Mortality due to visceral leishmaniasis in Brazil by municipalities, 2001-2018: a spatial-temporal analysis of estimates from the Global Burden of Disease study.

OBJECTIVES: In the American regions, Brazil accounts for 97% of visceral leishmaniasis (VL) cases, with a case fatality rate of approximately 10%. This study aimed to investigate the VL mortality distribution in Brazil and identify high-priority and high-risk areas for intervention strategies. STUDY DESIGN: This was an ecological study that analysed the spatial-temporal patterns of VL mortality in Brazilian municipalities. METHODS: Age-standardised VL mortality rates from the Global Burden of Disease study from 2001 to 2018 were used. The distribution of mortality in the municipalities was assessed, and subsequently the Local Index of Spatial Autocorrelation (LISA) analysis was conducted to identify contiguous areas with high mortality rates. Scan analysis identified clusters of high spatial-temporal risks. RESULTS: The highest mortality rates and clusters were in municipalities located in the Northeast region and in the states of Tocantins and Roraima (North region), Mato Grosso do Sul (Central-West region), and Minas Gerais (Southeast region). According to LISA, there was an increase in the number of municipalities classified as high priority from the first 3-year period (n = 434) to the last 3-year period (n = 644). The spatio-temporal analysis identified 21 high-risk clusters for VL mortality. CONCLUSION: Areas with a high risk of VL mortality should prioritise preventing transmission, invest in early diagnosis and treatment, and promote the training of healthcare professionals.

Gastrointestinal parasites in captive wild birds in Mineiros, Goiás, Brazil.

Studying parasites in captive wild birds is vital for their health, well-being, biodiversity preservation, species conservation, and safeguarding of both individual birds and ecosystems. It holds significance for public health by identifying potential zoonotic risks. We aimed to describe the occurrence of gastrointestinal parasites in captive wild birds from a Conservation Institute in Brazilian Cerrado biome. Fresh fecal samples were collected from 17 captive wild birds (Anodorhynchus hyacinthinus, Ara ararauna, Ara chloropterus, Ara macao, Megascops choliba, Pteroglossus castanotis, Ramphastos dicolorus, Ramphastos tucanus and Strix huhula) at a Conservation Institution in Mineiros, state of Goiás. The samples were processed for Willis' simple flotation and Hoffman's spontaneous sedimentation examinations to identify parasitic forms of gastrointestinal endoparasites. Macaw aviary birds (Ar. ararauna, Ar. chloropterus and Ar. macao) showed higher positivity, with all six fecal samples positive for helminths or protozoa. In contrast, captive toucans showed only two positive results (P. castanotis and R. dicolorus). An. hyacinthinus showed Ascarididae, Capillarinae and Trematoda eggs; whereas S. huhula had Ascarididae eggs. Regular parasitological examinations are essential for the timely detection and treatment of gastrointestinal infections in captive birds, thereby enhancing overall bird management.

Advances in Microfluidic-Based Core@Shell Nanoparticles Fabrication for Cancer Applications.

Current research in cancer therapy focuses on personalized therapies, through nanotechnology-based targeted drug delivery systems. Particularly, controlled drug release with nanoparticles (NPs) can be designed to safely transport various active agents, optimizing delivery to specific organs and tumors, minimizing side effects. The use of microfluidics (MFs) in this field has stood out against conventional methods by allowing precise control over parameters like size, structure, composition, and mechanical/biological properties of nanoscale carriers. This review compiles applications of microfluidics in the production of core-shell NPs (CSNPs) for cancer therapy, discussing the versatility inherent in various microchannel and/or micromixer setups and showcasing how these setups can be utilized individually or in combination, as well as how this technology allows the development of new advances in more efficient and controlled fabrication of core-shell nanoformulations. Recent biological studies have achieved an effective, safe, and controlled delivery of otherwise unreliable encapsulants such as small interfering RNA (siRNA), plasmid DNA (pDNA), and cisplatin as a result of precisely tuned fabrication of nanocarriers, showing that this technology is paving the way for innovative strategies in cancer therapy nanofabrication, characterized by continuous production and high reproducibility. Finally, this review analyzes the technical, biological, and technological limitations that currently prevent this technology from becoming the standard.

Freezing and thawing in Antarctica: characterization of antifreeze protein (AFP) producing microorganisms isolated from King George Island, Antarctica.

Antarctic temperature variations and long periods of freezing shaped the evolution of microorganisms with unique survival mechanisms. These resilient organisms exhibit several adaptations for life in extreme cold. In such ecosystems, microorganisms endure the absence of liquid water and exhibit resistance to freezing by producing water-binding molecules such as antifreeze proteins (AFP). AFPs modify the ice structure, lower the freezing point, and inhibit recrystallization. The objective of this study was to select and identify microorganisms isolated from different Antarctic ecosystems based on their resistance to temperatures below 0 °C. Furthermore, the study sought to characterize these microorganisms regarding their potential antifreeze adaptive mechanisms. Samples of soil, moss, permafrost, and marine sediment were collected on King George Island, located in the South Shetland archipelago, Antarctica. Bacteria and yeasts were isolated and subjected to freezing-resistance and ice recrystallization inhibition (IR) tests. A total of 215 microorganisms were isolated, out of which 118 were molecularly identified through molecular analysis using the 16S rRNA and ITS regions. Furthermore, our study identified 24 freezing-resistant isolates, including two yeasts and 22 bacteria. A total of 131 protein extracts were subjected to the IR test, revealing 14 isolates positive for AFP production. Finally, four isolates showed both freeze-resistance and IR activity (Arthrobacter sp. BGS04, Pseudomonas sp. BGS05, Cryobacterium sp. P64, and Acinetobacter sp. M1_25C). This study emphasizes the diversity of Antarctic microorganisms with the ability to tolerate freezing conditions. These microorganisms warrant further investigation to conduct a comprehensive analysis of their antifreeze capabilities, with the goal of exploring their potential for future biotechnological applications.

Impact of annual TB screening on stone quarry workers in high-incidence Portuguese municipalities.

The Portuguese municipalities of Penafiel and Marco de Canaveses are high TB incidence areas, where stone quarry workers represent a vulnerable population.To assess the annual rate of TB infection (ARI) in stone quarry workers and to compare it with the TB notification rate in the general community.An annual TB infection screening strategy using interferon-gamma release assay (IGRA) was implemented in 2018 for workers from high-risk stone quarries. A prospective cohort was enrolled and workers screened in periods of 2 years were included. IGRA-positive workers were referred for preventive treatment. ARI was calculated as the proportion of workers with IGRA conversion.Of the 232 IGRA-negative workers in 2018, 20 tested positive in 2019 (8.6% ARI). Of 171 IGRA-negative workers in 2019, eight tested positive in 2021 (4.7% in 2 years). Two of the 150 IGRA-negative workers in 2021 tested positive in 2022 (1.3% ARI). ARI decreased by 84.9% between 2019 and 2022. In the two municipalities, the TB notification rate declined 23.9% between 2018 and 2021.A more pronounced reduction in ARI was observed among stone quarry workers regularly screened for TB infection compared to the notification rate among the general population in high-incidence municipalities. A screening strategy for high-risk populations, together with enforced community measures, could foster risk reduction in the community..

The effect of TB patient delay on loss to follow-up in Portugal.

BACKGROUND: Early identification of TB cases, followed by treatment to completion, are essential for controlling and preventing the disease. Previous studies have found some factors associated with both loss to follow-up (LTFU) and patient delay. We aim to build a causal model to investigate the association between TB patient delay and LTFU.METHODS: Pulmonary TB cases were identified using the national surveillance system in Portugal between 2008 and 2017. A directed acyclic graph was used to identify the minimal set of variables to adjust for when studying the association between delay (exposure) and LTFU (outcome). Crude and adjusted hazard were estimated using Cox regression.RESULTS: Nearly 4% of the patients did not follow up treatment. There was no association between patient delay and LTFU, even after adjustment with the minimal set of covariates. Factors associated with a higher risk of LTFU were being younger, being unemployed, living in urban areas, having HIV and the abuse of alcohol and drugs.CONCLUSION: Patient delay was not associated with LTFU, while social conditions were. Future research should investigate the underlying reasons why patients discontinue TB treatment and use these findings to develop targeted interventions that can support patients in completing their treatment regimen.

COVID-19 vaccines effectiveness against symptomatic disease and severe outcomes, 2021-2022: a test-negative case-control study.

OBJECTIVES: This study evaluated the effectiveness of COVID-19 vaccines in preventing symptomatic and severe disease. STUDY DESIGN: This was an observational test-negative case-control study. METHODS: Study participants were adults with at least one symptom included in the World Health Organization COVID-19 definition who sought health care in a public emergency department between 1 November 2021 and 2 March 2022 (corresponding with the fifth pandemic wave in Portugal dominated by the Omicron variant). This study used multivariable logistic regression models to estimate and compare the odds ratio of vaccination between test-positive cases and test-negative controls to calculate the absolute and relative vaccine effectiveness. RESULTS: The study included 1059 individuals (522 cases and 537 controls) with a median age of 56 years and 58% were women. Compared with the effectiveness of the primary vaccination scheme that had been completed ≥180 days earlier, the relative effectiveness against symptomatic infection of a booster administered between 14 and 132 days earlier was 71% (95% confidence interval [CI]: 57%, 81%; P < 0.001). The effectiveness of the primary series against symptomatic infection peaked at 85% (95% CI: 56%, 95%) between 14 and 90 days after the last inoculation and decreased to 34% (95% CI: -43%, 50%) after ≥180 days. CONCLUSIONS: Despite the known immunological evasion characteristics of the Omicron variant, results from this study show that vaccine effectiveness increases after booster administration. COVID-19 vaccine effectiveness decreases to less than 50% between 3 and 6 months after completion of the primary cycle; therefore, this would be an appropriate time to administer a booster to restore immunity.

Decline of tuberculosis notification rate in different populations and regions in Portugal, 2010-2017.

BACKGROUND: Tuberculosis (TB) incidence declined in Portugal in recent decades, but trends differ between regions and population subgroups. We investigated these differences to inform prevention and control programmes. METHODS: We extracted TB notifications from the Portuguese National TB Surveillance System (SVIG-TB) in 2010-2017, disaggregated by region, age group, nationality and HIV status. We calculated notification rates using denominators from the Portuguese National Institute of Statistics and the Joint United Nations Programme on HIV/AIDS and performed stratified time series analysis. We estimated interannual decline percentages and 95% confidence intervals (CI) using Poisson and binomial negative regression models. RESULTS: The overall TB notification rate decreased from 25.7 to 17.5/100,000 population from 2010 to 2017 (5.2%/year) in Portugal. Interannual decline did not differ significantly between regions, but it was smaller amongst non-Portuguese nationals (-1.57% [CI: -4.79%, 1.75%] vs -5.85% [CI: -6.98%, -4.70%] in Portuguese nationals); children under five years of age (+1.77% [CI: -4.61%, 8.58%] vs -5.38% [CI: -6.33%, -4.42%] in other age groups); and HIV-negative people (-6.47% [CI: -9.10%, -3.77%] vs -11.29% [CI; -17.51%, -4.60%] in HIV-positive). CONCLUSIONS: The decline in TB notification rates in Portugal during the study period has been steady. However, the decline amongst non-Portuguese nationals, children under five years of age and non-infected-HIV patients was lower. No significant differences were observed between regions. Changes in TB epidemiology in specific risk groups and geographical areas should be closely monitored to achieve the objectives of the End TB Strategy. We recommend intensifying screening of TB in the subpopulations identified.

HLA class I and class II antigens in sarcoidosis.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disorder. Its exact cause is unknown, but it is believed that an external agent may cause the characteristic immune reaction in genetically susceptible individuals. There is therefore general recognition that genetic vulnerability to sarcoidosis is one of the potential risk factors. HLA is encoded by genes in the major histocompatibility complex on chromosome 6. These surface cells are important in presentation of antigen and play a key part in the body's immune response to external antigens. Various HLA subtypes are more common in people with sarcoidosis than in those without. Variances in vulnerability, presentation, progression and prognosis have been related to different HLA phenotypes. HLA genes offer information into the factors driving sarcoidosis and prognosticating tools. However, in Africa, including South Africa (SA), there are no data on HLA types in relation to sarcoidosis. OBJECTIVES: To determine HLA class I and II associations in SA sarcoidosis patients. METHODS: Phenotype frequencies of HLA-A, B and C and DQB1 and DRB1 were calculated for 51 consecutive patients with biopsy-proven sarcoidosis attending the respiratory clinic at Charlotte Maxeke Johannesburg Academic Hospital and 63 controls, who were potential organ donors. The frequencies of the tested HLA loci were determined by direct counting. The significance of the associations between the various loci tested for and the presence or absence of sarcoidosis was estimated from 2 × 2 tables using the χ2 test. RESULTS: Of the 51 patients, 70.6% were female. The mean age was 44.6 years. Analysis of HLA class I and class II phenotypes in sarcoidosis patients revealed a significant association with HLA-B15, C4, C7, C12, C15, C16, C17, DQ3, DR8 and DR11. In addition, a significant negative (protective) association with HLA A9, A28, B12, B17 and DR2 was observed. CONCLUSION: This HLA study in SA patients suggests that genetic factors play a role in the causation of sarcoidosis. Some HLA subtypes have a significant association with sarcoidosis in SA patients, while other subtypes may be protective. The study supported the association of HLA antigens with sarcoidosis and implies that there is a genetic predisposition to sarcoidosis in the SA population.

Ecological factors associated with areas of high tuberculosis diagnosis delay.

OBJECTIVE: We aimed to identify areas of high tuberculosis (TB) diagnosis delay in mainland Portugal in 2017 and ecological factors associated with these areas. STUDY DESIGN: This was an ecological study. METHODS: We considered all notified pulmonary TB cases from the Portuguese National Tuberculosis Surveillance System in mainland Portugal. Diagnostic delays were calculated at the municipality level. Demographic variables, proxies for TB awareness, health services capacity indicators, and socio-economic variables were included and extracted from official databases, such as Statistics Portugal, Ministeries, Foreigners and Border Services. We used spatial analysis to identify areas of high delay in 2017 and logistic generalised additive models to identify ecological factors associated with the identified cluster. RESULTS: We identified an area of high delay in 2017 in the South region of the country. Overall, municipalities with a smaller population density, smaller proportion of unemployed, fewer health centres and higher old-age dependency ratio, proportion of men, TB incidence, proportion of immigrants and high school dropout had a higher probability of belonging in a high delay area. CONCLUSION: The role of primary health care in TB diagnosis should be further explored. Interventions should address factors interplaying at the local and individual levels. Policies influencing social and health conditions, leading to changes in individual behaviour, can lead to sustained improvements over time.

Clinical standards for drug-susceptible pulmonary TB.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.