Abstract in English:We characterized the virologic failure after an initially successful 48-week course of antiretroviral therapy among HIV/AIDS patients in a retrospective cohort study involving patients from Santos, Brazil. Patients with plasma HIV RNA below 500 copies/mL for 48 weeks were included. Variables analyzed included gender, age, level of education, marital status, mode of HIV acquisition, viral load, and CD4 cell count upon admission. There were 4,909 patients registered with the clinic, of which 669 patients met all the inclusion criteria (41.6% female and 58.4% male). Only 27.5% of the patients maintained undetectable viral loads during up to one year of follow-up. After 48 weeks, virologic failure occurred earlier in females and in patients first treated with an antiretroviral regimen other than highly active antiretroviral therapy. Patients who were married or had a steady partner experienced virologic failure later than did those who were separated or widowed. The percentage of public health clinic patients who maintain undetectable viral loads for a period of over a year is much lower than that observed among patients enrolled in clinical trials. Females, individuals in unstable relationships, single individuals and widowed individuals should be given special attention in order to improve durability of viral suppression.
Abstract in English:This paper describes a methodological proposal based on secondary data and the main results of the HIV-Sentinel Study among childbearing women, carried out in Brazil during 2006. A probabilistic sample of childbearing women was selected in two stages. In the first stage, 150 health establishments were selected, stratified by municipality size (<50,000; 50,000-399,999; 400,000+). In the second stage, 100-120 women were selected systematically. Data collection was based on HIV-test results registered in pre-natal cards and in hospital records. The analysis focused on coverage of HIV-testing during pregnancy and HIV prevalence rate. Logistic regression models were used to test inequalities in HIV-testing coverage during pregnancy by macro-region of residence, municipality size, race, educational level and age group. The study included 16,158 women. Results were consistent with previous studies based on primary data collection. Among the women receiving pre-natal care with HIV-test results registered in their pre-natal cards, HIV prevalence was 0.41%. Coverage of HIV-testing during pregnancy was 62.3% in the country as a whole, but ranged from 40.6% in the Northeast to 85.8% in the South. Significant differences according to race, educational level and municipality size were also found. The proposed methodology is low-cost, easy to apply, and permits identification of problems in routine service provision, in addition to monitoring compliance with Ministry of Health recommendations for pre-natal care.
Abstract in English:The potential impact of the hepatitis C virus (HCV) on clinical, immunological and virological responses to initial highly active antiretroviral therapy (HAART) of patients infected with human immunodeficiency virus (HIV) is important to evaluate due to the high prevalence of HIV-HCV coinfection. A historical cohort study was conducted among 824 HIV-infected patients starting HAART at a public referral service in Belo Horizonte, Brazil, to assess the impact of HCV seropositivity on appearance of a new AIDS-defining opportunistic illness, AIDS-related death, suppression of viral load, and an increase in CD4-cell count. A total of 76 patients (9.2%) had a positive HCV test, 26 of whom (34.2%) had a history of intravenous drug use. In multivariate analysis, HCV seropositivity was associated with a smaller CD4-cell recovery (RH=0.68; 95% CI [0.49-0.92], but not with progression to a new AIDS-defining opportunistic illness or to AIDS-related death (RH=1.08; 95% CI [0.66-1.77]), nor to suppression of HIV-1 viral load (RH=0.81; 95% CI [0.56-1.17]) after starting HAART. These results indicate that although associated with a blunted CD4-cell recovery, HCV coinfection did not affect the morbidity or mortality related to AIDS or the virological response to initial HAART.
Abstract in English:Liver histological improvement after treatment for chronic hepatitis C in patients co-infected with human immunodeficiency virus-1 (HIV-1) has been described. Paired liver biopsies in twenty six HCV/HIV co-infected patients were compared to determine factors possibly associated with histological improvement. The patients were submitted to a liver biopsy before treatment for hepatitis C and 25 months after the end of treatment. Fragments of the liver biopsy obtained before and after treatment were compared regarding the following parameters: histological activity index (HAI) and degree of fibrosis (Knodell); intensity of collagen deposits (Sirius Red staining) and degree of stellate cell activation (alpha-smooth muscle actin labeling). The ratios of the post and pre-treatment variables were related through logistic regression to body mass index (BMI), alcohol ingestion, HCV genotype, HCV viremia, presence of hepatic iron and pre-treatment hepatic steatosis. A negative RNA test in the 24th week of treatment was associated with improvement in fibrosis, collagen deposits and stellate cell numbers. The other variables analyzed did not correlate to an improvement in hepatic histology after hepatitis C treatment. Reduction in HCV viremia during treatment may result in reduced hepatic fibrosis even in patients without a sustained virological response.
Abstract in English:Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, plays a significant role as a cofactor in the process of tumorigenesis, and has consistently been associated with a variety of malignancies especially in immunocompromised patients. Forty-four children and adolescents (21 liver transplant patients, 7 heart transplant, 5 AIDS, 3 autoimmune hepatitis, 2 nephritic syndromes, 2 medullar aplasia, 2 primary immunodeficiency disorder patients, 1 thrombocytopenic purpura and 1 systemic lupus erythematosus) presenting with chronic active EBV infection (VCA-IgM persistently positive; VCA-IgG > 20 AU/mL and positive IgG _ EBNA) had peripheral blood samples obtained during clinically characterized EBV reactivation episodes. DNA samples were amplified in order to detect and type EBV on the basis of the EBNA-2 sequence (EBNA2 protein is essential for EBV-driven immortalization of B lymphocytes). Although we have found a predominance of type 1 EBNA-2 virus (33/44; 75%), 10 patients (22.73%) carried type 2 EBNA-2, and one liver transplant patient (2.27%) a mixture of the two types, the higher proportion of type 2 EBV, as well as the finding of one patient bearing the two types is in agreement with other reports held on lymphoproliferative disorder (LPD) patients, which analyzed tumor biopsies. We conclude that EBNA-2 detection and typing can be performed in peripheral blood samples, and the high prevalence of type 2 in our casuistic indicates that this population is actually at risk of developing LPD, and should be monitored.
Abstract in English:Little information on the epidemiology and clinical characteristics of human parainfluenza virus (HPIV) infections, especially in children from tropical countries, has been published. The aim of this study was to determine the frequency of HPIV infections in children attended at a large hospital in Fortaleza in Northeast Brazil, and describe seasonal patterns, clinical and epidemiological characteristics of these infections. From January 2001 to December 2006, a total of 3070 nasopharyngeal aspirates collected from children were screened by indirect immunofluorescence for human parainfluenza viruses 1, 2, and 3 (HPIV-1, 2 and 3) and other respiratory viruses. Viral antigens were identified in 933 samples and HPIV in 117. The frequency of HPIV-3, HPIV-1 and HPIV-2 was of 83.76%, 11.96% and 4.27%, respectively. Only HPIV-3 showed a seasonal occurrence, with most cases observed from September to November, and with an inverse relationship to the rainy season. Most HPIV-3 infections seen in outpatients were diagnosed as upper respiratory tract infections.
Abstract in English:Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22%) received tigecycline for approved indications, and 88 (78%) for "off label" indications (56% with scientific support and 22% with limited or without any scientific support). The most frequent "off label" use was ventilator associated pneumonia (VAP) (63 patients). The etiology of infections was established in 105 patients (93%). MDR-Acinetobacter spp. was the microorganism most frequently isolated (50% of the cases). Overall, attending physicians reported clinical success in 86 of the 113 patients (76%). Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDR-Acinetobacter spp., where the therapeutic options are limited (eg: colistin). Physicians must evaluate the benefits/risks of using this antibiotic for indications that lack rigorous scientific support.
Abstract in English:Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 ± 19.8) were administered IVA (500mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study - EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1%) completed the study. At the end of treatment, 95.2% (CI95: 88.9% - 100%) reported cure or clinical improvement; at the end of the study, that figure was 88.9% (CI95: 74.1% - 91.7%). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40%), and 8 reported presumed eradication (53.3%). At end of study evaluation, 9 patients showed pathogen eradication (50%), and 7 showed presumed eradication (38.89%). Therefore, negative cultures were obtained from 93.3% of the patients at EOT, and from 88.9% at the end of the study. One patient (6.67% of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11%) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3% of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin associated to ceftriaxone and followed by oral azithromycin proved to be efficacious and well-tolerated in the treatment of Brazilian inpatients with CAP.
Abstract in English:In this study, we determined the accuracy of phenotypic tests (cefoxitin agar dilution, 30µg-cefoxitin and 1µg-oxacillin disks) to detect the oxacillin resistance/mecA gene among coagulase-negative staphylococci (CoNS) isolates. The presence of the mecA gene was detected by PCR technique (gold standard). A total of 176 CoNS isolates from blood of hospitalized patients were evaluated. Of these, 138 (78.4%) harbored the mecA gene. Using 30µg-cefoxitin and 1µg-oxacillin disks we obtained 100 and 98.3% accuracy, respectively. In addition, when cefoxitin was used as marker in an agar dilution method, the higher accuracy (99.4%) was established with 8mg cefoxitin per mL breakpoint. Thus, despite of the agar dilution method using cefoxitin as a marker not being standard for this detection, our results suggested that it is an excellent alternative to detect the oxacillin resistance/mecA gene among CoNS isolates.
Abstract in English:Methicillin-resistant Staphylococcus aureus (MRSA) commonly causes infection in hospitalized patients. Since its appearance in the 1960s, the SCCmec has evolved throughout the years into 5 different types (I-V), each bearing a different set of genes. Infection with MRSA SCCmec types I, II or III is almost exclusively restricted to hospitalised patients. However, recently, community acquired MRSA (CA-MRSA) infections have been reported with increasing frequency, usually caused by a type IV SCCmec MRSA in nosocomial settings. We studied the prevalence of SCCmec types in 50 nosocomial strains collected from 1995 to 1999. The SCCmec complex type and presence of Panton-Valentine leukocidin (PVL) were determined by PCR. Strains had been previously typed by PFGE and were now typed by MLST. We found that 3 of the isolates studied bore a type IVc SCCmec all having different PFGE and MLST profiles (ST3, ST5 and ST88). All strains bearing a type III SCCmec belonged to MLST ST239 (Brazilian/Iberian clone). Only the strain which presented the ST5 profile bore the pvl gene. The type IVc SCCmec strains presented relatively lower levels of resistance to oxacillin in comparison to the type III SCCmec strains. The pattern of dissemination of the type IV SCCmec remains to be elucidated. The finding of strains carrying a type IV SCCmec in the present study among strains isolated at least 7 years ago indicates that clones bearing a type IV SCCmec have been present in Brazil for quite some time, and must have gone by undetected.
Abstract in English:Milk may represent an important source of infectious agents to hospitalized pediatric patients. To describe the bacterial microflora isolated from the hands, stools, pharynx of all workers at milk kitchens in pediatric hospitals in the city of Salvador, Brazil, as well as in the formulas prepared by them, we carried out this cross-sectional study with all 91 workers from the 20 milk kitchens of all the public and private hospitals in Salvador, Brazil. Hand and pharynx swabs and stool samples were collected from all workers, as well as samples of the milk and formulas delivered by the kitchens. All samples were cultured for the detection of pathogenic and non-pathogenic bacteria. Pathogenic bacteria were isolated from 20 (22.0%) and 8 (8.8%) cultures of the hands and pharynx of the workers, respectively. No pathogenic bacteria were isolated from stool samples. Pathogenic bacteria were isolated from 17 (18.7%) milk samples. The prevalence of pathogenic bacteria in hand swabs was significantly higher in workers from public (37.8%) than from private (6.5%) hospitals (prevalence ratio [PR]=5.8; p<0.01). Pathogenic bacteria were isolated from two (4.4%) workers from public hospitals and six (13.0%) workers from private hospitals (PR=0.38; p=0.27). Pathogenic bacteria were isolated from 11 (24.4%) milk samples from public hospitals and 6 (13.0%) from private hospitals (PR=1.9; p=0.16). A high prevalence of contamination was found, mainly on the hands of workers on units for manipulation of milk. Preventive efforts should be intensified and focus primarily on effective hand washing and continuous work supervision.
Abstract in English:The current study determined the spectrum of biliary microflora with special emphasis on enteric fever organisms in patients with acute cholangitis with and without cholelithiasis or other biliary diseases. The patients were divided into three groups: Group A consisted of patients with acute cholecystitis with cholelithiasis; Group B consisted of patients with acute cholecystitis with gastrointestinal ailments requiring biliary drainage and group C consisted of patients with gallbladder carcinoma. Gallbladder, bile and gallstones were subjected to complete microbiological and histopathological examination. Antimicrobial susceptibility of the isolates was performed as per CLSI guidelines. Bacteria were recovered from 17 samples (32%) in Group A, 17 (51.4%) in Group B and 1 (1.6%) in Group C. The most common organisms isolated were Escherichia coli (11, 29.7%), Klebsiella pneumoniae (10, 27%), Citrobacter freundii (3, 8.1%), Salmonella enterica serovar Typhi (3, 8.1%), etc. The majority of Enterobacteriaceae isolates were susceptible to piperacillin-tazobactam and meropenem. As regards Salmonella spp., S. Typhi was isolated from 2 (3.8%) patients in Group A and 1 (16%) in Group C. Antimicrobial susceptibility of potential causative organisms, the severity of the cholecystitis, and the local susceptibility pattern must be taken into consideration when prescribing drugs. A protocol regarding the management of such cases should be formulated based on observations of similar studies.
Abstract in English:This study verified the correlation between the serum levels of TNF alpha and different clinical forms of tuberculosis. We described a group of 24 patients presenting several clinical forms of tuberculosis and a control group of 13 healthy individuals. The levels of TNF alpha were measured by bioassay method. The levels of TNF-alpha had significant differences between the tuberculosis and control groups. The patients with abnormal chest X-Ray findings had higher TNF alpha levels (15328.48 ± 4602.19 pg/mL) when compared to patients with normal X-Rays (3353.18 ± 1495.29 pg/mL) (p<0.05). Patients that lost weight had higher TNF alpha levels (15468.54 ± 4580.54 pg/mL) than those that didn't loose weight (2904.98 ± 1367.89) (p<0.05). The levels of TNF alpha were higher in patients with a positive PPD skin test than in those with a negative PPD test (p<0.05). There was a positive correlation between patients' clinical severity and the serum levels of TNF alpha. In patients with successive measurements of TNF alpha, we observed that there was a drop in cytokine levels, and also a clinical improvement concomitantly. We concluded that there was a correlation between serum TNF alpha levels and chest X-Ray alterations, loss of weight, positive PPD skin test and clinical severity in patients with tuberculosis. There was evidence of a worse clinical outcome in patients with tuberculosis that presented higher TNF alpha serum levels.
Abstract in English:The diagnostic test characteristics of detecting free and complex-dissociated IgG to three recombinant antigens of Mycobacterium tuberculosis (38-kDa, Ag16 and Ag85B), singly and in combination, were evaluated in sera from 161 tuberculous patients [smear-positive pulmonary TB (50), smear-negative pulmonary TB (pTBsm-) (60) and extrapulmonary TB (51)) and 214 control patients (mycobacteriosis (14), mycoses(14), leprosy(4), other underlying diseases (82) and healthy people (100)]. The individual antigens ranged from 25% to 42% in sensitivity and from 93% to 96% in specificity, while considering free IgG response. Addition of complex-dissociated antibodies against each individual antigen improved the sensitivity up to 55%. The number and levels of specific antibodies varied greatly from individual to individual. Combination of individual results for free and complex-dissociated IgG to 38-kDa, Ag16 and Ag85B offered 76% sensitivity and 83% specificity. When the three antigens were placed in the same well, the sensitivity was lower than that expected on the basis of single antigen (63%) but with a good specificity (95%), even in the group of mycobacteriosis or mycoses. The highest contribution of complex-dissociated IgG results to free IgG results was seen for the diagnosis of pTBsm- patients. In conclusion, although neither single recombinant antigen was reactive with most sera from TB patients even after the measurement of both free and complex-dissociated antibodies, the use of multi-antigen cocktails improved the diagnostic utility of the ELISA assay, allowing the identification of almost 70% of pTBsm-, with a high level of specificity; the use of additional, well selected antigens should lead to the detection of almost all patients with TB.
Abstract in English:Meningitis is a severe and potentially fatal form of tuberculosis. The diagnostic workup involves detection of acid-fast bacilli (AFB) in the cerebrospinal fluid (CSF) by microscopy or culture, however, the difficulty in detecting the organism poses a challenge to diagnosis. The use of the polymerase chain reaction (PCR) in the diagnostic approach to Mycobacterium tuberculosis (MTB) meningitis has been reported as a fast and accurate method, with several commercial kits available. As an alternative, some institutions have been developing inexpensive in house assays. In our institution, we use an in house PCR for tuberculosis. We analyzed the performance of our PCR for the diagnosis of MTB meningitis in 148 consecutive patients, using MTB culture as gold standard. The sensitivity and specificity of CSF PCR for the diagnosis of MTB meningitis was 50% and 98.6% respectively with a concordance with CSF mycobacterial culture of 96% (Kappa=0.52). In contrast to CSF cultures for MTB, our PCR test is a fast, simple and inexpensive tool to diagnose tuberculous meningitis with a performance similar to that obtained with the available commercial kits.
Abstract in English:Acute renal failure (ARF) is one of the most common complications of leptospirosis although the causal mechanisms are still unclear. Diverse mechanisms are implicated in leptospiral nephropathy and new data supports the role of peculiar ion transport defects. Besides antibiotic therapy, ARF management in leptospirosis requires dialytic therapy which is most efficient when started early. Dialysis is the standard supportive therapy even though recent evidence suggests clinical benefit from alternative treatments such as plasmapheresis and hemofiltration. Renal recovery is achieved soon after clinical improvement. The comprehension of the primary mechanisms of renal dysfunction will be helpful in the development of additional therapeutic tools for improving supportive therapy for leptospiral nephropathy. This review discusses new insights into mechanisms implicated in leptospiral ARF and recent advances in treatment.
Abstract in English:Viral Hepatitis B, C and D are a serious public health problem in Brazil and other South American countries, mainly in the Amazonian region. Despite the paucity of clinical and epidemiological studies, a high prevalence of Hepatitis viruses has often been described in this area. Genotype F of Hepatitis B and Genotype III of Hepatitis D have been found to be quite prevalent in this area and preliminary studies have implicated both genotypes in carcinogenesis and peculiar pathogenic liver mechanisms. Initial epidemiological studies have further demonstrated a high prevalence of Hepatitis C in the western Brazilian Amazon. The geographic, cultural, ethnic and environmental aspects of this region may favor hepatotropic virus dissemination, as well as rendering difficult the implementation of governmental programs in the treatment of patients and prevention of disease dissemination.
Abstract in English:A 51 year old woman without significant past medical history or risk factors for Nocardia infection developed primary Nocardia nova sternal osteomyelitis with mediastinal abscess, diagnosed with open biopsy. She required prolonged antibiotic therapy and had a favorable outcome. Primary sternal osteomyelitis develops in the absence of a contiguous focus of infection, as opposed to secondary sternal osteomyelitis, which is usually a complication of sternotomy. Staphylococcus aureus probably still is the most common cause of both forms of sternal osteomyelitis. Nocardia species invade humans usually through the respiratory tract and can cause a variety of localized infections through the hematogenous route. Pulmonary involvement may or may not coexist. Immunosuppressed patients are more prone to infection by Nocardia species, although cases involving seemingly immunocompetent patients are not rare. This is the first reported case in the English literature of primary sternal osteomyelitis due to Nocardia nova or any other Nocardia species.
Abstract in English:Mycobacteria other than tuberculosis (MOTT) have a low incidence as pathogens in human pathology. The most frequent clinical expression is the disseminated disease in subjects with compromised cellular immunity. Bacteriological characteristics in culture can generate confusion with other pathogens, which delays the appropriate diagnosis and treatment. We present a case of a disseminated infection due to Mycobacterium chelonae with scleritis, spondylodiscitis and spinal epidural abscess in a man with a medical background of cellular immunity deficit induced by therapeutic drugs. The antibiotic scheme of twenty-one weeks, during the follow-up period, controlled the infection, however, the optimum duration of treatment has not been established.