Paracoccidioidomycosis after eyebrow micropigmentation: Unusual reactivation or a new form of transmission by cutaneous inoculation?

We report a case of unusual paracoccidioidomycosis reactivation after eyebrow micropigmentation in a Brazilian patient. The cutaneous lesion was the only clinical manifestation. Direct cutaneous inoculation in dermal tissues with Paracoccidioides sp. is extremely rare, explaining why paracoccidioidomycosis is not classically considered a cutaneous implantation mycosis.

Clinical characteristics, diagnosis, and treatment of central nervous system sporotrichosis: Systematic review and meta-analysis.

BACKGROUND: The clinical features of central nervous system (CNS) sporotrichosis are derived from case reports and a limited series of cases. Our objective was to carry out a systematic review and meta-analysis of CNS sporotrichosis. METHODS: We searched PubMed/MEDLINE, Embase, Scopus, and LILACS on 9 September 2023. Our inclusion criteria were documentation of Sporothrix and demonstrated CNS involvement. A metaproportion or metamean analysis was performed to estimate a summary proportion with 95% confidence intervals. RESULTS: We included 52 cases of CNS sporotrichosis published from 1966 to 2023. Forty-six patients were male (88%, 95% CI: 77-95), and the mean age was 39 years (95% CI: 36-43). Close contact with cats was reported in 55% of cases (95% CI: 37-72). Thirty-two (61.5%) patients were from Brazil, 18 patients from the United State of America (34.6%). Only two Sporothrix species were reported: S. schenckii (26/41, 63%), and S. brasiliensis (15/41, 37%). The most common neurological symptom was headache. Meningitis was chronic in approximately 80% of cases. A significant majority of the patients were immunocompromised. HIV infection was the primary cause of immunosuppression (85%, 95% CI: 61-95). Overall mortality was 56% (22/39). The comparison of Kaplan-Meier survival curve showed a higher mortality with a statistically significant difference in immunosuppressed patients (p = .019). CONCLUSION: CNS sporotrichosis represents a notable cause of chronic meningitis, especially in individuals living in the Americas with HIV infection and concurrent skin lesions.

Itraconazole Serum Trough Concentrations Using Oral Capsules for the Treatment of Chronic Pulmonary Aspergillosis: What is the Target?

BACKGROUND: In regions where there is only itraconazole capsule as a therapeutic option for treatment of chronic pulmonary aspergillosis (CPA), measuring the serum concentrations becomes even more important for therapeutic success. OBJECTIVE: Evaluate the initial itraconazole serum trough concentrations after the administration of oral capsule of itraconazole for the treatment of CPA. METHODS: The measurement was performed at least 7-days after initiation of therapy. The standard treatment at our institution was a 200 mg capsule every 12 h. We defined that an adequate serum trough concentration of itraconazole during treatment was 1-4 mg/L. RESULTS: This study recruited 28 patients. The median value was 0.30 mg/L (IQR 0.01-0.70). Only 11% (n = 3) had adequate serum concentrations based on guideline recommendation. All patients with clinical deterioration had itraconazole serum levels ≤ 0.8 mg/L. CONCLUSION: The initial serum concentrations of itraconazole after capsule formulation administration were low. Increasing the dose should be considered when the itraconazole concentration is low, especially if it is ≤ 0.8 mg/L, and the patient presents with clinical deterioration. Larger studies are needed to evaluate the adequate concentrations recommended for CPA.

Systematic review and meta-analysis of galactomannan antigen testing in serum and bronchoalveolar lavage for the diagnosis of chronic pulmonary aspergillosis: defining a cutoff.

BACKGROUND: A clear cutoff value of galactomannan (GM) has not been established for chronic pulmonary aspergillosis (CPA) and is frequently extrapolated from invasive pulmonary aspergillosis. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of serum and bronchoalveolar lavage (BAL) GM, and to propose a cutoff. METHODS: We extracted from the studies the cutoff of serum or/and BAL GM associated with true positives, false positives, true negatives, and false negatives. We performed a multi-cutoff model and a non-parametric random effect model. We estimated the optimal cutoff and the area under the curve (AUC) for GM in serum and BAL samples. RESULTS: Nine studies from 1999 to 2021 were included. Overall, the optimal cutoff of serum GM was 0.96 with a sensitivity of 0.29 (95%CI: 0.14-0.51); specificity of 0.88 (95%CI: 0.73-0.95); and AUC of 0.529 (with a CI: [0.415-0.682] [0.307-0.713]). The AUC for the non-parametric ROC model was 0.631. For BAL GM the cutoff was 0.67 with a sensitivity of 0.68 (95%CI: 0.51-0.82), specificity of 0.84 (95%CI: 0.70-0.92), and AUC of 0.814 (with a CI: [0.696-0.895] [0.733-0.881]). The AUC for the non-parametric model was 0.789. CONCLUSION: The diagnosis of CPA requires the assessment of a combination of mycological and serological factors, as no single serum and/or BAL GM antigen test is adequate. BAL GM performed better than serum, with better sensitivity and excellent accuracy.

Clinical, radiological and laboratory characteristics of central nervous system histoplasmosis: A systematic review of a severe disease.

BACKGROUND: The knowledge of central nervous system (CNS) histoplasmosis is limited to case reports and series. OBJECTIVES: Our objective was to synthesise clinical, radiological and laboratory characteristics of CNS histoplasmosis to improve our understanding of this rare disease. METHODS: We performed a systematic review using Pubmed/MEDLINE, Embase and LILACS databases accessed on March 2023 without publication date restrictions. Inclusion criteria comprised: (1) histopathological, microbiological, antigen or serological evidence of histoplasmosis; (2) CNS involvement based on cerebrospinal fluid pleocytosis or neuroimaging abnormalities. We classified the certainty of the diagnosis in proven (CNS microbiological and histopathological confirmation), probable (CNS serological and antigen confirmation) or possible (non-CNS evidence of histoplasmosis). Metaproportion was used to provide a summary measure with 95% confidence intervals for the clinical, radiological and laboratory characteristics. Chi-squared test was used to compare mortality between pairs of antifungal drugs. RESULTS: We included 108 studies with 298 patients. The median age was 31 years, predominantly male, and only 23% were immunocompromised (134/276, 95%CI: 3-71), mainly due to HIV infection. The most common CNS symptom was headache (130/236, 55%, 95%CI: 49-61), with a duration predominantly of weeks or months. Radiological presentation included histoplasmoma (79/185, 34%, 95%CI: 14-61), meningitis (29/185, 14%, 95%CI: 7-25), hydrocephalus (41/185, 37%, 95%CI: 7-83) and vasculitis (18/185, 6%, 95%CI: 1-22). There were 124 proven cases, 112 probable cases and 40 possible cases. The majority of patients presented positive results in CNS pathology (90%), serology (CSF: 72%; serum: 70%) or CSF antigen (74%). Mortality was high (28%, 56/198), but lower in patients who used liposomal amphotericin B and itraconazole. Relapse occurred in 13% (23/179), particularly in HIV patients, but less frequently in patients who used itraconazole. CONCLUSION: Central nervous system histoplasmosis usually presents subacute-to-chronic symptoms in young adults. Neuroimaging patterns included not only focal lesions but also hydrocephalus, meningitis and vasculitis. Positive results were commonly found in CSF antigen and serology. Mortality was high, and treatment with liposomal amphotericin B followed by itraconazole may decrease mortality.

Challenges, Characteristics, and Outcomes of Chronic Pulmonary Aspergillosis: A 11-Year Experience in A Middle-Income Country.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is a research priority in fungal diseases with a need for new studies to reduce misdiagnosis with more common diseases, discuss improvement in diagnostic methods and better characterize gaps in antifungal and surgical treatments to improve clinical outcomes. METHODS: In this retrospective study, we reviewed medical records of patients diagnosed with CPA from January 2010 to June 2021 at University of São Paulo, São Paulo, Brazil. We evaluated clinical characteristics, radiological findings, serology, treatment, and outcomes. RESULTS: The study included 91 participants, with 43 (47.3%) patients who underwent surgery and 69 (75.8%) received antifungal therapy. We found a predominance of middle-aged adults (median 51 years), males (n = 58, 64%) with lower BMI (median 21.3 kg/m2). The most common underlying lung disease was pulmonary tuberculosis (n = 70, 76.9%). The commonest symptoms were cough (n = 67, 74%), haemoptysis, and dyspnea (n = 63, 70%). The most common chest computerized tomography abnormalities were cavity (n = 86, 94.5%), with a predominance of mycetomas (n = 78, 91%). The serology was positive in 81% (61/75). The one-year mortality was low (3.3%). Clinical improvement and stability occurred in 89% of participants for constitucional symptoms and 86% for pulmonary symptoms. While serological improvement and stability occurred in 71%. Radiological improvement and stability occurred in 75%. CONCLUSION: We observed a good outcome after 1-year follow-up, in which the majority had improvement or stability of pulmonary and constitutional symptoms, decrease in CIE titers and low mortality.

Sensitivity of Antigen, Serology, and Microbiology Assays for Diagnosis of the Subtypes of Chronic Pulmonary Aspergillosis at a Teaching Hospital in São Paulo, Brazil.

Chronic pulmonary aspergillosis (CPA) is divided into five subtypes. The diagnosis of CPA is complicated due to poor sensitivity of the laboratory tests. Diagnostic performance of different antigen, serological, and microbiological methods in subtypes of CPA is unknown. The purpose of this study was to evaluate the diagnostic performance in different subtypes of CPA. A total of 91 participants with CPA were included, and the study was performed at Hospital das Clínicas of University of São Paulo. Bronchoalveolar lavage galactomannan (73%, 11/15), serology by immunodiffusion test (81%, 61/75), and histology (78%, 39/50) had the best sensitivity. The counterimmunoelectrophoresis (CIE) titers had a significant statistical difference between the CPA subtypes (P < 0.001), in which the forms chronic fibrosing pulmonary aspergillosis (CFPA) and subacute invasive aspergillosis (SAIA) had higher titers: 1/64 (interquartile range [IQR]: 1/32-1/256) and 1/64 (1/32-1/128). C-reactive protein generally presented lower values (median 15 mg/L, IQR: 6-33), with higher values in SAIA and lower values for Aspergillus nodule. Overall, we found a low diagnostic sensitivity of current tests. Regarding the CPA subtypes, we did not find great differences in the performance of the tests, but it is observed that the inflammatory markers and CIE titers tend to be higher in forms of the more extensive lung parenchyma involvement, such as SAIA and CFPA.

Neisseria gonorrhoeae arthritis in a patient with systemic lupus: resistance and virulence profiles.

In this study, we describe a case report of gonococcal arthritis in a Systemic Lupus Erythematosus patient. Although several mechanisms favor disseminated gonococcal infection (DGI) in patients immunosuppressed by SLE, this association is rarely reported in literature. We performed whole genome sequencing (WGS) of the etiologic agent involved and molecular analysis using a global collection of Neisseria gonorrhoeae strains. Ours is the only sample derived from synovial fluid identified in this collection, the others being from the usual anatomical sites. Antimicrobial susceptibility was determined by disk diffusion and Etest, and WGS was conducted to determine multilocus sequence typing profiles, group isolates based on core genome single nucleotide polymorphisms (SNP), and identify virulence genes and antimicrobial resistance determinants. The N. gonorrhoeae samples in the global collection were highly heterogeneous. The SNP tree had a total 19,532 SNPs in 320 samples. Our sample displayed resistance to ciprofloxacin (MIC = 2 µg/mL) and tetracycline (zone diameter = 0 mm) belonged to ST 1588 and was not closely related to any isolate in the global collection of N. gonorrhoeae strains. The isolate had genetic features related to beta-lactam, tetracycline and quinolone resistance. Seventy-one virulence genes were identified in our sample, belonging to the following classes: adherence, efflux pump, immune modulator, invasion, iron uptake, protease and stress adaptation. Moreover, no virulence genes for immune evasion and toxin were identified.

Systematic review of neuroparacoccidioidomycosis: The contribution of neuroimaging.

BACKGROUND: Advanced neuroimaging demonstrated that neurological involvement occurs in up to 30% of paracoccidioidomycosis (PCM) cases. Current knowledge of neuroparacoccidioidomycosis (NPCM) is based on a 2009 systematic review. However, in the last decade, several new cases have been published, with modern neuroimaging techniques. OBJECTIVES: We believe a new systematic review is needed to summarise these advances. METHODS: We searched PubMed/MEDLINE, Embase and LILACS for studies from January 2010 to May 2022. Case series and case reports of NPCM were included. We performed a metaproportion to estimate a summary proportion with 95% confidence intervals (CI). RESULTS: Thirty-four studies including 104 patients were evaluated. We combined our data with the results from the previous review that included 257 cases, totalling 361 patients. We found no new important demographic, clinical or laboratory characteristics. On magnetic resonance imaging (MRI), we found that 72% (95%CI: 38-91) had hyperintensity on T1-weighted image; 84% (95%CI: 71%-92%) had hypointensity on T2-weighted image; 80% (95%CI: 66-89) had contrast enhancement with the classical ring-enhancing pattern. All 8 patients undergoing spectroscopy presented lipid peaks. We found a 16% mortality, lower than in the previous review (44%). CONCLUSION: NPCM presents a characteristic pattern on MRI that may help to differentiate it from other causes of single or multiple brain lesions. Albeit there is a frequent pattern, it is not specific, as other granulomatous diseases may show similar findings. Advances in neuroimaging with early diagnosis and appropriate management of the disease may have contributed to reducing its mortality.

Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Shedding and Predictors of Viral Culture Positivity on Vaccinated Healthcare Workers With Mild Coronavirus Disease 2019.

In this prospective cohort of 30 vaccinated healthcare workers with mild Omicron variant infection, we evaluated viral culture, rapid antigen test (RAT), and real-time reverse-transcription polymerase chain reaction (RT-PCR) of respiratory samples at days 5, 7, 10, and 14. Viral culture was positive in 46% (11/24) and 20% (6/30) of samples at days 5 and 7, respectively. RAT and RT-PCR (Ct ≤35) showed 100% negative predictive value (NPV), with positive predictive values (PPVs) of 32% and 17%, respectively, for predicting viral culture positivity. A lower RT-PCR threshold (Ct ≤24) improved culture prediction (PPV = 39%; NPV = 100%). Vaccinated persons with mild Omicron infection are potentially transmissible up to day 7. RAT and RT-PCR might be useful tools for shortening the isolation period.

Orthopedic infections due to Trichosporon species: Case series and literature review.

Reports of orthopedic fungal infections caused by Trichosporon species are extremely scarce, thus we aimed to describe a case series and review the cases published in the literature. Patients were retrospectively included if a previous culture of bone, joint, or soft tissues had resulted positive for Trichosporon species along with a clinical diagnosis of an orthopedic infection. Eight patients were included with diverse orthopedic conditions, most of them cases of osteomyelitis. The main isolated species was Trichosporon asahii. All patients were treated with antifungals, mainly voriconazole, and surgical management, resulting in high rates of clinical improvement and low associated mortality.

Reports of orthopedic infections caused by Trichosporon species are scarce. We described a case series of orthopedic infections caused by Trichosporon species and reviewed the previous published cases in the literature. We observed a high rate of clinical improvement and a low associated mortality.

Comparison of the Readiness for Interprofessional Learning and the rate of contact among students from nine different healthcare courses.

BACKGROUND: Despite the growth in the interprofessional literature, there are still few studies that have evaluated the differences among courses and periods in relation to Readiness for Interprofessional Learning. Likewise, the relationship between the influences of contact among students from different professions is still controversial. OBJECTIVES: To evaluate whether greater contact among students from diverse health courses could be associated with improved Readiness for Interprofessional Learning (RIPLS) at the undergraduate level and to compare the RIPLS among healthcare courses, analyzing differences among courses and periods of their academic training. DESIGN: Cross-sectional study. SETTING: A Brazilian public university. PARTICIPANTS: Students enrolled in the first and final periods of nine healthcare courses. METHODS: The rates of contact between students and the Readiness for Interprofessional Learning were assessed. A comparison between students from these nine healthcare courses was carried out. RESULTS: A total of 545 (73.45%) students answered the questionnaire. The highest RIPLS scores were from Nursing (42.39), Dentistry (41.33) and Pharmacy students (40.72) and the lowest scores were from Physical Education (38.02), Medicine (38.17) and Psychology (38.66) students. The highest rates of contact between students (RC) were from Physical Education, Nutrition and Psychology students and the lowest RC were from Pharmacy, Social service and Dentistry. There was a significant effect of "healthcare course" on RIPLS. Comparing RIPLS and RC between the first and final years we found that, considering all courses, there was an increase in the RC, whereas a decrease in RIPLS scores. No correlation was found between RIPLS and RC in general. CONCLUSION: The current study found that RIPLS scores are very different between healthcare students. Although we found a significant increase in the RC, there was a decrease in the RIPLS scores. These findings lead to a greater understanding of the difficulties facing and potential for interprofessional education.