Resumo em Inglês:

Background: Molecular tests allow the detection of high-risk human papillomavirus in cervical samples, playing an important role in the prevention of cervical cancer. Objectives: We performed a study to determine the prevalence of HPV 16, HPV 18 and other high-risk human papillomavirus (pool 12 genotypes) in Peruvian females from diverse urban areas using the cobas 4800 HPV test. Methods: Routine cervical samples collected in our laboratory were analyzed by cobas 4800 HPV test. Results: A total of 2247 samples from female patients aged 17–79 years were tested. high-risk human papillomavirus was positive in 775 (34.49%) samples. Of these, 641 (82.71%) were single infections and 134 (17.29%) were multiple infections. The positivity rates for HPV 16, HPV 18, and other high-risk human papillomavirus were 10.77%, 2.0%, and 28.08%, respectively. In multiple high-risk human papillomavirus infections, the concomitance of HPV 16 and other high-risk human papillomavirus was more prevalent (13.42%). Conclusion: Our study showed high prevalence of high-risk human papillomavirus in urban Peru, mainly among young women. In both single and multiple infections other high-risk human papillomavirus were more prevalent than HPV 16 and HPV 18, which might influence vaccine impact in our country. Furthermore, the cobas 4800 HPV test may be considered a useful tool for HPV molecular diagnosis.

Resumo em Inglês:

Objectives: A cross-sectional study on prevalence of HBV and HDV infection, risk factors and genotype distribution of HBV infection was conducted among 848 HIV-infected patients in Mato Grosso do Sul, Central Brazil. Methods: Serum samples of 848 participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis surface antibody (anti-HBs). HBsAg positive samples were tested for anti-HBc IgM, HBeAg, anti-HBe, anti-HCV, and total anti-HDV. HBsAg and anti-HBc positive were subjected to DNA extraction. Viral DNA was amplified by semi-nested PCR for the regions pre-S/S and then purified and genotyped/subgenotyped by direct sequencing. Student's t-test, chi-square test and Fisher's exact test were used to compare variables and to evaluate association between HBV positivity (defined as anti-HBc and/or HBsAg positivity) and risk factors. Results: Among the 848 HIV infected patients investigated 222 had serological markers of HBV infection. The prevalence rate of HIV-HBV coinfection was 2.5% (21/848; 95% CI: 1.4–3.5%); 484 (57.1%) patients were susceptible for HBV infection. There were no cases of anti-HDV positive and only one (0.1%) anti-HCV-positive case among the HIV-HBV coinfected patients. Male gender, increasing age, family history of hepatitis, use of illicit drug, and homosexual activity were independent factors associated with HBV exposure. The phylogenetic analysis based on the S gene region revealed the presence of genotypes D (76.9%), F (15.4%) and A (7.7%) in the study sample. Conclusion: This study demonstrates the low prevalence of HIV-HBV infection and also highlights the need for early vaccination against HBV as well as testing for HBV, HCV and HDV in all HIV-infected individuals.

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Objective: This study aims to assess the nutritional status of selenium, copper and zinc; and also the erythrocyte superoxide dismutase activity of HIV-infected children compared to a control group. Methods: A cross-sectional study was carried out with prepubertal HIV-infected children (n = 51) and their healthy siblings (n = 32). All biochemical measurements including plasma selenium, serum copper levels, serum and erythrocyte zinc levels and erythrocyte super-oxide dismutase activity were evaluated according to dietary, clinical and biochemical parameters. Results: Compared to the control group, the HIV-infected children had lower z-score values for height-for-age (p = 0.0006), higher prevalence of stunting (11.8%) (p = 0.047), lower selenium levels (p = 0.0006) and higher copper levels (p = 0.019). No difference was found concerning superoxide dismutase activity (p > 0.05). The HIV-infected group presented a higher proportion (45.1%) of children with zinc intakes below the estimated average requirement (p = 0.014); however, no association with zinc biochemical parameters was found. Conclusion: HIV-infected children have an inadequate selenium and copper nutritional status, which could influence the progression to AIDS. An adequate micronutrient status could improve the clinical conditions in these patients and minimize free radical production and cellular oxidative stress.

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Background: This study performed at the National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran, aimed to evaluate the effect of concomitant pulmonary hypertension on the outcome of pulmonary tuberculosis. Methods: New cases of pulmonary tuberculosis were recruited for the study. Pulmonary hypertension was defined as systolic pulmonary arterial pressure ≥35 mm Hg estimated by transthoracic Doppler echocardiography. We assessed the relationship between pulmonary hypertension and mortality during the six-month treatment of tuberculosis. Results: Of 777 new cases of pulmonary tuberculosis, 74 (9.5%) had systolic pulmonary arterial pressure ≥35 mm Hg. Ten of them (13.5%) died during treatment compared to 5% of cases with pulmonary arterial pressure less than 35 mm Hg (p = 0.007). Logistic regression analysis showed that pulmonary hypertension and drug abuse remained independently associated with mortality (OR = 3.1; 95% CI: 1.44–6.75 and OR = 4.4; 95% CI: 2.35–8.17, respectively). Conclusion: A significant association was found between mortality and presence of pulmonary hypertension and drug abuse among new cases of pulmonary tuberculosis.

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Background: The timing of highly active antiretroviral therapy (HAART) after a tuberculosis diagnosis in HIV-infected patients can affect clinical outcomes and survival. We compared survival after tuberculosis diagnosis in HIV-infected adults who initiated HAART and tuberculosis therapy simultaneously to those who delayed the start of HAART for at least two months. Methods: The THRio cohort includes 17,983 patients receiving HIV care in 29 public clinics in Rio de Janeiro, Brazil. HAART-naïve patients at the time of a new TB diagnosis between September 2003 and June 2008 were included. Survival was measured in days from diagnosis of TB. We compared survival among patients who initiated HAART within 60 days of TB treatment (simultaneous – ST) to those who started HAART >60 days of TB treatment or never started (deferred – DT). Kaplan–Meier plots and Cox proportional hazards regression analyses were conducted. Results: Of 947 patients diagnosed with TB, 572 (60%) were HAART naïve at the time of TB diagnosis; 135 were excluded because of missing CD4 count results. Among the remaining 437 TB patients, 56 (13%) died during follow-up: 25 (10%) among ST patients and 31 (16%) in DT group (p = 0.08). ST patients had lower median CD4 counts at TB diagnosis than DT patients (106 vs. 278, p < 0.001). Cox proportional hazards utilizing propensity score analysis showed that DT patients were more likely to die (adjusted HR = 1.89; 95% CI: 1.05–3.40; p = 0.03). Conclusion: HAART administered simultaneously with TB therapy was associated with improved survival after TB diagnosis. HAART should be given to patients with HIV-related TB as soon as clinically feasible.

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Objective: To evaluate whether or not highly active antiretroviral therapy is associated with carotid artery stiffness in human immunodeficiency virus-positive patients in Henan Province, China. Method: Fifty human immunodeficiency virus-positive patients with at least a 5-year history of highly active antiretroviral therapy use and 50 human immunodeficiency virus-positive patients without a history of highly active antiretroviral therapy use were enrolled in this study. Carotid artery intima-media thickness and stiffness were determined by quantitative inter-media thickness and quantitative artery stiffness, respectively. Results: No statistically significant difference in carotid artery intima-media thickness and stiffness was observed between groups. A significant association between human immunodeficiency virus infection time and carotid artery stiffness was observed, but no significant association between human immunodeficiency virus infection time and intima-media thickness was found. No significant association between intima-media thickness, stiffness, and CD4+ and CD8+ T-cell counts were observed. Conclusion: The first-line highly active antiretroviral therapy currently used in China is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients with good highly active antiretroviral therapy compliance. Human immunodeficiency virus may play a role in the development of atherosclerosis.

Resumo em Inglês:

Background: Intracranial abscesses are associated with high mortality. Staphylococcus aureus is one of the main pathogens that cause intracranial infection. Until now, there is no report to identify the key effectors of S. aureus during the intracranial infection. Methods: The murine intracranial abscesses model induced by S. aureuswas constructed. The vital sign and survival rate of mice were observed to evaluate the infection. Histological examination was used to diagnose the pathological alterations of mouse tissues. The sensitivity of S. aureus to whole blood was evaluated by whole-blood killing assay. Results: In murine intracranial abscesses model, it was shown that the mortality caused by the accessory gene regulator (agr) locus deficient strain was significant decreased compared with its parent strain. Moreover, we found that RNAIII, the effector of agr system, was essential for the intracranial infection caused by S. aureus. In the further investigation, it was shown that restoration the expression of α-toxin in agr deficient strain could partially recover the mortality in the murine intracranial abscesses model. Conclusion: Our data suggested that the agr system of S. aureus is an important virulence determinant in the induction and mortality of intracranial abscesses in mice.

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Introduction: A population-based survey conducted in Brazilian capital cities found that only 16% of the population had ever been tested for hepatitis C. These data suggest that much of the Brazilian population with HCV infection remains undiagnosed. The distribution of age ranges at diagnosis and its association with the degree of hepatitis C are still unknown in Brazilian patients. Material and methods: Patients with HCV infection, diagnosed by HCV RNA (Amplicor-HCV, Roche), were included in the study. Patients with HBV or HIV coinfection, autoimmune diseases, or alcohol intake > 20 g/day were excluded. HCV genotyping was performed by sequence analysis, and viral load by quantitative RT-PCR (Amplicor, Roche). The METAVIR classification was used to assess structural liver injury. The Chi-square (χ2) test and student's t-test were used for between-group comparisons. Spearman's rank correlation coefficient were used for analysing the correlation between parameters. Results: A total of 525 charts were reviewed. Of the patients included, 49.5% were male, only 10% of the patients were aged less than 30 years; peak prevalence of HCV infection occurred in the 51-to-60 years age range. Genotype 1 accounted for 65.4% of the cases. Information on HCV subtype was obtained in 227 patients; 105 had subtype 1a and 122 had 1b. According to the degree of structural liver injury, 8.3% had F0, 23.4% F1, 19.8% F2, 11.9% F3, and 36.5% F4. Age at diagnosis of hepatitis correlated significantly with fibrosis (rs = 0.307, p < 0.001). The degree of fibrosis increased with advancing age. Only age at diagnosis and fasting blood glucose were independently associated with disease stage. Those patients with subtype 1a had higher prevalence of F2–F4 than those with subtype 1b. Conclusion: In Brazil, diagnosis of hepatitis C is more commonly established in older patients (age 45–60 years) with more advanced disease. Reassessment of strategies for hepatitis C diagnosis in the country is required.

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Since antimicrobial resistance among uropathogens against current first line agents has affected the management of severe urinary tract infection, we determined the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem) commonly prescribed as initial empirical treatment of inpatients with severe community acquired urinary tract infections. Minimum inhibitory concentration determination by Etest was performed for 205 Brazilian community urinary tract infection Escherichia coli strains from 2008 to 2012 and 74 E. coli bloodstream strains recovered from a surveillance study. Pharmacodynamic exposure was modeled via a 5000 subject Monte Carlo simulation. All isolates were susceptible to ertapenem and meropenem. Piperacillin/tazobactam, ceftriaxone and ciprofloxacin showed 100%, 97.5% and 83.3% susceptibility among outpatient isolates and 98.6%, 75.7% and 64.3% among inpatient isolates, respectively. Against outpatient isolates, all drugs except ciprofloxacin (82.7% in aggressive and 77.6% in conservative scenarios) achieved high cumulative fraction of response: car-bapenems and piperacillin/tazobactam cumulative fraction of responses were close to 100%, and ceftriaxone cumulative fraction of response was 97.5%. Similar results were observed against inpatients isolates for carbapenems (100%) and piperacillin/tazobactam (98.4%), whereas ceftriaxone achieved only 76.9% bactericidal cumulative fraction of response and ciprofloxacin 61.9% (aggressive scenario) and 56.7% (conservative scenario) respectively. Based on this model, standard doses of beta-lactams were predicted to deliver sufficient pharmacodynamic exposure for outpatients. However, ceftriaxone should be avoided for inpatients and ciprofloxacin empirical prescription should be avoided in both inpatients and outpatients with complicated urinary tract infection.

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Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran) after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.

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With the advances in surgical treatment, antibiotic therapy and the current resources for accurate diagnosis and differentiated approaches to each type of osteomyelitis, better results are being obtained in the treatment of this disease. After a careful literature review carried out by a multiprofessional team, some conclusions were made in order to guide medical approach to different types of osteomyelitis, aiming to obtain better clinical outcomes and reducing the social costs of this disease. Acute and chronic osteomyelitis are discussed, with presentation of the general epidemiological concepts and the commonly used classification systems. The main guidelines for the clinical, laboratory and imaging diagnosis of infections are discussed, as well as the guidelines for surgical and antimicrobial treatments, and the role of hyperbaric oxygen as adjuvant therapy.

Resumo em Inglês:

Introduction: The human hepatitis B virus causes acute and chronic hepatitis and is considered one of the most serious human health issues by the World Health Organization, causing thousands of deaths per year. There are similar viruses belonging to the Hepadnaviridae family that infect non-human primates and other mammals as well as some birds. The majority of non-human primate virus isolates were phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial. However, there is a possibility that human hepatitis B virus originated in primates. Knowing whether these viruses might be common to humans and primates is crucial in order to reduce the risk to humans. Objective: To review the existing knowledge about the evolutionary origins of viruses of the Hepadnaviridae family in primates. Methods: This review was done by reading several articles that provide information about the Hepadnaviridae virus family in non-human primates and humans and the possible origins and evolution of these viruses. Results: The evolutionary origin of viruses of the Hepadnaviridae family in primates has been dated back to several thousand years; however, recent analyses of genomic fossils of avihepadnaviruses integrated into the genomes of several avian species have suggested a much older origin of this genus. Conclusion: Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the '90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly B virus in basal sister-relationship to the Old monkey human hepatitis World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate hosts because of the proximity between the phylogeny of Old and New World non-human primate and their human hepatitis B virus variants. The importance of further research, related to the subject in South American wild fauna, is paramount and highly relevant for understanding the origin of human hepatitis B virus.

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Several studies have demonstrated that piperacillin/tazobactam produces a false-positive result for the galactomannan antigen test. However, the most recent literature has demonstrated that this interaction is no longer a concern. There is little information regarding the drug–laboratory interaction with the generics of piperacillin/tazobactam or other broad-spectrum beta-lactams, such as ceftaroline, doripenem, imipenem/cilastatin, and meropenem. The purpose of this study was to determine if a drug–laboratory interaction exists with these antibiotics. Tests showed that one lot of imipenem/cilastatin by Hospira Healthcare India Private Limited produced a false-positive result for the galactomannan antigen test. All other medications tested, including piperacillin/tazobactam from seven manufacturers and imipenem/cilastatin by Hospira Inc., did not produce positive results. Since the reason for this drug–laboratory interaction with imipenem/cilastatin is unknown, more studies are needed to further investigate this interaction. Providers also should be educated of these findings: no drug–laboratory interaction with piperacillin/tazobactam and a possible drug–laboratory interaction with imipenem/cilastatin (Hospira Healthcare India Private Limited).

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Oligoadenylate synthetases play an important role in the immune response against dengue virus. Single nucleotide polymorphisms in the oligoadenylate synthetases genes are known to affect oligoadenylate synthetases activity and are associated with outcome of viral infections. Polymorphisms in the OAS1 SNPs (rs1131454), OAS2 SNPs (rs1293762, rs15895 and rs1732778) and OAS3 SNPs (rs2285932 and rs2072136) genes were studied using PCR followed by restriction fragment length polymorphism methods in 30 patients for dengue infection and 40 control group who have no documented evidence of symptomatic dengue. An increase in the frequency of OAS2 gene rs1293762 SNP G/T heterozygotes (p = 0.012), decrease in the frequency of SNP G/G homozygotes (p = 0.005) and decrease in the frequency of OAS2 gene rs1732778 SNP G/G homozygotes (p = 0.000017) and A/A homozygotes (p = 0.0000012) were observed among the dengue patients compared with control group. Our results suggest that OAS2 haplotypes are associated with differential susceptibility to clinical outcomes of dengue virus infection.

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The aim of this study was to investigate the immunomodulatory properties of cell wall extract from Enterococcus faecalis CECT7121, measuring the induction of cytokines TNF-α, IL-6, IL-10 and IL-12 from human peripheral blood mononuclear cells (PBMCs). Cell wall extract was prepared from their growth in brain heart infusion broth (18 h, 35 °C). Subsequently, toxicity of the obtained cell wall extract was tested in Balb-C mice. PBMCs were isolated from buffy coats at the Blood Transfusion Service of Hospital Ramón Santamarina (Tandil, Argentina). PBMCs were purified using standard Ficoll-Paque gradient centrifugation. Aliquots of purified leukocytes were incubated at 37 °C for 24 h with heat-killed E. faecalis CECT7121 and cell wall extract. Concentrations of IL-6, TNF-α, IL-10 and IL-12 (p70) were measured by solid phase sandwich ELISA. Changes in appearance and behavior of mice were evidenced only in the group with the maximal concentration of wall cell extract used (10,000 μg). Cell wall extract and heat-killed E. faecalisCECT7121 induced the production of significantly higher amounts of Il-12, IL-6, TNF-α and IL-10 cytokines compared to the nonstimulated PBMCs. These findings provide helpful information on immunomodulation activity by cell wall extract in sight of the application of this compound in controlling certain infectious diseases.

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In this paper a disseminated persistent Nocardia cyriacigeorgicainfection in an immunocompetent patient is described. The patient's long-term treatment, as well as its implications for managing similar cases in the future, is emphasized. Presenting with high fever, multiple nodules, and ulcerative cutaneous lesions of body sites, the patient was treated with various antimicrobials. Under combined therapy, empyema and arthritis, leading to disseminated nocardiosis, were seen. The overall treatment course was 28 months. It can be concluded that the choice of the antibiotics and optimal duration of treatment are uncertain; therefore the treatment of nocardiosis requires expertise.

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Rothia aeria is an uncommon pathogen mainly associated with endocarditis in case reports. In previous reports, endocarditis by R. aeria was complicated by central nervous system embolization. In the case we report herein, endocarditis by R. aeria was diagnosed after acute self-limited diarrhea. In addition to the common translocation of R. aeria from the oral cavity, we hypothesize the possibility of intestinal translocation. Matrix-assisted laser desorption ionization-time of flight mass spectrometry and genetic sequencing are important tools that can contribute to early and more accurate etiologic diagnosis of severe infections caused by Gram-positive rods.

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Malaria is endemic in the North of Brazil. However, Hyperreactive Malarious Splenomegaly (HMS) has been rarely described. Splenomegaly in HIV/Aids infection has a large differential diagnosis, but malaria is a cause of gross splenomegaly, regardless of the HIV status. In this paper, we report the case of a 50-year-old man, HIV positive, with massive splenomegaly and multiple malaria infections in the past. He fulfilled the criteria for HMS, received a short course of anti-malarial treatment and weekly quimioprofilatic Chloroquine. In 9 months, he had great clinical and laboratorial improvement confirming the HMS, a rare diagnosis in Brazil.