Designing a vaccination strategy against dengue

In this work we propose a mathematical approach to estimate the dengue force of infection, the average age of dengue first infection, the optimum age to vaccinate children against dengue in a routine fashion and the optimum age interval to introduce the dengue vaccine in a mass vaccination campaign. The model is based on previously published models for vaccination against other childhood infections, which resulted in actual vaccination programmes in Brazil. The model was applied for three areas of distinct levels of endemicity of the city of Recife in Northeastern State of Pernambuco, Brazil. Our results point to an optimal age to introduce the dengue vaccine in the routine immunization programme at two years of age and an age interval to introduce a mass vaccination between three and 14 years of age.

Factors Associated with Dengue Mortality in Latin America and the Caribbean, 1995-2009: An Ecological Study

In this study, we aimed to estimate the effect that environmental, demographic, and socioeconomic factors have on dengue mortality in Latin America and the Caribbean. To that end, we conducted an observational ecological study, analyzing data collected between 1995 and 2009. Dengue mortality rates were highest in the Caribbean (Spanish-speaking and non-Spanish-speaking). Multivariate analysis through Poisson regression revealed that the following factors were independently associated with dengue mortality: time since identification of endemicity (adjusted rate ratio [aRR] = 3.2 [for each 10 years]); annual rainfall (aRR = 1.5 [for each 10(3) L/m(2)]); population density (aRR = 2.1 and 3.2 for 20-120 inhabitants/km(2) and > 120 inhabitants/km(2), respectively); Human Development Index > 0.83 (aRR = 0.4); and circulation of the dengue 2 serotype (aRR = 1.7). These results highlight the important role that environmental, demographic, socioeconomic, and biological factors have played in increasing the severity of dengue in recent decades.

The incidence of pressure ulcers after the implementation of a prevention protocol

Even in the present, pressure ulcers still represent a severe health problem, particularly in Intensive Care Units (ICU). This study assesses the implementation of a protocol to prevent pressure ulcers in ICU inpatients. This prospective, descriptive and exploratory study verifies the incidence of pressure ulcers following the implementation of a prevention protocol. Data were collected from April 17th to July 15th 2009. The incidence observed in this study (23.1%) was below that reported in a similar study developed in the same institution (41.02%) before the implementation of the protocols to assess risk and prevent pressure ulcers. The prevention protocols are essential tools that have an impact on controlling the incidence of pressure ulcers, when used consistently.

Human immunodeficiency virus prevalence, incidence, and residual risk of transmission by transfusions at Retrovirus Epidemiology Donor Study-II blood centers in Brazil

BACKGROUND: In Brazil nationally representative donor data are limited on human immunodeficiency virus (HIV) prevalence, incidence, and residual transfusion risk. The objective of this study was to analyze HIV data obtained over 24 months by the Retrovirus Epidemiology Donor Study-II program in Brazil. STUDY DESIGN AND METHODS: Donations reactive to third-and fourth-generation immunoassays (IAs) were further confirmed by a less-sensitive (LS) IA algorithm and Western blot (WB). Incidence was calculated for first-time (FT) donors using the LS-EIA results and for repeat donors with a model developed to include all donors with a previous negative donation. Residual risk was projected by multiplying composite FT and repeat donor incidence rates by HIV marker-negative infectious window periods. RESULTS: HIV prevalence among FT donors was 92.2/ 105 donations. FT and repeat donor and composite incidences were 38.5 (95% confidence interval [CI], 25.651.4), 22.5 (95% CI, 17.6-28.0), and 27.5 (95% CI, 22.0-33.0) per 100,000 person-years, respectively. Male and community donors had higher prevalence and incidence rates than female and replacement donors. The estimated residual risk of HIV transfusion transmission was 11.3 per 106 donations (95% CI, 8.4-14.2), which could be reduced to 4.2 per 106 donations (95% CI, 3.2-5.2) by use of individual-donation nucleic acid testing (NAT). CONCLUSION: The incidence and residual transfusion risk of HIV infection are relatively high in Brazil. Implementation of NAT will not be sufficient to decrease transmission rates to levels seen in the United States or Europe; therefore, other measures focused on decreasing donations by at-risk individuals are also necessary.

Incidence of adverse events associated with percutaneous muscular biopsy among healthy and diseased subjects

The development of the percutaneous muscle biopsy technique is recognized as one of the most important scientific contributions in advancing our understanding of skeletal muscle physiology. However, a concern that this procedure may be associated with adverse events still exists. We reported the incidence of adverse outcomes associated with percutaneous muscle biopsy in healthy and diseased subjects. Medical records of 274 volunteers (496 muscle biopsies) were reviewed. This included 168 healthy subjects (330 muscle biopsies) as well as 106 chronically ill patients (166 muscle biopsies). This latter group encompassed patients with type II diabetes (n=28), osteoarthritis (n=39), inclusion body myositis (n=4), polymyositis (n=4), and chronic heart failure (n=31). The most common occurrences were pain (1.27%), erythema (1.27%), and ecchymosis (1.27%). Panic episode, bleeding, and edema were also reported (0.21%, 0.42%, and 0.84%, respectively), while infection, hematoma, inflammation, denervation, numbness, atrophy, and abnormal scarring were not verified. The percent of incidents did not differ between healthy and ill individuals. In conclusion, the incidence of complications associated with percutaneous muscle biopsy is scarce and of minor clinical relevance. Additionally, the rate of adverse events is comparable between healthy and chronically ill subjects.

Gender differences in incidence and determinants of disability in activities of daily living among elderly individuals: SABE study

Determining the groups that are most susceptible to developing disability is essential to establishing effective prevention and rehabilitation strategies. The aim of the present study was to determine gender differences in the incidence of disability regarding activities of daily living (ADL) and determinants among elderly residents of Sao Paulo, Brazil. In 2000, 1634 elderly with no difficulties regarding ADL (modified Katz Index) were selected. These activities were reassessed in 2006 and disability was the outcome for the analysis of determinants. The following characteristics were analyzed at baseline: sociodemographic, behavioral, health status, medications, falls, hospitalizations, depressive symptoms, cognition, handgrip, mobility and balance. The incidence density was 42.4/1000 women/year and 17.5/1000 men/year. After adjusting for socioeconomic status and health conditions, women with chronic diseases and social vulnerability continued to have a greater incidence of disability. The following were determinants of the incidence of disability: age and depressive symptoms in both genders; stroke and slowness on the sit-and-stand test among men; and osteoarthritis and sedentary lifestyle among women. Better cognitive performance and handgrip strength were protective factors among men and women, respectively. Adverse clinical and social conditions determine differences between genders regarding the incidence of disability. Decreased mobility and balance and health conditions that affect the central nervous system or lead to impaired cognition disable men more, whereas a sedentary lifestyle, reduction in muscle strength and conditions that affect the osteoarticular system disable women more. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Extensive structural change of the envelope protein of dengue virus induced by a tuned ionic strength: conformational and energetic analyses

The Dengue has become a global public health threat, with over 100 million infections annually; to date there is no specific vaccine or any antiviral drug. The structures of the envelope (E) proteins of the four known serotype of the dengue virus (DENV) are already known, but there are insufficient molecular details of their structural behavior in solution in the distinct environmental conditions in which the DENVs are submitted, from the digestive tract of the mosquito up to its replication inside the host cell. Such detailed knowledge becomes important because of the multifunctional character of the E protein: it mediates the early events in cell entry, via receptor endocytosis and, as a class II protein, participates determinately in the process of membrane fusion. The proposed infection mechanism asserts that once in the endosome, at low pH, the E homodimers dissociate and insert into the endosomal lipid membrane, after an extensive conformational change, mainly on the relative arrangement of its three domains. In this work we employ all-atom explicit solvent Molecular Dynamics simulations to specify the thermodynamic conditions in that the E proteins are induced to experience extensive structural changes, such as during the process of reducing pH. We study the structural behavior of the E protein monomer at acid pH solution of distinct ionic strength. Extensive simulations are carried out with all the histidine residues in its full protonated form at four distinct ionic strengths. The results are analyzed in detail from structural and energetic perspectives, and the virtual protein movements are described by means of the principal component analyses. As the main result, we found that at acid pH and physiological ionic strength, the E protein suffers a major structural change; for lower or higher ionic strengths, the crystal structure is essentially maintained along of all extensive simulations. On the other hand, at basic pH, when all histidine residues are in the unprotonated form, the protein structure is very stable for ionic strengths ranging from 0 to 225 mM. Therefore, our findings support the hypothesis that the histidines constitute the hot points that induce configurational changes of E protein in acid pH, and give extra motivation to the development of new ideas for antivirus compound design.

Correlates of the incidence of disability and mortality among older adult Brazilians with and without diabetes mellitus and stroke

Background: The combined effect of diabetes and stroke on disability and mortality remains largely unexplored in Brazil and Latin America. Previous studies have been based primarily on data from developed countries. This study addresses the empirical gap by evaluating the combined impact of diabetes and stroke on disability and mortality in Brazil. Methods: The sample was drawn from two waves of the Survey on Health and Well-being of the Elderly, which followed 2,143 older adults in Sao Paulo, Brazil, from 2000 to 2006. Disability was assessed via measures of activities of daily living (ADL) limitations, severe ADL limitations, and receiving assistance to perform these activities. Logistic and multinomial regression models controlling for sociodemographic and health conditions were used to address the influence of diabetes and stroke on disability and mortality. Results: By itself, the presence of diabetes did not increase the risk of disability or the need for assistance; however, diabetes was related to increased risks when assessed in combination with stroke. After controlling for demographic, social and health conditions, individuals who had experienced stroke but not diabetes were 3.4 times more likely to have ADL limitations than those with neither condition (95% CI 2.26-5.04). This elevated risk more than doubled for those suffering from a combination of diabetes and stroke (OR 7.34, 95% CI 3.73-14.46). Similar effects from the combination of diabetes and stroke were observed for severe ADL limitations (OR 19.75, 95% CI 9.81-39.76) and receiving ADL assistance (OR 16.57, 95% CI 8.39-32.73). Over time, older adults who had experienced a stroke were at higher risk of remaining disabled (RRR 4.28, 95% CI 1.53, 11.95) and of mortality (RRR 3.42, 95% CI 1.65, 7.09). However, risks were even higher for those who had experienced both diabetes and stroke. Diabetes was associated with higher mortality. Conclusions: Findings indicate that a combined history of stroke and diabetes has a great impact on disability prevalence and mortality among older adults in Sao Paulo, Brazil.

Immune transcript variations among Aedes aegypti populations with distinct susceptibility to dengue virus serotype 2

The innate immune response of insects is one of the factors that may dictate their susceptibility to viral infection. Two immune signaling pathways, Toll and JAK-STAT, and the RNA interference (RNAi) pathway are involved in Aedes aegypti responses against dengue virus (DENV), however natural differences in these antiviral defenses among mosquito populations have not been studied. Here, two field Ae. aegypti populations from distinct ecological environments, one from Recife and the other from Petrolina (Brazil), and a laboratory strain were studied for their ability to replicate a primary isolate of dengue virus serotype 2 (DENV-2). Virus infectivity and replication were determined in insect tissues collected after viral exposure through reverse-transcription real time PCR (RT-PCR). The expression of a transcript representing these defense mechanisms (Toll, JAK-STAT and RNAi) in the midgut and fat body was studied with RTPCR to evaluate variations in innate immune mechanisms possibly employed against DENV. Analyses of infection rates indicated that the field populations were more susceptible to DENV-2 infection than the lab strain. There were distinct expression patterns among mosquito populations, in both control and infected insects. Moreover, lower expression of immune molecules in DENV-2-infected insects compared to controls was observed in the two field populations. These results suggest that natural variations in vector competence against DENV may be partly due to differences in mosquito defense mechanisms, and that the down-regulation of immune transcripts after viral infection depends on the insect strain. (C) 2012 Elsevier B.V. All rights reserved.

Lithiasis in 1,313 Kidney Transplants: Incidence, Diagnosis, and Management

Background. Renal transplantation remains the optimal treatment of patients with end-stage renal disease. Urinary lithiasis represents an unusual urologic complication in renal transplantation, with an incidence of <1%. Today, recipients of kidneys from deceased donors are more likely to receive grafts with undiagnosed lithiasis, which does not occur in patients from living donors, owing to screening with computerized tomography. Objective. The aim of this study was to evaluate the incidence, diagnosis, and therapeutic management of renal lithiasis in transplanted kidneys at a single institution. Methods. We reviewed the medical records for 1,313 patients who underwent kidney transplantation from February 1968 to February 2011. Results. Among the grafts, 17 patients (1.29%) had nephrolithiasis: 9 women and 8 men. Ages ranged from 32 to 63 years (mean = 45.6 years). Fifteen patients received kidneys from cadaveric and only 2 from living related donors. Two stones, both located inside the ureter, were identified during transplant surgery (11.7%). Three instances of lithiasis were incidentally diagnosed by ultrasound during graft evaluation, within 7 days after surgery (17.6%); all 3 were in the calyces. The 12 remaining patients had the stones diagnosed later (70.58%): 6 in the calyces, 3 in the renal pelvis, and 3 inside the ureter. Conclusions. Urinary lithiasis is a rare complication in renal transplantation. In most patients the condition occurs without pain. The diagnosis and treatment options for graft urolithiasis are similar to those patients with nephrofithiasis in the general population. Extracorporeal shock wave lithotripsy (ESWL) was the most common treatment method.

Spatio-temporal patterns of tuberculosis incidence in Ribeirao Preto, State of Sao Paulo, southeast Brazil, and their relationship with social vulnerability: a Bayesian analysis

Introduction: The purpose of this ecological study was to evaluate the urban spatial and temporal distribution of tuberculosis (TB) in Ribeirao Preto, State of Sao Paulo, southeast Brazil, between 2006 and 2009 and to evaluate its relationship with factors of social vulnerability such as income and education level. Methods: We evaluated data from TBWeb, an electronic notification system for TB cases. Measures of social vulnerability were obtained from the SEADE Foundation, and information about the number of inhabitants, education and income of the households were obtained from Brazilian Institute of Geography and Statistics. Statistical analyses were conducted by a Bayesian regression model assuming a Poisson distribution for the observed new cases of TB in each area. A conditional autoregressive structure was used for the spatial covariance structure. Results: The Bayesian model confirmed the spatial heterogeneity of TB distribution in Ribeirao Preto, identifying areas with elevated risk and the effects of social vulnerability on the disease. We demonstrated that the rate of TB was correlated with the measures of income, education and social vulnerability. However, we observed areas with low vulnerability and high education and income, but with high estimated TB rates. Conclusions: The study identified areas with different risks for TB, given that the public health system deals with the characteristics of each region individually and prioritizes those that present a higher propensity to risk of TB. Complex relationships may exist between TB incidence and a wide range of environmental and intrinsic factors, which need to be studied in future research.

Imunocompetent Mice Model for Dengue Virus Infection

Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV). DENV belongs to the family Flaviviridae, genus Flavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease) in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFN gamma and TNF alpha cytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines.

Incidence and Predictors of Adverse Drug Reactions Caused by Drug-Drug Interactions in Elderly Outpatients: A Prospective Cohort Study

Purpose. The primary objective of this study was to investigate the incidence of drug-drug interactions (DDIs) related to adverse drug reactions (ADRs) in elderly outpatients who attended public primary healthcare units in a southeastern region of Brazil. The secondary objective was to investigate the possible predictors of DDI-related ADRs. Methods. A prospective cohort study was conducted between November 1, 2010, and November 31, 2011, in the primary public healthcare system in the Ourinhos micro-region in Brazil. Patients who were at least 60 years old, with at least one potential DDI, were eligible for inclusion in the study. Eligible patients were assessed by clinical pharmacists for DDI-related ADRs for 4 months. The causality of DDI-related ADRs was assessed independently by four clinicians using three decisional algorithms. The incidence of DDI-related ADRs during the study period was calculated. Logistic regression analysis was used to study DDI-related ADR predictors. Results. A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6.5%. A multivariate analysis indicated that the adjusted odds ratios (ORs) rose from 0.91 (95% confidence interval [CI] = 0.75-1.12, p = 0.06) in patients aged 65-69 years to 4.40 (95% CI = 3.00-6.12, p < 0.01) in patients aged 80 years or older. Patients who presented two to three diagnosed diseases presented lower adjusted ORs (OR = 0.93 [95% CI = 0.68-1.18, p = 0.08]) than patients who presented six or more diseases (OR = 1.12 [95% CI = 1.02-2.01, p < 0.01]). Elderly patients who took five or more drugs had a significantly higher risk of DDI-related ADRs (OR = 2.72 [95% CI = 1.92-3.12, p < 0.01]) than patients who took three to four drugs (OR = 0.93 [95% CI = 0.74-1.11, p = 0.06]). No significant difference was found with regard to sex (OR = 1.08 [95% CI 0.48-2.02, p = 0.44]). Conclusion. The incidence of DDI-related ADRs in elderly outpatients was significant, and most of the events presented important clinical consequences. Because clinicians still have difficulty managing this problem, highlighting the factors that increase the risk of DDI-related ADRs is essential. Polypharmacy was found to be a significant predictor of DDI-related ADRs in our sample.

Incidence of gastric extubation of users in a home care program of a university hospital

This quantitative, prospective study, aimed to characterize the profile of users and caregivers and to measure the incidence of gastric extubation, identifying the type and the reasons for the extubation of these users in a Home Care Program of a university hospital. The population consisted of 37 subjects and the date were collected from April to August 2010. For the analysis, descriptive statistics, test of significance of 5% and calculation of indicators were adopted. It was found that 51.4% of the users were female, 67.5% in the age group >= 60 years and 67.6% presented neurological diseases. Regarding the caregivers 89.2% were female and their mean age was 50.6 years. The incidence of extubation, considering 100 days of intubation, corresponded to 1.08, with 0.26 planned and 0.82 unplanned (p=0.009). These results allowed the rates to be calculated of the extubation of patients with gastric intubation for nutritional support in domicile care, providing support in establishing care and management goals for the continuous improvement of quality.