Molecular analysis of human adenoviral keratoconjunctivitis cases: Results of a 2-year survey

Yıl 2023, Cilt: 36 Sayı: 1, 1 - 6, 31.01.2023

Ayfer Guner Rabia Can Sarınoglu Fahri Onur Aydın Semra Akkaya Turhan Mert Ahmet Kuskucu Ayse Ebru Toker Aysegul Karahasan Yagcı

https://doi.org/10.5472/marumj.1244369

Öz

Objective: This study aimed to determine the adenovirus genotypes and their epidemiological features between January 2018 and
November 2019, in Istanbul, Turkey.
Material and Methods: Conjunctival swab samples were obtained from patients who were clinically diagnosed with keratoconjunctivitis.
Samples were screened with an Adeno Detector kit (Rapid Pathogen Screening, RPS Inc., South Williamsport, PA). Nucleic acid
extraction and amplification were performed with the ADENOVIRUS ELITe MGB® kit in the ELITe In Genius instrument (Elitech
Group, Torino, Italy). For subtyping of the strains, sequencing primers targeted the ‘Hypervariable Region 7’ (HVR-7) of the hexon
gene were used. DNA sequence analysis (n:72) was performed with ABI PRISM® 3100 Genetic Analyzer (Applied Biosystems, USA),
and subtyping was done by BLAST analysis.
Results: The median viral load in the samples (n: 77) was 7 log10 copies/mL (IQR: 4.5-7.4 log10 copies/mL). The clinical finding score
was found to be significantly higher in the high viral load group (Adenovirus DNA≥6 Log 10 copies/mL) than in the low viral load
group (Adenovirus DNA<6 Log 10 copies/mL) (p = 0.031).
Conclusion: Our study analyzing hAdV strains collected in 2018 and 2019 revealed that genotype 8 is the dominant type (94.0%) in our
region. Molecular methods are very useful for future epidemiological studies and the selection of a vaccine strain.

Anahtar Kelimeler

Adenovirus, Genotyping, Viral conjunctivitis, Epidemiological analyzes, Epidemic keratoconjunctivitis

Kaynakça

• Shenk T. Adenoviridae: the viruses and their replication. In Fields Virology. Philadelphia, PA: Lippincott Williams & Wilkins Co., 1996: 2111, 2148.
• Berk AJ. Adenoviridae. In: Knipe DM, Howley PM, eds. Fields Virology vol. 2, 6th ed. Philadelphia: Lippincott Williams and Wilkins, 2013:1704, 1731.
• Robinson CM, Singh G, Lee JY, et al. Molecular evolution of human adenoviruses. Sci Rep 2013; 3:1812. doi: 10.1038/ srep01812.
• Dhingra A, Hage E, Ganzenmueller T, et al. Molecular evolution of human adenovirus (HAdV) species C. Sci Rep 2019; 9:1039. doi:10.1038/s41598.018.37249-4
• Jhanji V, Chan TC, Li EY, Agarwal K, Vajpayee RB. Adenoviral keratoconjunctivitis. Surv Ophthalmol 2015; 60: 435-43. doi: 10.1016/j.survophthal.2015.04.001.
• Lenaerts L, De Clercq E, Naesens L. Clinical features and treatment of adenovirus infections. Rev Med Virol 2018; 18:357-74. doi: 10.1002/rmv.589. PMID: 18655013
• Gordon YJ, Gordon RY, E. Romanowski E, Araullo-Cruz TP. Prolonged recovery of desiccated adenoviral serotypes 5, 8, and 19 from plastic and metal surfaces in vitro. Ophthalmology 1993; 100:1835-1840. doi: 10.1016/s0161-6420(93)31389-8.
• Cheung D, Bremner J, Chan JT. Epidemic keratoconjunctivitis— Do outbreaks have to be epidemic? Eye 2003; 17:356-63. doi: 10.1038/sj.eye.6700330.
• Melendez CP, Florentino MM, Martinez IL, Lopez HM. Outbreak of epidemic keratoconjunctivitis caused by adenovirus in medical residents. Mol Vis 2009; 15:557-562.
• Binder AM, Biggs HM, Haynes AK, et al. Human adenovirus surveillance – United States, 2003-2016. MMWR Morb Mortal Wkly Rep 2017; 66(39):1039-42. doi: 10.15585/mmwr. mm6639a2
• Siamak NM, Kowalski RP, Thompson PP, Romanowski EG, Shanks RM, Gordon YJ. RPS adeno detector. Ophthalmology 2009; 116:591-1.e1. doi: 10.1016/j.ophtha.2008.10.025.
• Sarantis H, Johnson G, Brown M, Petric M, Tellier R. Comprehensive detection and serotyping of human adenoviruses by PCR and sequencing. J Clin Microbiol 2014; 42:3963-9. doi: 10.1128/JCM.42.9.3963-3969.2004.
• Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990; 215:403-10. doi: 10.1016/S0022-2836(05)80360-2.
• Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 2011;28:2731-9. doi: 10.1093/molbev/msr121.
• Banik U, Adhikary AK, Suzuki E, Inada T, Okabe N. Multiplex PCR assay for rapid identification of oculopathogenic Adenoviruses by amplification of the fiber and hexon genes. J Clin Microbiol 2005;43:1064-8. doi: 10.1128/JCM.43.3.1064- 1068.2005.
• Garcia-Zalisnak D, Rapuano C, Sheppard JD, Davis AR. Adenovirus ocular infections: prevalence, pathology, pitfalls, and practical pointers. Eye Contact Lens 2018;44:1-7. doi: 10.1097/ICL.000.000.0000000226.
• Nikitenko NA, Speiseder T, Lam E, et al. Regulation of human adenovirus replication by RNA interference. Acta Naturae 2015;7:100-107.
• IASR. Epidemic keratoconjunctivitis pathogens: 2007– 2011. Infectious agents surveillance report (IASR) (Available from: http:// idsc.nih.go.jp/iasr/prompt/s2graph-pke.html). (Accessed on November 2022 )
• Fedaoui N, Ben Ayed N, Ben Yahia A, et al. Molecular detection and characterization through analysis of the hexon and fiber genes of Adenoviruses causing conjunctivitis in Tunisia, North Africa. J Med Virol 2017;89:304-12. doi: 10.1002/jmv.24622.
• Gopalkrishna V, Ganorkar NN, Patil PR. Identification and molecular characterization of adenovirus types (HAdV-8, HAdV-37, HAdV-4, HAdV-3) in an epidemic of keratoconjunctivitis occurred in Pune, Maharashtra, Western India. J Med Virol 2016; 88:2100-5. doi: 10.1002/jmv.24565.
• Yagci R, Akcali A, Yagci S, et al. Molecular identification of adenoviral conjunctivitis in Turkey. Eur J Ophthalmol 2010; 20:669-74. doi: 10.1177/112.067.211002000404.
• Ersoy Y, Otlu B, Turkcuoglu P, Yetkin F, Aker S, Kuzucu C. Outbreak of adenovirus serotype 8 conjunctivitis inpreterm infants in a neonatal intensive care unit. J Hosp Infect 2012; 80:144-9. doi: 10.1016/j.jhin.2011.11.007.
• Erdin BN, Pas SD, Durak İ, Schutten M, Sayıner AA. A 5-year study of adenoviruses causing conjunctivitis in Izmir, Turkey. J Med Virol 2015; 87:472-7. doi: 10.1002/jmv.24071.
• Tezcan Ulger S, Bekci A, Yılmaz A, Aslan G. Detection and molecular characterization of human adenoviruses from acute conjunctivitis cases. Mikrobiyol Bul 2019;53:297-307.
• Adhikary AK, Banik U. Human adenovirus type 8: the major agent of epidemic keratoconjunctivitis (EKC). J Clin Virol 2014; 61:477-86. doi: 10.1016/j.jcv.2014.10.015.
• Sammons JS, Graf EH, Townsend S, et al. Outbreak of adenovirus in a neonatal ıntensive care unit: critical ımportance of equipment cleaning during ınpatient ophthalmologic examinations. Ophthalmology 2019;126:137- 43. doi: 10.1016/j.ophtha.2018.07.008.
• Li J, Lu X, Sun Y, et al. A swimming pool-associated outbreak of pharyngoconjunctival fever caused by human adenovirus type 4 in Beijing, China. Int J Infect Dis 2018;75:89-91. doi: 10.1016/j.ijid.2018.08.009.
• Nguyen TTH, Le TA, Nguyen VH, et al. Molecular typing of conjunctivitis-causing adenoviruses in Hanoi, Vietnam from 2017 to 2019 and complete genome analysis of the most prevalent type (HAdV-8). J Med Virol 2020;10.1002/ jmv.25844. doi:10.1002/jmv.25844
• Lee CS, Lee AY, Akileswaran L, et al. Determinants of outcomes of adenoviral keratoconjunctivitis. Ophthalmology 2018;125:1344-53. doi:10.1016/j.ophtha.2018.02.016