Search Results (14)

Accurate diagnosis of adenoviral conjunctivitis is critical for timely treatment and infection control. However, conventional lateral flow kits often lack sufficient sensitivity, especially in mild cases. This multicenter prospective study evaluated the diagnostic performance of silver-amplified lateral flow kits (SA-LFKs) compared with non-silver-amplified kits (NSA-LFKs), using real-time polymerase chain reaction (qPCR) as the reference standard. Tear samples from 200 patients with suspected adenoviral conjunctivitis were collected across four clinics and analyzed for sensitivity, specificity, and genotype coverage. The SA-LFK demonstrated significantly higher sensitivity (86.0%) than the NSA-LFK (72.0%) (p < 0.001), with both kits showing high specificity (100% and 98.1%, respectively). Pooled analysis revealed that sensitivity was significantly lower in mild-to-moderate cases than in severe cases for both kits, suggesting that clinical severity influences detection performance. Across all severity levels, the SA-LFK consistently demonstrated higher sensitivity than the NSA-LFK, including in mild-to-moderate cases (77.8% vs. 59.3%, p = 0.004), supporting its superior diagnostic performance. The SA-LFK showed robust performance across eight identified adenovirus genotypes and maintained higher positivity rates even at lower viral loads. These findings support the clinical utility of SA-LFKs for early diagnosis and outbreak containment in diverse settings. Full article

The ongoing mpox clade Ib outbreak was first detected in the eastern Democratic Republic of Congo (DRC) and was associated with sexual transmission. It emerged in Kamituga, a mining city and spread rapidly in surrounding health zones and reached cities like Bukavu and Goma. Here, we describe the clinical, epidemiological, and virological characteristics of the first case of clade Ib in Kinshasa, the capital city in the western DRC. The case involved a young adult woman from Kinshasa who reported unprotected sexual contact with an occasional partner, a former friend, and subsequently developed genital lesions, including vesicles and pustules. These lesions evolved and spread to the entire body, including the limbs, eyes, and soles. The diagnosis was confirmed by PCR and sequencing allowed us to assign clade Ib. We show that infection with mpox clade Ib through sexual transmission can lead to limbal nodular keratoconjunctivitis and focal conjunctivitis as complications. Importantly, these results suggest that clade Ib may have been circulating silently in Kinshasa prior to the official declaration by the Ministry of Health. This also raises concerns about the potential risk of global spread, as is currently being observed. Further studies are needed to investigate whether subsequent outbreaks of clade Ib in Kinshasa may have emerged independently of introductions from Kivu, pointing to a more complex pattern of co-circulation that could define the mpox epidemic in the capital. Full article

Viral conjunctivitis is a highly contagious ocular condition that significantly impacts patient quality of life and healthcare resources. Despite its self-limiting nature, the condition remains a significant public health concern due to its high transmissibility, prolonged symptoms, and potential complications such as subepithelial infiltrates (SEIs). This review aimed to synthesize and evaluate current management strategies for adenoviral conjunctivitis and provide an evidence-based treatment framework. A systematic literature search of PubMed and the Cochrane Library was conducted, identifying 25 eligible studies published between 2009 and 2024 that focused on clinical interventions including supportive care, antiseptics, corticosteroids, antivirals, and immune modulators. The findings indicate that while supportive therapy and hygiene measures remain central to care, antiseptic agents, specifically povidone–iodine, and topical steroids offer additional benefit in reducing symptom duration and complications. Combination therapies integrating antiseptics, corticosteroids, and immunomodulators show promise for more severe cases, especially those complicated by SEIs. This review proposes an evidence-based comprehensive, multimodal approach management algorithm while highlighting the need for future research in antiviral development and diagnostic innovation to avoid mistreatment and unnecessary antibiotic use. Full article

Purpose: Epidemic keratoconjunctivitis (EKC) is a common viral ocular infection that can lead to persistent subepithelial infiltrates (SEIs), resulting in significant visual impairment and patient discomfort, necessitating effective treatment strategies beyond corticosteroid monotherapy. This study aims to evaluate the efficacy of topical tacrolimus (0.1%) ointment alone versus its combination with prednisolone (1%) drops to provide optimal therapeutic strategies for SEIs secondary to EKC. Methods: This retrospective observational study evaluates 102 eyes of ninety-five individuals. The patients were divided into two groups based on the treatment approach. The first group received tacrolimus ointment alone (n = 34), whereas the second group received a combination of prednisolone drops and tacrolimus ointment (n = 68). Best-corrected visual acuity (BCVA), the corneal subepithelial infiltrate score (CSIS), the subjective symptom score (SSS), and the Fantes corneal haze grading score (FCHGS) were evaluated before treatment and at 1, 3, 6, 9, 12, and 18 months post-treatment. Results: Both groups showed significant improvements in the BCVA, CSIS, SSS, and FCHGS values, with no significant difference between the groups at 18 months (p > 0.05). The combination therapy resulted in a significantly faster treatment response than tacrolimus alone (p < 0.05) in terms of CSIS, SSS, and FCHGS values. An increase in intraocular pressure (IOP) was observed in four patients in the combination treatment group after three months. Conclusions: Topical tacrolimus, both alone and in combination with topical prednisolone, was effective in treating subepithelial infiltrates secondary to EKC. Combination therapy may be applied early for faster recovery; however, close monitoring of IOP is necessary in individuals using topical prednisolone. Full article

Certain species D human adenoviruses (HAdV-D19, -D37, and -D64) are causative agents of epidemic keratoconjunctivitis. HAdV-D37 has previously been shown to bind CD46 (membrane cofactor protein) and sialic acid as adhesion receptors. HAdV-D64 is genetically highly similar to HAdV-D37, with an identical fiber protein sequence, but differs substantially in its penton base and hexon proteins, two other major capsid components, due to genetic recombination. Here, we demonstrate that, like HAdV-D37, HAdV-D64 virions bind directly to CD46 and that CD46 and sialic acid also function as receptors for HAdV-D64 on multiple cell types. Expression of CD46 on CD46-negative cells conferred susceptibility to HAdV-D64 entry. Specifically blocking HAdV-D64 binding to CD46 on the host cell surface strongly inhibits viral entry and gene delivery into multiple cell lines that represent target tissues. We show that CD46 is expressed on human conjunctival epithelial cells and directly binds to the HAdV-D64 virion. Our results suggest that HAdV-D64 may be used to deliver genes to target conjunctival cells and that interrupting HAdV-D64 entry through its interaction with CD46 may prevent or lessen adenovirus-associated ocular disease. Full article

Human adenovirus (HAdV) is one of the most common causes of conjunctivitis worldwide. Depending on specific serotypes and other factors, it can lead to several ocular manifestations, ranging from isolated, self-limited disease to epidemic and potentially sight-threatening keratoconjunctivitis. To date, no antiviral agent against ocular adenovirus has been licensed, and its management is still based on hygienic and supportive measures alone. In this review, a literature search up to August 2021 was performed to find peer-reviewed articles, with the primary aim to investigate drugs or other compounds with any antiviral activity against adenovirus. Finally, we included 70 articles, consisting of both in vitro, and in vivo studies on animal models and clinical trials of any phase, as well as a case-report, and analyzed each compound separately. Many antiviral agents proved to be effective on in vivo and in vitro studies on animal models, and in pre-clinical trials, but lacked reliability in large, controlled clinical investigations. The design of such studies, though, presented several hurdles, due to the nature and the specific characteristics of adenovirus-induced ocular diseases. Nevertheless, some promising compounds are currently under study, and further investigations are needed to prove their efficacy in the management of adenovirus conjunctivitis. Full article

Mycoplasma mycoides subspecies capri (Mmc) is one of the six Mycoplasma mycoides cluster (Mm cluster) members, which can cause “MAKePS” (Mastitis, Arthritis, Keratoconjunctivitis, Pneumonia, Septicemia) syndrome in ruminants. These symptoms can occur alone or together in individuals or flocks of goats. However, little is known about the epidemic Mmc strains in Hainan Island, China. We aimed to isolate the endemic Mmc strains in Hainan Island and reveal their molecular characteristics by genomic sequencing and comparative genomics to mitigate the impact of Mmc on local ruminant farming. Here, the Mmc HN-A strain was isolated and identified for the first time in Hainan Island, China. The genome of Mmc HN-A was sequenced. It contains a 1,084,691 bp-long circular chromosome and 848 coding genes. The genomic analysis of Mmc HN-A revealed 16 virulence factors, 2 gene islands, and a bacterial type IV secretion system protein VirD4. Comparative genomics showed that the core genome of the five Mycoplasma mycoides contained 611 genes that could be exploited to develop drugs and endemic vaccines. Additionally, 36 specific genes were included in the Mmc HN-A genome, which could provide the possibility for the further control and prevention of the Mmc effects on local ruminants and enrich the information on Mmc strains. Full article

Notable among the many communicable agents known to infect the human cornea is the human adenovirus, with less than ten adenoviruses having corneal tropism out of more than 100 known types. The syndrome of epidemic keratoconjunctivitis (EKC), caused principally by human adenovirus, presents acutely with epithelial keratitis, and later with stromal keratitis that can be chronic and recurrent. In this review, we discuss the current state of knowledge regarding the molecular biology of adenovirus infection of corneal stromal cells, among which the fibroblast-like keratocyte is the most predominant, in order to elucidate basic pathophysiologic mechanisms of stromal keratitis in the human patient with EKC. Full article

Human adenoviruses cause disease at multiple mucosal sites, including the respiratory, gastrointestinal, and genitourinary tracts, and are common agents of conjunctivitis. One site of infection that has received sparse attention is the cornea, a transparent tissue and the window of the eye. While most adenovirus infections are self-limited, corneal inflammation (keratitis) due to adenovirus can persist or recur for months to years after infection, leading to reduced vision, discomfort, and light sensitivity. Topical corticosteroids effectively suppress late adenovirus keratitis but are associated with vision-threatening side effects. In this short review, we summarize current knowledge on infection of the cornea by adenoviruses, including corneal epithelial cell receptors and determinants of corneal tropism. We briefly discuss mechanisms of stromal keratitis due to adenovirus infection, and review an emerging therapy to mitigate adenovirus corneal infections based on evolving knowledge of corneal epithelial receptor usage. Full article

Human adenovirus infection of the ocular surface is associated with severe keratoconjunctivitis and the formation of subepithelial corneal infiltrates, which may persist and impair vision for months to years following infection. Long term pathology persists well beyond the resolution of viral replication, indicating that the prolonged immune response is not virus-mediated. However, it is not clear how these responses are sustained or even initiated following infection. This review discusses recent work from our laboratory and others which demonstrates different entry pathways specific to both adenovirus and cell type. These findings suggest that adenoviruses may stimulate specific pattern recognition receptors in an entry/trafficking-dependent manner, leading to distinct immune responses dependent on the virus/cell type combination. Additional work is needed to understand the specific connections between adenoviral entry and the stimulation of innate immune responses by the various cell types present on the ocular surface. Full article

Human adenoviruses (HAdV) are the most common cause of ocular infections. Species B human adenovirus type 3 (HAdV-B3) causes pharyngoconjunctival fever (PCF), whereas HAdV-D8, -D37, and -D64 cause epidemic keratoconjunctivitis (EKC). Recently, HAdV-D53, -D54, and -D56 emerged as new EKC-causing agents. HAdV-E4 is associated with both PCF and EKC. We have previously demonstrated that HAdV-D37 uses sialic acid (SA)-containing glycans as cellular receptors on human corneal epithelial (HCE) cells, and the virus interaction with SA is mediated by the knob domain of the viral fiber protein. Here, by means of cell-based assays and using neuraminidase (a SA-cleaving enzyme), we investigated whether ocular HAdVs other than HAdV-D37 also use SA-containing glycans as receptors on HCE cells. We found that HAdV-E4 and -D56 infect HCE cells independent of SAs, whereas HAdV-D53 and -D64 use SAs as cellular receptors. HAdV-D8 and -D54 fiber knobs also bound to cell-surface SAs. Surprisingly, HCE cells were found resistant to HAdV-B3 infection. We also demonstrated that the SA-based molecule i.e., ME0462, designed to bind to SA-binding sites on the HAdV-D37 fiber knob, efficiently prevents binding and infection of several EKC-causing HAdVs. Surface plasmon resonance analysis confirmed a direct interaction between ME0462 and fiber knobs. Altogether, we demonstrate that SA-containing glycans serve as receptors for multiple EKC-causing HAdVs, and, that SA-based compound function as a broad-spectrum antiviral against known and emerging EKC-causing HAdVs. Full article

Glycans on plasma membranes and in secretions play important roles in infection by many viruses. Species D human adenovirus type 37 (HAdV-D37) is a major cause of epidemic keratoconjunctivitis (EKC) and infects target cells by interacting with sialic acid (SA)-containing glycans via the fiber knob domain of the viral fiber protein. HAdV-D37 also interacts with sulfated glycosaminoglycans (GAGs), but the outcome of this interaction remains unknown. Here, we investigated the molecular requirements of HAdV-D37 fiber knob:GAG interactions using a GAG microarray and demonstrated that fiber knob interacts with a broad range of sulfated GAGs. These interactions were corroborated in cell-based assays and by surface plasmon resonance analysis. Removal of heparan sulfate (HS) and sulfate groups from human corneal epithelial (HCE) cells by heparinase III and sodium chlorate treatments, respectively, reduced HAdV-D37 binding to cells. Remarkably, removal of HS by heparinase III enhanced the virus infection. Our results suggest that interaction of HAdV-D37 with sulfated GAGs in secretions and on plasma membranes prevents/delays the virus binding to SA-containing receptors and inhibits subsequent infection. We also found abundant HS in the basement membrane of the human corneal epithelium, which may act as a barrier to sub-epithelial infection. Collectively, our findings provide novel insights into the role of GAGs as viral decoy receptors and highlight the therapeutic potential of GAGs and/or GAG-mimetics in HAdV-D37 infection. Full article

Epidemic keratoconjunctivitis (EKC) is a severe ocular disease and can lead to visual impairment. Human adenovirus type-37 (HAdV-D37) is one of the major causative agents of EKC and uses sialic acid (SA)-containing glycans as cellular receptors. Currently, there are no approved antivirals available for the treatment of EKC. Recently, we have reported that sulfated glycosaminoglycans (GAGs) bind to HAdV-D37 via the fiber knob (FK) domain of the viral fiber protein and function as decoy receptors. Based on this finding, we speculated that GAG-mimetics may act as artificial decoy receptors and inhibit HAdV-D37 infection. Repurposing of approved drugs to identify new antivirals has drawn great attention in recent years. Here, we report the antiviral effect of suramin, a WHO-approved drug and a widely known GAG-mimetic, against HAdV-D37. Commercially available suramin analogs also show antiviral effects against HAdV-D37. We demonstrate that suramin exerts its antiviral activity by inhibiting the attachment of HAdV-D37 to cells. We also reveal that the antiviral effect of suramin is HAdV species-specific. Collectively, in this proof of concept study, we demonstrate for the first time that virus binding to a decoy receptor constitutes a novel and an unexplored target for antiviral drug development. Full article

Epidemic keratoconjunctivitis (EKC) is an acute eye infection caused by adenovirus. We investigated an outbreak of EKC at an outpatient ophthalmology practice in the context of a suspected community wide increase in EKC activity. A site visit was made to the facility reporting the outbreak. A line list was created of patients clinically diagnosed with EKC at the practice during the previous 5 months. A questionnaire was faxed to all other licensed ophthalmologists in the county regarding recent EKC activity in their facility. Descriptive data analyses were conducted. The outbreak facility reported 37 patients clinically diagnosed with EKC during the previous 5 months. In addition, the single ophthalmologist at the practice also had symptoms compatible with EKC during the outbreak period. Specimens were collected on 4 patients and all were positive for adenovirus serotype 8. Forty percent of ophthalmologists surveyed in the county saw at least one EKC patient in the previous 3 months, and 20% reported a perceived increase in EKC activity in recent months over normal seasonal patterns. The outbreak at the facility likely began as part of a widespread community increase in EKC that may have been amplified at the facility through nosocomial transmission. Medical providers experiencing increases in EKC activity above seasonally expected norms should contact their public health department for assistance with etiologic diagnoses and outbreak control. Full article