Review Article Fluconazole Resistance and Heteroresistance in Cryptococcus spp.: Mechanisms and Implications Moreira, Izabela de Mesquita Bárcia Sousa, Naira Sulany Oliveira de Almeida, Juan Diego Ribeiro de Rosas Filho, Robert Langlady Lira Cruz, Katia Santana Matsuura, Ani Beatriz Jackisch Melhem, Márcia de Souza Carvalho Souza, Érica Simplício de Frickmann, Hagen Lacerda, Marcus Vinícius Guimarães Souza, João Vicente Braga de Abstract in English: ABSTRACT The reference methodology for evaluating antifungal susceptibility is based on determining the minimum inhibitory concentration (MIC), which is the lowest drug concentration capable of inhibiting fungal growth. However, such MIC data are insufficient to measure antifungal susceptibility if a strain is heteroresistant to the tested drug. In such cases, a minority subpopulation of fungal cells, originating from an initially susceptible lineage, can grow at antifungal drug concentrations above the MIC. In studies on fluconazole heteroresistance in Cryptococcus spp., chromosomal disomy has been shown to result in the overexpression of two genes located on chromosome 1 (Chr1) linked to antifungal resistance: ERG11 and AFR1. This review addresses the underlying mechanisms of antifungal resistance, the evolution of methods for determining antifungal susceptibility, and the clinical implications of Cryptococcus heteroresistance to fluconazole. The analysis of the findings indicated a correlation between heteroresistance and adverse clinical outcomes, although this observation still lacks definite confirmation in the literature. This highlights the need to implement more efficient therapeutic strategies and improve antifungal susceptibility and heteroresistance testing. |
Major Article New parameter for QRS complex low voltage in chagasic cardiomyopathy: the ADOC index Barbosa, Ana Gabriela Miranda Silva Júnior, José Antonio da Nascimento, Ellany Gurgel Cosme do Góes, Mariana de Moura Santos Filho, Antônio Almeida dos Melo, Rodrigo Alves de Martins, Remerson Russel Fernandes, Thales Allyrio Araújo de Medeiros Andrade, Micássio Fernandes de Andrade, Cléber de Mesquita Abstract in English: ABSTRACT Background: Low QRS complex voltage is an important predictor of death in Chagas disease. However, the parameters applied to the low-voltage classification were described by the Minnesota Code and not specifically for Chagas disease. This study aimed to analyze low QRS voltage by determining the ADOC index and averages in the frontal and horizontal electrocardiographic planes, establishing possible clinical implications. Methods: A cross-sectional study of patients with Chagas disease was performed using the Mann-Whitney U test and Spearman’s correlation. The amplitudes of each QRS were analyzed, and the sum of the DII and V5 derivations of the ADOC index and the arithmetic means of the QRS complexes in the frontal and horizontal planes were determined. Results: The ADOC index was correlated with the highest risk of stroke and death according to the Rassi score. The ADOC index (p=0.046) and mean mQRS were inversely proportional to the Rassi risk of death score (p=0.038). The ADOC index proved to be more sensitive (75.0%) and accurate (67.4%) in identifying patients at elevated death risk using the Rassi score. Finally, a positive correlation was observed between the QRSFm and QRSHm indicators and ADOC index (r=0.590 and r=0.857, respectively). Discussion: The ADOC index and mean of the QRS complexes are possible tools correlated with the Rassi score and risk of stroke in patients with Chagas disease. |
Major Article Advancements in Viral Genomics: Gated Recurrent Unit Modeling of SARS-CoV-2, SARS, MERS, and Ebola viruses Devaraj, Abhishak Raj Marianthiran, Victor Jose Abstract in English: ABSTRACT Background: Emerging infections have posed persistent threats to humanity throughout history. Rapid and unprecedented anthropogenic, behavioral, and social transformations witnessed in the past century have expedited the emergence of novel pathogens, intensifying their impact on the global human population. Methods: This study aimed to comprehensively analyze and compare the genomic sequences of four distinct viruses: SARS-CoV-2, SARS, MERS, and Ebola. Advanced genomic sequencing techniques and a Gated Recurrent Unit-based deep learning model were used to examine the intricate genetic makeup of these viruses. The proposed study sheds light on their evolutionary dynamics, transmission patterns, and pathogenicity and contributes to the development of effective diagnostic and therapeutic interventions. Results: This model exhibited exceptional performance as evidenced by accuracy values of 99.01%, 98.91%, 98.35%, and 98.04% for SARS-CoV-2, SARS, MERS, and Ebola respectively. Precision values ranged from 98.1% to 98.72%, recall values consistently surpassed 92%, and F1 scores ranged from 95.47% to 96.37%. Conclusions: These results underscore the robustness of this model and its potential utility in genomic analysis, paving the way for enhanced understanding, preparedness, and response to emerging viral threats. In the future, this research will focus on creating better diagnostic instruments for the early identification of viral illnesses, developing vaccinations, and tailoring treatments based on the genetic composition and evolutionary patterns of different viruses. This model can be modified to examine a more extensive variety of diseases and recently discovered viruses to predict future outbreaks and their effects on global health. |
Major Article Extrapulmonary tuberculosis in Morocco: A systematic review of observational studies Dellal, Mohamed Batoui, Sanaa Chetoui, Ahmed Kanouf, Mohamed Fatihi, Touria Habbari, Khalid Abstract in English: ABSTRACT Background: Tuberculosis remains a major global health concern and a leading cause of mortality. In Morocco, various forms of extrapulmonary tuberculosis are prevalent. This systematic review examines research findings on the prevalence, risk factors, and treatment outcomes of extrapulmonary tuberculosis in Morocco. Methods: We conducted searches for observational studies on extrapulmonary tuberculosis in Morocco, published between January 1991 and February 2023, using Scopus, ScienceDirect, and PubMed databases. Medical Subject Heading keywords were used to guide the search. Results: This review included 18 studies focusing on different forms of extrapulmonary tuberculosis, such as cold abscesses, lymph nodes, meningeal, cutaneous, osteoarticular, genital, breast, and gastrointestinal tuberculosis. These studies provided insights into the clinical, diagnostic, and therapeutic aspects of these extrapulmonary tuberculosis forms. Prevalence data were limited, and treatment outcomes varied considerably across studies. The only study providing prevalence data for all forms of extrapulmonary tuberculosis reported a prevalence of 43.5% among tuberculosis cases in Larach Province. Treatment success rates ranged from 64.7% to 100%. Common risk factors included low socioeconomic status, diabetes mellitus, pulmonary tuberculosis exposure, and HIV co-infection. Conclusions: This review highlights a lack of comprehensive on the prevalence of extrapulmonary tuberculosis in Morocco, with inconsistent findings on risk factors and treatment outcomes. Further controlled studies are recommended to obtain more robust evidence and inform more effective management strategies for extrapulmonary tuberculosis. |
Major Article “WhatsBarb” Citizen Surveillance: Survey of Insects Mistaken for Triatomines Paz, Matheus de Araújo Meireles, Anne Caroline Alves Galvão, Cleber Gil-Santana, Hélcio Reinaldo Julião, Genimar Rebouças Abstract in English: ABSTRACT Background: Triatomine recognition by the public is an important factor in Chagas disease (CD) prevention campaigns. Citizen surveillance has been demonstrated as an effective alternative strategy, increasing the possibility of monitoring vector populations on a broad geographic scale. Thus, our study aimed to explore a database built from pictorial/video records and specimens sent through citizen participation, identify the main groups confused with triatomines, and systematize the data on insect diversity. Methods: Due to demand from the local community, the “WhatsBarb” project was established using a digital platform application, to receive photos of suspected insects, or triatomines, and provide digital campaigns, with instructions for collecting insects and delivery to Entomological Surveillance Services. Results: In total, 465 insect records were obtained between 2019 and 2024. We identified taxonomic orders and families in 464 and 454 records, respectively, and estimated at least 68 genera, 42 species, and 101 distinct taxa. Triatomines represented 32.3% of the volunteer contacts. Records showed a predominance of true bugs (Hemiptera: Heteroptera), including phytophagous species and predator reduviids (54.6%; n=254). Contacts were received from 20 of the 26 states in Brazil, in addition to the Federal District. Conclusions: Our findings demonstrate the power of digital tools in public health, which could aid in describing, preventing, and controlling CD vectors, and could be applied to other neglected diseases. |
Short Communication Wing shape differences between flying and non-flying individuals of six Triatoma species (Hemiptera: Reduviidae: Triatominae) Firmino, Fernanda Cristina de Oliveira Galvão, Cleber Rocha, Dayse Abstract in English: ABSTRACT Background: Despite numerous reports of triatomines invading homes through flight, experimental studies investigating this ability under laboratory conditions remain scarce. Flight ability varies between individuals (males and females) of the same species, and wing shape modifications may be associated with the flight capacity of these vectors. Therefore, studies on this topic are crucial for the early identification of species with a greater propensity to invade human dwellings and for the implementation of appropriate surveillance and vector control strategies. However, even when exposed to the same nutritional and environmental conditions, triatomines demonstrate a range of flight abilities. To date, it remains unclear whether differences in wing morphology play a decisive role in determining this behavior. As an initial approach to addressing this issue, the present study aimed to determine whether morphometric differences exist in the wings of flying and non-flying individuals from six species of the genus Triatoma: Triatoma costalimai, Triatoma klugi, Triatoma matogrossensis, Triatoma rubrovaria, Triatoma vandae, and Triatoma williami. Methods: This study employed geometric morphometrics to investigate differences in wing size and shape between flying and non-flying individuals from six Triatoma species. Results: The findings indicated a variation in wing size between sexes. Additionally, shape variations were observed between flying and non-flying insects, particularly in females. Conclusions: Geometric morphometrics effectively identified distinct wing shape patterns in flying and non-flying specimens from six Triatoma species, revealing differences that may aid in identifying species with greater active dispersal capacity. |
Case Report Donor-derived Cryptococcus gattii complex infection after liver transplantation Carneiro, Bruno Hassunuma Breda, Giovanni Luis Cognialli, Regielly Caroline Raimundo Santos, Germana Davila dos Vicente, Vania Aparecida Perondi, Eduardo Gnoatto França, João Cesar Beenke Queiroz-Telles, Flávio Abstract in English: ABSTRACT Cryptococcal disease is the third most common invasive fungal infection in solid organ transplant recipients and is associated with high-morbidity and -mortality rates. Donor-derived Cryptococcus spp. infection typically manifests within the first month post-procedure and has historically been caused by C. neoformans complex, predominantly in kidney recipients, but also after liver transplantation. We report the first documented case of donor-derived, early-onset C. gattii complex meningoencephalitis following liver transplantation in a 54-year-old woman, successfully treated with amphotericin B and fluconazole, and review the relevant literature. |
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Erratum Erratum |