Search Results (279)

Invasive Mucormycosis (IM) is an extremely rare infection with a high mortality rate, caused by a group of fungi classified as Mucorales moulds. Rhizomucor pusillus is a saprophitic, thermophilic, and angioinvasive microorganism that grows and lives at about 45 °C and is usually found in different environmental spaces such as soil, air, water, food, and other organic matter. These features predispose the infection to wide dissemination, especially in immunocompromised patients and most often in children after chemotherapy for hematological malignancies (HMs). Mucormycosis in patients with hematologic malignancies and neutropenia represents between 0.07% and 4.29% of the concomitant diseases. IM can develop into an infection in different sites, but its most common manifestation is pulmonary, followed by rhino-orbital–cerebral and disseminated forms. In recent years, an increased morbidity rate has been associated with the ongoing COVID-19 pandemic, as cited in the literature. There are many publications with COVID-19-associated mucormycosis (CAM) cases. The present treatment protocol includes extensive and radical surgical debridement and systemic antifungal therapy with Liposomal Amphotericin B (L-AmB), Posaconazole, and Isavuconazole, either combined or as monotherapy. Despite these new treatment modalities, the mortality rate remains over 50%. We present a rare case of a 3-year-old child with acute lymphoblastic leukemia (ALL) and systemic Rhizomucor pusillus infection, diagnosed on the occasion of lung and brain abscesses. The patient underwent lung and brain surgery and is recovering well with no further complications. The two-year follow-up period shows no signs of recurrence of the disease. Full article

La Crosse virus (LACV) is a mosquito-borne virus (family Peribunyaviridae) that can result in severe human infection in children under sixteen. Historically, LACV comprised two lineages, predominantly in the Midwest and Appalachian regions of the US. In 2005, a virus of a third lineage was detected in the Northeast; however, this and subsequently isolated strains of lineage III have not, to date, been implicated in human disease. One hypothesis for this discrepancy is that vector mosquitoes have a reduced vector competency for LACV lineage III, thus preventing horizontal transmission and clinical cases. Here, we utilized two mosquito species, Aedes triseriatus, the native vector, and Aedes albopictus, an invasive potential vector, each from both a historic LACV range (Virginia) and from the region of lineage III (Connecticut). Utilizing oral feeding and intrathoracic inoculation methods of viral exposure, rates of LACV infection, dissemination, and transmission (proxied via salivary secretion) and capability for vertical transmission (proxied via virus-positive ovaries) were determined by harvesting mosquito bodies, legs, saliva, and ovaries, respectively. Overall, we did not detect consistent differences in transmission between any lineage, species, or state of origin, at day 14 post-infection. However, we highlight the transmission potential of LACV lineage III in all mosquito populations tested here, representing the first evidence of lineage III competency in Aedes triseriatus and Aedes albopictus, indicating the potential for human disease. We thus suggest that the absence of human cases of LACV lineage III is not modulated by a lack of vector competency in mosquitoes. Full article

Candidiasis remains one of the most challenging infections to treat in critical care, due to its diagnostic difficulties and uncertainty regarding whether it can be directly related to the death of patients with multiorgan failure. This study aims to verify that the statistically attributable mortality in this infection is as consistent as the post-mortem attributable mortality. A prospective study was conducted in non-neutropenic ICU patients in whom Candida was detected. Invasive candidiasis is defined based on evidence of disseminated or multifocal candidiasis. Post-mortem study is used as the gold standard for Candida-attributable mortality, and is compared with attributable mortality determined according to clinical study and statistically attributable mortality in relation to the overall mortality of ICU patients and colonized patients. The post-mortem attributable mortality was 30.6% and 22.6% according to the clinical study, while the statistically attributable mortality was 25% in relation to overall ICU mortality and 27% in relation to Candida colonization. Thus, the results of the different calculations of attributable mortality (statistical vs. crude death rate) due to Candida are in agreement. The use of this metric may help to improve ICU outcomes for non-neutropenic critically ill patients with candidiasis. Full article

Acute promyelocytic leukemia (APL) evolved from the most lethal to the most curable subtype of acute leukemia today, owing to targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide. Despite cure rates exceeding 90% and the rarity of relapse or refractoriness, early death (ED)—occurring within 30 days of diagnosis—remains unacceptably high, reaching up to 30% in population-based studies. ED is the major barrier to universal cure, with fatal hemorrhage as the predominant cause, followed by infection, differentiation syndrome, and thrombosis. Patients who survive the initial month generally achieve excellent long-term outcomes. This review synthesizes data from clinical trials and large real-world cohorts to provide a comprehensive overview of the incidence, causes, and predictors of ED in APL. Higher white blood cell count and older age emerge as the most consistently validated predictors, followed by increased IRB/BICcreatinine, low albumin, thrombocytopenia, and coagulopathy, although their predictive value is not uniform across studies. Risk scores such as the Sanz classification, the Österroos ED model, and dynamic disseminated intravascular coagulation (DIC) assessments represent practical tools for identifying patients at high risk of ED. Importantly, ED rates remain significantly higher in real-world populations than in clinical trials, highlighting the impact of age and comorbidities, delayed diagnosis, and barriers to immediate ATRA initiation and supportive care. Addressing ED in APL requires intensified early supportive strategies, physician awareness and education, and rapid treatment initiation. Refinement and validation of predictive models may guide tailored interventions and inform strategies to finally overcome this persistent unmet need. Full article

Wild boar (Sus scrofa) is a widespread invasive species in Poland and may act as a reservoir for various pathogens, including those associated with the porcine respiratory disease complex (PRDC). As data on bacterial respiratory pathogens in wild boar populations, particularly co-infections, in Poland and other European countries remain limited, the main goal of our study was to examine the frequency of selected bacterial respiratory agents and their co-occurrence in lung samples collected from culled wild boars during hunting. Two hundred and fifty-three lung samples were analysed for the presence of genetic material of A. pleuropneumoniae, M. hyopneumoniae, M. hyorhinis, and G. parasuis. In total, 159 out of the 253 (62.8%; 95% CI: 56.6–68.8) wild boars were infected with at least one pathogen. In general, 73 (28.9%; 95% CI: 23.3–34.9) of wild boar lung samples tested positive for G. parasuis, 106 (41.9%; 95% CI: 35.7–48.2) were positive for M. hyopneumoniae, and 10 (4%; 95% CI: 1.9–7.1) were positive for M. hyorhinis. No evidence of A. pleuropneumoniae infection was detected in any of the examined lung samples. Infection with a single pathogen was detected in 129 (51%; 95% CI: 44.6–57.3) of sampled wild boars, whereas co-occurrence of two infectious bacterial agents was revealed in 30 animals (11.9%; 95% CI: 8.1–16.5). Among single-pathogen infections, the highest positivity rate was observed for M. hyopneumoniae (31.6%; 95% CI: 25.9–37.7), whereas the most frequent co-infection involved M. hyopneumoniae and G. parasuis (9.1%; 95% CI: 5.8–13.3). This investigation indicated that wild boar in the study area are potential hosts for bacterial agents associated with PRDC. It is worth highlighting that wild boars can contribute to the maintenance and/or dissemination of bacterial pathogens to humans (especially hunters) and domestic animals, and it is essential to maintain active surveillance of these infectious agents. Full article

Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB), administered to >100 million neonates annually. It confers approximately 70–80% protection against tuberculous meningitis and miliary TB in early childhood, under-pinning its continued use in high-burden settings. As a live-attenuated vaccine, however, BCG can rarely cause adverse reactions ranging from self-limited local lesions to life-threatening disseminated BCG disease (BCGosis), which almost exclusively occurs in infants with severe primary or acquired immunodeficiencies such as SCID, MSMD, CGD, or symptomatic HIV infection. Implementation of universal newborn screening for severe combined immunodeficiency (SCID) using the T-cell receptor excision circle (TREC) assay now enables prospective identification and deferral of these high-risk neonates, virtually eliminating fatal BCGosis. Here we synthesize global data published since 2010 on the clinical spectrum, immunopathogenesis, and epidemiology of BCG-related complications, highlighting the impact of vaccine substrain, administration technique, and host immune status on adverse-event rates. On the basis of this evidence, we propose a practical, evidence-based risk-assessment checklist (BCG-RAKE) to support safer vaccine deployment while preserving the substantial TB-control benefits of universal BCG immunization. Full article

Background: The diagnosis of abdominal tuberculous lymphadenopathy (ATBL) remains challenging in clinical practice. Patients with ATBL and HIV infection may have atypical clinical and computed tomography (CT) features. The aim of this study was to investigate the impact of HIV infection on the clinical and CT features of ATBL patients. Methods: From January 2012 to March 2023, 178 patients with untreated ATBL were retrospectively analyzed. Patients with ATBL were classified into HIV-negative group (n = 152) and HIV-positive group (n = 26). In addition to the clinical characteristics of the patients, the features of ATBL (e.g., size and location) were evaluated via CT. The Mann–Whitney U test (for continuous variables) and Fisher’s exact test (for categorical variables) were used to compare clinical data and CT imaging features between the two groups. Missing values were handled using multiple imputation, and the Benjamini–Hochberg procedure was applied to control the false discovery rate (FDR) in multiple comparisons. Post hoc power analysis for key variables was performed. Results: Compared with the HIV-negative group, the HIV-positive group had older age, lower CD4⁺ T-cell counts, and larger ATBL diameter. The HIV-positive group also showed a stronger tendency for disease dissemination, with significantly higher rates of smear positivity, miliary pulmonary tuberculosis (PTB), and disseminated tuberculosis (TB). On CT imaging, the HIV-positive group had a higher frequency of ATBL involvement in the upper para-aortic region, portacaval space, and hepatogastric ligament. In contrast, abdominal distension was more common in the HIV-negative group. post hoc power analysis confirmed that most key variables had adequate statistical power (≥0.8), except for age (power = 0.597) and ATBL diameter (Power = 0.769). Conclusions: The clinical and CT features of ATBL differ significantly between HIV-negative and HIV-positive patients. Full article

Antimicrobial resistance in healthcare-associated infections represents one of the greatest threats to global health. The COVID-19 pandemic disrupted infection control and antimicrobial stewardship, potentially affecting the prevalence of pathogens and the development of resistance. This study aimed to investigate the prevalence, antimicrobial resistance, and clonal dissemination of ESKAPE pathogens isolated from bloodstream infections during the second year of the COVID-19 pandemic in four tertiary-care hospitals in Mexico. A total of 926 isolates were analyzed: Staphylococcus aureus (22.4%), Klebsiella pneumoniae (22%), Acinetobacter baumannii (21.5%), Pseudomonas aeruginosa (12.5%), Enterobacter cloacae (9.4%), Enterococcus faecalis (8.4%), and Enterococcus faecium (3.8%). High rates of multidrug resistance were observed in A. baumannii (70.9% XDR) and K. pneumoniae (71% XDR plus MDR with 79% ESBL). P. aeruginosa and E. cloacae showed the highest susceptibility rates (53% and 48%, respectively) to all antimicrobials. The main β-lactamases involved in resistance were bla_SHV, bla_CTX-M, and bla_TEM in K. pneumoniae, while the predominant carbapenemases were bla_OXA-24, bla_OXA-23 in A. baumannii, bla_NDM in K. pneumoniae, and bla_VIM in P. aeruginosa. Among Gram-positives, methicillin-resistant S. aureus accounted for 33.8% of isolates, and vancomycin resistance was higher in E. faecium (28%) than in E. faecalis (1.3%). Pulsed-field gel electrophoresis revealed endemic circulation of A. baumannii clones (Pulsotypes 1AC, 2AM), persistent for over a decade, and interhospital dissemination of S. aureus and K. pneumoniae clones. These findings underscore the epidemiological relevance of MDR ESKAPE pathogens during the COVID-19 pandemic and highlight the urgent need to optimize empirical therapy and maintain continuous genomic surveillance to enhance infection control in Mexican hospitals. Full article

Proteus mirabilis (P. mirabilis) serves as a multi-host–pathogen regarded as an alarming foodborne infectious disease, causing illnesses of variable severity in both livestock and human beings. The present study aimed to estimate the prevalence, antibiotic susceptibility profiles, and associated antimicrobial resistance genes (ARGs) of P. mirabilis isolates obtained from diseased broiler chickens and native Egyptian buffaloes in Kafr El-Sheikh and Dakahlia governorates, Egypt. In addition, this study investigated the antibacterial activity of chitosan (CS) and chitosan nanoparticles (CSNPs), including the estimation of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CS at concentrations of 1% and 2%, as well as CSNPs. Furthermore, the sub-MIC values were utilized to assess the inhibitory effects of CS and CSNPs on swarming motility. P. mirabilis was detected in 68% (34/50) of broiler chickens and 40.74% (11/27) of buffaloes. Interestingly, all P. mirabilis isolates were tested against 21 antimicrobial drugs and showed high resistance against either critical, highly important, or important antimicrobial drugs. For chicken-originated P. mirabilis, 50% (17/34) of isolates were revealed to be extensively drug-resistant (XDR) and 50% (17/34) of isolates were revealed to be pan-drug-resistant (PDR). Meanwhile, 9.09% (1/11) of buffalo-originated P. mirabilis isolates were revealed to be XDR and 90.91% (10/11) of the isolates were revealed to be PDR. Among P. mirabilis isolates from broiler chickens, the prevalence of resistance genes was as follows: int1 (97.06%), dfrA1 (100%), sul2 (97.06%), catA1 (44.12%), aadA1 (97.06%), tet(M) (81.82%), ermB (23.53%), msrA (0%), qnrA (47.06%), qnrS (0%), gyrA (0%), mcr-1 (11.76%), bla_TEM (97.06%), bla_CTX-M (26.47%), bla_OXA-10 (2.94%), bla_CMY-2 (41.18%), and bla_SHV (0%). The corresponding detection rates in buffalo-derived isolates were 100%, 100%, 90.91%, 63.64%, 100%, 70.59%, 18.18%, 0%, 9.09%, 0%, 0%, 18.18%, 81.82%, 18.18%, 18.18%, 63.64%, and 0%, respectively. Carbapenemase genes were found in none of the isolates from either species. CSNPs demonstrated superior antibacterial and anti-virulence activity against resistant P. mirabilis. CSNPs exhibited significantly lower MIC (0.067–0.081 mg/mL) and MBC (0.167–0.177 mg/mL) values compared with conventional CS formulations (MIC: 3.25–4.5 mg/mL; MBC: 6.67–9.08 mg/mL) in both broiler and buffalo isolates. In inhibition zone assays, the CSNPs + ciprofloxacin (CIP) combination showed the highest efficacy with a 50–58% increase in the inhibition area. Both CSNPs and CS 2% substantially reduced swarming motility by 45–52%, with CSNPs showing the strongest inhibitory effect. These outcomes highlight how P. mirabilis carries and disseminates antibiotic resistance, presenting serious threats to health policy and livestock. Also, CS or CSNPs, either alone or enhanced with CIP, are effective in vitro against resistant P. mirabilis, which promotes the treatment of Proteus infections to guarantee a bactericidal impact. Full article

Canine otitis externa is a common and recurrent ear infection in dogs, often caused by bacterial pathogens, and complicated by increasing antimicrobial resistance. The analysis of bacterial isolates from dogs with otitis externa revealed a predominance of Staphylococcus pseudintermedius, representing 41% of all cases, followed by Staphylococcus aureus (23%), and Pseudomonas aeruginosa (19%). Other less frequently isolated organisms included Escherichia coli, Streptococcus canis, and Proteus mirabilis. These results highlight the significant role of S. pseudintermedius in the pathogenesis of otitis externa in dogs, as well as the relevance of Gram-negative opportunistic pathogens like P. aeruginosa, which exhibits the highest recurrence rate, with 90% of the cases associated with highly resistant to β-lactams (93% for amoxicillin–clavulanic acid; >70% for third-generation cephalosporins). P. mirabilis showed complete resistance to tetracycline, partial resistance to doxycycline, and reduced susceptibility to carbapenems, nitrofurantoin, and polymyxin B. S. canis exhibited limited resistance to erythromycin and clindamycin, while S. epidermidis displayed extensive multidrug resistance, including β-lactams, fluoroquinolones, sulfonamides, and polymyxins. These findings highlight the high prevalence of multidrug-resistant pathogens in canine otitis externa, emphasizing the need for culture-guided therapy and raising concerns regarding One Health, due to potential zoonotic transmission and dissemination of genetic determinants of antimicrobial resistance. Full article

Human immunodeficiency virus (HIV), comprising two distinct types, HIV-1 and HIV-2, remains one of the most significant global health challenges, originating from multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) in the early 20th century. This review traces the evolutionary trajectory of HIV from zoonotic spillover to its establishment as a global pandemic. HIV-1, the principal strain responsible for AIDS, emerged from SIVcpz in Central African chimpanzees, with phylogenetic evidence indicating initial human transmission between the 1920s and 1940s in present day Democratic Republic of Congo. The virus disseminated through colonial trade networks, reaching the Caribbean by the 1960s before establishing endemic transmission in North America and Europe. HIV’s extraordinary genetic diversity—driven by high mutation rates (~10⁻⁵ mutations per base per replication cycle) and frequent recombination events—has generated multiple groups, subtypes, and circulating recombinant forms (CRFs) with distinct epidemiological patterns. HIV-1 Group M, comprising subtypes A through L, accounts for over 95% of global infections, with subtype C predominating in sub-Saharan Africa and Asia, while subtype B dominates in Western Europe and North America. The extensive genetic heterogeneity of HIV significantly impacts diagnostic accuracy, antiretroviral therapy efficacy, and vaccine development, as subtypes exhibit differential biological properties, transmission efficiencies, and drug resistance profiles. Contemporary advances, including next-generation sequencing (NGS) for surveillance, broadly neutralizing antibodies for cross-subtype prevention and therapy, and long-acting antiretroviral formulations to improve adherence, have transformed HIV management and prevention strategies. NGS enables near real-time surveillance of drug resistance mutations and inference of transmission networks where it is available, although access and routine application remain uneven across regions. Broadly neutralizing antibodies demonstrate cross-subtype efficacy, while long-acting formulations have the potential to improve treatment adherence. This review synthesizes recent evidence and offers actionable recommendations to optimize clinical and public health responses—including the routine use of genotypic resistance testing where feasible, targeted use of phylogenetic analysis for outbreak investigation, and the development of region-specific diagnostic and treatment algorithms informed by local subtype prevalence. While the understanding of HIV’s evolutionary dynamics has substantially improved and remains essential, translating this knowledge into universally implemented intervention strategies remains a key challenge for achieving the UNAIDS 95-95-95 targets and the goal of ending AIDS as a public health threat by 2030. Full article

Contemporary data on coccidioidomycosis death rates are sparse. Death certificate data for 2018–2023 from the US National Vital Statistics System were evaluated. Coccidioidomycosis deaths were identified using diagnosis codes B38.x listed anywhere on certificates. Deaths and age-adjusted mortality rates (AAMRs)/1,000,000 people, with 95% confidence intervals (CIs), were determined. We identified 1760 coccidioidomycosis-attributable deaths (AAMR = 0.75; 0.72–0.79). Most occurred in 55–74-year-olds (43.9%; corresponding AAMR = 1.72; 1.59–1.84). Males had a 2.69-fold increased AAMR versus females and American Indian or Alaska Native individuals had a 4.28-fold increased rate versus White individuals. Hispanics had a higher AAMR than the overall population (AAMR = 1.92; 1.76–2.08). AAMRs increased from 0.52 in 2019 to 0.79–0.94 in later years. Most (89.7%) death certificates were from endemic states, with Arizona having the highest AAMR. Seven hundred and thirteen certificates (40.5%) listed coccidioidomycosis as the primary cause of death, with 43.8% coded for pulmonary, 34.9% coded for disseminated, and 21.3% coded for unspecified coccidioidomycosis. Diabetes, COVID-19, and human immunodeficiency virus were more frequent on certificates with coccidioidomycosis versus without (RR range = 1.47–17.20). Mortality remained closely tied to demographic and geographic factors identified in prior studies, with county-level mapping revealing high-burden areas for targeted intervention. Coccidioidomycosis-attributable AAMRs rose over time, possibly influenced by concurrent COVID-19 infection. Only 40% of death certificates listed it as the primary cause, indicating that most patients experience chronic infection rather than death directly from the disease. These findings suggest the need for heightened clinical awareness of coccidioidomycosis, along with earlier diagnosis and prompt initiation of antifungal treatment in these high-risk groups. Full article

Introduction: Klebsiella variicola, a member of Klebsiella pneumoniae complex, has emerged as an opportunistic pathogen for human infection; however, antimicrobial resistance and hypervirulent characteristics of K. variicola have rarely been investigated in South Korea. Methods: We analyzed 76 clinical K. variicola isolates collected from 12 hospitals between September 2022 and October 2023. Bacterial identification was performed by MALDI-TOF MS. Antimicrobial susceptibility was tested by disk diffusion tests. Resistance determinants and virulence traits were investigated, and whole-genome sequencing was performed for hypermucoviscous or carbapenem-resistant K. variicola isolates. Results: Most (89.5%, 68/76) were susceptible to all 18 antimicrobials tested in this study, and 3 isolates harbored bla_CTX-M-15. One isolate carried bla_KPC-2 on its IncX3 plasmid, which is closely related to carbapenem-resistant K. pneumoniae plasmids. Capsular typing revealed 51 wzi allelic types. Ten isolates showed mucoid phenotype, mainly with KL60 and KL61. Conclusions: This study reveals relatively low resistance rates in K. variicola strains but the presence of multidrug-resistant and hypermucoviscous K. variicola strains. In addition, the evidence of interspecies dissemination of bla_KPC-2 highlights the need for continuous genomic surveillance. Full article

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, poses a significant public health threat in Asia. Although Culex species are primary vectors, the role of Aedes albopictus in JEV transmission has gained attention under changing ecological conditions. This study evaluated the vector competence of Ae. albopictus for three JEV genotypes: I (GI), III (GIII), and V (GV). Laboratory-reared Ae. albopictus were orally challenged with each genotype, and infection rate (IR), dissemination rate (DR), head–thorax positivity rate (HTR, proxy for potential transmission), and transmission rate (defined as saliva positivity) were assessed at 7 and 14 days post-infection (dpi). Ae. albopictus showed marked genotype-specific differences. By 14 dpi, GV had the highest DR (100.0%) and HTR (71.7%), with viral RNA detected in 36.7% of TR. GIII showed moderate competence (76.9% DR, 39.3% HTR), but low TR (6.6%). In contrast, GI-infected mosquitoes exhibited minimal infection and negligible transmission, with viral RNA rarely detected beyond the midgut. These findings indicate that Ae. albopictus is highly competent for transmitting JEV genotype V and moderately for genotype III, but not genotype I, under laboratory conditions. This highlights its potential role in the transmission dynamics of emerging JEV genotypes and underscores the need for continued surveillance. Full article

Invasive Fusarium infections pose a significant threat to immunocompromised patients and are characterised by high mortality rates. In this study, we examined 22 unique episodes of proven and probable Fusarium infections over a 14-year period at a tertiary hospital in Singapore. Cases were analysed from clinical, microbiological, and radiological perspectives. The most common risk factor for invasive Fusarium infections was hematologic malignancy. Fifty percent of patients achieved resolution of infection and were alive at the end of treatment. Conversely, the overall mortality was 50%, with 90% of deaths occurring within three months of the diagnosis of invasive fusariosis; associated risk factors include neutropenia, disseminated infection, and corticosteroid use. Although these deaths would be classified as treatment failures by established criteria; many (8/10; 80%) were due to causes not directly related to invasive fusariosis; such as progression of the underlying malignancy or another infection. We believe that it may be time to redefine how we assess treatment outcomes for invasive mould infections. Nevertheless; invasive fusariosis remains a formidable foe in the immunocompromised host. Early; aggressive treatment with appropriate adjunctive therapies; such as surgery; is crucial for controlling the infection and achieving the best outcomes. Full article