Resumo em Inglês:

Background: the impact of human immunodeficiency virus type 1 (HIV-1) on lung function is well known and associated with a reduction in pulmonary ventilation. Moreover, the use of highly active antiretroviral therapy has been associated with mitochondrial dysfunction and decreased muscle strength. However, there is scarce information about the factors associated with inspiratory muscle weakness in these patients. Objective: the purpose of the present study was to investigate the factors associated with inspiratory muscle weakness in patients with HIV-1. Methods: two-hundred fifty seven patients with HIV-1 were screened and categorized into two groups: (1) IMW+ (n = 142) and (2) IMW-(n = 115). Lung function (FEV1, FVC and FEV1 /FVC), maximum inspiratory pressure, distance on the six-minute walk test and CD4 cell count were assessed. Results: the mean duration of HIV infection was similar in the two groups. The following variables were significantly different between groups: mean duration of highly active antiretroviral therapy (81 ± 12 in IMW+ versus 38 ± 13 months in IMW-; p = 0.01), and CD4 cell count (327 ± 88 in IMW+ versus 637 ± 97 cells/mm3 in IMW-; p = 0.02). IMW+ presented reduced lung function (FEV1, FVC, FEV1/FVC). Conclusion: patients with IMW+ had lower distance on the six-minute walk test in comparison to the IMW- group. The duration of highly active antiretroviral therapy, distance traveled on the 6MWT and CD4 count were determinants of IMW in patients with HIV.

Resumo em Inglês:

A prospective study was conducted in four tertiary hospitals in Argentina and Mexico in order to describe the occurrence of Clostridium difficile infection (CDI) in these settings. The objective was to evaluate the incidence of CDI in at-risk populations in Argentina (one center) and Mexico (three centers) and to further explore potential study sites for vaccine development in this region. A prospective, descriptive, CDI surveillance study was conducted among hospitalized patients aged ≥40 years who had received ≥48 h of antibiotic treatment. Stool samples were collected from those with diarrhea within 30 days after starting antibiotics and analyzed for toxins A and B by ELISA, and positive samples were further tested by toxinogenic culture and restriction endonuclease analysis type assay. Overall, 466 patients were enrolled (193 in Argentina and 273 in Mexico) of whom 414 completed the follow-up. Of these, 15/414 (3.6%) experienced CDI episodes occurring on average 18.1 days after admission to hospital and 15.9 days after the end of antibiotics treatment. The incidence rate of CDI was 3.1 (95% CI 1.7-5.2) per 1000 patient-days during hospitalization, and 1.1 (95% CI 0.6-1.8) per 1000 patient-days during the 30-day follow-up period. This study highlighted the need for further evaluation of the burden of CDI in both countries, including the cases occurring after discharge from hospital.

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Introduction: in Brazil, chronic hepatitis C in patients coinfected with the human immunodeficiency virus (HIV) is treated with pegylated interferon (Peg-IFN) and ribavirin (RBV). However, few studies have evaluated the effectiveness of this treatment in this particular population. The identification of the factors that predict sustained virological response (SVR) under current clinical practice would enable clinicians to more accurately estimate the probability of achieving an SVR and therefore utilize the appropriate therapeutics, especially in the era of direct-acting antiviral (DAA) agents. Aims: the primary aim of our study was to determine the SVR rate under current clinical practice. The secondary aims were as follows: (1) to determine the factors before and during treatment that predict SVR; and (2) to identify the causes of treatment interruption. Methods: within a cohort of HIV/hepatitis C virus (HCV)-coinfected patients in Brazil, we performed a retrospective analysis of those individuals treated with Peg-IFN and RBV. Results: among the 382 analyzed patients, SVR was observed in 118 [30.9% (95% confidence interval (CI): 26.3-35.8)], which included 25.9% (75/289) of the patients with genotypes 1 and 4 and 48.2% (41/85) of those with genotypes 2 and 3. After multivariate analyses the independent positive predictors for SVR after treatment for chronic hepatitis C with PegIFN and RBV were: absence of an AIDS-defining illness (p = 0.001), HCV viral load lower than 600,000 IU/mL at the onset of treatment (p = 0.003), higher liver enzyme levels (p = 0.039) at baseline, infection with genotypes 2 or 3 (p = 0.003), and no transient treatment interruption (p = 0.001). The treatment was interrupted in 25.6% (98/382) of the patients because of adverse events (11.3%, 43/382), virologic failure (7.8%, 30/382), and dropout (6.5%, 43/382). The main adverse events were cytopenia and psychiatric disorders. Conclusions: in our Brazilian case series, the SVR rate under current clinical practice conditions was similar to that reported in other studies. There was a correlation between an SVR and being infected by genotypes 2 and 3, low viral load, high ALT levels at the onset of treatment, and absence of an AIDS-defining illness. Cytopenia and psychiatric disorders were the major causes of treatment interruption. Efforts should be focused on optimizing management of side effects and counseling to improve adherence and to keep patients on treatment.

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Objective: To evaluate the occurrence, clinical presentations and diagnostic methods for tuberculosis in a cohort of HIV-infected infants, children and adolescents from Latin America. Methods: A retrospective analysis of children with tuberculosis and HIV was performed within a prospective observational cohort study conducted at multiple clinical sites in Latin America. Results: Of 1114 HIV-infected infants, children, and adolescents followed from 2002 to 2011, 69 that could be classified as having confirmed or presumed tuberculosis were included in this case series; 52.2% (95% CI: 39.8-64.4%) had laboratory-confirmed tuberculosis, 15.9% (95% CI: 8.2-26.7%) had clinically confirmed disease and 31.9% (95% CI: 21.2-44.2%) had presumed tuberculosis. Sixty-six were perinatally HIV-infected. Thirty-two (61.5%) children had a history of contact with an adult tuberculosis case; however information on exposure to active tuberculosis was missing for 17 participants. At the time of tuberculosis diagnosis, 39 were receiving antiretroviral therapy. Sixteen of these cases may have represented immune reconstitution inflammatory syndrome. Conclusions: Our study emphasizes the need for adequate contact tracing of adult tuberculosis cases and screening for HIV or tuberculosis in Latin American children diagnosed with either condition. Preventive strategies in tuberculosis-exposed, HIV-infected children should be optimized.

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Aims: To determine the frequency of viral pathogens causing upper respiratory tract infections in non-hospitalized, symptomatic adults in the city of Rio de Janeiro. Methods: Respiratory samples (nasal/throat swabs) were collected between August 2010 and November 2012 and real time PCR was used to detect different viral pathogens. Results: Viruses were detected in 32.1% (43/134) of samples from 101 patients. Specifically, 9% (12/134) were positive for HBoV, 8.2% (11/134) were positive for HAdV, 5.2% (7/134) were positive for HRV, and 1.5% (2/134) were positive for FLUBV or HMPV, as single infections. HRSV-A, HPIV-3, and HCoV-HKU1 were detected in one (0.75%) sample each. Co-infections were detected in 4.8% (6/134) of the samples. Peaks of viral infections were observed in March, April, May, August, and October. However, positive samples were detected all year round. Only 23.3% (10/43) of the positive samples were collected from patients with febrile illness. Conclusion: Results presented in this report suggest that respiratory viral infections are largely under diagnosed in immunocompetent adults. Although the majority of young adult infections are not life-threatening they may impose a significant burden, especially in developing countries since these individuals represent a large fraction of the working force.

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Background: Visceral leishmaniasis (VL) or Kala-Azar (KA) is one of the most deadly forms of disease among all neglected tropical diseases. There are no satisfactory drugs or vaccine candidates available for this dreaded disease. Our previous studies showed promising therapeutic and prophylactic efficacy of the live, radio-attenuated parasites through intramuscular (I.M.) and intraperitoneal (I.P.) route in BALB/c mice model. Methods: The T-cell proliferation level, the mRNA expression level of inducible nitric oxide synthase (iNOS) and tumor growth factor-beta (TGF-β) genes and finally the phosphorylation levels of phosphoinositide dependent kinase 1 (PDK1), phosphoinositide 3 kinase (PI3K) and p38 mitogen activated protein kinase (p38MAPK) molecules were checked in BALB/c mice model immunized with radio-attenuated Leishmania donovani parasites through I.M. route. Results: Higher T-cell proliferation, increased iNOS level, and suppressed TGF-β level were found in treated infected animal groups (100 and 150 Gy) in relation to untreated infected animals. Likewise, phosphorylation levels of PDK1, PI3K and p38MAPK of these two groups were increased when compared to untreated infected controls. Conclusion: The clearance of the parasites from treated infected groups of animals may be mediated by the restoration of T-cell due to therapy with radio-attenuated L. donovani parasites. The killing of parasites was mediated by increase in nitric oxide release through PDK1, PI3K and p38MAPK signaling pathways. A lower TGF-β expression has augmented the restored Th1 ambience in the 100 and 150 Gy treated animal groups proving further the efficacy of the candidate vaccine.

Resumo em Inglês:

Objective: This study was aimed to evaluate the prevalence of pertussis in adolescents and adults with cough lasting more than 14 days and less than 30 days. Methods: This is a prospective observational study in interepidemic period of pertusis. Ten public health outpatient clinics in the city of Recife, Brazil, were randomly selected for the study. The study population consisted of individuals aged 10 years and over with cough that had lasted between 14 and 30 days. Nasopharyngeal swabs were collected for culture and PCR in order to identify Bordetella pertussis. We adopted the Centers for Disease Control and Prevention in the US (CDC) definition of cases of pertussis. Results: A total of 192 individuals were identified as suspected cases. Their mean age was 40.7 years. Pertussis was confirmed in 10 of the 192 suspected cases, with an estimated prevalence of 5.21% (95% confidence interval 2.03-8.38). All cases met the clinical case definition for pertussis; one suspect had both culture and PCR positive. PCR confirmed 100% of the cases, 7/10 by PCR and 3/10 by epidemiological linkage with a case confirmed by PCR. Conclusion: During an interepidemic period, 1 in 20 cases of prolonged cough had pertussis, suggesting this is an important cause of prolonged cough in adolescents and adults.

Resumo em Inglês:

Background: Tuberculosis is a leading cause of death among people living with human immunodeficiency virus. In sub-Saharan Africa, tuberculosis accounts for more than 78% of all deaths among people with human immunodeficiency virus. Objectives: To assess tuberculosis treatment outcome and the associated factors in adult tuberculosis/human immunodeficiency virus co-infected patients in four public hospitals of eastern and southern zone of Tigray region, Ethiopia. Methodology: Institution based cross-sectional study design was used to examine secondary data from tuberculosis/human immunodeficiency virus co-infected patients attending four public hospitals of eastern and southern zone of Tigray, from January 2009 to August 2011. Systematic random sampling technique was used to select individual patient cards from the respective hospitals. Univariate analysis and multivariate logistic regression modeling was used to assess the impact of each variable in predicting treatment outcome. Results: Out of 342 patients included, 199 (58.2%) patients completed treatment, 43 (12.6%) patients were cured, 88 (25.7%) died, 7 (2%) defaulted, and 5 (1.5%) patients failed treatment. Treatment success rate was around 71%. In the multivariate logistic regression analysis the factors that were strongly associated with unfavorable tuberculosis treatment outcomes were WHO stage IV (AOR = 3.2, CI = 1.58-6.82, p-value = 0.001), age greater than 45 years (AOR = 6.08, CI = 2.28-16.23) and baseline CD4 count less than 200 cells/L (AOR = 6.19, CI = 2.28-16.89, p-value = 0.001). Conclusion: The rate of treatment success in this study was lower than the rate newly recommended by WHO. Therefore, efforts should be undertaken to improve treatment success rates of both diseases.

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Aim: We assessed late onset sepsis (LOS) rates of neonates in a neonatal intensive care unit (NICU) before and after implementing an evidence-based bundle to prevent these infections in a country with poor resources. Methods: We evaluate trends of LOS between October 2010 and August 2012 in a large tertiary hospital in Brazil. We designed a protocol based of CDC guidelines for insertion of maintenance of central venous catheter targeted to reduction of bloodstream infections. During this period two major events occurred: a great increase of LOS rates in January months and relocation of the unit to a provisory place. Additionally we evaluated the risk factors and etiology of these infections. Results: A total of 112 (20.3%) cases defined as LOS were found. The overall incidence rate of LOS in the study was 16.1/1000 patient/days and 23.0/1000 CVC-days. Our monthly rates data of LOS/1000 patient-day reveal fluctuations over the studied period, with incidence rates of these infections in staff vacation period (January 2011 and 2012) significantly higher (59.6/1000 patients-days) than compared with the other months rates (16.6/1000 patients-days) (IRR = 3.59; p < 0.001). As opposite, the incidence rates of LOS during relocation period was lower (10.3/1000 patients-days) when compared with baseline period 26.7/1000 patients-days (IRR = 2.59; p = 0.007). After the intervention period, these rates decreased in the post intervention period, when compared with preintervention 14.7/1000 patients-days and 23.4/1000 patients-days, respectively (IRR = 1.59; p = 0.04). Conclusion: Through simple infection control measures, LOS can be successfully controlled especially in NICUs of limited resources countries such as ours.

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Background: Vancomycin-resistant enterococci colonization has been reported to increase the risk of developing infections, including bloodstream infections. Aim: In this study, we aimed to share our experience with the vancomycin-resistant enterococci bloodstream infections following gastrointestinal vancomycin-resistant enterococci colonization in pediatric population during a period of 18 months. Method: A retrospective cohort of children admitted to a 400-bed tertiary teaching hospital in Izmir, Turkey whose vancomycin-resistant enterococci colonization was newly detected during routine surveillances for gastrointestinal vancomycin-resistant enterococci colonization during the period of January 2009 and December 2012 were included in this study. All vancomycin-resistant enterococci isolates found within 18 months after initial detection were evaluated for evidence of infection. Findings: Two hundred and sixteen patients with vancomycin-resistant enterococci were included in the study. Vancomycin-resistant enterococci colonization was detected in 136 patients (62.3%) while they were hospitalized at intensive care units; while the remaining majority (33.0%) were hospitalized at hematology-oncology department. Vancomycinresistant enterococci bacteremia was present only in three (1.55%) patients. All these patients were immunosuppressed due to human immunodeficiency virus (one patient) and intensive chemotherapy (two patients). Conclusion: In conclusion, our study found that 1.55% of vancomycin-resistant enterococcicolonized children had developed vancomycin-resistant enterococci bloodstream infection among the pediatric intensive care unit and hematology/oncology patients; according to our findings, we suggest that immunosupression is the key point for developing vancomycinresistant enterococci bloodstream infections.

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Aim: This study evaluated the use of polymerase chain reaction for cryptococcal meningitis diagnosis in clinical samples. Materials and methods: The sensitivity and specificity of the methodology were evaluated using eight Cryptococcus neoformans/C. gattii species complex reference strains and 165 cere- brospinal fluid samples from patients with neurological diseases divided into two groups: 96 patients with cryptococcal meningitis and AIDS; and 69 patients with other neurological opportunistic diseases (CRL/AIDS). Two primer sets were tested (CN4-CN5 and the multiplex CNa70S-CNa70A/CNb49S-CNb-49A that amplify a specific product for C. neoformans and another for C. gattii). Results: CN4-CN5 primer set was positive in all Cryptococcus standard strains and in 94.8% in DNA samples from cryptococcal meningitis and AIDS group. With the multiplex, no 448-bp product of C. gattii was observed in the clinical samples of either group. The 695 bp products of C. neoformans were observed only in 64.6% of the cryptococcal meningitis and AIDS group. This primer set was negative for two standard strains. The specificity based on the negative samples from the CTL/AIDS group was 98.5% in both primer sets. Conclusions: These data suggest that the CN4/CN5 primer set was highly sensitive for the identification of C. neoformans/C. gattii species complex in cerebrospinal fluid samples from patients with clinical suspicion of cryptococcal meningitis.

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Epidemiological and molecular data on community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) are still scarce in both Egypt and Saudi Arabia. There is almost no data regarding methicillin resistant Staphylococcus aureus (MRSA) prevalence in both countries. This study was conducted to investigate the prevalence and molecular epidemiology of S. aureus and MRSA nasal carriage among outpatients attending primary health care centers in two big cities in both countries. A total of 206 nasal swabs were obtained, 103 swabs from each country. S. aureus isolates were characterized by antibiotic susceptibility, presence of mecA and PVL genes, SCCmec-typing and spa typing, the corresponding Multi locus sequence typing clonal complex was assigned for each spa type based on Ridom StaphType database. MRSA was detected in 32% of the Egyptian outpatients while it was found in 25% of the Saudi Arabian outpatients. All MRSA isolates belonged to SCCmec type V and IVa, where some isolates in Saudi Arabia remained nontypeable. Surprisingly PVL+ isolates were low in frequency: 15% of MRSA Egyptian isolates and 12% of MRSA isolates in Saudi Arabia. Two novel spa types were detected t11839 in Egypt, and t11841 in Saudi Arabia. We found 8 spa types among 20 isolates from Egypt, and 12 spa types out of 15 isolates from Saudi Arabia. Only two spa types t008 and t223 coexisted in both countries. Four clonal complexes (CC5, CC8, CC22, and CC80) were identified in both Egypt and Saudi Arabia. However, the data collected lacked a representation of isolates from different parts of each country as only one health center from each country was included, it still partially illustrates the CA-MRSA situation in both countries. In conclusion a set of control measures is required to prevent further increase in MRSA prevalence.

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Since the advent of highly active antiretroviral therapy in 1996, we have seen dramatic changes in morbi-mortality rates from human immunodeficiency virus-positive patients. If on the one hand, the immunologic preservation-associated with the use of current antiretroviral therapy markedly diminishes the incidence of opportunistic infections, on the other hand it extended life expectancy of human immunodeficiency virus-infected individuals similarly to the general population. However, the management of critically ill human immunodeficiency virus-infected patients remains challenging and troublesome for practicing clinician. Sepsis - a complex systemic inflammatory syndrome in response to infection - is the second leading cause of intensive care unit admission in both human immunodeficiency virus-infected and uninfected populations. Recent data have emerged describing a substantial burden of sepsis in the infected population, in addition, to a much poorer prognosis in this group. Many factors contribute to this outcome, including specific etiologies, patterns of inflammation, underlying immune dysregulation related to chronic human immunodeficiency virus infection and delays in prompt diagnosis and treatment. This brief review explores the impact of sepsis in the context of human immunodeficiency virus infection, and proposes future directions for better management and prevention of human immunodeficiency virus-associated sepsis.

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Kocuria rosea belongs to genus Kocuria (Micrococcaceae family, suborder Micrococcineae, order Actinomycetales) that includes about 11 species of bacteria. Usually, Kocuria sp are commensal organisms that colonize oropharynx, skin and mucous membrane; Kocuria sp infections have been described in the last decade commonly affecting immunocompromised patients, using intravenous catheter or peritoneal dialysis. These patients had mainly bacteremia/recurrent sepsis. We hereby describe the case of a 10-year-old girl, immunocompetent, who had endocarditis/sepsis by K. rosea which was identified in five different blood cultures by Vitek2 ID-GPC card (BioMérieux, France). Negative HIV serology, blood count within normal range of leukocytes/neutrophils and lymphocytes, normal fractions of the complement, normal level of immunoglobulins for the age; lymphocyte immunophenotyping was also within the expected values. Thymus image was normal at chest MRI. No catheters were required. Identification of K. rosea was essential to this case, allowing the differentiation of coagulase-negative staphylococci and use of an effective antibiotic treatment. Careful labo- ratory analysis of Gram-positive blood-born infections may reveal more cases of Kocuria sp infections in immunocompetent patients, which may collaborate for a better understanding, prevention and early treatment of these infections in pediatrics.

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Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly causing infective endocarditis over the past decade. Here we report a healthy man who developed a severe acute infective endocarditis with systemic embolism caused by CA- MRSA. The strain was recovered from repeated blood cultures and was characterized using molecular detection and genotyping. The S. aureus isolate was typed as ST630 SCCmecV with spa-type t4549, agrI/IV and was PVL-negative. This is the only case report, to our knowledge, of CA-MRSA infective endocarditis in China. This case highlights the emergence and geographical spread of life-threatening CA-MRSA infection within China.

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Disseminated infection by Fusarium is a rare, frequently lethal condition in severely immunocompromised patients, including bone marrow transplant recipients. However, autologous bone marrow transplant recipients are not expected to be at high risk to develop fusariosis. We report a rare case of lethal disseminated Fusarium infection in an autologous bone marrow transplant recipient during pre-engraftment phase.