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Abstract Introduction Community-Acquired Pneumonia (CAP) caused by pneumococcus and Invasive Pneumococcal Disease (IPD) pose a substantial economic burden on health systems. The objective of the present study is to explore hospitalization costs of pneumococcal disease in the public health system in Brazil, the Unified Health System. Methods Retrospective analysis of administrative data on hospitalized cases of pneumococcal disease from January 2019 to July 2023. Hospitalization cases recorded with ICD-10 codes of CAP due to S. pneumoniae and IPD were retrieved from DATASUS, the inpatient information system of the Unified Health System in Brazil. Costs were converted to US dollars by Using Purchasing Power Parity (USD-PPP). Absolute number of hospitalizations, costs of hospitalizations and healthcare resource utilization were presented descriptively. The annual cost estimate was calculated. Differences in costs by type of clinical presentation and age group were assessed. Factors associated with higher costs were explored by multiple linear regression models. Results A total of 22,498 hospitalization episodes were analyzed. Total cost of hospitalizations was USD-PPP 13,958,959 (BRL 34,659,578) with an annual mean estimate of USD-PPP 3,045,591 (BRL 7,562,090). Cost per hospitalization episode was significantly higher for meningitis, followed by septicemia, CAP and arthritis, with median values ranging from USD-PPP 190.93 to 615.14 (BRL 476.20 to 1529.02). (Kruskal-Wallis χ2 = 6473, df = 3, p-value < 0.0001). Costs were significantly higher among individuals aged 60-years and older. (Kruskal-Wallis test; χ2 = 773.53; df = 2, p-value < 0.0001). There were differences in age at hospitalization, length of stay, and ICU utilization among types of clinical presentations. Conclusions Our findings reveal the economic burden associated with pneumococcal disease in the Unified Health System in Brazil. Hospitalization costs were higher for cases of meningitis and among individuals aged 60-years and above.

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Abstract Specific Pathogen-Free (SPF) animals are bred and maintained to exclude pathogens associated with significant morbidity or mortality, which may pose a risk to research replicability. The BALB/c strain is distributed globally and is among the most commonly used inbred strains in immunology and infectious disease research. Despite being a widely distributed bacterium that causes chronic infection, Bartonella henselae infection has not been investigated in any protocol that characterizes SPF animals. The objective of this study was to investigate the potential natural infection of laboratory animals of the BALB/c lineage by B. henselae. To achieve this, ten immunocompetent BALB/c mice were obtained directly from the bioterium and euthanized for collection of samples, including blood, skin, spleen, liver, heart, eye, kidney, intestine, esophagus, and brain. DNA was extracted using a commercial kit and tested via nested PCR for the ftsZ gene, as well as conventional PCR and qualitative real-time PCR using Sybr® Green for the citrate synthase gene (gltA), all specific reactions for B. henselae. All animals showed detection of B. henselae DNA in at least two different reactions in different tissues. The sequenced amplicons showed 100 % similarity to B. henselae. The use of mice infected by B. henselae in experiments is undesirable, as the bacteria can affect several aspects of the animal's physiology and consequently influence the results of the project, especially when subjected to immunosuppression. More studies are needed to understand and confirm the natural infection in experimental animals by Bartonella spp.. To date, no additional published reports of contamination of experimental animals by these bacteria have been identified.

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Abstract Increased spread of antimicrobial resistance by Gram-Negative Bacilli (GNB) poses a global challenge, with exacerbated burden post-pandemic. The aim of this study was to investigate the in vitro activity of ceftolozane/tazobactam and its comparators against the frequently identified GNB isolated from patients admitted to Brazilian medical sites between the year 2018‒2019 and 2020‒2021. The impact of pandemic on antimicrobial resistance and presence of β-lactamase genes were also evaluated. Antimicrobial susceptibility testing and molecular characterization of ß-lactamase encoding genes using Polymerase Chain Reaction (PCR) and DNA sequencing were carried out from GNB isolated mostly from intra-abdominal, respiratory, and urinary tract infections and interpreted following BrCAST/EUCAST guidelines. A total of 3994 GNB isolates were evaluated which mostly included E. coli, K. pneumoniae and P. aeruginosa. Ceftolozane/tazobactam remained highly active against E. coli isolates during both 2018‒2019 (96.0 %) and 2020‒2021 (98.5 %). Among K. pneumoniae, ceftolozane/tazobactam (47.6 % and 43.0 % susceptible during 2018‒2019 and 2020‒2021, respectively) showed poor activity due to blaKPC-2. Colistin and ceftolozane/tazobactam were the most active β-lactam agents tested against P. aeruginosa in 2018‒2019 (99.3 % and 88.8 %) and 2020‒2021 (100 % and 92.8 %), including ceftazidime and meropenem resistant isolates. β-lactamase encoding gene characterization was carried out and both carbapenemases and Extended-Spectrum β-Lactamase (ESBL) producers were found in E. coli, K. pneumoniae and P. aeruginosa isolates. Ceftolozane/tazobactam documented remarkable in vitro activity against E. coli and P. aeruginosa isolates in Brazil, both pre- and post-pandemic periods and could constitute an effective therapeutic option for the treatment of urinary tract infections, intra-abdominal infections, and respiratory tract infections.

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Abstract Candidemia is the predominant form of invasive candidiasis and the most frequently occurring serious fungal infection in critically ill patients in Intensive Care Units (ICU). Studies carried out in Latin America reveal a higher incidence of candidemia and higher mortality rates when compared to North America or Europe. This highlights the need to develop guidelines for correctly diagnosing and treating candidemia in critically ill patients in the ICU. These guidelines are part of the efforts to implement antifungal optimization programs in the region to obtain better clinical outcomes and promote rational antifungal use. This evidence-based clinical standard, established through expert consensus for the Latin American context, contains recommendations and algorithms for diagnosing and treating candidemia in critically ill ICU patients.

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Abstract Objective To outline the features of COVID-19 in Brazil through a countrywide telephone survey. Methods Data from the Telephone Survey of Risk Factors for Chronic Noncommunicable Diseases During the Pandemic (Covitel), a telephone survey of individuals aged 18 years or older from all macro-regions of Brazil, were used. The questionnaire included sociodemographic characteristics and outcomes related to COVID-19 infection, severity, vaccination, and use of masks. Results Data revealed that 34.7 % (95 %CI 32.4 - 37.1) of the population had been diagnosed with COVID-19, and 10.1 % (95 %CI 7.9 - 12.7) of those required hospital admission. The prevalence of COVID-19 diagnosis increased with education level: <8 years (26.6 % [95 %CI 23.1 - 30.7]), 9-11 years (33.4 % [95 %CI 29.4 - 37.7]), and >11 years (53.2 % [95 % CI 49.7 - 56.8]). Nevertheless, the hospitalization rate of Brazilians with more than eleven years of education was lower (5.8 % [95 %CI 4.3 - 7.6]). In 2023, 92.9 % (95 %CI 90.9 - 94.4) of the Brazilian population was fully vaccinated against COVID-19, but only 37.2 % (95 %CI 33.5 - 40.9) have received the updated vaccinal scheme (two doses and two boosters). During the pandemic outbreak, 81.9 % (95 %CI 79.4 - 84.2) reported always using face masks. However, only 16.1 % (95 %CI 13.5 - 19.0) maintained this practice in 2023. Conclusion There were inequalities in COVID-19 testing in Brazil. Testing and vaccination policies implemented in the COVID-19 pandemic must be reevaluated by the Brazilian government.

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Abstract Background Human Cytomegalovirus (HCMV) remains a significant cause of morbidity and mortality among pregnant women and immunocompromised patients. HCMV transmission can occur through blood transfusions and typically results in asymptomatic infections in newborns and young individuals or causes symptoms like infectious mononucleosis when symptomatic infections arise. HCMV infection poses a notable risk to transfusion recipients, particularly in vulnerable groups such as premature newborns and immunosuppressed patients. The risk persists even after prophylaxis ends, especially in patients who undergo organ transplantation and receive blood or blood products from a seropositive donor while being seronegative themselves (D+/R-). Materials and methods Here, we investigated the serological and molecular prevalence of HCMV among 980 blood donors from the main blood bank in Rio de Janeiro, Brazil, using chemiluminescence and real-time PCR (TaqMan). The data underwent univariate, bivariate, and multivariate statistical analyses using the SPSS program, version 20.0. Results The average age of donors was 38.53 years, with a majority being male (53.9 %). The prevalence of cytomegalovirus was 88.5 %, and HCMV DNA was detected in 1.2 % of the samples. Discussion Given that there are approximately 100,000 blood donations per year, this prevalence rate is considerably high compared to that in developed countries. These findings underscore the critical need for ongoing surveillance and molecular testing to ensure the safety of blood supplies.

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Abstract Introduction Post-COVID Syndrome (PCS), occurs several weeks after Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2 infection), has a frequency of 10 %‒35 % of cases, presents a wide range of symptoms that can persist for months or years and markedly reduces the quality of life of patients. Objective To describe clinical, epidemiological and evolutionary aspects of a cohort of patients diagnosed with PCS followed on an outpatient basis. Methodology Individuals of both sexes, > 18-years old who presented symptoms suggestive of PCS and had previously confirmed SARS-CoV-2 infection were included. Clinical evaluation was carried out monthly by a multidisciplinary team, and if necessary laboratorial exams were performed. Results From June 2021 to June 2022, 92 cases of PCS were diagnosed, of which 60 (65.2 %) were female and the average age was 49.1 years. In 61 (66.3 %) of the cases, SARS-CoV-2 infection occurred between January and November 2021. In 55 (59.7 %) of the cases the symptoms were mild, while 31 (36.0 %) were moderate or severe cases. Most cases of PCS occurred in individuals with the mild form of COVID-19. The predominant symptoms were chronic fatigue in 59 (68.6 %) cases, brain fog in 68 (73.4 %), myalgias and arthralgias in 44 (47.8 %), cramps and paresthesia's in 40 (46.5 %). The main comorbidities observed were high blood pressure, obesity and diabetes mellitus. The persistence of symptoms was greater in those cases who presented severe forms of COVID-19. Most patients experienced gradual and progressive improvement over the months. Discussion The profile of patients with PCS in this cohort is similar to other reports. A great number of symptoms is remarkable with variable presentation and evolution and their frequency exceeds that previously described in a large meta-analysis. Inflammatory phenomena mediated by the virus, autoimmunity and direct organic damage have been implicated in the genesis of this syndrome.

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Abstract Introduction We aimed to create and validate the 30-day prognostic score for mortality in patients with surgical wound infection (SWICS-30) after cardiothoracic surgery. Methods This retrospective study enrolled patients with surgical wound infection following cardiothoracic surgery admitted to a Cardiologic Reference Center Hospital between January 2006 and January 2023. Clinical data and commonly used blood tests were analyzed at the time of diagnosis. An independent scoring system was developed through logistic regression analysis and validated using Artificial intelligence. Results From 1713 patients evaluated (mean age of 60 years (18-89), 55 % female), 143 (8.4 %) experienced 30-day mortality. The SWICS-30 logistic regression score comprised the following variables: age over 65 years, undergoing valve heart surgery, combined coronary and valve heart surgery, heart transplantation, time from surgery to infection diagnosis exceeding 21 days, leukocyte count over 13,000/mm3, lymphocyte count below 1000/mm3, platelet count below 150,000/mm3, and creatinine level exceeding 1.5 mg/dL. These patients were stratified into low (2.7 %), moderate (14.2 %), and high (47.1 %) in-hospital mortality risk categories. Artificial intelligence confirmed accuracy at 90 %.

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Abstract Background Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) share the same routes of transmission, therefore, co-infection by both viruses represents a challenge to the goal of eliminating viral hepatitis as a public health threat. There are an estimated 2.3 million people living with HIV/HCV worldwide. Most of these cases affect vulnerable populations located in places with low infrastructure. Because of this, the use of alternative samples such as Dried Blood on Spot (DBS) would facilitate access to diagnosis and HCV treatment. The aim of this study is to evaluate the HCV genetic variability in HIV/HCV individuals by correlating paired serum and DBS samples. Methods A total of 14 HIV/HCV individuals, recruited from reference outpatient clinics in the city of Rio de Janeiro/Brazil, were included. From them, 64 % were man, mean of age 54±7. HCV RNA from both serum and DBS samples was RT-PCR amplified and sequenced with HCV NS5B-specific oligonucleotides. All positive samples were submitted to phylogenetic analysis. Results Serum mean HCV load was 6.2 ± 0.5 log IU/mL. All patients presented undetectable HIV RNA. The distribution of HCV genotypes/subgenotypes was 1a (4/14); 1b (5/14); 3a (4/14); and 4d (1/14). Most paired serum and DBS samples showed concordant results (genetic distance: 0.0 to 0.16). One individual showed discordance in the subtypes between serum and DBS. Three individuals presented the 316 N Resistance Associated Mutation (RAS) in both serum and DBS. Conclusion Our results demonstrate the applicability of DBS for HCV molecular tracking in HIV/HCV coinfected patients for viral genomic surveillance in key and vulnerable populations.

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Abstract Background Dolutegravir (DTG) is widely used as a first-line Antiretroviral Therapy (ART) due to its high efficacy and safety. However, concerns about DTG resistance persist. This study investigated the prevalence and factors associated with transmitted DTG resistance in treatment-naive HIV-1-infected individuals in Brazil. Methods The study followed 150 treatment-naive HIV-1 individuals from May 2019 to May 2022 at a reference center for HIV/AIDS in Rio de Janeiro, Brazil. Baseline characteristics, viral load, and CD4 + cell counts were assessed. Genotypic resistance testing was conducted on plasma samples at baseline, and viral load was monitored during follow-up visits. Results One hundred and thirty-one patients completed the study. The mean age was 37.73-years; 107 were male, and 24 were female. The median baseline of viral load was 4.33 log (21,193 copies/mm3), and CD4 + count was 342 cells/mm3, with the lowest count being 8 cells/mm3. The mean CD4 + count increase was 112 cells/mm3 (p < 0.01). One hundred and nine patients achieved an undetectable viral load three months after starting ART, with only eight patients not reaching undetectable levels by six months (42‒106 copies/mm3). The most common early adverse effect was nausea (12.9 %), and the most common later effect was increased creatinine levels (9.1 %), leading to the suspension or substitution of Tenofovir Disoproxil Fumarate (TDF). Genotyping was successfully performed on 85 patients: 66 were subtype B, 9 subtype C, 8 subtype F, and two CRF47_BF, with no resistance mutations and one accessory mutation (T97A). Conclusion This study did not demonstrate transmitted DTG resistance among treatment-naive HIV-1-infected individuals. The findings suggest that DTG remains a safe and effective first-line ART option. However, close monitoring of viral load is recommended for all patients on DTG-containing ART regimens. Additionally, genotypic resistance testing should be performed on individuals who experience virological failure or a significant decline in CD4 + cell counts, with close attention to ART adherence.

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Abstract This study describes and estimates the social and economic impact of Invasive Meningococcal Disease (IMD) sequelae globally and in Brazil. An integrative review was conducted to identify IMD sequelae costs estimates worldwide. The evidence identified supported the development of a Delphi survey to estimate medical Resource Use (RU) and caregiver productivity loss during the first Year (Y1) of IMD and the Subsequent Year (SY) in Brazil. Treatment costs of long-term IMD sequelae were estimated through microcosting approach using Brazilian cost reference tables and taking into account the Delphi survey estimates. The review included eight studies from high-income countries. Mean costs of IMD sequelae in high-income countries varied substantially by type of sequelae in Y1 (hearing loss $14,511; amputation $144,087), type of care over a lifetime horizon (outpatient $28,498; inpatient $67,038), and medical procedure over a lifetime horizon (shunt revision $22,794; prosthesis $508,735). The Delphi survey indicated that medical RU was significantly higher in Y1 versus SY. Resource use was highest for patients with multiple limb amputations. In addition, the highest number of outpatient visits (32) were required for patients with skin scars; speech therapy (72) for hearing loss; and the most psychologist sessions (116) for mental health disorders in Y1. Similarly, estimated treatment costs were highest for patients with multiple limb amputations ($4,139.70 in Y1 and $1,874.39 for SY), followed by single limb amputation ($2,803.24 in Y1 and $902.73 for SY) and skin scarring ($2,307.69 in Y1 and $816.19 for SY). All sequelae resulted in multiple workdays lost for caregivers, ranging from 33 (skin scarring) to 85 (multiple limbs amputation) during the first year of treatment. This study informs decision-makers on the healthcare, social and educational services, and social protection needs of patients with long-term sequelae in Brazil and globally.

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Abstract Background Ceftazidime-Avibactam (CAZ-AVI) plays a key role in the treatment of Multidrug Resistant Gram-Negative Bacilli (MDR-GNB) infections. In pediatrics, CAZ-AVI is clinically approved for treatment of urinary tract or intra-abdominal infection. However, there is limited data available about its use in children with cancer who have complicated infections caused by MDR-GNB. Objective This study aims to describe our experience in using CAZ-AVI for the treatment of MDR GNB infections in children with cancer. Methods This retrospective observational study was conducted at the Pediatric Oncology Institute (IOP/GRAACC/UNIFESP), including pediatric oncologic patients who received CAZ-AVI for the treatment of infections caused by GNB. Results From Jan/2021 to Jun/2022, 11 patients with 13 episodes were included in the analysis. Among them, 45 % were female, with a median age of 7 years. Three patients had Acute lymphoblastic Leukemia (ALL), three had Acute Myeloid Leukemia (AML), two had Non-Hodgkin Lymphoma (NHL). Additionally, there was one case each of medulloblastoma, fibrosarcoma, and craniopharyngioma. All patients presented significant risk factors for MDR-GNB, such as neutropenia and two were submitted to Hematopoietic Stem Cell Transplantation (HSCT). The infection episodes included six Bloodstream Infections (BSI), two Urinary Tract Infections (UTI), two tracheobronchitis cases, along with one case each of necrotizing pneumonia, ventriculitis, and endocarditis. The identified pathogens included Klebsiella pneumoniae, Pseudomonas spp., Enterobacter cloacae, and Stenotrophomonas maltophilia. The primary reason for prescribing CAZ-AVI was either Multidrug-Resistant Gram-Negative Bacteria (MDR-GNB) infection or clinical worsening after initial therapy. Combination therapy was prescribed in eight episodes with a median prescription length of nine days. Microbiological sterilization was achieved in 92 % of episodes, and the 30-day survival rate was 84 %. Notably, no deaths were associated with treatment failure, and no adverse events associated with CAZ-AVI use were observed. Conclusion CAZ-AVI could be used for treating GNB infections in oncologic pediatric patients.

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Abstract Crimean-Congo Hemorrhagic Fever (CCHF) is a viral hemorrhagic fever common in many regions of the world. There are many diseases in the differential diagnosis of CCHF. In our study, we aimed to predict the diagnosis of CCHF at the time of initial presentation by using clinical and laboratory findings in patients with a preliminary diagnosis of CCHF. In our study, 74 patients with a definitive diagnosis of CCHF and 43 patients with a preliminary diagnosis of CCHF but not diagnosed with CCHF were compared in terms of demographic, clinical and laboratory findings. Multivariate logistic regression analysis and Receiver Operating Characteristics (ROC) curve were used to determine variables to predict the diagnosis of CCHF. Living in an endemic area, tick bite, fever, CRP below 48 mg/L and PCT below 0.52 ng/mL were determined as independent risk factors for CCHF diagnosis. The specificity for cut off values of 2485 mm3 for WBC and 970 mm3 for neutrophil count were 86 % and 93 %, respectively. The sensitivity for cut off values of 48 mg/L for CRP and 0.52 ng/mL for PCT were 90.5 % and 82.4 %, respectively. In-hospital and 28-day mortality were higher in the non-CCHF group. The differential diagnosis of CCHF is important for planning appropriate isolation procedures and treatments for patients. Additionally, by excluding CCHF, it allows for the early consideration of other diseases in the non-CCHF group that show high mortality. In patients living in endemic areas with tick bites and clinical findings compatible with CCHF, easily accessible tests such as WBC, neutrophil count, CRP and PCT, within the cut-off values identified in our study, will assist in diagnosing CCHF at the initial presentation.

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Abstract Aspergillosis is a disease caused by the filamentous fungus Aspergillus spp. with a spectrum of clinical presentation that includes invasive and noninvasive forms. The invasive clinical presentation of aspergillosis most frequently affects people with compromised immune systems. In patients with oncohematologic pathology, invasive lung aspergillosis is a significant opportunistic mycosis, because it occurs frequently and has a major impact on morbidity, mortality, and high costs. The global problem of antimicrobial resistance, to which improper use of antifungals contributes, has put Aspergilus spp. in the spotlight, so it is important to generate guidelines for guidance in the proper use of antifungals in the management of invasive lung aspergillosis, to obtain better clinical outcomes and promote rational use of antifungals. This guideline contains recommendations for diagnosing and treating invasive lung aspergillosis in patients with oncohematologic disease, based on evidence and defined through a participatory process of expert consensus, for the Latin American context.

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Abstract Methicillin-Resistant Staphylococcus Aureus (MRSA) is commonly transmitted among hospitalized patients through direct contact or contaminated objects. However, the dynamics of household transmission of MRSA remain unclear, posing challenges for effective prevention. This study evaluates the persistence of MRSA colonization in asymptomatic carriers over a period of at least 17-months and examines the potential for intra-household transmission. We conducted home visits to seven families, each with at least one MRSA-colonized member, to collect nasal swabs from all household members. Phenotypic and genotypic profiles of the isolates were determined through culture, antimicrobial susceptibility testing, and PCR. We compared these new samples with previous samples from a recent study involving the same individuals to assess spontaneous clearance of MRSA. A total of 25 samples were collected, with 56 % (14) identified as S. aureus and 44 % (11) as non-S. aureus; among the S. aureus isolates, four were MRSA. We observed spontaneous clearance of MRSA in six of the original cases. Unexpectedly, there was limited intra-household transmission of MRSA, although all families with MRSA colonization had at least one member with a history of skin disease. In the family where colonization persisted, one individual had recurrent cutaneous abscesses, suggesting a possible link to sustained colonization.

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ABSTRACT Introduction: Syphilis is a highly prevalent sexually transmitted infection worldwide. Patients living with Human Immunodeficiency Virus (HIV) have a higher risk of developing neurosyphilis. Actual guidelines advise to proceed with lumbar puncture only if neurologic symptoms are present. However, asymptomatic neurosyphilis patients are not rare in the HIV population and other risk factors should be defined to guide screening. Methods: We performed a retrospective cohort to evaluate risk factors related to neurosyphilis in HIV patients. Adults with HIV infection and laboratory confirmed syphilis between 2011 and 2021 were included. Patients with no record of syphilis treatment, VDRL titers ≤ 1:4, other neurologic diseases or non-HIV related immunological impairment were excluded. The patients were followed for 2-years after syphilis diagnosis. Results: One-hundred and forty patients (190 syphilis episodes) were included, with mean age of 45.0 ± 9.2-years-old, 111 (79.3 %) were male, 48 (25.8 %) had CD4 count ≤ 350 cells/mm3 at syphilis diagnosis (median: 522.5 cells/mm3; IQR: 315.5-703.5), 127 (66.8 %) of 172 had a HIV viral load ≤ 400 copies/mm3 and median serum VDRL titer was 1:64 (IQR: 1:16–1:128). In multivariate analysis, serum VDRL titers ≥ 1:32 and the presence of neurologic symptoms were associated with neurosyphilis, while HIV viral load ≤ 400 copies/mm3 was a protective factor. Discussion: In addition to the presence of neurological symptoms, HIV viral load > 400 copies/mm3 and VDRL titers ≥ 1:32 were shown to be risk factors for neurosyphilis in this study and diagnostic lumbar puncture should be considered in these cases.

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ABSTRACT Background: Infective Endocarditis (IE) is a serious disease, with high morbidity and mortality. Few case series come from middle- income countries. Our aim is to describe a case series of patients with IE treated at a reference center in Brazil and compare data to other countries. Methods: A retrospective analysis of a prospectively implemented endocarditis database was conducted, including adult patients with definite IE, January 2006–June 2023. A literature search and summary were done. Statistical analysis was performed using Jamovi®, version 1.2.2. Results: There were 502 episodes of IE; mean age ± SD was 48.4±17.2 years. Community-acquired IE occurred in 64.7 %. Main predispositions were rheumatic valve disease (30.7 %), prostheses (31.5 %), and congenital heart disease (13.9 %). Transthoracic and transesophageal echocardiograms were performed in 85 % and 78 %, respectively. Left-sided IE predominated. Fever occurred in 90.6 %, new murmurs in 50.7 %, and embolism in 45 %. Blood cultures were negative in 33.1 %; frequent pathogens were oral streptococci (15.6 %), Staphylococcus aureus (10.0 %), and enterococci (12.8 %). Main complications were heart failure (58 %), renal failure (32.8 %), and splenic embolization (35.2 %). Surgery was performed in 83.6 %; overall in-hospital mortality was 25 %; surgical mortality was 21.3 %. Conclusions: Blood culture negative left-sided IE predominated. The mortality rate was high but within the range of reported series. Surgery was performed frequently and patients who were operated on had lower mortality.

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ABSTRACT Gestational (GS) and congenital syphilis (CS) are important public health problems in Brazil. This study aims to estimate the prevalence of GS, the incidence of CS and the rate of vertical transmission (VT) of syphilis, as well as to evaluate the management indicators of GS in the State of Rio de Janeiro (RJS), the Brazilian state with the highest detection rate of GS and incidence of CS in 2022. A hospital-based, cross-sectional study was carried out in public and private hospitals located in RJS, in the period 2021-2023, with interviews with 1,923 women, analysis of prenatal care (PNC) cards and hospital records. The GS management indicators, the prevalence of GS, the incidence of CS and the rate of VT were estimated with the respective 95 % confidence intervals (95 % CI), according to the source of financing for hospitalizations for childbirth or abortion care. PNC was reported by 93.7 % of women, 82.7 % had the first test for syphilis and 52.6 % the second. The prevalence of GS was estimated at 14.5 % (95 % CI 9.2 %- 22.2 %), with higher values in women with public financing (18.2 % public; 3.6 % private). Nearly one-third-of women with GS were diagnosed only during hospitalization for childbirth or abortion care and 13.4 % were appropriately treated during PNC. The incidence of CS was estimated at 53.1 per 1,000 live births (68.4 per 1,000 public; 9.7 per 1,000 LB private) with a VT rate of 33.5 %, with no difference according to the source of financing. The detection rate of GS and the incidence rate of CS were double those reported to the Brazilian Notifiable Diseases Information System. Several missed opportunities for the control of CS were identified. Women with public financing had a higher prevalence of GS and incidence of CS, and should be the priority target of control strategies.

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Highlight In this randomized study of sequential therapy, intravenous and enteral antimicrobial therapy was similar in survival and clinical improvement. In hospitalized patients, after an initial clinical stabilization, 83 % of patients could be using intravenous antibiotics unnecessarily. Drug costs in the intravenous antibiotics increased by 207 % when compared with enteral antibiotics.

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Abstract Background World Health Organization (WHO) has recommended Multidrug Therapy (MDT/WHO) for Hansen’s Disease (HD) since 1982; nevertheless, relapse, antimicrobial resistance, and adverse reactions indicate the need for new therapeutic regimens. We evaluated the efficacy and safety of the new anti-HD regimen RIMOXCLAMIN (Rifampicin, Moxifloxacin, Clarithromycin, and Minocycline) compared with standard Multidrug Therapy provided by WHO (MDT/WHO). Methodology/principal findings 66 multibacillary HD new cases (46: RIMOXCLAMIN / 20: MDT/WHO) were evaluated between 2015 and 2023. Patients were followed up at least bimonthly by hansenologists for neurological and cutaneous findings and side effects of treatments. Hands/feet tactile sensitivity tests by Semmes Weinstein Monofilaments (SWM) and Physical Disability Grade (PDG) were carried out on the diagnosis, 3rd, 6th, and 12th months. 84.8 % and 80 % of the patients were classified as Borderline-Borderline (BB) in RIMOXCLAMIN and MDT/WHO groups, respectively, with no significant difference between them (p = 0.12). Nerve thickening was reduced by palpation in both groups: in RIMOXCLAMIN, reduction occurred early (65 % to 28 % at 6-months, p = 0.03; 9 % at 12-months, p = 0.03), while in MDT/WHO, it was later (95 % to 40 % at 12-months, p = 0.002). The greatest difference was at 6 months (p < 0.0001). A significant reduction was observed in pain scales on the 3rd month of treatment only with RIMOXCLAMIN; in the end, both groups showed significant reductions in pain scales, being greater in RIMOXCLAMIN group. 0.5 % reduction in the number of abnormal SWM points on the hands compared to baseline, while in the MDT/WHO group, there was an increase of abnormal points of 5.4 %. On the feet, RIMOXCLAMIN showed a reduction of 17.9 %, while in the MDT/WHO, it was 10.3 %. During follow-up, the RIMOXCLAMIN showed a significant decrease in the sum of altered SWM points compared to MDT/WHO (p < 0.05). Only RIMOXCLAMIN improved PDG monitoring. Both groups reported mild adverse effects. Conclusions/significance The results indicate that RIMOXCLAMIN was superior to MDT/WHO in terms of quick recovery of neurological damage, evidenced by the improvement of symptoms and sensitivity in hands and feet as early as the third month, with a progressive improvement, maintained after the end of treatment, including a reduce of patients with PDG.

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Abstract Background Neurologic manifestations of Coronavirus Disease-19 (COVID-19) have been associated with patients’ disease severity and outcome. This study aimed to describe the frequency and characteristics of the neurological manifestations in a group of hospitalized individuals with COVID-19 and their associations with patient outcomes. Methods Patients aged 18 years or older admitted to a local hospital between April and June 2020 with SARS-CoV-2 detected by RT-PCR were included in this retrospective observational study. The characteristics of participants were collected from electronic medical records using a structured questionnaire. A Poisson regression model was used to examine the influence of neurological manifestations on mortality. Results A total of 305 participants with COVID-19 were included, with 57.7 % of them presenting neurological symptoms. There were 62 (20.3 %) individuals with acute encephalopathy, with a mean age of 65.5 ± 15.9 years. In this group, higher Prevalence Ratios (PR) of comorbidities (1.6) and severe disease (3.6) were present, predisposing factors for acute encephalopathy. They were also more likely to be admitted to the intensive care unit (3.1) and to die (2.4). The median Neutrophil-Lymphocyte Ratio (NLR) was 7 (Interquartile Range [IQR: 4‒12]). Fifty-two (17 %) participants presented chemosensory dysfunction, with a mean age 53.3 ± 14 years and a lower PR of comorbidity (0.8) than those without. The severe diseases’ PR was slightly higher (1.1), but the PR of ICU admission (0.7), and deaths (0.4) was lower. The LNR was 3.8 (IQR: 2.2-7.8). Poisson regression analysis revealed that severe illness (PR = 3.13), cardiopathy (PR = 1.65), acute encephalopathy (PR = 1.49), diabetes (PR = 1.46), and neutrophil-lymphocyte ratio (PR = 1.04) were associated with death. Conversely, having chemosensory disorders (PR = 0.44) and a prolonged hospital stay (PR = 0.96) were associated with survival. Conclusion Patients with acute encephalopathy had more severe forms of COVID-19 and higher mortality. In contrast, chemosensory dysfunction was associated with milder disease manifestations and a better prognosis.

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Abstract Background Ventilator-Associated Pneumonia (VAP) is a critical healthcare-associated infection, but no universal surveillance standard exists. In 2013, the CDC revised its criteria, incorporating Ventilator-Associated Events (VAEs) with VAPs as a subset. In Brazil, however, the Health Regulatory Agency (ANVISA) chose to retain the traditional VAP criteria. This study aimed to evaluate the incidence of VAP using both the traditional and revised criteria. Method We conducted a prospective multicentric cohort of critically ill adult patients who required mechanical ventilation in 12 Brazilian Intensive Care Units (ICU) over six months. We evaluated the level of agreement between the two criteria considering frequency and kappa coefficient. This study was registered at ClinicalTrials.gov, NCT05589727. Results The study included 987 patients and revealed that 85.7 % of VAP reported by the centers according to ANVISA criteria were not confirmed by the adjudicators. Among the adjudicators, a 16.7 % disagreement (kappa = 0.32) suggested subjectivity in applying VAP criteria. Between the two sets of criteria, an 11% disagreement (kappa = 0.12) was observed. However, manual adjudication of automatically generated VAEs showed only a 4 % disagreement, indicating greater objectivity in the VAE criteria. Despite the high agreement in VAE adjudication, this did not necessarily translate to a more reliable exclusion of non-events, which is essential for accurate surveillance. Conclusion The findings highlight the challenges in identifying and classifying VAP, emphasizing the need for improved surveillance methods. The results could inform enhancements in VAP monitoring in Brazil and potentially impact other countries using similar criteria.

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Abstract Introduction and objectives HCV Self-Testing (HCVST) can be used to uptake HCV testing. We aimed to evaluate the acceptability/usability and re-reading/re-testing agreement of oral fluid HCVST among health-facility users in the Primary Care Systemin Brazil. Materials and methods Consecutive people aged 18‒79 years using the Primary Care System (PCS) from 04-July-2022 to 30-September-2022 were invited for this cross-sectional study. The professional use OraQuick® HCV Rapid Antibody Test was used as a HCVST prototype. Oral fluid HCVST was performed relying on a step-by-step video and written/pictorial instructions. Usability was assessed by observed errors and documented need of assistance by a Healthcare Worker (HCW). After HCVST, a second HCV test was performed by the HCW using the same test-kit. Re-reading and re-testing concordances were evaluated (Cohen’s kappa, κ). Post-testing participant’s perspectives were assessed. Results 685 participants (74.5% female; median age = 52 [IQR 39‒61] years, 52.5% with schooling ≤ 10 years) were included. Major observed errors [%(95%CI)] were incorrect sample collection [32.8% (29.4‒36.5)] and wrong placing the test device in the tube [15.0% (12.6‒17.9)]. A total of 35.6% (95% CI 32.1‒39.3) of participants needed assistance in at least one step of HCVST. Re-reading and re-testing agreements were 95.2% (κ = 0.56) and 99.7% (κ = 0.67; n = 626 excluding invalid tests), respectively. After HCVST, 93% felt safe, 99% would be willing to test again, and 99% would recommend HCVST. Most participants rated the HCVST experience as easy (73%) or very easy (24%). Conclusion Oral-fluid HCVST was feasible and well-accepted among users of the PCS in Brazil. HCVST can be an alternative to scale-up HCV testing.

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Abstract Ventilator-associated pneumonia is one of the most common infections in Intensive Care Units (ICU). It is frequently caused by multidrug-resistant pathogens (including carbapenems) and is an important health issue. It may result in severe clinical consequences, with higher healthcare utilization and high economic burden. Timely and appropriate treatment is key to obtaining better outcomes and allocational efficiency. Currently, the treatment options for carbapenem-resistant pathogen infections are limited, usually based on polymyxin, aminoglycosides, or combination therapy, as well as novel antibiotic therapies including Ceftazidime/Avibactam (CAZ-AVI). CAZ-AVI has shown activity against gram-negative pathogens and is currently used for the treatment of Ventilator-Associated Pneumonia (VAP). To better inform healthcare professionals and help promote a rational use of antibiotic therapy, a cost-effectiveness analysis was conducted to compare the cost-effectiveness of CAZ-AVI versus polymyxin B in ICU patients with VAP from the Brazilian National Supplementary Health Agency perspective over a 5-year time horizon. CAZ-AVI had higher total costs and resulted in more Quality-Adjusted Life Years (QALY) gained when compared with polymyxin B. At a willingness-to-pay threshold of BRL 40,000.00/QALY gained, CAZ-AVI was the cost-effective strategy (ICER: BRL 35,298.65/QALY gained). Nephrotoxicity in patients treated with polymyxin B, hospitalization utility, and treatment duration were the variables that most influenced the results. In the probabilistic sensitivity analysis, CAZ-AVI was cost-effective in 55 %-89 % of the interactions. The evidence suggests that CAZ-AVI results in lower mortality and nephrotoxicity rates, which might have contributed to more QALYs gained and a favorable ICER, despite the higher costs. This study was registered on the Open Science Framework database (Protocol https://doi.org/10.17605/OSF.IO/SP2EJ).

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Abstract Introduction Streptococcus B is a commensal infectious agent of the intestinal and genitourinary tract. It is often implicated in early neonatal infections. Some 10 %-30 % of women are colonised by this bacterium. Screening for carriage in women before delivery prior to antibiotic prophylaxis is thus essential. In recent years, real-time PCR tests have been developed. Our main objective was to determine whether screening for Streptococcus B carriage by PCR on admission (gold standard GeneXpert) permits complete antibiotic prophylaxis. Materials and methods This was an observational, retrospective study. Data set from all patients with a delocalised PCR for Streptococcus B (GeneXpert Instrument System) on arrival at the maternity hospital were collected between January 2022 and February 2023. We recorded 3467 test results, of which 344 were positive for Streptococcus B carriage. A total of 236 positive patients were included in the analysis. Antibioprophylaxis was considered complete when the patient had received at least one dose more than 4-hours before birth. Results Of the 236 patients, antibiotic therapy was incomplete in 53 cases (22.4 %) because vaginal delivery or caesarean section occurred less than 4-hours after the first dose. Antibioprophylaxis was not initiated in 33 cases. The main reason was for rapid labour in 28 cases (11.9 %). The 5 remaining cases did not receive antibiotics because probable omission by the team (2.1 %). Conclusion Delocalised PCR allows complete antibiotic prophylaxis against Streptococcus B in 63.6 % of cases, offering scope for improvement. While it will not be possible to improve antibioprophylaxis in case of rapid labour (within 3 hours after arrival), we should be able to prevent omissions (2.1 %) and, above all, reduce the birth rate before the second dose (22.4 %) by administering the first dose more quickly.

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Abstract Escherichia coli is an opportunistic pathogen and a leading cause of Community-Acquired Urinary Tract Infections (CA-UTIs). E. coli can harbor multiple genetic resistant determinants, such as Extended Spectrum Beta-lactamases (ESBL) and Plasmid-Mediated Quinolone Resistance (PMQR) genes, complicating the empirical treatment of UTIs with β-lactams and quinolones. The aim of his study was to characterize ESBL and PMQR genes among E. coli isolates from CA-UTI in Mexicali, Mexico Isolates were collected from January to December 2023. Identification was performed by MALDI-TOF, and ESBL-producing determination and antimicrobial susceptibility by Vitek 2. Detection of ESBL and PMQR, and phylotyping were performed by PCR. Genetic diversity was determined by Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR). Eighty-nine E. coli isolates were collected from CA-UTIs. All exhibited resistance to ciprofloxacin, ceftriaxone, and cefotaxime, while being susceptible to carbapenems and ceftazidime/avibactam. All isolates tested positive for an ESBL gene, with blaCTX−M (98.9 %) being the most prevalent. Five isolates tested negative for PMQR genes; the remaining showed aac(6′)-lb-cr present in 85.3 %. Coexistence between ESBL and PMQR genes was noted in 95.5 %. Most prevalent plylogenetic group was group B2 (74.2 %). This study provides valuable regional data, highlighting a public health problem due to the high prevalence of ESBL and PMQR genes in E. coli responsible for CA-UTI, which are linked to multidrug resistance. Genetic diversity was found, suggesting multiple sources of resistant strains in the community. These findings underline the need for surveillance and control to limit the spread of resistant E. coli, locally and globally. Data summary The authors confirm all supporting data, code, and protocols have been provided within the article or through supplementary data files.

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Abstract Urinary Tract Infections (UTI) are among the most common public health problems worldwide, mostly caused by Escherichia coli. High-risk pandemic clones, especially ST131, are known for their association with multidrug resistance. A better understanding of epidemiologic and molecular characteristics may provide insights into the dissemination and evolution of this pathogen. The present study aims to investigate selected clonal characteristics of a large collection of UTI-causing E. coli isolates from Rio de Janeiro, an urban center in Brazil. We set up a collection of 992 E. coli isolates from patients with UTI in 2019. We determined antimicrobial susceptibility, Extended Spectrum Betalactamase (ESBL) production and clonal composition of isolates and compared results with data from 2015. Frequencies of four most isolated pandemic clones (ST131, ST69, ST73 and ST95) were determined by PCR; ST131 clades were determined by PCR and fimH gene sequence; ESBL-producing isolates underwent MLST. Resistance frequencies were > 30 % for ampicillin and ciprofloxacin. ST131 isolates were the most frequent clone (14 %), increasing significantly from 2015, comprising 52 % of all ESBL-producing strains. Clade C formed most ST131 isolates (56 %), including 40 % of all ESBL-producing isolates, most in Clade C2; almost all fimH30. ST131, formed by heterogeneous lineages, was established as a major source of ESBL isolates in the community, with a major contribution to antimicrobial resistant UTI.

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ABSTRACT COVID-19, caused by SARS-CoV-2 infection, left widespread impacts worldwide. In Brazil, immunization reduced incidence rates. However, six months later, waning neutralizing antibody titers and new immune-evading variants increased cases, resulting in recurring waves. This study evaluated hospitalized COVID-19 patients after the vaccination rollout, comparing the clinical outcomes between vaccinated and unvaccinated patients. Positive samples underwent nucleotide sequencing. A total of 218 patients were included; 202 (92 %) had vaccination data, 98 received at least one dose, and 64 completed the vaccination schedule, predominantly with CoronaVac®. Vaccinated individuals were older on average since the campaign was primarily conducted among the elderly. The Gamma variant predominated during the study period. While not statistically significant, trends indicated greater respiratory assistance needs, more extended hospital stays, and increased ICU time among unvaccinated patients. Mortality was 45 % in vaccinated and 37 % in unvaccinated groups, with no notable difference. However, patients with a complete vaccination schedule showed a higher chance of survival, though not significant (p = 0.11). The factors significantly associated with higher mortality were older patients, those requiring vasopressor drugs, and mechanical ventilation. These findings provide clinical, epidemiological, and phylogenetic insights into COVID-19 patients during vaccination implementation. They underscore the need to evaluate vaccine effectiveness against circulating variants and highlight the importance of complete vaccination schedules for improving patient outcomes.

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Abstract Background Ascariasis is a parasitic infection caused by Ascaris lumbricoides and infects over 1.2 billion people worldwide. Benzimidazole (BZ) drugs remain the standard treatment in large-scale deworming programs globally. The prevalence of Single Nucleotide Polymorphisms (SNPs) in the β-tubulin gene of A. lumbricoides (F200Y, E198A and F167Y) is increasing due to the widespread use of BZ drugs. Aim To investigate the prevalence of the above-mentioned SNPs in a South African adult population. Methods This was a sub-study of the main cross-sectional study with participants (n = 414) who had been recruited from five public health clinics in the peri‑urban areas South of Durban, KwaZulu-Natal, South Africa. For the current study, a purposive selection of 20 stool samples that were positive for A. lumbricoides eggs was made. A. lumbricoides worm extracts (n = 4) were used as a positive control. Sanger sequencing and RFLP-PCR were used to identify the presence of mutations. Results No mutations were detected, and all genotypes observed at codons F167Y, E198A and F200Y were the homozygous wild-type genotype. Conclusion Although no mutations were found in this small study, the potential occurrence of mutations in a larger sample subset cannot be ruled out.

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Abstract Syphilis has reemerged worldwide, and knowledge about at-risk populations can assist in disease prevention and control. This study aimed to estimate the prevalence of syphilis among attendees at a Brazilian sexual health center and explore the association between sociodemographic and sexual behavioral factors with syphilis infection. A cross-sectional study was conducted at a Counselling and Testing Center (CTC) in Goiás, Brazil. We collected data from January to December 2018 to conduct a population-based study. Of 3526 patient records included in the analysis, 344 (9.8 %) belonged to participants who had syphilis, mainly at the age of 20 to 39 years old (63.1 %, p = 0.0683) and not married (62.1 %, p = 0.0042). Individuals who reported having homosexual relationships (Odds Ratio [OR = 2.93], p < 0.0001), previous sexually transmitted infections (OR = 2.36, p < 0.0001), and use of drugs (OR = 1.29, p < 0.0001) were more frequently diagnosed with the disease. Among patients with syphilis, MSM had a higher HIV co-infection rate (OR = 2.37, p = 0.0195) and also higher co-infection rates with other previous STIs (OR = 2.84, p = 0.00883). A high prevalence of syphilis among patients who attended the CTC in Goiás was revealed. Effective control of syphilis among populations at higher risk needs to be addressed to achieve disease control in Brazil.

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Abstract Rapid detection of Carbapenemase-Producing Enterobacterales (CPE) is essential for informing infection prevention and control actions to curb the spread of antimicrobial resistance. Immunochromatographic Tests (ICTs) offer a quick and cost-effective alternative to molecular methods but are typically designed for bacterial isolates rather than direct clinical specimens. We developed a protocol using the O.K.N.V.I. RESIST-5 ICT (Coris Bioconcept, Gembloux, Belgium) to detect KPC, NDM, OXA-48, VIM, and IMP carbapenemases from broth-enriched mock rectal swabs. A total of 35 well-characterized carbapenemase-producing isolates were inoculated into a 10 % stool matrix to create mock swabs. Swabs were incubated in Brain-Heart Infusion (BHI) broth, with and without a 10 μg meropenem disk, at 37 °C for 4 and 6 h. After incubation, broths were centrifuged, and pellets were tested using the ICT. Sensitivity, specificity, and accuracy were calculated for each method (with/without meropenem disk and incubation period). Optimal performance was achieved with swabs incubated in BHI broth without meropenem for 6 h, showing 100 % sensitivity, specificity, and accuracy for all the five enzymes tested. Incubation with meropenem or shorter incubation times resulted in lower sensitivities, with per-enzyme sensitivities ranging from 0 % to 100 %. The developed protocol enables rapid and accurate detection of five common carbapenemases directly from broth-enriched rectal swabs within 6 h. This method offers a practical alternative to culture-based and molecular techniques, potentially enhancing infection control measures through timely identification of CPE.

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Abstract Herpes Zoster (HZ) and its complications, such as Postherpetic Neuralgia (PHN), are associated with significant burden in elderly. In Brazil, data on economic and epidemiologic HZ burden is still limited. We conducted a Delphi panel to assess healthcare resource use in HZ outpatients aged 50-years and older. Diagnosis and treatment resources, proportion of referral and hospitalization were estimated considering HZ, PHN, ophthalmic and neurologic zoster typical cases. A diverse group of 20 medical specialists was selected, and responded anonymously to an online questionnaire. Consensus was met if ≥ 75 % agreement was reached in the 1st round, and if not met, a 2nd round was held. Summary statistics are reported stratified by age-groups and healthcare system (public and private). Responses were obtained from 19 and 17 panel members in the 1st and 2nd rounds, respectively. The proportion HZ outpatients with PHN increased significantly with age (4 % in 50‒59; 14 % in ≥ 80 years). Ophtalmic and neurological complications ranged from 5 %‒13 % across age groups. Absenteeism was high, ranging from 30 %‒68 % of patients depending on the clinical presentation. HZ patients required 2‒3 medical visits, and referral to another medical specialty varied from 10 %‒22 % across age ranges, doubling for NPH patients. Proportion of hospitalization varied from 1–8 %. HZ diagnosis was mainly clinical (93 %). Acyclovir (95 %) and valaciclovir (80 %) were the therapy of choice in the public and private systems, respectively. Pain management included dipyrone and codeine (63 %), pregabalin (58 %), and gabapentin (Neurontin) (48 %). Our results report significant healthcare resource utilization by elderly HZ patients in Brazil.

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Abstract Introduction Diabetic Foot Infections (DFI) are severe complications of diabetes, often resulting in poor clinical outcomes, including amputations. The objective of this study is to identify the main pathogens causing infections in the diabetic foot ulcers, as well as the antibiotic resistance profile. Methods This study included all patients treated for diabetic foot infections at a private tertiary hospital between 2013 and 2022. Demographic data, including age, sex, Body Mass Index (BMI), and the level of amputation were extracted from electronic medical records and collected for all patients. Microbiological and resistance patterns were evaluated following standardized protocols. Cases with incomplete demographic or microbiological data were excluded. Results This retrospective cohort study analyzed data from 459 diabetic patients, among them, 337 patients with positive cultures were included, resulting in 507 culture results from surgical samples. Gram-negative bacteria accounted for 55.2 % of isolates, with Enterobacterales (41 %) and non-fermenters (14.2 %) being most prevalent. Proteus sp. (10.3 %) and Escherichia coli (8.3 %) were the most common Gram-negative organisms, with significant resistance to ESBL (15.4 %) and quinolones (29.3 %). Among Gram-positive cocci (43.6 %), Staphylococcus aureus (16.8 %) showed 21.1 % methicillin resistance, while Enterococcus sp. exhibited vancomycin resistance (7 %). Multidrug resistance was identified in 16 % of Pseudomonas sp. and 63.6 % of Acinetobacter sp., raising concerns about limited therapeutic options. Conclusion The predominance of Gram-negative bacteria and high levels of antimicrobial resistance highlight the need for regular monitoring of local microbiological profiles. Targeted antimicrobial strategies can significantly reduce the morbidity associated with DFI and improve clinical outcomes in diabetic patients.

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Abstract Inappropriate use of antibiotics plays a key role in increasing bacterial resistance. The aim was to determine the prescription patterns and approved and unapproved indications for the use of penicillins in a group of patients from Colombia. This was a cross-sectional study on the use of penicillins in outpatients. The subjects were identified from a population-based drug dispensing database. Approved and unapproved indications were determined from records of the Food and Drug Administration (FDA) of the United States and the National Institute of Food and Drug Surveillance (INVIMA) of Colombia. Descriptive and multivariate analyses were performed. A total of 137,070 patients were identified; the average age was 35.8 ± 23.5 years, and 56.2 % were women. Amoxicillin (73.4 %), dicloxacillin (11.7 %) and sultamicillin (6.0 %) were the most prescribed penicillins, mainly for upper respiratory tract infections (43.0 %). In 68.9 % cases, penicillins were used for approved indications, especially to treat Helicobacter pylori (17.3 %). In 31.1 % of cases, penicillin prescriptions were used for unapproved indications (acute rhinopharyngitis: 8.1 %). Patients with skin and soft tissue infections (aOR = 2.82; 95 % CI 2.57‒3.09), with lower respiratory tract infections (aOR = 2.02; 95 % CI 1.89‒2.16), and those treated with dicloxacillin (aOR = 2.84; 95 % CI 2.07‒3.89) were more likely to be prescribed penicillins for unapproved indications. Amoxicillin was the most widely used penicillin in outpatients. Penicillins were frequently used for unapproved indications not recommended by drug regulatory agencies.

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Abstract Introduction Staphylococcus aureus causes potentially life-threatening infections, with a somber prognosis when the infection is caused by methicillin-resistant S. aureus due to limited treatment options. The present study describes serious infections by S. aureus in patients hospitalized in an infectious disease’s unit in Rio de Janeiro, Brazil, between 2016 and 2021. Material and methods This was a retrospective study based on data from positive samples diagnosed by the microbiology laboratory and by review of medical records. Clinical-demographic variables and outcomes were compared between Patients Living with HIV (PLHIV) and non-HIV patients. Data were analyzed using Jamovi 1.6 and R 4.0.1 statistical software. Results A total of 67 patients with a serious S. aureus infection were identified, of whom 29 presented bacteremia and 38 other infections. Thirty-one of 67 (46.3%) were PLHIV. The median age of all patients was 46years, although PLHIV were significantly younger than non-HIV individuals (36 vs. 60 years-old, p < 0.001). The median CD4 lymphocyte count was 95 cells/mm3. Community infection occurred in 36/67 (53.7%) patients, of whom 19/36 (52.7%) had bacteremia. A total of 20 MRSA infections (29.9% of the patients) were identified, which accounted for 14/36 (38.8%) of the community infections. More than a third of PLHIV (38.7%) had MRSA, and all these were sensitive to cotrimoxazole. No difference in mortality was found between PLHIV and non-HIV patients, nor between the MRSA and MSSA groups. Bacteremia was present in 29 patients; MRSA accounted for 9 (31.0%) of these. The 30-day mortality was 4/9 (44.4%) and 2/20 (10%) in MRSA and MSSA bacteremia, respectively. Conclusions The most frequent comorbidity in patients with severe S. aureus infections was HIV, with a high rate of MRSA infections recorded in PLHIV. PLHIV were younger, but did not suffer higher mortality, although they did have more relapses and new staphylococcal infections.

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Abstract Introduction Chagas Disease (CD) is caused by the protozoan Trypanosoma cruzi and is endemic to 21 Latin American countries. It is estimated that 6 to 7 million people in Latin America are infected. Clinical manifestations occur in two phases, acute and chronic. The chronic phase may present as indeterminate, cardiac, digestive, or mixed. Few studies have investigated why some infected individuals remain asymptomatic, while others develop more severe clinical forms of the disease. The present study aimed to evaluate the frequency of Single Nucleotide Polymorphisms (SNPs) in the ACE2 and TNF-alpha genes in chronic and indeterminate forms of CD and assess their association with clinical data and comorbidities. Methods The study included 51 male patients with the indeterminate chronic forms of CD and 22 male patients with cardiac chronic forms of CD. All patients were treated at the HC-FMB/UNESP outpatient clinic. Deoxyribonucleic Acid (DNA) was extracted from blood samples and genotyped using Sanger sequencing and Restriction Fragment Length Polymorphism (RFLP) to analyze the ACE2 rs2074192 and TNF-alpha rs1800629 polymorphisms. Results Analysis of the ACE2 rs2074192 SNP revealed no significant differences in the frequencies of the Guanine (G) and Adenine (A) alleles. Similarly, analysis of the TNF-alpha rs1800629 SNP revealed no significant differences in the frequencies of the GG, GA, and AA genotypes. Conclusion No significant associations were found between the studied polymorphisms and the clinical forms of CD. However, further studies with larger sample sizes are needed to confirm these findings.

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Abstract Hepatitis B remains a global health concern due its high prevalence and association with chronic liver disease. Although vaccination is safe and effective in immunocompetent individuals, patients with hematological malignancies often exhibit immune dysfunction and reduced vaccine responses, increasing their susceptibility to vaccine-preventable infections. This study aimed to assess the hepatitis B vaccination status and immunoprotection in pediatric oncology patients treated at a tertiary public hospital in southern Brazil. A retrospective, single-center study was conducted with patients aged 0 to 15 years undergoing treatment for hematological malignancies between 2020 and 2022. Clinical and demographic data were obtained from electronic medical records, including vaccination history and hepatitis B serology profile. Vaccination status was verified through the National Immunization Program Information System. A total of 101 patients were evaluated, comprising 58 (57.4 %) males and 43 (42.6 %) females. The predominant diagnosis was acute lymphoblastic leukemia, reported in 67 cases (66.3 %). All patients underwent chemotherapy protocols, and 28 (27.7 %) died during the study period. Serological data for hepatitis B were available for 66 patients (65.3 %), with the highest proportions of missing data for anti-HBs (25.7 %) and total anti-HBc (13.9 %). None tested positive for HBsAg, 2 (2.3 %) were positive for total anti-HBc and 33 (44.0 %) for anti-HBs. Regarding vaccination status, 62 (61.4 %) had completed the hepatitis B vaccine series, 12 (11.9 %) had incomplete schedules, and 27 (26.7 %) had no records available. Only 10 patients (13.5 %) received additional vaccination after oncological diagnosis. Among those with a complete vaccination schedule, 27 (55.1 %) did not develop protective antibodies. These findings demonstrate low level of immunoprotection and suboptimal vaccine coverage against hepatitis B in this population. Optimizing vaccination protocols and monitoring strategies are essential to ensure adequate immunization against hepatitis B and other preventable diseases in immunosuppressed pediatric patients receiving care in Brazil.

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Abstract Background Fracture-Related Infection (FRI) is an increasing and challenging complication following orthopedic trauma surgery. Preventive and microbial diagnostic measures vary significantly particularly in low- and middle-income countries. The objectives of this national questionnaire were to investigate clinical practices towards preventive and diagnostic strategies adopted by Brazilian orthopedic trauma centers and to assess the impact of Multidisciplinary Teams (MDT) on the management of FRI. Methods A 34-item electronic questionnaire was developed via REDCap® and distributed to all trauma surgeons registered of the Brazilian Society of Orthopedics and Traumatology (SBOT). Results With a response rate of 24 %, the survey was fully responded by 140 trauma surgeons, 63.6 % of them working in southeast region centers. Collaborative work with MDT focused on musculoskeletal infections was reported by only 41.0 %. Cephalosporins were universally prescribed as Perioperative Antibiotic Prophylaxis (PAP), while association with an aminoglycoside increased (35.0 %) for severe open fracture. One-day duration of PAP for closed fracture was prescribed in 68.1 %, while it often exceeded current recommendations. Diagnostic practices for FRI patients were primarily based on clinical signs and standard radiological and laboratory tests, with limited use of microbiological techniques. Trauma services working collaboratively with MDT significantly improved FRI management, including, use of sonication fluid for diagnosis (46.6 % vs. 26.8 %; p = 0.02), body weight-adjusted antibiotic dosing for PAP (50.0 % vs. 24.4 %; p = 0.02), appropriate duration of PAP according to the severity of soft-tissue damage (80.7 % vs. 59.3 %; p = 0.01), infection risk stratification in elderly patients with fractures (45.6 % vs. 21.0 %; p < 0.001), use of negative-pressure wound therapy (87.9 % vs. 54.9 %; p < 0.001) and regular collaboration with orthoplastic surgeon (44.8 % vs. 17.5 %; p = 0.01). Conclusions This national survey revealed marked heterogeneity in FRI management across Brazilian trauma services. Ongoing MDT collaboration improved clinical practice, especially diagnostic work-up and antimicrobial stewardship.

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Abstract The Human T-Lymphotropic Virus (HTLV) is a retrovirus belonging to the Retroviridae family and the Deltaretrovirus genus, which has a tropism for T lymphocytes. Despite being the first human retrovirus identified, knowledge about its infection remains limited, highlighting the need for further research, especially in Northern Brazil.. This study aimed to phylogenetically characterize HTLV-1 and HTLV-2 samples identified in blood donors from the state of Pará. The phylogenetic characterization was performed using DNA samples from blood donors at the HEMOPA Foundation, collected between January 2015 and December 2021. The 5′LTR regions of HTLV-1 and HTLV-2 were amplified using specific primers with Nested PCR. The amplified products were purified and sequenced using the dideoxynucleotide method, with the same primers used in the Nested PCR, for subsequent phylogenetic analysis and the construction of a sequence database, as well as deposits in GenBank. The phylogenetic analysis of the 5′LTR sequences of HTLV-1 from this study, compared with isolates available in GenBank, showed that 100 samples clustered with Cosmopolitan subtype isolates, Transcontinental subgroup, while 2 samples clustered with Cosmopolitan subtype isolates, Japanese subgroup. Regarding the phylogenetic analysis of HTLV-2 from this study in comparison with other GenBank isolates, most of the isolates clustered with strains described as HTLV-2c, and only three samples clustered with strains described as HTLV-2a. The epidemiological profile found in the analyzed samples consisted mainly of women, with an average age of 40 years and a low level of education. The molecular characterization of the viral genome provides information about the viral subtypes circulating in the population. This information may be important for increasing investments in screening and monitoring individuals infected with HTLV, thereby contributing to prophylactic practices related to infection and the dissemination of knowledge about HTLV.

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Abstract Objective Nucleoside/nucleotide reverse transcriptase inhibitors, particularly tenofovir, can cause long-term side effects such as decreased bone mineral density and estimated glomerular filtration rate. A strategy to mitigate these effects is the simplification of antiretroviral therapy, which involves withdrawing one of the nucleoside/nucleotide reverse transcriptase inhibitors from the therapeutic scheme. While clinical trials and real-world studies have demonstrated that the simplified therapy maintains undetectable viral loads, its impact on bone mineral density and kidney function remains unclear owing to the lack of real-world evidence. Methods This retrospective cohort study compared 152 patients who underwent antiretroviral therapy simplification (primarily due to osteopenia, osteoporosis, or decreased estimated glomerular filtration rate) with 306 patients who maintained triple therapy, between April 2013 and September 2022. The simplified regimens included lamivudine plus dolutegravir or ritonavir-boosted darunavir. The groups were analyzed based on their demographic characteristics using Student's t-test in the case of symmetric data. Therapeutic success (undetectable viral load at the end of follow-up) was assessed using Kaplan Meier survival analysis. The estimated glomerular filtration rate variation before and after simplification was analyzed using the Mann-Whitney test. Pre-and post-simplification bone mineral density values were evaluated using the chi-square test for trends and assessed in the simplified therapy group. A significance level of 5% (α = 0.05) was adopted for all tests. Results Simplified antiretroviral therapy was non-inferior to triple therapy in maintaining undetectable viral load. Patients receiving simplified regimens showed a positive variation in estimated glomerular filtration rate. A small subset of patients also exhibited improvements in bone mineral density after antiretroviral therapy simplification. Conclusions These findings suggest that simplified therapy is as effective as triple therapy and has the additional benefit of reducing tenofovir-related adverse events.

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Abstract Background Mucormycosis is a rare but life‑threatening fungal infection that has shown an increased incidence in Brazil, especially during the COVID‑19 pandemic. Objective To provide an evidence‑based, context‑specific guideline for the diagnosis and management of mucormycosis within the Brazilian healthcare system. Clinical features: Rhino‑orbito‑cerebral disease predominates, followed by pulmonary, cutaneous, gastrointestinal and disseminated forms; delayed recognition dramatically increases mortality. Epidemiology The global incidence of mucormycosis is increasing, particularly among patients with diabetes mellitus, hematologic malignancies, transplantation, and corticosteroid exposure. The most frequently isolated species is Rhizopus arrhizus, and regional variations in species distribution may be present. In Brazil, comprehensive epidemiological data remain scarce. Treatment Early, aggressive surgical debridement plus induction with liposomal amphotericin B (5–10 mg/kg/day) followed by isavuconazole or posaconazole is recommended; strict control of hyperglycemia and immunosuppression is essential. Conclusion Standardized national guidance, improved rapid diagnostics, systematic surveillance and equitable drug availability are critical to reduce Brazil’s mucormycosis burden.

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Abstract Healthcare-associated infections are among the most significant complications in hospitalized patients, posing a major challenge due to the antimicrobial resistance of pathogenic agents such as Staphylococcus spp. The study aims to identify and evaluate the phenotypic and molecular resistance profile of Staphylococcus spp. in co-infection with respiratory viruses, including COVID-19, as a respiratory virus, in samples from children admitted to ICUs. Nasopharyngeal samples from the biorepository were stored at -80 °C in medium containing gentamicin and amphotericin B. Bacterial strains were isolated, and antibiograms were performed using the Kirby-Bauer method with antimicrobials specific to Staphylococcus spp. and the method of evaluating molecular resistance, carrying out the amplification of resistance genes, using specific oligonucleotides. A multidrug-resistant profile was observed in Staphylococcus spp., highlighting the need for monitoring to ensure appropriate treatment. Antimicrobial resistance emphasized the importance of strict control over antibiotic use in hospital environments. This study contributes to the understanding of antimicrobial resistance in bacterial co-infections, providing insights for more effective treatments and HAI control strategies.

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Abstract The transfusion of blood components is a critical therapeutic intervention for certain clinical conditions for which alternative treatments are often unavailable. Despite the benefits, transfusions can pose health risks to the recipients, including potential transmission of infectious agents. Post-donation, blood components undergo testing for major transmissible agents such as Human Immunodeficiency Virus (HIV), Hepatitis B and C Viruses (HBV and HCV), Treponema pallidum (syphilis), and Trypanosoma cruzi (Chagas disease). This retrospective study assessed the prevalence of donor unsuitability due to these agents and examined potential influences on the profile of blood-borne infections among healthy blood donors in the region. This study was conducted at a public institution in Brazil from January 2014 to December 2021. All effective blood donations were included, totaling 600,001. The donor demographic profile was as follows: 60.5% male, 52.2% single, 44.5% self-identified as white, 39.6% completed high school, and the 31–40 year age group had the highest number of donors, comprising 28%, with the majority being regular donors (70.4%). The prevalence of hemotransmissible agents was 2.13% (T. pallidum), 1.54% (HBV), 0.44% (HIV), 0.36% (T. cruzi), 0.26% (HCV), and 0.23% (HTLV). Specific associations were noted among the sociodemographic data for each condition. T. pallidum and HBV infections are the most frequent causes of donor ineligibility. The data indicate that prevalence rates remained relatively constant with minor fluctuations throughout the study period, although the frequency of HIV infection was notably higher in 2021.

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Abstract Influenza viruses cause 3-5 million severe cases and 300,000-600,000 deaths worldwide. Most of the disease burden is in Low- and Middle-Income Countries (LMICs) owing to factors such as high population density, infrastructure challenges, poor quality healthcare, lack of consistent recommendations, less prioritization of all high-risk groups, and prevalent use of trivalent influenza vaccines. Although influenza vaccines are effective in reducing the annual influenza disease burden, existing vaccines have several limitations. In this narrative review, we address the unmet needs of existing influenza vaccines in LMICs in Africa, Asia Pacific, Latin America and the Middle East and discuss the characteristics of novel vaccines in clinical development. We also describe features of a successful vaccination program that LMICs could emulate to improve their current vaccination coverage and reduce the public health burden of influenza.

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Abstract Viral hepatitis is a public health problem, about 1 million people die due to complications of this viral disease, the etiological agents responsible for inducing cirrhosis and cellular hepatocarcinoma are HBV and HCV, both hepatotropic viruses that cause asymptomatic infection in most cases. The regulation of the microbiota performs many physiological functions, which can induce normal intestinal function and produce essential nutrients for the human body. Metabolites derived from gut microbiota or direct regulation of host immunity and metabolism have been reported to profoundly affect tumorigenesis in liver disease. If the microbiota is unbalanced, both exogenous and symbiotic microorganisms can affect a pathological process. It is well understood that the microbiota plays a role in viral diseases and infections, specifically the hepatic portal pathway has been linked to the gut-liver axis. In HBV and HCV infections, the altered bacterial representatives undergo a state of dysbiosis, with subsequent establishment of the pathobiome with overexpression of taxons such as Bacteroides, Clostridium, Lactobacillus, Enterobacter, and Enterococcus. This dysregulated microbiome induces a microenvironment conducive to the development of hepatic complications in patients with acute and chronic HBV and HCV infection, with subsequent dysregulation of cytokines IFN-α/β, TNF-α, IL-1β, TGF-β, IL-6 and IL-10, which alter the dysfunction and damage of the hepatic portal system. In view of the above, this review aimed to correlate the pathophysiological mechanisms in HBV and HCV infection, the dysregulation of the microbiome in patients infected with HBV and HCV, the most altered cytokines in the microbiome, and the most altered bacterial representatives in the pathobiome of infection.

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Abstract Although international guidelines are available, a national consensus is crucial to address the unique challenges faced in Brazil regarding the management of infections caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). These challenges include marked regional disparities in antimicrobial access, variability in pathogen prevalence and resistance patterns, and unequal availability of diagnostic resources. This guideline, developed by a consensus of infectious diseases experts nominated by the Brazilian Society of Infectious Diseases, aims to support clinicians, particularly non-specialists, in the management of MDR-GNB infections across diverse healthcare settings in the country. The document focuses on pathogens classified as critical or high-priority by the World Health Organization (WHO), including Carbapenem-Resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPA), ESBL- and AmpC-producing Enterobacterales, as well as Stenotrophomonas maltophilia, and Burkholderia cepacia. Therapeutic recommendations are organized by pathogen and infection site, including respiratory tract, skin and soft tissue, bloodstream, intra-abdominal, and both complicated and uncomplicated urinary tract infections.

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Abstract A 22-year-old woman presented with an ulcer on her right earlobe 2 months ago, with inflammation and enlarged ipsilateral lymph nodes in her neck. She was treated with antibiotics without success and then was referred to an infectious disease specialist. She has a cat at home with sporotrichosis, but without direct contact with the lesion, she did not remember any scratching by the cat. She also mentioned wearing a semi-jewel earring. This is a rare and unusual case of sporotrichosis in the earlobe, probably caused by wearing an earring contaminated by the cat's fungus that was present in the home environment. The delay in diagnosis and treatment led to the worsening of the injury and loss of the earlobe.

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ABSTRACT Introduction: Prosthetic Vascular Graft Infection (PVGI) is a rare but serious complication of open surgical repair of abdominal aortic aneurysm. We report a case of gas-forming abscesses associated with PVGI caused by Bacteroides fragilis identified from the drainage fluid and blood cultures. Case presentation: A 67-year-old man with a complaint of worsening low back pain underwent an emergency open surgery due to abdominal aortic aneurysm. On postoperative day 18, an abdominal CT showed gas formation within the aneurysm. Gram staining of the drainage fluid revealed Gram-negative rods and 16S rRNA gene sequencing performed on the fluid identified B. fragilis, although the culture of the fluid was negative. PVGI caused by anaerobic bacteria such as Bacteroides spp. is relatively rare. The sensitivity of 16S rRNA gene sequencing for culture-negative specimens is generally low, but 16S rRNA sequencing-positive rate increases when a Gram stain of specimen is positive.

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ABSTRACT Prototheca, an opportunistic pathogenic algae widely found in nature, has emerged as a potential public health concern. Most cases occur in immunocompromised individuals, with infections in immunocompetent patients being relatively rare. Due to their non-specific clinical presentation and limited awareness among clinicians, Prototheca infections are often misdiagnosed, resulting in delayed treatment. Recent advances in species identification and antifungal susceptibility testing have provided important tools for diagnosis and therapy. Here, we report a case of recurrent facial infection in a 76-year-old immunocompetent man. Skin biopsy revealed an infectious granuloma, and fungal culture identified yeast-like colonies. Fluorescence staining and scanning electron microscopy revealed abundant spores, while metagenomic sequencing confirmed the infection as Prototheca wickerhamii. The patient was successfully treated with long-term itraconazole and dipotassium glycyrrhizinate capsules. This case highlights the importance of early and accurate diagnosis in the management of Prototheca skin infections and reviews the therapeutic strategies used.

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ABSTRACT Background: Bartonella henselae is responsible for disseminated infections in immunocompromised patients. Upadacitinib is a JAK inhibitor used since 2021 for the treatment of severe atopic dermatitis in adolescents over 12-years. We report here the case of disseminated Bartonellosis in a 15-year-old male treated with upadacitinib. Case presentation: This patient presented with fever and abdominal pain. Laboratory tests showed inflammation, rhabdomyolysis and acute renal failure. Imaging studies revealed lymphadenopathies, hepatosplenic, renal and pulmonary nodules, pleural and peritoneal effusions and spleen abscesses. Bartonella henselae serology was positive for IgG and IgM. Treatment with doxycycline resolved the symptoms. We detected a concomitant EBV reactivation. Conclusions: Bartonella henselae infection should be suspected in immunocompromised patients presenting with fever of unknown origin. Upadacitinib is responsible for rapid immunodepression, which can lead to viral reactivation and severe bacterial infections. Randomized controlled trials are needed to establish a consensus on treatments for the various forms of Bartonellosis.

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Abstract Prion diseases are significant contributors to rapidly progressive dementia. Among these conditions, sporadic Creutzfeldt-Jakob Disease (CJD) is the most prevalent, characterized by its rarity, lack of treatment options, and rapid progression to fatality. Diagnosis relies on a combination of clinical symptoms and specific alterations detected in brain MRI, EEG, and CSF analysis. The present study details the case of a 53-year-old individual from Fortaleza, Brazil, diagnosed with sporadic CJD, confirmed through clinical presentation and a series of diagnostic evaluations, including 14-3-3 protein detection and RT-QuIC analysis. Differential diagnoses were considered to rule out other rapidly progressing conditions, such as infectious and immune-related diseases, ultimately leading to a likely diagnosis of sporadic CJD.

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Abstract A retrospective and cross-sectional study was carried out on blood donors from Piauí State located at Northeastern Brazil to evaluate the prevalence of Hepatitis E Virus (HEV) infection. Serum samples were tested for anti-HEV IgG and IgM using electrochemiluminescence and HEV RNA was tested using real time PCR. A total of 890 individuals were included with median age of 33.4 years and most of them were male and lived at Mid-Northern region of the State. Prevalences of anti-HEV IgG and IgM were 1.35 % and 0.11 %, respectively. None HEV-RNA was detected. This study demonstrated low prevalence of HEV infection in blood donors in this region.

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Abstract Background Treating NDM-producing bacteria poses a significant challenge, especially for those bacteria inherently resistant to polymyxin, such as Serratia marcescens, necessitating combined therapies. Objective To assess in vitro the synergistic effect of different antimicrobial combinations against NDM-producing S. marcescens. Methods Four clinical isolates were tested with various antibiotic combinations: polymyxin, amikacin, meropenem, and aztreonam. Concentrations used were those maximized by pharmacokinetic and pharmacodynamic assessments. Synergy evaluation involved a static macrodilution test followed by a time-kill curve assay. Results All four isolates demonstrated resistance according to CLSI and EUCAST standards for the tested antibiotics (polymyxin, amikacin, meropenem, and aztreonam). In the macrodilution synergy test, the combination of aztreonam and amikacin was active in 2 out of 4 isolates within 24 h, and polymyxin with meropenem in only one isolate, despite of intrinsic resistance to polymyxin. However, time-kill curve analysis revealed no synergism or additive effect for combinations with the tested antimicrobials. Conclusion Combinations of polymyxin, meropenem, aztreonam, and amikacin at doses optimized by pharmacokinetic/pharmacodynamic were insufficient to demonstrate any synergism in NDM-producing S. marcescens isolates in time-kill curves.

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Abstract Introduction Dengue cases in the Americas in 2024 have reached record highs, especially in Brazil. However, surveillance remains suboptimal and new methods are needed to monitor Dengue Virus (DENV) spread. To assess whether wastewater-based epidemiology would be a useful tool, we investigated the presence of DENV RNA in dengue patients’ urine and oral fluid from an endemic area to inform how shedding in these fluids occurs and provide insight for wastewater surveillance. Methods We examined how often DENV RNA is detected in urine and oral fluid from dengue patients confirmed by serum RT-qPCR, NS1 ELISA or IgM seroconversion in Salvador, Brazil. Results Of 88 confirmed cases, 9.1 % were positive for DENV RNA in urine (7/88) or oral fluid (1/88). Of 53 serum RT-qPCR-positive patients, 6 (11.3 %) showed detectable DENV RNA in acute- or convalescent-phase urine. Patients with RT-qPCR-positive urine had a lower frequency of DENV IgG in acute-phase serum (a proxy for secondary infection) (57 % vs. 74 %) and a lower median serum RT-qPCR cycle threshold than those with negative urine (21.8 vs. 23.9). Conclusion The low presence of DENV RNA in urine suggests that additional research is needed to evaluate whether using wastewater-based epidemiology to monitor DENV transmission is possible.

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Abstract Background The incidence of Late-Onset Sepsis (LOS) increases as gestational age decreases in newborns. The clinical signs of neonatal sepsis are not specific for diagnosis in preterm infants. The gold standard for its diagnosis is the blood culture test, which requires more than 24 h to obtain results, with positive results obtained in 10-3 % of cases analysed. As the molecular markers on the lymphocyte surface CD64 and CD69 are involved in early innate immune activation, they may be helpful for faster diagnosis. Aim Measure the expression of CD64 and CD69 on lymphocytes in clinical and confirmed sepsis patients and compared to that in infants without sepsis. Methodology We used peripheral blood samples from three groups of preterm babies with suspected sepsis (n = 31), confirmed sepsis (n = 10) and without sepsis (n = 47). Using flow cytometry, we measure the expression of CD64 on neutrophils and CD69 on NK cells. Results Expression of CD64 on neutrophils and CD69 on NK cells did not increase in the clinical or confirmed sepsis groups compared to the without sepsis group. Conclusions Leukocytes from infants born prematurely may have tightly regulated mechanisms that control their activation phenotype, rendering them unsuitable for diagnosing sepsis.

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ABSTRACT Carbapenem-Resistant Pseudomonas Aeruginosa (CRPA) is considered as one of the high priority pathogens by the World Health Organization. As CRPA carbapenemase producers have increased worldwide, the aim of this study was to evaluate the carbapenemase prevalence in CRPA at a tertiary care hospital in Brazil”. All 395 CRPA identified in the period of September 2021 to May 2024 were evaluated by multiplex real-time polymerase chain reaction (qPCR-HRM) for the following carbapenemase genes: blaKPC, blaNDM, blaOXA48like, blaIMP, blay^ blaSPM and blaGES. In the first period analyzed (September to December 2021), almost 70 % of the isolates were negative for the 7 tested genes, and the blaNDM was found in 27.3 % of the CRPA. In the following semesters there was an increase of blaNDM as follows: January to June of 2022 = 29.8 %; July to December of 2022 = 43.8 %; January to June of 2023 = 42.4 %; July to December 2023 = 58.9 % and January to May of 2024 = 59.5 % of blaNDM. The prevalence of the other carbapenemases remained low. These results indicated an important increase of the blaNDM gene, overcoming the CRPA non-carbapenemase producers in our institution.

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ABSTRACT Standard anti-tuberculosis regimens (Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol [RHZE]) remain challenging for critically ill patients and those with a non-functioning gastrointestinal tract. In Brazil, these challenges are amplified by the lack of Intravenous (IV) rifampicin, isoniazid, and ethambutol, which often results in suboptimal outcomes. This brief communication synthesized evidence on parenteral therapies and proposed a structured, five-step protocol for critically ill patients unable to receive oral drugs. A narrative review of the guidelines and key studies was also conducted. IV formulations of RHZE are approved in only some countries and are not available everywhere. Alternative IV drug classes, such as fluoroquinolones, aminoglycosides, carbapenems, and oxazolidinones, can address malabsorption or intolerance to oral RHZE. However, no standardized regimen exists for this population. Our five-step protocol advises: (1) Characterizing each TB case, (2) determining IV necessity, (3) Consulting specialized TB services, (4) Designing a safe and effective regimen, and (5) Re-evaluating therapy for transition to oral treatment. Given the morbidity and mortality from severe TB in Intensive Care Units (ICU), a formalized approach is essential. Further research and policy initiatives regarding IV first-line drugs are crucial to improve treatment outcomes in this vulnerable group. This strategy unifies practice across diverse clinical settings.

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Abstract Since the emergence of the novel coronavirus SARS-CoV-2, public health measures have adapted as the virus evolve and acquired greater transmissibility and escape from the previous immune response. Genomic surveillance is a reliable and decisive tool for monitoring the evolutionary dynamics of the virus and its nucleotide diversity. Rio Grande do Sul is a southern Brazilian state that borders Argentina and Uruguay, and genomic and epidemiological surveillance led to early detection of COVID-19 variants, as seen in P.1 lineage. The study aimed to investigate the genetic characterization of SARS-CoV-2 Omicron sublineages in Rio Grande do Sul, Brazil, during 2023. By obtaining viral RNA from nasopharyngeal swabs positive for SARS-CoV-2, we performed high-throughput sequencing and data were analyzed using bioinformatic approaches. Our results revealed a dynamic change in Omicron sublineages during 2023, with the occurrence of JN.1+JN.1* reads during December 2023, parallel to the first JN.1 official record in Brazil, occurred in Ceará state, which is in the northeast region of Brazil. These data revealed a distinct nucleotide diversity in S gene of JN.1 reads, highlighting the importance of genomic surveillance in Rio Grande do Sul for the early detection of the entry of future SARS-CoV-2 variants into Brazil.

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ABSTRACT Rapid Antigen Tests (Ag-RDTs) for the detection of SARS-CoV-2 is an important diagnostic tool for containing virus spread. However, their accuracy – the proportion of correct results (both true positives and true negatives) – still needs to be proven when used in a real large-scale context. Accordingly, we provide data from a cross-sectional study conducted in Toledo – PR, Brazil, on the accuracy of rapid tests compared with qPCR within the Brazilian Unified Health System. A total of 2882 thousand individuals presenting symptoms suggestive of COVID-19 were screened. Overall, the antigen tests showed a sensitivity, specificity, and accuracy of 59 % (0.56–0.62), 99 % (0.98–0.99), and 82 % (0.81–0.84) respectively. However, a significant difference was found when analysing two brand tests individually. In addition, for patients with a low quantification Cycle (Cq) < 20 (which indicates a high viral load), the agreement between test results was high (90.85 %). However, this agreement decreased significantly when the viral load decreased, dropping to 5.59 % for samples with Cq ≥ 33, which indicates a lower viral load. While rapid antigen tests are a valuable tool in combating virus spread, their accuracy can vary significantly between manufacturers and under conditions of low viral load.

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Abstract SARS-CoV-2 predominantly affects the respiratory system; however, during the first pandemic wave, there was a concern about its neuroinvasive potential due to its ability to replicate in neural cells and the neurological signs widely reported as impaired taste or smell. This study aimed to evaluate the presence of SARS-CoV-2 in cerebrospinal fluid (CSF) from suspected cases of meningitis. During the first year of the pandemic, from January 2020 to February 2021, CSF samples were first submitted to multiplex qPCR to detect the three main bacteria causing meningitis (Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae), as the routine of the laboratory, but also, they were submitted to RT-qPCR to SARS-CoV-2 detection. Some samples (20 %) were positive for one bacterium; however, none were positive for the virus, suggesting that the incidence of SARS-CoV-2 in meninges is extremely low. This study with other data in the literature contributes to the epidemiologic surveillance of SARS-CoV-2.