A contemporary investigation of burden and natural history of aspergillosis in people living with HIV/AIDS.

BACKGROUND: Untreated HIV infection can lead to profound immunosuppression and increase susceptibility of people living with HIV/AIDS (PLHA) to aspergillosis. OBJECTIVES: Reporting the burden and natural history of aspergillosis documented in PLHA admitted in five medical centres in Brazil. PATIENTS AND METHODS: Clinical, epidemiological and laboratory data were collected in all sequential cases of proven or probable aspergillosis documented in PLHA hospitalised in five medical centres between 2012 and 2020. RESULTS: We enrolled 25 patients ageing between 23 and 58 years (mean = 39) including 11 patients with invasive aspergillosis (IA) and 14 with chronic pulmonary aspergillosis (CPA). The prevalence rate of aspergillosis was 0.1% of 19.616 PLHA. Overall, 72.7% of patients with IA exhibited CD4 < 100 cells/mL and 42.8% of patients with CPA exhibited CD4 count >200 cells/mL. Most patients had a history of tuberculosis, especially those with CPA (85.7%). IA was documented after a mean of 16.5 days of hospitalisation, mainly in critically ill patients exposed to corticosteroids and broad-spectrum antibiotics. In the CPA group, a positive culture (71.4%) and radiological alterations were the most frequent findings supporting their diagnosis. Episodes of IA were mostly documented by tissue biopsies. Crude mortality rates were 72.7% and 42.8% in patients with IA and CPA, respectively. CONCLUSIONS: Despite being considered an unusual complication in PLHA (0.1%), IA should be considered in patients with profound immunosuppression and pneumonia refractory to conventional therapy. CPA should be investigated in PLHA with chronic deterioration of pulmonary function and previous diagnosis of tuberculosis.

The impact and the challenges of implementing a faculty development program on health professions education in a Brazilian Medical School: a case study with mixed methods.

PURPOSE: Faculty development in health professions education is still challenging in developing countries like Brazil. Work overload and the lack of financial support hinder faculty members' participation. Ribeirão Preto Medical School founded its Center for Faculty Development in 2016. Since then, an essential skills module (ESMo) on health professions education (HPE) has been offered regularly to faculty members and preceptors of seven undergraduate programs. This case study aims to evaluate the impact of this Essential Skills Module on the educational practices of participants two years after attending the module and the challenges faced during the process. METHOD: The study used a mixed-method approach with a description of the demographic and professional profile data of the ESMo participants. Immediate post-ESMo perceptions (satisfaction and learning) of the participants were determined with structured instruments. Two years later, a semi-structured interview was conducted and recorded to determine the long-term effects (application of learning and behavior changing as an educator). NVIVO® software was used to store and systematize the thematic discourse analysis with a socio-constructivist theoretical framework interpretation. RESULTS: One hundred forty-six participants were included: 86 (59%) tenured faculty members, 49 (33,5%) clinical preceptors, and 11 (7,5%) invited teachers. Most were female (66%), and 56% had teaching experience shorter than ten years. 52 (69%) out of 75 eligible participants were interviewed. The immediate reaction to participating in the module was quite positive and 80% have already implemented an educational intervention in their daily activities. Discourses thematic analysis showed five emerging themes appearing in different frequencies: Changes in teaching activities (98%); Lack of previous pedagogical training (92.3%); Commitment and enthusiasm towards teaching (46.15%); Overlapping functions inside the institution (34.6%) and Challenges for student assessment (23%). CONCLUSION: This first in-depth evaluation of the long-term effects of a faculty development intervention in a Brazilian Health Profession Education school showed that participation positively changed participants' teaching & learning practices. These interventions consistently fostered a community of practice and valued faculty development processes in local and national scenarios.

Pharmacogenetic predictors of variability in efavirenz pharmacokinetics in an admixed Brazilian HIV cohort.

AIMS: To investigate the influence of pharmacogenetic polymorphisms on efavirenz (EFV) exposure and metabolism in HIV-infected Brazilians under treatment with EFV-containing antiretroviral (ART) regimens. METHODS: HIV-positive adults (n = 82) on stable ART regimens containing 600 mg EFV once daily for at least 6 months were recruited at 2 university hospitals. Blood samples collected at mid-dose interval were used to quantify the plasma concentrations of EFV (denoted [EFV]), its major metabolite 8-OH-EFV ([8-OH-EFV]) and [8-OH-EFV]/[EFV] metabolic ratio, and to genotype single nucleotide polymorphisms in CYP2B6 (rs3745274, c.516G > T; rs28399499, c.983 T > C) and ABCB1 (rs3842, c.4036G > A). CYP2B6 metabolic phenotypes were inferred from the CYP2B6 diplotypes. Linear regression modelling was applied to identify sociodemographic, clinical and pharmacogenetic predictors of [EFV] and [8-OH-EFV]/[EFV] metabolic ratio. RESULTS: Wide (50-fold) interindividual variation in [EFV], [8-OH-EFV] and [8-OH-EFV]/[EFV] was observed; 69.5% of participants had [EFV] within the nominal therapeutic range (1000-4000 ng/mL), while 19.5 and 11.0% had [EFV] below and above this range, respectively. Multiple regression modelling retained only CYP2B6 metabolic phenotypes or the combined rs3745274 and rs28399499 genotypes, as significant predictors of [EFV] and [8-OH-EFV]/[EFV]. CONCLUSION: EFV exposure and disposition varied widely among HIV-infected Brazilians under stable treatment with EFV-containing ART regimens. About 1/10 of the participants had [EFV] exceeding nominal supratherapeutic concentration (4000 ng/mL), but reported tolerance to the ARV regimens, while 1/5 of participants had nominal subtherapeutic [EFV] (<1000 ng/mL) but adequate virological response. Genotype for the 2 CYP2B6 single nucleotide polymorphisms studied explained 48% of variation in [EFV] and 35% of variation in [8-OH-EFV]/[EFV].

Increased diversity, fungal burden, and virulence of oral Candida spp. in patients undergoing anti-tuberculosis treatment.

Some studies have demonstrated a high prevalence of Candida species in patients with tuberculosis (TB). This is most likely due to long-term antimicrobial therapy. To date, no longitudinal studies addressed the effects of anti-TB treatment on the fungal burden and virulence of Candida spp. This study investigated the prevalence and virulence of Candida spp. in the oral cavity of 30 TB patients at different stages of treatment through a cohort study. These results were compared with those of 60 systemically healthy individuals in a cross-sectional study. Oral rinse samples from TB patients were collected before 45 and after 120 days of treatment. In the control group, the biological samples were collected only once. Candida spp. were identified by restriction fragment length polymorphism (RFLP) assays, and the following virulence factors were studied: phospholipase C and proteinase production, as well as Candida spp. biofilm and hyphae formation. The clinical diagnosis of TB and its treatment time were associated with the greater fungal burden (p < 0.0001), presence of non-albicans Candida (NAC) species (p = 0.0003), and increased virulence factors when compared with the Candida spp. isolated from systemically healthy individuals. The results showed that anti-TB treatment time was responsible for the increased fungal burden and isolation of NAC in TB patients (p = 0.0233). The increased prevalence, quantification, and virulence of Candida spp. isolated from the oral cavity of TB patients highlight the greater risk of oral lesions and cases of systemic dissemination in these patients.

Molecular epidemiology of Mycobacterium tuberculosis in Brazil before the whole genome sequencing era: a literature review.

Molecular-typing can help in unraveling epidemiological scenarios and improvement for disease control strategies. A literature review of Mycobacterium tuberculosis transmission in Brazil through genotyping on 56 studies published from 1996-2019 was performed. The clustering rate for mycobacterial interspersed repetitive units - variable tandem repeats (MIRU-VNTR) of 1,613 isolates were: 73%, 33% and 28% based on 12, 15 and 24-loci, respectively; while for RFLP-IS6110 were: 84% among prison population in Rio de Janeiro, 69% among multidrug-resistant isolates in Rio Grande do Sul, and 56.2% in general population in São Paulo. These findings could improve tuberculosis (TB) surveillance and set up a solid basis to build a database of Mycobacterium genomes.

Are Candida albicans isolates from the oral cavity of HIV-infected patients more virulent than from non-HIV-infected patients? Systematic review and meta-analysis.

Candida albicans is the main causative agent of oral lesions in HIV-infected patients and its oral colonization is a potential source of systemic dissemination. Although the high prevalence of lesions in HIV patients can be explained by the immunosuppressive condition, several studies have reported that natural selection can make C. albicans more virulent in this group of patients. Comparisons of the activity of exoenzymes (phospholipase, proteinase and hemolysin) in C. albicans isolated from HIV-infected and uninfected patients have yielded conflicting results. This study aimed, through a systematic review and meta-analysis, to answer the question: "Is the hydrolytic enzymatic activity of C. albicans, isolated from the oral cavity, different in individuals infected and not infected with HIV?" The question was addressed using the PECO framework: P (Population): children and adults, E (Exposure): HIV infection, C (Comparator): non-HIV-infected patients; O (Outcomes): exoenzymes activity i.e. phospholipase, proteinase and hemolysin. We conducted a systematic search on Pubmed, Embase, Scopus, Livivo, Lilacs, Web of Science, and Science Direct databases, and Google Scholar. The MAStARI tool was used to evaluate the risk of bias in the selected studies. From 2259 studies, 19 were included in this review and 11 comprised the meta-analysis. The activity of phospholipase (M-H = 0.15; Z = 2,76; p = 0.0006) and hemolysin exoenzymes (M-H = 0.07; z = 1,94; p = 0.05) was higher in C. albicans isolated from the oral cavity of HIV-infected patients, whereas the levels of protease activity were not different compared with non-HIV-infected individuals. This study showed a higher phospholipase and hemolysin activity in C. albicans isolates from the oral cavity of HIV-infected patients.

Determinants of multidrug-resistant tuberculosis in São Paulo-Brazil: a multilevel Bayesian analysis of factors associated with individual, community and access to health services.

OBJECTIVE: Multidrug-resistant tuberculosis (MDR-TB) remains a serious public health problem worldwide. Accordingly, this study sought to identify individual, community and access to health services risk factors for MDR-TB. METHODS: Retrospective cohort of all TB cases diagnosed between 2006 and 2016 in the state of São Paulo. A Bayesian spatial hierarchical analysis with a multilevel design was carried out. RESULTS: It was identified that the history of previous TB treatment (Odds Ratios [OR]:13.86, 95% credibility interval [95% CI]:12.06-15.93), positive sputum culture test (OR: 5.26, 95% CI: 4.44-6.23), diabetes mellitus (OR: 2.34, 95% CI: 1.87-2.91), residing at a standard address (OR: 2.62, 95% CI: 1.91-3.60), positive sputum smear microscopy (OR: 1.74, 95% CI: 1.44-2.12), cavitary pulmonary TB (OR: 1.35, 95% CI: 1.14-1.60) and diagnosis performed due to spontaneous request (OR: 1.26; 95% CI: 1.10-1.46) were associated with MDR-TB. Furthermore, municipalities that performed HIV tests in less than 42.65% of patients with TB (OR: 1.50, 95% CI: 1.25-1.79), that diagnosed TB cases only after death (OR: 1.50, 95% CI: 1.17-1.93) and that had more than 20.16% of their population with income between » and ½ of one minimum wage (OR: 1.56, 95% CI: 1.30-1.87) were also related to the MDR-TB. CONCLUSIONS: Knowledge of these predictive factors may help to develop more comprehensive disease prevention strategies for MDR-TB, avoiding the risks expressed regarding drug resistance expansion.

OBJECTIF: La tuberculose multirésistante (TB-MDR) reste un grave problème de santé publique dans le monde. Cette étude visait à identifier les facteurs de risque individuels, communautaires et d'accès aux services de santé pour la TB-MDR. MÉTHODES: Analyse de cohorte rétrospective de tous les cas de TB diagnostiqués entre 2006 et 2016 dans l'Etat de São Paulo par analyse bayésienne spatiale à plusieurs niveaux. RÉSULTATS: Les antécédents de traitements antituberculeux (Rapports de cotes [OR]: 13,86, Intervalle de confiance à 95% [IC95%]: 12.06-15.93), un test de culture d'expectorations positif (OR: 5,26, IC95%: 4,44-6,23), le diabète sucré (OR: 2,34, IC95%: 1,87-2,91), la résidence à une adresse standard (OR: 2,62, IC95%: 1,91-3,60), la microscopie à frottis positif (OR: 1,74, IC95%: 1,44-2,12), la TB pulmonaire (OR: 1,35, IC95%: 1,14-1,60) et le diagnostic réalisé en raison d'une demande spontanée (OR: 1,26; IC95%: 1,10-1,46) étaient associés à la TB-MDR. Les municipalités qui ont effectué des tests de dépistage du VIH chez moins de 42,65% des patients atteints de TB (OR: 1,50, IC95%: 1,25-1,79), qui ont diagnostiqué des cas de TB uniquement après le décès (OR: 1,50, IC95%: 1,17-1,93) et qui avaient plus de 20,16% de leur population avec un revenu entre » et ½ d'un salaire minimum (OR: 1,56, IC95%: 1,30-1,87) étaient également associées à la TB-MDR. CONCLUSIONS: La connaissance de ces facteurs prédictifs peut aider à développer des stratégies plus complètes de prévention des maladies pour la TB-MDR, en évitant les risques d'extension de la résistance aux médicaments.

Correction to: Malaria and other febrile diseases among travellers: the experience of a reference centre located outside the Brazilian Amazon Region.

Following publication of the original article [1], one of the authors flagged that unfortunately their last name, Doltario, was incorrectly spelled as 'Dotrário'. This has since been corrected in the original article [1].

Immune Response Against Salmonella Enteritidis Is Unsettled by HIV Infection.

The human immunodeficiency virus (HIV) is responsible for more than 2 million new infections per year and opportunistic infections such as Salmonella spp. Gastroenteritis is an important cause of mortality and morbidity in developing countries. Monocytes and macrophages play a critical role in the innate immune response against bacterial infections. However during HIV infection the virus can infect these cells and although they are more resistant to the cytopathic effects, they represent an important viral reservoir in these patients. Our aim was to evaluate the monocyte functions from HIV-1 infected patients after in vitro exposition to Salmonella Enteritidis. Our results suggest impairment of monocytes phagocytic and microbicidal activity in HIV-1 non-treated patients, which was more evident in women, if compared with men. Moreover, monocytes from HIV-1 infected and non-treated patients after stimulation with the bacteria, produced more pro-inflammatory cytokines than monocytes from HIV-treated patients, suggesting that HIV-1 infected patients have their functions unbalanced, once in the presence of an opportunistic infection in vitro.

Malaria and other febrile diseases among travellers: the experience of a reference centre located outside the Brazilian Amazon Region.

BACKGROUND: Malaria is endemic in countries located in tropical and sub-tropical regions. The increasing flow of domestic and international travellers has made malaria a relevant health problem even in non-endemic regions. Malaria has been described as the main diagnosis among travellers presenting febrile diseases after returning from tropical countries. In Brazil, malaria transmission occurs mainly in the Amazon region. Outside this area, malaria transmission is of low magnitude. METHODS: This cross-sectional study aimed to describe the experience in the diagnosis of malaria in a reference centre located outside the Brazilian Amazon Region, emphasizing the differences in clinical and laboratory markers between cases of malaria and those of other febrile diseases (OFD). Medical charts from adult patients (≥18 years) who underwent a thick smear test (TST) for malaria, between January 2001 and December 2014, were retrospectively reviewed. RESULTS: A total of 458 cases referred to perform the TST were included. Malaria was diagnosed in 193 (42 %) episodes. The remaining 265 episodes (58 %) were grouped as OFD. The majority of malaria episodes were acquired in the Brazilian Amazon Region. The median time between the onset of symptoms and the TST was 7 days. Only 53 (11.5 %) episodes were tested within the first 48 h after symptom onset. Comparing malaria with OFD, jaundice, nausea, vomiting, and reports of fever were more prevalent in the malaria group. Low platelet count and elevated bilirubin levels were also related to the diagnosis of malaria. CONCLUSIONS: The results indicate that outside the endemic area travellers presenting febrile disease suspected of being malaria underwent diagnostic test after considerable delay. The reporting of fever combined with a recent visit to an endemic area should promptly evoke the hypothesis of malaria. In these cases, specific diagnostic tests for malaria should be a priority. For cases that jump this step, the presence of elevated bilirubin or thrombocytopaenia should also indicate a diagnosis of malaria.

Drug-resistant tuberculosis in Central Mozambique: the role of a rapid genotypic susceptibility testing.

BACKGROUND: Genotypic molecular testing may be very helpful for tuberculosis (TB) drug-resistance surveillance and for treatment guidance in low resource settings. METHODS: Descriptive analysis of M. tuberculosis isolates from Beira Central Hospital, Mozambique, during 2014-2015. Genotype MTBDRplus and MTBDRsl were used and patient medical records reviewed. To explore genotypic susceptibility profile of Mycobacterium tuberculosis, to first and second line drugs (SLD) in Beira Mozambique. RESULTS: Of 155 isolates, 16.1 % (25) were multidrug resistant (MDR), 8.4 % (13) isoniazid-monoresistant and 1.3 % (2) rifampicin-monoresistant. Among MDR-TB, 22.2 % showed primary and 77.8 % represented acquired resistance. The majority of patients with drug resistance had a history of previous TB treatment. Among 125 isolates tested for ethambutol and SLD, 7.2 % (9) were resistant to ethambutol, 4.8 % (6) to fluoroquinolones and 0.8 % (1) to ethambutol and fluoroquinolones. Resistance to injectable SLD was not detected. CONCLUSIONS: As far as we know this is the first report of a genotypic testing used to provide information about SLD resistance in Mozambique, where phenotypic susceptibility testing is usually unavailable. Extensively drug resistant TB was not detected in this isolates from Beira Mozambique.

Plasma eicosanoid profiles determined by high-performance liquid chromatography coupled with tandem mass spectrometry in stimulated peripheral blood from healthy individuals and sickle cell anemia patients in treatment.

Eicosanoids play an important role in homeostasis and in the pathogenesis of various human diseases. Pharmacological agents such as Ca(2+) ionophores and Ca(2+)-ATPase inhibitors, as well as natural agonists such as formylmethionine-leucyl-phenylalanine (fMLP), can stimulate eicosanoid biosynthesis. The aims of this work were to develop a method to determine the eicosanoid profile of human plasma samples after whole blood stimulation and to assess differences between healthy and sick individuals. For this purpose, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was partially validated for the quantification of 22 eicosanoids using human plasma from healthy volunteers. In addition, we optimized a method for the stimulation of eicosanoids in human whole blood. LC-MS/MS analyses were performed by negative electrospray ionization and multiple reaction monitoring. An assumption of linearity resulted in a regression coefficient ≥0.98 for all eicosanoids tested. The mean intra-assay and inter-assay accuracy and precision values had relative standard deviations and relative errors of ≤15%, except for the lower limit of quantification, where these values were ≤20%. For whole blood stimulation, four stimuli (fMLP, ionomycin, A23187, and thapsigargin) were tested. Results of the statistical analysis showed that A23187 and thapsigargin were potent stimuli for the production or liberation of eicosanoids. We next compared the eicosanoid profiles of stimulated whole blood samples of healthy volunteers to those of patients with sickle cell anemia (SCA) under treatment with hydroxyurea (HU) or after chronic red blood cell (RBC) transfusion. The results indicate that the method was sufficient to find a difference between lipid mediators released in whole blood of SCA patients and those of healthy subjects, mainly for 5-HETE, 12-HETE, LTB4, LTE4, TXB2, and PGE2. In conclusion, our analytical method can detect significant changes in eicosanoid profiles in stimulated whole blood, which will contribute to establishing the eicosanoid profiles associated with different inflammatory and infectious diseases.

Expression Profiles of Cytokine mRNAs in the Pleural Fluid Reveal Differences Among Tuberculosis, Malignancies, and Pneumonia-Exudative Pleural Effusions.

INTRODUCTION: Tuberculosis (TB) and malignant diseases are the most common causes of lymphocytic pleural effusion in adults. Serum and pleural fluid cytokine levels have been analyzed to help in the differential diagnosis, but with limited results. PURPOSE: This study investigates transcription levels of selected cytokine genes in pleural effusion of patients under investigation for TB. METHODS: This was a prospective study that included adult patients under investigation for pleural effusion in Brazil. The expression of 19 cytokine genes was analyzed by RT-qPCR. RESULTS: The majority of cytokine-related genes expressed in pleural fluid of TB patients were similar in non-TB patients, except for RORA and RORC genes, which showed a statistically higher level in TB. All cytokines in the Th17 pattern were induced in TB patients' pleural fluid. Patients with malignant pleural effusion expressed higher levels of IFN-α1, IFN-ß1, TNF-α, IL-4 and IL-6, and suppression of TGFß-1. CONCLUSION: There is still a lot to understand about the cytokine roles in the pro- and anti-inflammatory environment of exudative pleural effusions. The data presented here showed an increased expression of Th17 pattern cytokines genes in TB patients that could be used as markers to differentiate tuberculous pleuritis from other common causes of exudative pleural effusion.

Operational indicators for pulmonary tuberculosis diagnosis in people living with HIV before and after Xpert MTB/RIF implementation in the state of São Paulo, Brazil.

Tuberculosis (TB) in people living with HIV (PLHIV) is usually paucibacillary and the smear microscopy has limitations and may lead to high proportions of non-confirmed pulmonary tuberculosis (NC-PTB). Despite culture being the reference method, it usually takes 6 to 8 weeks to produce the results. This study aimed to analyze the effect of a rapid molecular test (Xpert) in the confirmatory rate of PTB among PLHIV, from 2010 to 2020, in São Paulo state, Brazil. This is an ecological study with time series analysis of the trend and the NC-PTB rates before and after Xpert implementation in 21 municipalities. The use of Xpert started and gradually increased after 2014, while the rate of NC-PTB in PLHIV decreased over this time, being more significant between late 2015 and mid-2017. The city of Ribeirão Preto stands out for having the highest percentage (75.0%) of Xpert testing among PLHIV and for showing two reductions in the NC-PTB rate. The cities with low Xpert coverage had a slower and smaller decrease in the NC-PTB rate. Despite being available since 2014, a significant proportion of PLHIV suspected of PTB in the state of São Paulo did not have an Xpert ordered by the doctors. The implementation of Xpert reduced the NC-PTB rates with growing effect as the coverage increased in the municipality.

Endemic paracoccidioidomycosis: relationship between clinical presentation and patients' demographic features.

Paracoccidioidomycosis (PCM) is a systemic fungal disease endemic to Latin America and characterized by two clinical presentations, i.e., patients develop either acute/subacute or chronic clinical manifestations. The differences in clinical presentations are mainly dependent on the host immune response, but may also be related to demographic characteristics of some patients. In this retrospective study, 1,219 PCM cases treated between 1970 and 2009 in a university medical center, located in southeastern Brazil, were analyzed according to their clinical and demographic features. The most affected anatomical sites were lungs (63.8%) and oral mucosa (50.0%), with increasing involvement of these sites in accord with the age of the patients. Generalized lymphadenopathy (28.1%) and skin lesions (29.6%) were more frequent on the first decades of life. Involvement of the larynx (16.1%), gut (7.5%), spleen (4.7%), central nervous system (3.4%), bones and joints (2.2%), and adrenal (2.1%) were also variable according to the age of the host. The acute/subacute form of the disease accounted for 26.4% of PCM cases and, on a multivariate analysis, was inversely associated with aging (OR = 0.8 per year, P < 0.001), and directly associated with female sex (OR = 7.2, P < 0.001), mixed black and white racial background (OR = 2.3, P < 0.001) or black skin color (OR = 4.6, P < 0.001). Based on these findings, we have shown that host immune response, as well as age, gender and ethnicity may influence the clinical presentation of PCM.

Significance of Aspergillus spp. isolation in defining cases of COVID-19 Associated Pulmonary Aspergillosis - CAPA.

COVID-19-Associated Pulmonary Aspergillosis (CAPA) is a relatively common complication in patients with severe forms of the disease caused by the SARS-CoV-2 virus. Diagnosing and confirming CAPA is challenging. In this study, Aspergillus spp. isolation in respiratory specimens from patients with COVID-19 was evaluated for identifying cases of CAPA. In 2020‒2021, 17 Aspergillus spp. were isolated from 15 COVID-19 patients admitted to a university hospital in Brazil. Patient records were retrospectively reviewed to obtain clinical-epidemiological data and other markers of Aspergillus spp. infection and then compared with the ECMM/ISHAM criteria for defining CAPA. Probable CAPA was defined in 5/10 patients, who had Aspergillus spp. isolated from Bronchoalveolar Lavage (BAL) or a positive galactomannan blood test. Additionally, anti-Aspergillus antibodies were detected in two of these patients, during active or follow-up phases of CAPA. In another seven patients with Aspergillus spp. isolated from tracheobronchial aspirate or sputum, CAPA was presumed, mainly due to deterioration of clinical conditions and new lung imaging suggestive of fungal infection. Antifungal agents to control CAPA, particularly voriconazole, were used in 9/15 cases. In cases of probable CAPA and remaining patients, clinical conditions and comorbidities were similar, with lethality being high, at 60% and 71%, respectively. The number of CAPA cases defined by scientific criteria was lower than that assumed in the clinical context. This was largely due to the lack of BAL collection for fungal culture and the non-intensive use of other markers of invasive aspergillosis. The isolation of Aspergillus spp. in different respiratory specimens should alert clinicians to the diagnosis of CAPA.

Chylothorax and chylous ascites due to juvenile paracoccidioidomycosis: a case report.

Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides species. Chylothorax is a rare complication of PCM. A 16-year-old adolescent presented daily fever, lymphadenomegaly, sweating, weight loss, ventilatory-dependent pain, and dysphagia, which confirmed PCM. During treatment, the patient developed chylothorax and chylous ascites. Chronic inflammatory and fibrotic lymphadenopathy may obstruct lymphatic vessels, resulting in the extravasation of lymph into the abdomen or pleural cavities. Chylothorax is one of several complications of PCM and can lead to respiratory insufficiency, even in patients undergoing antifungal therapy.

New insights on tuberculosis transmission dynamics and drug susceptibility profiles among the prison population in Southern Brazil based on whole-genome sequencing.

BACKGROUND: The rate of tuberculosis (TB) infection among the prison population (PP) in Brazil is 28 times higher than that in the general population, and prison environment favors the spread of TB. OBJECTIVE: To describe TB transmission dynamics and drug resistance profiles in PP using whole-genome sequencing (WGS). METHODS: This was a retrospective study of Mycobacterium tuberculosis cultivated from people incarcerated in 55 prisons between 2016 and 2019; only one isolate per prisoner was included. Information about movement from one prison to another was tracked. Clinical information was collected, and WGS was performed on isolates obtained at the time of TB diagnosis. RESULTS: Among 134 prisoners included in the study, we detected 16 clusters with a total of 58 (43%) cases of M. tuberculosis. Clusters ranged from two to seven isolates with five or fewer single nucleotide polymorphism (SNP) differences, suggesting a recent transmission. Six (4.4%) isolates were resistant to at least one anti-TB drug. Two of these clustered together and showed resistance to rifampicin, isoniazid, and fluoroquinolones, with 100% concordance between WGS and phenotypic drug-susceptibility testing. Prisoners with clustered isolates had a high amount of movement between prisons (two to eight moves) during the study period. CONCLUSIONS: WGS demonstrated the recent transmission of TB within prisons in Brazil. The high movement among prisoners seems to be related to the transmission of the same M. tuberculosis strain within the prison system. Screening for TB before and after the movement of prisoners using rapid molecular tests could play a role in reducing transmission.