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Immunogenicity of influenza vaccine in transplant recipients is suboptimal and alternative vaccination regimens are necessary.We compared the immunogenicity of a standard-dose trivalent inactivated influenza vaccination (SDTIIV), double-dose trivalent inactivated influenza vaccination (DDTIIV), and booster-dose trivalent inactivated influenza vaccination (BDTIIV) of the 2014 seasonal trivalent inactivated influenza vaccine in kidney transplant recipients. We randomized 176 participants to SDTIIV (59), DDTIIV (59), and BDTIIV regimens (58). Antibody titers were determined by hemagglutination inhibition at enrollment and 21 d postvaccination. Seroprotection rates (SPRs), seroconversion rates (SCRs), and geometric mean ratios (GMRs) were analyzed separately for participants with low (1:40) and high (≥1:40) prevaccination antibody titers.Vaccination was confirmed for 172 participants. Immunogenicity analysis was done for 149 participants who provided postvaccination blood samples. In the subgroup with high prevaccination antibody titers, all vaccination regimens induced SPR70% to all antigens, but SCR and GMR were below the recommendations. In the subgroup with low prevaccination antibody titers, DDTIIV and BDTIIV regimens induced adequate SCR40% and GMR2.5 for all antigens, whereas SDTIIV achieved the same outcomes only for influenza B. SPRs were70% only after DDTIIV (A/H1N1-77.8%) and BDTIIV (A/H3N2-77.8%). BDTIIV regimen independently increased seroprotection to A/H1N1 (PR = 2.58; P = 0.021) and A/H3N2 (PR = 2.21; P = 0.004), whereas DDTIIV independently increased seroprotection to A/H1N1 (PR = 2.59; P = 0.021).Our results suggest that DDTIIV and BDTIIV regimens are more immunogenic than SDTIIV, indicating the need for head-to-head multicenter clinical trials to further evaluate their efficacy.

We evaluated the interference of the mucosal barrier injury (MBI) laboratory-confirmed bloodstream infection (MBI-LCBI) criteria on the central-line–associated bloodstream infection (CLABSI) incidence density, and the proportion of catheter-related bloodstream infections (CRBSIs) among those classified as MBI. We detected 339 CLABSIs: 15.0% were classified as MBI-LCBIs, and among these, 19.6% were classified as CRBSIs.

RESUMO Descrever uma estratégia para facilitar o acesso à vacina conjugada pneumocócica 13-valente (PCV-13) para pessoas vivendo com HIV (PVHIV), durante a pandemia de COVID-19. Método: relato de experiência sobre a organização de um serviço de atendimento para PVHIV na cidade de São Paulo, para facilitar o acesso à PCV-13 no decorrer da campanha de vacinação de influenza de 2020, durante a pandemia de COVID-19. Resultados: por meio da integração entre um serviço de atendimento para PVHIV e um Centro de Imunizações (CRIE) foi possível oferecer a PCV-13 para as PVHIV em seu local de atendimento, diminuindo barreiras físicas de acesso à imunização. Dessa forma, das 1906 PVHIV que passaram pelo serviço durante o período de 23 de março a 31 de julho de 2020, 84,4% (1609) receberam a vacina influenza, PCV-13 ou ambas. Dos 1609 vacinados, 50,6% (814) foram elegíveis e receberam a PCV-13. Conclusão: oferecer a vacina em seu local de tratamento e orientar as PVHIV sobre a importância da vacinação como estratégia de prevenção de doenças, identificando os elegíveis a recebê-las, foi uma importante ação realizada pela instituição em conjunto com a equipe de enfermagem, como estratégia de facilitar o acesso à vacinação.

The article describes a strategy to facilitate access to pneumococcal conjugate vaccine 13 (PCV-13) for people living with HIV/AIDS (PLHIV) during the COVID-19 pandemic. Method: report on the experience regarding the organization of a care service for PLHIV in the city of São Paulo to facilitate access to PCV-13 in the framework of the 2020 influenza vaccination campaign during the COVID-19 pandemic. Results: through the integration between a PLHIV care service and an Immunization Center (CRIE in Portuguese), it was possible to offer PCV-13 to PLHIV at the point of care, reducing physical barriers to access to immunization. Thus, of the 1,906 PLHIV who passed through the service during the period March 23-July 31, 2020, 84.4% (1,609) received the influenza vaccine, PCV-13 or both. Of the 1609 vaccinated, 50.6% (814) were eligible and received PCV-13. Conclusion: offering the vaccine at the point of care and orienting PLHIV on the importance of vaccination as a disease prevention strategy, identifying those eligible to receive it, was an important action carried out by the institution together with the nursing team, as a strategy to facilitate access to vaccination.

Background: People living with HIV (PLWH) may have a poor or delayed response to vaccines, mainly when CD4+ T cell counts are low. There are limited data concerning the safety and immunogenicity of COVID-19 vaccines in PLWH. Methods: This prospective controlled study evaluated the safety and immunogenicity of the SARS-CoV-2 inactivated vaccine CoronaVac in PLWH compared with controls with no known immunosuppression. Immunogenicity was assessed with SARS-CoV-2 IgG seroconversion (SC), neutralizing antibodies (NAb) activity, and factor increase in IgG geometric mean titers (FI-GMT). We also investigated if levels of CD4+ T cell counts (< or ≥500 cells/mm3) were associated with CoronaVac immunogenicity. Findings: 511 participants (215 PLWH and 296 controls) were eligible for the immunogenicity analysis. At vaccine completion (D69), although the percentage of participants with SC and NAb positivity was high for both PLWH and controls, it was somewhat lower in PLWH. CD4+ T cell was identified as a relevant factor for immunogenicity, with lower SC and NAb positivity in PLWH with CD4+ counts

To evaluate the prognostic factors in adult cancer patients with pneumococcal bacteremia, describe episode features and the phenotypic characteristics of the isolated strains. We evaluated the episodes in patients admitted to a cancer hospital between 2009 and 2015. The outcomes were defined as 48 h mortality and mortality within 10 days after the episode. The variables evaluated were: age, sex, ethnicity, ECOG, Karnofsky score, SOFA, cancer type, metastasis, chemotherapy, radiotherapy, neutropenia, previous antibiotic therapy, community or healthcare-acquired infection, comorbidities, smoking, pneumococcal vaccination, infection site, presence of fever, polymicrobial infection, antimicrobial susceptibility, serotype and treatment. 165 episodes were detected in 161 patients. The mean age was 61.3 years; solid tumors were the most prevalent (75%). 48 h and 10-day mortality were 21% (34/161) and 43% (70/161) respectively. The 48 h mortality- associated risk factors were SOFA and polymicrobial bacteremia; 10-day mortality-associated risk factors were fever, neutropenia, ECOG 3/4, SOFA and fluoroquinolones as a protective factor. Pneumococcal bacteremia presented high mortality in cancer patients, with prognosis related to intrinsic host factors and infection episodes features. Fluoroquinolone treatment, a protective factor in 10-day mortality, has potential use for IPDs and severe community-acquired pneumonia in cancer patients.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. the rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR), 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa. the application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development., ESGBIES study group; ESGICH study group; Spanish Plan Nacional de I+D+i 2013-2016; Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0001]; European Development Regional Fund A Way To Achieve Europe, Operative Program Intelligent Growth 2014-2020; Promex Stiftung fur die Forschung (Carigest SA); GileadGilead Sciences; PfizerPfizer, We thank the ESGBIES and the ESGICH study groups for supporting the study.; This study was supported by the Spanish Plan Nacional de I+D+i 2013-2016 and the Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (grant REIPI RD16/0016/0001), cofinanced by the European Development Regional Fund A Way To Achieve Europe, Operative Program Intelligent Growth 2014-2020.; A.-S.B. received a grant from Promex Stiftung fur die Forschung (via Carigest SA) and funding from Gilead to attend the ECCMID Congress (2018). O.R.S. received speaker honoraria from MSD, Astellas, Novartis, and Pfizer. S.S.K. received speaker honoraria from Pfizer, MSD, Astellas. F.H. received speaker honoraria from MSD, and Pfizer and a research and educational grant from Pfizer. the rest of the authors declare no conflicts of interest.

OBJECTIVES: The impact of Chagas disease (CD) in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi) using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10), those with Chagas disease and HIV infection (CO, n=11), those with only HIV (HIV, n=14) and healthy individuals (C, n=15). RESULTS: We found 1) a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2) a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3) a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4) a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease.

Introduction: Vaccination with tetanus-diphtheria-acellular pertussis (Tdap) has been recommended for healthcare workers (HCWs) by Brazilian Ministry of Health since November 2014. Objective: To describe the strategies implemented to improve Tdap uptake, cumulative vaccine coverage after each intervention, variables associated to Tdap vaccination, and reasons for non-vaccination among HCWs of the main building of a quaternary hospital attached to the Sao Paulo University Medical School. Methods: A list of HCWs eligible for pertussis vaccination was generated. From April to December 2015, the following interventions were implemented: note on intern journal reminding the importance of pertussis vaccination; email to the head nurses strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians of Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. Vaccine coverage was accessed at the end of each month. Multivariate Poisson regression model with a robust error variance was used to evaluate variables associated with Tdap vaccination. Reasons for non-vaccination were evaluated from January to May 2017 through phone calls for HCWs who had not received Tdap. Results: The study included 456 HCWs. After the interventions, Tdap coverage raised from 2.8% to 41.2%. In the multivariate analysis, occupation (physician), working place (obstetrics or anesthesiology) and influenza vaccination in 2015 were independently associated to Tdap vaccination. The main reason for non-vaccination was unawareness of Tdap recommendations. Conclusions: Tdap uptake among HCWs was low in our hospital. Providing vaccination at convenient places/times for HCW seems to be the most efficient strategy to increase vaccine uptake. Keywords: Pertussis vaccine, Diphtheria-tetanus-acellular pertussis vaccines, Bordetella pertussis, Whopping cough, Health personnel

OBJECTIVES: The purpose of this study was to evaluate the incidence of urinary tract infection (UTI) in patients with cystitis symptoms who underwent pelvic radiation therapy and identify correlated predictive factors. METHODS: A prospective cohort study was conducted of patients who met the following: primary pelvic cancer treated with curative intent, older than 18 years old, and good performance status. The exclusion criteria were patients being treated for a UTI, using a urinary catheter, in dialysis or with cystostomy or nephrostomy, and using antibiotics during treatment. Urinalysis and urine culture were collected before the beginning of radiation therapy. Weekly evaluations of urinary symptoms were subsequently performed. In cases of new or worsening symptoms, a questionnaire was applied, and new urine exams were collected. The UTI diagnosis was defined by uroculture as bacterial growth greater than 104 CFU/mL. RESULTS: From September 2014 to November 2015, 112 patients were sequentially recruited, and 72 (64%) fulfilled the inclusion criteria. During follow-up, 24 (33%) patients had new urinary symptoms or worse preexisting symptoms. A UTI was confirmed in the second urinary culture in only one (1.4%) patient. CONCLUSIONS: The incidence of UTI was much lower than expected, suggesting that asymptomatic bacteriuria develops symptoms due to radiotherapy. Due to the low rate of UTI, no predictive factor was identified.

Introduction Pseudomonas aeruginosa (PA) has historically been one of the major causes of severe sepsis and death among neutropenic cancer patients. There has been a recent increase of multidrug-resistant PA (MDRPA) isolates that may determine a worse prognosis, particularly in immunosuppressed patients. The aim of this study is to establish the impact of antibiotic resistance on the outcome of neutropenic onco-haematological patients with PA bacteraemia, and to identify the risk factors for MDRPA bacteraemia and mortality. Methods and analysis This is a retrospective, observational, multicentre, international study. All episodes of PA bacteraemia occurring in neutropenic onco-haematological patients followed up at the participating centres from 1 January 2006 to 31 May 2018 will be retrospectively reviewed. The primary end point will be overall case-fatality rate within 30 days of onset of PA bacteraemia. The secondary end points will be to describe the following: the incidence and risk factors for multidrug-resistant and extremely drug-resistant PA bacteraemia (by comparing the episodes due to susceptible PA with those produced by MDRPA), the efficacy of ceftolozane/tazobactam, the rates of persistent bacteraemia and bacteraemia relapse and the risk factors for very early (48 hours), early (7 days) and overall (30 days) case-fatality rates. Ethics and dissemination The Clinical Research Ethics Committee of Bellvitge University Hospital approved the protocol of the study at the primary site. To protect personal privacy, identifying information of each patient in the electronic database will be encrypted. The processing of the patients’ personal data collected in the study will comply with the Spanish Data Protection Act of 1998 and with the European Directive on the privacy of data. All data collected, stored and processed will be anonymised. Results will be reported at conferences and in peer-reviewed publications.

During the last decades pertussis incidence raised globally. Several vaccination strategies targeting adults to reduce pertussis among young infants have been proposed, including vaccination of healthcare workers (HCWs). The aim of this study was to analyse, by performing a systematic review of literature, published papers that evaluated Tdap coverage among HCWs, variables associated with vaccine uptake and efforts implemented to raise vaccination rates. We searched the MedLine, Embase, SCOPUS, LILACS, Web of Science and Cochrane for full-text studies that evaluated Tdap coverage in HCW. Two independent reviewers screened the articles and extracted the data.Twenty-eight studies published from 2009 to 2018 were reviewed. Most studies were conducted in the USA. Initial Tdap coverage varied from 6.1% to 63.9%. USA and France are the only two countries with studies evaluating Tdap coverage within HCWs using national data. In the USA, Tdap coverage in HCWs raised from 6.1% to 45.1% from 2007 to 2015. In the analysis of French national data, a Tdap coverage of 63.9% was observed. Five studies used interventions to raise Tdap coverage in HCWs. Two intervention studies implemented mandatory vaccination and three used educational strategies. All of them achieved coverages over 86%. Only eleven studies analysed the association of Tdap vaccination with variables of interest. Previous immunization with other vaccines recommended for HCWs (like influenza, hepatitis B and MMR) was positively associated with Tdap uptake in four studies. In conclusion, overall Tdap coverage among HCWs is low, but seems to increase over the years after the vaccine introduction and with implementation of interventions to increase coverage.

The management of long-term central venous catheter (LTCVC) infections by multidrug-resistant (MDR) bacteria in cancer patient is a challenge. The objectives of this study were to analyze outcomes in cancer patients with LTCVC-associated infection, identify risks for unfavorable outcomes, and determine the impact of MDR bacteria and antibiotic lock therapy (ALT) in managing such infections. We evaluated all LTCVC-associated infections treated between January 2009 and December 2016. Infections were reported in accordance with international guidelines for catheter-related infections. The outcome measures were 30-day mortality and treatment failure. We analyzed risk factors by Cox forward-stepwise regression. We identified 296 LTCVC-associated infections; 212 (71.6%) were classified as bloodstream infections (BSIs). The most common agent was Staphylococcus aureus. Forty-six (21.7%) infections were due to MDR Gram-negative bacteria. ALT was used in 62 (29.2%) patients, with a 75.9% success rate. Risk factors identified for failure of the initial treatment were having a high sequential organ failure assessment (SOFA) score at diagnosis of infection and being in palliative care; introduction of ALT at the start of treatment was identified as a protective factor. Risk factors identified for 30-day mortality after LTCVC-associated infection were a high SOFA score at diagnosis, infection with MDR bacteria, and palliative care; introduction of ALT at the start of treatment, hematological malignancies, and adherence to an institutional protocol for the management of LTCVC-associated infection were identified as protective factors. Despite the high incidence of infection with MDR bacteria, ALT improves the outcome of LTCVC-associated infection in cancer patients.

Neutropenic patients are at risk of the development of hyalohyphomycosis and mucormycosis. Correct identification is essential for the initiation of the specific treatment, but concomitant mold infections are rarely reported. We report one unprecedented case of concomitant mucormycosis and fusariosis in a neutropenic patient with acute myeloid leukemia. The patient developed rhino-orbital infection by Rhizopus arrhizus and disseminated infection by Fusarium solani. The first culture from a sinus biopsy grew Rhizopus, which was consistent with the histopathology report of mucormycosis. A second sinus biopsy collected later during the patient’s clinical deterioration was reported as hyalohyphomycosis, and the culture yielded F. solani. Due to the discordant reports, the second biopsy was reviewed and two hyphae types suggestive of both hyalohyphomycetes and mucormycetes were found. The dual mold infection was confirmed by PCR assays from paraffinized tissue sections. Increased awareness of the existence of dual mold infections in at-risk patients is necessary. PCR methods in tissue sections may increase the diagnosis of dual mold infections. In case of sequential biopsies showing discrepant results, mixed infections have to be suspected.

OBJECTIVE To estimate the prevalence of hepatitis C virus infection in Brazil’s inmate population.METHODS Systematic review on hepatitis C virus infection in the inmate population. Brazilian studies published from January 1, 1989 to February 20, 2014 were evaluated. The methodological quality of the studies was assessed using a scale of 0 to 8 points.RESULTS Eleven eligible studies were analyzed and provided data on hepatitis C virus infection among 4,375 inmates from seven states of Brazil, with a mean quality classification of 7.4. The overall hepatitis C virus prevalence among Brazilian inmates was 13.6% (ranging from 1.0% to 41.0%, depending on the study). The chances of inmates being seropositive for hepatitis C virus in the states of Minas Gerais (MG), Sergipe (SE), Mato Grosso do Sul (MS), Rio Grande do Sul (RS), Goiás (GO) and Espirito Santo (ES) were 84.0% (95%CI 0.06;0.45), 92.0% (95%CI 0.04;0.13), 88.0% (95%CI 0.09;0.18), 74.0% (95%CI 0.16;0.42), 84.0% (95%CI 0.08;0.31) and 89.0% (95%CI 0.01;0.05) respectively, lower than that observed in the Sao Paulo state (seroprevalence of 29.3%). The four studies conducted in the city of Sao Paulo revealed a lower prevalence in more recent studies compared to older ones.CONCLUSIONS The highest prevalence of hepatitis C virus infection in Brazil’s inmate population was found in Sao Paulo, which may reflect the urban diversity of the country. Despite Brazilian studies having good methodological quality to evaluate the prevalence of the hepatitis C virus, they are scarce and lack data on risk factors associated with this infection, which could support decisions on prevention and implementation of public health policies for Brazilian prisons. RESUMOOBJETIVO Estimar prevalência de infecção pelo vírus da hepatite C entre a população carcerária no Brasil.MÉTODOS Revisão sistemática sobre infecção pelo vírus da hepatite C em populações carcerárias. Foram avaliados estudos brasileiros publicados a partir de 1 de janeiro de 1989 até 20 de fevereiro de 2014. A qualidade metodológica dos estudos foi avaliada utilizando-se escala de zero a oito pontos.RESULTADOS Onze estudos elegíveis foram analisados, os quais forneceram dados sobre a infecção pelo vírus da hepatite C de 4.375 detentos de sete estados do Brasil, com classificação em média de qualidade de 7,4. A prevalência de infecção pelo vírus da hepatite C na população carcerária brasileira foi 13,6%, (variando de 1,0% a 41,0%, dependendo do estudo). As chances de os indivíduos serem soropositivos para o vírus da hepatite C nos estados de Minas Gerais, Sergipe, Mato Grosso do Sul, Rio Grande do Sul, Goiás e Espírito Santo foram 84,0% (IC95% 0,06;0,45), 92,0% (IC95% 0,04;0,13), 88,0% (IC95% 0,09;0,18), 74% (IC95% 0,16;0,42), 84,0% (IC95% 0,08;0,31) e 89,0% (IC95% 0,01;0,05), respectivamente, inferiores àquela observada no estado de São Paulo (soroprevalência de 29,3%). Os quatro estudos realizados na cidade de São Paulo mostraram menor prevalência em estudos mais recentes em comparação aos mais antigos.CONCLUSÕES A maior prevalência de infecção pelo vírus da hepatite C em população carcerária do Brasil foi encontrada em São Paulo, o que pode refletir a diversidade urbana do País. Apesar de os estudos brasileiros apresentarem boa qualidade metodológica para avaliação da prevalência do vírus da hepatite C, são escassos e faltam dados sobre fatores de risco associados a esta infecção, dados esses que poderiam auxiliar nas decisões de prevenção e implementação de políticas em saúde pública para as prisões brasileiras.

The frequency of histoplasmosis among solid organ transplant (SOT) recipients appears to be low where there are only a few case series, mostly among renal and liver transplant recipients. Herein we report a case of a 44-year-old woman who underwent a living-related renal transplant 18 years prior to evaluation, developed a nodule after followed by ulceration upon her posterior right leg and a second one upon her left leg 3 months and 2 months before her hospitalisation, respectively. The biopsy of lesion revealed the presence of Histoplasma spp. Bone marrow aspiration was performed and also revealed the same organism. She had initially received itraconazole without improvement of lesions, while a new lesion appeared on her left arm. Healing of all lesions could be observed after 40 days of liposomal amphotericin B when she was submitted to skin grafts on the legs and a surgical treatment on the arms, and the myelosuppression improved simultaneously. Histoplasmosis seems to be very uncommon among patients who underwent to organ solid transplantation. Most cases occur within 12-18 months after transplantation, although unusual cases have been presented many years post-transplant. There are cases reported in the literature, occurring from 84 days to 18 years after organ transplantation, but without cutaneous involvement. Our patient developed lesions on limbs and myelosuppression after 18 years of chronic immunosuppression medication. This case suggests that besides cutaneous histoplasmosis is an uncommon infection following iatrogenic immunosuppression and even rarer over a long period after the transplantation. Clinicians who care SOT recipient patients must bear in mind histoplasmosis infection as differential diagnosis in any case of cutaneous injury with prolonged fever and try to use as many tools as possible to make the diagnosis, once this disease presents a good prognosis if it is diagnosed and treated promptly.

Fungi are an important cause of infection in patients undergoing solid organ transplantation and bone marrow or hematopoietic stem cell transplantation (BMT/HSCT). The incidence and mortality of fungal infections differ according to the organ and the time since transplantation. In the first 30 days after transplantation, yeast (primarily Candida spp.) predominate. After the first month, filamentous fungi, such as Aspergillus spp., are the most frequent agents of infection (1-6). In BMT/HSCT patients, however, invasive aspergillosis has two peaks of incidence: one at one month post-transplantation and another approximately 90 days after the transplant if the patient develops chronic graft versus host disease (7,8). Among solid organ transplantation, liver and lung transplant have the highest risk for fungal infection due to underlying diseases, surgical techniques and the graft itself (4,9). Antifungal prophylaxis use is well established following some transplant types, such as BMT/HSCT and liver (10,11). However, few studies have evaluated heart and pancreas transplants. One of the major challenges is the prevention of filamentous fungal infections, especially by Aspergillus spp., in high-risk patients, such as those who have undergone an allogeneic BMT and developed chronic graft versus host disease or undergone a lung transplantation (12,13). To standardize the use of primary prophylaxis in transplant patients, we analyzed the literature related to the following transplants: liver, kidney, heart, lung, and HSCT. The IDSA (Infectious Diseases Society of America) system was used to determine the levels of evidence.

We present a case of a 16-year-old male patient with sudden-onset, rash, arthritis and meningitis by Neisseria meningitidis one week after an acute upper respiratory infection. On the 10th day of treatment followed by neurological and arthritis clinical improvement, he presented once again a tender and swollen left knee with a moderate effusion, and active and passive range of motion was severely limited secondary to pain, and when he was submitted to surgical drainage and synovial fluid analysis he showed inflammatory characteristics. A non-steroidal anti-inflammatory drug was taken for five days with complete improvement of symptoms. The case is notable for its combination of features of septic and immune-mediated arthritis, which has rarely been reported in the same patient. Paciente de 16 anos do sexo masculino apresentou-se ao serviço de emergência com quadro de erupção cutânea súbita, artrite e meningite por Neisseria meningitidis, uma semana após apresentar sintomas de infecção de vias aéreas superiores. No décimo dia de tratamento, seguido da melhora clínica neurológica e da artrite, ele volta a apresentar derrame articular moderado com limitação importante da amplitude dos movimentos passivo e ativo secundária à dor. Em seguida, foi submetido à drenagem cirúrgica e a análise do líquido sinovial mostra características inflamatórias. Foi iniciado tratamento com antiinflamatório não esteroidal por cinco dias com melhora completa dos sintomas. Esse caso tem como característica peculiar o fato do indivíduo apresentar tanto as características de artrite séptica pelo meningococo quanto de artrite imunomediada, o que tem sido pouco usual no mesmo paciente.

INTRODUÇÃO: Pacientes em terapia anti-retroviral podem apresentar escapes transitórios de viremia plasmática (blip), porém os preditores desse evento e seu impacto sobre a incidência de falência virológica são ainda controversos na literatura. Neste estudo de coorte estimou-se a incidência de blip e de falência virológica e investigaram-se possíveis preditores de tais desfechos. Blip foi definido como carga viral superior a 50 cópias/mL com subseqüente supressão da viremia plasmática e falência virológica como duas medidas consecutivas de carga viral plasmática superiores a 50 cópias/mL. Adicionalmente, pesquisou-se, por ocasião desses eventos, a presença de mutações genotípicas de HIV capazes de conferir resistência aos anti-retrovirais e as concentrações plasmáticas de inibidores não nucleosídicos da transcriptase reversa e inibidores da protease, comparando-as com o relato dos participantes sobre adesão à medicação. MÉTODOS: 350 participantes infectados pelo HIV (250 homens e 100 mulheres) foram selecionados no Serviço de Extensão ao Atendimento de Pacientes com HIV/Aids Casa da Aids do Hospital das Clínicas da FMUSP, São Paulo, Brasil. Na admissão ao estudo e trimestralmente, ao longo de 78 semanas, foram coletadas informações sobre dados sóciodemográficos, forma presumida de aquisição do vírus, uso de e adesão a medicações anti-retrovirais, ocorrência de outras comorbidades, bem como uso de álcool e de drogas ilícitas. Investigaram-se fatores potencialmente associados à incidência dos desfechos de interesse, tais como ocorrência de outras doenças, exposição a imunizações e falha na adesão a práticas de sexo mais seguro. Amostras de sangue periférico foram coletadas a cada visita para determinação de carga viral plasmática por RT-PCR ultrassensível, e contagem de linfócitos T CD4+ por citometria de fluxo. Nos indivíduos que apresentaram os desfechos de interesse do estudo, procedeu-se ao seqüenciamento dos genes da transcriptase reversa e da protease de HIV e à dosagem plasmática dos anti-retrovirais por método de Cromatografia Líquida de Alta Performance. As incidências de blip e falência virológica foram estimadas e os fatores associados a ambos investigados em modelo de regressão logística múltipla. RESULTADOS: As incidências de blip e falência virológica foram 9,4 e 4,2/100 pessoas-ano, respectivamente. Três indivíduos apresentaram falência virológica precedidos por blip. À análise multivariada, a não adesão às praticas de sexo mais seguro no mês precedente se mostrou independentemente associada à ocorrência de blip (OR 24,64, IC 95% 4,40 137,88, p

This study aimed to describe severe infections with extensively drug-resistant Acinetobacter baumannii-calcoaceticus complex (XDR-ABC), as well as to investigate risk factors for mortality, in cancer patients. It was a retrospective study including all patients diagnosed with XDR-ABC bacteraemia during hospitalization in the intensive care unit of a cancer hospital between July 2009 and July 2013. Surveillance cultures were collected weekly during the study period, and clonality was analysed using pulsed field gel electrophoresis (PFGE). We analysed underlying diseases, oncology therapy, neutrophil counts, infection site and management of infection, in terms of their correlation with 30-day mortality. During the study period, 92 patients with XDR-ABC bacteraemia were identified, of whom 35 (38.0%) were patients with haematological malignancy. We identified XDR-ABC strains with four different profile patterns, 91.3% of patients harbouring the predominant PFGE type. Of the 92 patients with XDR-ABC bacteraemia, 66 (71.7%) had central line-associated bloodstream infections; infection occurred during neutropenia in 22 (23.9%); and 58 (63.0%) died before receiving the appropriate therapy. All patients were treated with polymyxin, which was used in combination therapy in 30 of them (32.4%). The 30-day mortality rate was 83.7%. Multivariate analysis revealed that septic shock at diagnosis of XDR-ABC infection was a risk factor for 30-day mortality; protective factors were receiving appropriate therapy and invasive device removal within the first 48 h. Among cancer patients, ineffective management of such infection increases the risk of death, more so than do features such as neutropenia and infection at the tumour site.

Com o objetivo de descrever os fatores epidemiológicos e clínicos-laboratoriais e avaliar os fatores associados ao desenvolvimento de fibrose moderada e grave, realizou-se a revisão de 426 prontuários médicos de pacientes com infecção crônica pelo vírus da hepatite C, atendidos na Clínica de Moléstias Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo, no período de 01/01 a 31/12/2000. Dos pacientes incluídos no estudo, 56,3% eram do sexo masculino e 43,7% do sexo feminino. A idade deles variou de 18 a 69 anos. A hemotransfusão foi a forma mais freqüente de transmissão do vírus da hepatite C, encontrada em 128 (30%) dos casos e em 187 (43,9%) pacientes não foi encontrado nenhum fator de risco. A distribuição dos pacientes quanto à alteração arquitetural visto na biópsia hepática foi: grau 0 (14,1%), grau 1 (51,2%), grau 2 (20,6%), grau 3 (8%) e grau 4 (6,1%). Na análise multivariada, encontramos associação positiva entre intensidade da fibrose e idade maior que 40 anos na data da biópsia hepática, níveis séricos de albumina abaixo do limite inferior normal, gama-glutamiltransferase maior ou igual a duas vezes o limite superior da normalidade, plaquetas em número menor que 150.000/mm³ e alta atividade necro-inflamatória. Os dados foram inconclusivos para testar a associação entre gravidade da fibrose e alcoolismo. To assess the factors associated with the development of moderate and severe fibrosis, the medical records of 426 patients with chronic hepatitis C virus infection attended at the Infectious and Parasitic Diseases Clinic of the University of São Paulo Faculty of Medicine from January 1 to December 31, 2000 were reviewed. Of the patients included in the study, 56.3% were male and 43.7%, female. Patient age ranged from 18 to 69 years. Blood transfusion was the most frequent form of hepatitis C virus transmission, detected in 128 (30%) cases, and no risk factor was detected in 187 (43.9%) patients. Patient distribution regarding architectural changes observed in a liver biopsy was: grade 0 (14.1%); grade 1 (51.2%); grade 2 (20.6%); grade 3 (8%); grade 4 (6.1%). Multivariate analysis revealed a positive correlation between fibrosis severity and age greater than 40 years at the time of the liver biopsy, serum albumin levels below normal lower limits, gamma-glutamyltransferase levels equal to or higher than twice upper normal limits, platelet numbers less than 150,000/mm³ and high necroinflammatory activity. The data obtained were inconclusive regarding a possible correlation between severity of fibrosis and alcoholism.

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) is an emergent pathogen in healthcare-associated infections (HAIs). The aim of this study was to describe HAIs due to KPC-Kp, as well as identify mortality risk factors in cancer patients. In patients diagnosed with HAIs due to KPC-Kp between January 2009 and July 2013, we evaluated only the first infection episode of each patient, analyzing mortality separately for patients treated for ≥48 h with at least one antimicrobial agent proven to display in vitro activity against KPC-Kp. We evaluated variables related to the malignancy, the severity and characteristics of the HAI, and the antimicrobial therapy. We identified 83 HAIs due to KPC-Kp. The 30-day mortality was 57.8 % for all infections and 72.7 % for bacteremic infections. Of the 83 patients, 60 patients received ≥48 h of appropriate treatment and 44 (53 %) developed bacteremia. Ten patients (12 %) were neutropenic at HAI diagnosis and 33 (39.8 %) had infection at the tumor site. The most common HAI was urinary tract infection, seen in 26 patients (31.3 %), followed by primary bloodstream infection, seen in 24 patients (28.9 %). Forty-four patients (73.3 %) received combination antimicrobial therapy, most often including polymyxin (68.3 %). Risk factors for 30-day mortality are high sequential organ failure assessment (SOFA) score, need for intensive care stay at diagnosis of infection, and acute kidney injury; the removal of invasive devices related to infection and treatment with effective antibiotics for KPC-Kp are protective factors. In cancer patients, high mortality is associated with HAI due to KPC-Kp and mortality risk factors are more often related to acute infection than to the underlying disease.

AIDS-associated Kaposi's sarcoma (AIDS-KS) caused by human herpes virus 8 (HHV-8) is the most severe and resistant form of KS tumor. Our aim was to verify whether there is an association between HHV-8 variability and development of AIDS-KS in Brazil by comparing the HHV-8 variability between individuals without and with KS. Saliva samples and blood, when available, were analyzed by polymerase chain reaction (PCR) techniques for detection of the fragments of ORF K1 of HHV-8, which were then genotyped and analyzed regarding the genetic variability. Our study described 106 positive cases for HHV-8 in the saliva from 751 AIDS patients without previous KS. In addition, we performed a phylogenetic analysis of HHV-8 in 34 of the 106 AIDS patients without KS and in 33 of the 37 patients with active KS. The distribution of HHV-8 genotypes A, B, C, and F in AIDS individuals was indistinguishable by comparing non-KS and KS groups, as well as regarding ethnicity. Considering the KS group, genotype B was associated with better prognosis of KS tumor. Interestingly, we found a particular profile of diversity within clade C and 2 recombinant patterns of HHV-8 in the saliva of AIDS individuals without KS. We emphasize the need to achieve standard genotyping protocol for ORF K1 amplification, thus allowing for substantial detection of HHV-8 variants. Our findings can shed light on the role of HHV-8 variability in the pathogenesis of AIDS-KS.

Objective.To describe the epidemiology of infections related to the use of implantable central venous access devices (CVADs) in cancer patients and to evaluate measures aimed at reducing the rates of such infections.Design.Prospective cohort study.Setting.Referral hospital for cancer in São Paulo, Brazil.Patients.We prospectively evaluated all implantable CVADs employed between January 2009 and December 2011. Inpatients and outpatients were followed until catheter removal, transfer to another facility, or death.Methods.Outcome measures were bloodstream infection and pocket infection. We also evaluated the effects that the creation of a multidisciplinary team for CVAD care, avoiding in-hospital implantation of CVADs, and limiting CVAD insertion in neutropenic patients have on the rates of such infections.Results.During the study period, 966 CVADs (mostly venous ports) were implanted in 933 patients, for a combined total of 243,792 catheter-days. We identified 184 episodes of infection: 154 (84%) were bloodstream infections, 21 (11%) were pocket infections, and 9 (5%) were surgical site infections. During the study period, the rate of CVAD-related infection dropped from 2.2 to 0.24 per 1,000 catheter-days (P< .001). Multivariate analysis revealed that relevant risk factors for such infection include surgical reintervention, implantation in a neutropenic patient, in-hospital implantation, use of a cuffed catheter, and nonchemotherapy indication for catheter use.Conclusions.Establishing a multidisciplinary team specifically focused on CVAD care, together with systematic reporting of infections, appears to reduce the rates of infection related to the use of these devices.

We present a prospective method of surveillance of health care-associated infection in hematology-oncology inpatients with neutropenia. Incidence rates were calculated on the basis of the number of hospitalized patients, the duration of hospital stay (in days), the number of days of neutropenia, and (in cases of central line-associated blood stream infection) the number of central line-days. We detected 11.4 and 66.4 episodes of febrile neutropenia per 1,000 hospital-days and per 1,000 days of neutropenia, respectively. The incidence of central line-associated blood stream infection was 2.6 per 1,000 central line-days. Gram-negative bacteria were the most prevalent pathogens. Efforts should be made to monitor infection rates on hematology-oncology wards.

Background Reactivation of chronic Chagas disease, which occurs in approximately 20% of patients coinfected with HIV/Trypanosoma cruzi (T. cruzi), is commonly characterized by severe meningoencephalitis and myocarditis. The use of quantitative molecular tests to monitor Chagas disease reactivation was analyzed. Methodology Polymerase chain reaction (PCR) of kDNA sequences, competitive (C-) PCR and real-time quantitative (q) PCR were compared with blood cultures and xenodiagnosis in samples from 91 patients (57 patients with chronic Chagas disease and 34 with HIV/T. cruzi coinfection), of whom 5 had reactivation of Chagas disease and 29 did not. Principal Findings qRT-PCR showed significant differences between groups; the highest parasitemia was observed in patients infected with HIV/T. cruzi with Chagas disease reactivation (median 1428.90 T. cruzi/mL), followed by patients with HIV/T. cruzi infection without reactivation (median 1.57 T. cruzi/mL) and patients with Chagas disease without HIV (median 0.00 T. cruzi/mL). Spearman's correlation coefficient showed that xenodiagnosis was correlated with blood culture, C-PCR and qRT-PCR. A stronger Spearman correlation index was found between C-PCR and qRT-PCR, the number of parasites and the HIV viral load, expressed as the number of CD4+ cells or the CD4+/CD8+ ratio. Conclusions qRT-PCR distinguished the groups of HIV/T. cruzi coinfected patients with and without reactivation. Therefore, this new method of qRT-PCR is proposed as a tool for prospective studies to analyze the importance of parasitemia (persistent and/or increased) as a criterion for recommending pre-emptive therapy in patients with chronic Chagas disease with HIV infection or immunosuppression. As seen in this study, an increase in HIV viral load and decreases in the number of CD4+ cells/mm3 and the CD4+/CD8+ ratio were identified as cofactors for increased parasitemia that can be used to target the introduction of early, pre-emptive therapy., Author Summary Chagas disease is endemic in Latin America and is caused by the flagellate protozoan T. cruzi. The acute phase is asymptomatic in the majority of the cases and rarely causes inflammation of the heart or the central nervous system. Most infected patients progress to a chronic phase, characterized by cardiac or digestive involvement when not asymptomatic. However, when patients are also exposed to an immunosuppressant (such as chemotherapy), neoplasia, or other infections such as HIV, T. cruzi infection may develop into a severe disease (Chagas disease reactivation) involving the heart and central nervous system. The current microscopic methods for diagnosing Chagas disease reactivation are not sensitive enough to prevent the high rate of death observed in these cases. Therefore, we propose a quantitative method to monitor blood levels of the parasite, which will allow therapy to be administered as early as possible, even if the patient has not yet presented symptoms.

Between June 1989 and December 2005, an observational study of adults co-infected with HIV and Trypanosoma cruzi was conducted, to investigate the spectrum of manifestations of chronic Chagas disease (American trypanosomiasis) in the HIV-positive. The 31 men and 22 women investigated were aged 23-59 years. Each subject was investigated by ambulatory (Holter) and non-ambulatory electrocardiography, chest X-ray, oesophagography and echocardiography (to determine the clinical form of trypanosomiasis), by xenodiagnosis, blood culture and the microscopical examination of blood (to explore their T. cruzi parasitaemia), and by counting their CD4 T cells (to stage their HIV infection). The subjects were followed-up for 1-190 months (median = 58 months) and checked for re-activation of their Chagas disease, which was usually defined by the occurrence of unusual clinical manifestations and/or the detection, by microscopical examination, of trypanosomes in the blood or cerebrospinal fluid. Eleven (20.8%) of the subjects showed re-activation, another nine (17.0%) were found to have developed high T. cruzi parasitaemias but these were only detected by xenodiagnosis or culture, and 15 (28.3%) had illnesses typical of chronic Chagas disease in HIV-negative individuals, with low parasitaemias. Anti-T. cruzi therapy (benznidazole), recommended for 17 patients, resulted in the sustained reduction of parasitaemia in 11 of the 12 subjects who completed treatment. Chagas disease was the cause of death of eight of the 14 subjects who died during the study. Four of the women investigated gave birth, each to a single child, during follow-up, and three of the four babies showed evidence of the congenital transmission of T. cruzi.

INVESTIGATION OF POLYMORPHISMS IN DNA/HHV8 ASSOCIATED WITH THE RISK OF KS Tania Regina Tozetto Mendoza, Laura M. Sumita, Roberto Ribeiro, Sideny Lima, Maria Cristina Domingues Fink, Marli De Paula Estevam, Silvia Lima, Cynthia L.M. Canto, Lucy S. Vilas Boas, Camila Malta Romano, Paulo Henrique Braz Silva, Claudio Sergio Pannuti, Laboratorio de Virologia LIM52Instituto de Medicina Tropical de Sao PauloUniversidade de Sao Paulo; Departamento de Molestias Infeciosas e Parasitarias e HCFMUSP; Faculdade de Odontologia e USP; Faculdade de Medicina da Universidade de Sâo Paulo Objective: Single nucleotide polymorphisms (SNPs) detection in conserved regions such as ORFK12-DNA/HHV-8sequence can suggest the possibility of altered microRNA production and consequently it might reflect in cellular and viral gene expression control. Study Design: Therefore, this study aimed to investigate polymorphisms in HHV-8/ORFK12 sequences obtained from a HIV group of patients without Kaposi’s sarcoma (KS), and to compare them with those of the control group with KS. Results: We identified forty-two A/C, C and B subtypes of K12/HHV-8: 26.4 % (28/106) in cryopreserved saliva from group without KS and 41.2 % (14/34) in cryopreserved blood from control group. We found 6/59 polymorphic sites in miR12 encoding regions between the 117417nt-118055nt positions (U75698). Of these SNPs, few were detected in the group without KS (33%). Conclusions: The detection and description of these SNPs may be useful as a prognostic tool for KS, since they are present in coding regions of microRNA associated with tumorigenesis.

Background: Vancomycin-resistant enterococcus (VRE) has become a nosocomial pathogen of increasing importance. First identified in Europe in 1988, it has since been identified in multiple sites in the United States and Canada, as well as in Latin America. A 20-fold increase in the percentage of enterococci associated with nosocomial infections that were resistant to vancomycin, from 0.4% in 1989 to 7.9% in 1993, has been reported by the Centers for Disease Control and Prevention. VRE outbreak has been identified on February 2012 in hematology-oncology unit. It has since implemented some outbreak measures in order to control this outbreak, and as part of the control program during this outbreak of VRE infection in oncology-hematology unit of our tertiary care hospital, swab anal cultures have been performed weekly for inpatients as well as at the moment of their hospitalization. Objectives: To assess the incidence of colonization and infection by VRE of admitted patients in oncology-hematology unit and to evaluate the role of neutropenia and central line as well as their impact on blood stream infection (BSI) by VRE in previous colonized patients. Methods: All patients admitted to hematology-oncology unit in Instituto do Câncer do Estado de São Paulo São Paulo (ICESP) were undertaken to surveillance for VRE by Hospital Infection Control Committee from March 1, 2012 to May 31, 2014. It is important to highlight that ICESP has not promoted bone marrow transplantation. Neutropenia was defined as a neutrophil count ≤0.5 x 109/L. Feces (in patients with neutropenia) or rectal swab for those with a neutrophil count >0.5 x 109/L were collected for research VRE on admission and weekly for those that persist with negative results. Enterococci were isolated by standard microbiological methods. It was considered patients with colonized VRE when a bacterium is present, without any signs or symptoms of infection. BSI by VRE was defined in patients with positive blood culture for VRE. Results: A total of 1,666 patients had been screening for VRE colonization. One hundred sixty-one cases of VRE colonization were detected among them. The rate of VRE colonization during hospitalization was 9.7%. The incidence rate of VRE colonization was 9.4 cases per 1,000 inpatient-days. Twenty (12.4%) out of 161 VRE colonized patients developed BSI by VRE. The incidence of BSI by VRE was 1.2 cases per 1,000 inpatient-days. Eleven (55%) patients with BSI by VRE presented Acute Leukemia. A hundred percent of patients with BSI by VRE presented neutropenia and 14 (70%) out of 20 had central venous catheter inserted as well. Conclusions: We conclude that it is important to perform surveillance for VRE due to our incidence of patients colonized by VRE such as BSI by VRE. We believe these data may justify surveillance attendance and contact precautions. It was observed the importance of neutropenia to BSI by VRE in patients previously colonized. Thus, this fact could suggest that others studies are necessary in order to evaluate the role of antibiotic as linezolid for febrile neutropenia treatment in patients colonized by VRE. Disclosures No relevant conflicts of interest to declare.

O cumprimento do calendário vacinal no período estabelecido é uma ferramenta importante para a redução da mortalidade infantil, e a não efetivação deste objetivo pode gerar sérios problemas de saúde pública. Para garantir a imunização como proposta pelo PNI, e evitar a oportunidade perdida em imunização, é preciso que tanto os profissionais que atuam diretamente na sala de vacina, como os que atuam na orientação da população sobre vacinação, estejam adequadamente informados sobre as verdadeiras e falsas contraindicações à vacinação. Este trabalho teve como objetivo identificar o conhecimento da equipe de enfermagem e dos agentes comunitários de saúde a respeito de imunizações. Trata-se de estudo com abordagem quantitativa do tipo descritivo-exploratório, com desenho pré e pós- exposição, em amostra de conveniência. Participaram da pesquisa 39 agentes comunitários de saúde, 12 auxiliares de enfermagem e 4 enfermeiros. A pesquisa foi realizada através da aplicação de questionário individual, inicialmente; a seguir foi realizada ação educativa sobre imunização; e, por fim, o questionário foi reaplicado. Os dados foram tabulados e analisados por frequência simples. Pode-se observar que os participantes orientavam os responsáveis pelas crianças com falsas contraindicações à imunização, tais como doença e infecção na criança, pós- operatório, uso de antibiótico e antialérgico. Também se evidencia que os mesmos orientavam corretamente quanto às contraindicações ou adiamento nas seguintes situações: alergia à componente da vacina, questões de saúde específicas, febre e uso de corticoide. Todos os participantes demonstraram ciência e sensibilização quanto à importância do conhecimento dos pais ou responsáveis pela criança acerca das doenças imunopreveníveis e registro correto das vacinas aplicadas pelos profissionais. Houve aumento do conhecimento dos profissionais quanto à associação da redução da mortalidade infantil a maiores taxas de cobertura vacinal, recomendação de vacinar as crianças pequenas, interferência das crenças dos pais quanto a não importância ou não efetividade das vacinas na adesão à vacinação, aumento do risco de transmissão de doenças e reintrodução de doenças erradicadas quando não se permite a vacinação, controle de qualidade das vacinas aplicadas no SUS, oportunidade perdida de vacinação, responsabilidade da equipe de saúde na busca ativa de faltosos, importância do acolhimento dos profissionais para melhor adesão à vacinação e associação das vacinas com as doenças contra as quais protege. Durante a aplicação do questionário, algumas perguntas foram questionadas pelos participantes, e observou-se que a forma como foram elaboradas algumas questões pôde induzir a dúvidas nas respostas. Observou-se que houve aumento das respostas corretas por parte dos profissionais em 66,7% das questões, manutenção da totalidade de profissionais que responderam de forma adequada, antes e após a ação, em 8,3% das questões, e diminuição das respostas corretas em 25% das questões, sendo que neste último cenário, a maior parte das diminuições está relacionada à formulação incorreta das perguntas. Diante do exposto, considera-se que a ação educativa foi eficaz para o incremento do conhecimento dos profissionais sobre imunização, porém propõe-se adequação do instrumento de coleta de dados para maior clareza do conhecimento que se pretende avaliar em cada questão, e maior aproximação deste ao conteúdo da ação educativa. Compliance with the vaccination schedule within the established period is an important tool for reducing child mortality, and failure to achieve this goal can lead to serious public health problems. To ensure immunization as proposed by the PNI, and to avoid the missed opportunity in immunization, it is necessary that both professionals working directly in the vaccine room, as well as those guiding the population on vaccination, are adequately informed about the true and false contraindications to vaccination. This study aimed to identify the knowledge of the nursing staff and community health agents about immunizations. This is a study with a quantitative descriptive-exploratory approach, with pre and post-exposure design, in a convenience sample. The study included 39 community health agents, 12 nursing assistants and 4 nurses. The research was conducted by applying an individual questionnaire initially; next, an educational action on immunization was carried out; and finally, the questionnaire was reapplied. Data were tabulated and analyzed by simple frequency. It can be observed that the participants advised the children\'s responsible with false contraindications to immunization, such as postoperative illness and infection in children, antibiotic and antiallergic use. It is also evident that they correctly advised against contraindications or postponement in the following situations: allergy to the vaccine component, specific health issues, fever and corticosteroid use. All participants were aware of the importance of parents \'or guardians\' knowledge about immunopreventable diseases and correct registration of vaccines applied by professionals. Professionals knowledge increased regarding the association of reduced infant mortality with higher rates of vaccination coverage, recommendation to vaccinate young children, interference of parents\' beliefs about the importance or ineffectiveness of vaccines in vaccination adherence, increased risk transmission of diseases and reintroduction of diseases eradicated when vaccination is not allowed, quality control of vaccines applied in SUS, missed opportunity for vaccination, responsibility of health team in the active search for absentees, importance of welcoming professionals to better adhere to vaccination and association of vaccines with the diseases against which it protects. During the application of the questionnaire, some questions were asked by the participants, and it was observed that the way some questions were elaborated could induce doubts in the answers. It was observed that there was an increase in the correct answers by professionals in 66.7% of the questions, maintenance of all professionals who answered adequately, before and after the action, in 8.3% of the questions, and a decrease in the answers correct in 25% of the questions; and in this last scenario most of the decreases are related to the incorrect formulation of the questions. Given the above, it is considered that the educational action was effective to increase the knowledge of professionals about immunization, but it is proposed to adapt the data collection instrument for greater clarity of knowledge to be evaluated in each question, and greater approximation you gave to the content of the educational action.

INTRODUÇÃO: A terapia antirretroviral (TARV) determinou diminuição da incidência de aids e da mortalidade em pessoas vivendo com o vírus da imunodeficiência humana (HIV). Outras comorbidades assumiram, consequentemente, maior relevância no cuidado integral a esses indivíduos. Destaca-se, nesse contexto, a infecção crônica pelo vírus da hepatite B (VHB), dada a influência negativa que a infecção pelo HIV tem sobre a história natural da infecção pelo VHB nos coinfectados. Sabendo-se que medicamentos antirretrovirais podem também inibir a replicação do VHB, justifica-se analisar o impacto da TARV no manejo da hepatite B nessa população. OBJETIVOS: Verificar a frequência de detecção do ácido desoxirribonucleico (DNA) do VHB entre indivíduos coinfectados pelo HIV em uso de antirretrovirais e fatores associados. MÉTODOS: Em estudo transversal de uma série de casos, acompanhada no Serviço de Extensão ao Atendimento de Pacientes HIV/Aids da Divisão de Moléstias Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, avaliaram-se pacientes com coinfecção HIV/VHB, idade acima de 18 anos e em uso de TARV por mais de seis meses, que passaram em consulta no ano de 2015. Não houve critério de exclusão. Coletaram-se dados sociodemográficos, de exposição ao HIV e VHB, clínico-laboratoriais e de avaliação da fibrose hepática por meio de entrevistas, revisão de prontuários e exames complementares. A viremia pelo VHB foi aferida por reação em cadeia pela polimerase quantitativa em tempo real. Nos casos em que se detectou DNA do VHB em concentração superior a 900 UI/mL, realizou-se sequenciamento para genotipagem viral e identificação de mutações conferidoras de resistência aos antivirais. RESULTADOS: Em 2015, 2 946 pessoas vivendo com HIV foram atendidas no serviço, sendo 83 elegíveis para o estudo, das quais 56 puderam ser avaliadas. Viremia pelo VHB foi identificada em 16 (28,6%) delas (IC 95%: 18,0-41,3%), sendo que todas faziam uso de lamivudina e tenofovir no momento da inclusão no estudo. Mostraram-se diretamente associadas à viremia pelo VHB: escolaridade mais baixa (p = 0,015), valores mais elevados da relação normalizada internacional (RNI) (p = 0,045), antecedente de doença definidora de aids [OR: 3,43 (IC 95%: 1,10-11,50); p = 0,040] e detecção sérica de AgHBe [OR: 6,60 (IC 95%: 1,84-23,6); p = 0,003]. Em contraste, a última contagem de linfócitos T CD4+ acima de 500 células/mm3 nos 365 dias prévios à inclusão no estudo [OR: 0,18 (IC 95%: 0,04-0,71); p = 0,016] e a detecção sérica de anti-HBe [OR: 0,21 (IC 95%: 0,04-0,99); p = 0,043] mostraram-se inversamente associados à ocorrência de viremia pelo VHB. Nos quatro pacientes que apresentaram carga plasmática do VHB superior a 900 UI/mL, verificou-se predominantemente infecção pelo genótipo A1 (75%). Nesses indivíduos foram identificadas mutações capazes de conferir resistência total à lamivudina e parcial ao entecavir. CONCLUSÕES: Mesmo em uso de TARV, porcentagem significativa dos pacientes coinfectados pelo HIV permanece com viremia do VHB. A caracterização dos fatores associados a esse desfecho pode orientar os profissionais no manejo mais apropriado desses indivíduos INTRODUCTION: Antiretroviral therapy (ART) has decreased the incidence of acquired immunodeficiency syndrome (AIDS) and mortality rate of people infected with human immunodeficiency virus (HIV). Other comorbidities have, therefore, gained more relevance in the comprehensive care provided to these individuals. In this context, we highlight chronic infection with hepatitis B virus (HBV) because HIV coinfection is known to have a negative influence on the natural history of HBV infection. Given that antiretroviral drugs may also inhibit HBV replication, it is important to analyze the impact of ART on the management of hepatitis B in this population. OBJECTIVES: To verify the frequency of HBV-DNA among HIV-coinfected individuals under ART and its associated factors. METHODS: In this cross-sectional study, we evaluated a series of HIV/HBV-coinfected cases, followed up at the HIV outpatient clinic affiliated to Hospital das Clínicas University of São Paulo Medical School. Patients aged over 18, who were under ART for more than 6 months and had a medical consultation at the clinic in 2015 were included in the study. There was no exclusion criterion. We collected socio-demographic data, information about exposure to HIV and HBV and findings of clinical assessment, laboratory tests and evaluation of liver fibrosis by means of interviews and chart reviews. HBVDNA was measured by quantitative real-time polymerase chain reaction. In cases who had HBV-DNA detected in concentrations above 900 IU/mL, additional HBV genome sequencing for viral genotyping and identification of drug resistance-conferring mutations was conducted. RESULTS: In 2015, 2946 people living with HIV attended medical consultations at the clinic. Out of 83 who were eligible for the study, 56 could be evaluated. HBV-DNA was detected in 16 (28.6%) (95% CI: 18.0-41.3%), all of whom were receiving lamivudine and tenofovir treatment. In bivariate analysis, HBV-DNA was associated with lower education (p = 0.015), higher international normalized ratios (INR) (p = 0.045), history of an AIDS-defining illness [OR: 3.43 (95% CI: 1.10-11.50); p = 0.040] and HBeAg detection in serum [OR: 6.60 (95% CI: 1.84-23.6); p = 0.003]. In contrast, the last CD4+ T-lymphocyte count above 500 cells/mm3 in the 365 days prior to inclusion in the study [OR: 0.18 (95% CI: 0.04-0.71); p = 0.016] and detection of anti-HBe in serum [OR: 0.21 (95% CI: 0.04-0.99); p = 0.043] were negatively associated with the occurrence of HBV viremia. In the 4 patients with HBV-DNA concentrations above 900 IU/mL, HBV subgenotype A1 was predominant (75%). In these individuals we detected drug resistanceconferring mutations associated with total resistance to lamivudine and partial resistance to entecavir. CONCLUSIONS: Though under ART, a significant proportion of HIV/HBV-coinfected individuals present HBV viremia. The characterization of factors that are associated with this finding may guide professionals to provide the most appropriate management to these individuals

Introdução: O tecido linfoide gastrointestinal é o principal reservatório de células T humanas e a depleção de células T CD4 + intestinais após a infecção pelo HIV leva a uma persistente disfunção da barreira mucosa, aumento da permeabilidade intestinal e translocação microbiana mesmo entre pacientes infectados pelo HIV em tratamento antirretroviral supressivo. Alguns estudos sugerem que os probióticos podem ajudar a restaurar a função intestinal. Métodos: Estudo randomizado duplo-cego, controlado por placebo, em pacientes adultos vivendo com HIV em terapia supressora e com baixa recuperação de LTCD4 +, para abordar o efeito do uso diário de 12 semanas de Lactobacillus casei Shirota oral na contagem de células T CD4 +, relação CD4 / CD8, ativação imune e avaliação do microbioma em 6 e 12 semanas de uso do composto ativo, e 12 semanas após a interrupção. Resultados: De jan / 2015 a jul / 2016, 48 pacientes foram randomizados para intervenção ativa (n = 24) ou placebo (n = 24). Os grupos tinham características demográficas e clínicas comparáveis; apenas o nadir de células T CD4 + foi estatisticamente diferente entre os grupos. Usando modelos mistos não ajustados, a intervenção foi associada com aumento médio de 58,8 células / mL em células TCD4 + nas visitas 6, 12 e 24 (IC 95% -11 a 129, p = 0,099) e aumento de 0,18 na relação CD4 / CD8 (IC 95% 0,03 a 0,33, p = 0,020). No entanto, essa diferença foi perdida após o ajuste para o nadir de células T CD4 +. Na visita 12, não foram encontradas diferenças significativas nos marcadores de ativação imune nas subpopulações CD4 + e CD8 +, níveis de sCD14 ou células NK entre os grupos. A avaliação do microbioma demonstrou um aumento estatisticamente significativo na família Bacteroidaceae na semana 12 (média 12,52% IC95% 5,89-19,06) em comparação com o valor basal (média 6,99%, IC 1,84-12,13; p=0,0422) restrito ao grupo que recebeu o composto ativo. Conclusão: Não encontramos nenhum efeito estatisticamente significativo do uso de Lactobacillus casei Shirota na contagem de células TCD4 + ou ativação imune entre pacientes vivendo com o HIV em terapia supressiva com baixa recuperação de LT CD4 + Background: Gastrointestinal lymphoid tissue is the main human T-cell reservoir and depletion of intestinal CD4+ T cells following HIV infection leads to persisting mucosal barrier disfunction, increased gut permeability and microbial translocation even among HIV-infected patients on suppressive antiretroviral treatment. Some suggest probiotics may help restore intestinal function. Methods: In this double-blind, placebo-controlled trial, we enrolled adult HIVinfected patients on suppressive ART with poor CD4+ recovery to address the effect of a 12-week daily use of oral Lactobacillus casei Shirota on CD4+ T cell count, CD4/CD8 ratio, immune activation and microbiome analysis at 6 and 12 weeks on study product, and 12 weeks after interruption. Results: From Jan/2015 to Jul/2016, 48 patients were randomized to active intervention (n=24) or placebo (n=24). Groups had comparable demographic and clinical characteristics; only CD4+ T cell nadir was statistically different between groups. All participants were virologically-suppressed under antiretroviral treatment. Using unadjusted mixed models, the intervention was associated with mean increase of 58.8 cells/mL in post-baseline CD4+ cells at visits 6, 12 and 24 (95%CI -11 to 129, p=0.099) and 0.18 increase in CD4/CD8 ratio (95%CI 0.03 to 0.33, p=0.020). However, this difference was lost following adjustment for CD4+ T cell nadir. At visit 12, no significant differences in immune activation markers on CD4+ and CD8+ subpopulations, sCD14 levels or NK cells were found between groups. Microbiome analysis showed a statistically significant increase in the Bacteroidaceae family at week 12 (mean 12.52% CI 95% 5.89-19.06) compared to baseline (mean 6.99%, CI 1.84-12 , 13; p = 0.0422) restricted to the group that received the active compound Conclusions: We found no statistically significant effect of Lactobacillus casei Shirota probiotic on CD4+ T cell counts or immune activation among HIVinfected patients on suppressive ART with poor CD4+ recovery

A doença pneumocócica invasiva é um grande desafio global. Bacteremia está fortemente relacionada às condições clínicas de imunodepressão. Pacientes com câncer raramente são alvo de estudos clínicos. Neste estudo, nosso objetivo primário foi avaliar os fatores prognósticos em pacientes com câncer com bacteremia pneumocócica. Os objetivos secundários foram descrever os episódios de bacteremia e as características fenotípicas das cepas isoladas. O desenho foi uma coorte retrospectiva, que incluiu pacientes com câncer com mais de 18 anos de idade que tiveram bacteremia pneumocócica, de janeiro de 2009 a junho de 2015, no Instituto do Câncer do Estado de São Paulo. Os critérios de infecção foram aqueles delineados pelo NHSN/CDC. Os desfechos avaliados foram mortalidade em 48h e em 10 dias, e sobrevida dos pacientes. As variáveis independentes analisadas foram: idade, sexo, etnia, ECOG, Karnofsky escore, SOFA, diagnóstico do câncer, presença de metástases, quimioterapia, radioterapia, neutropenia, uso prévio de antibióticos, internação hospitalar prévia, internação prévia em UTI, comorbidades (DPOC sistêmica, Hipertensão Arterial, Diabetes Mellitus e Insuficiência Cardíaca), tabagismo, vacinação antipneumocócica prévia, sítio de infecção, infecção polimicrobiana, suscetibilidade antimicrobiana, sorotipo e tratamento. A associação das características com os desfechos foi verificada por meio dos testes qui-quadrado, teste de razão de verossimilhança ou teste exato de Fisher. A análise multivariada foi realizada por regressão logística stepwise, incluindo todas as variáveis com P < 0,10. A sobrevida foi estimada de acordo com cada característica avaliada pela função de Kaplan-Meier, seguida de testes log-rank para comparar a sobrevida entre as categorias das variáveis qualitativas. As Razões de Risco (HR) foram calculadas com os respectivos intervalos de confiança de 95% usando regressão de Cox bivariada. Todas as variáveis que apresentaram nível de significância de 0,10 (p < 0,1) foram testadas no modelo múltiplo, e as variáveis do modelo final foram selecionadas pelo método stepwise com critério de seleção Backward com entrada e saída de 5%. Os testes foram realizados com nível de significância de 5%. Foram detectadas 165 bacteremias pneumocócicas no período do estudo em 161 pacientes oncológicos; destas, 4 episódios foram excluídos por se tratarem de recidivas. Assim, 161 episódios foram incluídos para análise descritiva e estatística. A casuística foi composta em sua maioria por homens (62,7%), com uma média de idade de 61,3 anos. A maioria da casuística foi composta por indivíduos com tumores sólidos (121/75,2%). Entre os tumores sólidos, os mais prevalentes foram os do trato gastrointestinal, seguido dos tumores de cabeça e pescoço e trato respiratório. Entre as neoplasias hematológicas (40/24,8%), as mais prevalentes foram mieloma múltiplo (20/50,0%), seguidos de linfomas não Hodgkin (14/35,0%). A mortalidade em 48h e em 10 dias foi, respectivamente, de 20,5% e 33,5%. Entre 120 cepas testadas, 61 (50,8%) corresponderam aos encontrados na vacina VCV13 e 89 (74,2%) na VPV23. As variáveis associadas a mortalidade em 48h, na análise multivariada, foram: SOFA (OR 1,37, p < 0,001) bacteremia polimicrobiana (OR 3,78, p0,018). Na análise multivariada para mortalidade em 10 dias, os fatores associados foram: febre 48h antes da bacteremia (OR 0,35, p0,026), neutropenia vigente (OR 4,01, p0,011), ECOG ¾ (OR 5,83, p0,001), SOFA (OR 1,41, P < 0,001 - um aumento unitário do SOFA resultou em um aumento de 59% na chance de mortalidade) e uso de quinolonas (OR 0,08, p0,023). Na sobrevida global, as variáveis relacionadas detectadas foram: presença de metástases (HR 1,97, p < 0,001), KARNOFSKY < 90 (HR 1,56, p0,021), SOFA (HR 1,27, p < 0,001), uso de anticorpos no último mês (HR 3,25, p0,026) e bacteremia polimicrobiana (HR 1,69, p0,046). Em conclusão, a bacteremia pneumocócica apresentou alta mortalidade em pacientes oncológicos, com prognóstico relacionado a fatores intrínsecos do hospedeiro e aos episódios de infecção, como o SOFA presente como preditor de mortalidade em 48h, 10 dias e piora da sobrevida global. A presença de bacteremia polimicrobiana associou-se a mortalidade em 48h e piorou a sobrevida. Presença de febre e uso de quinolonas foram fatores de proteção para a mortalidade em 10 dias; a presença de febre provavelmente encurtou o tempo entre o início da sepse e a demanda por serviços de saúde, com antibioticoterapia mais precoce. Não foi possível estimar o efeito protetor da vacinação antipneumocócica devido ao pequeno número de pacientes vacinados Invasive pneumococcal disease is a major global challenge. Bacteremia is strongly related to the clinical conditions of immunodepression. Patients with cancer are rarely the target of clinical trials. In this study, our primary objective was to evaluate the prognostic factors in patients with pneumococcal bacteremia. The secondary objectives were to describe the episodes of bacteremia and the phenotypic characteristics of the isolated strains. The design was a retrospective cohort that included cancer patients over 18 years of age who had pneumococcal bacteremia from January 2009 to June 2015 at the \"Instituto do Câncer do Estado de São Paulo\". The criteria for infection were those outlined by the NHSN / CDC. The outcomes evaluated were mortality in 48h and 10 days and overall survival. The independent variables analyzed were: age, sex, ethnicity, ECOG, Karnofsky score, SOFA, diagnosis of cancer, presence of metastasis, chemotherapy, radiotherapy, neutropenia, previous use of antibiotics, previous hospital admission, previous ICU admission, comorbidities (systemic COPD, Hypertension, Diabetes mellitus and Congestive Heart Failure), smoking, previous antipneumococcal vaccination, site of infection, polymicrobial infection, antimicrobial susceptibility, serotype and treatment. The association of the characteristics with the outcomes was verified using chi-square tests, likelihood ratio test or Fisher\'s exact test. Multivariate analysis was performed by stepwise logistic regression, including all variables with P < 0.10. Survival was estimated according to each characteristic assessed by the Kaplan-Meier function, followed by log-rank tests to compare survival between categories of qualitative variables. The Hazard Ratios (HR) were calculated with the respective 95% confidence intervals using bivariate Cox regression. All variables that presented a significance level of 0.10 (p < 0.1) were tested in the multiple model, and the variables of the final model were selected by stepwise method with Backward selection criterion with input and output of 5%. The tests were performed with a significance level of 5%. We detected 165 pneumococcal bacteremias during the study period in 161 cancer patients; of these, 4 episodes were excluded because they were recurrences. Thus, 161 episodes were included for descriptive and statistical analysis. Our study consisted mostly of men (62.7%), with a mean age of 61.3 years. The majority of cases were individuals with solid tumors (121 / 75.2%). Among the solid tumors, the most prevalent tumors were those of the gastrointestinal tract, followed by tumors of the head and neck and respiratory tract. Among the hematological malignancies (40/24.8%), the most prevalent were multiple myeloma (20 / 50.0%), followed by non-Hodgkin\'s lymphomas (14 / 35.0%). Mortality in 48h and 10 days was, respectively, 20.5% and 33.5%. Among 120 strains tested, 61 (50.8%) corresponded to those found in the VCV13 vaccine and 89 (74.2%) in the VPV23. The variables associated with 48-h mortality in the multivariate analysis were: SOFA (OR 1.37, p < 0.001) and polymicrobial bacteremia (OR 3.78, p 0.018). In the multivariate analysis for 10-day mortality, the associated factors were: fever 48h before bacteremia (OR 0.35, p 0.026), current neutropenia (OR 4.01, p 0.011), ECOG ¾ (OR 5.83 , p 0.001), SOFA (OR 1.41, P < 0.001 - a unit increase of SOFA resulted in a 59% increase in chance of mortality) and use of quinolones (OR 0.08, p0.023). In the overall survival, the related variables detected were: presence of metastases (HR 1.97, p < 0.001), KARNOFSKY < 90 (HR 1.56, p0.021), SOFA (HR 1.27, p < 0.001), use of antibodies in the last month (HR 3.25, p0.026) and polymicrobial bacteremia (HR 1.69, p0.046). In conclusion, pneumococcal bacteremia presented high mortality in cancer patients, with a prognosis related to intrinsic host factors and infection episodes, such as SOFA present as a predictor of mortality in 48h, 10 days and worsening of overall survival. The presence of polymicrobial bacteremia was associated with 48-h mortality and worsened survival. Presence of fever and use of quinolones were protective factors for mortality in 10 days; the presence of fever probably shortened the time between the onset of sepsis and the demand for health services, with earlier antibiotic therapy. It was not possible to estimate the protective effect of anti-pneumococcal vaccination due to the small number of patients vaccinated