; JR, Almir Ribeiro da Silva; FREIRE, Wilton; ESPINOZA, Evelyn Patricia Sanchez; MANULI, Erika R.; ROMANO, Camila M.; JESUS, Jaqueline G. de; SABINO, Ester C.; WITKIN, Steven S.
Introduction-The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods-We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested via RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results-A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS-CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.
Seasonality of sporotrichosis in Brazil: A modelled analysis of the epidemic in Sao Paulo, 2011-2020
(2023) FREITAS, Vera Lucia Teixeira de; ROCHA, Francisco Marcelo Monteiro; RIBEIRO, Emanoella Nogueira; LINDOSO, Jose Angelo Laulleta; BITTENCOURT, Amanda Azevedo; PIVETTA, Dhara Nicole Araujo Greco; BENARD, Gil; FREITAS-XAVIER, Roseli Santos de
Background: Sporotrichosis is an endemic subcutaneous mycosis classically caused by the Sporothrix schenckii species complex. Recently, sporotrichosis has emerged in Brazil as a cat-transmitted epidemic caused by a new species, Sporothrix brasiliensis. Objectives: To survey the clinical-epidemiological profile of all sporotrichosis cases diagnosed between 2011 and 2020 at a reference hospital in Sao Paulo metropolitan area and evaluate the annual distribution of cases in relation to seasonality. Methods: Patients' demographic and clinical-epidemiological data were surveyed. A generalized linear model was fitted to relate the quarterly number of sporotrichosis cases detected between 2015 and 2019 with precipitation and temperature series. Prediction of the number of cases from 2011 to 2014 was attempted based on the fitted model without the trend component that appears from 2015. Results: Among 271 suspected cases admitted during 2011-2020, 254 were confirmed by fungal isolation and/or clinical-epidemiological criteria. We observed that 2015 onwards the number of cases regularly increased during Autumn and Winter, the driest and coldest stations of the year. We verified that temperature series affected the number of cases (p = .005) because an increase of 1 degrees C in the temperature series was associated with a 14.24% decrease in the average cases number, with the average number of cases increasing by 10.96% (p < .0001) every quarter, corresponding to an annual increase of 52%. Between 2011 and 2014, the predicted number of sporotrichosis cases averaged 10-12 per year, with 33%-38% occurring in the winter. Conclusion: We hypothesize that sporotrichosis seasonality is associated with the felines' oestrus cycle, which may provide alternative, cat-directed approaches to the sporotrichosis epidemic control.
Prevalence of Trypanosoma cruzi infection in a cohort of people living with HIV/AIDS from an urban area
(2023) KESPER, Norival; IGNACIO JUNIOR, Jose Carlos; ROCCI, Rafael Avila; CUNHA, Mirela A.; LINDOSO, Jose Angelo Lauletta
The prevalence rate of coinfection Chagas disease (CD) and HIV in Brazil is between 1.3 and 5%. Serological tests for detecting CD use total antigen, which present cross reactivity with other endemic diseases, such as leishmaniasis. It is urge the use of a specific test to determinate the real prevalence of T. cruzi infection in people living with HIV AIDS (PLWHA). Here, we evaluated the prevalence of T. cruzi infection in a cohort of 240 PLWHA living in urban area from Sao Paulo, Brazil. Enzyme Linked Immunosorbent Assay, using epimastigote alkaline extract antigen from T. cruzi (ELISA EAE), returned a 2.0% prevalence. However by Immunoblotting, using trypomastigote excreted-secreted antigen (TESA Blot) from T. cruzi, we detected a prevalence of 0.83%. We consider that the real prevalence of T. cruzi-infection in PLWHA is 0.83%, lower than reported in literature; this is due to TESA Blot specificity, probably excluding false positives for CD immunodiagnosis. Our results demonstrate a real need to apply diagnostic tests with high sensitivity and specificity that can help assess the current status of CD/HIV coinfection in Brazil in order to stratify the effective risk of reactivation and consequently decreasing mortality.
Recombinant protein KR95 as an alternative for serological diagnosis of human visceral leishmaniasis in the Americas
(2023) FUJIMORI, Mahyumi; VALENCIA-PORTILLO, Ruth Tamara; LINDOSO, Jose Angelo Lauletta; CELESTE, Beatriz Julieta; ALMEIDA, Roque Pacheco de; COSTA, Carlos Henrique Nery; CRUZ, Alda Maria da; DRUZIAN, Angelita Fernandes; DUTHIE, Malcolm Scott; FORTALEZA, Carlos Magno Castelo Branco; OLIVEIRA, Ana Lucia Lyrio de; PANIAGO, Anamaria Mello C. Miranda; QUEIROZ, Igor Thiago; REED, Steve; VALLUR, Aarthy; GOTO, Hiro; SANCHEZ, Maria Carmen Arroyo
In the Americas, visceral leishmaniasis (VL) is caused by the protozoan Leishmania infantum, leading to death if not promptly diagnosed and treated. In Brazil, the disease reaches all regions, and in 2020, 1,933 VL cases were reported with 9.5% lethality. Thus, an accurate diagnosis is essential to provide the appropriate treatment. Serological VL diagnosis is based mainly on immunochromatographic tests, but their performance may vary by location, and evaluation of diagnostic alternatives is necessary. In this study, we aimed to evaluate the performance of ELISA with the scantily studied recombinant antigens, K18 and KR95, comparing their performance with the already known rK28 and rK39. Sera from parasitologically confirmed symptomatic VL patients (n = 90) and healthy endemic controls (n = 90) were submitted to ELISA with rK18 and rKR95. Sensitivity (95% CI) was, respectively, 83.3% (74.2-89.7) and 95.6% (88.8-98.6), and specificity (95% CI) was 93.3% (85.9-97.2) and 97.8% (91.8-99.9). For validation of ELISA with the recombinant antigens, we included samples from 122 VL patients and 83 healthy controls collected in three regions in Brazil (Northeast, Southeast, and Midwest). When comparing the results obtained with the VL patients' samples, significantly lower sensitivity was obtained by rK18-ELISA (88.5%, 95% CI: 81.5-93.2) compared with rK28-ELISA (95.9%, 95% CI: 90.5-98.5), but the sensitivity was similar comparing rKR95-ELISA (95.1%, 95% CI: 89.5-98.0), rK28-ELISA (95.9%, 95% CI: 90.5-98.5), and rK39-ELISA (94.3%, 95% CI: 88.4-97.4). Analyzing the specificity, it was lowest with rK18-ELISA (62.7%, 95% CI: 51.9-72.3) with 83 healthy control samples. Conversely, higher and similar specificity was obtained by rKR95-ELISA (96.4%, 95% CI: 89.5-99.2), rK28-ELISA (95.2%, 95% CI: 87.9-98.5), and rK39-ELISA (95.2%, 95% CI: 87.9-98.5). There was no difference in sensitivity and specificity across localities. Cross-reactivity assessment, performed with sera of patients diagnosed with inflammatory disorders and other infectious diseases, was 34.2% with rK18-ELISA and 3.1% with rKR95-ELISA. Based on these data, we suggest using recombinant antigen KR95 in serological assays for VL diagnosis.
In vitro miltefosine and amphotericin B susceptibility of strains and clinical isolates of Leishmania species endemic in Brazil that cause tegumentary leishmaniasis
(2023) FERREIRA, Bianca A.; COSER, Elizabeth M.; SABORITO, Cristiele; YAMASHIRO-KANASHIRO, Edite H.; COELHO, Adriano C.; LINDOSE, Jose Angelo L.
Tegumentary leishmaniasis encompasses a spectrum of clinical manifestations caused by the parasitic protozoa of the genus Leishmania. In Brazil, there are at least seven Leishmania species that are endemic and responsible for this set of clinical manifestations of the disease. Current treatment is limited to a restricted number of drugs that in general have several drawbacks including parenteral use, toxicity, and severe side effects. Amphotericin B is considered a second-line drug for tegumentary leishmaniasis in Brazil, while miltefosine was recently approved for clinical use in the treatment of this disease. In this study, we investigated the in vitro susceptibility of Leishmania strains representative of the species endemic to Brazil, as well as a panel of thirteen clinical isolates of tegumentary leishmaniasis, to both amphotericin B and miltefosine. A moderate variation in the susceptibility to both drugs was found, where the EC50 values varied from 11.43 to 52.67 mu M for miltefosine and from 12.89 to 62.36 nM for amphotericin B in promastigotes, while for the intracellular amastigotes, values ranged from 1.08 to 9.60 mu M and from 1.69 to 22.71 nM for miltefosine and amphotericin B respectively. Furthermore, the clinical isolates and strains of the subgenus Viannia were evaluated for the presence of Leishmania RNA virus 1 (LRV1), as this is an important factor associated with disease severity and treatment outcome. These findings provide a preclinical dataset of the activity of these drugs against the causative species of tegumentary leishmaniasis in Brazil.

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