Association of seasonality and serum albumin concentration with vitamin D deficiency in subjects with chronic hepatitis C infection living in a sunny country.

OBJECTIVE: This study aimed to analyse the relationship between vitamin D deficiency and the season when the blood sample was obtained from subjects with chronic hepatitis C (CHC) infection. DESIGN: A cross-sectional study was conducted on a representative sample. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/l, based on the values set forth by the Endocrine Society guideline for higher-risk populations. Seasonality was defined according to solstices and equinoxes. The association of seasonality and clinical/laboratory characteristics with vitamin D deficiency was assessed using a multivariate logistic regression analysis. SETTING: NUPAIG Viral Hepatitis Outpatient Clinic of the Universidade Federal de São Paulo - Brazil. PARTICIPANTS: Adult subjects with CHC infection (n 306). RESULTS: The prevalence of vitamin D deficiency was 16 %, whereas the median serum 25(OH)D concentration was 87 (interquartile range, 59; third quartile = 118) nmol/l. Serum concentration was consistently lower in samples collected in spring and winter than in other seasons. In multivariate analysis, vitamin D deficiency was found to be independently associated with male gender, serum albumin concentration and with samples drawn in winter and spring. CONCLUSIONS: The findings show not only the relevance to consider season as a factor influencing 25(OH)D concentration but also the need to actively screen for hypovitaminosis D in all patients with CHC infection, especially in females and those with low albumin concentration.

The management of HIV-infected pregnant women.

PURPOSE OF REVIEW: The purpose of this article is to update the current practice in the management of HIV-infected pregnant women and present evidence-based recommendations for the reduction of mother-to-child transmission. RECENT FINDINGS: Early and sustained control of HIV viral replication is associated with decreasing residual risk of transmission and favors initiating antiretroviral drugs sufficiently early in naive women to suppress viral replication by the third trimester; however, this potential benefit must be balanced against the unknown long-term outcome of first-trimester drug exposure. Efavirenz should whenever possible be avoided in the first trimester of gestation, but its use seems well tolerated for 39 days after last menstrual period when the neural tube closes. Raltegravir may be considered in special circumstances in pregnancy. SUMMARY: The HIV viral load and the risk factors for prematurity must be considered when deciding when to start antiretroviral treatment in each individual pregnant woman. A ritonavir-boosted protease inhibitor combined with two nucleoside reverse transcriptase inhibitors is currently the most widely used regimen. Among protease inhibitors, lopinavir combined with ritonavir is the most frequently used; however, atazanavir combined with ritonavir is a good alternative. Elective cesarean section is the best delivery mode for pregnant women with viral loads more than 50  copies/ml.

The immunoexpression of heparanase 2 in normal epithelium, intraepithelial, and invasive squamous neoplasia of the cervix.

OBJECTIVE: Heparanase 2 (HPSE2) is expressed in various tissues, including the brain, intestine, prostate, breast, and endometrium. The aim of this study was to investigate the role of HPSE2 in cervical carcinogenesis, which has not been clarified to date. MATERIALS AND METHODS: The immunoexpression of HPSE2 in normal and neoplastic cervical squamous epithelia was determined using a semiquantitative (SQ) method and an index of expression (IE) method, using Image Lab Software. A total of 230 cervical tissue samples were analyzed and segregated into the following diagnostic groups: normal (27.4%), cervical intraepithelial neoplasia 1 (CIN 1, 15.2%), CIN 2 (16.5%), CIN 3 (15.2%), and invasive neoplasia (25.7%). The mean HPSE2 expression in the normal group was significantly lower than that of the other groups individually or combined (p < .001, for all combinations). The immunoexpression via the SQ method was significantly greater in the CIN 3 group compared with that in the CIN 1 group (p = .02). The mean immunoexpression of the high-grade squamous intraepithelial lesion groups was significantly greater than those of the normal and low-grade squamous intraepithelial lesion groups (p < .001) and lower compared with that of the invasive neoplasia group (p < .001). There were no statistically significant differences in the immunoexpression of HPSE2 among the different clinical states within the invasive neoplasia group. CONCLUSIONS: The SQ method produced a greater sensitivity and specificity than did the index of expression method. There was a progressive increase in the mean HPSE2 immunoexpression according to the severity of the cervical lesion from the low-grade squamous intraepithelial lesion group to the invasive neoplasm group, whereas the normal group displayed the lowest level of expression. This is a novel study concerning HPSE2 in the cervix and cervical cancer carcinogenesis.

Antiretroviral Drug-Resistance Mutations on the Gag Gene: Mutation Dynamics during Analytic Treatment Interruption among Individuals Experiencing Virologic Failure.

We describe drug-resistance mutation dynamics of the gag gene among individuals under antiretroviral virologic failure who underwent analytical treatment interruption (ATI). These mutations occur in and around the cleavage sites that form the particles that become the mature HIV-1 virus. The study involved a 12-week interruption in antiretroviral therapy (ART) and sequencing of the gag gene in 38 individuals experiencing virologic failure and harboring triple-class resistant HIV strains. Regions of the gag gene surrounding the NC-p2 and p1-p6 cleavage sites were sequenced at baseline before ATI and after 12 weeks from plasma HIV RNA using population-based Sanger sequencing. Fourteen of the sixteen patients sequenced presented at least one mutation in the gag gene at baseline, with an average of 4.93 mutations per patient. All the mutations had reverted to the wild type by the end of the study. Mutations in the gag gene complement mutations in the pol gene to restore HIV fitness. Those mutations around cleavage sites and within substrates contribute to protease inhibitor resistance and difficulty in re-establishing effective virologic suppression. ART interruption in the presence of antiretroviral resistant HIV strains was used here as a practical measure for more adapted HIV profiles in the absence of ART selective pressure.

Fitness Cost of Antiretroviral Drug Resistance Mutations on the pol Gene during Analytical Antiretroviral Treatment Interruption among Individuals Experiencing Virological Failure.

HIV cure studies require patients to enter an analytical treatment interruption (ATI). Here, we describe previously unanalyzed data that sheds light on ATI dynamics in PLHIV (People Living with HIV). We present drug resistance mutation dynamics on the pol gene among individuals with antiretroviral virological failure who underwent ATI. The study involved a 12-week interruption in antiretroviral therapy (ART), monitoring of viral load, CD4+/CD8+ T cell counts, and sequencing of the pol gene from 38 individuals experiencing virological failure and harboring 3-class resistant HIV strains: nucleoside reverse transcriptase inhibitors (NRTI) non-nucleoside inhibitors (NNRTI), and protease inhibitors (PI). Protease and reverse transcriptase regions of the pol gene were sequenced at baseline before ATI and every four weeks thereafter from PBMCs and at baseline and after 12 weeks from plasma HIV RNA using population-based Sanger sequencing. Average viral load increased 0.559 log10 copies per milliliter. CD4+ T cell count decreased as soon as ART was withdrawn, an average loss of 99.0 cells/mL. Forty-three percent of the mutations associated with antiretroviral resistance in PBMCs disappeared and fifty-seven percent of the mutations in plasma reverted to wild type, which was less than the 100% reversion expected. In PBMC, the PI mutations reverted more slowly than reverse transcriptase mutations. The patients were projected to need an average of 33.7 weeks for PI to revert compared with 20.9 weeks for NRTI and 19.8 weeks for NNRTI. Mutations in the pol gene can cause virological failure and difficulty in re-establishing effective virological suppression.

Chronic alcohol abuse and spontaneous clearance of hepatitis C virus.

Spontaneous clearance of hepatitis C virus (HCV) is an uncommon occurrence in the course of chronic infection. We reported a rare case of a 41-year-old male patient infected with HCV genotype 3a who presented spontaneous viral elimination after increasing his daily consumption of alcoholic beverage. In this short review, we overview how modulation of the hepatic inflammatory response could have a role in the viral elimination process.

Individual factors associated with time to non-adherence to ART pick-up within HIV care and treatment services in three health facilities of Zambézia Province, Mozambique.

INTRODUCTION: Mozambique has made significant gains in addressing its HIV epidemic, yet adherence to visit schedules remains a challenge. HIV programmatic gains to date could be impaired if adherence and retention to ART remains low. We investigate individual factors associated with non-adherence to ART pick-up in Mozambique. METHODS: This was a retrospective cohort of patients initiating ART between January 2013 and June 2014. Non-adherence to ART pick-up was defined as a delay in pick-up ≥ 15 days. Descriptive statistics were used to calculate socio-demographic and clinical characteristics. Adherence to ART pick-up was assessed using Kaplan Meier estimates. Cox proportional hazards model was used to determine factors associated with non-adherence. RESULTS: 1,413 participants were included (77% female). Median age was 30.4 years. 19% of patients remained adherent to ART pick-up during the evaluation period, while 81% of patients were non-adherent to ART pick-up. Probability of being non-adherent to ART pick-up by 166 days following initiation was 50%. In univariate analysis, being widowed was associated with higher adherence to ART pick-up than other marital status groups (p = 0.01). After adjusting, being ≥35 years (aHR: 0.843, 95% CI: 0.738-0.964, p = 0.012); receiving efavirenz (aHR: 0.932, 95% CI: 0.875-0.992, p = 0.026); and being urban (aHR: 0.754, 95% CI: 0.661-0.861, p<0.0001) were associated with improved adherence. Non-participation in a Community ART Support Group (CASG) was associated with a 43% increased hazard of non-adherence to ART pick-up (aHR 1.431, 1.192-1.717, p<0.0001). CONCLUSIONS: Interventions should focus on the first 6 months following ARV initiation for improvements. Younger persons and widows are two target groups for better understanding facilitators and barriers to visit schedule adherence. Future strategies should explore the benefits of joining CASGs earlier in one´s treatment course. Finally, greater efforts should be made to accelerate the scale-up of viral load capacity and HIV resistance monitoring.

Previous hepatitis E virus infection, cirrhosis and insulin resistance in patients with chronic hepatitis C.

BACKGROUND: Hepatitis E virus (HEV) infection in patients with pre-existing liver disease has shown high morbidity and lethality. The consequences of HEV superinfection in patients with chronic hepatitis C virus (HCV) infection are not fully understood. This study aimed to evaluate the association between the presence of anti-HEV antibodies, liver cirrhosis, and insulin resistance. METHODS: A total of 618 patients chronically infected with HCV were included from three reference centers for viral hepatitis in São Paulo, Brazil. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA). RESULTS: The seroprevalence of anti-HEV in patients with cirrhosis was significantly higher than in patients without cirrhosis (13.2% vs 8%, OR=1.74, p=0.04). Seropositivity for anti-HEV, adjusted for sex, age, and HCV genotype showed an association trend with hepatic cirrhosis (aOR=1.75, p=0.059). Presence of HEV antibodies, adjusted for age, body mass index and cirrhosis, was shown to be independently associated with insulin resistance (aOR: 4.39; p=0.045). CONCLUSION: Patients with chronic hepatitis C are under risk of hepatitis E virus superinfection in Brazil. The trend toward association between cirrhosis and previous HEV infection suggests that it may accelerate liver fibrosis in patients with chronic hepatitis C. In addition, previous infection by HEV is independently associated with insulin resistance in the studied population, which may be an extra-hepatic manifestation of hepatitis E that persists after resolution of the active infection, and may contribute to fibrosis progression.

How accurate is cytological diagnosis of cervical glandular lesions?

Gynecological cytology has some inaccurate morphological categorization and poor interobserver reproducibility especially for glandular lesions. Liquid-based cytology (LBC) preparations are presumed to reduce artifacts that interfere in diagnosis performance, but its value to correctly identify glandular alterations has not been sufficiently reported. The objective of this study was to compare the diagnostic performance and interobserver agreement of LBC and conventional Pap smear to identify histologically confirmed glandular lesions according to five cytologists. Sensitivity ranged from 55.8 to 73.1% and 32.7 to 48.1% for Pap smear and LBC, respectively. Specificity ranged from 66.1 to 87.1% and 69.4 to 94.4%, respectively. In general, agreement between pairs of cytologists was poor with kappa-values around 0.45. In conclusion, relying entirely on cervical cytology to rule out glandular lesions may be risky. The use of HPV DNA test alone or combined to screening glandular lesions may contribute to minimize the limitations of both conventional and LBC preparations to diagnose glandular abnormalities.

Mother-to-child transmission of hepatitis C virus.

Hepatitis C virus (HCV) infection is a worldwide health problem. Based on results of a serosurvey, global prevalence is estimated to be 2,5%, and women account for about 35.8% of the cases. For pregnant women the prevalence is lower and showed a range between 0.24% to 4.3%. Sinse mechanisms and timing of mother to child transmission are not fully understood, efforts are made to assess and understand its risk factors. The purpose of this review was to synthesize the evidence about the mother-to-child transmission of hepatitis C virus and review its risk factors.

Seroprevalence of hepatitis E virus in chronic hepatitis C in Brazil.

BACKGROUND AND AIMS: Hepatitis E virus infection in patients with underlying chronic liver disease is associated with liver decompensation and increased lethality. The seroprevalence of hepatitis E virus in patients with chronic hepatitis C in Brazil is unknown. This study aims to estimate the seroprevalence of hepatitis E virus in patients with chronic hepatitis C and to describe associated risk factors. METHODS: A total of 618 patients chronically infected with hepatitis C virus from three reference centers of São Paulo, Brazil were included. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA). RESULTS: Out of the 618 patients tested, 10.2% turned out positive for anti-HEV IgG (95% CI 8.0-12.8%). Higher seroprevalence was found independently associated with age over 60 years (OR=2.04; p=0.02) and previous contact with pigs (OR=1.99; p=0.03). CONCLUSIONS: Patients with chronic hepatitis C are under risk of hepatitis E virus superinfection in São Paulo. Contact with pigs is a risk factor for the infection, suggesting a possible zoonosis with oral transmission.

HEPATITIS C IN THE BRAZILIAN PUBLIC HEALTH CARE SYSTEM: BURDEN OF DISEASE.

BACKGROUND: Infection by hepatitis C virus is one of the leading causes of chronic hepatitis C and cause severe burden for patients, families and the health care system. OBJECTIVE: The aims of this research were to assess the severity of liver fibrosis, comorbidities and complications of hepatitis C virus; to examine health-related quality of life (HRQoL), productivity loss and resource use and costs in a sample of Brazilian chronic hepatitis C, genotype 1, patients. METHODS: This was a cross-sectional multicenter study performed in genotype-1 chronic hepatitis C patients to assess disease burden in the Brazilian public health care system between November 2014 and March 2015. Patients were submitted to a liver transient elastography (FibroScan) to assess liver fibrosis and answered an interview composed by a questionnaire specifically developed for the study and three standardized questionnaires: EQ-5D-3L, HCV-PRO and WPAI:HepC. RESULTS: There were 313 subjects enrolled, with predominance of women (50.8%), caucasian/white (55.9%) and employed individuals (39.9%). Mean age was 56 (SD=10.4) years old. Moreover, 42.8% of patients who underwent FibroScan were cirrhotic; the most frequent comorbidity was cardiovascular disease (62.6%) and the most frequent complication was esophageal varices (54.5%). The results also showed that "pain and discomfort" was the most affected HRQoL dimension (55.0% of patients reported some problems) and that the mean HCV-PRO overall score was 69.1 (SD=24.2). Regarding productivity loss, the most affected WPAI:HepC component was daily activity (23.5%) and among employed patients, presenteeism was more frequent than absenteeism (18.5% vs 6.5%). The direct medical costs in this chronic hepatitis C sample was 12,305.72USD per patient in the 2 years study period; drug treatment costs represented 95.9% of this total. CONCLUSION: This study showed that most patients are cirrhotic, present high prevalence of cardiometabolic diseases and esophageal varices, reduced HRQoL mainly in terms of pain/discomfort, and work productivity impairment, especially presenteeism. Additionally, we demonstrated that hepatitis C virus imposes an economic burden on Brazilian Health Care System and that most of this cost is due to drug treatment.

Association analysis of GRK3 gene promoter variants in cocaine abuse.

The G protein-coupled receptor kinase 3 gene (GRK3) is a candidate gene for cocaine addiction because it is involved in the regulation of several neurotransmitter receptors, including the response to dopaminergic agonists such as methamphetamine and cocaine. We hypothesized that genetic variants in the GRK3 gene might be associated with an increased risk of cocaine addiction. To test this, we genotyped three variants located in 5' untranslated and promoter regions of the gene in a sample of 711 cocaine users and 862 healthy control individuals from Sao Paulo, Brazil. Genotypic, allelic and haplotypic analyses provided no evidence for an association between alleles at these polymorphisms and cocaine abuse in this sample. Population stratification was tested for and its effect corrected for, but this did not affect the association test results. In conclusion, our results do not support a major role for GRK3 gene promoter variants in cocaine addiction.

HIV-infected pregnant women have greater adherence with antiretroviral drugs than non-pregnant women.

The objective of the study was to evaluate the influence of pregnancy on the level of adherence with antiretroviral (ARV) drugs, in a prospective cohort of 72 pregnant women and 79 non-pregnant women. Adherence was measured by pill counting and self-reporting. Women were deemed adherent if 95% or more of all ARV had been taken as prescribed, in two occasions. According to pill counting, 43.1 and 17.7% of pregnant and non-pregnant women, respectively, met the criteria of adherence (P = 0.001); in the postpartum, adherence declined to 20.6% (P = 0.002). In both groups, adherence rates by self-reporting were significantly higher as compared with pill counting (P = 0.001). In multivariate regression analysis, age >29 years (odds ratio [OR] 3.58, confidence interval [CI] 95% 0.10-0.75, P = 0.011), mean number of pills/day <6 (OR 2.53, CI 95% 1.07-6.01, P = 0.035), and being pregnant (OR 3.33, CI 95% 1.36-8.13, P = 0.008) were independently associated to greater adherence.

High levels of primary antiretroviral resistance genotypic mutations and B/F recombinants in Santos, Brazil.

This study characterized HIV-1 among antiretroviral-naïve populations presenting recent infection (RI) or long-standing infection (LSI). Sera collected from January 1999 to December 2001 at an anonymous HIV testing site in Santos, Brazil, were submitted to serologic testing algorithm for recent HIV seroconversion (STARHS). The STARHS methodology uses a combination of a sensitive and a less sensitive version of an anti-HIV enzyme immunoassay (EIA), and specimens found to be positive on the sensitive EIA and negative on the less sensitive EIA are considered to represent RI. HIV-1 V3 and pol regions of those with RI and LSI were compared. Antiretroviral resistance was defined solely by genotypic analysis. Ninety samples were evaluated representing those taken from an original cohort of 345 individuals, for whom adequate samples were available. Of 90 HIV-positive individuals, 25 presented RI. Cumulatively, 36.8% of those with RI and 25% of those with LSI presented resistance to at least one antiretroviral class. In the pol and V3 regions, 47% and 53% of those with RI presented clade B viruses and B/F recombinant viruses, respectively, whereas 56.2%, 41.7%, and 2.1% of those with LSI harbored clades B, B/F, and clade C viruses, respectively. Primary resistance and the prevalence of B/F recombinants was high in this population. Monitoring HIV-1 genetic diversity is important for developing vaccines and treatment strategies.

Efficacy of a program of prevention and control for methicillin-resistant Staphylococcus aureus infections in an intensive-care unit.

Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in most Brazilian Hospitals, and there are few studies which show the efficacy of control measures in such situations. This study evaluated intensive care unit (ICU) patients, in two years divided in control, intervention and post-intervention group. Intervention measures: hands-on educational programs for healthcare workers; early identification of MRSA infected or colonized patients, labeled with a bed-identification tag for contact isolation; nasal carriers, patients, and healthcare professionals treated with topical mupirocin for five days. The hospital infection rates in the control period were compared to the ones in the post-intervention period. Hospital infection rates were found by means of the NNISS methodology The incidence coefficients of MRSA hospital infection (monthly average of 1,000 pts/day) in the control, intervention and post-intervention groups were respectively: 10.2, 5.1 and 2.5/1,000 pts/day (p<0.001) and MRSA-originated bloodstream infections were 3.6, 0.9 and 1.8/1,000 central venous catheter/day (p=0.281). Nasal colonization in both intervention and post-intervention periods was of 30.9% and 22.1% among the hospitalized patients, respectively 54.4% and 46.1% of whom were already MRSA-positive when admitted to the unit. In the intervention period, most of those MRSA infected patients (76.2%) were nasal carrier. Mortality rates were, respectively 26.6%; 27.3% and 21.0% (p<0.001). Nasal carriers, both patients (93.7%) and healthcare professionals (88.2%), were successfully treated with topical mupirocin. Intervention measures for the prevention and control of MRSA infections in ICUs, have been efficient in the reduction of the bloodstream and MRSA-originated hospital infections incidence, and reduced the overall mortality rate significantly.

[Cost estimates of chronic hepatitis B virus for the Brazilian unified health system in 2005]. / Estimativas de custo da hepatite crônica B no sistema único de saúde Brasileiro em 2005.

BACKGROUND: Chronic Hepatitis B Virus (CHBV) is a disease that places a large financial burden on healthcare systems and society. OBJECTIVE: The aim of this study was to estimate patient management patterns, and associated medical resource utilization and expenses, for each of the four stages of chronic HBV infection in the public unified healthcare system settings, in 2005. METHODS. An expert panel comprised of ten physicians, leading specialists in hepatology and infectious diseases, was convened to obtain information regarding management of CHBV patients in Brazil. Expense inputs were mainly obtained from government fee schedules and pharmaceutical price tables. Costs were estimated under the perspective of the public health system. Data were analyzed using Windows SPSS version 12.0. RESULTS: Estimated patient expenses were calculated for the four stages of CHBV infection. The estimated annual expenses per patient were: R$ 980.89 (US$ 392) for chronic hepatitis B with no cirrhosis and without antiviral therapy; R$ 1,243.17 (US$ 496) for compensated cirrhosis without antiviral therapy; R$ 22,022.61 (US$ 8809) for decompensated cirrhosis; R$ 4,764.95 (US$ 1,905) for hepatocellular carcinoma; and R$ 87,372.60 (US$ 34,948) for liver transplant. CONCLUSION: Estimated expenses associated with drugs and procedures represented the main components of the expenses of CHBV infection. In this model, expenses increase dramatically as the disease progresses to more advanced stages, suggesting that over the long term delaying progression may reduce costs.

Universal Collection Medium (UCM) is as suitable as the Standard Transport Medium (STM) for Hybrid Capture II (HC-2) assay.

BACKGROUND: Collection of cervical-vaginal material in liquid media enables simultaneous evaluation of both oncologic cytology and molecular tests for the detection of Human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). Universal Collection Medium (UCM) has been developed to fulfill this objective. OBJECTIVES: To compare Hybrid Capture II (HC-2) to diagnose HPV, NG and CT in specimens collected in UCM and in the current Digene Standard Transport Medium (STM). STUDY DESIGN: The study was cross-sectional. Three collections of endocervical and ectocervical material were performed in each of 893 women referred for colposcopy in the following order: (1) to prepare a conventional Pap smear slide using the accompanying brush of the STM kit and with Ayre spatula; (2) for HC-2 test and liquid-based cytology using a 1 ml UCM vial as transport medium; material was collected with another similar brush; (3) for HC-2 test using a 1 ml STM vial as transport medium; material was collected with the same brush that we used in the procedure no. (1) (conventional Pap smear). HC-2 results from samples taken from STM and UCM media were compared by using simple linear regression analysis and Kappa statistic. RESULTS AND CONCLUSIONS: HC-2 results from the two media were highly correlated: high-risk HPV (kappa=0.92; r(2)=0.92), low-risk HPV (kappa=0.85; r(2)=0.86) and NG/CT (kappa=0.96; r(2)=0.81). Despite being obtained from a second specimen, the UCM HC-2 results were equivalent to those obtained with the standard medium STM and the UCM medium.

Nosocomial bloodstream infections caused by Klebsiella pneumoniae: impact of extended-spectrum beta-lactamase (ESBL) production on clinical outcome in a hospital with high ESBL prevalence.

BACKGROUND: The frequency of ESBL producing Klebsiella pneumoniae bloodstream infections (BSI) is high in Brazilian hospitals, however little is known regarding what role, if any, resistance plays in the expected outcome in hospitals with a high prevalence of these pathogens. METHODS: From 1996 to 2001, hospital acquired K. pneumoniae BSI were evaluated retrospectively. Each patient was included only once at the time of BSI. ESBL producing strains were identified using the E-test method. The association of variables with the mortality related to bacteremia was included in a stepwise logistic regression model. RESULTS: One hundred and eight hospital acquired K. pneumoniae BSI met criteria for inclusion. Fifty two percent were due to ESBL producing strains. The overall in-hospital mortality was 40.8%. Variables independently predicting death by multivariate analysis were the following: mechanical ventilation (p = 0.001), number of comorbidities (p = 0.003), antimicrobials prescribed before bacteremia (p = 0.01) and fatal underlying disease (p = 0.025). CONCLUSION: Bacteremia due to ESBL producing K. pneumoniae strains was not an independent predictor for death in patients with BSI. An increased mortality in hospital-acquired BSI by K. pneumoniae was related to the requirement for mechanical ventilation, more than two comorbidities, the previous use of two or more antibiotics, and the presence of a rapidly fatal disease.

Prevalence of IFNL3 gene polymorphism among blood donors and its relation to genomic profile of ancestry in Brazil.

The recent development of interferon-free regimens based on direct-acting antivirals for the treatment of chronic hepatitis C virus infection has benefited many but not all patients. Some patients still experience treatment failure, possibly attributed to unknown host and viral factors, such as IFNL3 gene polymorphism. The present study assessed the prevalence of rs12979860-CC, rs12979860-CT, and rs12979860-TT genotypes of the IFNL3 gene, and its relationship with ancestry informative markers in 949 adult Brazilian healthy blood donors. Race was analyzed using ancestry informative markers as a surrogate for ancestry. IFNL3 gene was genotyped using the ABI TaqMan single nucleotide polymorphisms genotyping assays. The overall frequency of rs12979860-CC genotype was 36.9%. The contribution of African ancestry was significantly higher among donors from the northeast region in relation to southeast donors, whereas the influence of European ancestry was significantly higher in southeast donors. Donors with rs12979860-CC and rs12979860-CT genotypes had similar ancestry background. The contribution of African ancestry was higher among rs12979860-TT genotype donors in comparison to both rs12979860-CC and rs12979860-CT genotypes. The prevalence of rs12979860-CC genotype is similar to that found in the US, despite the Brazilian ancestry informative markers admixture. However, in terms of ancestry, rs12979860-CT genotype was much closer to rs12979860-CC individuals than to rs12979860-TT.