Incidence of Adenoviral Keratoconjunctivitis In Malabar region of Kerala, India Kashinatha M. Shenoy, MS
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1 57 Incidence of Adenoviral Keratoconjunctivitis In Malabar region of Kerala, India Kashinatha M. Shenoy, MS Abstract Objective: The study was conducted to document the incidence of adenoviral conjunctivitis, its complications and methods to prevent transmission from a public health perspective. Methods: A retrospective study was held between March 2009 to September 2010, Department of Ophthalmology, Malabar Medical College, Calicut. Patients were followed up for 3 months. A total of 578 cases of adenoviral conjunctivitis were documented. All patients with viral conjunctivitis were diagnosed by clinical picture. A total of 578 patients (including 364 males, 214 females, aged from 4 years to 70 years) were treated with usual topical antibiotics/antibiotic steroid drops and lubricants. Results: Highest incidence of the disease was seen in the months of April to July. In most of cases both eyes were affected. Acute illness lasted from 6 days to 12 days. Commonly observed symptoms included redness, watering, follicular conjunctivitis, subconjunctival hemorrhage, discharge, chemosis of conjunctiva, pain in the eyes.spontaneous recovery was observed in 480 patients and the remaining 158 patients developed sub epithelial opacities, which was treated with topical steroids. Conclusion: Prevention of any disease is better than cure which happens to be very true especially with regard to epidemic viral keratoconjunctivitis. In our preliminary study, we find that subjectively and objectively the risk of transmission of EKC was drastically reduced after following strict asepsis from ophthalmic care givers. We want to reiterate established standard opinion that Indian health workers should be trained in basics of ophthalmic asepsis, nature of the EKC and prevention of EKC in community and schools. Keywords: Epidemic keratoconjunctivitis (EKC), Incidence, follicular conjunctivitis, Punctate Epithelial Keratoconjunctivitis (PEK) Introduction Epidemic keratoconjunctivitis is caused by adenoviruses (1). The 54 types of adenovirus now known to be pathogenic in man are classified in seven groups, which are labeled A through G. Adenoviruses are double-stranded DNA viruses roughly 80 to 110 nm in size (1,2). They are surrounded by an icosahedral capsid bearing group- and type-specific antigens; they have no outer lipid bilayer. They are highly resistant to environmental influences and can survive contact with many of the usual commercially available types of disinfectant. They remain infectious for weeks when kept at room temperature and thus have a high aptitude for causing nosocomial infections (3). Adenoviruses are found all over the world and are transmitted through droplets and smears of infected bodily fluids that enter the human body through the nose, throat, and conjunctiva (3). The viral incubation time is 2 to 12 days. The disease is probably contagious even before symptoms arise, and it certainly remains so as long as the virus can still be demonstrated in bodily fluids; this period (for tear fluid) usually lasts two to three weeks from the date of transmission of the virus (3). The disease can be transmitted on the hands as well as on objects such as tissues and handkerchiefs, doorknobs, etc. Nosocomial EKC contracted in eye clinics and doctors offices is usually due to contaminated instruments (e.g., tonometers) and eye drops (4,12,15). Adenoviruses cause a wide variety of diseases not just ocular infections, but also respiratory and gastrointestinal ones. Individual serotypes typically cause specific types of disease; thus, EKC is usually due to serotypes 8, 19, and 37, follicular conjunctivitis to serotypes 3, 4 and 7, and pharyngeal-conjunctival fever to serotypes 3, 7, and rarely 14. Respiratory infections such as pneumonia, tonsillitis, and pharyngitis are caused by serotypes 1 5, 7, 14, and 21, while serotypes 1, 2, 5,
2 58 31, 40 und 41 cause gastroenteritis. Serotypes 1, 2, and 5 can produce sepsis-like manifestations, particularly in severely immunocompromised patients (5,6). Corneal involvement causes intense photophobia due to punctate epithelial lesions (6). Later, subepithelial infiltrates appear at the level of Bowman membrane as a hypersensitivity reaction to viral antigen that coalesces to form deeper sub-epithelial lesions called nummular keratitis. Keratitis occurs in 80 % of cases and is divided into 5 stages as below: (6) Stage 0: Mild punctate epithelial erosions developing within the first 2 to 4 days; stain poorly with rose bengal and fluorescein. Stage 1: Fine, diffuse punctate epithelial keratitis (PEK) which persists for 2 to 5 days; either resolving or progressing to Stage 2. Stage 2: Fine and coarse punctate epithelial keratitis (stains brilliantly with rose bengal; involves the deeper subepithelium); persists for 2 to 5 days (Day 4 through 8). Stage 3: Coarse, granular infiltrates within deep epithelium; appearance of faint subepithelial infiltrates (scattered, fine and coarse punctate epithelial keratitis may remain); persists for 2 to 5 days (Days 6 through 12). Stage 4: Classic subepithelial infiltrates: Punctate epithelial keratitis ( PEK) is resolved; no staining; can occur as early as 2 weeks, may persist for weeks to months to even several years; loss of symmetry of distribution. Stage 5: Punctate epithelial granularity (superficial and deep epithelium) developing late-weeks to months after onset occurs; continuous and separate from subepithelial opacities. May cause permanent scars. It has been observed that many Iatrogenic epidemics have been initiated in ophthalmology outpatient clinics by direct contact with contaminated diagnostic instruments (6,7). Iatrogenic Ophthalmic Disease can commonly spread by the contaminated fingers of the ophthalmologists or through contaminated instruments or eye drops (7), and it can also be spread even by contaminated instruments like applanation tonometers (7). In 20-50% of cases, corneal opacities can persist for a few weeks to months (rarely up to 2 years). This phenomenon can decrease visual acuity significantly and cause glare. In rare cases conjunctival scarring and symblepharon can occur secondary to membranous conjunctivitis (8). Treatment for adenoviral conjunctivitis is supportive and no evidence exists that demonstrates efficacy of antiviral agents like acyclovir or cidofovir. Most infections are mild and require no therapy or require at the most only symptomatic treatment (9). Serious adenovirus illness can be managed only by treating symptoms and complications of the infection (10). Topical steroids are known to reduce the quantity and density of subepithelial infiltrates but cause exacerbation of infiltrates upon discontinuation (10,11). Fig 1. EKC: follicular conjunctivitis.
3 59 Fig 2. EKC: pseudomembrane conjunctivitis. Fig 3. EKC showing subepithelial infiltrates. Materials and Methods: This retrospective study was conducted between March 2009 to September 2010 at the Ophthalmology department of Malabar Medical College, Calicut. A total number of 578 patients of adenoviral conjunctivitis were documented during the study period. In our study we included subjects in the age group between 4 years to 70 years. All patients were followed up for 3 months as our institution is located in a rural area and patients long term follow up is poor. We excluded age group below 4 years and above 70 years and patients diagnosed as herpetic keratitis. All the suspected Epidemic viral keratoconjunctivitis patients underwent thorough clinical examinations like vision, slit lamp examination under standard aseptic precautions in a separate room to prevent the nosocomial spread 9 and the findings were documented. Ocular Management: No topical ophthalmic anti-adenoviral drugs are approved for use till date (10,11). In our study, for mild cases topical Moxifloxacin drops were given to prevent secondary bacterial infections. We removed symptomatic membranes with wet cotton swab or forceps and followed it up with topical applications of antibiotic/steroid ointment/drops. Topical corticosteroids were used only for complications like sub epithelial infiltrates and punctuate epithelial keratitis.
4 60 Results: Table I: Distribution of sex: Total cases= n = 578 Male 364 (62.97 %) Female 274 (47.40% ) Table II: Laterality of the spread: n=578 Unilateral 62 ( 10.72% ) Bilateral 516 (89.27 %) Table III: Monthly distribution of EKC patients (n= 578) Month 2009 ( n=316) 2010 ( n= 262 ) January - 31 February - 36 March April May June July August September October 22 - November 24 - December 20 - Table IV: showing the Mean duration of EKC in days (0-90 days) Symptoms/signs Mean duration of illness ( days) First visit Upto 2 weeks 2 weeks to 90 days Lid edema,chemosis +++ No/recovery No/recovery N=480 Subconjunctival hemorrhage No/recovery N=480 pseudomembranes NO + N= 54 No/recovery N=480 Subepithelial opacities NO ++ + (n=158) Discussion: Epidemic keratoconjunctivitis (EKC) is a highly contagious infectious disease (12,13) and mainly involves the surface of the eye. It is caused by adenoviruses that are highly resistant to environmental influences and are transmitted from person to person by way of infectious secretions, mainly as tear fluid. The transmission often occurs in places where large number of people gather such as schools, homes for the elderly, and factories as well as in health-care institutions such as hospitals and doctors offices (including ophthalmologists offices (12,13).
5 61 The purpose of our study was to minimize the patient's symptoms, complications and to prevent the EKC infection in the community in the Malabar region of Calicut, Kerala. All EKC infected patients were treated with topical antibiotics/topical steroid drops. Antiviral medications were not administered as therapeutic benefits have not been proven till date (17,20). We noted that, in a total of 578 cases, the disease was more common in the males than the females in our area (Table No I).This could be due to the hot weather and humid conditions prevalent in this part of Malabar region of Kerala. Further, we found that about 89% of the total cases were bilateral and only 10 percent of the cases were unilateral (Table II). Our findings are in agreement with similar studies done in Pakistan by Majeed A et al (9). The highest incidence of the disease was seen in the months of March to June in the Malabar region of Calicut, Kerala which could be again due to environmental conditions. (see Table III) Further, in our study, the mean duration of illness in EKC was found to be 8 to 14 days (Table IV). Most commonly observed symptoms were discharge, redness of eyes, watering from the eyes, subconjunctival hemorrhage, and pain (including itching and burning). Spontaneous recovery occurred in 480 cases (83.04%) while 158 patients (27.33%) developed sub epithelial opacities (Table IV). In our study we have not found any cases of conjunctival scarring/symblepharon because we resorted to prompt removal of membranes, and only few cases developed pseudomembranes (n=54). Further, we could hypothesize that the higher bilateral incidence could be due to self infection by the patients themselves due to infected hands which probably could have been prevented had there been community awareness about ophthalmic hygiene. Further studies are needed in large samples to find out the possible benefits of ophthalmic health education. It has been established time and again that EKC is a highly contagious disease (14,15) and often spreads in epidemics, particularly in people with poor hygiene. It is extremely important to teach the patients about the nature of the disease, its treatment and prevention of its spread (14,15). Prevention of transmission is the most important therapeutic measure particularly in the ophthalmic clinics of the hospitals (14). Hand washing with soap and water before and after examining each patient, thorough cleansing of instruments that touch the patient's eye and frequent changing of multiuse eye drops is extremely important as noted in our study. Contaminated hands are also a major source of person-to-person transmission of adenovirus, both from patients to health care personnel and from healthcare personnel to patients (16,17). Hand washing, glove use, and disinfection of instruments can go a long way in primary prevention of adenoviral epidemics in communities (18-20). Conclusions: It is often said that prevention of any disease is better than cure which happens to be very true especially with regard to epidemic viral keratoconjunctivitis. In our preliminary study, we clearly noted that subjectively and objectively the risk of transmission of EKC was drastically reduced after following strict asepsis from ophthalmic care givers. We want to reiterate established standard opinion that Indian health workers should be trained in basics of ophthalmic asepsis, nature of the EKC and prevention of EKC in community and schools. Courtesy: All pictures above are courtesy Google Free images, available online.
6 62 References: 1. Smolin G, Thoft RA: Viral Keratitis & Conjunctivitis. In: Cornea: Scientific Foundations & Clinical Practice. 3rd edition. Boston. Little Browns & Co. 1994; Tasman W, Jaeger EA: Epidemic keratoconjunctivitis. Duane's Clinical Ophthalmology 1998; 4: Kanski JJ. Adenoviral Epidemic keratoconjunctivitis. Clinical Ophthalmology. (Textbook) 3rd ed. 1998; Hodge W, Wohl T, Whitcher JP, Margolis TP. Corneal sub-epithelial infiltrate recurrence with adenovirus. Cornea 1995;14: Buehler JW, Finton RJ and Goodman RA. Epidemic keratoconjunctivitis: report of an outbreak in an ophthalmology practice and recommendations for prevention. Infect Control 1984;5: Leibowitz HM, Waring GO: Superficial punctate keratopathy. In: Clinical Disorders of eye: Clinical Diagnosis and Management. 2nd edition. St. Louis CVV. Mosby & Co. 1998; Wright KW, Liesegang TJ: Conjunctiva. In: Textbook of Ophthalmology. First Edition. Baltimore: Williams & Wilkins 1997; Krashmer JH, Mannis MJ, Holland E: Conjunctivitis: an overview and classification of viral conjunctivitis. Cornea 1996; 5:750-51, Majeed A, Naeem Z, Khan DA, Ayaz A: Epidemic Adenoviral Conjunctivitis report of an Outbreak in a Military Garrison and Recommendations for its Management and Prevention Vol. 55, No. 7, July 2005 pp Gordon JS: Adenovirus and other non-herpetic viral diseases. In: Smolin G,Thoft RA (ed): The Cornea. Third Edition. Boston: Little Brown & Co 1994; Romanowski EG, Araullo-Cruz T, Gordon YJ. Topical corticosteroids reverse the antiviral effect of topical cidofovir in the Ad5-inoculated New Zealand rabbit ocular model. Invest Ophthalmol Vis Sci. 1997; 38: Takeuchi S. Adenovirus Strains of Subgenus D Associated with Nosocomial Infection as New Etiological Agents of Epidemic Keratoconjunctivitis in Japan.Journal of Clinical Microbiology, October 1999, p , Vol Azar MJ, Dhaliwal DK & Bower KS.Possible Consequences of Shaking Hands with Your Patients with Epidemic Keratoconjuctivitis. Pa Am J Ophthalmol 121: , Garner JS & Simmons BP. Guidelines for isolation precautions in hospitals. Atlanta: US Department of Health and Human Services, Public Health Service, CDC, 1985; DHHS publication no Nagington J, Stehall GM, and Whipp P. Tonometer disinfection and viruses. Br J Ophthalmol 1983; 67: Aoki K, Kaneko H, Kitaichi N, Ohguchi T, Tagawa Y & Ohno S.Clinical Features of Adenoviral Conjunctivitis At the Early Stage of Infection. Jpn J Ophthalmol 2011; 55:11 15 DOI /s x 17. Rosenbach KA, Nadiminti U, Vincent AL et al: An outbreak of adenoviral keratoconjunctivitis. Infect Med 2002; 19: Butt AL, Chodosh J. Adenoviral keratoconjunctivitis in a tertiary care eye clinic. Cornea 2006; 25: Pleyer U. Viral ocular infections: Topical treatment and prevention Developments in Ophthalmology. In: Behrens-Baumann W, Kramer A, editors. Antiseptic prophylaxis and therapy of ocular infections. Basel: Karger; pp Hillenkamp J, Reinhard T, Ross RS, et al. Topical treatment of acute adenoviral keratoconjunctivitis with 02% cidofovir and 1% cyclosporine: a controlled clinical pilot study. Arch Ophthalmol. 2001;119(10): Conflict of Interest: None Author Information: Dr. Kashinatha Manikara Shenoy is Associate Professor, Department of Ophthalmology, Malabar Medical College, Calicut, Kerala, India. Pin Telephone: kashinath_sullia@yahoo.co.in
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