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The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) or genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates. [ABSTRACT FROM AUTHOR]

Aims The present study aimed to use a conventional and metagenomic approach to investigate the microbiological diversity of water bodies in a network of drainage channels and rivers located in the central area of the city of Belém, northern Brazil, which is considered one of the largest cities in the Brazilian Amazon. Methods and results In eight of the analyzed points, both bacterial and viral microbiological indicators of environmental contamination—physical–chemical and metals—were assessed. The bacterial resistance genes, drug resistance mechanisms, and viral viability in the environment were also assessed. A total of 473 families of bacteria and 83 families of viruses were identified. Based on the analysis of metals, the levels of three metals (Cd, Fe, and Mn) were found to be above the recommended acceptable level by local legislation. The levels of the following three physicochemical parameters were also higher than recommended: biochemical oxygen demand, dissolved oxygen, and turbidity. Sixty-three bacterial resistance genes that conferred resistance to 13 different classes of antimicrobials were identified. Further, five mechanisms of antimicrobial resistance were identified and viral viability in the environment was confirmed. Conclusions Intense human actions combined with a lack of public policies and poor environmental education of the population cause environmental degradation, especially in water bodies. Thus, urgent interventions are warranted to restore the quality of this precious and scarce asset worldwide. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between the availability of GeneXpert®MTB/RIF in municipalities and the proportion of people who have access to this diagnostic technology for tuberculosis (TB), as well as the resistance detected by the surveillance system in Brazil. Methods: We analysed 4998 Brazilian municipalities that reported 432,937 new TB cases between 2015 and 2020. We compared municipalities with and without the availability of GeneXpert®MTB/RIF regarding the effective access to GeneXpert®MTB/RIF diagnosis and the prevalence of detected resistance. Results: Municipalities with at least one GeneXpert®MTB/RIF system had three times (95% CI 2.9–3.0) the access to diagnostic tests and 80.4% (95% CI 70.6%–90.2%) higher detection of resistance, compared with municipalities without this technology. We estimated that there have been 1890 cases of undetected resistance during this period in the country. Conclusions: The availability of GeneXpert®MTB/RIF system in the municipality increased the sensitivity of the surveillance for detecting TB resistance. Public Health Implications: It is a priority to strengthen laboratory networks and narrow the gap in access to rapid diagnosis in remote areas to improve the detection and control of drug‐resistant tuberculosis. [ABSTRACT FROM AUTHOR]

Purpose: To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil. Methods: Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB. Results: Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35–64 years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes. Conclusion: We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors. [ABSTRACT FROM AUTHOR]

To evaluate the genetic diversity and clustering rates of M. tuberculosis strains to better understand transmission among persons deprived of liberty (PDL) in Rio Grande do Sul (RS), southern Brazil. This is a cross-sectional study, including strains of M. tuberculosis isolated from PDL, stored at the Central Laboratory of RS, in the period from 2013 to 2018. The molecular characterization was performed using the MIRU-VNTR 15 loci method. A total of 598 M. tuberculosis strains were genotyped, and 37.5% were grouped into 53 clusters. Cluster sizes ranged from 2 to 34 strains. The largest cluster of the study had strains from 34 PDL, and 58.8% of the PDL of this cluster were in P01. Among the clusters formed, in 60.3%, there was at least one strain from P01. The most common strains in RS were LAM (53.2%) and Haarlem (31.1%). The LAM strain was the most likely to form clusters, and Haarlem was associated with anti-TB drug resistance. This was translational research, and the results can collaborate with the TB control programs, leading to improved strategies that allow the reduction of the TB burden in prisons. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of MDRO infection on hospital mortality and the risk factors among critically ill patients with sepsis at hospital admission. Patients and Methods: A cross-sectional study was performed between April 2019 and May 2020, followed by a cohort to evaluate hospital mortality that prospectively included all consecutive patients 18 years or older with sepsis admitted within 48 hours of hospital admission to an adult ICU in Brazil. Patients' characteristics, blood samples within one hour of ICU admission, and microbiological results within 48h of hospital admission were collected. In addition, descriptive statistics, binary logistic regression, and propensity score matching were performed. Results: At least one MDRO was isolated in 85 patients (9.8%). The extended-spectrum beta-lactamase-producing Enterobacterales are the most frequent organism (56.1%). Hypoxemic acute respiratory failure (OR 1.87, 95% CI 1.02– 3.40, p = 0.04), Glasgow Coma Score below 15 (OR 2.57, 95% CI 1.38– 4.80, p < 0.01), neoplasm (OR 2.66, 95% CI 1.04– 6.82, p = 0.04) and hemoglobin below 10.0 g/dL (OR 1.82, 95% CI 1.05– 3.16, p = 0.03) were associated with increased MDRO. Admission from the Emergency Department (OR 0.25, 95% CI 0.14– 0.43, p < 0.01) was associated with decreased MDRO. In the multivariate analysis, MDRO at hospital admission increased hospital mortality (OR 2.80, 95% CI 1.05– 7.42, p = 0.04). After propensity score-matching adjusted to age, APACHE II, SOFA, and dementia, MDRO at hospital admission was associated with significantly high hospital mortality (OR 2.80, 95% CI 1.05– 7.42, p = 0.04). The E-value of adjusted OR for the effect of MDRO infection on hospital mortality was 3.41, with a 95% CI of 1.31, suggesting that unmeasured confounders were unlikely to explain the entirety of the effect. Conclusion: MDRO infection increased hospital mortality, and MDRO risk factors should be accessed even in patients admitted to ICU within 48 hours of hospital admission. [ABSTRACT FROM AUTHOR]

Objective. To map the policies related to the prevention and control of antimicrobial resistance from a human health perspective in Brazil and systematize the historical course of these policies. Method. A scoping review was performed following Joana Briggs Institute and PRISMA guidelines. A literature search was performed in December 2020 in the LILACS, PubMed and EMBASE databases. The terms "antimicrobial resistance" AND "Brazil" as well as their synonyms were used. Using the same keywords, Brazilian government websites were searched for documents published until December 2021. Studies of all designs were included, with no language or date restrictions. Clinical documents, reviews and epidemiological studies that did not focus on antimicrobial resistance management policies in Brazil were excluded. Categories based on World Health Organization documents were used for data systematization and analysis. Results. In Brazil, policies related to antimicrobial resistance such as the National Immunization Program and hospital infection control programs can be traced back to before the creation of the Unified Health System. In the late 1990s and 2000s, the first specific policies on antimicrobial resistance (surveillance networks and programs) and education strategies were established; especially noteworthy is The National Action Plan for the Prevention and Control of Antimicrobial Resistance in the Single Health Scope (PAN-BR) of 2018. Conclusions. Despite the long history of policies related to antimicrobial resistance in Brazil, gaps were identified, particularly in monitoring the use of antimicrobials and surveillance of antimicrobial resistance. The PAN-BR, the first government document prepared from a One Health perspective, represents an important milestone. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) mutations associated with antiviral resistance have become a major problem related to high mortality in kidney transplant patients. The aim of the study was to investigate mutations in the CMV genes UL97 and UL54 associated with antiviral resistance. A retrospective observational cohort study was carried out at Hospital Ophir Loyola (HOL), a reference in Kidney Transplantation. A total of 81 patients who underwent kidney transplantation were followed up between 2016 and 2018 were monitored for CMV viral load by performing qPCR. Sanger sequencing was performed on 66 patients. All CMV-positive kidney transplant recipients were included. Mutations were observed in 15 samples (22.72%) from patients. Most cases involved UL97 mutations. Mutation in UL54 without mutation in UL97 was detected in only 2 cases. Resistance mutations in UL97 were identified, such as M460V, L595S, H520Q, two co-mutations D465R + Del524 and A594P + D413A and a 3 codon deletion (del598-601). The search for mutations in the CMV genes identified mutations that confer resistance to conventional antivirals, such as ganciclovir and cidofovir, used in the treatment of these patients. Confirmation of the association with increased CMV viral load in transplanted patients, due to mutation in resistance genes, requires phenotypic analysis for confirmation purposes. These were the first findings in patients in northern Brazil that we know of. [ABSTRACT FROM AUTHOR]

The Drug Resistance Educational Program (PROERD) is Brazil's most widespread school-based prevention program; its current curriculum is based on the North American Keepin' it REAL (kiR) program. There is no evidence of the effectiveness of PROERD in preventing drug use, pointing to the need for further studies to understand these findings. The aim of the study was to synthesis the evidence of the effect of the kiR curriculum (PROERD) through a systematic review. We found 17studies that reported the effects of different versions of kiR on drug use and/or violence. Except for the Brazilian study, no studies were found that assessed the effect on drug use of the version applied by police officers (DARE-kiR), the same one implemented by PROERD. Favorable evidence of kiR in drug use prevention was found for the 7th-grade curriculum, which contradicts the PROERD's null-effect results. No international evidence of the effect of kiR was found in the 5th-grade curriculum, in the same line as the PROERD's study. It is suggested that PROERD's 7th-grade curriculum should be re-vised to reflect international results and that the 5th-grade curriculum should be reconsidered in light of the negative international evidence. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant chemotherapy (NACT) is offered to breast cancer (BC) patients to downstage the disease. However, some patients may not respond to NACT, being resistant. We used the serum metabolic profile by Nuclear Magnetic Resonance (NMR) combined with disease characteristics to differentiate between sensitive and resistant BC patients. We obtained accuracy above 80% for the response prediction and showcased how NMR can substantially enhance the prediction of response to NACT. Neoadjuvant chemotherapy (NACT) is offered to patients with operable or inoperable breast cancer (BC) to downstage the disease. Clinical responses to NACT may vary depending on a few known clinical and biological features, but the diversity of responses to NACT is not fully understood. In this study, 80 women had their metabolite profiles of pre-treatment sera analyzed for potential NACT response biomarker candidates in combination with immunohistochemical parameters using Nuclear Magnetic Resonance (NMR). Sixty-four percent of the patients were resistant to chemotherapy. NMR, hormonal receptors (HR), human epidermal growth factor receptor 2 (HER2), and the nuclear protein Ki67 were combined through machine learning (ML) to predict the response to NACT. Metabolites such as leucine, formate, valine, and proline, along with hormone receptor status, were discriminants of response to NACT. The glyoxylate and dicarboxylate metabolism was found to be involved in the resistance to NACT. We obtained an accuracy in excess of 80% for the prediction of response to NACT combining metabolomic and tumor profile data. Our results suggest that NMR data can substantially enhance the prediction of response to NACT when used in combination with already known response prediction factors. [ABSTRACT FROM AUTHOR]

The emergence of clinically relevant mutations in the hepatitis B virus (HBV) genome has been a matter of great debate because of the possibility of escape from the host's immune system, the potential to cause more severe progression of liver diseases and the emergence of treatment-resistant variants. Here we characterized the circulating variants of HBV in Rondônia State, in the north of Brazil. Serum samples of 62 chronic HBV carriers were subjected to PCR assays and clinical data were collected. Mutations and genotypes were characterized through direct sequencing. The findings show the presence of subgenotypes A1 (54.83%, 34/62), D3 (16.13%, 10/62), F2 (16.13%, 10/62), A2 (4.84%, 3/62), D2 (3.23%, 2/62), D1 (1.61%, 1/62), D4 (1.61%, 1/62) and F4 (1.61%, 1/62). Deletions in the pre-S2 region were found in 13.79% (8/58) of the samples, mutations in the S gene in 59.68% (37/62) and RT mutations in 48.39% (30/62). We found a variable genotypic distribution in different locations and important mutations related to immune escape and drug resistance in Western Amazonia, which contributed to genetic surveillance and provided important information to help control the disease. [ABSTRACT FROM AUTHOR]

Rhipicephalus microplus is among the most important ectoparasites for livestock. The use of synthetic acaricides has raised some concerns due to the selection of tick populations that are resistant to acaricides and environmental contamination. Therefore, plant extracts have been used as alternatives for the treatment of animals infested with ticks. In this study, R. microplus populations from seven different dairy farms were collected and assessed for their resistance to the acaricides cypermethrin or trichlorfon. Larvae of the most resistant population were used in assays to evaluate the acaricide effect of leaf extracts from plants of the Brazilian savanna. The most active extracts were also tested against fully engorged females. Among seven tick populations, five and three showed resistance level ≥ III for cypermethrin or trichlorfon, respectively. The most resistant tick population was evaluated in mortality assays with the plants Piptadenia viridiflora, Annona crassiflora, Caryocar brasiliense, Ximenia americana, and Schinopsis brasilienses. The ethanolic extracts of C. brasiliense, X. americana and S. brasilienses showed higher larvicidal effects in comparison to the other extracts and cypermethrin. The ethanolic extract of X. americana showed 60.79 % efficacy against fully engorged females of the acaricide resistant tick strain. The ethanolic extracts of C. brasiliense, X. americana, and S. brasilienses showed peaks in HPLC-DAD, indicating the presence of tannins and flavonoids. Three of the plants showed promising results and should be explored in further studies to develop novel tools to control R. microplus in cattle., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The human immunodeficiency virus type 1 (HIV-1) can be transmitted via parenteral, sexual, or vertical exposure routes. The number of HIV-1 cases detected yearly in children and adolescents in Brazil did not decrease over the last decade, representing ~5% of total cases described in the country. In recent years, the HIV-1 diversity and the prevalence of transmitted drug resistance mutations (TDRM) are moving toward a marked increase. In this study, we retrospectively evaluated the diversity of HIV-1 subtypes and the TDRM prevalence in 135 treatment-naïve HIV-1 vertically infected children and adolescents born in between 1993 and 2012. These children were assessed in either 2001–2007 or 2008–2012 when they were 0 to 17 years old. The individuals assessed in 2001–2007 (n = 38) had median CD4+ T cell counts of 1218 cells/mm3 (IQR: 738–2.084) and median HIV-1 plasma viral load of 4.18 log10 copies/mL (IQR: 3.88–4.08). The individuals (n = 97) evaluated in 2008–2012 showed median CD4+ T cell counts of 898.5 cells/mm3 (IQR: 591.3–1.821) and median HIV-1 plasma viral load of 4.69 log10 copies/mL (IQR: 4.26–5.33). A steady decrease in the median CD4 T+ cell counts was observed with age progression, as expected. The majority HIV-1 pol sequences (87%) were classified as pure HIV-1 subtypes (77% subtype B, 9% subtype F1 and 1.5% subtype C), while 13% of sequences were classified as recombinants (CRF45_cpx, n = 4; CRF28/29_BF1, n = 2; CRF02_AG, n = 1; CRF40_BF1, n = 1, CRF99_BF1, n = 1, URF_BF1, n = 8). The overall prevalence of TDRM was 14% (19/135), conferring resistance to the nucleoside reverse transcriptase inhibitors (NRTI, 13/135–9.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI, 8/135–5.9%), and protease inhibitors (PI, 2/135–1.5%). The main TDRM observed for NNRTI was the K103N (n = 8), while the mutations T215I/Y/D/E (n = 7) and M184V (n = 4) were the main TDRM for NRTI. Only two TDRM were observed for PI in one individual each (M46I and V82A). Most TDRM were found in the HIV-1 subtype B (84%) sequences. This study reveals an HIV-1 epidemic with high diversity and moderate prevalence of TDRM in the pediatric population of Rio de Janeiro, indicating the existence of possible problems in the clinical management of prophylactic therapy to prevent mother-to-child transmission and future treatment options for the affected children. [ABSTRACT FROM AUTHOR]

Copyright of Saúde Coletiva is the property of MPM Comunicacao and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The aim of this work was to identify gram‐positive bacteria and their respective resistance profiles of free‐living capuchin monkeys. Methods: For this, 15 Sapajus nigritus were captured in a municipal urban park in the northern region of the state of Paraná, Brazil, and under pharmacological restraint, samples were collected with sterile swabs from the oral, rectal, ocular, nasal, and auricular regions. After isolation of the 22 gram‐positive bacteria, each isolate was subjected to the catalase and coagulase tests for presumptive identification. Subsequently, phenotypic tests for bacterial resistance were performed using the agar diffusion disc method. The samples resistant to oxacillin were submitted to the PCR technique to search for the mecA gene. Results: Of the 22 gram‐positive cocci of these two (9.09%) are Streptococcus spp. and twenty (90.91%) Staphylococcus spp. Among Staphylococcus spp. three (13.64%) were coagulate‐negative (CoNS) and seventeen (86.36%) coagulate‐positive (CoPS). Of the antimicrobials tested, enrofloxacin had the best performance, with only one (04.54%) isolate resistant to it, on the other hand, the antimicrobials with the lowest performance were cefotaxime and penicillin with 19 (82.36%) and 18 (81.81%) resistant isolates, respectively. Only five isolates had MAR less than 0.2, being one ocular, one oral, and three nasal, they had multiple resistance index varied between 0.07 and 0.92, with an average of 0.45 and a mode of 0.3. Among the samples with the highest resistance index, a positive coagulase Staphylococcus stood out, being intermediate to gentamicin and resistant to other antibiotics and an intermediate streptococcus to gentamicin, enrofloxacin, and resistant to other antibiotics. No sample was positive to mecA gene. Conclusions: Future studies should be conducted to identify the Staphylococcus species, the high rate of antimicrobial resistance of the monkeys in this study suggests that Grooming's behavior may be contributing to the sharing of the resistant microorganism among the members of this group of primates. [ABSTRACT FROM AUTHOR]

Sheep respiratory disease (SRD) is a multifactorial illness commonly affecting sheep. Mesomycoplasma (Mycoplasma) ovipneumoniae is one of the most important etiological agents of SRD and should be better understood, especially in countries where it was recently detected, such as Brazil. Also, the intensive use of quinolones in mycoplasmal infections increases the selective pressure for resistance to this drug class, and no data about antimicrobial resistance in Brazil is available. Therefore, this study aimed to perform a comparative genomic analysis of newly isolated Brazilian M. ovipneumoniae strains, identify point mutations in target genes that may be associated with antibiotic resistance, and perform a phylogenomic analysis of these strains with available genome representatives of M. ovipneumoniae. Glucose-fermenting fried egg-like colonies identified as M. ovipneumoniae were obtained after a culture of tracheobronchial lavage from infected sheep. The genomes were sequenced, de novo assembled and comparatively evaluated. Important putative virulence factors were detected in all isolates: the analysis of the average nucleotide homology of all these genes with the M. ovipneumoniae ATCC 29419 revealed associations between clpB, lgt, tuf, and dnaJ genes and geographic location. In addition, nucleotide substitutions in a few positions of the Quinolone-Resistant Determinant Region of the gyrA gene, including the Ser83Ala, were detected. The phylogenomic analysis showed that the Brazilian isolates belonged to two different clades corresponding to geographic location, and the isolates from São Paulo showed high similarity, which differs from isolates from Rio de Janeiro. This first genomic analysis of the Brazilian M. ovipneumoniae genomes demonstrates strain segregation according to location and health status, reinforcing the importance of continuous surveillance and diagnostics of this bacteria causing sheep respiratory disease in the Brazilian flocks. • Genomic analysis of newly isolated Brazilian M. ovipneumoniae strains was performed. • Mutations in the Quinolone-resistant determinant Region of gyrA gene were detected. • Brazilian isolates belong to two different clades regarding the location. • Isolates from São Paulo show high similarity compared to those from Rio de Janeiro. [ABSTRACT FROM AUTHOR]

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Those derived from recombination between subtype B and subsubtype F1, with 18 reported, most of them of South American origin, are among the most diverse. In this study, we identified a HIV-1 BF1 recombinant cluster that is expanding in Spain, transmitted mainly via heterosexual contact, which, analyzed in near full-length genomes in four viruses, exhibited a coincident BF1 mosaic structure, with 12 breakpoints, that fully coincided with that of two viruses (10BR_MG003 and 10BR_MG005) from Brazil, previously classified as CRF72_BF1. The three remaining Brazilian viruses (10BR_MG002, 10BR_MG004, and 10BR_MG008) previously identified as CRF72_BF1 exhibited mosaic structures highly similar, but not identical, to that of the Spanish viruses and to 10BR_MG003 and 10BR_MG005, with discrepant subtypes in two short genome segments, located in pol and gp120env. Based on these results, we propose that the five viruses from Brazil previously identified as CRF72_BF1 actually belong to two closely related CRFs, one comprising 10BR_MG002, 10BR_MG004, and 10BR_MG008, which keep their CRF72_BF1 designation, and the other, designated CRF122_BF1, comprising 10BR_MG003, 10BR_MG005, and the viruses of the identified Spanish cluster. Three other BF1 recombinant genomes, two from Brazil and one from Italy, previously identified as unique recombinant forms, were classified as CRF72_BF1. CRF122_BF1, but not CRF72_BF1, was associated with protease L89M substitution, which was reported to contribute to antiretroviral drug resistance. Phylodynamic analyses estimate the emergence of CRF122_BF1 in Brazil around 1987. Given their close phylogenetic relationship and similar structures, the grouping of CRF72_BF1 and CRF122_BF1 in a CRF family is proposed. [ABSTRACT FROM AUTHOR]

Background: Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described.Methods: We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation.Results: 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5-7 days/week and 300(13%) 2-3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5-7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (HR = 0.68; 95% CI = 0.51-0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5-7 days/week vs. 2-3 days/week (HR 0.75, 95%CI 0.55-1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83-2.45; P = 0.20).Conclusions: TB treatment 5-7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America. [ABSTRACT FROM AUTHOR]

Copyright of Brazilian Journal of Biology is the property of Instituto Internacional de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Paulista de Enfermagem is the property of Universidade Federal de Sao Paulo, Escola Paulista de Enfermagem and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The Hepatitis C virus (HCV) infection is a public health problem. The high level of HCV replication and its lack of post-transcriptional correction mechanisms results in the emergence of viral variants and the difficulty in determining polymorphisms and variants that contain the substitutions associated with resistance towards new antivirals. The main focus of this study was to map the NS5A and NS5B polymorphisms and resistance mutations to new antiviral drugs in HCV strains genotype 1 from patients with chronic hepatitis C infection. Serum samples were collected from patients who underwent routine viral load tests at the Instituto Adolfo Lutz, Sao Paulo city, Brazil. A total of 698 and 853 samples were used for the characterization of NS5A and NS5B regions, respectively, which comprise the HCV genotypes 1a and 1b. The prevalence of resistance mutations found in the NS5A region was 6.4%, with Y93H, L31M, Q30R, and Y93N as the main resistance-associated substitutions (RAS). No NS5B-associated RAS was observed for any of the analyzed drugs. These findings support that the RAS test should be offered to individuals with poor response to double combination regimens prior to treatment initiation, thereby assisting strain vigilance and selection of effective treatment or retreatment options using DAA regimens. [ABSTRACT FROM AUTHOR]

Background: Leishmania infantum is the most important etiological agent of visceral leishmaniasis in the Americas and Mediterranean region, and the dog is the main host. Miltefosine was authorized to treat canine leishmaniasis (CanL) in Brazil in 2017, but there is a persistent fear of the emergence of parasites resistant not only to this drug but, through cross-resistance mechanisms, also to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are drivers of parasite virulence. In this context, the aim of this study was to analyze the impact of treating a dog with miltefosine and allopurinol on the generation of parasites resistant to miltefosine, amphotericin B and meglumine antimoniate. Methods: In vitro susceptibility tests were conducted against miltefosine, amphotericin B and meglumine antimoniate with T0 (parasites isolated from a dog before treatment with miltefosine plus allopurinol), T1 (after 1 course of treatment) and T2 (after 2 courses of treatment) isolates. The rates of cell proliferation, infectivity and metacyclogenesis of the isolates were also evaluated. Results: The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. An increasing trend in the metacyclogenesis rate of the parasites was also observed as drug resistance increased. Conclusion: The data indicates an increased L. infantum resistance to miltefosine and amphotericin B after the treatment of a dog with miltefosine plus allopurinol. Further studies with a larger number of L. infantum strains isolated from dogs with varied immune response profiles and undergoing different treatment regimes, are advocated. [ABSTRACT FROM AUTHOR]

We analysed mutations in katG, inhA and rpoB genes, and isoniazid phenotypic resistance levels in Mycobacterium tuberculosis isolates from drug-resistant TB patients from São Paulo state, Brazil. Isolates resistant to the critical concentration of isoniazid in MGIT (0.1 µg/mL) were screened for mutations in katG 315 codon, inhA promoter region and rpoB RRDR by MTBDRplus assay and subjected to determination of isoniazid resistance levels by MGIT 960. Discordances were resolved by Sanger sequencing. Among the 203 isolates studied, 109 (54%) were isoniazid-monoresistant, 47 (23%) MDR, 29 (14%) polydrug-resistant, 12 (6%) pre-XDR and 6 (3%) XDR. MTBDRplus detected isoniazid mutations in 75% (153/203) of the isolates. Sequencing of the entire katG and inhA genes revealed mutations in 18/50 wild-type isolates by MTBDRplus (10 with novel mutations), resulting in a total of 32/203 (16%) isolates with no mutations detected. 81/83 (98%) isolates with katG 315 mutations alone had intermediate resistance. Of the 66 isolates with inhA C-15T mutation alone, 51 (77%) showed low-level, 14 (21%) intermediate and 1 (2%) high-level resistance. 5/6 (83%) isolates with mutations in both katG and inhA had high-level resistance. Inferred mutations corresponded to 22% (16/73) of all mutations found in rpoB. Mutations detected in katG regions other than codon 315 in this study might be potential new isoniazid resistance markers and could explain phenotypic resistance in some isolates without katG and inhA classic mutations. In our setting, 16% of isoniazid-resistant isolates, some with high-level resistance, presented no mutations either in katG or inhA. [ABSTRACT FROM AUTHOR]

Background: Acaricide resistance in cattle ticks is a significant concern in (sub)tropical regions, particularly Brazil. The Larval Packet Test (LPT) is the standard laboratory bioassay for resistance diagnosis, which requires triplicates of seven acaricidal dilutions plus controls to cover larval mortalities ranging between 0 and 100%. The value of the LPT lies in providing resistance ratios based on the ratio between the LC50 calculated with potentially resistant and susceptible ticks. However, LC50 ratios are difficult to translate into practical advice for farmers. Moreover, LPT requires laboratory facilities to maintain susceptible tick colonies, and it takes 6 weeks to obtain the larvae to be tested by LPT derived from engorged female ticks collected from cattle in the field. Our novel approach was twofold: first, we upgraded the LPT to the Resistance Intensity Test (RIT) by adopting the latest WHO guidelines for resistance detection in mosquitoes, which combines a 1 × recommended dose with 5 × and 10 × concentrated doses to reveal low, moderate and high resistance intensity, respectively. This reduced the number of test papers and tick larvae and, more importantly, provided relevant information on the resistance level. Our second innovative step was to abolish testing larvae entirely and expose partly engorged adult ticks to the same acaricidal doses immediately after removing them from cattle in the field. This resulted in the Rapid Tick exposure Test (RaTexT®), wherein partly engorged adult ticks were exposed to an acaricide-impregnated, specially designed matrix providing test results within 24 h. This approach directly compared resistance detection in tick larvae in the RIT with resistance in adult ticks in RaTexT®., Methods: Laboratory validation was conducted in Brazil with resistant and susceptible colonies of Rhipicephalus microplus ticks. For field validation, adult R. microplus ticks collected from different cattle farms in Brazil were evaluated for resistance to RaTexT®, and the results regarding their larval progenies were compared with those for the RIT. Partly engorged adult ticks derived from cattle infested with laboratory and field strains of R. microplus were exposed to deltamethrin in RaTexT® containers, which contained six rows of four interconnected compartments, accommodating five to eight semi-engorged female ticks with a preferred size ranging between 5 and 8 mm. The corresponding larvae of each strain were exposed in the RIT to the same deltamethrin concentrations in filter papers., Results: In RaTexT®, mortality in adult ticks from a resistant strain of R. microplus from Seropédica in Brazil was 38.4%, 54.2% and 75.0% at the 1 ×, 5 × and 10 × doses of deltamethrin, respectively. In RIT, mortality of larvae from the same resistant strain was 2.0%, 4.9% and 19.5% at 1 ×, 5 × and 10 × doses, respectively. The results of RaTexT® and RIT agreed since both tests identified a high level of resistance based on a cut-off of 90% mortality. In RaTexT®, mortality of adult ticks from a susceptible strain originating from Porto Alegre was 73.8%, 92.9% and 97.6% at the 1 ×, 5 × and 10 × doses, respectively. In RIT, mortality of larvae from the susceptible strain was 95.2%, 95.2% and 96.8% at the 1 ×, 5 × and 10 × doses, respectively. Interestingly, both tests identified a low number of unexpected resistant individuals in the susceptible strain since the mortality of neither larvae nor adults reached 100%. This effect remained unnoticed in the LPT, wherein a resistance ratio of 159.5 was found based on the LC50 of the resistant strain divided by the LC50 of the susceptible strain. Next, RaTexT® was compared with RIT using adult and larval ticks derived from three field strains of R. microplus in Brazil. RaTexT® detected high levels of resistance to deltamethrin in adult ticks in all strains, which was confirmed in larvae tested by the RIT. Both tests agreed on the same resistance level with significantly lower mortality rates in larvae than in adult ticks., Conclusions: RaTexT® is a novel rapid pen-site test for detecting acaricide resistance in adult livestock ticks. It potentially replaces laborious tests using larval ticks and provides results within 24 h relevant to acaricide resistance management of livestock ticks., (© 2024. The Author(s).)

This review outlines the current state of anthelmintic resistance (AHR) of gastrointestinal nematodes (GINs) among cattle in Argentina and Brazil, emphasizing the economic repercussions, animal health and welfare. The analysis explores factors associated with AHR and proposes a potential solution: the use of drug combinations. Both countries are grappling with a severe AHR scenario in cattle, having progressed through incipient, established, and advanced phases, leading to extreme cases of animal mortality due to ineffective control strategies. Genera such as Cooperia and Haemonchus have the highest reports of resistance, with Oesophagostomum radiatum also posing significant problems. While oral benzimidazoles and levamisole remain effective in most herds, moxidectin is entering an advanced resistance phase, and avermectins are increasingly deemed ineffective. The review explores the impact ofclimate, mixed grazing, animal movement and other husbandry practices, and the relationship between ectoparasite control and the emergence of resistant helminths. Notably, the discussion includes the strategic use of drug combinations as a valuable approach to address resistant GINs control in livestock, highlighting its significant potential to mitigate the challenges posed by AHR in the cattle industry of these countries.

Background: Urinary tract infections (UTIs) can lead to neonatal complications like sepsis, worsened by empirical treatment, contributing to antimicrobial resistance (AMR). This study examined the incidence, etiology, risk factors, and antimicrobial susceptibility of uropathogens in a Neonatal Intensive Care Unit (NICU) in Brazil., Methods: Medical records of neonates hospitalized in the NICU from January 2015 to June 2022 were retrospectively analyzed through the National Healthcare Safety Network system., Results: Among 1,474 neonates, 3.9% developed UTI, with an alarming 24-fold increase in incidence from 2015 to 2021. Genitourinary complications (odds ratio = 4.8) were a major risk factor. Of the 71 uropathogens, 74.6% were Gram-negative bacteria (GNB), 21.2% Gram-positive bacteria (GPB), and 4.2% Candida albicans. AMR was notable, with 13.3% of GPB and 20.7% of GNB exhibiting multidrug-resistant (MDR), while 6.6% of GPB and 1.9% of GNB showed extensive drug-resistant (XDR). UTI was associated with prolonged hospitalization (16-59 days). In 57 neonates with UTI, 40.3% had bloodstream infections, elevating the risk of death (odds ratio = 1.8)., Conclusions: The study underscores the urgency of implementing infection prevention and control measures in the NICU to curb rising UTI incidences, combat AMR, and mitigate severe complications in critically ill neonates., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Ticks are parasitic arthropods that cause significant economic losses to livestock production worldwide. Although Rhipicephalus (Boophilus) microplus, the cattle tick, occurs throughout the Brazilian territory, there is no official program to control this tick, which is the vector of tick fever pathogens. We address the situation of R. (B.) microplus resistance to synthetic acaricides in Brazil, including cattle tick management; the status of tick resistance per Brazilian state; the history of resistance occurrence of different acaricides; multiple resistance occurrence; and the main strategies for integrated tick management. Tick control in Brazil is characterized by management errors. Local laboratories affiliated with federal and state research institutions and universities employ the Adult Immersion Test as a primary diagnostic method to assess acaricide resistance to topically applied drugs. Only three states (Acre, Amapá, and Amazonas) have no reports on resistant populations. Misinformation on tick control strategies, misuse of available products for tick control, no adoption of Integrated Parasite Management (IPM) practices, low technical support to producers, and the high-speed emergence of acaricide-resistant tick populations are the main problems. We also propose a list of needs and priorities for cattle tick control regarding communication, research, and policies.

Background: The first potential focus for artemisinin resistance in South America was recently confirmed with the presence of the C580Y mutation in the Plasmodium falciparum kelch 13 gene (pfk13) in Guyana.Objectives: This study aimed to strengthen pfk13 monitoring in the Amazon basin countries, to compile the available data and to evaluate the risk of spreading of mutations.Methods: Sanger sequencing was done on 862 samples collected between 1998 and 2019, and a global map of pfk13 genotypes available for this region was constructed. Then, the risk of spreading of mutations based on P. falciparum case importation between 2015 and 2018 within countries of the Amazon basin was evaluated.Results: No additional pfk13 C580Y foci were identified. Few mutations (0.5%, 95% CI = 0.3%-0.8%) in the propeller domain were observed in the general parasite population of this region despite a high proportion of K189T mutations (49.1%, 95% CI = 46.2%-52.0%) in the non-propeller domain. Case information revealed two patterns of intense human migration: Venezuela, Guyana and the Roraima State in Brazil; and French Guiana, Suriname and the Amapá State in Brazil.Conclusions: There are few pfk13 mutant foci, but a high risk of dispersion in the Amazon basin, mainly from the Guiana Shield, proportionate to mining activities. Therefore, access to prompt diagnosis and treatment, and continuous molecular monitoring is essential in these geographical areas. [ABSTRACT FROM AUTHOR]

Background: Treatment outcomes were evaluated of a cohort of new pulmonary tuberculosis (TB) cases that were rifampicin resistant, multidrug-resistant, or extensively resistant during 2013 and 2014 in Brazil. The objective of this study is to identify factors associated with unfavorable treatment outcomes for drug-resistant TB cases.Methods: The Brazilian Special Tuberculosis Treatment Information System (SITE-TB) was the main data source. The independent variables were classified into four blocks (block I: individual characteristics; block II: clinical characteristics and proposed treatment; block III: treatment follow-up characteristics; and block IV: TB history). The category of successful therapeutic outcome was compared with lost to follow-up, failure, and death. Considering the multiple outcomes as the dependent variable, the odds ratios (OR) and its respective 95% confidence interval (95% CI) were estimated by multinomial logistic regression.Results: After applying the exclusion criteria, 980 (98.8%) individuals were included in the study. Of these, 621 (63.4%) had successful treatment, 163 (16.6%) lost to follow-up, 76 (7.8%) failed, and 120 (12.2%) died. Important factors associated with lost to follow-up in the final model included use of illicit drugs (OR = 2.5 95% CI: 1.57-3.82). Outcome failure was associated with having disease in both lungs (OR = 2.0; 95% CI: 1.09-3.62) and using more than one or not using injectable medication (OR = 2.8; 95% CI: 1.05-7.69). Major factors for the death outcome were at least 60 years old (OR = 3.4; 95% CI: 1.90-6.03) and HIV positive (OR = 2.7; 95% CI: 1.45-4.83).Conclusions: The factors associated with unfavorable treatment outcomes were different. Some of these factors are specific to each outcome, which reflects the complexity of providing care to these individuals. [ABSTRACT FROM AUTHOR]

We evaluate the genetic characterization of 132 HIV‐1 pol sequences from children and adolescents undergoing antiretroviral therapy in Northeast Brazil. Phylogenetic and recombination analyses were performed using the maximum likelihood method using SeaView version 4 and SIMPLOT software. Most individuals harbored HIV‐1 B (84.8%) and BF recombinants (9.8%), although other non‐B subtypes were detected: HIV‐1 C (1.5%), HIV‐1 F (2.4%), and BC recombinants (1.5%). Antiretroviral resistance was 47% (95% confidence interval [CI]: 38.7%–55.4%). Non‐nucleoside reverse transcriptase inhibitors (NNRTIs) showed higher frequencies of primary mutations, with 40.9% (95% CI: 32.9%–49.4%), followed by nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PIs) with 34.8% (95% CI: 27.3–43.3) and 6.1% (95% CI: 3.1%–11.5%), respectively. Among NRTIs, higher resistance levels were observed for abacavir, emtricitabine, and lamivudine; for NNRTI, nevirapine and efavirenz. The most common primary mutations found were M184V (29.5%), K103N (25%), M41L (9.8%), T215Y (8.3%), and G190A (8.3%). Our findings highlight the importance of surveillance of resistance mutations, which contributes to the continuous updating and implementation of preventive measures to decrease mother‐to‐child‐transmission and transmitted drug resistance. Highlights: The predominance of HIV‐1 subtype B (84.8%) and BF recombinants (9.8%) in children (Brazil).Antiretroviral resistance was observed in 47% of children under virological failure.Nucleoside and Nonnucleoside Reverse transcriptase Inhibitors demonstrated higher drug resistance rates than protease inhibitors.NRTI and NNRTI‐resistants participants harboured resistance to three or more drugs in 91.3% and 79.6% patients, respectively.Most frequent Drug Resistance Mutations: NRTI (M184V, M41L, T215Y, D67N, K70R); NNRTI (K103N, G190A, K101E). [ABSTRACT FROM AUTHOR]

Background Female sex workers (FSWs) are an especially vulnerable group for syphilis and other sexually transmitted infection (STIs). This study determined the prevalence of syphilis in FSWs and factors associated with this disease in the Marajó Archipelago (northern Brazil), as well as the frequency of point mutations (A2058G and A2059G) in the 23S rRNA gene of Treponema pallidum and coinfections with hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV). Methods FSWs were diagnosed using a rapid qualitative test and the isolates were evaluated for the presence of point mutations by real-time PCR. Blood samples with T. pallidum were tested for the presence of HBV, HCV and HDV by ELISA and confirmed by real-time PCR. The factors associated with syphilis were identified using Poisson regression models. Results Overall, 41.1% FSWs tested positive for syphilis and 23.5% were infected with strains having A2058G/A2059G point mutations. HBV (23.0%) and HCV (8.1%) were detected among FSWs with syphilis. Six factors were associated with syphilis: low levels of education, reduced income, drug use, unprotected sex, a lengthy career in prostitution and a lack of regular medical check-ups. Conclusions These findings indicate an urgent need for implementation of effective strategies to diagnose, prevent and treat syphilis, as well as other STIs, in this Brazilian region. [ABSTRACT FROM AUTHOR]

Virologic failure may occur because of poor treatment adherence and/or viral drug resistance mutations (DRM). In Brazil, the northern region exhibits the worst epidemiological scenarios for the human immunodeficiency virus (HIV). Thus, this study is aimed at investigating the genetic diversity of HIV-1 and DRM in Manaus. The cross-sectional study included people living with HIV on combined antiretroviral therapy and who had experienced virological failure during 2018-2019. Sequencing of the protease/reverse transcriptase (PR/RT) and C2V3 of the viral envelope gp120 (Env) regions was analyzed to determine subtypes/variants of HIV-1, DRMs, and tropism. Ninety-two individuals were analyzed in the study. Approximately 72% of them were male and 74% self-declared as heterosexual. Phylogenetic inference (PR/RT-Env) showed that most sequences were B subtype, followed by BF1 or B C mosaic genomes and few F1 and C sequences. Among the variants of subtype B at PR/RT, 84.3% were pandemic ( B PAN ), and 15.7% were Caribbean ( B CAR ). The DRMs most frequent were M184I/V (82.9%) for nucleoside reverse transcriptase inhibitors (NRTI), K103N/S (63.4%) for nonnucleoside reverse transcriptase inhibitor (NNRTI), and V82A/L/M (7.3%) for protease inhibitors (PI). DRM analysis depicted high levels of resistance for lamivudine and efavirenz in over 82.9% of individuals; although, low (7.7%) cross-resistance to etravirine was observed. A low level of resistance to protease inhibitors was found and included patients that take atazanavir/ritonavir (16.6%) and lopinavir (11.1%), which confirms that these antiretrovirals can be used—for most individuals. The thymidine analog mutations-2 (TAM-2) resistance pathway was higher in B CAR than in B PAN . Similar results from other Brazilian studies regarding HIV drug resistance were observed; however, we underscore a need for additional studies regarding subtype B CAR variants. Molecular epidemiology studies are an important tool for monitoring the prevalence of HIV drug resistance and can influence the public health policies. [ABSTRACT FROM AUTHOR]

Background: Acquisition of HIV primary drug resistant (PDR) infection can lead to poor virologic and clinical outcomes in individuals and hampers public health efforts in epidemic control. Monitoring PDR in HIV‐positive blood donors can be used to inform nationwide trends in the spread of drug‐resistant HIV strains. Methods: We conducted a cross‐sectional study using genetic sequence analysis to assess HIV pol sequences, PDR, and risk factors for infection using audio computer‐assisted structured interviews in four large blood centers in Brazil from 2007 to 2017. Results: Of 716 HIV‐positive blood donors, 504 (70.4%) were successfully sequenced. HIV clade B (73.2%) was the most prevalent subtype, followed by a mix of non‐B (21.2%) sub‐types. A twofold increase (from 4% to 8%) in recombinants prevalence was observed during the study period. Sixty‐four (12.7%) presented PDR. Overall, HIV PDR prevalence remained stable during the study period. Drug resistance mutations for non‐nucleoside reverse transcriptase inhibitors were found in 39 (7.7%) donors, while for nucleoside reverse transcriptase inhibitors were found in 26 (5.1%), and for protease inhibitors in 24 (4.8%) of HIV‐infected donors. We did not find statistically significant differences in demographics, behavioural risk factors, or HIV genotypes when comparing volunteers with and without PDR. Conclusion: The HIV PDR rate among donors remained stable during the study period. HIV‐positive blood donors can be an informative population to monitor primary HIV resistance and ultimately may help to increase the knowledge and awareness of HIV risk factors and PDR. [ABSTRACT FROM AUTHOR]

This research aimed to investigate the genotypic relatedness of 18 Staphylococcus aureus strains isolated from intramammary infections in primiparous cows and extramammary sites on five dairy herds by rep-PCR using RW3A primers, and by PFGE using the endonuclease SmaI. The isolates were also evaluated in vitro for the susceptibility against beta-lactam antimicrobials drugs (penicillin and oxacillin), considering that beta-lactams are frequently used for treating staphylococcal intrammamary infections. The rep-PCR typing was highly discriminatory (D value= 0.9804) and a total of 15 patterns were detected. The PFGE method was also highly discriminatory (D value= 0.9667) and a total of 13 patterns were observed. A total of 15 out of 18 (83%) isolates were resistant to penicillin and one out of 18 (6%) to oxacillin. In conclusion, these findings confirmed the occurrence of a high genetic diversity of S. aureus strains at the herds and the presence of clonally-related strains only at the same herd, emphasizing a variety of genotypic profiles among the isolates. [ABSTRACT FROM AUTHOR]

Line Probe Assay (LPA) is a rapid molecular technique used for the diagnosis of Mycobacterium Tuberculosis (MTB) presence and resistance to first-line drugs such as Rifampicin and Isoniazid. The study presented here is part of an initiative of the Brazilian Tuberculosis Network (REDE-TB) researchers, together with the National Brazilian Tuberculosis Control Program from Health Ministry for the development of mechanisms that improve the clinical and epidemiological impact of LPA use in reference centers in Brazil. Here we use the operational model concept to see sharply the whole flow of processes in order to evaluate diagnostics cascades. Based on that, first, we developed a design of tuberculosis system operations in discrete-time based model, then we made a description of an agent-based transmission model developed to be incorporated to the operational design. After the implementation of the design, we can make a prediction that directly influences the choice of the most appropriate intervention and consequently the result of the cost-effectiveness analysis, translated by the feasibility of the chosen test to future works. [ABSTRACT FROM AUTHOR]

Objective: to analyze, in the clinical practice of large hospitals, how the adoption of measures to prevent and control the spread of bacterial resistance has occurred, and to propose a score for the institutions' adherence. Method: a cross-sectional study carried out in 30 large hospitals of Minas Gerais, from February 2018 to April 2019, after approval by the Ethics and Research Committee. Interviews were conducted with hospital managers, with Hospital Infection Control Services coordinators, and with the care coordinators of the Inpatient Units and Intensive Care Center. In addition, observations were made of the adoption of preventive measures by the multidisciplinary team in the care units. Results: in the 30 participating hospitals, 93.3% (N=28) had protocols for prophylactic antibiotics, and 86.7% (N = 26) performed their audit, 86.7% (N = 26) for therapeutic antibiotics and 83.3% (N = 25) their audit; 93.3% (N = 56) used gloves and cloaks for patients in contact precautions, and 78.3% (N=47) of the professionals were unaware of or answered incompletely on the five moments for hand hygiene. In the score to identify the adoption of measures to control bacterial resistance, 83.3% (N = 25) of the hospitals were classified as partially compliant, 13.3% (N=04) as deficient, and 3.4% (N=01) as non-adoption. Conclusion: it was found that the recommended measures to contain bacterial resistance are not consolidated in the clinical practice of the hospitals. [ABSTRACT FROM AUTHOR]

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In Brazil, Leishmania amazonensis is the etiological agent of cutaneous and diffuse cutaneous leishmaniasis. The state of Maranhão in the Northeast of Brazil is prevalent for these clinical forms of the disease and also has high rates of HIV infection. Here, we characterized the drug susceptibility of a L. amazonensis clinical isolate from a 46-year-old man with diffuse cutaneous leishmaniasis coinfected with HIV from this endemic area. This patient underwent several therapeutic regimens with meglumine antimoniate, liposomal amphotericin B, and pentamidine, without success. In vitro susceptibility assays against promastigotes and intracellular amastigotes demonstrated that this isolate had low susceptibility to amphotericin B, when compared with the reference strain of this species that is considered susceptible to antileishmanial drugs. Additionally, we investigated whether the low in vitro susceptibility would affect the in vivo response to amphotericin B treatment. The drug was effective in reducing the lesion size and parasite burden in mice infected with the reference strain, whereas those infected with the clinical isolate and a resistant line (generated experimentally by stepwise selection) were refractory to amphotericin B treatment. To evaluate whether the isolate was intrinsically resistant to amphotericin B in animals, infected mice were treated with other drugs that had not been used in the treatment of the patient (miltefosine, paromomycin, and a combination of both). Our findings demonstrated that all drug schemes were able to reduce lesion size and parasite burden in animals infected with the clinical isolate, confirming the amphotericin B-resistance phenotype. These findings indicate that the treatment failure observed in the patient may be associated with amphotericin B resistance, and demonstrate the potential emergence of amphotericin B-resistant L. amazonensis isolates in an area of Brazil endemic for cutaneous leishmaniasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Haemonchus contortus and Trichostrongylus colubriformis are the most important gastrointestinal nematodes causing serious losses in sheep production of tropical and subtropical regions. Prophylaxis of gastrointestinal nematode infections is based on anthelmintics use, but their frequent administration selects multiple-resistant parasites. To evaluate how the situation has changed over the last decades, the anthelmintic resistance status of gastrointestinal nematodes in sheep flocks was assessed in the current study and compared to previous surveys. In each one of the 15 flocks evaluated, animals (n ≥ 7) were allocated into at least five groups and treated as follows: 1) untreated control; 2) albendazole; 3) levamisole; 4) ivermectin; and 5) monepantel. If more animals were available, two additional groups were included: 6) closantel, and 7) moxidectin. The faecal egg count reduction test (FECRT) was carried out to evaluate the pre- and post-treatment using the SHINY tool. Haemonchus spp. was the most prevalent nematode from faecal cultures. The mean efficacy of albendazole was 40%. Only in two farms, levamisole presented a relatively high percentage of reduction in the FECRT about 90%, while ivermectin and moxidectin presented the worst mean efficacy of 34% and 21% among all farms, respectively. Like other anthelmintics, closantel demonstrated low efficacy (63%) across all farms evaluated. Monepantel presented an overall mean efficacy of 79%, but it was the only anthelmintic that presented efficacy ≥95%, in five farms. The results revealed that gastrointestinal nematodes with multiple anthelmintic resistance were prevalent in all 15 sheep herds. The research suggests that nematodes are becoming more and more resistant to various anthelmintic compounds, which has made the problem worse. This circumstance highlights the necessity to put into practice sustainable and long-lasting methods to prevent gastrointestinal nematode infections in sheep husbandry., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acinetobacter baumannii and Pseudomonas aeruginosa are the most relevant Gram-negative bacteria associated with hospital and opportunistic infections. This study aimed to evaluate the dynamics of drug-resistant A. baumannii and P. aeruginosa and biofilm formers from two public hospitals in northeastern Brazil. One hundred isolates (35 from A. baumannii and 65 from P. aeruginosa) were identified using the automated Vitek®2 Compact method (bioMérieux) and confirmed using the MALDI-TOF (MS) mass spectrometry technique. Molecular experiments were performed by polymerase chain reaction (PCR) to detect the frequency of blaKPC, blaIMP, blaVIM, and blaSHV genes. The biofilm formation potential was evaluated using crystal violet in Luria Bertani Miller and trypticase soy broth culture media under the following conditions: at standard concentration, one quarter (25%) of the standard concentration and supplemented with 1% glucose. In addition, the genetic diversity of the isolates was verified by the ERIC-PCR technique. Isolates presented distinct resistance profiles with a high level of beta-lactam resistance. The highest index of genes detected was blaKPC (60%), followed by blaSHV (39%), blaVIM (8%), and blaIMP (1%). All the isolates were sensitive to the polymyxins tested and formed biofilms at different intensities. Twelve clones of A. baumannii and eight of P. aeruginosa were identified, of which few were indicative of intra- and interhospital dissemination. This study reveals the dispersion dynamics of these isolates in the hospital environment. The results demonstrate the importance of monitoring programs to combat the spread of these pathogens. [ABSTRACT FROM AUTHOR]

Background: Milk is a reservoir for several groups of microorganisms, which may pose health risks. The aim of this work was to assess the antibiotic resistance and biofilm production in catalase-positive Gram-positive cocci isolated from Brazilian pasteurized milk. Methods: The bacteria were isolated using Baird-Parker agar and identified by Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF) mass spectrometer. Disk diffusion technique was used to evaluate antimicrobial susceptibility. For qualitative evaluation of biofilm production, the growth technique was used on Congo Red Agar. Results: Totally, 33 out of 64 isolates were identified, including Staphylococcus epidermidis (n=3; 4.7%), Macrococcus caseolyticus (n=14; 21.9%), and Kocuria varians (n=16; 25%). Twenty-two isolates were resistant to at least one antibiotic. Biofilm production was detected in only 5 isolates of K. varians and 1 isolate of S. epidermidis. All 14 M. caseolyticus isolates were resistant to at least one antibiotic; but, multidrug resistant (MDR) isolates were not detected. Among all K. varians isolates, 4 were resistant to at least one antibiotic from three different classes and were considered to be MDR. Conclusion: The presence of antibiotic-resistant M. caseolyticus, S. epidermidis, and K. varians isolates, especially MDRs, in milk samples highlights the possible role of milk as a reservoir of resistance genes. [ABSTRACT FROM AUTHOR]

Background: Visceral leishmaniasis/HIV-co-infected patients (VL/HIV) accounts for around 8% of VL reported cases in Brazil. Relapses of Leishmania infection after anti-leishmanial treatment constitute a great challenge in the clinical practice because of the disease severity and drug resistance. We have shown that non-relapsing-VL/HIV (NR-) evolved with increase of CD4+ T-cell counts and reduction of activated CD4+ and CD8+ T cells after anti-leishmanial treatment. This immune profile was not observed in relapsing-VL/HIV patients (R-), indicating a more severe immunological compromising degree. Elevated activation status may be related to a deficient immune reconstitution and could help to explain the frequent relapses in VL/HIV co-infection. Our aim was to evaluate if this gain of T cells was related to changes in the peripheral TCRVβ repertoire and inflammatory status, as well as the possible thymus involvement in the replenishment of these newly formed T lymphocytes. Methods: VL/HIV patients, grouped into non-relapsing (NR- = 6) and relapsing (R- = 12) were evaluated from the active phase up to 12 months post-treatment (mpt). HIV-infected patients (non-VL) and healthy subjects (HS) were included. The TCRVβ repertoire was evaluated ex vivo by flow cytometry, whereas the plasmatic cytokine levels were assessed by Luminex assay. To evaluate the thymic output, DNA was extracted from PBMCs for TCR rearrangement excision circles (TREC) quantification by qPCR. Results: VL/HIV cases presented an altered mobilization profile (expansions or retractions) of the TCRVβ families when compared to HS independent of the follow-up phase (p < 0.05). TCRVβ repertoire on CD4+ T-cells was more homogeneous in the NR-VL/HIV cases, but heterogeneous on CD8+ T-cells, since different Vβ-families were mobilized. NR-VL/HIV had the inflammatory pattern reduced after 6 mpt. Importantly, VL/HIV patients showed number of TREC copies lower than controls during all follow-up. An increase of recent thymic emigrants was observed in NR-VL/HIV individuals at 10 mpt compared to R- patients (p < 0.01), who maintained lower TREC contents than the HIV controls. Conclusions: VL/HIV patients that maintain the thymic function, thus generating new T-cells, seem able to replenish the T lymphocyte compartment with effector cells, then enabling parasite control. [ABSTRACT FROM AUTHOR]

The selection of fungal isolates resistant to available therapy associated with an increase in the number of immunosuppressed patients has contributed to the incidence of infections caused by dematiaceous fungi. Thus, this study evaluated the therapeutic efficacy of the main antifungal agents currently used in clinical practice in relation to Curvularia spp. and Hortaea werneckii from cases of superficial phaeohyphomycosis from southern Brazil. The susceptibility profile of amphotericin B, fluconazole, itraconazole, terbinafine and voriconazole against dematiaceous fungi (Curvularia lunata, C. pallescens and H. werneckii) was evaluated by microdilution in broth. Terbinafine showed greater efficacy against C. lunata - gemometric mean (GM = 0.38 µg/mL), C. pallescens (MIC = 0.125 µg/mL) and H. werneckii (GM = 0.031 µg/mL) when compared to the other antifungals tested. Most of species showed sensitivity to itraconazole and voriconazole, with a minimum inhibitory concentration (MIC) range from 1 - 8.0 µg/mL and 0.5 - 2.0 µg/mL, respectively. All isolates tested show low sensitivity to fluconazole (MIC range 4 - 16 µg/mL). Although itraconazole is considered gold standard, terbinafine has been showed to be a good alternative for the treatment of superficial phaeohyphomycosis. Lastly, antifungal susceptibility testing is essential to indicate the ideal therapy against these infections. [ABSTRACT FROM AUTHOR]

Background: Reports of a lack of efficacy of most of the anthelmintic compounds for ruminants associated with the long-time necessity for creating new molecules have stressed the urgency to adopt alternative methods to control gastrointestinal parasites infection, such as strategies of sharing grazing areas. Therefore, this study aimed to evaluate nematode populations affecting cattle and sheep that share grazing areas before and after treatment with different anthelmintic compounds, and investigate the efficacy of anthelmintic treatment in these naturally infected ruminants at farms in the state of Rio Grande do Sul, Brazil. Methods: The presence of co-infections by Haemonchus species was investigated by polymerase chain reaction (PCR) for groups treated with a benzimidazole. Farms were selected by: farmers' consent, presence of 42–60 (or more) calves and sheep per farm with counts of ≥ 200 eggs per gram of feces (EPG), availability of calves and lambs aging from 6 to 9 months, absence of anthelmintic treatment for both species for 60 days before the experimental period, and shared grazing areas between this species on each farm. Animals were distributed into six treatment groups for each ruminant species per farm and treated with: ivermectin, doramectin, moxidectin, levamisole, albendazole, and closantel. Results: Levamisol was the most effective anthelmintic compound for both ruminant species. In general, Cooperia spp., Haemonchus spp., and Trichostrongylus spp. were the genus present after tested treatments that were ineffective. PCR showed the presence of Haemonchus species co-infections between cattle and sheep. Conclusion: Therefore, this study demonstrated the similarity between nematode population, the presence of multi-resistant nematodes, and the presence of Haemonchus species co-infections affecting different ruminant species that share pastures. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic importance of resistant hypertension (RHT) for the development of complications in a cohort of individuals with type 2 diabetes.Research Design and Methods: A total of 646 patients had the diagnosis of apparent treatment-resistant hypertension (aRHT) based on mean office blood pressure (BP) levels during the 1st year of follow-up. They were reclassified as white-coat/controlled or true/uncontrolled RHT according to 24-h ambulatory BP monitoring (ABPM), using the traditional BP cutoffs and the new 2017 American College of Cardiology (ACC)/American Heart Association (AHA) criteria. Multivariate Cox analyses examined the associations between RHT diagnoses and the occurrence of microvascular and cardiovascular complications and all-cause and cardiovascular mortality.Results: During a median follow-up of 10 years, 177 patients had a cardiovascular event (145 major ones); 222 patients died (101 from cardiovascular diseases); 200 had a renal event; 156 had a retinopathy event; and 174 patients had a neuropathy event. In relation to non-RHT individuals, aRHT (present in 44.6% and 50% by the traditional and new criteria, respectively) predicted all cardiovascular and mortality outcomes, with hazard ratios (HRs) between 1.64 and 2.16, but none of the microvascular outcomes. True RHT increased the HRs (from 1.81 to 2.25) and additionally predicted renal outcomes. White-coat/controlled RHT implied an increased risk (HRs 1.33-1.86) that was intermediate between non-RHT and true RHT individuals. Classifications using the traditional and the new ACC/AHA criteria were equivalent.Conclusions: In patients with type 2 diabetes, the presence of aRHT implied an increased risk of cardiovascular and mortality outcomes, and classification based on ABPM predicted renal outcomes and improved cardiovascular/mortality risk stratification. [ABSTRACT FROM AUTHOR]

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This study aimed to analyze ESBL-producing Escherichia coli prevalence in urine samples collected between 2011-2019 in Curitiba, a large city in Brazil, and relating it to antibiotic consumption and sanitary conditions. This is a longitudinal study correlating prevalence of ESBL-producing E. coli isolates from urine samples with district-level antibiotic consumption and sociodemographic data during 2011-2019. E. coli isolates were tested for antibiotic susceptibility and ESBL by an automated method. Statistical analysis applied linear regressions, pooled ordinary least squares, and fixed effects models for districts or years. The Chow and Hausman tests indicated that the fixed effects model for individual districts fitted best. Chi-square test was used for qualitative variables (statistical significance was set when P < 0.05). Among the 886 535 urine sample cultures, 9.9% of isolates were ESBL-producing E. coli. Their prevalence increased from 4.7% in 2012 to 19.3% in 2019 (P < 0.0001; R2 = 0.922). This progressive increase correlated with age (P = 0.007; R2 = 0.8725) and male gender (P < 0.001) and increased antibiotic consumption (P = 0.0386; R2 = 0.47). The fixed effects model showed that district influences ESBL prevalence and that antibiotic consumption explains 20%-30% of this variation, with an increase of one defined daily dose accounting for an increase of 0.02084 percentage points of ESBL. The increasing prevalence of ESBL-producing E. coli can, to a considerable extent, be explained by increasing antibiotic consumption., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Background: Protease inhibitors (PI) are especially important in salvage therapy. Previous treatment failure with a PI containing regimen may elicit resistance mutations, reducing PI susceptibility and limiting treatment options. The aim of this study was to describe major PI mutations among patients exposed to at least one PI to evaluate predictors of mutation emergence and the impact of subtypes on resistance. Methodology: Partial HIV-1 pol sequences (Sanger Sequencing) from patients exposed to PI with virological failure were genotyped from January 2014 to December 2017. Drug resistance mutations (DRM), antiretroviral susceptibility (GSS) and subtypes, along clinical and laboratory parameters, were evaluated using logistic regression to access the predictors of mutation emergence. Results: In 27.5% (466/1696) of the cases at least one major PI mutations was identified, most commonly M46 (14.7%), V82 (13.8%) and I54 (13.3%). Mutations to NRTI and NNRTI were observed in 69.6% and 59.9%, respectively, of the 1696 sequences. Full activity to darunavir was predicted in 88% (1496/1696), but was only 57% among those with at least one PI-DRM. Subtype C sequences had less major PI-DRMs (10%, 9/87) compared to B (28%, 338/1216) or F (35%, 58/168) (p <0.001) but adjusted analysis suggested that this association is not independent from a shorter treatment time and fewer regimens (OR 0.59, Confidence Interval 95: 0.2–2.5, p = 0.48). Subtype F, together with NRTI mutations and longer time on treatment was associated to presence of PI-DRM, to a lower darunavir GSS and to mutations at codon I50. Conclusions: Among patients with PI-DRM, full activity to darunavir was compromised in almost half of the cases and efforts to detect failure at earlier time are warranted, particularly for HIV-1 subtype F that showed association to the emergence of resistance, with potential impact in protease inhibitors sequencing. Furthermore, NRTI mutations may serve as an indicative of sufficient adherence to allow PI-DRM emergence. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a major health concern globally and treating infections caused by MDR-isolates unarguably a humongous challenge that remains an unmet need in modern medicine. To determine patterns and mechanisms of antimicrobial resistance and its spread over the years in Rio de Janeiro, Brazil, 88 P. aeruginosa isolates were selected from 1995 to 2015. Phenotypic and genotypic characterization of antimicrobial resistance was evaluated and isolates were submitted to clonality by PFGE and MLST. PFGE analysis showed a great variability of clonal groups mainly over the past 10 years of this study. STs predominant in the early years (ST804, ST1860, ST487 and ST1602) associated to multidrug resistance (MDR) phenotype were replaced by ST277, ST244, ST1945, ST1791 with extensive drug resistance (XDR) in last years, with significant increase in resistance to carbapenems, fluoroquinolones and aminoglycosides. Colistin resistance was detected in 3.5%. The main mechanisms of antimicrobial resistance were mutational mechanisms (mutations in oprD, mexT and gyrA genes). We found the ESBL genes bla TEM (n = 2), bla SHV (n = 3) and bla CTX (n = 1).The carbapenemases genes was present in ST277 (bla SPM , n = 3), ST1560 (bla KPC , n = 3) and ST1944 (bla KPC , n = 2). The 16S RNA methylase gene (rmt D) was found in five isolates belonged to ST277. In conclusion, molecular epidemiological investigation reveals an increase of antimicrobial resistance in P. aeruginosa over 21 years in Rio de Janeiro with higher population structure and occurrence of high risk clone in the last years. The mutational mechanisms of resistance were present in all XDR isolates. • Resistance in Pseudomonas aeruginosa increased over the 21 years. • The phenotype of MDR was replaced by the XDR phenotype. • The carbapenemases genes bla KPC-2 and bla SPM-1 were detected. • Mutations were found in opr D, mex T and gyr A in MDR and XDR. • High-risk clones (ST277 and ST244) detected in the last years. [ABSTRACT FROM AUTHOR]