Conjunctivitis refers to a category of disorders marked by inflammation of the conjunctiva. The predominant etiology of infectious conjunctivitis is viral infection, accounting for around 80% of cases, succeeded by bacterial causes. [2]. The noninfectious types include allergic, mechanical/irritative/toxic, immune-mediated, and neoplastic.Citation1 The allergic variant of noninfectious conjunctivitis is the most prevalent, impacting almost 40% of the US population. Conjunctivitis may be categorized as acute, chronic, or recurring based on the onset and severity of the clinical reaction.Most instances of viral and bacterial conjunctivitis are classified as acute, with hyperacute cases occurring less commonly. The mechanical, irritative, toxic, immune-mediated, and neoplastic variants are often linked to chronic inflammation, with the toxic variant potentially exhibiting an immediate onset. Conjunctivitis is a prevalent condition encountered in primary care. It accounts for around 2% of all medical consultations in the United States and numerous self-referrals to community pharmacists. Accurately capturing the real epidemiology of conjunctivitis is challenging due to the significant number of patients who may self-medicate, postpone, or forgo medical attention, as well as the prevalence of erroneous diagnoses in primary care settings.  Approximately 70% of patients with acute red eye seek treatment in primary and urgent care, resulting in significant economic and social burdens. The pharmacoeconomic implications of infectious conjunctivitis are significant, encompassing expenses related to repeated diagnosis, referrals, insurance copayments, patient prescriptions, and productivity losses due to absenteeism from work or school. In the United States, acute conjunctivitis impacts around 6 million individuals yearly, with the treatment of bacterial conjunctivitis alone costing between $377 million and $857 million each year.  To our knowledge, no research on health-related quality of life for patients with acute infectious conjunctivitis have been published. Patients with infectious conjunctivitis receive inadequate management in primary care due to a lack of recognition of the prevalence of viral conjunctivitis, coupled with frequent antibiotic prescriptions (approximately 80%) for this condition, despite guidelines that advise against antibiotic use for minor self-limiting illnesses. Antibiotic prescription indicates an assumed diagnosis of bacterial conjunctivitis; nevertheless, the clinical accuracy in identifying viral conjunctivitis may be below 50% [15]. The aim of this study is to  evaluate the prevalence of Adenovirus serotypes in epidemic keratoconjunctivitis patients and its clinical manifestation.

From March 1, 2024, to December 10, 2024, a total of 115 individuals aged 4 to 17 years were recruited at the ophthalmology emergency department of Azadi Teaching Hospital using a simple random sampling method. Additionally, 60 healthy, age-matched individuals without diabetes or other chronic illnesses were selected as the control group to serve as a baseline for comparison.

The respective ones were those showing symptoms for a period of more than two weeks due to conjunctivitis at study enrollment. The symptoms were of redness, discomfort, tearing, follicular response, eye discharge, and swelling of preauricular lymph nodes. All patients were excluded when they had bacterial conjunctivitis, history of recent eye surgery, too current or protracted use of eye drops, use of contact lenses, past of allergic conjunctivitis, glaucoma, and history of herpes simplex keratitis.

The research was conducted using ethically expected protocols, including approval by the Kirkuk Health Directorate Ethics Committee having the approval number 212 dated February 28, 2024. The study protocol and any documents were seen and agreed upon with most patients or their guardians who would provide formal written consent before taking the study into consideration of all ethical standards and applicable norms.

Data were collected via a structured questionnaire with the help of the examining physician for all patients. The questionnaire collected demographic details, the clinical history, and the occurrence of prior episodes of conjunctivitis and other related medical conditions. Following this, there was a comprehensive eye examination for all participants by the ophthalmologist to confirm conjunctivitis off the features like redness, eye discomfort/pain, tearing, follicular response (lymphoid reaction), preauricular lymphadenopathy, puffy eyelids, and photophobia. Other specific symptoms characterizing adenoviral keratoconjunctivitis were itching, foreign body sensation, and auricular lymphadenopathy.

Blood samples (4 mL) were collected from all subjects by venous puncture using sterile Vacutainer tubes. The sample was centrifuged to separate serum, stored at 20°C, and lastly analyzed for various components. Enzyme-linked immunosorbent assay (ELISA) was used to detect individual adenoviral keratoconjunctivitis IgM antibodies (Bioteck USA). The control group comprised 60 healthy persons who did not have any chronic disease, conjunctivitis, or symptoms related to it for comparison.

The laboratory used standard equipment and materials, for example ELISA kits which was used for serological virus antibody detection, sterile blood collection supplies, centrifuges for serum separation, and freezers set at -20°C for sample storage. Also used were ELISA-specific buffer solutions and substrates to get highly accurate diagnostic results.

The statistical analysis was made with the help of ANOVA Statistical Software (version 11). The methodological approach in the study was based on multiple tests such as the Chi-Square (X²) test, T-test, F-ratio and p-value < 0.05 was considered to be statistically significant. All these steps made the methodology very stringent, organized, systematic data collection, and robust analysis, making it a study with which whole disease can be analyzed.

The data shown in Table 1 refers to the seroprevalence of Adenoviral IgM Antibodies in patients suffering from conjunctivitis in contrast to the control group. Twenty-five patients (21.74%) tested positive for the said Ab in the Conjunctivitis group, a high amount of this recent or acute adenoviral infection on this group. Conversely, in the control group, only 2 individuals (3.3%) were serologically positive, indicating a lower prevalence of recent adenoviral exposure in healthy individuals. Predominantly, negative sera were prevailed in both the cases, with 90 patients (78.26%) in conjunctivitis group and 58 individuals (96.67%) in the control group proving to be negative.

Table 1: Seroprevalence of adenovirus among Conjunctivitis patients with and the control groups.

P-value: 0.001

Figure 1 illustrates the distribution of adenovirus infection among conjunctivitis patients based on their place of residence. The data reveals that 60% of the cases originated from urban areas, while 40% were from rural areas.

Figure 1: Residence  distribution of adenovirus infection among Conjunctivitis patients

The data in Table 2 provides the distribution of adenovirus infection among patients with renal failure across different age groups. The highest infection rate is observed in the youngest age group (4–6 years), with 14 cases, accounting for 56.0% of the total infections. This is followed by the 7–12 years age group, which has 6 cases (24.0%), and the 13–16 years group, with 4 cases (16.0%). The lowest infection rate is found in patients aged 17 years and older, with only 1 case (4.0%).

Table 2: Distribution of  adenovirus infection  among patients with renal failure according to age.

The study showed that 11 patients (44%) with ocular adenoviral infection experienced flu-like illness before or during their ocular complaint and 14 patients (56%) with ocular adenoviral infection didn’t have any systemic manifestation, Figure 2.

Figure 2: Relation of ocular adenoviral infection with experienced flu-like illness

The data in Table 3 highlights the clinical features observed in patients with keratoconjunctivitis, comparing those who tested positive for adenovirus (Adeno +ve) to those who tested negative (Adeno -ve). Among adenovirus-positive patients, itching was the most common symptom, affecting 21 individuals (84%), followed by redness in 19 patients (76%) and grittiness in 17 patients (68%). Tearing and clear mucinous discharge were equally reported in 15 patients (60%). In contrast, among adenovirus-negative patients, itching remained the most frequent symptom (66.96%), followed by redness (56.52%), clear mucinous discharge (51.30%), tearing (49.57%), and grittiness (41.74%).

Table 3: Clinical features patients with keratoconjunctivitis plus Adenovirus infection

Table 4 highlights the gender distribution of adenovirus infection among the study population. Among adenovirus-positive cases (Adeno +ve), males constitute a higher proportion with 15 cases (60%) compared to females with 10 cases (40%). Conversely, among adenovirus-negative cases (Adeno -ve), females predominate, accounting for 70 cases (60.87%), whereas males represent 45 cases (39.13%). Overall, males constitute 52.17% of the total population, while females make up 47.83%. These findings indicate a higher susceptibility to adenovirus infection among males, whereas females represent a larger proportion of adenovirus-negative cases.

Table 4: Gender Distribution of Adenovirus Infection

P-value:0.016

Adenoviral keratoconjunctivitis outbreaks in ophthalmology departments constitute a significant public health concern [15]. The predominant cases of conjunctivitis are viral in origin, and distinguishing them from bacterial infections is critically important due to the reduction in antibiotic usage and the emergence of new antivirals for the specific treatment of viral etiologies. 65–90% of viral conjunctivitis cases are attributed to adenovirus, underscoring the need of differentiating it from other viral pathogens [16,17]. Adenovirus-mediated conjunctivitis is a condition with a transmission rate of up to 50%. Multiple viral genotypes and serotypes are associated with different kinds and severities of infection [12]. Group D, which includes types 8, 19, 37, and 11 (from group B), are the predominant viruses responsible for keratoconjunctivitis epidemics globally; however, less study has been conducted on the common serotypes in the Middle East. Numerous studies [19] were conducted in our region to examine the prevalence of adenoviruses in persons with acute conjunctivitis. Shafiei et al. found adenovirus serotype 8 as the predominant cause of conjunctivitis in Ahvaz, southwest Iran [11]. The objective of this study was to examine the prevalence of adenovirus and its associated serotypes during two extended outbreaks of epidemic keratoconjunctivitis at Khalili Referral Hospital, the largest city in the southern region of the country. Conversely, AL-research by Mousawi in Iraq indicated that the female gender is a significant risk factor in groups [20]. Moreover, Li et al. discovered that the prevalence was much higher among male students. The greatest incidence of adenoviral keratoconjunctivitis infection (17.05 percent) was observed in individuals aged 30 to 39 [21]. Conversely, Shafiei et al. [11] indicated that the lowest incidence rate occurred in the 10-year age group. This Iranian study indicated that adenovirus accounted for 94.4 percent of ocular infection cases, with no notable variations in gender, age, or socioeconomic status related to the illness. These findings are inconsistent with our investigation, as several demographic characteristics, including gender and direct exposure to an infected family member or friend, were identified as risk factors for EKC [10]. The relationship between Adenovirus infection and clinical signs in the clinic is little investigated. Conjunctival injection, ocular discharge, conjunctival hemorrhage, epiphora, follicular reaction, and the sensation of a foreign body were the most common symptoms, affecting more than fifty percent of patients. Das and Basu recognized erythema (63.7% of cases) and serous discharge (42.1% of cases) as the predominant symptoms [22]. Epidemic keratoconjunctivitis is the most severe variant of conjunctivitis, distinguished by a serous discharge, hyperemia, chemosis, and ipsilateral lymphadenopathy [23]. Preauricular lymphadenopathy or pain was seen in 1,406 individuals (7.3%). Other studies [21, 24] indicated that the predominant manifestations of EKC were follicular hyperplasia, pseudomembrane formation, preauricular lymphadenopathy, corneal involvement, and visual impairment, which differed from our clinical findings. Aoki et al. found that chemosis, subepithelial infiltration, and pre-auricular lymphadenopathy were more closely associated with EKC than with other ocular disorders caused by bacterial or viral pathogens [25]. Moreover, pre-auricular lymphadenopathy and subepithelial infiltrates were seen in 23.5% and 43.5% of 68 cases, respectively, of adenoviral keratoconjunctivitis attributed to various adenovirus types [25]. This analysis revealed a significant association between viral identification and conjunctival injection, ocular discharge, preauricular lymphadenopathy, and the symptoms described.

A significant association was observed between adenovirus infection and conjunctival injection in patients with EKC. This study emphasizes the need for accurate viral diagnostics to guide effective management and reduce unnecessary antibiotic use.

The authors declare that they have no conflict of interest

No funding sources

The study was approved by the AL-Kitab University, Kirkuk, Iraq

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