Resumo em Inglês:

The aim of this meta-analysis was to compare the efficacy of metronidazole and vancomycin for the treatment of Clostridium difficile infection, especially to investigate which agent was superior for treating either mild or severe C. difficile infection. A meta-analysis of randomized controlled trials and cohort studies identified in Pubmed, Embase, and the Cochrane Library was conducted. Four randomized controlled trials and two cohort studies involving 1218 patients were included in this meta-analysis. Metronidazole was inferior to vancomycin for treating C. difficile infection in terms of both initial clinical cure rates (risk ratio, RR = 0.91, 95% confidence interval, CI = 0.84-0.98, p = 0.02) and sustained cure rates (RR = 0.88, 95% CI = 0.82-0.96, p = 0.003). For mild C. difficile infection, the efficacy of metronidazole and vancomycin resulted in similar clinical cure rates (RR = 0.94, 95% CI = 0.84-1.04, p = 0.21) and sustained cure rates (RR = 0.93, 95% CI = 0.83-1.05, p = 0.26). For severe C. difficile infection the efficacy of vancomycin was superior to metronidazole in terms of clinical cure rates (RR = 0.81, 95% CI = 0.69-0.95, p = 0.009), whereas sustained cure rates were similar (RR = 0.86, 95% CI = 0.72-1.02, p = 0.08). Regarding microbiological cure metronidazole therapy was as effective as vancomycin therapy (RR = 0.88, 95% CI = 0.64-1.21, p = 0.43). Recurrence rates with metronidazole and vancomycin for both mild C. difficile infection (RR = 0.95, 95% CI = 0.56-1.60, p = 0.85) and severe C. difficile infection (RR = 1.27, 95% CI = 0.85-1.91, p = 0.25) were not different. Likewise, no difference in all-cause mortality was found as well (RR = 0.87, 95% CI = 0.56-1.35, p = 0.53). In conclusion, vancomycin provides improved initial clinical and sustained cure rates in patients with C. difficile infection compared with metronidazole, especially in patients with severe C. difficile infection. In view of these data, vancomycin may be considered first line therapy for severe C. difficile infection.

Resumo em Inglês:

Background: In Brazil, ventilator-associated pneumonia (VAP) caused by carbapenem resis- tant Acinetobacter baumannii and Pseudomonas aeruginosa isolates are associated with significant mortality, morbidity and costs. Studies on the clonal relatedness of these isolates could lay the foundation for effective infection prevention and control programs. Objectives: We sought to study the epidemiological and molecular characteristics of A. baumannii vs. P. aeruginosa VAP in an adult intensive care unit (ICU). Methods: It was conducted a cohort study of patients with VAP caused by carbapenem resistant A. baumannii and P'. aeruginosa during 14 months in an adult ICU. Genomic studies were used to investigate the clonal relatedness of carbapenem resistant OXA-23-producing A. baumannii and P. aeruginosa clinical isolates. The risk factors for acquisition of VAP were also evaluated. Clinical isolates were collected for analysis as were samples from the environment and were typed using pulsed field gel electrophoresis. Results: Multivariate logistic regression analysis identified trauma diagnosed at admission and inappropriate antimicrobial therapy as independent variables associated with the development of A. baumannii VAP and hemodialysis as independent variable associated with P. aeruginosa VAP. All carbapenem resistant clinical and environmental isolates of A. baumannii were OXA-23 producers. No MBL-producer P. aeruginosa was detected. Molecular typing revealed a polyclonal pattern; however, clone A (clinical) and H (surface) were the most frequent among isolates of A. baumannii tested, with a greater pattern of resistance than other isolates. In P. aeruginosa the most frequent clone I was multi-sensitive. Conclusion: These findings suggest the requirement of constant monitoring of these microor- ganisms in order to control the spread of these clones in the hospital environment.

Resumo em Inglês:

Background: Human parainfluenza viruses account for a significant proportion of lower respiratory tract infections in children. Objective: To assess the prevalence of Human parainfluenza viruses as a cause of acute respiratory infection and to compare clinical data for this infection against those of the human respiratory syncytial virus. Methods: A prospective study in children younger than five years with acute respiratory infection was conducted. Detection of respiratory viruses in nasopharyngeal aspirate samples was performed using the indirect immunofluorescence reaction. Length of hospital stay, age, clinical history and physical exam, clinical diagnoses, and evolution (admission to Intensive Care Unit or general ward, discharge or death) were assessed. Past personal (premature birth and cardiopathy) as well as family (smoking and atopy) medical factors were also assessed. Results: A total of 585 patients were included with a median age of 7.9 months and median hospital stay of six days. No difference between the HRSV+ and HPIV+ groups was found in terms of age, gender or length of hospital stay. The HRSV+ group had more fever and cough. Need for admission to the Intensive Care Unit was similar for both groups but more deaths were recorded in the HPIV+ group. The occurrence of parainfluenza peaked during the autumn in the first two years of the study. Conclusion: Parainfluenza was responsible for significant morbidity, proving to be the second-most prevalent viral agent in this population after respiratory syncytial virus. No difference in clinical presentation was found between the two groups, but mortality was higher in the HPIV+ group.

Resumo em Inglês:

Background: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective. Methods: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2). Results: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n= 325,900) and decompen- sated (n = 45,000) cirrhosis; hepatocellular carcinoma (n = 19,100); and liver-related deaths (n = 16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively. Conclusions: While the incidence and prevalence of hepatitis C virus in Brazil are decreasing; cases of advanced liver disease continue to rise. Besides higher sustained virological response rates; new strategies focused on increasing the proportion of diagnosed patients and eligibility to treatment should be adopted in order to reduce the burden of hepatitis C virus infection in Brazil.

Resumo em Inglês:

Background: To analyse knowledge, attitudes and sexual practices on HIV/AIDS, and estimate HIV prevalence among residents of Sucre (Bolivia). Methodology: Population-based survey of residents aged 15-49 randomly selected during 2008/2009. Blood samples were collected on Whatman-filter paper and tested with enzyme-linked immunosorbent assay. Knowledge on HIV/AIDS, sexual risk practices and discriminatory attitudes against people living with HIV/AIDS (PLWHA) were modelled with multiple logistic regression. Results: Of 1499 subjects, 59% were women. All subjects were HIV-negative. Inadequate knowledge of HIV/AIDS transmission and prevention was observed in 67% and risk factors varied by gender (interaction p-value < 0.05). Discriminatory attitudes were displayed by 85% subjects; associated factors were: rural residence, low educational level and low income. Unsafe sex was reported by 10%; risk factors varied by residence area (interaction p-value < 0.05). In urban areas, risk factors were male sex, younger age and being in common-law union. Conclusions: Prevalence of HIV infection is very low and unsafe sex is relatively uncommon. Inadequate knowledge on HIV/AIDS and discriminatory attitudes towards PLWHA are extremely high and are associated to gender, ethnic and economic inequalities.

Resumo em Inglês:

Paracoccidioidomycosis is a systemic and endemic mycosis, restricted to tropical and subtropical areas of Latin America. The infection is caused by the thermal dimorphic fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. The diagnosis of paracoccidioidomycosis is usually performed by microscopic examination, culture and immunodiagnostic tests to respiratory specimens, body fluids and/or biopsies; however these methods require laboratory personnel with experience and several days to produce a result. In the present study, we have validated and evaluated a nested PCR assay targeting the gene encoding the Paracoccidioides gp43 membrane protein in 191 clinical samples: 115 samples from patients with proven infections other than paracoccidioidomycosis, 51 samples as negative controls, and 25 samples from patients diagnosed with paracoccidioidomycosis. Additionally, the specificity of the nested PCR assay was also evaluated using purified DNA isolated from cultures of different microorganisms (n = 35) previously identified by culture and/or sequencing. The results showed that in our hands, this nested PCR assay for gp43 protein showed specificity and sensitivity rates of 100%. The optimized nested PCR conditions in our laboratory allowed detection down to 1 fg of P. brasiliensis DNA.

Resumo em Inglês:

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most frequently isolated agents in both nosocomial and community settings. It is a constant challenge for antibacterial therapy. Therefore, it becomes essential to understand the epidemiology of MRSA isolates in the institution and/or region to guide empirical therapy. The objective of this study was to evaluate the epidemiological characteristics of MRSA isolates in the state of Santa Catarina, Brazil, and determine if there is a clonal spread. We evaluated 124 clinical isolates of MRSA obtained from various anatomical sites from patients in the state of Santa Catarina in Southern Brazil. The antimicrobial susceptibility profile was evaluated by disk diffusion and minimum inhibitory concentration (MIC) was determined by Etest and broth macrodilution. SCCmec types were determined by multiplex PCR and the clonal relationship among isolates was assessed by pulsed field gel electrophoresis. Antimicrobials that have demonstrated lower rates of resistance were tetracycline (20.2%), sulfamethoxazole-trimethoprim (20.2%) and chloramphenicol (12.9%). We did not detect any resistance to glycopeptides, daptomycin, linezolid, and tigecycline. SCCmec type III was predominant (54%), followed by type II (21.8%), consistent with other Brazilian studies. Twenty-six clones were observed grouping 72 (58%) isolates and no clonal relationship was observed between our isolates and the major epidemic clones circulating in Brazil. An intriguing distinct MRSA epidemiology was observed in Santa Catarina, compared to other Brazilian regions.

Resumo em Inglês:

Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expen- sive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1 log10 IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.Z%). Analysis on the validation group demonstrated a positive predictivevalue of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in predicting sustained virologic response of chronic genotype 1 hepatitis C virus infected patients, and can be used to guide anti-hepatitis C virus treatment, especially in resource-limited areas.

Resumo em Inglês:

Background: For clinicians, a practical bedside tool for severity assessment and prognosis of patients with Clostridium difficile infection is a highly desirable unmet medical need. Setting: Two general teaching hospitals in northeast Mexico. Population: Adult patients with C. difficile infection. Methods: Prospective observational study. Results: Patients included had a median of 48 years of age, 54% of male gender and an average of 24.3 days length of hospital stay. Third generation cephalosporins were the antibiotics most commonly used prior to C. difficile infection diagnosis. Patients diagnosed with C. difficile infection had a median ATLAS score of 4 and 56.7% of the subjects had a score between 4 and 7 points. Patients with a score of 8 through 10 points had 100% mortality. Conclusion: The ATLAS score is a potentially useful tool for the routine evaluation of patients at the time of C. difficile infection diagnosis. At 30 days post-diagnosis, patients with a score of ≤3 points had 100% survival while all of those with scores ≥8 died. Patients with scores between 4 and 7 points had a greater probability of colectomy with an overall cure rate of 70.1%.

Resumo em Inglês:

Human cytomegalovirus is a ubiquitous pathogen that infects the majority of the world's population. After long period of time co-evolving with human being, this pathogen has developed several strategies to evade host immune surveillance. One of the major trick is encoding homologous to those of the host organism or stealing host cellular genes that have significant functions in immune system. To date, we have found several viral immune analogous which include G protein coupled receptor, class I major histocompatibility complex and chemokine. Chemokine is a small group of molecules which is defined by the presence of four cysteines in highly conserved region. The four kinds of chemokines (C, CC, CXC, and CX3C) are classified based on the arrangement of 1 or 2 N-terminal cysteine residues. UL128 protein is one of the analogous that encoded by human cytomegalovirus that has similar amino acid sequences to the human CC chemokine. It has been proved to be one of the essential particles that involved in human cytomegalovirus entry into epithelial/endothelial cells as well as macrophages. It is also the target of potent neutralizing antibodies in human cytomegalovirus-seropositive individuals. We had demonstrated the chemotactic trait of UL128 protein in our previous study. Recombinant UL128 in vitro has the ability to attract monocytes to the infection region and enhances peripheral blood mononuclear cell proliferation by activating the MAPK/ERK signaling pathway. However, the way that this viral encoded chemokine interacting with peripheral blood mononuclear cells and the detailed mechanism that involving the virus entry into host cells keeps unknown. Here we performed in vitro investigation into the effects of UL128 protein on peripheral blood mononuclear cell's activation and receptor binding, which may help us further understand the immunomodulatory function of UL128 protein as well as human cytomegalovirus diffusion mechanism.

Resumo em Inglês:

Objectives: Men who have sex with men are at risk of tenofovir nephrotoxicity due to its wide use in both treatment and prophylaxis for human immunodeficiency virus infection, but little is known about the urinary biomarkers of early renal dysfunction in this population. This study aims to identify useful biomarkers of early renal dysfunction among human immunodeficiency virus-infected men who have sex with men exposed to tenofovir. Methods: In a cross-sectional study urinary alpha1-microglobulin, beta2-microglobulin, N-acetyl-B-n-glucosaminidase and albumin were measured and expressed as the ratio-to-creatinine in 239 human immunodeficiency virus-infected men who have sex with men who were treatment naïve or receiving antiretroviral therapy with tenofovir-containing or non-tenofovir-containing regimens. Additionally, 56 patients in the non-antiretroviral therapy group started a tenofovir-containing regimen and were assessed after 3 and 6 months on antiretroviral therapy. Results: Both the frequency of alpha1-microglobulin proteinuria (alpha1-microglobulin-creatinine ratio >25.8 mg/g) and the median urinary alpha1-microglobulin-creatinine ratio were higher in the tenofovir disoproxil fumarate group than the other two groups (all p < 0.05). A higher frequency of beta2-microglobulin proteinuria (beta2-microglobulin-creatinine ratio >0.68 mg/g) was also observed in the tenofovir group (28.9%) compared to the non-tenofovir group (13.6%, p = 0.024). There were no significant differences between groups for N-acetyl-β-n-glucosaminidase and albumin. In the longitudinal study, the median urinary alphat-microglobulin-creatinine ratio after 3 and 6 months on tenofovir-containing therapy (16.8 and 17.3 mg/g) was higher than baseline (12.3 mg/g, p = 0.023 and 0.011, respectively), while no statistically important changes were observed in urinary beta2-microglobulin-creatinine ratio or in the other biomarkers after 3 and 6 months on antiretroviral therapy (all p > 0.05). Conclusion: Urinary alphat-microglobulin seems to be a more sensitive and stable indicator of tubular dysfunction than urinary beta2-microglobulin for assessing tenofovir-related nephrotoxicity and can be significantly altered after tenofovir exposure.

Resumo em Inglês:

Natural killer cells are a unique type of lymphocytes with cytotoxic capacity, and play important roles against tumors and infections. Recently, natural killer cells have been increasingly valued in their effects in hepatitis B virus infection. Since hepatitis B virus is not cytopathic, the subsequent antiviral immune responses of the host are responsible for sustaining the liver injury, which may result in cirrhosis and even hepatocellular carcinoma. Many studies have confirmed that natural killer cells participate in anti-hepatitis B virus responses both in the early phase after infection and in the chronic phase via cytolysis, degranulation, and cytokine secretion. However, natural killer cells play dichotomic roles: they exert antiviral and immunoregulatory functions whilst contribute to the pathogenesis of liver injury. Here, we review the roles of natural killer cells in hepatitis B virus infection, introducing novel therapeutic strategies for controlling hepatitis B virus infection via the modulation of natural killer cells.

Resumo em Inglês:

This study aimed to estimate the prevalence of infection by the hepatitis B virus (HBV) and hepatitis C virus (HCV) in people infected by the human immunodeficiency virus (HIV) and analyze sociodemographic and behavioral factors associated with such co-infection. A cross-section study was performed in 495 individuals treated at a public center in the city of Goiânia. Participants were interviewed and blood collected for evaluation of serological and molecular markers for HBV and HCV. The rate of exposure to HBV was 33.5% (95% CI 29.4-37.9). Nineteen patients (3.8%) were diagnosed as HBV carriers, of whom 68.4% were HBV DNA positive. The prevalence of anti-HCV was 9.7% (95% CI 7.3-12.7). Genotype 1a was identified in 72.7% of the PCR samples positive for HCV. Co-infection by all three viruses was 4.4% (95% CI 2.9-6.8). Being, male, aged ≥40 years, history of sexually transmitted disease (STD), and having homosexual practices were independently associated with the presence of markers of HBV exposure. A history of injectable drugs use and STDs showed association with HCV seropositivity. Approximately 50% of participants were not aware of their HBV and HCV serostatus. The results obtained may contribute to assess the burden of viral hepatitis in people living with HIV and to guiding preventive measures for more vulnerable groups.

Resumo em Inglês:

Background: Cardiovascular disease in the context of human immunodeficiency virus infection has become a major clinical concern in recent years. In the current report we assess hospitalizations due to cardiovascular disease in human immunodeficiency virus patients in a Social Security reference hospital in Peru. Methods : A retrospective study was carried out between January 1996 and December 2012 in a General Hospital in Lima, Peru. Results: We included 26 patients hospitalized due to cardiovascular disease. Mean age was 46.3 years (SD 12.5), predominantly male (57.7%). Ten patients (38.4%) were in Acquired Immunodeficiency Syndrome stages. Seventeen (65.4%) received high-active-antiretroviral therapy. Eleven (42.3%) had cardiac involvement and 15 (57.7%) had non-cardiac vascular involvement. The most frequent causes of cardiac involvement were pericardial effusion and myocardial infarction. On the other hand, deep vein thrombosis and stroke were the most frequent for non-cardiac vascular involvement. Conclusions: Cardiovascular disease is an important cause of hospitalization in Peruvian human immunodeficiency virus patients, with differences between immunosuppression stages. Further studies analyzing associated factors are warranted.

Resumo em Inglês:

In this study, we aimed to evaluate the performance of different phenotypic tests to detect carbapenem-resistant Enterobacteriaceae. Three different phenotypic methods were evaluated: (1) combined-disk test of meropenem plus phenylboronic acid or EDTA reading after 24 h and 48 h; (2) selective/chromogenic read after 24 h and after 48 h; and (3) overnight selective enrichment broth containing 10 µg ertapenem disk followed by culture on MacConkey agar. A positive result in at least one of the methods was submitted to PCR for blaNDM-1, blaOXA-48, blaKPC, blaSPM-1, blaIMP, and blaGES detection. Carbapenem-resistant Enterobacteriaceae was detected in 31 (30.4%) of 102 rectal swabs evaluated. All isolates showed to be KPC-2-producing organisms. Results showed excellent agreement among the evaluated tests (positive and negative) (kappa = 0.88). It is important to state that combined-disk test with phenylboronic acid is not suitable for bacterial identification/isolation. Conversely, selective/chromogenic agar after 48h of incubation showed to be a useful tool, with the advantage of presumptive bacterial identification.

Resumo em Inglês:

Human immunodeficiency virus (HIV) positive patients may develop vasculitis, either mediated by immunological factors or by direct vascular injury. We describe a patient who developed manifestations suggestive of extremities vasculitis with no identifiable risk factors other than HIV, Epstein Barr and Herpes Simplex Virus (HSV) type 1 co-infection. Physicians should be aware that vasculitis may have a heterogeneous presentation and occur associated with HIV infection. Although unusual, this association should be recognized for early proper treatment and prevention of ischemia.