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Abstract Background The mechanism underlying the coexistence of hepatitis B surface antigen and antibodies to HBsAg in chronic hepatitis B patients remains unknown. Aims This research aimed to determine the clinical and virological features of the rare pattern. Methods A total of 32 chronic hepatitis B patients infected by HBV genotype C were included: 15 carrying both HBsAg and anti-HBs (group I) and 17 solely positive for HBsAg (group II). S gene and reverse transcriptase region sequences were amplified, sequenced and compared with the reference sequences. Results The amino acid variability within major hydrophilic region, especially the “a” determinant region, and within reverse transcriptase for regions overlapping the major hydrophilic region in group I is significantly higher than those in group II. Mutation sI126S/T within the “a” determinant was the most frequent change, and only patients from group I had the sQ129R, sG130N, sF134I, sG145R amino acid changes, which are known to alter immunogenicity. Conclusions In chronic patients, the concurrent HBsAg/anti-HBs serological profile is associated with an increased aa variability in several key areas of HBV genome. Additional research on these genetic mutants are needed to clarify their biological significance for viral persistence.

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Abstract Background Clostridium difficile infections caused by the NAP1/B1/027 strain are more severe, difficult to treat, and frequently associated with relapses. Methods A case–control study was designed to examine a C. difficileinfection (CDI) outbreak over a 12-month period in a Mexican hospital. The diagnosis of toxigenic CDI was confirmed by real-time polymerase chain reaction, PCR (Cepheid Xpert C. difficile/Epi). Results During the study period, 288 adult patients were evaluated and 79 (27.4%) patients had confirmed CDI (PCR positive). C. difficilestrain NAP1/B1/027 was identified in 31 (39%) of the patients with confirmed CDI (240 controls were included). Significant risk factors for CDI included any underlying disease (p < 0.001), prior hospitalization (p < 0.001), and antibiotic (p < 0.050) or steroid (p < 0.001) use. Laboratory abnormalities included leukocytosis (p < 0.001) and low serum albumin levels (p < 0.002). Attributable mortality was 5%. Relapses occurred in 10% of patients. Risk factors for C. difficileNAP1/B1/027 strain infections included prior use of quinolones (p < 0.03). Risk factors for CDI caused by non-027 strains included chronic cardiac disease (p < 0.05), chronic renal disease (p < 0.009), and elevated serum creatinine levels (p < 0.003). Deaths and relapses were most frequent in the 027 group (10% and 19%, respectively). Conclusions C. difficile NAP1/BI/027 strain and non-027 strains are established pathogens in our hospital. Accordingly, surveillance ofC. difficile infections is now part of our nosocomial prevention program.

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Abstract In this study, 275 patients in use of tenofovir were retrospectively followed-up for three years to evaluate risk factors involved in impaired renal function. Analysis of variance (ANOVA) and Tukey's test were used to verify any differences in creatinine levels and estimated clearance at 0, 6, 12, 24 and 36 months, adjusting for the co-variables sex, skin color, age >50 years, arterial hypertension, diabetes and the use of the ritonavir-boosted protease inhibitors (PI/r) lopinavir/r or atazanavir/r. The software package STATISTICA 10® was used for statistical analysis. The patients’ mean age was 43.2 ± 10.7 years. Systemic arterial hypertension (SAH) and diabetes were found in 20.4% and 8.7% of the patients, respectively. Overall, 96.7% were on tenofovir associated with lamivudine (TDF + 3TC), 39.3% on lopinavir/r, 29.8% on efavirenz, and 17.6% on atazanavir/r. There was a statistically significant difference in estimated creatinine clearance at 24 months, when the co-variables male (F = 3.95; p = 0.048), SAH (F = 6.964; p = 0.009), and age over 50 years (F = 45.81; p < 0.001) were taken into consideration. Analysis of the co-variable use of atazanavir/r showed a tendency toward an increased risk over time (F = 2.437; p = 0.063); however, no significant time interaction was seen. At 36-month, a statistically significant difference was found for age over 50 years, (F = 32.02; p < 0.05) and there was a significant time-by-sex interaction (F = 3.117; p = 0.0149). TDF was discontinued in 12 patients, one because of a femoral neck fracture (0.7%) and 11 due to nephrotoxicity (4%). Of these latter cases, 9/11 patients were also using protease inhibitors. These data strongly alert that tenofovir use should be individualized with careful attention to renal function especially in male patients, over 50 years, with SAH, and probably those on ATV/r.

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Abstract Background The timing of most recurrences after neonatal urinary tract infection is during the first year of life, with peak incidence 2–6 months after the initial infection. Information on the microbiologic characteristics of recurrent urinary tract infection episodes in relation to the microbiology of the initial episodes is limited. Objectives To analyze the epidemiologic/microbiological characteristics of 1st and recurrent urinary tract infection in infants <2 months of age. Methods A retrospective study including all infants <2 months of age with urinary tract infection admitted during 2005–2009 and followed till the age of 1 year. Results 151 neonates were enrolled (2.7% of all 5617 febrile infants <2 months of age admitted). The overall incidence of urinary tract infection occurring during the first 2 months of life was 151/73,480 (0.2%) live births during 2005–2009 in southern Israel (2.1 cases/1000 live births). One pathogen was isolated in 133 (88.1%); Escherichia coli, Klebsiella spp., Enterococcus spp., Morganella morganii, Proteus spp., and Enterobacter spp. represented the most common pathogens (57.9%, 12.2%, 7.9%, 6.7%, 6.1%, and 5%, respectively). Trimethoprim/sulfamethoxazole, ampicillin, and cefuroxime-axetil were the most commonly recommended prophylactic antibiotics (45%, 13.2%, and 8%, respectively). Twenty-three recurrent urinary tract infection episodes were recorded in 20 (13.2%) patients; 6/23 (26%) were diagnosed within one month following 1st episode. E. coli was the most frequent recurrent urinary tract infection pathogen (12/23, 52.2%). No differences were recorded in E. coli distribution between first urinary tract infection vs. recurrent urinary tract infection. Seventeen (74%) recurrent urinary tract infection episodes were caused by pathogens different (phenotypically) from those isolated in 1st episode. Recurrent urinary tract infection occurred in 25.0%, 8.3%, and 0 patients recommended trimethoprim/sulfamethoxazole, cefuroxime-axetil, or amoxicillin prophylaxis, respectively. Conclusions (1) The study determined the incidence of urinary tract infection in febrile infants <2 months of age in Southern Israel; (2) E. coli was responsible for the majority of first and recurrent urinary tract infection; (3) recurrent urinary tract infection was caused mostly by pathogens different than the pathogens isolated at initial episode.

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Abstract Increased serum CA 19-9 levels in patients with nonmalignant diseases have been investigated in previous reports. This study evaluates the clinical significance of serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease and pulmonary tuberculosis. The median CA 19-9 level was higher in patients with pulmonary nontuberculous mycobacterial disease than in patients with pulmonary tuberculosis (pulmonary nontuberculous mycobacterial disease: 13.80, tuberculosis: 5.85, p < 0.001). A multivariate logistic regression analysis performed in this study showed that Mycobacterium abscessus (OR 9.97, 95% CI: 1.58, 62.80; p = 0.014) and active phase of pulmonary nontuberculous mycobacterial disease (OR 12.18, 95% CI: 1.07, 138.36, p = 0.044) were found to be risk factors for serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease. The serum CA 19-9 levels showed a tendency to decrease during successful treatment of pulmonary nontuberculous mycobacterial disease but not in pulmonary tuberculosis. These findings suggest that CA 19-9 may be a useful marker for monitoring therapeutic responses in pulmonary nontuberculous mycobacterial disease, although it is not pulmonary nontuberculous mycobacterial disease-specific marker.

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Abstract The current study was aimed to evaluate the performance of direct 2,3,5-triphenyl tetrazolium chloride assay and direct microscopic observation drug susceptibility assay with indirect Löwenstein-Jensen proportion method directly on Ziehl-Neelsen smear positive sputum specimens. Methods Direct acid fast bacilli smear positive sputum specimens (n = 264) were subjected to isoniazid and rifampicin drug susceptibility testing by direct 2,3,5-triphenyl tetrazolium chloride assay, direct microscopic observation drug susceptibility assay, and the performances were compared with indirect Löwenstein-Jensen proportion method. Results The direct 2,3,5-triphenyl tetrazolium chloride assay demonstrated an overall sensitivity, specificity, positive predictive value, and negative predictive value of 99.2%, 82.4%, 99.2%, and 88.5%, respectively, for the detection of isoniazid and rifampicin resistant Mycobacterium tuberculosis isolates when compared to indirect Löwenstein-Jensen proportion method. Likewise, the overall sensitivity, specificity, positive predictive value and negative predictive value of direct microscopic observation drug susceptibility assay were 98.8%, 82.4%, 99.2%, and 78.2%, respectively. Conclusion The direct 2,3,5-triphenyl tetrazolium chloride assay was found to be an economical alternative method for the rapid and accurate detection of isoniazid and rifampicin resistance from direct acid fast bacilli smear positive sputum specimens.

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Abstract Background Fluoroquinolones are the backbone of multidrug resistant tuberculosis treatment regimens. Despite the high burden of multidrug resistant tuberculosis in the country, little is known about drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance among multidrug resistant tuberculosis patients from Pakistan. Objective To evaluate drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients. Methods This was a cross-sectional study conducted at a programmatic management unit of drug resistant tuberculosis, Lady Reading Hospital Peshawar, Pakistan. Two hundred and forty-three newly diagnosed multidrug resistant tuberculosis patients consecutively enrolled for treatment at study site from January 1, 2012 to July 28, 2013 were included in the study. A standardized data collection form was used to collect patients’ socio-demographic, microbiological, and clinical data. SPSS 16 was used for data analysis. Results High degree of drug resistance (median 5 drugs, range 2–8) was observed. High proportion of patients was resistant to all five first-line anti-tuberculosis drugs (62.6%), and more than half were resistant to second line drugs (55.1%). The majority of the patients were ofloxacin resistant (52.7%). Upon multivariate analysis previous tuberculosis treatment at private (OR = 1.953, p = 0.034) and public private mix (OR = 2.824, p = 0.046) sectors were predictors of ofloxacin resistance. Conclusion The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public–private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains.

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Abstract In the present context of emergence of resistance aligned with the conventional anti-leishmanial drugs and occasional treatment failure compelled us to continue the search for replaceable therapeutic leads against Leishmaniainfection. Various ginger spices of the Zingiberaceae family are widely used as spices, flavouring agents, and medicines in Southeast Asia because of their unique flavour as well as due to their medicinal properties. Zerumbone, a natural component of Zingiber zerumbet (L.) Smith, has been studied for its pharmacological potential as antiulcer, antioxidant, anticancer, and antimicrobial. In this study, we have shown that zerumbone could induce ROS mediated apoptosis in Leishmania donovani promastigotes and also found effective in reducing intracellular amastigotes in infected-macrophages. We emphasized the potential of zerumbone to be employed in the development of new therapeutic drugs against L. donovaniinfection and provided the basis for future research on the application of transitional medicinal plants.

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Abstract Invasive pneumococcal disease is a relevant public health problem in Brazil, especially among children and the elderly. In July/2010 a 10-valent pneumococcal conjugate vaccine was introduced to the immunization schedule of Brazilian children under two years of age. Between July/2010 and December/2013 we conducted a case-series study on invasive pneumococcal disease in Salvador, Brazil to describe the clinical and bacteriological profile of invasive pneumococcal disease cases during the post-implementation period. Eighty-two cases were eligible. Mean age was 31 years (interquartile range, 3–42); 17.1% and 30.5% were under 2 years and 5 years, respectively. Pneumococcal meningitis (n = 64, 78.1%), bacteraemic pneumococcal pneumonia (n = 12, 14.6%) and bacteraemia (n = 6, 7.3%) were the clinical syndromes identified. Thirty-three different serotypes were found. Of these, serotype 14 (n = 12, 14.6%) was the most common, followed by 23F (n = 10, 12.2%), 12F (n = 8, 9.8%), 18 C (n = 5, 6.1%) and 6B (n = 5, 6.1%). Investigations conducted in Salvador in the pre-vaccine period did not identify serotype 12F as one of the most prevalent serotypes. Increase of serotype 12F was observed in different regions of Brazil, in the post-vaccine period. Among children under two years of age, the target group for 10-valent pneumococcal conjugate vaccine, 11 (78.6%) of the 14 isolated strains of Streptococcus pneumoniae belonged to vaccine serotypes; at least 50% of these children were not vaccinated. The relatively recent implementation of 10-valent pneumococcal conjugate vaccine in Brazil reinforces the need to maintain an active surveillance of invasive pneumococcal disease cases, considering the possible increase of invasive pneumococcal disease cases related to non-vaccine serotypes and the changes on the clinical presentation of the disease.

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Abstract Human papillomavirus (HPV) infection is common in sexually active women and viral persistence may cause intraepithelial lesions and eventually progress to cervical cancer (CC). The present study aimed to investigate epidemiological factors related to HPV infection and to evaluate viral persistence and CC precursor lesions frequencies in women from a city in the countryside of South Brazil. Three hundred women were recruited from a primary public health care clinic. The patients were interviewed and underwent sampling with cervical brushes for HPV-DNA detection/typing by a PCR-based assay and cytological analysis by Pap smear test. HPV was detected in 47 (15.7%) women. HPV infection was significantly associated with young age (<30 years) and low socio-economic status. Seventeen (5.7%) women presented cytological abnormalities, three of them with precursor CC intraepithelial lesions. A subgroup of 79 women had been previously analyzed and thirteen (16.4%) were persistently infected, two with precursor CC intraepithelial lesions and high-risk HPV types infection (both of them without cervical abnormalities in the first exam). In conclusion, HPV infection was associated with young age (<30 years) and low family income; viral persistence was low (16.4%) but related to CC precursor lesions; and HPV-DNA high risk types detection would help to screen CC in the population.

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Abstract Setting Patients HIV+ attending in a reference clinic, Southern Brazil. Objective To compare the interferon-gamma-release assay (IGRA – QuantiFERON® TB Gold In-Tube) with the tuberculin skin test (TST – PPD-Rt 23) for latent tuberculosis infection (LTBI) in patients with HIV. Design Cohort study. Patients were simultaneously submitted to the TST and blood collection for the IGRA. Results A total of 140 subjects were included. Nine (6.4%) were IGRA+/TST+, 12 (8.6%) were IGRA+/TST−, 4 (3%) were IGRA−/TST+, and 115 (82%) IGRA−/TST−. There was poor agreement between tests (kappa = 0.2), and no correlation between these results and CD4+ T lymphocyte counts. During follow-up, one patient with negative results on both tests died from sepsis, and another with discordant results (IGRA+/TST−) exhibited TST seroconversion. Compared to the TST, IGRA showed a sensitivity and specificity of 69% and 90%, respectively. The IGRA detected 8% more positive results than the TST. All patients were followed up for 2 years. Conclusion The higher accuracy of the IGRA would result in LTBI treatments being administered to patients who would have otherwise been overlooked, decreasing the number of active tuberculosis cases. The long-term survival of HIV carriers requires further evaluation.

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Abstract Introduction HIV infection and its therapy which can affect their aerobic capacity and health-related quality of life of patients. Objective We conducted a cross-sectional study to determine if aerobic capacity and health related quality of life was decreased in HIV-infected patients receiving highly active antiretroviral therapy and comparing patients with and without lipodystrophy. Research design and methods HIV-infected patients older than 18 years, and in current use of highly active antiretroviral therapy drugs, were evaluated for blood count, fasting total cholesterol, high density lipoprotein, triglycerides, glucose, HIV viral load and CD4/CD8 counts, body composition, peak oxygen consumption (peak VO2) and metabolic equivalent. Health related quality of life was assessed by using Short Form-36 (SF-36). Statistical analysis was carried out using SPSS version 20.0. Results A total of 63 patients with mean age of 43.1 ± 6.4 years were evaluated, of these 34 (54%) had lipodystrophy. The average peak VO2 (31.4 ± 7.6 mL kg−1 min−1) was significantly lower (p < 0.01) than expected values (37.9 ± 5.6 mL kg−1 min−1) according to the characteristics of the patients. The lipodystrophy group presented with a significant difference in muscle mass, body fat, peak VO2 and metabolic equivalent and in functional capacity domains of SF-36. Conclusion Aerobic capacity values were reduced in HIV-infected patients under highly active antiretroviral therapy when compared to predicted values. Lipodystrophy was associated with reduced aerobic capacity and higher frequency of metabolic syndrome. Lifestyle modification should be a priority in the management of chronic HIV disease.

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Abstract Data on the burden of disease and circulation patterns of influenza B lineages for Brazil are limited. This review aims to describe the pattern of influenza B occurrence in Brazil to have a better understanding of its epidemiology and its relevance when considering seasonal influenza vaccine composition. A review of the data including analysis of international and local surveillance data as well as information from online search of databases using Medical Subject Headings terms in conjunction with screening of abstracts from scientific events was performed. Based on international epidemiologic surveillance data, moderate levels of influenza B disease (19%; 2006–2014) were observed. Of these nine years, it was possible to compare data from three years (2007, 2008 and 2013) which have information on the circulating influenza B lineage. Co-circulation of influenza B lineages was observed in all these three influenza seasons, of which, during one season, a high degree of mismatch between the vaccine lineage and the predominant circulating lineage (91.4% [2013]) was observed. Local surveillance data reveal a distinct and dynamic distribution of respiratory viruses over the years. Data from published literature and abstracts show that influenza B is a significant cause of disease with an unpredictable circulation pattern and showing trends indicating reemergence of the B/Victoria lineage. The abstracts report notable levels of co-circulation of both influenza B lineages (2000–2013). Mismatch between the Southern hemisphere vaccine and the most prevalent circulating viruses in Brazil were observed in five influenza seasons. The evidence on co-circulation of two influenza B lineages and mismatched seasons in Brazil indicates the benefit of quadrivalent influenza vaccines in conferring broader seasonal influenza protection. Additionally, improving influenza surveillance platforms in Brazil is important for monitoring disease trends and the impact of introducing seasonal influenza vaccination.

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Abstract Chikungunya is an arthropod-borne virus transmitted by Aedes mosquito bites. A viral mutation has allowed Aedes albopictus to become the preferred vector extending the geographic spread of the condition. The virus causes an acute febrile illness occasionally followed by a chronic rheumatic condition causing severe impairment. The diagnosis is usually confirmed with serology. No specific treatment is currently available. This article reviews the condition with emphasis on his dissemination in the Americas.

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Abstract Presarcopenia and sarcopenia were evaluated in HIV-infected individuals and in healthy elderly controls according to the consensus definitions of the European Working Group on Sarcopenia in Older People. Bioelectrical impedance, a hydraulic hand dynamometer, and gait speed were used to evaluate muscle mass, muscle strength, and physical performance, respectively. Adjusted and unadjusted binary logistic regression predicted the risk of sarcopenia. Predictor contribution was assessed by the Wald test. Significance was established at p ≤ 0.05. The HIV-infected group consisted of 33 patients on treatment (42.4% women; mean age 59 ± 7 years; mean BMI 25 ± 6 kg/m2; viral load undetectable in 30 cases). The HIV-uninfected group consisted of 60 individuals (71.7% women; mean age 70 ± 7 years; mean BMI 28 ± 6 kg/m2). Of the controls, 4 (6.7%) individuals had presarcopenia and 4 (6.7%) sarcopenia compared to 4 (12.1%) and 8 (24.2%), respectively, in the HIV-infected group. The HIV-infected patients had a 4.95 higher risk (95% CI: 1.34–18.23) for sarcopenia compared to the controls. It should be pointed out that the control group was on average 10 years older. This risk increased further (RR = 5.20; 95% CI: 1.40–19.20) after adjusting for age and BMI. HIV-infected patients were shown to be at a greater risk of sarcopenia, an indicator of frailty, even following adjustment for age and BMI.