Medicine and Pharmacology

Abstract: Background: Staphylococcus argenteus is a recently recognized member of the Staphylococcus aureus complex that is almost identical to S. aureus phenotypically and by 16S rRNA gene sequences. Although genomic analyses demonstrate that S. argenteus is phylogenetically distinct from S. aureus, the two species exhibit more than 90% nucleotide identity and routine identification methods—including routine biochemical assays and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)—cannot reliably distinguish between the two. Objectives: We develop and validate a MALDI-TOF MS–based model for accurate identification of S. argenteus. Methods: A multiplex PCR assay targeting crtM and NRPS genes served as the reference standard. MALDI-TOF MS spectra from 25 S. argenteus and 25 methicillin-susceptible S. aureus (MSSA) isolates were analyzed using ClinProTools to identify characteristic peaks and develop the identification model. The model was validated using 40 S. argenteus and 80 MSSA isolates, then applied to 130 randomly selected clinical isolates. Results: Five characteristic peaks—m/z values 5005, 5285, 5323, 6440, and 6526—were identified. Isolates exhibiting at least 4 of these 5 peaks were classified as S. argenteus; those exhibiting fewer than 4 were classified as S. aureus. The model achieved 100% specificity and 100% sensitivity in both the development and validation phases. In the clinical application phase, the model correctly classified all isolates, whereas conventional MALDI-TOF MS yielded several misidentifications. Conclusions: The identification model, and the simple peak-based rule it is based on, can accurately distinguish S. argenteus from MSSA, offering a practical diagnostic tool for clinical microbiology laboratories.

Abstract: Isavuconazole is increasingly being used for the treatment of invasive fungal disease (IFD), although real-world pediatric data remain limited. We retrospectively reviewed patients aged ≤18 years who received isavuconazole for fungal infection at two tertiary centers in Chile between 2021 and 2025. Twenty patients were included, with a median age of 13.7 years (IQR, 9.4–15.5); 14 (70%) had an underlying malignancy, and 6 (30%) were allogeneic hematopoietic cell transplant recipients. Isavuconazole was used for treatment in 16 patients and for prophylaxis in 4, predominantly as second-line therapy due to prior antifungal intolerance, inadequate response, drug–drug interactions, or QT prolongation. Fifteen patients had IFD, with Mucorales (n=3) being the most frequently identified pathogens in proven cases and pulmonary involvement predominating in probable IFD. A succesful response at 90 days was achieved in 60% (6/10) of evaluable cases. No breakthrough fungal infections occurred during treatment or prophylaxis. Hepatic enzyme elevations were observed in four patients. Isavuconazole was associated with favorable outcomes and an acceptable safety profile, supporting its use as an alternative antifungal in pediatric patients.

Abstract: Background: Respiratory infections in critically ill patients remain a major challenge in intensive care units (ICUs), with high morbidity and mortality. Conventional microbiological methods often fail to identify the causative pathogen promptly, particularly in patients previously exposed to antibiotics. Multiplex molecular platforms, such as the BioFire FilmArray® Pneumonia Panel Plus (FAPP), allow rapid detection of multiple respiratory pathogens and resistance markers, potentially improving early therapeutic decision-making. Objectives: To evaluate the impact of implementing FAPP on antimicrobial therapeutic decisions in critically ill patients with suspected respiratory infection. Methods: We conducted a retrospective cohort study in two mixed ICUs between 2023 and 2024. All respiratory samples in which FAPP was requested were analyzed. Results were compared with conventional cultures, and changes in antimicrobial therapy following FAPP results were assessed, classified as escalation/initiation or de-escalation/discontinuation. Concordance between FAPP and culture was evaluated, and clinical and demographic variables were analyzed. Differences between groups were assessed using p-values obtained from the chi-square test or the Mann–Whitney test. Results: A total of 363 respiratory samples were included, 88.4% from mechanically ventilated patients. FAPP was positive in 65.3% of samples, whereas cultures were positive in 23.1%. Overall concordance between FAPP and culture was 57.3%. In 42.4% of cases, pathogens were detected exclusively by FAPP. Antimicrobial therapy was modified in 29.8% of patients, predominantly through de-escalation or discontinuation (69.4% of changes). Therapeutic modifications were more frequent in nosocomial infections and in patients with a positive FAPP result. Conclusions: The use of FAPP in critically ill patients with suspected respiratory infection provides rapid microbiological information that significantly influences antimicrobial decision-making, particularly by facilitating antibiotic de-escalation. Although discrepancies with conventional cultures remain and require careful clinical interpretation, FAPP represents a valuable tool for antimicrobial stewardship in the ICU setting.

Abstract: Background: Aerobic vaginitis (AV) is characterized by dysbiotic vaginal microflora with overgrowth of aerobic pathogens of enteric origin, presence of vaginal inflammation and immature epithelial cells. This study aimed to evaluate, over a period of 10 years, women of reproductive age (non-pregnant and pregnant) as well as menopausal women affected by AV. Methods: We included non-pregnant, pregnant and menopausal women diagnosed with AV over a period of 10 years. Diagnosis of AV was determined according to the criteria proposed by Donders in 2002. The isolated pathogens were identified with the rapid identification system I-dOne (Alifax S.r.l, Polverara, Italy) and the automated system VITEK2 (Biomerieux, Marcy l’Etoile, France), which was used for antimicrobial susceptibility testing. Results: The overall aerobic vaginitis prevalence rate during the studied period was 9.5%. The most common isolated pathogens were Escherichia coli 27.3%, Enterococcus faecalis 25.0%, Streptococcus agalactiae 22.2%, Klebsiella pneumoniae 8.9%, Proteus spp 4.7%, Staphylococcus aureus 3.5%. E. coli infection significantly increased the odds of mild AV by 1.65 times (p=0.002) and Proteus species infection was over 6 times more likely to progress to severe disease (p=0.000). Furthermore, pregnant women were more likely to be infected with E. faecalis (p=0.000) while menopausal women were diagnosed significantly more with severe AV (p=0.000) compared to the other groups. Conclusions: The prevalence of aerobic vaginitis in the population studied was in concordance to global rates. Menopausal women displayed significantly more severe AV cases while, in contrast, mild cases were recorded during pregnancy. The most commonly isolated pathogens were of enteric origin.

Abstract:

Background: Streptococcus agalactiae (group B Streptococcus, GBS) remains a leading cause of invasive infections in pregnant women, fetuses, and neonates. Universal screening at 36-37 weeks of gestation followed by intrapartum antibiotic prophylaxis is essential to prevent adverse outcomes. However, data on GBS serotype distribution are limited in several regions, including Greece. This study aimed to determine the prevalence, serotype distribution, and antimicrobial susceptibility of GBS isolates among pregnant women in Greece. Methods: Vaginal and rectal swabs were collected from pregnant women undergoing routine GBS screening between January 2021 and December 2025. Samples were processed using selective enrichment broth and cultured on blood agar and chromogenic media. Identification was based on standard microbiological methods, CAMP test, and VITEK2 system. Antimicrobial susceptibility testing and macrolide-lincosamide-streptogramin B (MLS_B) phenotyping were performed. Serotyping was conducted using a commercial latex agglutination assay. Results: Among 941 women screened, 118 (12.5%) were colonized with GBS. The most prevalent serotypes were III (29.7%), V (18.6%), Ib (14.4%), IX (10.2%), Ia (9.3%), and II (9.3%). All isolates were susceptible to penicillin. Resistance to erythromycin and clindamycin was observed in 29.7% and 22.9% of isolates, respectively. The predominant MLSB phenotype was constitutive (cMLSB, 78.4%), followed by inducible (iMLSB, 13.5%), L (5.4%), and M (2.7%) phenotypes. Conclusions: GBS colonization was detected in 12.5% of pregnant women, with serotype III predominating, underscoring its clinical relevance due to its association with invasive neonatal disease. Although penicillin remains fully effective, the observed resistance to macrolides and lincosamides, primarily mediated by the cMLS_B phenotype, raises concerns regarding alternative therapies.

Abstract: Background: Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies. Serum galactomannan (GM) is widely used for diagnosis, but the prognostic value of the initial GM level is not well established. Objective: To assess the association between the initial serum GM level at IPA diagnosis and the radiological and clinical outcomes at 42 and 90 days. Methods: We retrospectively reviewed adult patients with hematological malignancies, including hematopoietic stem cell transplant (HSCT) recipients, diagnosed with proven or probable IPA at Sultan Qaboos University Hospital between 2014 and 2017, according to the EORTC/MSG criteria. Demographic, microbiological, radiological, and clinical data were collected. Outcomes were assessed using three GM cut-off categories. Results: Seventy-eight patients were included. The median age was 44.5 years (range 18–76); 53.8% were male. Lymphoma (30.7%) and acute leukemia (25.6%) were the leading underlying diseases. Voriconazole was the most frequently used antifungal agent (74.3%). Prolonged neutropenia was present in 61.9%, and 30.7% had received HSCT. The mean serum GM at diagnosis was 1.95 (range 0.5–7.89). At 90 days, 30% had a complete radiological response, 51.4% partial, and 32.8% no response. Overall, 90-day mortality was 35.9%. There was no statistically significant association between initial GM level and 90-day mortality across categories (GM 0.5–3.0: 34.2% mortality; GM > 3.0: 60%; p = 0.243). Within the GM 0.5–3.0 group, complete radiological response was strongly associated with survival (95.2% alive at 90 days; p < 0.001). Conclusions: The initial serum GM level was not significantly associated with clinical or radiological outcomes at 42 or 90 days in patients with hematological malignancies and IPA. However, an early complete radiological response was strongly associated with improved survival, supporting the use of follow-up CT chest imaging to guide management.

Abstract:

This review provides a comprehensive overview of the genetic diversity and epidemiological potential of Yersinia pestis in Kazakhstan’s natural plague foci, emphasizing the link between genotypic variation and outbreak capacity. Integrating historical epidemiological records with contemporary microbiological and genomic data (including PCR, VNTR/MLVA, SNP analysis, and whole-genome sequencing), we evaluate core and accessory genome variations. The data reveal substantial regional heterogeneity. High-risk desert foci (Caspian and Aral regions) are dominated by the Medievalis biovar, including atypical genovariants lacking canonical markers. Conversely, high-mountain foci (Sarydzhaz, Talas) harbor Antiqua and Talas biovars primarily linked to enzootic circulation. Notably, the Ili River focus exhibits extreme genomic variability, featuring strains with plesiomorphic traits. Furthermore, the widespread distribution of mobile elements like the cryptic plasmid pCKF suggests significant horizontal transfer contributing to pathogen adaptation. Ultimately, Central Asian plague dynamics are driven by complex evolutionary and ecological interactions. Given climate change and expanding human-wildlife interfaces, continuous genomic and ecological surveillance is essential for the early detection of high-risk Y. pestis genovariants and improving public health preparedness.

Abstract: Congenital Cytomegalovirus (cCMV) infection is the leading non-genetic cause of sensorineural hearing loss in newborns. Systematic nationwide screening programs are lacking. Antiviral valganciclovir therapy could improve auditory outcomes if initiated within the first 30 days of life, making timely diagnosis crucial. To address this, we investigated whether a hearing screening-based protocol is suitable. Between 2015 and 2019, newborns ≤21 days of age with repeated abnormal Newborn Hearing Screening (NHS) were prospectively enrolled at University Hospital Frankfurt. Oral mucosal swabs were tested for CMV DNA by real-time PCR, with confirmatory urine and blood-diagnostics in positive cases. Of 2,741 infants presenting for repeat NHS, 2,059 (75.1%) showed normal bilateral findings. Of the 682 (24.9%) with abnormal results, 575 (84.3%) were >21 days and thus ineligible. 107 infants (3.9%) met both criteria — abnormal NHS and age ≤21 days — of whom 100 entered per-protocol analysis. Two (2%) were confirmed cCMV-positive and received valganciclovir. Among the 48 infants who additionally underwent DBS testing, diagnostic sensitivity and specificity were 100%. The presented NHS–driven cCMV protocol reliably identified cCMV-infected newborns timely to offer antiviral therapy. In the absence of universal cCMV screening, this targeted approach offers a challenging, but WHO-screening-criteria-compliant strategy to enable timely antiviral intervention.

Abstract: Plague remains a significant natural focal zoonotic infection, maintaining epidemiological relevance in the Republic of Kazakhstan. This study provides a comprehensive assessment of epizootological dynamics in natural plague foci during 2020–2025, integrating historical epidemiological data, phenotypic and molecular characterization of Yersinia pestis, and GIS-based spatial analysis. The study utilized long-term surveillance data (1920–2025), epidemiological records of human cases (1926–2003), analysis of 1,526 strains, and whole-genome sequencing of 75 isolates. Epizootological monitoring demonstrated high coverage and stable surveillance capacity, alongside a marked increase in molecular diagnostics. By 2025, expansion of epizootically active areas, a threefold increase in isolated strains, and a substantial rise in PCR-positive detections were observed, indicating intensified pathogen circulation. Despite this, Y. pestis populations remained highly stable, with 94.9% phenotypically typical and 97.5% genotypically typical strains, and no evidence of antimicrobial resistance. Spatial analysis revealed significant clustering (Moran’s I = 1.627; p < 0.001), persistent directional spread, and stable high-risk zones in the North Aral, Betpakdala, Moyynkum, and Kyzylkum foci. No human cases have been recorded since 2003, reflecting effective surveillance. These findings support the integration of spatial modeling and molecular surveillance into risk-oriented plague control strategies.

Abstract: Camels are increasingly recognized as an important epizootological and epidemiological link in natural plague foci, facilitating the transmission of Yersinia pestis from wildlife to humans. In the Republic of Kazakhstan, where natural plague foci occupy up to 40% of the territory, the rapid growth of camel populations may significantly enhance epidemiological risks. The aim of this study was to perform a comprehensive assessment of the role of camels in the epizootology and epidemiology of plague based on retrospective data (1907–2003) and contemporary monitoring (2000–2025), including spatial analysis and risk zoning. A total of 64 cases of camel plague and 43 epizootic foci were identified during the historical period, associated with more than 400 human cases and deaths. Direct contact during slaughter and meat processing accounted for 94.7% of human infections. Modern data demonstrate that over 90% of the camel population is concentrated in plague-endemic regions. Spatial analysis and epidemiological zoning revealed a heterogeneous risk distribution, with western and southern regions representing the highest-risk areas. Serological investigation (n = 2726) showed 75.6% seropositivity, indicating a high level of population immunity, largely associated with vaccination. Despite increasing camel population size (from 227.7 to 304.0 thousand heads in 2020–2025), vaccination coverage varied between 32.0% and 51.0%, reflecting risk-based preventive strategies. The absence of recent camel plague cases confirms the effectiveness of integrated control measures, including vaccination, surveillance, and establishment of protective zones. These findings demonstrate that camels remain a critical component of plague transmission systems and should be systematically integrated into surveillance programs within a One Health framework.

Abstract: Background: Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) co-circulate across the Americas and share Aedes mosquito vectors, creating conditions for concurrent infections. Whether coinfection increases clinical severity remains uncertain because clinical syndromes overlap, diagnostic windows are short, and flavivirus serology is prone to cross-reactivity. Objective: To synthesize evidence on the association between DENV, CHIKV, and ZIKV coinfection and clinical severity in the Americas. Methods: An integrative review was structured according to the framework proposed by Whittemore and Knafl. PubMed/MEDLINE, Scopus, Web of Science, LILACS, and SciELO were searched for publications from 2015 to 2026. Eligible studies involved human populations in the Americas and laboratory-confirmed dual or triple infection. Evidence was narratively synthesized by epidemiology, clinical severity, laboratory phenotype, neurologic or perinatal outcomes, diagnostic validity, and methodological quality. Results: Coinfection was repeatedly documented in settings of intense arboviral co-circulation, particularly when multiplex molecular assays were used. Evidence does not support a uniform increase in hemodynamic severity or mortality in all coinfected patients. Instead, DENV-CHIKV coinfection appears to produce a mixed phenotype combining dengue-like hematologic abnormalities with chikungunya-like arthralgia, whereas DENV-ZIKV interactions raise greater concern for diagnostic misclassification and immune-mediated neurologic or congenital outcomes. Conclusions: Arboviral coinfection in the Americas is better understood as a context-dependent interaction shaped by vector ecology, timing of infection, host immune history, and diagnostic method than as a simple additive syndrome. Prospective multicenter studies using standardized severity definitions and multiplex molecular confirmation are needed.

Abstract: Background: Large language models (LLMs) are increasingly used as diagnostic support tools. However, their sensitivity to prompt framing (especially the gender assigned to the physician persona) is poorly understood for neglected tropical diseases (NTDs). Objective: Compare the diagnostic performance of four LLMs prompted as male or female infectious disease specialists using anonymized cases of Chagas disease (CD) and visceral leishmaniasis (VL). Methods: This experimental, paired study evaluated ChatGPT-4o, LLaMA 3 70B, Meditron-70B, and Mixtral 8x7B across 12 cases per disease (n=24), from real records at a Brazilian teaching hospital. The primary outcome was top-five diagnostic accuracy. A committee of five infectious disease specialists assessed the biological plausibility of all differentials. Paired comparisons used Wilcoxon signed-rank tests; 95% confidence intervals were calculated using the Wilson score method. Results: For VL, the female prompt yielded numerically higher accuracy in all four models (gains of 8.3–16.7 percentage points), with ChatGPT-4o reaching 91.7%. For CD, ChatGPT-4o achieved 100% under both conditions; LLaMA 3 70B and Mixtral 8x7B improved by 16.7 percentage points with the female prompt, while Meditron-70B remained at 16.7%. No between-prompt differences reached statistical significance (all p&gt;0.05). ChatGPT-4o produced the highest proportion of biologically plausible diagnoses, while Meditron-70B generated the most implausible hypotheses. Conclusion: The gender assigned to the physician persona produced subtle, nonsignificant variations in LLM diagnostic accuracy, with a consistent numerical trend favoring the female prompt in open-weight models. These findings underscore the importance of prompt standardization and systematic bias evaluation in AI-assisted diagnostics for NTDs.

Abstract: Non-O1/non-O139 Vibrio cholerae (NOVC) species are typically non-toxic and are regarded as etiological agents of infrequent, but mild to severe human gastroenteritis. In response to the 2022-2023 cholera outbreak in Tshwane, this study investigated the occurrence of NOVC isolates in wastewater within the Tshwane district, South Africa. A total of 341 wastewater samples were screened using Thiosulfate citrate bile salts sucrose (TCBS) media, with subsequent confirmation of Vibrio cholerae (V. cholerae) isolates by multiplex-PCR assays. Rep-PCR was performed to determine genetic relatedness of the isolates. Selected isolates were subjected to whole genome sequencing (WGS). Of the 341 samples; PCR confirmed 143 isolates as NOVC. Genetic fingerprinting grouped these isolates into 12 distinct clusters, from which 12 representative isolates were selected for WGS, all of which were confirmed as NOVC. The isolates harboured pathogenicity-related genes, such as hlyA, rtxA, trkH, tnaA, gyrB and gyrA. Drug resistance was mostly observed to first-line antibiotics, ciprofloxacin, chloramphenicol, and trimethoprim-sulfamethoxazole. Plasmid analysis showed seven isolates harboured plasmids (pA, p21L, PVN84) bearing multiple resistance determinants. Phylogenetic analysis showed evidence of genetic diversity amongst the isolates. Although the isolates lacked classical toxigenic genes, they carried other virulence determinants associated with pathogenicity, posing a potential risk for clinical infection, highlighting the need for sustained surveillance.

Abstract: Honeybee populations face significant threats from a range of viral and parasitic pathogens, contributing to declining colony health, reduced pollination services, and economic losses in agriculture. In recent years, RNA interference (RNAi) has emerged as a novel and promising approach for mitigating these threats. This review explores the applications and advancements of RNAi as a targeted, species-specific, and environmentally sustainable strategy for managing honeybee health. In addition, symbiont-mediated RNAi delivery —a promising avenue for overcoming current limitations in RNAi application — is discussed.

Abstract: Cardiovascular disease (CVD), the leading cause of global mortality, is intrinsically linked to atherosclerosis. Recent research suggests that respiratory function may be associated with the development of atherosclerosis. Alterations in the composition of the respiratory microbiome can negatively affect pulmonary function, which in turn may impact cardiovascular health through mechanisms that remain incompletely understood. To analyze the upper airway microbiome abundance and diversity in adults with subclinical atherosclerosis. A case–control study was conducted for atherosclerosis. Oropharyngeal swab samples were collected from participants in the CaRes cohort, for whom carotid Doppler, spirometry, blood chemistry, and clinical history data were available. Sequencing of the 16S ribosomal RNA gene was performed, followed by comparative analyses between subjects with and without atherosclerosis. A total of 100 subjects were analyzed (50 cases and 50 controls). The phylum Bacteroidetes was the most prevalent in both groups, followed by Firmicutes and Proteobacteria. Family Enterobacteriaceae was more abundant among case group, which included species such as Serratia, Klebsiella spp., and Campylobacter. Evaluation of alpha diversity indices revealed lower levels for cases group, with a Shannon diversity index of 2.61 compared to 4.07 in controls (p = 0.006). Differences in microbiota composition were observed between cases and controls. Specifically, the family Enterobacteriaceae was associated with the presence of atherosclerosis, suggesting its potential involvement in the progression of cardiovascular disease.

Abstract: Coxiella burnetii is an intracellular bacterium responsible for an anthropozoonosis that can be asymptomatic or manifest as acute or chronic Q fever . This extensive series of 588 patients represents one of the largest single-center studies on sporadic acute Q fever, highlighting the Canary Islands as a high-incidence region in Spain. Epidemiologically, the domestic cycle is the primary driver of infection, with caprine livestock serving as the main reservoir, showing a local prevalence of 60.4%. Transmission is predominantly airborne via aerosols; the environmental resilience of C. burnetii facilitates its transport into urban areas, where the majority of patients reside despite lacking direct animal contact. While fever, headache, and sweating are hallmark symptoms, over 90% of patients exhibit transient urinalysis abnormalities, a finding that often leads to misdiagnosis and inappropriate antimicrobial use. Clinically, the non-specific (45.7%) and hepatic (44.1%) forms are most prevalent, whereas the pulmonary form (7.8%) is strongly associated with smoking and alcohol consumption. Although localized forms affecting the nervous system or skin (such as panniculitis) were observed, the overall prognosis remains excellent with no progression to chronic Q fever in this series. In summary, the extensive series described characterizes acute Q fever patients in the Autonomous Community of the Canary Islands, with features that are similar in some cases but also show notable differences compared to other national and international series. Furthermore, depending on the patients' age, the time elapsed between the onset of clinical manifestations and hospital evaluation, and the clinical form, acute Q fever displays significant differences.

Abstract: The study presented here is the first one in which surface disinfectants active against Candida auris were tested with the, state of the art, German/EU Technical Normative DIN/EN 17387. The results give a better understanding of the real efficacy of surface disinfectants for the use in medical health care facilities with respect to Candida auris. Therefore DIN/EN 17387 is an emphasized tool to get comparable robust surface disinfectants test results EU wide.

Abstract: Background: Tuberculosis remains a leading cause of infectious disease mortality, with over 10 million new cases annually. The standard first-line regimen—isoniazid, rifampicin, pyrazinamide, and ethambutol—has dramatically improved survival, yet drug-induced micronutrient depletion, particularly zinc, is an underappreciated complication that may contribute to treatment-related morbidity. Ethambutol-induced optic neuropathy (EON) affects 1–5% of treated patients, and accumulating evidence implicates zinc chelation as its central mechanism. We hypothesize that anti-TB therapy creates a “multi-hit” zinc depletion state through convergent drug- and disease-mediated pathways.Methods: We conducted a systematic search of PubMed, Scopus, Web of Science, and Cochrane databases from 1944 (discovery of streptomycin) through March 2026. Search terms combined anti-TB drug names with zinc, copper, micronutrient, optic neuropathy, and visual loss. We included randomized controlled trials, cohort studies, case-control studies, case series, in vitro investigations, and animal models. PRISMA 2020 guidelines were followed. Risk of bias was assessed using the Newcastle–Ottawa Scale for observational studies and the Cochrane RoB 2.0 tool for trials.Results: From 2,847 initial records, 186 studies met inclusion criteria. Serum zinc was significantly lower in TB patients versus controls (pooled mean difference: −12.1 μmol/L; 95% CI: −14.5 to −9.7; I² = 68%). Ethambutol directly chelates zinc and copper in retinal ganglion cells via its metabolite EDBA, causing lysosomal membrane permeabilization and mitochondrial dysfunction. Isoniazid depletes pyridoxine, impairing zinc-dependent enzymatic cascades. Rifampicin induces CYP3A4 via PXR activation, accelerating retinol catabolism and functionally coupling zinc deficiency to vitamin A insufficiency through impaired retinol-binding protein synthesis. The zinc–vitamin A axis demonstrates a strong positive correlation (r = 0.86, p < 0.01) in TB cohorts. Zinc supplementation (50 mg elemental zinc/day) improved sputum conversion rates and reduced hepatotoxicity markers in three randomized trials.Conclusions: Anti-TB drugs collectively create a “multi-hit” zinc depletion syndrome that extends beyond simple ethambutol chelation. We propose a clinical algorithm for baseline zinc assessment, risk stratification, and prophylactic supplementation during TB therapy. Persistent visual loss despite ethambutol discontinuation should prompt evaluation of concurrent zinc depletion from isoniazid, rifampicin, and the underlying TB disease itself.

Abstract: Histoplasmosis, blastomycosis, and coccidioidomycosis - the three major endemic mycoses - have long been taught as geographically confined diseases requiring travel to classic endemic zones for clinical consideration. Emerging epidemiologic data challenges this paradigm. National surveillance studies now document clinically significant incidence of all three fungi across 47–94% of US states, with locally acquired cases confirmed well outside historical boundaries. Climate-driven range expansion, rising immunosuppressed populations, and improved diagnostics are converging drivers. The diagnostic delay - averaging 29 days, with 42% of patients initially misdiagnosed - carries measurable clinical and economic cost. This mini review synthesizes contemporary data on geographic redistribution, identifies key drivers of expansion, and proposes a risk-stratified, geography-independent diagnostic framework centered on immune status and clinical pattern rather than zip code.

Abstract: Background: Risk factors for severe COVID 19 and in hospital mortality are well described, but it remains unclear whether the same factors predict mortality after hospital discharge. Distinguishing risk profiles across clinical phases may improve patient management and follow up strategies. Methods: We conducted a retrospective observational cohort study of 595 adults hospitalized with PCR‑confirmed SARS-CoV-2 infection in Portugal (September and November 2020). The primary outcome was all‑cause mortality during hospitalization and up to 120 days post-discharge. Secondary outcomes included intensive care unit (ICU) admission, maximum disease severity (WHO Clinical Progression Scale), oxygen supplementation, and length of stay. Univariate and multivariable regression analyses were performed. Results: Overall mortality was 22.5%, rising from 14.1% in-hospital to 22.5% at 120‑day follow‑up (p < 0.001), with 37.3% of deaths occurring post-discharge. ICU admission was required in 17.6% of patients and was significantly associated with obesity (OR = 2.12, 95% CI: 1.39–3.23, p < 0.001) and male sex (OR = 1.78, 95% CI: 1.14–2.78, p = 0.010) in univariate analysis. In contrast, post‑discharge mortality was associated with longer hospital stay (18.4 vs. 9.9 days, p < 0.001) and a higher prevalence of malignancy (28.0% vs. 13.1%, p = 0.032), but not with ICU admission. In multivariable analysis, oxygen supplementation was the strongest predictor of mortality (β = 0.563, p < 0.001). Only pulmonary diseases and obesity were independently associated with maximum disease severity. Conclusions: Risk factors for acute COVID‑19 severity differ from those for late mortality. These findings support a phase‑specific approach to risk stratification, suggesting that patients with obesity are at increased risk of early respiratory deterioration, while patients with malignancy may benefit from closer post discharge follow up regardless of ICU admission status.