Infectious Disease

Infectious Disease Publications

Singh RB, Parmar UPS, Ichhpujani P, Jeng BH, Jhanji V. Herpetic Eye Disease After SARS-CoV-2 Vaccination: A CDC-VAERS Database Analysis. Cornea 2023;Abstract
PURPOSE: The aim of this study was to evaluate the cases of herpes simplex and zoster ophthalmicus after SARS-CoV-2 vaccination and assess the clinical presentations in patients. METHODS: A retrospective analysis of cases reported to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS) between December 11, 2020, and July 1, 2022. Patients diagnosed with herpes simplex ophthalmicus (HSO) and herpes zoster ophthalmicus (HZO) after vaccination with BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Janssen) were included in the study. We performed a descriptive analysis of patient demographics, history, and ophthalmic and systemic clinical presentations. The correlations between vaccine type and continuous variables were assessed by the one-way analysis of variance test. In addition, we used the Pearson χ2 test to assess the association between 3 vaccines and categorical variables. A post hoc analysis was performed between HSO and HZO onset intervals after vaccination, dose, and vaccine type. The 30-day risk analysis was also performed for HSO and HZO onset postvaccination using the reverse Kaplan-Meier analysis. RESULTS: A total of 1180 cases of HZO (983, 83.30%) and HSO (180, 15.25%) were reported. The mean age of patients with HZO and HSO was 59.02 ± 19.05 and 52.68 ± 17.83 years, respectively. Most of the cases of HZO (795, 80.87%) and HSO (131, 72.78%) were reported in patients who received BNT162b2. In the cohort, 63.28% and 65.56% diagnosed with HZO and HSO were women. About one third of HZO (36.52%) and HSO (35.56%) cases were reported after the first dose. More than half of the cases of HZO (61.34%) and HSO (64.45%) were reported within the first 2 weeks after vaccination. The estimated crude reporting rate (per million doses) in the United States was 0.25, 0.22, and 0.47 for BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively. The onset interval for HZO was significantly shorter in patients who received BNT162b2 (20.51 ± 56.20 days, P = 0.030) compared with patients who received mRNA-1273 (36.56 ± 108.67 days) and Ad26.COV2.S (39.66 ± 60.15 days) vaccines. The 30-day risk analysis showed a significantly higher risk of HZO after BNT162b2 than the other 2 vaccines (P = 0.011). CONCLUSIONS: The low crude reporting rate suggests that HZO and HSO after SARS-CoV-2 vaccination occur rarely. This study provides insights into the possible temporal association between reported HSO and HZO after SARS-CoV-2 vaccines; however, further investigations are required to delineate the possible underlying immunological mechanisms.
Bispo PJM, Belanger N, Li A, Liu R, Susarla G, Chan W, Chodosh J, Gilmore MS, Sobrin L. An all-in-one highly multiplexed diagnostic assay for rapid, sensitive and comprehensive detection of intraocular pathogens. Am J Ophthalmol 2023;Abstract
PURPOSE: Intraocular infections are sight-threatening conditions that can lead to vision loss. Rapid identification of the etiologies plays a key role in early initiation of effective therapy to save vision. However, current diagnostic modalities are time-consuming, lack sensitivity and inclusiveness. We present here a newly developed comprehensive ocular panel designed to improve diagnostic yields and provide a tool for rapid and sensitive pathogen detection. DESIGN: Experimental laboratory investigation. METHODS: A panel containing 46 pathogens and 2 resistance/virulence markers that are commonly detected in intraocular infections was developed. Genomic targets were scrutinized for stretches predicted to be specific for a particular species while being conserved across different strains. A set of primers for sample enrichment, and two 50mer NanoString compatible probes were then designed for each target. Probe-target hybrids were detected and quantified using the NanoString nCounter SPRINT Profiler. Diagnostic feasibility was assessed in a pilot clinical study testing samples from infectious retinitis (n=15) and endophthalmitis (n=12) patients for which the etiologies were confirmed by PCR or culture. RESULTS: Analytical studies demonstrated highly sensitive detection of a broad spectrum of pathogens, including bacteria, viruses and parasites, with limits of detection being as low as 2.5 femtograms per reaction. We also found excellent target specificity, with minimal cross-reactivity detected. The custom-designed NanoString ocular panel correctly identified the causative agent from all clinical specimens positive for a variety of pathogens. CONCLUSION: This highly multiplexed panel for pathogen detection offers a sensitive, comprehensive, and uniform assay run directly on ocular fluids that could significantly improve diagnostics of sight-threatening intraocular infections.
Pons S, Frapy E, Sereme Y, Gaultier C, Lebreton F, Kropec A, Danilchanka O, Schlemmer L, Schrimpf C, Allain M, Angoulvant F, Lecuyer H, Bonacorsi S, Aschard H, Sokol H, Cywes-Bentley C, Mekalanos JJ, Guillard T, Pier GB, Roux D, Skurnik D. A high-throughput sequencing approach identifies immunotherapeutic targets for bacterial meningitis in neonates. EBioMedicine 2023;88:104439.Abstract
BACKGROUND: Worldwide, Escherichia coli is the leading cause of neonatal Gram-negative bacterial meningitis, but full understanding of the pathogenesis of this disease is not yet achieved. Moreover, to date, no vaccine is available against bacterial neonatal meningitis. METHODS: Here, we used Transposon Sequencing of saturated banks of mutants (TnSeq) to evaluate E. coli K1 genetic fitness in murine neonatal meningitis. We identified E. coli K1 genes encoding for factors important for systemic dissemination and brain infection, and focused on products with a likely outer-membrane or extra-cellular localization, as these are potential vaccine candidates. We used in vitro and in vivo models to study the efficacy of active and passive immunization. RESULTS: We selected for further study the conserved surface polysaccharide Poly-β-(1-6)-N-Acetyl Glucosamine (PNAG), as a strong candidate for vaccine development. We found that PNAG was a virulence factor in our animal model. We showed that both passive and active immunization successfully prevented and/or treated meningitis caused by E. coli K1 in neonatal mice. We found an excellent opsonophagocytic killing activity of the antibodies to PNAG and in vitro these antibodies were also able to decrease binding, invasion and crossing of E. coli K1 through two blood brain barrier cell lines. Finally, to reinforce the potential of PNAG as a vaccine candidate in bacterial neonatal meningitis, we demonstrated that Group B Streptococcus, the main cause of neonatal meningitis in developed countries, also produced PNAG and that antibodies to PNAG could protect in vitro and in vivo against this major neonatal pathogen. INTERPRETATION: Altogether, these results indicate the utility of a high-throughput DNA sequencing method to identify potential immunotherapy targets for a pathogen, including in this study a potential broad-spectrum target for prevention of neonatal bacterial infections. FUNDINGS: ANR Seq-N-Vaq, Charles Hood Foundation, Hearst Foundation, and Groupe Pasteur Mutualité.
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.
Varela APM, Sant'Anna FH, Dos Santos AV, Prichula J, Comerlato J, Dos Santos GT, Wendland E. Genomic evidence of SARS-CoV-2 reinfection cases in southern Brazil. Arch Virol 2023;168(1):19.Abstract
Cases of reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported worldwide. We investigated reinfection cases in a set of more than 30,000 samples, and the SARS-CoV-2 genomes from selected samples from four patients with at least two positive diagnoses with an interval ≥ 45 days between tests were sequenced and analyzed. Comparative genomic and phylogenetic analysis confirmed three reinfection cases and suggested that the fourth one was caused by a virus of the same lineage. Viral sequencing is crucial for understanding the natural course of reinfections and for planning public health strategies for management of COVID-19.
Kaufman AR, Chodosh J, Pineda R. Monkeypox Virus and Ophthalmology-A Primer on the 2022 Monkeypox Outbreak and Monkeypox-Related Ophthalmic Disease. JAMA Ophthalmol 2023;141(1):78-83.Abstract
IMPORTANCE: An ongoing global monkeypox virus outbreak in 2022 includes the US and other nonendemic countries. Monkeypox ophthalmic manifestations may present to the ophthalmologist, or the ophthalmologist may be involved in comanagement. This narrative review creates a primer for the ophthalmologist of clinically relevant information regarding monkeypox, its ophthalmic manifestations, and the 2022 outbreak. OBSERVATIONS: Monkeypox virus is an Orthopoxvirus (genus includes variola [smallpox] and vaccinia [smallpox vaccine]). The 2022 outbreak is of clade II (historically named West African clade), specifically subclade IIb. In addition to historic transmission patterns (skin lesions, bodily fluids, respiratory droplets), sexual transmission has also been theorized in the current outbreak due to disproportionate occurrence in men who have sex with men. Monkeypox causes a characteristic skin eruption and mucosal lesions and may cause ophthalmic disease. Monkeypox-related ophthalmic disease (MPXROD) includes a spectrum of ocular pathologies including eyelid/periorbital skin lesions, blepharoconjunctivitis, and keratitis). Smallpox vaccination may reduce MPXROD occurrence. MPXROD seems to be rarer in the 2022 outbreaks than in historical outbreaks. MPXROD may result in corneal scarring and blindness. Historical management strategies for MPXROD include lubrication and prevention/management of bacterial superinfection in monkeypox keratitis. Case reports and in vitro data for trifluridine suggest a possible role in MPXROD. Tecovirimat, cidofovoir, brincidofovir and vaccinia immune globulin intravenous may be used for systemic infection. There is a theoretical risk for monkeypox transmission by corneal transplantation, and the Eye Bank Association of America has provided guidance. Smallpox vaccines (JYNNEOS [Bavarian Nordic] and ACAM2000 [Emergent Product Development Gaithersburg Inc]) provide immunity against monkeypox. CONCLUSIONS AND RELEVANCE: The ophthalmologist may play an important role in the diagnosis and management of monkeypox. MPXROD may be associated with severe ocular and visual morbidity. As the current outbreak evolves, up-to-date guidance from public health organizations and professional societies are critical.
Harris CK, Christensen BB, Kwan M, Foreman RK, Stagner AM. Pseudomonas species may appear strikingly filamentous in tissue sections: an important consideration for surgical pathologists and a reminder of the utility of modified silver impregnation methods. Histopathology 2023;82(2):359-364.Abstract
Although tissue culture is the gold standard for diagnosing infection, histologic examination of surgically resected tissue can be a critical component in the diagnosis of tissue infection. The goal of this brief report is to alert surgical pathologists that Pseudomonas species can appear strikingly filamentous histologically and may somewhat mimic the appearance of filamentous bacteria, such Actinomyces or Nocardia, or thin fungal hyphae. A secondary aim is to raise awareness that Pseudomonas can sometimes only be identified histologically through the use of a modified silver impregnation method (Steiner stain). Five cases of filamentous Pseudomonas were encountered in three different surgical pathology subspecialities (ophthalmic pathology, cardiovascular pathology, and dermatopathology) over a 1-year period. All cases were of formalin-fixed, paraffin-embedded tissue, stained using hematoxylin & eosin (H&E) and multiple histochemical stains. Four cases grew Pseudomonas aeruginosa in culture and, in the fifth case, a nonaeruginosa species was detected using polymerase chain reaction-based methods. The markedly filamentous-appearing Pseudomonas organisms were identified in five different tissue sites: vascular graft, enucleation (whole eye) specimen, scleral biopsy, soft-tissue excision, and skin punch biopsy. In one of the five cases the organisms were seen on H&E, and in only two of the five were the organisms seen on Brown-Hopps stain. In all five cases, the organisms were identified on Steiner stain. It is therefore important to recognize that Pseudomonas can appear markedly filamentous, Pseudomonas or other bacterial infection is suspected, the surgical pathologist would be advised to employ the Steiner stain to most consistently detect the organisms.
Alnahdi MA, Alkharashi M. Ocular manifestations of COVID-19 in the pediatric age group. Eur J Ophthalmol 2023;33(1):21-28.Abstract
The coronavirus disease 2019 (COVID-19) is now known to be associated with several ocular manifestations. The literature thoroughly discussed those that affect adults, with a lesser focus in the pediatric age group. We aim to outline the various pediatric ocular manifestations described in the literature. The manifestations may be divided into isolated events attributed to COVID-19 or occurring in the new multisystem inflammatory syndrome in children (MIS-C), a novel entity associated by COVID-19 infection. Ocular manifestations have virtually affected all ages. They manifested in neonates, infants, children, and adolescents. Episcleritis, conjunctivitis, optic neuritis, cranial nerve palsies, retinal vein occlusion, retinal vasculitis, retinal changes, orbital myositis, orbital cellulitis were reported in the literature with this emerging viral illness. Conjunctivitis was the most common ocular manifestation in MIS-C in nearly half of the patients. Other ocular manifestations in MIS-C were anterior uveitis, corneal epitheliopathy, optic neuritis, idiopathic intracranial hypertension, and retinitis. The clinical outcome was favorable, and children regain their visual ability with minimal or no deficits in most of the cases. Further follow-up may be warranted to better understand the long-term effects and visual prognosis.
André C, Islam MM, Paschalis E, Bispo PJM. Comparative In Vitro Activity of New Lipoglycopeptides and Vancomycin Against Ocular Staphylococci and Their Toxicity on the Human Corneal Epithelium. Cornea 2022;Abstract
PURPOSE: The purpose of this study was to assess the potential of new lipoglycopeptides as novel topical therapies for improved treatment of recalcitrant ocular infections. We evaluated the in vitro antimicrobial activity of oritavancin, dalbavancin, and telavancin compared with vancomycin (VAN) against a large collection of ocular staphylococcal isolates and their cytotoxicity on human corneal epithelial cells (HCECs). METHODS: Antimicrobial susceptibility testing was performed by broth microdilution against 223 Staphylococcus spp. clinical isolates. Time-kill kinetics were determined for methicillin-resistant strains of Staphylococcus aureus (MRSA) (n = 2) and Staphylococcus epidermidis (MRSE) (n = 1). In vitro cytotoxicity assays were performed with AlamarBlue and live/dead staining on HCECs. RESULTS: All new lipoglycopeptides showed strong in vitro potency against ocular staphylococci, including multidrug-resistant MRSA strains, with dalbavancin showing a slightly higher potency overall [minimum inhibitory concentration (MIC)90 0.06 μg/mL] compared with telavancin and oritavancin (MIC90 0.12 μg/mL), whereas VAN had the lowest potency (MIC90 2 μg/mL). Oritavancin exerted rapid bactericidal activity within 1 h for MRSA and 2 h for MRSE. All other drugs were bactericidal within 24 h. At a concentration commonly used for topical preparations (25 mg/mL), cytotoxicity was observed for VAN after 5 min of incubation, whereas reduction in HCEC viability was not seen for telavancin and was less affected by oritavancin and dalbavancin. Cytotoxicity at 25 mg/mL was seen for all drugs at 30 and 60 min but was significantly reduced or undetected for lower concentrations. CONCLUSIONS: Our study demonstrates that new lipoglycopeptides have substantially better in vitro antimicrobial activity against ocular staphylococcal isolates compared with VAN, with a similar or improved toxicity profile on HCECs.
Belanger NL, Kim SJ, Bispo PJM. Molecular characterization of fungal Endophthalmitis and keratitis caused by yeasts. Med Mycol 2022;Abstract
Candida species are the most common causes of sight-threatening fungal ocular infections in temperate regions of the world. Despite their relevance, little is known about the emergence of novel species and the molecular epidemiology of these infections. Here we molecularly characterized 38 yeast isolates collected from patients diagnosed with endophthalmitis or keratitis at Massachusetts Eye and Ear from 2014-2021. Sequencing of the ITS1-5.8S-/ITS2 regions demonstrated that this population of yeasts was dominated by Candida spp. (37 out of 38; 97%), with 58% of the cases caused by C. albicans (n = 22), and the remaining by emerging non-albicans species, predominantly by C. parapsilosis (n = 8) and C. dubliniensis (n = 6). One isolate each was identified as C. tropicalis and Clavispora lusitaniae. Interestingly, all C. dubliniensis were isolated from endophthalmitis and most C. parapsilosis from keratitis. MLST analysis of C. albicans showed a prevalence of CC-1 isolates that has DST69 as the putative founder, with 64% of them belonging to this clonal complex. Isolates grouped within this cluster were more predominant in endophthalmitis (10 out of 14; 71%). One C. albicans CC-1 isolate was multi-azole resistant. In conclusion, we observed that nearly half of the ocular infections caused by yeasts are associated with C. albicans, with evidence for the emergence of non-albicans species that are differentially enriched in distinct ocular niches. Candida albicans isolates clustered within the predominant CC-1 group were particularly more common in endophthalmitis, demonstrating a potential pattern of ocular disease enrichment within this clade.
Nakamichi K, Akileswaran L, Meirick T, Lee MD, Chodosh J, Rajaiya J, Stroman D, Wolf-Yadlin A, Jackson Q, Holtz BW, Lee AY, Lee CS, Van Gelder RN, Van Gelder RN. Machine Learning Prediction of Adenovirus D8 Conjunctivitis Complications from Viral Whole-Genome Sequence. Ophthalmol Sci 2022;2(4):100166.Abstract
OBJECTIVE: To obtain complete DNA sequences of adenoviral (AdV) D8 genome from patients with conjunctivitis and determine the relation of sequence variation to clinical outcomes. DESIGN: This study is a post hoc analysis of banked conjunctival swab samples from the BAYnovation Study, a previously conducted, randomized controlled clinical trial for AdV conjunctivitis. PARTICIPANTS: Ninety-six patients with AdV D8-positive conjunctivitis who received placebo treatment in the BAYnovation Study were included in the study. METHODS: DNA from conjunctival swabs was purified and subjected to whole-genome viral DNA sequencing. Adenovirus D8 variants were identified and correlated with clinical outcomes, including 2 machine learning methods. MAIN OUTCOME MEASURES: Viral DNA sequence and development of subepithelial infiltrates (SEIs) were the main outcome measures. RESULTS: From initial sequencing of 80 AdV D8-positive samples, full adenoviral genome reconstructions were obtained for 71. A total of 630 single-nucleotide variants were identified, including 156 missense mutations. Sequence clustering revealed 3 previously unappreciated viral clades within the AdV D8 type. The likelihood of SEI development differed significantly between clades, ranging from 83% for Clade 1 to 46% for Clade 3. Genome-wide analysis of viral single-nucleotide polymorphisms failed to identify single-gene determinants of outcome. Two machine learning models were independently trained to predict clinical outcome using polymorphic sequences. Both machine learning models correctly predicted development of SEI outcomes in a newly sequenced validation set of 16 cases (P = 1.5 × 10-5). Prediction was dependent on ensemble groups of polymorphisms across multiple genes. CONCLUSIONS: Adenovirus D8 has ≥ 3 prevalent molecular substrains, which differ in propensity to result in SEIs. Development of SEIs can be accurately predicted from knowledge of full viral sequence. These results suggest that development of SEIs in AdV D8 conjunctivitis is largely attributable to pathologic viral sequence variants within the D8 type and establishes machine learning paradigms as a powerful technique for understanding viral pathogenicity.
Singh RB, Li J, Parmar UPS, Jeng BH, Jhanji V. Vaccine-associated corneal graft rejection following SARS-CoV-2 vaccination: a CDC-VAERS database analysis. Br J Ophthalmol 2022;Abstract
PURPOSE: To evaluate the cases of corneal graft rejection following SARS-CoV-2 vaccination reported to Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System. METHODS: A descriptive analysis of the demographics, clinical history and presentation was performed. We evaluated the correlation between the vaccines and duration of vaccine-associated graft rejection (VAR) onset following vaccination using a one-way analysis of variance test. A post hoc analysis was performed between VAR onset-interval following vaccination dose and vaccine type. Finally, a 30-day cumulative incidence analysis was performed to assess the risk of VAR in short term following different doses, vaccines and type of corneal transplantation. RESULTS: A total of 55 eyes of 46 patients were diagnosed with VAR following vaccination with BNT162b2 (73.91%) and mRNA-1273 (26.09%). The mean age of the patients was 62.76±15.83 years, and 28 (60.87%) were female. The patients diagnosed with VAR had undergone penetrating keratoplasty (61.82%), Descemet membrane endothelial keratoplasty (12.73%), descemet stripping endothelial keratoplasty (18.18%), anterior lamellar keratoplasty (3.64%) and corneal limbal allograft transplantation (1.82%). The mean time for VAR since penetrating and endothelial keratoplasty was 8.42±9.23 years and 4.18±4.40 years, respectively. 45.65% of the cases of VAR were reported after the second dose of vaccine. The duration of VAR onset was significantly shorter after the second dose compared with the first and booster doses (p=0.0165) and in patients who underwent endothelial keratoplasty compared with penetrating keratoplasty (p=0.041). CONCLUSIONS: This study outlines a possible temporal relationship between corneal graft rejection and SARS-CoV-2 vaccination. An earlier onset of VAR was observed in patients who had a history of endothelial keratoplasty and following the second dose of vaccination.
Haseeb A, Elhusseiny AM, ElSheikh RH, Tahboub MA, Kwan JT, Saeed HN. Ocular involvement in Mycoplasma induced rash and mucositis: A systematic review of the literature. Ocul Surf 2022;Abstract
Mycoplasma pneumoniae induced rash and mucositis (MIRM) is a relatively newly identified clinical entity which is characterized by mucocutaneous manifestations in the setting of Mycoplasma infection. Though a clinically distinct disease, MIRM exists on a diagnostic continuum with entities including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and the recently described reactive infectious mucocutaneous eruption (RIME). In this systematic review, we discuss published findings on the epidemiology, clinical manifestations, diagnosis, and management of MIRM, with an emphasis on ocular disease. Lastly, we discuss some of the most recent developments and challenges in characterizing MIRM with respect to the related diagnosis of RIME.