ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

Pig bite in Brazil: a case series from a teaching hospital

A retrospective survey done from 1987 till 1990 revealed that 23 patients bitten by pigs sought medical help at a teaching hospital in Uberlândia, in southeastern Brazil. Most cases (21) were from Uberlândia. The cases were evenly distributed by month and by year; most of them (14/16; 87.5%) occurred between 7. OOa.m. and 7.00 p. m. The male to female ratio was 6.7:1. Age ranged from 6 to 73 (mean 38.95 ± SD 22.06, median 36). The bites were more common on the upper limbs, particularly on the forearms. In 11(47.8%) cases the injury was described as deep. In most cases where information was available the injury was related to capture, transport or immobilisation ofthe pigfor slaughter. The following medical procedures were performed: local cleansing in 19(82.6%) cases, rabies vaccine (12; 52.2%), antirabies serum (2; 8.7%), suturing (6; 26.1%) and tetanus vaccine (12; 52.2%). There was no case of infection at the bite site, neither of rabies or tetanus. By our data, the annual incidence of pig bite in Uberlândia can be estimated to be about 1.5/100.000.

Predictors of adherence to influenza vaccination for healthcare workers from a teaching hospital: a study in the prepandemic era

INTRODUCTION: Even before the 2009 pandemics, influenza in healthcare workers (HCW) was a known threat to patient safety, while Influenza vaccine coverage in the same group was generally low. Identification of predictors for HCW adherence to Influenza vaccination has challenged infection control committees. METHODS: Our group conducted a cross-sectional survey in December 2007, interviewing 125 HCWs from a teaching hospital to identify adherence predictors for Influenza vaccination. The outcomes of interest were: A - adherence to the 2007 vaccination campaign; B - adherence to at least three yearly campaigns in the past five years. Demographic and professional data were assessed through univariate and multivariate analysis. RESULTS: Of the HCWs interviewed, 43.2% were vaccinated against Influenza in 2007. However, only 34.3% of HCWs working in healthcare for more than five years had adhered to at least three of the last five vaccination campaigns. Multivariate analysis showed that working in a pediatric unit (OR = 7.35, 95%CI = 1.90-28.44, p = 0.004) and number of years in the job (OR = 1.32, 95%CI = 1.00-1.74, p = 0.049) were significant predictors of adherence to the 2007 campaign. Physicians returned the worst outcome performances in A (OR = 0.40, 95%CI = 0.16-0.97, p = 0.04) and B (OR = 0.17, 95%CI = 0.05-0.60, p = 0.006). CONCLUSIONS: Strategies to improve adherence to Influenza vaccination should focus on physicians and newly-recruited HCWs. New studies are required to assess the impact of the recent Influenza A pandemics on HCW-directed immunization policies.

Antimicrobial use and incidence of multidrug-resistant Pseudomonas aeruginosa in a teaching hospital: an ecological approach

INTRODUCTION: Multidrug-resistant Pseudomonas aeruginosa is a major threat in healthcare settings. The use of antimicrobials can influence the incidence of resistant strains by direct and indirect mechanisms. The latter can be addressed by ecological studies. METHODS: Our group attempted to analyze the relation between the use of antipseudomonal drugs and the incidence of MDR-PA among 18 units from a 400-bed teaching hospital. The study had a retrospective, ecological design, comprising data from 2004 and 2005. Data on the use of four antimicrobials (amikacin, ciprofloxacin, ceftazidime and imipenem) were tested for correlation with the incidence of MDR-PA (defined as isolates resistant to the four antimicrobials of interest) in clinical cultures. Univariate and multivariate linear regression analyses were performed. RESULTS: Significant correlations were determined between use and resistance for all antimicrobials in the univariate analysis: amikacin (standardized correlation coefficient = 0.73, p = 0.001); ciprofloxacin (0.71, p = 0.001); ceftazidime (0.61, p = 0.007) and imipenem (0.87, p < 0.001). In multivariate analysis, only imipenem (0.67, p = 0.01) was independently related to the incidence of multidrug-resistant strains. CONCLUSIONS: These findings share similarities with those reported in individual-based observational studies, with possible implications for infection control.

Use of Poisson spatiotemporal regression models for the Brazilian Amazon Forest: malaria count data

INTRODUCTION: Malaria is a serious problem in the Brazilian Amazon region, and the detection of possible risk factors could be of great interest for public health authorities. The objective of this article was to investigate the association between environmental variables and the yearly registers of malaria in the Amazon region using Bayesian spatiotemporal methods. METHODS: We used Poisson spatiotemporal regression models to analyze the Brazilian Amazon forest malaria count for the period from 1999 to 2008. In this study, we included some covariates that could be important in the yearly prediction of malaria, such as deforestation rate. We obtained the inferences using a Bayesian approach and Markov Chain Monte Carlo (MCMC) methods to simulate samples for the joint posterior distribution of interest. The discrimination of different models was also discussed. RESULTS: The model proposed here suggests that deforestation rate, the number of inhabitants per km², and the human development index (HDI) are important in the prediction of malaria cases. CONCLUSIONS: It is possible to conclude that human development, population growth, deforestation, and their associated ecological alterations are conducive to increasing malaria risk. We conclude that the use of Poisson regression models that capture the spatial and temporal effects under the Bayesian paradigm is a good strategy for modeling malaria counts.

Relationship between antibiotic consumption, oropharyngeal colonization, and ventilator-associated pneumonia by Staphylococcus aureus in an intensive care unit of a Brazilian teaching hospital

INTRODUCTION: his study evaluated the consumption of major classes of antibiotics, the colonization of the oropharynx of patients on mechanical ventilation, and the risk of ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus in an intensive care unit for adults. METHODS: A case-control study was carried out using colonized patients (cases) by oxacillin-resistant S. aureus (ORSA) and (controls) oxacillin-sensitive S. aureus (OSSA) from May 2009 to August 2010. The occurrence of VAP by S. aureus was also evaluated in the same period. Antibiotic consumption was expressed as the number of defined daily doses (DDD)/1,000 patient-days for glycopeptides, carbapenems, and extended-spectrum cephalosporins. RESULTS: Three hundred forty-six (56.1%) patients underwent mechanical ventilation with a frequency of oropharyngeal colonization of 36.4%, corresponding to 63.5% for ORSA and 36.5% for OSSA. The risk of illness for this organism was significant (p<0.05), regardless of whether colonization/infection was by ORSA or OSSA. The consumption of antibiotics was high, mainly for broad-spectrum cephalosporins (551.26 DDDs/1,000 patient-days). The high density of use of glycopeptides (269.56 DDDs/1,000 patient-days) was related to colonization by ORSA (Pearson r=0.57/p=0.02). Additionally, age >60 years, previous antibiotic therapy, and previous use of carbapenems were statistically significant by multivariate analysis. CONCLUSIONS: There was a significant relationship between the colonization of the oropharyngeal mucosa and the risk of VAP by both phenotypes. The use of glycopeptides was related to colonization by ORSA.

Successful prevention of the transmission of vancomycin-resistant enterococci in a Brazilian public teaching hospital

INTRODUCTION: Vancomycin-resistant enterococci (VRE) can colonize or cause infections in high-risk patients and contaminate the environment. Our objective was to describe theepidemiological investigation of an outbreak of VRE, the interventions made, and their impact on its control. METHODS: We conducted a retrospective, descriptive, non-comparative study by reviewing the charts of patients with a VRE-positive culture in the University Hospital of Campinas State University, comprising 380 beds, 40 of which were in intensive care units (ICUs), who were admitted from February 2008-January 2009. Interventions were divided into educational activity, reviewing the workflow processes, engineering measures, and administrative procedures. RESULTS: There were 150 patients, 139 (92.7%) colonized and 11 (7.3%) infected. Seventy-three percent were cared for in non-ICUs (p = 0.028). Infection was more frequent in patients with a central-line (p = 0.043), mechanical ventilation (p = 0.013), urinary catheter (p = 0.049), or surgical drain (p = 0.049). Vancomycin, metronidazole, ciprofloxacin, and third-generation cephalosporin were previously used by 47 (31.3%), 31 (20.7%), 24 (16%), and 24 (16%) patients, respectively. Death was more frequent in infected (73%) than in colonized (17%) patients (p < 0.001). After the interventions, the attack rate fell from 1.49 to 0.33 (p < 0.001). CONCLUSIONS: Classical risk factors for VRE colonization or infection, e.g., being cared for in an ICU and previous use of vancomycin, were not found in this study. The conjunction of an educational program, strict adhesion to contact precautions, and reinforcement of environmental cleaning were able to prevent the dissemination of VRE.

Bloodstream infection in patients with end-stage renal disease in a teaching hospital in central-western Brazil

Introduction Vascular access in patients undergoing hemodialysis is considered a critical determinant of bloodstream infection (BSI) and is associated with high morbidity and mortality. The purpose of this study was to investigate the occurrence of BSI in patients with end-stage renal disease using central venous catheters for hemodialysis. Methods A cohort study was conducted in a public teaching hospital in central-western Brazil from April 2010 to December 2011. For every patient, we noted the presence of hyperemia/exudation upon catheter insertion, as well as fever, shivering, and chills during hemodialysis. Results Fifty-nine patients were evaluated. Thirty-five (59.3%) patients started dialysis due to urgency, 37 (62.7%) had BSI, and 12 (20%) died. Hyperemia at the catheter insertion site (64.9%) was a significant clinical manifestation in patients with BSI. Statistical analysis revealed 1.7 times more cases of BSI in patients with hypoalbuminemia compared with patients with normal albumin levels. The principal infective agents identified in blood cultures and catheter-tip cultures were Staphylococcus species (24 cases), non-fermentative Gram-negative bacilli (7 cases of Stenotrophomonas maltophilia and 5 cases of Chryseobacterium indologenes), and Candida species (6). Among the Staphylococci identified, 77.7% were methicillin-resistant, coagulase-negative Staphylococci. Of the bacteria isolated, the most resistant were Chryseobacterium indologenes and Acinetobacter baumannii. Conclusions Blood culture was demonstrated to be an important diagnostic test and identified over 50% of positive BSI cases. The high frequency of BSI and the isolation of multiresistant bacteria were disturbing findings. Staphylococcus aureus was the most frequently isolated microorganism, although Gram-negative bacteria predominated overall. These results highlight the importance of infection prevention and control measures in dialysis units.

Predictive factors of post-discharge surgical site infections among patients from a teaching hospital

Introduction Surgical site infections (SSIs) often manifest after patients are discharged and are missed by hospital-based surveillance. Methods We conducted a case-reference study nested in a prospective cohort of patients from six surgical specialties in a teaching hospital. The factors related to SSI were compared for cases identified during the hospital stay and after discharge. Results Among 3,427 patients, 222 (6.4%) acquired an SSI. In 138 of these patients, the onset of the SSI occurred after discharge. Neurological surgery and the use of steroids were independently associated with a greater likelihood of SSI diagnosis during the hospital stay. Conclusions Our results support the idea of a specialty-based strategy for post-discharge SSI surveillance.

Frequency of the toxic shock syndrome toxin-1 gene in methicillin-susceptible and -resistant Staphylococcus aureus isolates from teaching hospitals in Shiraz, Iran

INTRODUCTION: Staphylococcus aureus produces a range of virulence factors such as toxic shock syndrome toxin-1. METHODS: In this cross-sectional study of 345 clinical S. aureus isolates, the presence of the tst gene was assessed by polymerase chain reaction (PCR). RESULTS: The study revealed 53/345 (15.4%) isolates were positive for the tst gene. The tst gene was present in 18.1% of methicillin-susceptible S. aureus (MSSA) isolates and 11.6% of methicillin-resistant S. aureus (MRSA) isolates (p = 0.136). CONCLUSIONS: These results reveal the remarkable risk of S. aureus infections in hospitals, regardless of methicillin-resistance status.

Opportunistic infections among individuals with HIV-1/AIDS in the highly active antiretroviral therapy era at a Quaternary Level Care Teaching Hospital

INTRODUCTION : In this study, clinical-laboratory and epidemiological characteristics are described for a group of 700 individuals with HIV (human immunodeficiency virus)/AIDS (acquired immunodeficiency syndrome) in the ART (antiretroviral therapy) era at a teaching hospital that provides a quaternary level of care, with an emphasis on opportunistic infections (OIs), co-infections and immune profile. METHODS : A retrospective cross-sectional study of AIDS cases was conducted from 1998 to 2008 by reviewing medical records from the Base Hospital/FUNFARME (Fundação Faculdade Regional de Medicina), São José do Rio Preto, São Paulo, Brazil. RESULTS: The individuals were 14 to 75 years of age, and 458 were males. Heterosexuals accounted for 31.1% of all patients. Eighty-three percent were on ART, and 33.8% of those presented difficulties with treatment adherence. OIs were analyzed from medical records, and Pneumocystis jiroveci pneumonia was the most prevalent, regardless of the LTCD4+ (TCD4+ Lymphocytes) levels. Individuals whose viral loads were ≥10,000 showed a 90% greater chance of neurotoxoplasmosis. For P. jiroveci pneumonia, neurotoxoplasmosis, esophageal candidiasis, pulmonary tuberculosis and neurocryptococcosis, the chances of infection were higher among patients with LTCD4+ levels below 200 cells/mm3. HIV/hepatitis C virus (HCV) and HIV/hepatitis B virus (HBV) co-infections were significantly associated with death. CONCLUSIONS : OIs remain frequent in the ART era even in populations where the access to medical care is considered satisfactory.

Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital

ABSTRACTINTRODUCTION: Monte Carlo simulations have been used for selecting optimal antibiotic regimens for treatment of bacterial infections. The aim of this study was to assess the pharmacokinetic and pharmacodynamic target attainment of intravenous β-lactam regimens commonly used to treat bloodstream infections (BSIs) caused by Gram-negative rod-shaped organisms in a Brazilian teaching hospital.METHODS: In total, 5,000 patients were included in the Monte Carlo simulations of distinct antimicrobial regimens to estimate the likelihood of achieving free drug concentrations above the minimum inhibitory concentration (MIC; fT > MIC) for the requisite periods to clear distinct target organisms. Microbiological data were obtained from blood culture isolates harvested in our hospital from 2008 to 2010.RESULTS: In total, 614 bacterial isolates, including Escherichia coli, Enterobacterspp., Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, were analyzed Piperacillin/tazobactam failed to achieve a cumulative fraction of response (CFR) > 90% for any of the isolates. While standard dosing (short infusion) of β-lactams achieved target attainment for BSIs caused by E. coliand Enterobacterspp., pharmacodynamic target attainment against K. pneumoniaeisolates was only achieved with ceftazidime and meropenem (prolonged infusion). Lastly, only prolonged infusion of high-dose meropenem approached an ideal CFR against P. aeruginosa; however, no antimicrobial regimen achieved an ideal CFR against A. baumannii.CONCLUSIONS:These data reinforce the use of prolonged infusions of high-dose β-lactam antimicrobials as a reasonable strategy for the treatment of BSIs caused by multidrug resistant Gram-negative bacteria in Brazil.

Prevalence rates of infection in intensive care units of a tertiary teaching hospital

OBJECTIVE: To determine the prevalence rates of infections among intensive care unit patients, the predominant infecting organisms, and their resistance patterns. To identify the related factors for intensive care unit-acquired infection and mortality rates. DESIGN: A 1-day point-prevalence study. SETTING:A total of 19 intensive care units at the Hospital das Clínicas - University of São Paulo, School of Medicine (HC-FMUSP), a teaching and tertiary hospital, were eligible to participate in the study. PATIENTS: All patients over 16 years old occupying an intensive care unit bed over a 24-hour period. The 19 intensive care unit s provided 126 patient case reports. MAIN OUTCOME MEASURES: Rates of infection, antimicrobial use, microbiological isolates resistance patterns, potential related factors for intensive care unit-acquired infection, and death rates. RESULTS: A total of 126 patients were studied. Eighty-seven patients (69%) received antimicrobials on the day of study, 72 (57%) for treatment, and 15 (12%) for prophylaxis. Community-acquired infection occurred in 15 patients (20.8%), non- intensive care unit nosocomial infection in 24 (33.3%), and intensive care unit-acquired infection in 22 patients (30.6%). Eleven patients (15.3%) had no defined type. The most frequently reported infections were respiratory (58.5%). The most frequently isolated bacteria were Enterobacteriaceae (33.8%), Pseudomonas aeruginosa (26.4%), and Staphylococcus aureus (16.9%; [100% resistant to methicillin]). Multivariate regression analysis revealed 3 risk factors for intensive care unit-acquired infection: age > 60 years (p = 0.007), use of a nasogastric tube (p = 0.017), and postoperative status (p = 0.017). At the end of 4 weeks, overall mortality was 28.8%. Patients with infection had a mortality rate of 34.7%. There was no difference between mortality rates for infected and noninfected patients (p=0.088). CONCLUSION: The rate of nosocomial infection is high in intensive care unit patients, especially for respiratory infections. The predominant bacteria were Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus (resistant organisms). Factors such as nasogastric intubation, postoperative status, and age ³60 years were significantly associated with infection. This study documents the clinical impression that prevalence rates of intensive care unit-acquired infections are high and suggests that preventive measures are important for reducing the occurrence of infection in critically ill patients.

Modelling Amazonian forest eddy covariance data: a comparison of big leaf versus sun/shade models for the C-14 tower at Manaus I. Canopy photosynthesis

In this study, we concentrate on modelling gross primary productivity using two simple approaches to simulate canopy photosynthesis: "big leaf" and "sun/shade" models. Two approaches for calibration are used: scaling up of canopy photosynthetic parameters from the leaf to the canopy level and fitting canopy biochemistry to eddy covariance fluxes. Validation of the models is achieved by using eddy covariance data from the LBA site C14. Comparing the performance of both models we conclude that numerically (in terms of goodness of fit) and qualitatively, (in terms of residual response to different environmental variables) sun/shade does a better job. Compared to the sun/shade model, the big leaf model shows a lower goodness of fit and fails to respond to variations in the diffuse fraction, also having skewed responses to temperature and VPD. The separate treatment of sun and shade leaves in combination with the separation of the incoming light into direct beam and diffuse make sun/shade a strong modelling tool that catches more of the observed variability in canopy fluxes as measured by eddy covariance. In conclusion, the sun/shade approach is a relatively simple and effective tool for modelling photosynthetic carbon uptake that could be easily included in many terrestrial carbon models.