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

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.

[This corrects the article doi: 10.1590/S1678-9946202567040].

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.

Trypanosoma cruzi can be transmitted by blood transfusion in non-endemic areas, and in endemic areas the risks may be higher. We investigated the seroprevalence of anti-T. cruzi antibodies in 1,500 blood donors from a blood bank in an endemic area where Triatoma dimidiata constitutes the main vector and in 2,800 healthy young subjects. Choosing antigens is crucial in diagnostic tests as it directly influences performance across regions. We screened 1,500 blood donors in parallel for chimeric Trypanosoma cruzi antigens with the ABBOTT PRISM Chagas assay at the State Blood Transfusion Center and with an in-house ELISA assay using local T. cruzi antigenic extracts at a Biomedical Research Center laboratory. Overall, 13 T. cruzi isolates from the Yucatan Peninsula, Mexico, were characterized for their antigenic profiles before being used in an in-house ELISAs. All T. cruzi isolates shared immunodominant antigens among themselves and with South American strains (particularly those below 100 kDa). Seroprevalence of anti-T. cruzi antibodies in blood donors totaled 0.2% (3/1500) in the ABBOTT PRISM Chagas assay and 0.26% (4/1500) in the in-house ELISA. We found low sensitivity (33%; 95%CI 0.01710 to 0.8815), high specificity (99.8%; 95%CI 0.9941 to 0.9995), and a low kappa index (0.2). Seroprevalence in young subjects totaled 0.14 %. We found comparable seroprevalence to blood banks in large Mexican municipalities free of vector transmission. Thus, optimal public immunodominant antigens are needed to cover the broad immune spectrum induced by T. cruzi infection.

This study aims to evaluate strategies for diagnosing Chagas disease (CD) using rapid tests and risk questions in an endemic area. This is an analytical cross-sectional study conducted with 751 individuals from two municipalities in an endemic region for CD in the North of Minas Gerais State, Brazil. Participants answered a questionnaire with personal information and the risk criteria for CD infection recommended by the Clinical Protocol and Therapeutic Guidelines for Chagas disease (PCDT). Subsequently, they underwent capillary blood collection for the rapid diagnostic test (RDT). Individuals with a positive RDT result, along with negative controls, underwent venipuncture for serological testing. The mean age of participants was 51.4 (±18.2) years, most were female (n=434/57.8%). In the RDT, 699 (93.1%) individuals tested negative; of these, 109 (15.6%) underwent serology and 4 (3.7%) tested positive. Among the 52 (6.9%) individuals with a positive RDT result, 48 (94.1%) had their result confirmed by the serological tests. RDT result, age, and risk factors-except for blood transfusion before 1992-were statistically associated with positive serology for CD. The RDT demonstrated high sensitivity (0.92; 95% CI: 0.81-0.92) and specificity (0.97; 95%CI: 0.92-0.99).

The Candida genus colonizes the oral mucosa of immunocompetent individuals and healthy people, which is maintained by the innate immune system. However, any disturbance in this relationship, such as immunodepression, can turn this normally harmless yeast into a dangerous pathogen. This study evaluates the prevalence and risk factors for oral candidiasis (OC) among patients hospitalized in the dermatology department of a tertiary public hospital and identifies the Candida species involved. This cross-sectional study involves 240 patients. Oral candidiasis was diagnosed via clinical evaluation and mycological examination, with species confirmed using MALDI-TOF mass spectrometry. The prevalence of Candida species was 32.1%, in which C. albicans was the most common (92.1% of OC cases), followed by Nakaseomyces glabrata, Pichia kudriavzevii, C. tropicalis, and C. parapsilosis. Univariate analysis indicated that aging, use of oral prostheses, need for dental intervention, immunosuppression, and autoimmune diseases increase the risk of candidiasis. Multivariate analysis confirmed that aging, necessity for dental treatment, and immunosuppression were in 80% of OC cases. Given the great prevalence of oral candidiasis in hospitalized patients, dentists need to assess them for oral candidiasis and provide information on oral hygiene and healthy practices. Although C. albicans is the main microorganism responsible for these infections, other species have also been identified, highlighting the need for immediate identification and awareness of risk factors.

Loss to follow-up (LTFU) among people living with HIV (PLHIV) is a concerning reality in various healthcare services and can occur at any stage of HIV care. LTFU can lead to a decline in overall health and quality of life for PLHIV; moreover, antiretroviral therapy (ART) interruption increase the risk of HIV sexual transmission. This systematic review investigated factors related to LTFU among PLHIV. The review included sources from PubMed, Cochrane Library, Embase, and others. We included observational studies published in English, Spanish, or Portuguese, from January 1, 2004, to December 31, 2024. We identified 36 studies from 20 countries in North and South America, Europe, Asia, and Africa. The studies included 69,789 PLHIV, of whom 22% were classified as LTFU. The time frame used to define LTFU varied across studies, ranging from 14 to 365 days. The most frequently reported factors associated with LTFU were younger age, low educational level, financial instability, illicit drug use, stigma, absence of family and social support, and ART side effects. Other relevant factors included long commuting time to healthcare facilities, long waiting time at health units, and issues with provider-patient relationships. Multiple factors may contribute to LTFU among PLHIV in complex and context-dependent ways. To address this issue, healthcare services must develop a comprehensive understanding of the communities they assist, recognizing distinct subgroups and their specific needs. Public health policies should be implemented to promote continuous care for PLHIV, including early diagnosis, multidisciplinary assessment, and social support.

A 52-year-old female patient suffering from chronic suppurative otitis media had a bacterial strain isolated from her ear swab specimens, which could not be identified using conventional methods, but it was eventually identified as Kerstersia gyiorum via whole genome sequencing (WGS). Antimicrobial drug susceptibility testing was conducted on the isolated strain and the results demonstrated its susceptibility to a range of antimicrobial drugs, including ofloxacin, ceftriaxone, and other agents. However, resistance to chloramphenicol was observed. The patient was treated with ofloxacin, ceftriaxone, and dexamethasone, resulting in an improvement in symptoms. This report describes the first documented case of Kerstersia gyiorum causing chronic suppurative otitis media in China. WGS provided definitive species identification in which conventional methods failed, demonstrating its critical role in diagnosing atypical pathogens.