Memorias do Instituto Oswaldo Cruz最新文献

Plants represent an important source of compounds for treating malaria, highlighting the rich biodiversity of Brazilian flora as a vital resource for developing new, effective antimalarial drugs. The present study sought to shed light on the search for new compounds with antimalarial activity obtained from the Brazilian flora. In this sense, a systematic review was conducted using screening techniques based on "The Preferred Reporting Items for Systematic Reviews and Meta-Analysis" (PRISMA) protocol. Most of the plants collected in the studies were from the Amazon Rainforest, north of Brazil. Most of the isolated compounds were from the Apocynaceae family and the alkaloids were the main compounds isolated with significant antiplasmodial activity, followed by flavonoids and phenolic compounds. The Brazilian flora can source many compounds with potential antimalarial activity that can challenge Plasmodium drug resistance. However, new studies are still needed to elucidate the natural compounds activity for future application in Malaria treatment.

Background: Miltefosine (MIL) is the only oral drug approved for leishmaniasis treatment, but its use is limited by gastrointestinal toxicity. Novel alkylphospholipid analogues may provide safer and more effective alternatives.

Objectives: This study aimed to assess the antileishmanial activity, cytotoxicity, and membrane interactions of three MIL analogues TC387, TC388, and TC437 against Leishmania amazonensis.

Methods: Antileishmanial and cytotoxic activities were evaluated in L. amazonensis, J774.A1 macrophages, and erythrocytes. Membrane interactions were characterized using spin-label electron paramagnetic resonance (EPR) spectroscopy.

Findings: TC387, TC388, and TC437 demonstrated EC50 values of 10-16 µM for intracellular amastigotes, compared to 17 µM for MIL, with selectivity indices (SI) ranging from 43-163, significantly higher than MIL's SI of 5. EPR data revealed that the analogues increased membrane protein dynamics and caused greater disruption at the lipid-protein interface of parasite membranes relative to MIL. This disruption likely enhances pore formation, ion leakage, and reactive oxygen species (ROS) production, leading to parasite death.

Main conclusions: The MIL analogues TC387, TC388, and TC437 exhibited superior SI and comparable or slightly enhanced antileishmanial activity relative to MIL, along with very low hemolytic potential. These findings support further investigation of these analogues as promising oral therapeutic candidates for leishmaniasis.

Background: Leprosy is an infectious disease that remains hyperendemic in several Brazilian regions. Patient contacts face a higher risk for infection and illness, which can subsequently contribute to the persistence of the disease.

Objective: This study investigates the risk factors associated with anti-phenolic glycolipid-I (anti-PGL-I) seropositivity and leprosy development among contacts of leprosy patients in a highly endemic region.

Methods: A cohort of 629 contacts from the Almenara microregion, Minas Gerais, Brazil, was followed from 1998 to 2018. Our research group assessed risk factors, including sociodemographic determinants, bacillus exposure, and genetic susceptibility.

Findings: Analysis revealed that living with a multibacillary (MB) leprosy patient [odds ratio (OR): 3.01, 95% confidence interval (CI): 1.02-8.86] and with a patient with grade II disabilities (OR: 4.43, 95% CI: 1.08-18.1) significantly increased the likelihood of anti-PGL-I seropositivity among asymptomatic contacts. Risk factors for leprosy included living with a patient in a shared residence (OR: 2.84, 95% CI: 1.21-6.67) and blood relation to the patient (OR: 2.56, 95% CI: 1.18-5.54). Notably, 98% of contacts who developed leprosy had lived with more than one patient.

Main conclusions: Clinical characteristics of index patients play a critical role in infection risk among contacts. Leprosy progression appears to depend on genetic susceptibility, type of contact, and extent of bacillus exposure.

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.