Whole genome analysis of Human Mastadenovirus D causing Keratoconjunctivitis in India - A multicentre study.

INTRODUCTION: Human mastadenovirus (HAdV) types 8, 37, 64 have been considered the major contributors in Epidemic keratoconjunctivitis (EKC) epidemics, but recent surveillance data have shown the involvement of emerging recombinants, including HAdV-53, HAdV-54, and HAdV-56. In our initial work, positive samples for adenovirus revealed that our strains were closer to HAdV-54 than HAdV-8. Hence, the current study aimed to use whole genome technology to identify the HAdV strain correctly. METHODOLOGY: Oxford Nanopore technique was used, wherein a Targeted sequencing approach using long-range PCR amplification was performed. Primers were designed using HAdV-54 (AB448770.2) and HAdV-8 (AB897885.1) as reference sequences. Amplicons were sequenced on the GridION sequencer. Sequences were annotated using Gatu software, and similarities with standard reference sequence was calculated using Bioedit software. The phylogenetic tree was built after alignment in MEGA v7.0 using Neighbour joining method for each of the genes: Penton, Hexon, and Fiber. The effect of novel amino acid changes was evaluated using the PROVEAN tool. The Recombination Detection Program (RDP) package Beta 4.1 was used to identify recombinant sequences. RESULTS: Of the five samples sequenced, OL450401, OL540403, and OL540406 showed nucleotide similarity to HAdV-54 in the penton region. Additionally, OL450401 showed a statistically significant recombination event with HAdV-54 as minor and HAdV-8 as major parents. This was further supported by phylogenetic analysis as well. CONCLUSIONS: In the present study, we have found evidence of a shift from HAdV-8 towards HAdV-54, thus stressing the need for surveillance of HAdVs and to stay updated on the rise of new recombinants.

Epidemiology of Keratoconjunctivitis Across India from 2017 to 2019: A Multicentric Hospital-Based Study.

PURPOSE: Conjunctivitis is one of the most common ocular conditions in clinical practice. Human adenoviruses have been the common causative agents known to cause epidemic kerato-conjunctivitis (EKC) in India from 1996 to 2019 with a positivity range of 13.8%-65.2%. The current study was initiated to throw light on the distribution of keratoconjunctivitis causing agents across India covering a span of 3 years. METHODS: A total of 709 swabs were collected from patients in viral transport medium (VTM), and real-time PCR was done to identify agents including Adenovirus (HAdV), Enterovirus, HSV, and Chlamydia. RESULTS: 47.8% of the samples were positive for HAdV followed by HSV (3.4%), Enterovirus (2.7%), and Chlamydia (0.6%). Overall, 386 people (54.4%) tested positive for one of these infections, with Chandigarh (88.4%) and Port Blair (71.7%) showing higher positivity rate. Pre-auricular lymphadenopathy and follicles were significantly associated with increased risk of conjunctivitis. CONCLUSION: Epidemiology of keratoconjunctivitis in the current study revealed HAdV to be predominant causative agent. Knowledge gained in such epidemiological studies guide us in outbreak expectations, limit antibiotic over-prescription, and enhance disease prevention.

Adenoviral Conjunctivitis in the Andaman Islands: A Clinical and Molecular Epidemiological Study.

Introduction Human adenoviruses are common causes of many acute illnesses, and keratoconjunctivitis is one of them. Acute infections, if left untreated, can progress to severity, thus causing morbidities and mortalities. It belongs to the mastadenovirus family and is characterized by seven subgenus, i.e., A-G; among those, Adenovirus D8 is the most common type associated with keratoconjunctivitis. Methodology A hospital-based study was conducted, and the samples were collected from GB Pant Hospital, Port Blair, Dr Agarwals Eye Hospital, Port Blair, from August 2017 to December 2022. Clinical data and demographic details were followed by conjunctival swab sample collection from suspected keratoconjunctivitis patients. Samples were subjected to molecular screening, and Sanger sequencing was carried out for positive samples. Results Out of 506 conjunctival samples, a prevalence of 24.9% (n=126) was observed, and the commonest type circulating among the population of Andaman was Adenovirus D8. The major symptoms associated were eye redness (87.30%, n=110), followed by watering (81.75%, n=103), eye pain (72.22%, n=91), eye itching (61.11%, n=77), and discharge (50%, n=63). Conclusion In clinical research, ocular infections are one of the underrated fields. However, the study revealed the high prevalence of adenoviral infection among the suspected patients. Thus, there is a need for proper surveillance and timely diagnosis of such infections, as their severity may lead to loss of vision.

Correction to: Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event.

The article "Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event," written by Joseph R. Berger, Vineeta Malik, Stuart Lacey, Paul Brunetta, and Patricia B. Lehane3, was originally published electronically on the publisher's internet portal (currently SpringerLink).

Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event.

This report assesses the observed risk of PML in patients treated with the anti-CD20 monoclonal antibody rituximab in the regulatory authority-approved autoimmune indications rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). This was a cumulative analysis of confirmed PML cases in patients receiving rituximab for RA or GPA/MPA from both spontaneous reports and clinical trial sources, as captured in the manufacturer global company safety and clinical databases. Overall reporting rates were calculated and patient case details were summarized. As of 17 November 2015, there were nine confirmed PML cases among patients who had received rituximab for RA and two for GPA. Corresponding estimated reporting rates were 2.56 per 100,000 patients with RA (estimated exposure ≈ 351,396 patients) and < 1 per 10,000 patients with GPA/MPA (estimated exposure 40,000-50,000 patients). In all cases, patients had ≥ 1 potential risk factor for PML independent of rituximab treatment. In the RA population, the estimated reporting rate of PML generally remained stable and low since 2009 despite increasing rituximab exposure. There was no pattern of latency from time of rituximab initiation to PML development and no association of PML with the number of rituximab courses. Global post-marketing safety and clinical trial data demonstrated that the occurrence of PML is very rare among rituximab-treated patients with RA or GPA/MPA and has remained stable over time.