Molecular detection of Histoplasma capsulatum in organ samples from bats randomly captured in urban areas of Araraquara, São Paulo state, Brazil.

The mycosis histoplasmosis is also considered a zoonosis that affects humans and other mammalian species worldwide. Among the wild mammals predisposed to be infected with the etiologic agent of histoplasmosis, bats are relevant because they are reservoir of Histoplasma species, and they play a fundamental role in maintaining and spreading fungal propagules in the environments since the infective mycelial phase of Histoplasma grows in their accumulated guano. In this study, we detected the fungal presence in organ samples of bats randomly captured in urban areas of Araraquara City, São Paulo, Brazil. Fungal detection was performed using a nested polymerase chain reaction to amplify a molecular marker (Hcp100) unique to H. capsulatum, which revealed the pathogen presence in organ samples from 15 out of 37 captured bats, indicating 40.5% of infection. Out of 22 Hcp100-amplicons generated, 41% corresponded to lung and trachea samples and 59% to spleen, liver, and kidney samples. Data from these last three organs suggest that bats develop disseminated infections. Considering that infected bats create environments with a high risk of infection, it is important to register the percentage of infected bats living in urban areas to avoid risks of infection to humans, domestic animals, and wildlife.

Comprehensive analysis of ADA2 genetic variants and estimation of carrier frequency driven by a function-based approach.

BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by deleterious ADA2 variants. The frequency of these variants in the general population, and hence the expected disease prevalence, remain unknown. OBJECTIVE: We aimed to characterize the functional impact and carrier frequency of ADA2 variants. METHODS: We performed functional studies and in silico analysis on 163 ADA2 variants, including DADA2-associated variants and population variants identified in the Genome Aggregation Database. We estimated the carrier rate using the aggregate frequency of deleterious variants. RESULTS: Functional studies of ADA2 variants revealed that 77 (91%) of 85 of DADA2-associated variants reduced ADA2 enzymatic function by >75%. Analysis of 100 ADA2 variants in the database showed a full spectrum of impact on ADA2 function, rather than a dichotomy of benign versus deleterious variants. We found several in silico algorithms that effectively predicted the impact of ADA2 variants with high sensitivity and specificity, and confirmed a correlation between the residual function of ADA2 variants in vitro and the plasma ADA2 activity of individuals carrying these variants (n = 45; r = 0.649; P < .0001). Using <25% residual enzymatic activity as the cutoff to define potential pathogenicity, integration of our results with the database population data revealed an estimated carrier frequency of at least 1 in 236 individuals, corresponding to an expected DADA2 disease prevalence of ~1 in 222,000 individuals. CONCLUSIONS: Functional annotation guides the interpretation of ADA2 variants to create a framework that enables estimation of DADA2 carrier frequency and disease prevalence.

SARS-CoV-2-specific T cell responses in patients with multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infections that occurs in the pediatric population. We sought to characterize T cell responses in MIS-C compared to COVID-19 and pediatric hyperinflammatory syndromes. MIS-C was distinct from COVID-19 and hyperinflammatory syndromes due to an expansion of T cells expressing TRBV11-2 that was not associated with HLA genotype. Children diagnosed with MIS-C, but who were negative for SARS-CoV-2 by PCR and serology, did not display Vß skewing. There was no difference in the proportion of T cells that became activated after stimulation with SARS-CoV-2 peptides in children with MIS-C compared to convalescent COVID-19. The frequency of SARS-CoV-2-specific TCRs and the antigens recognized by these TCRs were comparable in MIS-C and COVID-19. Expansion of Vß11-2+ T cells was a specific biomarker of MIS-C patients with laboratory confirmed SARS-CoV-2 infections. Children with MIS-C had robust antigen-specific T cell responses to SARS-CoV-2.

Considerations about the Geographic Distribution of Histoplasma Species.

Histoplasmosis is a mycotic infection principally affecting pulmonary tissue; sometimes, histoplasmosis can progress into a systemic disease. This infection involves immunocompetent and immunosuppressed human and other mammalian hosts, depending on particular circumstances. Histoplasmosis infection has been documented worldwide. The infection is acquired by inhaling infective mycelial propagules of the dimorphic fungus Histoplasma capsulatum. New reports of clinical cases of histoplasmosis in extreme latitudes could be related to human social adaptations and climate changes in the world, which are creating new favorable environments for this fungus and for bats, its major natural reservoirs and dispersers. Histoplasma has been isolated from most continents, and it is considered a complex of cryptic species, consisting of various groups of isolates that differ genetically and correlate with a particular geographic distribution. Based on updated studies, Histoplasma taxonomy is adjusting to new genetic data. Here, we have suggested that Histoplasma has at least 14 phylogenetic species distributed worldwide and new genotypes that could be under deliberation. Histoplasma's geographic radiation began in South America millions of years ago when the continents were joined and the climate was favorable. For fungal spreading, the role of bats and some birds is crucial, although other natural factors could also participate.

Accuracy of bedside point of care testing in critical emergency department patients.

BACKGROUND: Point-of-care (POC) testing reduces laboratory turn-around having the potential to improve timely diagnosis and management. We compared the accuracy of nurse performed POC and core laboratory testing and determined whether deviations between the two were clinically meaningful. METHODS: We performed a prospective, observational study on a convenience sample of 50 critical care ED patients in whom a POC chemistry and hematocrit was ordered. Blood samples were divided into 2 aliquots; one sample was tested by the treating nurse using a handheld POC device and the other sample was tested in the core laboratory. Paired comparisons of test results were performed using Pearson's correlation coefficients, Lin concordance coefficients, and Bland Altman plots. RESULTS: Mean patient age was 67, 50% were male, 82% were admitted. Pearson's correlation and Lin concordance coefficients were excellent (0.84-1.00) for all 8 analytes. Mean (95%CI) paired differences between POC and core laboratory measurements were Na+ 0.30 (-0.22 to 0.82) mmol/L, K+-0.12 (-0.14 to - 0.09) mmol/L, Cl- 2.10 (1.41 to 2.78) mmol/L, TCO2-1.68 (-2.06 to -1.30) mmol/L, glucose 2.46 (1.46 to 3.46) mg/dL, BUN, 1.69 (0.95 to 2.42) mg/dL, creatinine 0.13 (0.08 to 0.17) mg/dL, and hematocrit -0.39 (-0.93 to 0.15) %. In 3 of 400 measurements, the difference between POC and core lab exceeded the maximal clinically acceptable deviation based on physician surveys. CONCLUSIONS: Bedside POC by ED nurses is reliable and accurate and does not deviate significantly from core laboratory testing by trained technicians.

Multiplex polymerase chain reaction as an improved method for screening Histoplasma capsulatum mating types.

Histoplasmosis is a systemic mycosis infection caused by Histoplasma capsulatum, a heterothallic ascomycete. The sexual reproduction of this fungus is regulated by the mating type (MAT1) locus that contains MAT1-1 and MAT1-2 idiomorphs, which were identified by uniplex polymerase chain reaction (PCR). This study aimed to optimise single-step multiplex PCR for the accurate detection of the distinct mating types of H. capsulatum. Among the 26 isolates tested, 20 had MAT1-1 genotype, while six showed MAT1-2 genotype, in agreement with the uniplex PCR results. These results suggest that multiplex PCR is a fast and specific tool for screening H. capsulatum mating types.

Comparison of Levetiracetam Dosing Regimens in End-Stage Renal Disease Patients Undergoing Intermittent Hemodialysis.

BACKGROUND: Levetiracetam (LEV) is primarily renally eliminated. In end-stage renal disease (ESRD) patients on hemodialysis (HD), pharmacokinetic studies recommend daily dosing with 50% supplemental doses after 4-hour HD sessions. However, poor medication adherence after HD could result in fluctuating plasma drug levels. OBJECTIVE: To compare two LEV dosing regimens, daily versus twice-daily (BID), in ESRD patients undergoing HD. METHODS: Consecutive ESRD patients (April 2013 to May 2014) receiving maintenance inpatient HD and prescribed LEV prior to admission to our academic tertiary hospital were prospectively analyzed. Demographics, initial lab values, adverse reactions, seizures, and LEV regimens were recorded. LEV levels were obtained pre-HD and post-HD along with levels after receiving post-HD doses. Recovery of plasma levels after HD was assessed by comparison of levels predialysis versus postdialysis and post-HD doses. RESULTS: We identified 22 patients who met inclusion criteria; 14 BID and 8 daily dosing. Mean predialysis, postdialysis, and post-HD dose plasma levels were higher in patients receiving LEV BID compared with daily (43.1 ± 6.3, 19.4 ± 5.2, 34.9 ± 4.3 vs 21.1 ± 3.9, 6.9 ± 1.5, 11.9 ± 1.7 µg/mL; P < 0.05). BID post-HD levels were 41.9 ± 4.6% of predialysis levels versus 36.9 ± 7.3% with daily dosing ( P = 0.275). Post-HD dose levels were 81.4±4.3% of predialysis on LEV BID versus 65.7 ± 8.8% on LEV daily ( P = 0.045). No seizures were reported during hospital admission in either group. CONCLUSIONS: Compared to LEV daily, BID dosing achieved significantly higher levels and a better recovery to predialysis levels. Although limited by small numbers, a similar relationship between postdialysis levels was not detected.

Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response.

Pulmonary surfactant is a complex fluid that comprises phospholipids and four proteins (SP-A, SP-B, SP-C, and SP-D) with different biological functions. SP-B, SP-C, and SP-D are essential for the lungs' surface tension function and for the organization, stability and metabolism of lung parenchyma. SP-A and SP-D, which are also known as pulmonary collectins, have an important function in the host's lung immune response; they act as opsonins for different pathogens via a C-terminal carbohydrate recognition domain and enhance the attachment to phagocytic cells or show their own microbicidal activity by increasing the cellular membrane permeability. Interactions between the pulmonary collectins and bacteria or viruses have been extensively studied, but this is not the same for fungal pathogens. SP-A and SP-D bind glucan and mannose residues from fungal cell wall, but there is still a lack of information on their binding to other fungal carbohydrate residues. In addition, both their relation with immune cells for the clearance of these pathogens and the role of surfactant proteins' regulation during respiratory fungal infections remain unknown. Here we highlight the relevant findings associated with SP-A and SP-D in those respiratory mycoses where the fungal infective propagules reach the lungs by the airways.

International Society of Human and Animal Mycology (ISHAM)-ITS reference DNA barcoding database--the quality controlled standard tool for routine identification of human and animal pathogenic fungi.

Human and animal fungal pathogens are a growing threat worldwide leading to emerging infections and creating new risks for established ones. There is a growing need for a rapid and accurate identification of pathogens to enable early diagnosis and targeted antifungal therapy. Morphological and biochemical identification methods are time-consuming and require trained experts. Alternatively, molecular methods, such as DNA barcoding, a powerful and easy tool for rapid monophasic identification, offer a practical approach for species identification and less demanding in terms of taxonomical expertise. However, its wide-spread use is still limited by a lack of quality-controlled reference databases and the evolving recognition and definition of new fungal species/complexes. An international consortium of medical mycology laboratories was formed aiming to establish a quality controlled ITS database under the umbrella of the ISHAM working group on "DNA barcoding of human and animal pathogenic fungi." A new database, containing 2800 ITS sequences representing 421 fungal species, providing the medical community with a freely accessible tool at http://www.isham.org/ and http://its.mycologylab.org/ to rapidly and reliably identify most agents of mycoses, was established. The generated sequences included in the new database were used to evaluate the variation and overall utility of the ITS region for the identification of pathogenic fungi at intra-and interspecies level. The average intraspecies variation ranged from 0 to 2.25%. This highlighted selected pathogenic fungal species, such as the dermatophytes and emerging yeast, for which additional molecular methods/genetic markers are required for their reliable identification from clinical and veterinary specimens.

Comprehensive bedside point of care testing in critical ED patients: a before and after study.

OBJECTIVE: We determined the effects of comprehensive point-of-care testing (POCT) on process of care in critically ill emergency department (ED) patients. We hypothesized that POCT would shorten ED length of stay (LOS), reduce time to test results, and reduce time to completion of intravenous (IV) contrast computed tomography (CT) imaging compared with central lab testing. METHODS: A before and after study was performed in ED patients triaged to the critical care area. During the before period, traditional lab testing was performed, whereas in the after period, bedside POCT devices were introduced in all 15 critical care beds with 5 testing cartridges (chemistry with hemoglobin and hematocrit, troponin I, brain natriuretic peptide, lactate, and international normalized ratio [INR]). Clinical protocols indicated when POCT should be used. RESULTS: The numbers of critical ED patients before and after introducing POCT were 1405 and 981 respectively. Test turnaround (minutes) was significantly reduced with bedside POCT for all five tests. Use of POCT reduced the median [interquartile range] time to completion of IV contrast CT by 81 minutes (96 [55-214] vs 177 [78-300]; P = .004). Point-of-care testing significantly reduced median ED LOS in patients who received an IV contrast CT (260 [180-410] vs 347 [347 (202-523]; P = .03). CONCLUSIONS: Introduction of comprehensive bedside POCT in critical ED patients is associated with significant reductions in test turnaround, and time to completion of CT scanning when IV contrast is required. ED LOS was also reduced in the latter population.

Evaluation of a liquid dressing for minor nonbleeding abrasions and class I and II skin tears in the emergency department.

BACKGROUND: Minor abrasions and skin tears are usually treated with gauze dressings and topical antibiotics requiring frequent and messy dressing changes. OBJECTIVE: We describe our experience with a low-cost, cyanoacrylate-based liquid dressing applied only once for minor abrasions and skin tears. METHODS: We conducted a single-center, prospective, noncomparative study in adult emergency department (ED) patients with minor nonbleeding skin abrasions and class I and II skin tears. After cleaning the wound and achieving hemostasis, the wounds were covered with a single layer of a cyanoacrylate liquid dressing. Patients were followed every 1-2 days until healing. RESULTS: We enrolled 40 patients with 50 wounds including 39 abrasions and 11 skin tears. Mean (standard deviation) age was 54.5 (21.9) years and 57.5% were male. Wounds were located on the face (n = 16), hands (n = 14), legs (n = 11), and arms (n = 9). Pain scores (0 to 10 from none to worst) after application of the liquid dressing were 0 in 62% and 1-3 in the remaining patients. Follow-up was available on 36 patients and 46 wounds. No wounds re-bled and there were no wound infections. Only one wound required an additional dressing. Median (interquartile range [IQR]) time to complete sloughing of the adhesive was 7 (5.5-8) days. Median (IQR) time to complete healing and sloughing of the overlying scab was 10 (7.4-14) days. CONCLUSIONS: Our study suggests that a single application of a low-cost cyanoacrylate-based liquid adhesive is a safe and effective treatment for superficial nonbleeding abrasions and class I and II skin tears that eliminates the need for topical antibiotics and dressings.

Histoplasma capsulatum and Pneumocystis spp. co-infection in wild bats from Argentina, French Guyana, and Mexico.

BACKGROUND: Histoplasma capsulatum and Pneumocystis organisms cause host infections primarily affecting the lung tissue. H. capsulatum is endemic in the United States of America and Latin American countries. In special environments, H. capsulatum is commonly associated with bat and bird droppings. Pneumocystis-host specificity has been primarily studied in laboratory animals, and its ability to be harboured by wild animals remains as an important issue for understanding the spread of this pathogen in nature. Bats infected with H. capsulatum or Pneumocystis spp. have been found, with this mammal serving as a probable reservoir and disperser; however, the co-infection of bats with both of these microorganisms has never been explored. To evaluate the impact of H. capsulatum and Pneumocystis spp. infections in this flying mammal, 21 bat lungs from Argentina (AR), 13 from French Guyana (FG), and 88 from Mexico (MX) were screened using nested-PCR of the fragments, employing the Hcp100 locus for H. capsulatum and the mtLSUrRNA and mtSSUrRNA loci for Pneumocystis organisms. RESULTS: Of the 122 bats studied, 98 revealed H. capsulatum infections in which 55 of these bats exhibited this infection alone. In addition, 51 bats revealed Pneumocystis spp. infection of which eight bats exhibited a Pneumocystis infection alone. A total of 43 bats (eight from AR, one from FG, and 34 from MX) were found co-infected with both fungi, representing a co-infection rate of 35.2% (95% CI = 26.8-43.6%). CONCLUSION: The data highlights the H. capsulatum and Pneumocystis spp.co-infection in bat population's suggesting interplay with this wild host.

Frequency and genetic diversity of the MAT1 locus of Histoplasma capsulatum isolates in Mexico and Brazil.

The MAT1-1 and MAT1-2 idiomorphs associated with the MAT1 locus of Histoplasma capsulatum were identified by PCR. A total of 28 fungal isolates, 6 isolates from human clinical samples and 22 isolates from environmental (infected bat and contaminated soil) samples, were studied. Among the 14 isolates from Mexico, 71.4% (95% confidence interval [95% CI], 48.3% to 94.5%) were of the MAT1-2 genotype, whereas 100% of the isolates from Brazil were of the MAT1-1 genotype. Each MAT1 idiomorphic region was sequenced and aligned, using the sequences of the G-217B (+ mating type) and G-186AR (- mating type) strains as references. BLASTn analyses of the MAT1-1 and MAT1-2 sequences studied correlated with their respective + and - mating type genotypes. Trees were generated by the maximum likelihood (ML) method to search for similarity among isolates of each MAT1 idiomorph. All MAT1-1 isolates originated from Brazilian bats formed a well-defined group; three isolates from Mexico, the G-217B strain, and a subgroup encompassing all soil-derived isolates and two clinical isolates from Brazil formed a second group; last, one isolate (EH-696P) from a migratory bat captured in Mexico formed a third group of the MAT1-1 genotype. The MAT1-2 idiomorph formed two groups, one of which included two H. capsulatum isolates from infected bats that were closely related to the G-186AR strain. The other group was formed by two human isolates and six isolates from infected bats. Concatenated ML trees, with internal transcribed spacer 1 (ITS1) -5.8S-ITS2 and MAT1-1 or MAT1-2 sequences, support the relatedness of MAT1-1 or MAT1-2 isolates. H. capsulatum mating types were associated with the geographical origin of the isolates, and all isolates from Brazil correlated with their environmental sources.

ED bedside point-of-care lactate in patients with suspected sepsis is associated with reduced time to iv fluids and mortality.

OBJECTIVE: Early recognition and treatment of sepsis improves outcomes. We determined the effects of bedside point-of-care (POC) lactate measurement on test turnaround time, time to administration of IV fluids and antibiotics, mortality, and ICU admissions in adult ED patients with suspected sepsis. We hypothesized that bedside lactate POC testing would reduce time to IV fluids and antibiotics. METHODS: We compared 80 ED patients with suspected sepsis and a lactate level of 2 mmol/L or greater before and 80 similar patients after introduction of POC lactate measurements. Groups were compared with Χ(2) and Mann Whitney U tests. A sample size of 80 patients in each group had 85% power to detect a 30-minute difference in time to IV fluids or antibiotics. RESULTS: Study groups were similar in age, gender, baseline lactate levels, sepsis severity, and Sequential Organ Failure Assessment (SOFA) scores. Introduction of POC lactate was associated with significant reductions in test turnaround time (34 [26-55] vs. 122 [82-149] minutes; P < 0.001), time to IV fluids (55 [34-83] vs. 71 [42-110] minutes; P = 0.03), mortality (6% vs. 19%; P = 0.02), and ICU admissions (33% vs. 51%, P = 0.02), but not time to IV antibiotics (89 [54-156] vs. 88 [60-177] minutes; P = 0.35). CONCLUSIONS: Implementation of bedside POC lactate measurement in adult ED patients with suspected sepsis reduces time to test results and time to administration of IV fluids but not antibiotics. A significant reduction in mortality and ICU admissions was also demonstrated, which is likely due, at least in part, to POC testing.

Language tests and tests of competence for registration purposes - a scoping review of the experiences of overseas nurses.

BACKGROUND: The overseas applicant's capability of practising safely and effectively is proven through the tests of competence which consist of computer-based tests and the Objective Structured Clinical Examination (OSCE). All prospective applicants to the Nursing and Midwiferey Council (NMC) register must be able to demonstrate that their skills, knowledge and behaviours are at the level required to meet the NMC preregistration nursing or midwifery standards for the United Kingdom (UK). AIM: The aim of this review is to explore the challenges faced whilst undertaking these tests of competence, the OSCE, by overseas educated nurses who aspire for Nursing and Midwifery Council (NMC) registration in the UK. METHODS: A scoping review using the Arksey and O'Malley (2005) framework was conducted to explore and produce a profile of the existing literature on the registration requirements of the NMC. A search of CINAHL, Medline and Scopus resulted in 150 records, which were then screened against the inclusion criteria - English Language, publication between 2015 onwards and discussed the language tests/competency tests required for gaining entry to the NMC register. A total of nine articles met the criteria and are included in this scoping review. The PRISMA-ScR framework is used to present the review. RESULTS: There was a paucity of studies that addressed the experience of overseas nurses who faced the OSCE. An interpretative stance was adopted to formulate the themes which were: competence/practice disparity, arbitrary issues for failing, failure to capture the digital health agenda, financial implications, and consequences of failing the OSCE. The results raise concern whether the nurses from overseas are held to higher standards than those trained in the UK and whether the assessment process is realistic and not pedantic. CONCLUSIONS: This scoping review demonstrates there is a lack of robust research evaluating the effectiveness of tests of competencies. The review indicates there is no due acknowledgement of the previous skills and knowledge of the overseas nurses. Future research should focus on exploring the feasibility of tests of competence and its role in the integration of the nursing workforce.

Ibuprofen vs acetaminophen vs their combination in the relief of musculoskeletal pain in the ED: a randomized, controlled trial.

Non-opioid analgesics are often administered to emergency department (ED) patients with musculoskeletal pain but if inadequate, opioids are given with associated potential adverse events. We tested the hypothesis that the reduction in pain scores with the combination of ibuprofen and acetaminophen would be at least 15 mm greater than with either of the agents alone. We conducted a double-blind, randomized, controlled trial of adult ED patients with acute musculoskeletal pain. Patients were randomized to oral ibuprofen 800 mg, acetaminophen 1 g, or their combination. Pain scores across the groups were compared with repeated measures analysis of variance at 20, 40, and 60 minutes. A sample of 30 patients in each group had 80% power to detect a 15 mm difference in pain scores across the groups (α = .05). Thirty patients were randomized to each study group. Mean (SD) age was 36 (15), 54% were male, 73% were white, and 13% were Hispanic. Groups were well balanced in baseline characteristics including initial pain scores (59, 61, and 62 for ibuprofen, acetaminophen, and their combination). Pain decreased over the one hour study period for all groups (P < .001) with mean (SD) scores about 20 mm lower on the Visual Analogue Scale than the mean initial score. However, there was no significant difference among treatments (P = .59). The need for rescue analgesics was similar across groups. We conclude that the combination of ibuprofen and acetaminophen did not reduce pain scores or the need for rescue analgesics compared with either agent alone in ED patients with pain secondary to acute musculoskeletal injuries.

Molecular detection of Histoplasma capsulatum in the lung of a free-ranging common noctule (Nyctalus noctula) from France using the Hcp100 gene.

Histoplasma capsulatum is a dimorphic fungus that is widely distributed in the tropical or subtropical areas of the world and infects several mammalian hosts, mainly bats. Infective propagules grow in bat and bird droppings. A specific molecular marker, a highly sensitive fragment of a co-activator protein-coding gene (Hcp100), was used to detect H. capsulatum in lung samples of wild and captive bats from France using a nested polymerase chain reaction. To determine whether bats in France are potential carriers of H. capsulatum, 83 bats were sampled from two regions in France. Sixty-one specimens belonging to the Pteropus rodricensis (n = 45) and Rousettus aegyptiacus (n = 16) species were collected from a zoologic park (La Palmyre, western France). Twenty-two specimens were recovered from the Natural History Museum (Bourges) including the species Plecotus austriacus (n = 1), Pipistrellus pipistrellus (n = 3), and Nyctalus noctula (n = 18). From the lung DNA samples of 83 dead bats, only one sample of an N. noctula bat from Bourges amplified the H. capsulatum Hcp100 marker. The amplified product was sequenced and revealed a high similarity to the G217B H. capsulatum reference strain sequence that was deposited in the GenBank database. This finding suggests that H. capsulatum is an environmental pathogen in France that may infect bats.

Central Nervous System Histoplasmosis: An Updated Insight.

Histoplasmosis is one of the systemic mycoses that can involve the Central Nervous System (CNS), and it is caused by the dimorphic ascomycete species of the Histoplasma capsulatum complex. Once in the CNS, this pathogen causes life-threatening injuries that are associated with clinical manifestations of meningitis, focal lesions (abscesses, histoplasmomas), and spinal cord injuries. The present review provides updated data and highlights a particular vision regarding this mycosis and its causative agent, as well as its epidemiology, clinical forms, pathogenesis, diagnosis, and therapy, focusing on the CNS.

Unusual Differences in the Pulmonary Histopathology of Mice after Intranasal Infection with Mycelial Propagules of Histoplasma capsulatum Strains Classified as LAm A2 and NAm 2 Phylogenetic Species.

The ascomycete Histoplasma capsulatum is the causative agent of systemic respiratory mycosis histoplasmosis, which sometimes develops acute disseminated or chronic clinical forms, with the latter usually associated with granuloma formation. The present report shows differential histopathological changes in the pulmonary inflammatory response of mice infected intranasally with the mycelial morphotype of H. capsulatum strains with distinct genotypes, EH-46 and G-217B, classified as LAm A2 and NAm 2 phylogenetic species, respectively. Infected male BALB/c mice were sacrificed at different postinfection times, and their serial lung sections were stained with periodic acid-Schiff and analyzed via microscopy. In mice infected with the LAm A2 strain, the results showed progressive changes in the inflammatory infiltrate of the lung parenchyma during the first hours and days postinfection as well as granulomas with macrophages containing intracellular yeast cells, which prevailed at 14 and 21 days postinfection. Bronchiolar-associated lymphoid tissue was induced in mice infected with both strains, primarily in mice infected with the NAm 2 strain. Several lung sections from mice infected with the LAm A2 strain showed PAS-positive yeast cells aggregated in a perinuclear crown-like arrangement in macrophages from 3 h to 21 days postinfection. These findings highlight differences in the host pulmonary inflammatory response associated with distinct H. capsulatum species.

Incidence and Risk Factors for Eosinophilia and Lung Disease in Biologic-Exposed Children With Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: Although interleukin-1 (IL-1)/IL-6 inhibitors are effective therapies for systemic juvenile idiopathic arthritis (JIA), some patients develop eosinophilia and lung disease during treatment. This study was undertaken to retrospectively evaluate incidence and risk factors for eosinophilia and describe lung disease outcomes in IL-1/IL-6 inhibitor-exposed patients with systemic JIA. METHODS: Among JIA patients at our institution exposed to interleukin-1 (IL-1)/IL-6 inhibitors (1995-2022), we compared incidence rate of eosinophilia in systemic JIA compared to other JIA, stratified by medication class (IL-1/IL-6 inhibitors, other cytokine inhibitors, methotrexate). We used Cox models to identify predictors of eosinophilia during IL-1/IL-6 inhibitor use and summarized treatment changes and outcomes after eosinophilia, including lung disease. HLA typing was performed on a clinical or research basis. RESULTS: There were 264 new medication exposures in 75 patients with systemic JIA and 41 patients with other JIA. A total of 49% of patients with systemic JIA with HLA typing (n = 45) were positive for HLA-DRB1*15 alleles. Eosinophilia was common during IL-1/IL-6 inhibitor use and did not differ by systemic JIA compared to other JIA (0.08 and 0.07 per person-year, respectively; P = 0.30). Among systemic JIA patients, pretreatment macrophage activation syndrome (MAS) was associated with a higher rate of subsequent eosinophilia on biologic therapy (unadjusted hazard ratio 3.2 [95% confidence interval 1.2-8.3]). A total of 4 of 5 patients who switched therapy within 10 weeks of eosinophilia experienced disease flare compared to none of the patients who continued the original therapy. A total of 8 of 25 patients with pulmonary evaluations had lung disease, and all had severe manifestations of systemic JIA (MAS, intensive care unit stay). One death was attributed to systemic JIA-lung disease. CONCLUSION: Eosinophilia is common in JIA patients using IL-1/IL-6 inhibitors. Severe disease may be associated with eosinophilia and lung disease in systemic JIA.