Revista Do Instituto De Medicina Tropical De Sao Paulo最新文献

Multidrug-resistant (MDR) Klebsiella pneumoniae, particularly the lineages resistant to carbapenems and aminoglycosides, is an escalating global public health threat across human, animal, and environmental reservoirs. We examined phenotypic and genetic features of MDR K. pneumoniae isolates. A total of 70 K. pneumoniae strains were collected from clinical (n=55), environmental (n=7), and animal (n=8) sources. To better understand the evolutionary relationship between these isolates, a phylogenetic analysis was performed alongside 35 publicly available K. pneumoniae genomes from NCBI and Pathogenwatch. Whole-genome sequencing (WGS) revealed that 43 isolates carried the blaKPC gene, including blaKPC-2 and blaKPC-3 variants, with different susceptibility profiles to aminoglycosides. Among all isolates, 84% (n = 59/70) were resistant to amikacin and 53% (n = 37/70) were resistant to gentamicin. Aminoglycoside resistance was primarily associated with aminoglycoside-modifying enzymes, including aph(3')-Ia (52%), aac(3)-IIa/aadA2 (49%), and aac(6')-Ib-cr (37%). Additionally, 16S rRNA methyltransferases rmtB and rmtG were detected in 14% of isolates and were associated with high-level amikacin MICs. Overall, 81% of strains were non-susceptible to at least one aminoglycoside, underscoring the clinical importance of these determinants. Phylogenetic analysis based on WGS data showed two main clusters (A and B), and the multilocus sequence type ST11 predominated among Brazilian isolates. Our findings showed a heterogeneous distribution of sequence type profiles across the two clusters and a close relationship between K. pneumoniae strains from human, animal, and environmental sources, highlighting the need for integrated One Health surveillance.

Catheter-associated urinary tract infections (CAUTIs) are a prevalent and preventable healthcare-associated infection that significantly impacts healthcare systems, contributing to increased patient morbidity, length of stay, and costs. This systematic review aims to evaluate the effectiveness of various interventions in reducing CAUTI incidence in healthcare settings. Following the PRISMA guidelines, we conducted a thorough literature search across multiple databases-Web of Science, Scopus, PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Google Scholar-up to August 8, 2024. Eligible studies included randomized controlled trials, case-control studies, and experimental designs that met inclusion criteria, namely CAUTIs prevention among hospitalized adult patients. After screening 9,476 titles and abstracts, we reviewed 163 texts in full. Of these, 12 studies were included in this review. Results showed that antiseptic solutions like chlorhexidine, specialized catheters (e.g., BIP Foley and silver alloy-coated types) and educational sessions all significantly reduced CAUTI rates, with some interventions achieving reductions as high as 94%. Reminder systems promoting timely catheter removal and amikacin bladder washing also showed notable effectiveness. Adverse effects were minimal. This review underscores the importance of evidence-based CAUTI prevention strategies and the need for consistent implementation across healthcare facilities. Enhanced catheter maintenance practices and judicious catheter use can significantly reduce CAUTI rates, thereby improving patient outcomes and reducing healthcare-associated costs. Future research should continue exploring diverse, context-specific interventions to address barriers to CAUTI prevention.

Mycoplasma pneumoniae pneumonia (MPP) is a common pediatric respiratory infection linked to excessive immune-inflammatory responses. This study investigated the role of the Notch ligand DLL4 in the immunopathogenesis of MPP by assessing its expression in peripheral blood mononuclear cells of affected children. A total of 128 children with MPP and 35 controls were recruited. PBMCs were analyzed for the expression of Notch ligands (Jagged1, Jagged2, DLL1, DLL4) using real-time PCR. Lymphocyte subsets were assessed via flow cytometry, and cytokine levels were measured using ELISA. Clinical data were compared between severe and mild MPP cases, and correlations between DLL4 expression and immune indicators were evaluated. DLL4 expression was significantly higher in the MPP and severe MPP groups than in controls (P < 0.01). MPP patients showed lower CD3+ and CD3+CD4+ lymphocyte levels, and higher CD3+CD8+ and CD3-CD19+ levels compared with controls (P < 0.001). Plasma levels of IFN-γ, IL-17, and IL-36α were elevated in MPP patients (P < 0.001), whereas IL-4 and IL-10 levels were reduced (P < 0.01). Severe cases had higher IFN-γ, IL-17, and IL-36α levels than mild cases (P < 0.05). DLL4 expression positively correlated with plasma IFN-γ and IL-17 levels in MPP patients (P < 0.05). Elevated DLL4 expression in MPP patients, particularly in severe cases, suggests its role in enhancing Th1/Th17-mediated immune responses while suppressing Th2 pathways. Such findings implicate the Notch signaling pathway, via DLL4, in the immunopathogenesis of MPP and highlight its potential as a therapeutic target for modulating immune responses in severe MPP.

Candidemia is a leading cause of bloodstream infection-associated morbidity and mortality, particularly among critically ill patients. Time to detection (TTD) is crucial, but standard blood culture systems often fail to recover yeasts, filamentous fungi, or identify fungi in polymicrobial infections. The BD BACTEC™ Mycosis IC/F bottle was designed to improve fungal detection, yet comparative performance data are limited. This study aimed to compare the detection rate and TTD of BD BACTEC™ Mycosis IC/F with those of standard BD BACTEC™ Plus Aerobic/F and BD BACTEC™ Plus Anaerobic/F bottles using simulated models of fungemia and mixed fungal-bacterial bloodstream infections. This in vitro study included 333 blood culture bottles inoculated with Candida spp., Cryptococcus neoformans, Trichosporon asahii, Fusarium spp., and Aspergillus terreus, as well as bottles simulating coinfections with multidrug-resistant Gram-negative bacteria. All bottles were incubated in the BD BACTEC™ FX system for up to 14 days. BD BACTEC™ Mycosis IC/F achieved 100% detection for Candida spp., outperforming BD BACTEC™ Plus Anaerobic/F (58.5%) and matching BD BACTEC™ Plus Aerobic/F. It showed shorter TTDs for Nakaseomyces glabratus, Candidozyma haemuli, Meyerozyma guilliermondii, and molds. In mixed infections, BD BACTEC™ Mycosis IC/F provided better fungal recovery, especially at low inocula, although recovery was impaired when coinoculated with carbapenemase-producing bacteria. In conclusion, BD BACTEC™ Mycosis IC/F improved fungal detection and recovery compared with standard bottles, including in polymicrobial settings. Its use may enhance diagnostic yield in suspected fungemia, though cost and limited availability may limit widespread adoption.

This study examines the prevalence of anti-Leishmania IgG antibodies and Leishmania spp. infections among Brazilian kidney transplant recipients and their living donors before and after transplantation. A total of 48 donor-recipient pairs were recruited from July 14, 2022, to December 18, 2023. ELISA was used to test donors and recipients with a crude antigen of Leishmania major-like (Lm-ELISA), along with recombinant Lb6H (rLb6H-ELISA) and K39 (rK39-ELISA). Additionally, PCR was used to test recipients. Of the 48 donors, 25 (52.1%, 95%CI: 38.3-65.5) tested positive with Lm-ELISA, 4 (8.3%, 95%CI: 2.8-20.1) with rLb6H-ELISA, and 2 (4.2%, 95%CI: 0.4-14.8) with rK39-ELISA. Before transplantation, 31 recipients (64.6%, 95%CI: 50.4-76.6) were positive with Lm-ELISA, 5 (10.4%, 95%CI: 4.1-22.6) with rLb6H-ELISA, 1 (2.1%, 95%CI: <0.01-11.9) with rK39-ELISA, and 2 (4.2%, 95%CI: 0.4-14.8) with PCR. At 365 days post-transplant, 35 recipients underwent serological and molecular testing. Of these, 14 (40.0%, 95%CI: 25.5-56.5) tested positive with Lm-ELISA, 4 (11.4%, 95%CI: 3.9-26.5) with rLb6H-ELISA, 0 (0.0%, 95%CI: 0.0-11.8) with rK39-ELISA, and 2 (5.7%, 95%CI: 0.6-19.6) with PCR. Combining serological and molecular methods showed promising potential for early detection and ongoing monitoring of leishmaniasis in kidney transplant recipients and their donors. These findings highlight the urgent need for regulatory measures to implement Leishmania-specific donor screening and recipient monitoring using PCR and targeted serological tests, as well as close observation of signs and symptoms of leishmaniasis.

For decades, research and development toward malaria vaccine has prioritized infections caused by Plasmodium falciparum, since it is the species responsible for the most severe cases of malaria, which results in a comparatively smaller number of studies devoted to Plasmodium vivax. This disparity is due to complexities inherent in the biology of P. vivax, including the formation of hypnozoites in the pre-erythrocytic phase, difficulties in establishing robust in vitro culture systems, and the absence of fully representative experimental models. Among the antigens investigated for vaccine formulations, the Plasmodium vivax circumsporozoite surface protein (PvCSP) stands out for its immunogenic potential and the partial protection observed in preclinical studies. However, clinical trials with PvCSP-based vaccines have not yet demonstrated a consistent protective response. This review aims to show a historical overview of the studies that have evaluated the potential of vaccines based on the PvCSP protein, as well as to explore the innovative approaches that have been investigated in the last decade to overcome the challenges and advance the development of an effective vaccine against malaria caused by P. vivax.

Despite its 100% lethality and approximately 59,000 human deaths every year, rabies still lacks an effective treatment. Numerous trials have aimed to impair the life cycle of Lyssavirus rabies (RABV), the primary worldwide lyssavirus causing rabies, but with limited success. Treatments targeting host factors and attempting to mitigate the damage caused by RABV have also been unsatisfactory. This article describes the effects of intracerebral transfection of anti-RABV recombinant monoclonal nanobodies as antivirals against rabies in vivo, in a post-exposure protocol. Mice were intranasally inoculated with the RABV CVS strain and, 72 h later, were injected via the intracerebral route with two different anti-RABV llama-derived VHH nanobodies complexed with a transfection agent. One of the VHHs was able to reduce the viral load in mice, but no significant effect on survival was detected. Though not completely effective, nanobody therapy could be attempted in association with other antivirals to improve therapies against rabies.

The COVID-19 pandemic continues to highlight the significant impact of pre-existing comorbidities on disease progression and patient outcomes due to the risk factors for severe disease in unvaccinated patients. We evaluated the association between several clinical/laboratory findings and comorbidities in a cohort of unvaccinated patients hospitalized in the intensive care unit in Recife, Pernambuco State, Brazil. We enrolled 36 unvaccinated volunteers, and performed clinical, biochemical, hematological, and microbiological analyses. Cellular immunity, cytokine measurement, and gene expression were also analyzed. Additionally, serum samples were submitted to serological and neutralization assays by using SARS-CoV-2 B.1 Lineage, Gamma (P.1), Delta (B.1.617.2-like), and Omicron (BA.1) variants. Hypertension was the most common comorbidity in patients requiring oxygen supplementation, followed by diabetes and metabolic syndrome. Such conditions were linked to increased disease severity, with elevated levels of inflammatory biomarkers (D-dimer, C-reactive protein), neutrophilia, and lymphopenia. Chronic inflammation, which is often seen in diabetes and metabolic syndrome, worsens the inflammatory response triggered by COVID-19, which exacerbates endothelial injury and leads to a hypercoagulable state. Additionally, patients with comorbidities had impaired humoral immunity, and showed reduced seroconversion and neutralizing activity, which hindered their ability to combat the virus effectively. Furthermore, this study revealed that patients with diabetes and metabolic syndrome had an exaggerated Th17-driven immune response, which contributed to severe outcomes and multi-organ failure. These findings underscore the importance of personalized care and targeted interventions for patients with comorbidities, thus highlighting the need for further research on metabolic disorders, immune dysfunction, and COVID-19.

Leptospirosis, a neglected zoonotic disease of global relevance, particularly affects populations in socio-environmentally vulnerable regions. In tropical countries such as Brazil, the prevalence of leptospirosis increases significantly during floods, increasing human exposure to contaminated environments. This study aims to investigate the spatiotemporal distribution and prevalence of confirmed leptospirosis cases in Espirito Santo State, Brazil, from 2020 to 2024. This ecological study used secondary data from the Espirito Santo State Health Department and population estimates from the Brazilian Institute of Geography and Statistics. Prevalence rates were calculated by municipality. Kernel density estimation was used to assess spatial clustering. A total of 344 confirmed cases were reported during the study period, with the highest prevalence in the Southern and Metropolitan mesoregions. Most cases occurred in urban areas and predominantly affected economically active men aged 20-59 years. These findings highlight the influence of socio-environmental determinants on leptospirosis distribution and reinforce the importance of geospatial tools in finding high-risk areas and supporting targeted public health strategies.

Chikungunya virus (CHIKV) is globally distributed and transmitted by Aedes mosquitoes, with a mortality rate of 0.8/1,000 cases. The heart is the second most affected organ, with the osteoarticular system being the first. Cardiac involvement ranges from acute symptoms like myocarditis and exacerbation of pre-existing conditions to long-term complications such as dilated cardiomyopathy. While a direct association between CHIKV and acute myocardial infarction (AMI) is rare, systemic inflammation associated with chronic post-Chikungunya arthritis may destabilize atherosclerotic plaques, increasing AMI risk. This case report describes an AMI with non-obstructive coronary arteries in a previously healthy 24-year-old male infected with CHIKV. He presented low back pain, nausea, sweating, dyspnea, progressive leg edema, fever, and polyarticular pain in the knees and ankles. He was in critical condition upon admission, with decreased consciousness and hemodynamic instability, requiring transfer to the intensive care unit. He died 24 h later. Autopsy revealed a significantly enlarged heart, no visible atherosclerosis in the coronary arteries, and an extensive infarction in the interventricular septum. Histology showed coagulation necrosis, alveolar hemorrhage, and hepatic congestion. RT-PCR for CHIKV was detected in the lungs and heart tissues, while tests for other infectious diseases were negative. Studies highlight the role of mitochondrial antiviral signaling protein (MAVS) in protecting cardiac tissue from chronic CHIKV-related effects. Impaired MAVS signaling may enable continued viral replication, leading to myocarditis and vascular inflammation. Co-infection with dengue fever further increases the risk of cardiac complications. Postmortem analysis is essential to confirm CHIKV-related cardiac deaths and improve understanding and management of severe manifestations.