Resumo em Inglês:

ABSTRACT Background: HIV infection harms adaptive cellular immunity mechanisms. Long-term virological control by combined antiretroviral therapy (cART) reduces the risk of mycobacterial infections. Thus, we aimed to study cellular responses to mycobacterial antigens in 20 HIV-infected adolescents with at least one year of virological control (HIV-RNA <40 copies/mL) and 20 healthy adolescents. Methods: We evaluated CD8 and γδ T-cell degranulation by measurement of CD107a membrane expression after stimulation with lysates from BCG (10 µg/mL) and H37RA Mycobacterium tuberculosis (Mtb, 10 µg/mL). Immune activation and antigen-presenting ability were also assessed by determination of HLA-DR, CD80, and CD86 markers. Results: TCR γδ T-cell CD107a expression was similar between groups in response to mycobacterial antigens, and lower in the HIV-infected group in response to mitogen. Higher baseline HLA-DR expression and lower mycobacterial-stimulated expression was found within the HIV-infected group. Conclusions: Similar degranulation in stimulated CD8+ and TCR γδ T-cells from HIV-infected adolescents, when compared to healthy controls suggests long-term immunological preservation with immune reconstitution under successful cART. However, differences in HLA-DR expression may represent ongoing inflammation and lower specific responses in HIV-infected youth. These features may be relevant in the context of the precocity and severity of vertically acquired HIV infection.

Resumo em Inglês:

ABSTRACT Highly active antiretroviral therapy (HAART) has significantly improved survival of people living with HIV/Aids (PLWHA). However, poor treatment adherence to HAART and other problems, still cause therapy failure and contribute to increased morbidity and mortality of PLWHA. In this retrospective cohort study (2013-2015), we sought to evaluate the factors associated with mortality of PLWHA failing HAART in 2013, who were receiving care at a reference center for sexually transmitted diseases (STD) and HIV/AIDS. A total of 165 individuals over 18 years of age who were failing antiretroviral therapy were evaluated. In two-year follow-up, 19 (11.5%) deaths were documented. There were a significant association between mortality and report of illicit drug use (53%, p < 0.01), being attended by a larger number of medical professionals (6.3 ± 3.2, p = 0.02), use of firstline non-nucleoside reverse transcriptase inhibitor (74%, p = 0.01), and history of interrupting HAART ≥3 months (90%), p = 0.02). Patients who died had a significantly higher viral load (mean 49,192.4 ± 35,783.6 copies/mL) than survivors (26,389.2 ± 27,416 copies/mm3, p < 0.01), lower mean CD4 cell counts (127.8 ± 145.6 cells/mm3 vs. 303.3 ± 202.4 cells/mm3, p < 0.01), and higher frequency of previous virologic failure (89% vs. 74.7%, p < 0.01). Our results reinforce the importance of early detection and prevention of virologic failure, to reduce the mortality associated with this event.

Resumo em Inglês:

ABSTRACT Bloodstream infections (BSIs) are serious infections associated with high rates of morbidity and mortality. Every hour delay in initiation of an effective antibiotic increases mortality due to sepsis by 7%. Turnaround time (TAT) for conventional blood cultures takes 48 h, forcing physicians to streamline therapy by exposing patients to broad-spectrum antimicrobials. Our objective was (1) to evaluate the accuracy and TAT of an optimized workflow combining direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and in-house real-time polymerase chain reaction (PCR) for bacterial identification and antimicrobial resistance profiling directly from positive blood bottles for diagnosing bloodstream infections and (2) to verify the effect of reporting results to medical staff. A total of 103 BSI episodes from 91 patients admitted to three hospitals in São Paulo, Brazil were included. TAT from molecular versus conventional methods was measured and compared. Our protocol showed an overall agreement of 93.5% for genus and 78.5% for species identification; 74.2% for methicillin resistance detection, 89.2% for extended-spectrum β-lactamase profiling, 77.8% for metallo-β-lactamase profiling, and 100% for carbapenemase profile and vancomycin-resistance detection when compared with conventional testing. TAT of molecular sample processing according to our protocol was 38 h shorter than conventional methods. Antimicrobial interventions were possible in 27 BSI episodes. Antimicrobial discontinuation was achieved in 12 BSI episodes while escalation of therapy occurred in 15 episodes. Antimicrobial therapy was inadequate in three (12%) BSI episodes diagnosed using results of molecular testing. Our in-house rapid protocol for identifying both bacteria and antimicrobial resistance provided rapid and accurate results, having good agreement with conventional testing results. These results could contribute to faster antimicrobial therapy interventions in BSI episodes.

Resumo em Inglês:

ABSTRACT Background: The prison system in Paraná, Brazil, is experiencing serious problems related to the increasing number of prisoners. Control of hepatitis C virus (HCV) has become more intense because the incarcerated population is considered a high-risk group for contagious diseases due to the favorable conditions found in prisons for the spread of these morbidities. The objective of this study was to identify features associated with hepatitis C infection among male prisoners in correctional institutions of Paraná state, Brazil. Methods: This was a case-control study (27 cases and 54 controls) of men incarcerated in 11 penitentiaries in Paraná, Brazil. Information was obtained through a questionnaire in a cross-sectional epidemiological survey on HCV infection during the period from May 2015 to December 2016. Eligible men were recruited after testing positive for anti-HCV antibodies. Cases and controls were selected based on serological results of enzyme-linked immunosorbent assays and were matched by age, location of the penitentiary, and time in prison. Logistic regression analysis was used to identify risk factors for HCV seropositivity. Results: The main significant independent risk factor for the acquisition of HCV infection was the use of injectable drugs (OR = 4.00; 95%CI:1.41-11.35; p < 0.001). Conclusions: This study provides evidence that HCV infection is associated with drug use by this population. This information is pivotal for tailoring prevention programs and guiding specific socioeducational measures that aim to reduce or prevent HCV transmission within the prison setting.

Resumo em Inglês:

ABSTRACT Introduction and aim: Hepatitis C is a key challenge to public health in Brazil. The objective of this paper was to describe the Brazilian strategy for hepatitis C to meet the 2030 elimination goal proposed by World Health Organization (WHO). Methods: A mathematical modeling approach was used to estimate the current HCV-infected Brazilian population, and to evaluate the relative costs of two different scenarios to address HCV disease burden in Brazil: (1) if no further changes are made to the HCV treatment program in Brazil; (2) where the WHO targets for 2030 elimination are met through diagnosis and treatment efforts peaking before 2024. Results: An anti-HCV prevalence of 0.53% was calculated for the total population. It was estimated that the number of HCV-RNA+ individuals in Brazil in 2017 was 632,000 (0.31% of the population). Scale-up of treatment and diagnosis over time will be necessary in order to achieve WHO targets beginning in 2018. Direct costs (diagnostic, treatment and healthcare costs) are projected to increase significantly during the scale-up of treatment and diagnosis in the initial years of the intervention scenario, but then fall below the base case on an annual basis by 2025-2036, once HCV is eliminated, due to health sectors savings from the prevention of HCV liver-related morbidity and mortality. Conclusion: Achieving the WHO targets is technically feasible in Brazil with a scale-up of treatment and diagnosis over time, beginning in 2018. However, elimination of hepatitis C requires policy changes to substantially scale-up prevention, screening and treatment of HCV, together with public health advocacy to raise awareness among affected populations and healthcare providers.

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ABSTRACT Backgroud: Daptomycin has been used in bone and joint infections (BJI) and prosthesis joint infections (PJI) considering spectrum of activity and biofilm penetration. However, the current experience is based on case reports, case series, cohorts, and international surveys. The aim of this systematic review was to evaluate studies about daptomycin treatment efficacy in BJI/PJI compared to other antibiotic regimens. Methods: PubMed, LILACS, Scielo and Web of Science databases were searched for articles about daptomycin and treatment of BJI and PJI from inception to March 2018. Inclusion criteria were any published researches that included patients with BJI treated with daptomycin. Diagnosis of BJI was based on clinical, laboratory and radiological findings according to IDSA guidelines. Results: From 5107 articles, 12 articles were included. Only three studies described the outcomes of patients with BJI treated with daptomycin with comparator regimen (vancomycin, teicoplanin and oxacillin). Studies presented large heterogeneity regarding device related infections, surgical procedures, and daptomycin regimens (varied from 4 mg/kg to 10 mg/kg). A total of 299 patients have been included in all studies (184 infections associated with orthopedic disposal and 115 osteomyelitis/septic arthritis). Two hundred and thirty-three patients were treated with daptomycin. The clinical cure rates on device related and non-device related infections (i.e. osteomyelitis) were 70% and 78%, respectively. Compared to all regimens evaluated, daptomycin group outcomes were non-inferior. Conclusion: Although a randomized clinical trial is needed, this systematic review tends to support daptomycin usage for bone and joint infections.

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ABSTRACT We report a patient with fungal keratitis caused by a multiresistant Fusarium solani in a tertiary care hospital located in southern Brazil. A 55-year-old man with a history of ocular trauma presented with keratitis in left eye. The patient has a complicated clinical course and failed to respond to local and systemic antifungal treatment, and required eye enucleation. Despite multiple topical, intraocular and systemic antifungal treatments, hyphal infiltration persisted in the corneal transplant causing continuous recurrences. The cultures of corneal biopsy scrapings were positive for Fusarium spp. The organism was identified to species level by multi-locus sequencing for translation elongation factor 1 alpha (EF-1α), and RNA polymerase II subunit (RPB2). In vitro antifungal susceptibility testing of the isolate by the broth microdilution method, according to CLSI M38-A2, disclosed susceptibility to natamycin and resistance to amphotericin B, voriconazole, itraconazole and fluconazole. Considering previous unsuccessful antifungal treatments due to multiple drug resistance, the eye was enucleated. Our case report illustrates that management of fungal keratitis remains a therapeutic challenge. Optimal treatment for F. solani infection has not yet been established and should include susceptibility testing for different antifungal agents.

Resumo em Inglês:

ABSTRACT Ciguatera poisoning is the most common form of non-bacterial food-poisoning from fish worldwide. The incidence among Brazilians returning from high-risk regions is unclear because it is not a mandatory reportable disease. We describe a previously healthy 53-year-old Brazilian woman developed Ciguatera fish poisoning while traveling to Havana, Cuba. Physicians and health care professionals should advise travelers to avoid eating ciguatoxic fish species and potentially toxic fish species in the Caribbean islands. Despite the prognosis for most cases is good with a short duration of self-limited symptoms, early recognition of the identifying clinical features of ciguatera can result in improved patient care.

Resumo em Inglês:

ABSTRACT Global dissemination of mcr-like genes represents a serious threat to public health since it jeopardizes the effectiveness of colistin, an antibiotic used as a last-resort treatment against highly antibiotic-resistant bacteria. In 2017, a mcr-1-positive isolate of Escherichia coli was found in Chile for the first time. Herein we report the genetic features of this strain (UCO-457) by whole-genome sequencing (WGS) and conjugation experiments. The UCO-457 strain belonged to ST4204 and carried a 285 kb IncI2-type plasmid containing the mcr-1 gene. Moreover, this plasmid was transferred by conjugation to an E. coli J53 strain at high frequency. The isolate harbored the cma, iroN, and iss virulence genes and did carry resistance genes to trimethoprim/sulfamethoxazole and fluoroquinolones. Other antibiotic resistance determinants such as β-lactamases-encoding genes were not detected, making the isolate highly susceptible to these antibiotics. Our results revealed that such susceptible isolates could be acting as platforms to disseminate plasmid-mediated colistin resistance. Based on this evidence, we consider that mcr-like prevalence deserves urgent attention and should be examined not only in highly resistant bacteria but also in susceptible isolates.