Memorias do Instituto Oswaldo Cruz最新文献

Background: Single nucleotide polymorphisms (SNP) in genes encoding cytokines influence tuberculosis (TB) outcomes.

Objectives: To characterise genotypes of the SNPs IFN-gamma +874 T > A, TNF-alpha -308 G > A, IL-6 -174 G > C, IL-10 -1082A > G, TGF-beta codon 10 T > C, and TGF-beta codon 25 G > C in patients with pulmonary (PTB) and extrapulmonary TB (EPTB).

Methods: 82 PTB and 45 EPTB cases were compared, concerning genotype distribution of the mentioned SNPs, characterised via sequence-specific primer polymerase chain reaction (PCR).

Findings: Regarding IFN-gamma +874 T > A, AA genotype was the most frequent in both groups, TA was more frequent in PTB and TT in EPTB, with no statistical significance. For SNP TNF-alpha -308 G > A, GG was more frequent in both groups of patients. Regarding the IL-6 -174 G > C polymorphism, GG predominated in both groups, while CG and GG were significantly more frequent in patients with PTB and EPTB, respectively. Concerning IL-10 -1082 A > G, AA predominated in both PTB and EPTB. Concerning TGF-beta codon 10 T > C, CC predominated in PTB while TC predominated in EPTB, but the differences were not statistically significant. Genotype GG of TGF-beta codon 25 G > C predominated among PTB and EPTB patients.

Main conclusions: Except for IL-6, the genotype profile could not differentiate PTB and EPTB. Hence, the studied SNPs are not significantly associated with the extrapulmonary involvement of TB.

Background: Schistosomiasis is one of the most devastating tropical diseases in developing countries and is usually misdiagnosed with colitis because the prevalence of co-occurrence of both diseases is high. Previously, infection of Schistosoma japonicum cercariae has been shown to provide immediate protection against dextran sodium sulphate (DSS)-induced acute colitis in mice models. Studies using synthesised peptides or soluble proteins from parasites also revealed similar protection against colitis. However, most of these studies were done within a short timeframe, which cannot completely represent the actual situation where natural infection of Schistosoma or colitis is usually chronic.

Objectives: This study aims to investigate how chronic schistosomiasis affects chronic intestinal inflammation.

Methods: Mice were infected with Schistosoma mansoni and induced simultaneously with chronic colitis. The symptoms and severity of intestinal inflammation and fibrosis were investigated by disease activity index, histology, enzyme-linked immunosorbent assay (ELISA), and quantitative polymerase chain reaction (qPCR). Furthermore, immune analysis by ELISA and qPCR and microbiome analysis by 16S rDNA sequencing were done to investigate the underlying mechanism.

Findings: Concomitant occurrence of chronic schistosomiasis and chronic colitis significantly alleviated colitis symptoms, lessened intestinal inflammation, and reduced egg-induced fibrosis. Further analysis revealed an alternation of the intestinal immunity and gut microbiome community in mice with both diseases, which could be the potential reason for this outcome.

Main conclusions: Our results represent a mechanism of how schistosomiasis and chronic intestinal inflammation affect each other.

Background: Despite insufficient parasitological and clinical evidence, infections attributed to a putative protozoan named "Urbanorum spp." have been associated with gastrointestinal disease and treated with anti-parasitic drugs.

Objectives: This study aimed to clarify the nature of "Urbanorum spp." and provide guidance for health and biomedical professionals encountering this structure in human stool, emphasising the importance of rigor and quality in biomedical research.

Methods: Coprological analyses were employed to detect intestinal parasites, lipids, and "Urbanorum spp." in 249 samples. Samples positive for "Urbanorum spp." underwent staining with trichrome, acid-fast, and Sudan IV and contrasted with positive controls. Examination with polarised light microscopy and a fragility test using ethanol were conducted.

Findings: Of the tested samples, 19.4%, 2.5% and 1.3% were positive for intestinal parasites, lipids, and "Urbanorum spp." respectively. Following trichrome and acid-fast staining, few "Urbanorum spp." structures remained intact and exhibited no discernible eukaryotic characteristics; Sudan IV stain, polarized light microscopy and fragility test approaches indicated a cholesterol-based content.

Main conclusions: "Urbanorum spp." is not a protozoan parasite; therefore, antiparasitic drugs are unwarranted. This structure should be identified as lipid-based material and investigated for possible malabsorption syndrome. Rigorous scientific standards were missed in related publications and peer review, contributing to the spread of this pseudoparasitism case.

Background: Coinfections of Plasmodium parasites and the dengue virus have been linked to severe disease in some patients. The interactions between these two pathogens, particularly their effects on disease progression, highlight the clinical importance of understanding the mechanisms underlying the potential synergistic effects.

Objectives: The primary objective of this study was to investigate the adhesion dynamics of Plasmodium vivax-infected erythrocytes (Pv-iRBCs) in the presence of dengue virus (DENV) infection. By examining the interaction between these pathogens, the study aimed to provide insights into how coinfections might influence disease severity and progression.

Methods: HepG2 cells were infected with DENV to observe changes in adhesion receptors and Pv-iRBCs adhesion capacity. Experiments using trypsin-treated Pv-iRBCs and UV-inactivated DENV dissected the adhesion process. Small molecule inhibitors were used to assess innate activation. ICAM-1 expression and its functional significance was quantified using a monoclonal anti-ICAM-1 antibody.

Findings: We noted a significant increase in cytoadherence of Pv-iRBCs following DENV infection compared to mock conditions. Both trypsin treatment of Pv-iRBCs and UV inactivation of DENV led to a reduction in cytoadherence, underscoring their impact on the adhesion process. Notably, DENV infection induces an innate immune activation upregulating ICAM-1 on the cell surface and blocking with a monoclonal anti-ICAM-1 antibody significantly reduced the cytoadherence of Pv-iRBCs.

Main conclusions: Elevated ICAM-1 levels on DENV-permissive cells may not only trap parasites within several niches but also contribute to endothelial and haematological disturbances in individuals with coinfections. Further research is required to fully elucidate the roles of cytoadherence and immune activation in the pathogenesis of dengue and malaria coinfections.

Background: The experience of the USP Tropical Medicine Centre (NUMETROP) team in providing medical care during acute Chagas disease (ACD) outbreaks in Santarém, Pará, motivated this study.

Objectives: To study the epidemiological, clinical-laboratory, and socio-cultural aspects of confirmed cases of ACD in outbreaks in Santarém from March 2016 to March 2018.

Methods: Observational case series study of ACD outbreaks in two communities: Marimarituba in 2016 and Cachoeira do Aruã in 2017. Diagnostic characterisation included classification into discrete typing units (DTUs).

Findings: Eight cases were diagnosed as ACD TcIV in Marimarituba and seven cases were identified as ACD TcI in Cachoeira do Aruã. Women of childbearing age were numerous in both groups, and one miscarriage and two possible vertical transmissions were observed. Fever and rash were the most common findings in Marimarituba, with a fatality rate of 12.5%. In both outbreaks, serological surveillance was performed three to 21 months after treatment, with no confirmation of a "serological cure".

Main conclusions: We observed possible vertical transmission, diverse DTUs in the same municipality, and a lack of knowledge about patient outcomes. We highlight that, despite the importance of ACD in the Amazon region, there is no institutional follow-up of patients from diagnosis to cure.

Background: Coronavirus disease 2019 (COVID-19) is caused by the new coronavirus 2 (severe acute respiratory syndrome coronavirus 2 - SARS-CoV-2). Long COVID is a new condition associated with persistent COVID-19 symptoms and/or new emerging symptoms. Telomeres are specialised structures for genome protection at the end of chromosomes and telomerase is the enzyme that synthesises telomere DNA.

Objectives: Patients with Long COVID symptoms were recruited at the Pedro Ernesto University Hospital (HUPE) in Rio de Janeiro, Brazil, with the main purpose of investigating the association between telomere length and Long COVID.

Methods: Leukocyte telomere length (LTL) was determined by quantitative real-time polymerase chain reaction (qPCR) in 34 Long COVID patients compared to a control group (n = 122). Telomerase activity was determined by qPCR assays using the commercial kit from ScienCell. A questionnaire on symptoms, vaccine doses and blood count was completed.

Findings: The Long COVID patients were found to have an increase in LTL. Telomerase activity was also examined in a smaller number of patients and found to be reactivated in the blood.

Main conclusions: It will be necessary to conduct further studies and monitor Long COVID patients to determine if future health issues could be linked to telomerase activity and elongated telomeres.

Background: Escherichia coli is a commensal organism but may become pathogenic by the acquisition of virulence factors involved with intestinal (IPEC) or extraintestinal (ExPEC) infections. Some strains, known as hybrids, may harbour virulence determinants of both IPEC and ExPEC pathotypes, increasing their virulence potential. Reports of hybrid E. coli in Brazil are rare, and the associated lineages were poorly explored.

Objectives: This study characterised ExPEC E. coli strains focusing on the occurrence of hybrid pathotypes.

Methods: Fifteen clinical ExPEC strains were submitted to multilocus sequence typing (MLST), susceptibility test, and polymerase chain reaction (PCR) targeting IEC/ExPEC virulence markers.

Findings: All strains were multidrug-resistant, and 11 STs were determined among the 15 ExPEC strains, including local/new and pandemic lineages, such as ST69 and ST131. Twelve/15 isolates were classified as hybrids, due to the presence of virulence markers of both Enteroaggregative E. coli (EAEC) and ExPEC or UPEC pathotypes. These UPEC/EAEC (n = 10) and ExPEC/EAEC (n = 2) hybrid strains were found among distinct phylogroups and lineages, including new STs. Interestingly, most hybrids belonged to the pandemic ST131 lineage, and this genotype had never been previously reported in the ST131 circulating in Brazil.

Main conclusions: Therefore, this study provides new information on the epidemiological scenario of hybrid E. coli, contributing to a better understanding of the occurrence and pathogenic potential of these organisms.

Background: Leprosy, a neglected tropical disease caused by Mycobacterium leprae, presents significant public health challenges in Brazil due to its slow progression, dermato-neurological manifestations, and potential for disability. Understanding leprosy's spatial distribution and temporal trends is important for effective control and elimination strategies.

Objectives: This study aimed to identify clusters of leprosy in Brazilian states using agglomerative hierarchical clustering and to analyse their temporal trends from 2012 to 2022.

Methods: An ecological study was conducted using data from the National System of Notifiable Diseases (SINAN). The agglomerative hierarchical clustering method was used to group states using the new case detection rate (NCDR) of leprosy per 100,000 inhabitants, the proportion of new cases of leprosy with grade 2 physical disability at the time of diagnosis (G2R), and the Gini index, a measure of socioeconomic inequality. Temporal trends within the clusters were assessed using Prais-Winsten regression analysis.

Findings: In the period 2012-2022, 293,030 new cases of leprosy were reported in Brazil. Five distinct clusters were identified. Cluster 4, comprising Mato Grosso and Tocantins, had the highest NCDR and stable temporal trends (APC: 3.2%, 95% CI: -0.1%, 6.7%). Clusters 1 and 3 had the highest proportions of grade 2 disability, indicating late diagnosis. Clusters 4 and 5 had the lowest percentages of individuals with incomplete/complete higher education (7.6% and 7.4%, respectively). Cluster 4 had the highest percentage of individuals with the Diforma clinical form (69.8%) and with cases classified as multibacillary (84.5%).

Main conclusions: The use of agglomerative hierarchical clustering, a novel application of a non-supervised algorithm in this context, highlighting the integration of multiple epidemiological and socioeconomic variables for a better understanding the dynamics of leprosy transmission in Brazil. Significant variations in the spatial distribution and temporal trends of leprosy were observed across Brazilian states. To improve leprosy surveillance and control in Brazil, targeted interventions are needed, particularly in high-endemicity regions with late diagnosis.

Background: Chronic Chagas cardiomyopathy (CCC) is the most severe clinical form of the Chagas disease. There is a strong correlation between soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2) and cardiac and functional parameters in CCC, but their prognostic value remains unknown.

Objective: To verify the prognostic value of sTNFR1 and sTNFR2 in CCC.

Methods: A longitudinal study was conducted. Sixty-nine patients with CCC (53.70 ± 9.66 years, NYHA I-II) were submitted to blood collection and echocardiography, and followed for 43.81 ± 1.21 months. The outcome was determined by the combination of cardiac death, heart transplantation, or stroke.

Findings: After the follow-up, 15 patients (22%) presented adverse cardiovascular events. Only left ventricular ejection fraction (LVEF) [heart rate at rest (HR): 0.935, 95% CI 0.878 to 0.994; p = 0.033] and sTNFR2 (HR: 1.002, 95% CI 1.001 to 1.003; p = 0.006) remained as independent predictors of adverse cardiovascular events. The optimal cutoff point to identify these patients was the value of 1784.00 pg/mL. There was a significant difference between the groups with lower and higher sTNFR2 levels (long-rank < 0.001).

Main conclusions: High serum levels of sTNFR2, together with lower LVEF, are strong independent predictors of adverse cardiovascular events in CCC, making them valuable for risk stratification.

Background: Tanychlamys indica (Godwin-Austen, 1883) was reported as a serious pest in India. The snails are voracious and feed on a wide range of commercial crops. It has also been identified as an intermediate nematode host of Angiostrongylus cantonensis in Bombay, India. T. indica was recently introduced in Brazil by international trade of citrus fruit seedlings. First in the State of Santa Catarina and then in Paraná. Recently, it has been detected in the city of São Paulo threatening to spread to other Brazilian states.

Objectives: We report the first record, in Brazil, of the natural infection by L3 larvae of A. cantonensis isolated from T. indica collected in the Vila Leopoldina neighbourhood, located in the west zone of São Paulo city.

Methods: In January 2023, a team from LABFAUNA and UVIS Lapa collected 36 molluscs identified as T. indica in Vila Leopoldina, São Paulo city. Of these, 20 molluscs were subjected to individual parasitological analysis at the Instituto Adolfo Lutz, using the modified Rugai methodology.

Findings: A total of 145 larvae were identified morphologically and classified according to Ash's criteria. These larvae were identified as third - stage larvae (L3) of A. cantonensis by real time polymerase chain reaction (PCR).

Main conclusions: It is evident that further research is imperative to map the distribution of T. indica in Brazil and to assess its potential as an intermediate host for the nematode A. cantonensis, as well as the economic risks to agriculture. Over the past two decades, human cases of neuroangiostrongyliasis have been documented in the Southeast, North, Northeast, and South regions of Brazil. Additionally, there are records of natural infection with A. cantonensis in molluscs and rodents.