Infectious Disease

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Kuziez L, Eleiwa TK, Chauhan MZ, Sallam AB, Elhusseiny AM, Saeed HN. Corneal Adverse Events Associated with SARS-CoV-2/COVID-19 Vaccination: A Systematic Review. Vaccines (Basel) 2023;11(1)Abstract
Vaccines against coronavirus disease 2019 (COVID-19) have played an important global role in reducing morbidity and mortality from COVID-19 infection. While the benefits of vaccination greatly outweigh the risks, adverse events do occur. Non-ocular adverse effects of the vaccines have been well-documented, but descriptions of ophthalmic effects remain limited. This systematic review aims to provide an overview of reported cases of corneal adverse events after receiving vaccination against COVID-19 and to compile existing clinical data to bring attention to these phenomena. Our review discusses corneal graft rejection, including proposed mechanisms, herpetic keratitis, and other reported corneal complications. Ophthalmologists and primary care physicians should be aware of such possible associations.
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La Rosa SL, Snipen L-G, Murray BE, Willems RJL, Gilmore MS, Diep DB, Nes IF, Brede DA. A Genomic Virulence Reference Map of Enterococcus faecalis Reveals an Important Contribution of Phage03-Like Elements in Nosocomial Genetic Lineages to Pathogenicity in a Caenorhabditis elegans Infection Model. Infect Immun 2015;83(5):2156-67.Abstract
In the present study, the commensal and pathogenic host-microbe interaction of Enterococcus faecalis was explored using a Caenorhabditis elegans model system. The virulence of 28 E. faecalis isolates representing 24 multilocus sequence types (MLSTs), including human commensal and clinical isolates as well as isolates from animals and of insect origin, was investigated using C. elegans strain glp-4 (bn2ts); sek-1 (km4). This revealed that 6 E. faecalis isolates behaved in a commensal manner with no nematocidal effect, while the remaining strains showed a time to 50% lethality ranging from 47 to 120 h. Principal component analysis showed that the difference in nematocidal activity explained 94% of the variance in the data. Assessment of known virulence traits revealed that gelatinase and cytolysin production accounted for 40.8% and 36.5% of the observed pathogenicity, respectively. However, coproduction of gelatinase and cytolysin did not increase virulence additively, accounting for 50.6% of the pathogenicity and therefore indicating a significant (26.7%) saturation effect. We employed a comparative genomic analysis approach using the 28 isolates comprising a collection of 82,356 annotated coding sequences (CDS) to identify 2,325 patterns of presence or absence among the investigated strains. Univariate statistical analysis of variance (ANOVA) established that individual patterns positively correlated (n = 61) with virulence. The patterns were investigated to identify potential new virulence traits, among which we found five patterns consisting of the phage03-like gene clusters. Strains harboring phage03 showed, on average, 17% higher killing of C. elegans (P = 4.4e(-6)). The phage03 gene cluster was also present in gelatinase-and-cytolysin-negative strain E. faecalis JH2-2. Deletion of this phage element from the JH2-2 clinical strain rendered the mutant apathogenic in C. elegans, and a similar mutant of the nosocomial V583 isolate showed significantly attenuated virulence. Bioinformatics investigation indicated that, unlike other E. faecalis virulence traits, phage03-like elements were found at a higher frequency among nosocomial isolates. In conclusion, our report provides a valuable virulence map that explains enhancement in E. faecalis virulence and contributes to a deeper comprehension of the genetic mechanism leading to the transition from commensalism to a pathogenic lifestyle.
Lebreton F, Manson AL, Saavedra JT, Straub TJ, Earl AM, Gilmore MS. Tracing the Enterococci from Paleozoic Origins to the Hospital. Cell 2017;169(5):849-861.e13.Abstract
We examined the evolutionary history of leading multidrug resistant hospital pathogens, the enterococci, to their origin hundreds of millions of years ago. Our goal was to understand why, among the vast diversity of gut flora, enterococci are so well adapted to the modern hospital environment. Molecular clock estimation, together with analysis of their environmental distribution, phenotypic diversity, and concordance with host fossil records, place the origins of the enterococci around the time of animal terrestrialization, 425-500 mya. Speciation appears to parallel the diversification of hosts, including the rapid emergence of new enterococcal species following the End Permian Extinction. Major drivers of speciation include changing carbohydrate availability in the host gut. Life on land would have selected for the precise traits that now allow pathogenic enterococci to survive desiccation, starvation, and disinfection in the modern hospital, foreordaining their emergence as leading hospital pathogens.
Lebreton F, Valentino MD, Schaufler K, Earl AM, Cattoir V, Gilmore MS. Transferable vancomycin resistance in clade B commensal-type Enterococcus faecium. J Antimicrob Chemother 2018;73(6):1479-1486.Abstract
Objectives: Vancomycin-resistant Enterococcus faecium is a leading cause of MDR hospital infection. Two genetically definable populations of E. faecium have been identified: hospital-adapted MDR isolates (clade A) and vancomycin-susceptible commensal strains (clade B). VanN-type vancomycin resistance was identified in two isolates of E. faecium recovered from blood and faeces of an immunocompromised patient. To understand the genomic context in which VanN occurred in the hospitalized patient, the risk it posed for transmission in the hospital and its origins, it was of interest to determine where these strains placed within the E. faecium population structure. Methods: We obtained the genome sequence of the VanN isolates and performed comparative and functional genomics of the chromosome and plasmid content. Results: We show that, in these strains, VanN occurs in a genetic background that clusters with clade B E. faecium, which is highly unusual. We characterized the chromosome and the conjugative plasmid that carries VanN resistance in these strains, pUV24. This plasmid exhibits signatures of in-host selection on the vanN operon regulatory system, which are associated with a constitutive expression of vancomycin resistance. VanN resistance in clade B strains may go undetected by current methods. Conclusions: We report a case of vancomycin resistance in a commensal lineage of E. faecium responsible for an atypical bacteraemia in an immunocompromised patient. A reservoir of transferable glycopeptide resistance in the community could pose a concern for public health.
Lebreton F, van Schaik W, McGuire AM, Godfrey P, Griggs A, Mazumdar V, Corander J, Cheng L, Saif S, Young S, Zeng Q, Wortman J, Birren B, Willems RJL, Earl AM, Gilmore MS. Emergence of epidemic multidrug-resistant Enterococcus faecium from animal and commensal strains. MBio 2013;4(4)Abstract
UNLABELLED: Enterococcus faecium, natively a gut commensal organism, emerged as a leading cause of multidrug-resistant hospital-acquired infection in the 1980s. As the living record of its adaptation to changes in habitat, we sequenced the genomes of 51 strains, isolated from various ecological environments, to understand how E. faecium emerged as a leading hospital pathogen. Because of the scale and diversity of the sampled strains, we were able to resolve the lineage responsible for epidemic, multidrug-resistant human infection from other strains and to measure the evolutionary distances between groups. We found that the epidemic hospital-adapted lineage is rapidly evolving and emerged approximately 75 years ago, concomitant with the introduction of antibiotics, from a population that included the majority of animal strains, and not from human commensal lines. We further found that the lineage that included most strains of animal origin diverged from the main human commensal line approximately 3,000 years ago, a time that corresponds to increasing urbanization of humans, development of hygienic practices, and domestication of animals, which we speculate contributed to their ecological separation. Each bifurcation was accompanied by the acquisition of new metabolic capabilities and colonization traits on mobile elements and the loss of function and genome remodeling associated with mobile element insertion and movement. As a result, diversity within the species, in terms of sequence divergence as well as gene content, spans a range usually associated with speciation. IMPORTANCE: Enterococci, in particular vancomycin-resistant Enterococcus faecium, recently emerged as a leading cause of hospital-acquired infection worldwide. In this study, we examined genome sequence data to understand the bacterial adaptations that accompanied this transformation from microbes that existed for eons as members of host microbiota. We observed changes in the genomes that paralleled changes in human behavior. An initial bifurcation within the species appears to have occurred at a time that corresponds to the urbanization of humans and domestication of animals, and a more recent bifurcation parallels the introduction of antibiotics in medicine and agriculture. In response to the opportunity to fill niches associated with changes in human activity, a rapidly evolving lineage emerged, a lineage responsible for the vast majority of multidrug-resistant E. faecium infections.
Lee DH, Cohen LM, Yoon MK, Tao JP. Punctal stenosis associated with dupilumab therapy for atopic dermatitis. J Dermatolog Treat 2021;32(7):737-740.Abstract
In this case series, the authors report three patients with severe atopic dermatitis who presented with epiphora and conjunctivitis while undergoing dupilumab therapy. On clinical examination, all patients were found to have punctal stenosis, with one case having progressed to punctal obstruction. An assortment of strategies was elected, including discontinuation of dupilumab, treatment of conjunctivitis, and surgical intervention with probing, punctoplasty, and silicone intubation. This report spotlights punctal stenosis as an important new side effect of dupilumab and suggests that additional cases of dupilumab-associated lacrimal drainage impairment will continue to emerge.
Lee JS, Ismail AM, Lee JY, Zhou X, Materne EC, Chodosh J, Rajaiya J. Impact of dynamin 2 on adenovirus nuclear entry. Virology 2019;529:43-56.Abstract
The large GTPase dynamin 2 controls both endosomal fission and microtubule acetylation. Here we report that dynamin 2 alters microtubules and regulates the trafficking of human adenovirus type 37. Dynamin 2 knockdown by siRNA in infected cells resulted in accumulation of acetylated tubulin, repositioning of microtubule organizing centers (MTOCs) closer to cell nuclei, increased virus in the cytosol (with a compensatory decrease in endosomal virus), reduced proinflammatory cytokine induction, and increased binding of virus to the nucleoporin, Nup358. These events led to increased viral DNA nuclear entry and viral replication. Overexpression of dynamin 2 generated opposite effects. Therefore, dynamin 2 inhibits adenovirus replication and promotes innate immune responses by the infected cell. MTOC transposition in dynamin 2 knockdown promotes a closer association with nuclear pore complexes to facilitate viral DNA delivery. Dynamin 2 plays a key role in adenoviral trafficking and influences host responses to infection.
Lee JY, Lee JS, Materne EC, Rajala R, Ismail AM, Seto D, Dyer DW, Rajaiya J, Chodosh J. Bacterial RecA Protein Promotes Adenoviral Recombination during Infection. mSphere 2018;3(3)Abstract
Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as Chi, were identified immediately 5' to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an lysate increased recombination; this was blocked in a RecA mutant strain, DH5α, or upon RecA depletion. Recombination increased in the presence of lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to Chi sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism. Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota.
Lee CS, Lee AY, Akileswaran L, Stroman D, Najafi-Tagol K, Kleiboeker S, Chodosh J, Magaret A, Wald A, Van Gelder RN, Van Gelder RN. Determinants of Outcomes of Adenoviral Keratoconjunctivitis. Ophthalmology 2018;125(9):1344-1353.Abstract
PURPOSE: To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis. DESIGN: Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT01877694). PARTICIPANTS: Five hundred participants from United States, India, Brazil, and Sri Lanka with clinical diagnosis of keratoconjunctivitis and positive rapid test results for adenovirus. METHODS: Clinical signs and symptoms and bilateral conjunctival swabs were obtained on days 1, 3, 6, 11, and 18. Polymerase chain reaction (PCR) analysis was performed to detect and quantify adenovirus in all samples. Regression models were used to evaluate the association of various variables with keratoconjunctivitis outcomes. Time to resolution of each symptom or sign was assessed by adenoviral species with Cox regression. MAIN OUTCOME MEASURES: The difference in composite scores of clinical signs between days 1 and 18, mean visual acuity change between days 1 and 18, and time to resolution of each symptom or sign. RESULTS: Of 500 participants, 390 (78%) showed evidence of adenovirus by PCR. Among adenovirus-positive participants, adenovirus D species was most common (63% of total cases), but a total of 4 species and 21 different types of adenovirus were detected. Adenovirus D was associated with more severe signs and symptoms, a higher rate of subepithelial infiltrate development, and a slower decline in viral load compared with all other adenovirus species. The clinical courses of all patients with non-adenovirus D species infection and adenovirus-negative keratoconjunctivitis were similar. Mean change in visual acuity between days 1 and 18 was a gain of 1.9 letters; worse visual outcome was associated with older age. CONCLUSIONS: A substantial proportion of keratoconjunctivitis is not associated with a detectable adenovirus. The clinical course of those with adenovirus D keratoconjunctivitis is significantly more severe than those with non-adenovirus D species infections or adenovirus-negative keratoconjunctivitis; high viral load at presentation and non-United States origin of participants is associated with poorer clinical outcome.
Leme RCP, Martins Bispo PJ, Salles MJ. Community-genotype methicillin-resistant Staphylococcus aureus skin and soft tissue infections in Latin America: a systematic review. Braz J Infect Dis 2021;:101539.Abstract
BACKGROUND: Community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) emerged in the 1990s as a global community pathogen primarily involved in skin and soft tissue infections (SSTIs) and pneumonia. To date, the CG-MRSA SSTI burden in Latin America (LA) has not been assessed. OBJECTIVE: The main objective of this study was to report the rate and genotypes of community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) causing community-onset skin and soft tissue infections (CO-SSTIs) in LA over the last two decades. In addition, this research determined relevant data related to SSTIs due to CG-MRSA, including risk factors, other invasive diseases, and mortality. DATA SOURCES: Relevant literature was searched and extracted from five major databases: Embase, PubMed, LILACS, SciELO, and Web of Science. METHODS: A systematic review was performed, and a narrative review was constructed. RESULTS: An analysis of 11 studies identified epidemiological data across LA, with Argentina presenting the highest percentage of SSTIs caused by CG-MRSA (88%). Other countries had rates of CG-MRSA infection ranging from 0 to 51%. Brazil had one of the lowest rates of CG-MRSA SSTI (4.5-25%). In Argentina, being younger than 50 years of age and having purulent lesions were predictive factors for CG-MRSA CO-SSTIs. In addition, the predominant genetic lineages in LA belonged to sequence types 8, 30, and 5 (ST8, ST30, and ST5). CONCLUSION: There are significant regional differences in the rates of CG-MRSA causing CO-SSTIs. It is not possible to conclude whether or not CG-MRSA CO-SSTIs resulted in more severe SSTI presentations or in a higher mortality rate.
Letko E, Yeh S, Foster SC, Pleyer U, Brigell M, Grosskreutz CL, Grosskreutz CL. Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy. Ophthalmology 2015;122(5):939-48.Abstract
PURPOSE: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to patients with active, chronic, noninfectious uveitis. This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in patients with noninfectious uveitis. DESIGN: Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial. PARTICIPANTS: Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy. METHODS: Patients were randomized to secukinumab 300 mg SC every 2 weeks for 4 doses, secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or secukinumab 30 mg/kg IV every 4 weeks for 2 doses. Intravenous or SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose). MAIN OUTCOME MEASURES: Percentage of patients with treatment response, defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening. Percentage of patients with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening. RESULTS: Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC dose, produced higher responder rates (72.7% and 61.5% vs. 33.3%, respectively) and remission rates (27.3% and 38.5% vs. 16.7%, respectively). Statistical and clinical superiority for the 30 mg/kg IV dose compared with the 300 mg SC dose was established in a Bayesian probability model. Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring IV dosing. Secukinumab, administered in IV or SC formulations, appeared safe and was well tolerated. CONCLUSIONS: Intravenous secukinumab was effective and well tolerated in noninfectious uveitis requiring systemic corticosteroid-sparing immunosuppressive therapy. Greater activity with IV dosing suggests that patients may not receive sufficient drug with SC administration. High-dose IV secukinumab may be necessary to deliver secukinumab in therapeutic concentrations.
Li H, Reksten TR, Ice JA, Kelly JA, Adrianto I, Rasmussen A, Wang S, He B, Grundahl KM, Glenn SB, Miceli-Richard C, Bowman S, Lester S, Eriksson P, Eloranta M-L, Brun JG, Gøransson LG, Harboe E, Guthridge JM, Kaufman KM, Kvarnström M, Cunninghame Graham DS, Patel K, Adler AJ, Farris DA, Brennan MT, Chodosh J, Gopalakrishnan R, Weisman MH, Venuturupalli S, Wallace DJ, Hefner KS, Houston GD, Huang AJW, Hughes PJ, Lewis DM, Radfar L, Vista ES, Edgar CE, Rohrer MD, Stone DU, Vyse TJ, Harley JB, Gaffney PM, James JA, Turner S, Alevizos I, Anaya J-M, Rhodus NL, Segal BM, Montgomery CG, Scofield HR, Kovats S, Mariette X, Rönnblom L, Witte T, Rischmueller M, Wahren-Herlenius M, Omdal R, Jonsson R, Ng W-F, for Registry UKPS's S, Nordmark G, Lessard CJ, Sivils KL. Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons. PLoS Genet 2017;13(6):e1006820.Abstract
Sjögren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 × 10-14). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (Pmeta = 2.59 × 10-9; odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.
Liao XL, Li CQ, Ge QM, Tang L, Su T, Li QY, Pan YC, Shu HY, Zhang LJ, Shao Y. Investigation of Altered Spontaneous Brain Activity Patterns in Herpes Zoster Keratitis Using the Percent Amplitude of Fluctuation Method: A Resting-State Functional Magnetic Resonance Imaging Study. Neuropsychiatr Dis Treat 2023;19:1781-1789.Abstract
PURPOSE: The purpose of this study was to use the percent amplitude of fluctuation (PerAF) to study the changes in brain activity and nerve function of herpes zoster keratitis (HZK) patients. METHODS: We recruited 20 HZK patients and 20 healthy controls (HCs). Each of these groups included ten males and ten females and were matched in weight and age. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The percent amplitude of fluctuation (PerAF) method was used for analysis and detected differences between the two groups in the neurological function of brain areas. We also applied the receiver operating characteristic (ROC) curve to analyze the two groups and did a correlation analysis between the PerAF value, anxiety and depression score, and visual acuity. RESULTS: The PerAF signal at the right putamen and right precentral gyrus was significantly higher in patients than in HCs. However, the PerAF value of the left inferior temporal was lower in patients than in HCs. In addition, the HZK patients' anxiety and depression score (HADS) and visual acuity (V.A.) Log MAR negatively correlated with the PerAF value at the left inferior temporal gyrus. CONCLUSION: HZK patients had some changes in brain regions, and the changes were also related to their mood and visual acuity. These findings might contribute to other studies on the potential pathological mechanism, disease development, prognosis, and brain function in HZK patients.
Lieberman MT, Van Tyne D, Dzink-Fox JA, Ma EJ, Gilmore MS, Fox JG. Long-Term Colonization Dynamics of Enterococcus faecalis in Implanted Devices in Research Macaques. Appl Environ Microbiol 2018;84(18)Abstract
is a common opportunistic pathogen that colonizes cephalic recording chambers (CRCs) of macaques used in cognitive neuroscience research. We previously characterized 15 strains isolated from macaques at the Massachusetts Institute of Technology (MIT) in 2011. The goal of this study was to examine how a 2014 protocol change prohibiting the use of antimicrobials within CRCs affected colonizing strains. We collected 20 isolates from 10 macaques between 2013 and 2017 for comparison to 4 isolates previously characterized in 2011 with respect to the sequence type (ST) distribution, antimicrobial resistance, biofilm formation, and changes in genes that might confer a survival advantage. ST4 and ST55 were predominant among the isolates characterized in 2011, whereas the less antimicrobial-resistant lineage ST48 emerged to dominance after 2013. Two macaques remained colonized by ST4 and ST55 strains for 5 and 4 years, respectively. While the antimicrobial resistance and virulence factors identified in these ST4 and ST55 strains remained relatively stable, we detected an increase in biofilm formation ability over time in both isolates. We also found that ST48 strains were typically robust biofilm formers, which could explain why this ST increased in prevalence. Finally, we identified mutations in the DNA mismatch repair genes and in separate ST55 and ST4 strains and confirmed that strains bearing these mutations displayed a hypermutator phenotype. The presence of a hypermutator phenotype may complicate future antimicrobial treatment for clinically relevant infections in macaques. is a common cause of health care-associated infections in humans, largely due to its ability to persist in the hospital environment, colonize patients, acquire antimicrobial resistance, and form biofilms. Understanding how enterococci evolve in health care settings provides insight into factors affecting enterococcal survival and persistence. Macaques used in neuroscience research have long-term cranial implants that, despite best practices, often become colonized by This provides a unique opportunity to noninvasively examine the evolution of enterococci on a long-term indwelling device. We collected strains from cephalic implants over a 7-year period and characterized the sequence type, antimicrobial resistance, virulence factors, biofilm production, and hypermutator phenotypes. Improved antimicrobial stewardship allowed a less-antimicrobial-resistant strain to predominate at the implant interface, potentially improving antimicrobial treatment outcomes if future clinical infections occur. Biofilm formation appears to play an important role in the persistence of the strains associated with these implants.
Lin JB, Eliott D, Sobrin L, Stryjewski TP. ENDOGENOUS ENDOPHTHALMITIS DUE TO STREPTOCOCCUS ANGINOSUS IN A HEALTHY, YOUNG WOMAN. Retin Cases Brief Rep 2023;17(5):524-527.Abstract
PURPOSE: The purpose of this study was to present a case of indolent endogenous endophthalmitis in a young, seemingly healthy woman. METHODS: This study is a retrospective case report. RESULTS: A 25-year-old woman with no significant medical history presented with vision loss in the left eye over the course of 1 month. Examination showed vitritis and a white-yellow lesion overlying the macula and optic nerve in the left eye. Initial laboratory testing for infectious and inflammatory causes was unrevealing. A diagnostic vitrectomy was performed, and the patient was found to have presumed endogenous endophthalmitis due to Streptococcus anginosus, an extremely uncommon bacterium. Subsequent workup did not reveal evidence of bacteremia, endocarditis, or orbital infection. This case is unique because, unlike the three previously reported cases of S. anginosus endophthalmitis, this patient was seemingly healthy, never had an elevated white blood cell count, never had documented bacteremia, had a normal echocardiogram, and had normal orbital findings on magnetic resonance imaging and computed tomography scans. Further questioning revealed a remote history of facial cellulitis and possible sinusitis treated with oral antibiotics, which are the presumed etiology. CONCLUSION: Streptococcus anginosus endophthalmitis can occur in young, seemingly healthy patients. Endogenous endophthalmitis should be considered in the differential diagnosis even without systemic comorbidities or other risk factors. Detailed questioning about medical history and thorough review of systems, including nonocular symptoms, are essential.
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Ma KK, Kinde B, Doan T, Jacobs DS, Ong Tone S. Dual Molecular Diagnosis of Microsporidia (Encephalitozoon hellem) Keratoconjunctivitis in an Immunocompetent Adult. Cornea 2021;40(2):242-244.Abstract
PURPOSE: To report a case of microsporidia (Encephalitozoon hellem) keratoconjunctivitis acquired through avian transmission in an immunocompetent adult, diagnosed by metagenomic deep sequencing (MDS), and confirmed by polymerase chain reaction. METHODS: A case report. RESULTS: An 18-year-old woman was referred with unilateral keratoconjunctivitis unresponsive to topical and systemic therapy after exposure to birdcage debris. Slit-lamp examination of the left eye revealed a follicular papillary reaction of the palpebral conjunctiva and multiple corneal punctate epithelial opacities that stained minimally with fluorescein. In vivo confocal microscopy revealed bright double-walled structures and smaller bright round structures in the superficial epithelial debris and epithelium. Molecular diagnosis with MDS of E. hellem was confirmed by polymerase chain reaction. Clinical resolution and normalization of in vivo confocal microscopy was observed after a 6-week course of topical azithromycin. The patient elected a 3-week course of topical voriconazole 1% for definitive antimicrosporidial treatment, with no evidence of persistent infection 1 month later. CONCLUSIONS: Microsporidial (E. hellem) keratoconjunctivitis can occur through avian transmission in immunocompetent hosts. Topical azithromycin may be effective against this pathogen. MDS has utility in the diagnosis of atypical keratoconjunctivitis.
Maciorowski D, Diop C, Bhatt U, Estelien R, Li D, Chauhan R, Vandenberghe LH, Zabaleta N. Immunogenicity of an AAV-Based COVID-19 Vaccine in Murine Models of Obesity and Aging. Viruses 2022;14(4)Abstract
The SARS-CoV-2 pandemic has had a disastrous impact on global health. Although some vaccine candidates have been effective in combating SARS-CoV-2, logistical, economical, and sociological aspects still limit vaccine access globally. Recently, we reported on two room-temperature stable AAV-based COVID-19 vaccines that induced potent and protective immunogenicity following a single injection in murine and primate models. Obesity and old age are associated with increased mortality in COVID-19, as well as reduced immunogenicity and efficacy of vaccines. Here, we investigated the effectiveness of the AAVCOVID vaccine candidates in murine models of obesity and aging. Results demonstrate that obesity did not significantly alter the immunogenicity of either vaccine candidate. In aged mice, vaccine immunogenicity was impaired. These results suggest that AAV-based vaccines may have limitations in older populations and may be equally applicable in obese and non-obese populations.
Manson AL, Van Tyne D, Straub TJ, Clock S, Crupain M, Rangan U, Gilmore MS, Earl AM. Chicken Meat-Associated Enterococci: Influence of Agricultural Antibiotic Use and Connection to the Clinic. Appl Environ Microbiol 2019;85(22)Abstract
Industrial farms are unique, human-created ecosystems that provide the perfect setting for the development and dissemination of antibiotic resistance. Agricultural antibiotic use amplifies naturally occurring resistance mechanisms from soil ecologies, promoting their spread and sharing with other bacteria, including those poised to become endemic within hospital environments. To better understand the role of enterococci in the movement of antibiotic resistance from farm to table to clinic, we characterized over 300 isolates of cultured from raw chicken meat purchased at U.S. supermarkets by the Consumers Union in 2013. and were the predominant species found, and antimicrobial susceptibility testing uncovered striking levels of resistance to medically important antibiotic classes, particularly from classes approved by the FDA for use in animal production. While nearly all isolates were resistant to at least one drug, bacteria from meat labeled as raised without antibiotics had fewer resistances, particularly for Whole-genome sequencing of 92 isolates revealed that both commensal- and clinical-isolate-like enterococcal strains were associated with chicken meat, including isolates bearing important resistance-conferring elements and virulence factors. The ability of enterococci to persist in the food system positions them as vehicles to move resistance genes from the industrial farm ecosystem into more human-proximal ecologies. Bacteria that contaminate food can serve as a conduit for moving drug resistance genes from farm to table to clinic. Our results show that chicken meat-associated isolates of are often multidrug resistant, closely related to pathogenic lineages, and harbor worrisome virulence factors. These drug-resistant agricultural isolates could thus represent important stepping stones in the evolution of enterococci into drug-resistant human pathogens. Although significant efforts have been made over the past few years to reduce the agricultural use of antibiotics, continued assessment of agricultural practices, including the roles of processing plants, shared breeding flocks, and probiotics as sources for resistance spread, is needed in order to slow the evolution of antibiotic resistance. Because antibiotic resistance is a global problem, global policies are needed to address this threat. Additional measures must be taken to mitigate the development and spread of antibiotic resistance elements from farms to clinics throughout the world.
Marmalidou A, Kheirkhah A, Dana R. Conjunctivochalasis: A Systematic Review. Surv Ophthalmol 2017;Abstract
Conjunctivochalasis (CCH) is a conjunctival condition characterized by loose, redundant conjunctival folds, most typically in the inferior bulbar conjunctiva of both eyes. Although CCH is a common cause of ocular irritation and discomfort, especially in the elderly, it is often overlooked in clinical practice. Conjunctivochalasis may be associated with various ocular and non-ocular conditions; however, the most important risk factor is aging. Although often asymptomatic, CCH may cause symptoms related to tear film instability and/or delayed tear clearance. Pathogenesis of CCH remains largely unknown, but may involve different elements such as aged conjunctiva, unstable tear film, mechanical friction, ocular surface inflammation, and delayed tear clearance. Contradictory results have been reported on histopathologic changes in CCH, with some studies showing a normal microscopic structure. For symptomatic CCH, medical treatment may include lubrication and anti-inflammatory medications. For symptomatic patients who fail to respond to medical treatment, a surgical procedure may be considered. Although various surgical procedures have been used for CCH, more often it consists of conjunctival cauterization or excision of the redundant conjunctiva, with or without amniotic membrane transplantation.
Marsiglia M, Chwalisz BK, Maher M. Neuroradiologic Imaging of Neurologic and Neuro-Ophthalmic Complications of Coronavirus-19 Infection. J Neuroophthalmol 2021;41(4):452-460.Abstract
BACKGROUND: To review the literature and provide a summary of COVID-19-related neurologic and neuro-ophthalmic complications. METHODS: The currently available literature was reviewed on PubMed and Google Scholar using the following keywords for searches: CNS, Neuro-Ophthalmology, COVID-19, SARS-CoV-2, coronavirus, optic neuritis, pseudotumor cerebri, Acute Disseminated Encephalomyelitis, posterior reversible encephalopathy syndrome (PRES), meningitis, encephalitis, acute necrotizing hemorrhagic encephalopathy, and Guillain-Barré and Miller Fisher syndromes. RESULTS: Neuroradiologic findings of neurologic and neuro-ophthalmologic complications in relationship to COVID-19 infection were reviewed. Afferent visual pathway-related disorders with relevant imaging manifestations included fundus nodules on MRI, papilledema and pseudotumor cerebri syndrome, optic neuritis, Acute Disseminated Encephalomyelitis, vascular injury with thromboembolism and infarct, leukoencephalopathy, gray matter hypoxic injury, hemorrhage, infectious meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy, and PRES. Efferent visual pathway-related complications with relevant imaging manifestations were also reviewed, including orbital abnormalities, cranial neuropathy, Guillain-Barré and Miller Fisher syndromes, and nystagmus and other eye movement abnormalities related to rhombencephalitis. CONCLUSION: COVID-19 can cause central and peripheral nervous system disease, including along both the afferent and efferent components of visual axis. Manifestations of disease and long-term sequela continue to be studied and described. Familiarity with the wide variety of neurologic, ophthalmic, and neuroradiologic presentations can promote prompt and appropriate treatment and continue building a framework to understand the underlying mechanism of disease.

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