Serial Mass Screening for Tuberculosis among Incarcerated Persons in Brazil.

BACKGROUND: Active search for tuberculosis cases through mass screening is widely described as a tool to improve case detection in hyperendemic settings. However, its effectiveness in high-risk populations, such as incarcerated people, is debated. METHODS: Between 2017 and 2021, three rounds of mass screening were carried out in three Brazilian prisons. Social and health questionnaires, chest X-rays and Xpert MTB/RIF were performed. RESULTS: Over 80% of the prison population was screened. Overall, 684 cases of pulmonary tuberculosis were diagnosed. Prevalence across screening rounds was not statistically different. Among incarcerated persons with symptoms, the overall prevalence of tuberculosis per 100,000 persons was 8,497 (95% CI, 7,346-9,811), 11,115 (95% CI, 9,471-13,082), and 7,957 (95% CI, 6,380-9,882) in screening rounds one, two and three, respectively. Similar to our overall results, there were no statistical differences between screening rounds and within individual prisons. We found no statistical differences in CAD4TB scores across screening rounds among people with tuberculosis - the median scores in rounds 1, 2, and 3 were 82 (IQR, 63-97), 77 (IQR, 60-94), and 81 (IQR, 67-92), respectively. CONCLUSIONS: In this environment with hyperendemic rates of tuberculosis, three rounds of mass screening did not reduce the overall tuberculosis burden. In prisons, where a substantial amount of TB is undiagnosed annually, a range of complementary interventions and more frequent TB screening may be required.

Effect of BCG vaccination against Mycobacterium tuberculosis infection in adult Brazilian health-care workers: a nested clinical trial.

BACKGROUND: The effectiveness of BCG vaccine for adult pulmonary tuberculosis remains uncertain. In this study, we aimed to evaluate the effect of vaccination with BCG-Denmark to prevent initial and sustained interferon-γ release assay conversion in Brazilian health-care workers. METHODS: This substudy is a nested randomised controlled trial embedded within the BRACE trial (NCT04327206). Specifically, this substudy enrolled Brazilian health-care workers (aged ≥18 years) from three sites in Brazil (Manaus, Campo Grande, and Rio de Janeiro) irrespective of previously receiving BCG vaccination. Participants were excluded if they had contraindications to BCG vaccination, more than 1 month of treatment with specific tuberculosis treatment drugs, previous adverse reactions to BCG, recent BCG vaccination, or non-compliance with assigned interventions. Those eligible were randomly assigned (1:1) to either the BCG group (0·1 mL intradermal injection of BCG-Denmark [Danish strain 1331; AJ Vaccines, Copenhagen]) or the placebo group (intradermal injection of 0·9% saline) using a web-based randomisation process in variable-length blocks (2, 4, or 6), and were stratified based on the study site, age (<40, ≥40 to <60, ≥60 years), and comorbidity presence (diabetes, chronic respiratory disease, cardiac condition, hypertension). Sealed syringes were used to prevent inadvertent disclosure of group assignments. The QuantiFERON-TB Gold (QFT) Plus test (Qiagen; Hilden, Germany) was used for baseline and 12-month tuberculosis infection assessments. The primary efficacy outcome was QFT Plus conversion (≥0·35 IU/mL) by 12 months following vaccination in participants who had a negative baseline result (<0·35 IU/mL). FINDINGS: Between Oct 7, 2020, and April 12, 2021, 1985 (77·3%) of 2568 participants were eligible for QFT Plus assessment at 12 months and were included in this substudy; 996 (50·2%) of 1985 were in the BCG group and 989 (49·8%) were in the placebo group. Overall, 1475 (74·3%) of 1985 participants were women and 510 (25·7%) were men, and the median age was 39 years (IQR 32-47). During the first 12 months, QFT Plus conversion occurred in 66 (3·3%) of 1985 participants, with no significant differences by study site (p=0·897). Specifically, 34 (3·4%) of 996 participants had initial QFT conversion in the BCG group compared with 32 (3·2%) of 989 in the placebo group (risk ratio 1·09 [95% CI 0·67-1·77]; p=0·791). INTERPRETATION: BCG-Denmark vaccination did not reduce initial QFT Plus conversion risk in Brazilian health-care workers. This finding underscores the need to better understand tuberculosis prevention in populations at high risk. FUNDING: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the United Health Group Foundation, Epworth Healthcare, and individual donors. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Seroprevalence Of SARS-COV-2 infection in asymptomatic indigenous from the largest Brazilian periurban area.

This study assessed the seroprevalence of SARS-CoV-2 in 496 asymptomatic individuals from Mato Grosso do Sul, located in Dourados, the largest periurban indigenous area in Brazil, from January 25 to February 4, 2021. The volunteers participated before receiving their first dose of the CoronaVac inactivated vaccine. For screening, blood samples were collected and analyzed using SARS-CoV-2 rapid tests and the enzyme-linked immunosorbent assay (ELISA). We observed varying trends in total anti-SARS-CoV-2 antibodies across different variables. Seropositivity among the participants tested was 63.70% (316/496) using the rapid test and 52.82% (262/496) were positive using the ELISA method. The majority of participants identified with the Guarani-Kaiowá ethnic group, with 66.15% (217/328), and other ethnic groups with 58.84% (193/328). The median age of the subjects was 30.5 years, with 79.57% (261/328) being femaleThis research showed the elevated seroprevalence of SARS-CoV-2 antibodies in asymptomatic Brazilians. The findings indicate a high seropositivity rate among the asymptomatic indigenous population of Midwest Brazil. This underscores the overlooked status of these communities and underscores the need for targeted national initiatives that emphasize the protection of vulnerable ethnic groups in the fight against COVID-19.

Evaluation of chest X-ray with automated interpretation algorithms for mass tuberculosis screening in prisons: a cross-sectional study.

Background: The World Health Organization (WHO) recommends systematic tuberculosis (TB) screening in prisons. Evidence is lacking for accurate and scalable screening approaches in this setting. We aimed to assess the accuracy of artificial intelligence-based chest x-ray interpretation algorithms for TB screening in prisons. Methods: We performed prospective TB screening in three male prisons in Brazil from October 2017 to December 2019. We administered a standardized questionnaire, performed a chest x-ray in a mobile unit, and collected sputum for confirmatory testing using Xpert MTB/RIF and culture. We evaluated x-ray images using three algorithms (CAD4TB version 6, Lunit version 3.1.0.0 and qXR version 3) and compared their accuracy. We utilized multivariable logistic regression to assess the effect of demographic and clinical characteristics on algorithm accuracy. Finally, we investigated the relationship between abnormality scores and Xpert semi-quantitative results. Findings: Among 2075 incarcerated individuals, 259 (12.5%) had confirmed TB. All three algorithms performed similarly overall with area under the receiver operating characteristic curve (AUC) of 0.88-0.91. At 90% sensitivity, only LunitTB and qXR met the WHO Target Product Profile requirements for a triage test, with specificity of 84% and 74%, respectively. All algorithms had variable performance by age, prior TB, smoking, and presence of TB symptoms. LunitTB was the most robust to this heterogeneity but nonetheless failed to meet the TPP for individuals with previous TB. Abnormality scores of all three algorithms were significantly correlated with sputum bacillary load. Interpretation: Automated x-ray interpretation algorithms can be an effective triage tool for TB screening in prisons. However, their specificity is insufficient in individuals with previous TB. Funding: This study was supported by the US National Institutes of Health (grant numbers R01 AI130058 and R01 AI149620) and the State Secretary of Health of Mato Grosso do Sul.

Phylogeography and transmission of Mycobacterium tuberculosis spanning prisons and surrounding communities in Paraguay.

Recent rises in incident tuberculosis (TB) cases in Paraguay and the increasing concentration of TB within prisons highlight the urgency of targeting strategies to interrupt transmission and prevent new infections. However, whether specific cities or carceral institutions play a disproportionate role in transmission remains unknown. We conducted prospective genomic surveillance, sequencing 471 Mycobacterium tuberculosis complex genomes, from inside and outside prisons in Paraguay's two largest urban areas, Asunción and Ciudad del Este, from 2016 to 2021. We found genomic evidence of frequent recent transmission within prisons and transmission linkages spanning prisons and surrounding populations. We identified a signal of frequent M. tuberculosis spread between urban areas and marked recent population size expansion of the three largest genomic transmission clusters. Together, our findings highlight the urgency of strengthening TB control programs to reduce transmission risk within prisons in Paraguay, where incidence was 70 times that outside prisons in 2021.

Serum biomarkers associated with SARS-CoV-2 severity.

Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.

Detection of M. tuberculosis in the environment as a tool for identifying high-risk locations for tuberculosis transmission.

Tuberculosis (TB) remains a leading cause of infectious mortality globally, yet most cases cannot be epidemiologically linked even with extensive contact investigations and whole genome sequencing. Consequently, there remain major gaps in our understanding of where and when M. tuberculosis (Mtb) exposures occur. We aimed to investigate whether Mtb can be detected in environments where TB patients were recently present, which could serve as a tool for characterizing exposure risk. We collected 389 environment surface (ES) swabs from two high TB burden prisons in Brazil, sampling 41 (n = 340) cells occupied by individuals with active TB and 7 (n = 49) cells from individuals without TB. In a subset of pooled swabs (n = 6) and a swab from a cigarette lighter from the cell with active TB patients, we enriched Mtb DNA using RNA-bait hybrid capture assays and performed whole genome sequencing. In prison cells, Mtb DNA was detected in 55/340 (16 %) of ES swabs from cells occupied by active TB patients and none (0/49) from cells in which no active TB patients were present. Mtb was detected in 13/16 (81 %) prison cells occupied by the individuals with high/medium sputum Xpert Mtb load and 8/25 (32 %) with low/very low sputum Mtb load (p = 0.003). Seven hybrid capture samples had a median genomic coverage of 140×. rpoB mutations conferring high-level rifampin resistance were detected in 3/7 ES swabs. Mtb was frequently detectable in environments recently occupied by individuals with active TB. This approach could be applied in congregate environments to identify and characterize high-risk settings for Mtb exposure.

The role of prisons in disseminating tuberculosis in Brazil: A genomic epidemiology study.

Background: Globally, prisons are high-incidence settings for tuberculosis. Yet the role of prisons as reservoirs of M. tuberculosis, propagating epidemics through spillover to surrounding communities, has been difficult to measure directly. Methods: To quantify the role of prisons in driving wider community M. tuberculosis transmission, we conducted prospective genomic surveillance in Central West Brazil from 2014 to 2019. We whole genome sequenced 1152 M. tuberculosis isolates collected during active and passive surveillance inside and outside prisons and linked genomes to detailed incarceration histories. We applied multiple phylogenetic and genomic clustering approaches and inferred timed transmission trees. Findings: M. tuberculosis sequences from incarcerated and non-incarcerated people were closely related in a maximum likelihood phylogeny. The majority (70.8%; 46/65) of genomic clusters including people with no incarceration history also included individuals with a recent history of incarceration. Among cases in individuals with no incarceration history, 50.6% (162/320) were in clusters that included individuals with recent incarceration history, suggesting that transmission chains often span prisons and communities. We identified a minimum of 18 highly probable spillover events, M. tuberculosis transmission from people with a recent incarceration history to people with no prior history of incarceration, occurring in the state's four largest cities and across sampling years. We additionally found that frequent transfers of people between the state's prisons creates a highly connected prison network that likely disseminates M. tuberculosis across the state. Interpretation: We developed a framework for measuring spillover from high-incidence environments to surrounding communities by integrating genomic and spatial information. Our findings indicate that, in this setting, prisons serve not only as disease reservoirs, but also disseminate M. tuberculosis across highly connected prison networks, both amplifying and propagating M. tuberculosis risk in surrounding communities. Funding: Brazil's National Council for Scientific and Technological Development and US National Institutes of Health.

Pooling Sputum Samples for Efficient Mass Tuberculosis Screening in Prisons.

BACKGROUND: Although systematic tuberculosis screening in high-risk groups is recommended by the World Health Organization (WHO), implementation in prisons has been limited due to resource constraints. Whether Xpert Ultra sputum pooling could be a sensitive and efficient approach to mass screening in prisons is unknown. METHODS: In total, 1280 sputum samples were collected from incarcerated individuals in Brazil during mass screening and tested using Xpert G4. We selected samples for mixing in pools of 4, 8, 12, and 16, which were then tested using Ultra. In each pool, a single positive sample of differing Xpert mycobacterial loads was used. Additionally, 10 pools of 16 negative samples each were analyzed as controls. We then simulated tuberculosis screening at prevalences of 0.5-5% and calculated the cost per tuberculosis case detected at different sputum pooling sizes. RESULTS: The sensitivity and specificity of sputum pooling were high (sensitivity: 94%; 95% confidence interval [CI]: 88-98; specificity: 100%, 95% CI: 84-100). Sensitivity was greater in pools in which the positive sample had a high mycobacterial load compared to those that were very low (100% vs 88%). In settings with a higher tuberculosis prevalence, pools of 4 and 8 were more efficient than larger pool sizes. Larger pools decreased the costs by 87% at low prevalences, whereas smaller pools led to greater cost savings at higher prevalence at higher prevalences (57%). CONCLUSIONS: Sputum pooling using Ultra was a sensitive strategy for tuberculosis screening. This approach was more efficient than individual testing across a broad range of simulated tuberculosis prevalence settings and could enable active case finding to be scaled while containing costs.

Blood-based host biomarker diagnostics in active case finding for pulmonary tuberculosis: A diagnostic case-control study.

BACKGROUND: There is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority. METHODS: We performed a diagnostic case-control study of point-of-care C-reactive protein (CRP) and Prototype-Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. All incarcerated individuals irrespective of symptoms were screened by sputum Xpert MTB/RIF and sputum culture. Among consecutive, Xpert MTB/RIF or culture-confirmed cases and Xpert MTB/RIF and culture-negative controls, CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks. FINDINGS: Two hundred controls (no TB) and 100 culture- or Xpert MTB/RIF-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0·79 (95% CI: 0·73-0·84) and for Xpert-MTB-HR was 0·84 (95% CI: 0·79-0·89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53·0%, 95% CI: 45·0-69·0%) than CRP (28·1%, 95% CI: 20·2-41·8%) (p = 0·003), both well below the TPP benchmark of 70%. Among individuals with medium or high sputum Xpert MTB/RIF semi-quantitative load, sensitivity (at 70% specificity) of CRP (90·3%, 95% CI: 74·2-98·0) and Xpert-MTB-HR (96·8%, 95% CI: 83·3-99·9%) was higher. INTERPRETATION: For active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden. FUNDING: National Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4).

Local and Travel-Associated Transmission of Tuberculosis at Central Western Border of Brazil, 2014-2017.

International migrants are at heightened risk for tuberculosis (TB) disease. Intensified incarceration at international borders may compound population-wide TB risk. However, few studies have investigated the contributions of migration, local transmission, or prisons in driving incident TB at international borders. We conducted prospective population-based genomic surveillance in 3 cities along Brazil's central western border from 2014-2017. Although most isolates (89/132; 67%) fell within genomic transmission clusters, genetically unique isolates disproportionately occurred among participants with recent international travel (17/42; 40.5%), suggesting that both local transmission and migration contribute to incident TB. Isolates from 40 participants with and 76 without an incarceration history clustered together throughout a maximum-likelihood phylogeny, indicating the close interrelatedness of prison and community epidemics. Our findings highlight the need for ongoing surveillance to control continued introductions of TB and reduce the disproportionate burden of TB in prisons at Brazil's international borders.

Occlusion Heightened by Metal Crown Cementation is Aggressive for Periodontal Tissues.

PURPOSE: To investigate the effect of experimental traumatic occlusion (ETO) induced by metal crowns on alveolar bone loss. MATERIALS AND METHODS: Metal crowns were custom-made for the lower first molars with occlusal discrepancy of 0.4 and 0.7 mm from the maximum intercuspation. Thirty-six animals were randomly divided into three groups (n = 12 animals per group): 0.4-mm hyperocclusion group, 0.7-mm hyperocclusion group and the sham group (no metal crown). Twenty-eight days after crown cementation, the animals were euthanized and gingival tissue was collected to assess cytokine levels of IL-17, IL-6, and TNF-α using enzyme-linked immunosorbent assay (ELISA). Mandibles were stained with 1% methylene blue and alveolar bone levels were quantified. Western blotting was used to quantify the expression of receptor activator of nuclear factor κ B (RANK), and its ligand (RANKL), secreted osteoclastogenic factor of activated T cells (SOFAT) and TNF-α-converting enzyme (TACE). Also, mandibles were histologically processed and stained with hematoxylin and eosin, from which the presence of osteoclast-like cells, multinucleated cells containing ≥3 nuclei was counted at 100× magnification. The data were analyzed using one-way ANOVA and Tukey tests. RESULTS: Experimental occlusal trauma for 28 consecutive days significantly increased alveolar bone loss and multinucleated cell counts (p < 0.05). RANK, RANKL, SOFAT, TACE, IL-6, and TNF-α were significantly higher in gingival tissues of ETO groups (p < 0.05). IL-17 titers were unchanged among the groups (p > 0.05). CONCLUSION: Experimental traumatic occlusion activates and sustains bone resorption pathways in the periodontium inducing alveolar bone resorption. As the intensity of occlusal trauma increased, alternative osteoclastic pathways were activated, such as TACE and SOFAT.

Primary Prophylaxis to Prevent Tuberculosis Infection in Prison Inmates: A Randomized, Double-Blind, Placebo-Controlled Trial.

In many low- and middle-income countries, tuberculosis (TB) incidence in prisons is high, exposing incarcerated populations to an elevated risk of TB infection. We conducted a randomized, double-blind, placebo-controlled trial among HIV-negative male inmates of a high TB burden prison to determine whether isoniazid given twice weekly (900 mg) for 12 months prevents TB infection. The primary outcome was QuantiFERON-TB Gold in Plus (QFT) conversion to ≥ 0.35 international units per milliliter (IU/mL) at 6 months; secondary outcomes included alternative QFT thresholds (≥ 0.7, ≥ 2.0, and ≥ 4.0 IU/mL). In total, 467 participants were randomly assigned to intervention (N = 258) or control (N = 209). In an interim analysis of participants who had completed 6 months of follow-up (N = 170), QFT conversion occurred in 20.8% (19/91) and 21.5% (17/79) of participants in intervention and control arms (efficacy: 2.9%, P = 0.91), respectively. The trial was then stopped according to the trial protocol, and the remaining participants prematurely discontinued. In an analysis of secondary outcomes, the intervention arm had significantly lower rates of conversion at a cutoff of ≥ 2.0 IU/mL (efficacy: 82.6%, P < 0.01). In conclusion, 900 mg of isoniazid, administered twice a week, did not effectively prevent QFT conversion at a cutoff point ≥ 0.35 IU/mL in a trial of QFT-negative inmates. Higher QFT cutoffs are associated with sustained conversion and greater protection. Future clinical trials that evaluate protection for latent infection should use the highest cutoff than that recommended by the manufacturer.

Two complementary model-based methods for calculating the risk of international spreading of a novel virus from the outbreak epicentre. The case of COVID-19.

We present two complementary model-based methods for calculating the risk of international spread of the novel coronavirus SARS-CoV-2 from the outbreak epicentre. One model aims to calculate the number of cases that would be exported from an endemic country to disease-free regions by travellers. The second model calculates the probability that an infected traveller will generate at least one secondary autochthonous case in the visited country. Although this paper focuses on the data from China, our methods can be adapted to calculate the risk of importation and subsequent outbreaks. We found an average R0 = 5.31 (ranging from 4.08 to 7.91) and a risk of spreading of 0.75 latent individuals per 1000 travellers. In addition, one infective traveller would be able to generate at least one secondary autochthonous case in the visited country with a probability of 23%.

Genetic Diversity and Molecular Epidemiology of Mycobacterium tuberculosis in Roraima State, Brazil.

National border areas are special places for the spread of Mycobacterium tuberculosis (MTB). These regions concentrate vulnerable populations and constant population movements. Understanding the dynamics of the transmission of MTB is fundamental to propose control measures and to monitor drug resistance. We conducted a population-based prospective study of tuberculosis (TB) to evaluate molecular characteristics of MTB isolates circulating in Roraima, a state on the border of Venezuela and Guyana. Eighty isolates were genotyped by IS6110-RFLP (restriction fragment length polymorphism), spoligotyping, and 24-locus mycobacterial interspersed repetitive unit-variable number of repeats tandem (MIRU-VNTR). Drug susceptibility tests were performed by using the proportion method and GeneXpert® MTB/RIF (Cepheid, Sunnyvale, CA). Isolates showing a phenotypic resistance profile were submitted to polymerase chain reaction (PCR) and sequencing. Spoligotyping showed 40 distinct patterns with a high prevalence of Latin-American and Mediterranean (LAM), Haarlem (H), and the "ill-defined" T clades. Mycobacterial interspersed repetitive unit -VNTR and IS6110-RFLP showed clustering rates of 21.3% and 30%, respectively. Drug resistance was detected in 11 (15.1%) isolates, and all were found to have primary resistance; among these, six (8.2%) isolates were streptomycin mono-resistant, four (5.4%) isoniazid mono-resistant, and one (1.3%) multidrug resistant. This is the first study on the molecular epidemiology and drug resistance profile of MTB from Roraima. Herein, we describe high diversity of genetic profiles circulating in this region that may be driven by the introduction of new strain types because of large population flow in this region. In summary, our results showed that analyses of these circulating strains can contribute to a better understanding of TB epidemiology in the northern Brazilian border and be useful to establish public health policies on TB prevention.

Experimental evidences that P21 protein controls Trypanosoma cruzi replication and modulates the pathogenesis of infection.

P21 is a protein secreted by Trypanosoma cruzi (T. cruzi). Previous studies have shown a spectrum of biological activities performed by P21 such as induction of phagocytosis, leukocyte chemotaxis and inhibition of angiogenesis. However, the activity of P21 in T. cruzi infection remains unknown. Here, we reported the role of P21 in mice harboring late T. cruzi infection. Treatment with recombinant P21 protein (rP21) reduced parasite load and angiogenesis, and induced fibrosis in the cardiac tissue of infected mice. In addition, rP21 reduced the growth of epimastigotes, inhibited intracellular replication of amastigotes and modulated the parasite cell cycle. Our data suggest that P21 controls parasite replication in the host, supporting the survival of both parasite and host.

Experimental evidences that P21 protein controls Trypanosoma cruzi replication and modulates the pathogenesis of infection

P21 is a protein secreted by Trypanosoma cruzi (T. cruzi). Previous studies have shown a spectrum of biological activities performed by P21 such as induction of phagocytosis, leukocyte chemotaxis and inhibition of angiogenesis. However, the activity of P21 in T. cruzi infection remains unknown. Here, we reported the role of P21 in mice harboring late T. cruzi infection. Treatment with recombinant P21 protein (rP21) reduced parasite load and angiogenesis, and induced fibrosis in the cardiac tissue of infected mice. In addition, rP21 reduced the growth of epimastigotes, inhibited intracellular replication of amastigotes and modulated the parasite cell cycle. Our data suggest that P21 controls parasite replication in the host, supporting the survival of both parasite and host.

Experimental evidences that P21 protein controls Trypanosoma cruzi replication and modulates the pathogenesis of infection

P21 is a protein secreted by Trypanosoma cruzi (T. cruzi). Previous studies have shown a spectrum of biological activities performed by P21 such as induction of phagocytosis, leukocyte chemotaxis and inhibition of angiogenesis. However, the activity of P21 in T. cruzi infection remains unknown. Here, we reported the role of P21 in mice harboring late T. cruzi infection. Treatment with recombinant P21 protein (rP21) reduced parasite load and angiogenesis, and induced fibrosis in the cardiac tissue of infected mice. In addition, rP21 reduced the growth of epimastigotes, inhibited intracellular replication of amastigotes and modulated the parasite cell cycle. Our data suggest that P21 controls parasite replication in the host, supporting the survival of both parasite and host.

High rates of methicillin-resistant Staphylococcus aureus colonisation in a Brazilian Intensive Care Unit.

OBJECTIVE: To evaluate the colonisation rate of Staphylococcus aureus in the oropharynx and the insertion site of central venous catheters in intensive care unit patients. DESIGN: Cross-sectional study. SETTING: Brazilian intensive care unit. MEASUREMENTS: Samples were collected from October to December 2015 from the oropharyngeal cavity and central venous catheter insertion site of 110 patients. Samples that presented growth of Staphylococcus aureus were isolated and their sensitivity profiles were tested for several antimicrobials. FINDINGS: The study participants (110) were mostly females older than 60 years (53.6%). The mean length of hospitalisation was 15.5 days (±31.3). A total of 188 biological samples were collected: 110 collected from the oropharynx and 78 from the central venous catheter insertion site. A 35% (n = 38/110) S. aureus colonisation rate of the patients was observed in at least one collection site. In the oropharynx alone, a 31% rate (n = 34/110) was found, and a 12.8% rate (n = 10/78) at central venous catheter insertion sites only. MRSA colonisation in the oropharynx or at the central venous catheter occurred in 29 (26.4%) patients and vancomycin resistant Staphylococcus aureus was present in 24 (22.4%) of the patients studied. Patients hospitalised for seven days or more were 4.8 times more likely to be colonised compared to patients hospitalised less than seven days (95% CI = 1.2-28.5). CONCLUSION: The oropharynx and the central venous catheter are important reservoirs of this bacterium that in critical conditions may become pathogenic. The data showed a high degree of resistance of the bacterial populations isolated to different drugs, which may hinder the control of these organisms.