HSV-1-derived amplicon vectors: recent technological improvements and remaining difficulties - a review

Amplicons are defective and non-integrative vectors derived from herpes simplex virus type 1. As the vector genome carries no virus genes, amplicons are both non-toxic for the infected cells and non-pathogenic for the inoculated organisms. In addition, the large transgenic capacity of amplicons, which allow delivery of up to 150 Kbp of foreign DNA, makes these vectors one of the most powerful, interesting and versatile gene delivery platforms. We present here recent technological developments that have significantly improved and extended the use of amplicons, both in cultured cells and in living organisms. In addition, this review also discusses the many difficulties still pending to be solved, in order to achieve stable and physiologically regulated transgene expression.

Ambivalent implications of health care information systems: a study in the Brazilian public health care system

This article evaluates social implications of the "SIGA" Health Care Information System (HIS) in a public health care organization in the city of São Paulo. The evaluation was performed by means of an in-depth case study with patients and staff of a public health care organization, using qualitative and quantitative data. On the one hand, the system had consequences perceived as positive such as improved convenience and democratization of specialized treatment for patients and improvements in work organization. On the other hand, negative outcomes were reported, like difficulties faced by employees due to little familiarity with IT and an increase in the time needed to schedule appointments. Results show the ambiguity of the implications of HIS in developing countries, emphasizing the need for a more nuanced view of the evaluation of failures and successes and the importance of social contextual factors.

Professional and community satisfaction with the Brazilian family health strategy

OBJECTIVE: To analyze the strengths and limitations of the Family Health Strategy from the perspective of health care professionals and the community. METHODS: Between June-August 2009, in the city of Vespasiano, Minas Gerais State, Southeastern Brazil, a questionnaire was used to evaluate the Family Health Strategy (ESF) with 77 healthcare professionals and 293 caregivers of children under five. Health care professional training, community access to health care, communication with patients and delivery of health education and pediatric care were the main points of interest in the evaluation. Logistic regression analysis was used to obtain odds ratios and 95% confidence intervals as well as to assess the statistical significance of the variables studied. RESULTS: The majority of health care professionals reported their program training was insufficient in quantity, content and method of delivery. Caregivers and professionals identified similar weaknesses (services not accessible to the community, lack of healthcare professionals, poor training for professionals) and strengths (community health worker-patient communications, provision of educational information, and pediatric care). Recommendations for improvement included: more doctors and specialists, more and better training, and scheduling improvements. Caregiver satisfaction with the ESF was found to be related to perceived benefits such as community health agent household visits (OR 5.8, 95%CI 2.8;12.1), good professional-patient relationships (OR 4.8, 95%CI 2.5;9.3), and family-focused health (OR 4.1, 95%CI 1.6;10.2); and perceived problems such as lack of personnel (OR 0.3, 95%CI 0.2;0.6), difficulty with access (OR 0.2, 95%CI 0.1;0.4), and poor quality of care (OR 0.3, 95%CI 0.1;0.6). Overall, 62% of caregivers reported being generally satisfied with the ESF services. CONCLUSIONS: Identifying the limitations and strengths of the Family Health Strategy from the healthcare professional and caregiver perspective may serve to advance primary community healthcare in Brazil.

Prevalence and determinants of child undernutrition and stunting in semiarid region of Brazil

OBJECTIVE : To analyze the evolution in the prevalence and determinants of malnutrition in children in the semiarid region of Brazil. METHODS : Data were collected from two cross-sectional population-based household surveys that used the same methodology. Clustering sampling was used to collect data from 8,000 families in Ceará, Northeastern Brazil, for the years 1987 and 2007. Acute undernutrition was calculated as weight/age < -2 standard deviation (SD); stunting as height/age < -2 SD; wasting as weight/height < -2 SD. Data on biological and sociodemographic determinants were analyzed using hierarchical multivariate analyses based on a theoretical model. RESULTS : A sample of 4,513 and 1,533 children under three years of age, in 1987 and 2007, respectively, were included in the analyses. The prevalence of acute malnutrition was reduced by 60.0%, from 12.6% in 1987 to 4.7% in 2007, while prevalence of stunting was reduced by 50.0%, from 27.0% in 1987 to 13.0% in 2007. Prevalence of wasting changed little in the period. In 1987, socioeconomic and biological characteristics (family income, mother’s education, toilet and tap water availability, children’s medical consultation and hospitalization, age, sex and birth weight) were significantly associated with undernutrition, stunting and wasting. In 2007, the determinants of malnutrition were restricted to biological characteristics (age, sex and birth weight). Only one socioeconomic characteristic, toilet availability, remained associated with stunting. CONCLUSIONS : Socioeconomic development, along with health interventions, may have contributed to improvements in children’s nutritional status. Birth weight, especially extremely low weight (< 1,500 g), appears as the most important risk factor for early childhood malnutrition.

Consumption of alcoholic beverages, driving vehicles, a balance of dry law, Brazil 2007-2013

The study analyzes the trend in frequency of adults who drive under the influence of alcohol in major Brazilian cities after the passing of laws, which prohibit drunk driving. Data from the Surveillance System for Risk and Protective Factors for Chronic Diseases by Telephone Survey (VIGITEL) between 2007 and 2013 were analyzed. The frequency of adults who drove after abusive alcohol consumption was reduced by 45.0% during this period (2.0% in 2007 to 1.1% in 2013). Between 2007 and 2008 (-0.5%) and between 2012 and 2013 (-0.5%), significant reductions were observed in the years immediately after the publication of these laws that prohibit drunk driving. These improvements towards the control of drunk driving show a change in the Brazilian population’s lifestyle.

Correlation between specific IgM levels and percentage IgG-class antibody avidity to Toxoplasma gondii

Toxoplasmosis is an usually asymptomatic worldwide disseminated infection. In its congenital presentation it may lead to abortion or fetal malformations. Antenatal evaluation is considered of paramount importance to identify seronegative women and allow for prophylaxis. Recent improvements in sensitivity of IgM tests has made IgM detection an extremely protracted acute phase marker, and IgG avidity evaluation test became necessary. Observation has shown that a correlation can be established between IgM levels and avidity percentages, suggesting that frequently the avidity test may not be necessary. In this study we analyzed Toxoplasma gondii IgM levels of 202 samples and their IgG avidity percentages, in order to define specific levels whose IgM quantification could by itself define serodiagnosis and therefore make the avidity evaluation unnecessary. We showed that for IgM levels bellow 2.0 and above 6.0 serodiagnosis of toxoplasmosis could be established without need of IgG avidity test. IgM levels between these two parameters are associated with varying avidity indexes highlighting the importance of its evaluation as a means to confirm toxoplasmosis. Following this demonstration it was possible to avoid the avidity test for 75% of the cases, to reduce the turnaround time and to reduce costs.

THE EFFECT OF HOOKWORM INFECTION AND URINARY SCHISTOSOMIASIS ON BLOOD HEMOGLOBIN CONCENTRATION OF SCHOOLCHILDREN LIVING IN NORTHERN MOZAMBIQUE

This study aims to assess the association between schistosomiasis and hookworm infection with hemoglobin levels of schoolchildren in northern Mozambique. Through a cross-sectional survey, 1,015 children from five to 12 years old in the provinces of Nampula, Cabo Delgado and Niassa were studied. Hookworm infection and urinary schistosomiasis were diagnosed, through Ritchie and filtration methods, with a prevalence of 31.3% and 59.1%, respectively. Hemoglobin levels were obtained with a portable photometer (Hemocue®). The average hemoglobin concentration was 10.8 ± 1.42 g/dL, and 62.1% of the children presented levels below 11.5 g/dL, of which 11.8% of the total number of children had hemoglobin levels below 9 g/dL. A multiple linear regression analysis demonstrated negative interactions between hemoglobin levels and ancylostomiasis, this being restricted to the province of Cabo Delgado (β = -0.55; p < 0.001) where an independent interaction between hemoglobin levels and urinary schistosomiasis was also observed (β = -0.35; p = 0.016). The logistical regression model indicated that hookworm infection represents a predictor of mild (OR = 1.87; 95% CI = 1.17-3.00) and moderate/severe anemia (OR = 2.71; 95% CI = 1.50 - 4.89). We concluded that, in the province of Cabo Delgado, hookworm and Schistosoma haematobium infections negatively influence hemoglobin levels in schoolchildren. Periodical deworming should be considered in the region. Health education and improvements in sanitary infrastructure could achieve long-term and sustainable reductions in soil-transmitted helminthiases and schistosomiasis prevalence rates.

Nutritional assessment and lipid profile in HIV-infected children and adolescents treated with highly active antiretroviral therapy

INTRODUCTION: HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART) regimens that include a protease inhibitor (PI) can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336), and 136 (63 - 271) versus control group: 54.5 (20 - 162); p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58) and 36 (23 - 43); control 49.5 (34 - 69); p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.

Cases distribution of leptospirosis in City of Manaus, State of Amazonas, Brazil, 2000-2010

INTRODUCTION: Leptospirosis is an infectious disease caused by microorganisms of the genus Leptospira that affects several species of animals, including the human beings. The study described the confirmed cases of leptospirosis in Manaus, from 2000 to 2010. METHODS: A descriptive study based on secondary data analysis of Secretaria Municipal de Saúde (SEMSA), Sistema de Informação de Agravos de Notificação SINAN and Sistema de Informação sobre Mortalidade (SIM) analyzing the variables: age group, gender, clinical aspects and geographic area and lethality. RESULTS: Were reported 665 cases of leptospirosis, 339 were confirmed and 35 (10.3%) died. The largest number of cases occurred in May (16.8%), March (13.3%) and April (11.4%), a period of intense rainfall. The city areas with the greatest occurrence of the disease were South (26.6%), West (23.5%) and East (19.7%), areas of the greatest precariousness socio-environment. The largest number of cases, including deaths, occurred in the age group from 14 to 44.9 years (74%), being that 291 (85.8%) were male and 48 (14.1%) females. The most frequent symptoms were fever, myalgia, headache and jaundice. In relation to the social conditions were identified low education, poor housing, absence of sanitation and low income. CONCLUSIONS: In Manaus, despite the implementation of the Social and Environmental Program of Igarapés of Manaus (PROSAMIM), there are still areas that need a proper urbanization and improvements in socio-environmental conditions, reducing the level of exposure of the human beings that living in these locations.

Rapid detection and differentiation of mycobacterial species using a multiplex PCR system

Introduction The early diagnosis of mycobacterial infections is a critical step for initiating treatment and curing the patient. Molecular analytical methods have led to considerable improvements in the speed and accuracy of mycobacteria detection. Methods The purpose of this study was to evaluate a multiplex polymerase chain reaction system using mycobacterial strains as an auxiliary tool in the differential diagnosis of tuberculosis and diseases caused by nontuberculous mycobacteria (NTM) Results Forty mycobacterial strains isolated from pulmonary and extrapulmonary origin specimens from 37 patients diagnosed with tuberculosis were processed. Using phenotypic and biochemical characteristics of the 40 mycobacteria isolated in LJ medium, 57.5% (n=23) were characterized as the Mycobacterium tuberculosis complex (MTBC) and 20% (n=8) as nontuberculous mycobacteria (NTM), with 22.5% (n=9) of the results being inconclusive. When the results of the phenotypic and biochemical tests in 30 strains of mycobacteria were compared with the results of the multiplex PCR, there was 100% concordance in the identification of the MTBC and NTM species, respectively. A total of 32.5% (n=13) of the samples in multiplex PCR exhibited a molecular pattern consistent with NTM, thus disagreeing with the final diagnosis from the attending physician. Conclusions Multiplex PCR can be used as a differential method for determining TB infections caused by NTM a valuable tool in reducing the time necessary to make clinical diagnoses and begin treatment. It is also useful for identifying species that were previously not identifiable using conventional biochemical and phenotypic techniques.

Occurrence and sensitivity profile of extended spectrum beta-lactamase-producing Enterobacteriaceae at a tertiary hospital in Southern Brazil

Abstract: INTRODUCTION: Nosocomial infections are closely associated with antimicrobial drug resistance. One of the most important mechanisms of resistance to β-lactam antibiotics is the production of extended spectrum β-lactamases (ESBLs). The objective of the present study was to evaluate the prevalence and antimicrobial susceptibility profile of ESBL-producing strains and to assess the evolution of antimicrobial drug resistance between 2007 and 2013 at the Hospital São Vicente de Paulo, Passo Fundo, State of Rio Grande do Sul, Brazil. METHODS: We conducted a descriptive, observational, cross-sectional study. Bacterial culture was performed from January to December 2013. The antimicrobial susceptibility profile of these cultures was determined using the disk diffusion method. Phenotypic screening for ESBL production was performed using the disk approximation method. RESULTS : We analyzed a total of 19,112 cultures, 11.5% of which were positive for Enterobacteriaceae. Of these, 30.3% of the isolates were positive for ESBL production, and the most prevalent species was Klebsiella sp. (37.5%). Over 95% of these isolates showed reduced susceptibility to all cephalosporins, aztreonam, and amoxicillin/clavulanic acid. The isolates also showed high sensitivity to the following antimicrobials: amikacin, meropenem, and piperacillin/tazobactam. Overall, the resistance rates among ESBL-producing Enterobacteriaceae decreased from 2007 to 2013. CONCLUSIONS : In our hospital, the increased sensitivity to certain antimicrobial agents seems to be directly related to the implementation of improvements in the methods to prevent and control nosocomial infections in addition to the natural development of other resistance mechanisms.

Epidemiology of infectious meningitis in the State of Amazonas, Brazil

INTRODUCTION: In the State of Amazonas, particularly in the capital Manaus, meningitis has affected populations of different cultures and social strata over the years. Bacterial meningitis is caused by several different species and represents a major issue of public health importance. The present study reports the meningitis case numbers with different etiologies in Amazonas from January 1976 to December 2012. METHODS: Since the 1970s, the (currently named) Tropical Medicine Foundation of Doutor Heitor Vieira Dourado [Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD)] has remained a reference center in Amazonas for the treatment of meningitis through the diagnosis and notification of cases and the confirmation of such cases using specific laboratory tests. RESULTS: The foundation has achieved coverage of over 90% of the state medical records for many years. Between 1990 and 2012, meningitis cases caused by Haemophilus influenzae decreased with the introduction of the H. influenzae vaccine. Meningococcal disease previously had a higher frequency of serogroup B disease, but starting in 2008, the detection of serogroup C increased gradually and has outpaced the detection of serogroup B. Recently, surveillance has improved the etiological definition of viral meningitis at FMT-HVD, with enteroviruses, Epstein-Barr virus (EBV) and varicella zoster virus (VZV) prevailing in this group of pathogens. With the advent of acquired immunodeficiency syndrome (AIDS), cryptococcal meningitis has become an important disease in Amazonas. Additionally, infectious meningitis is an important burden in the State of Amazonas. CONCLUSIONS: Changes in the epidemiological profile for the different etiology-defined cases are the result of continuous epidemiological surveillance and laboratory capacity improvements and control measures, such as Haemophilus influenzae vaccination.

Prognostic factors influencing morbidity and mortality in esophageal carcinoma

PURPOSE: In 1980, operative mortality for esophageal resection was 29%. Over the last 15 years, technical and critical care improvements contributed to the reduction of postoperative mortality rate to 8%. The aim of this study is to analyze retrospectively the role of different factors (surgical procedure, stage of the disease, and anesthetic risk) on the postoperative mortality of 63 patients that underwent esophagectomy with gastric interposition for cancer. METHODS: Seventy-two patients underwent esophagectomy. The stomach was the esophageal substitute in 63 cases. Surgical procedures included transthoracic esophagectomy in 49 patients and transhiatal esophagectomy in 14 cases. Among the 49 transthoracic esophagectomy patients, there were 18 patients with a high anesthetic risk (ASA III). Among the patients that underwent transhiatal esophagectomy, there were 10 patients with a high anesthetic risk (ASA III). RESULTS: The operative mortality rate was 14% (2/14) in transhiatal esophagectomy group and 22% (11/49) in transthoracic esophagectomy group (P = ns). The postoperative mortality of patients with a high anesthetic risk (ASA III) was 47% (8/17) after transthoracic esophagectomy and 10% (1/10) after transhiatal esophagectomy (P <0.05). DISCUSSION: In our experience, the operative mortality was nearly 18% (16.6% after transhiatal esophagectomy and 20.8% after transthoracic esophagectomy). Among the patients with a high anesthetic risk (ASA III) that underwent surgery, the postoperative mortality was significantly lower after transhiatal esophagectomy (10%) compared to transthoracic esophagectomy (47%) (P <0.05).

Critical analysis of the allocation policy for liver transplantation in Brazil

Liver transplantation is now the standard treatment for end-stage liver disease. Given the shortage of liver donors and the progressively higher number of patients waiting for transplantation, improvements in patient selection and optimization of timing for transplantation are needed. Several solutions have been suggested, including increasing the donor pool; a fair policy for allocation, not permitting variables such as age, gender, and race, or third-party payer status to play any role; and knowledge of the natural history of each liver disease for which transplantation is offered. To observe ethical rules and distributive justice (guarantee to every citizen the same opportunity to get an organ), the "sickest first" policy must be used. Studies have demonstrated that death has no relationship with waiting time, but rather with the severity of liver disease at the time of inclusion. Thus, waiting time is no longer part of the United Network for Organ Sharing distribution criteria. Waiting time only differentiates between equally severely diseased patients. The authors have analyzed the waiting list mortality and 1-year survival for patients of the State of São Paulo, from July 1997 through January 2001. Only the chronological criterion was used. According to "Secretaria de Estado da Saúde de São Paulo" data, among all waiting list deaths, 82.2% occurred within the first year, and 37.6% within the first 3 months following inclusion. The allocation of livers based on waiting time is neither fair nor ethical, impairs distributive justice and human rights, and does not occur in any other part of the world.

Trends in male contraception

Methods that are available for male contraception, namely coitus interruptus, condoms, and vasectomy, have been used since the 19th century. With the exceptions of a few improvements of these methods, no major progress has been made with respect to introducing new male contraceptives since then. It is extremely urgent to develop new, safe, effective, and reversible male contraceptive methods. Among all male contraceptive methods that are being investigated, the hormonal approach is the closest to clinical application. Hormonal contraception provides pregnancy protection by means of spermatogenic suppression. Androgen-progestin regimens currently represent the best available hormonal combination for induction of a profound suppression of spermatogenesis. Further development of new steroids is mandatory for increasing the choices of available contraceptive formulations and to optimize long-term safety of these regimens.