Outbreak of acute conjunctivitis in the period 2017-2018 in Recife, Brazil

Purpose: To evaluate the epidemiological and clinical profile and economic impact of the acute conjunctivitis outbreak in the period of 2017-2018 in Recife-PE. Methods: Cross-sectional study based on the analysis of medical records of patients diagnosed with conjunctivitis at the emergency room of the Altino Ventura Foundation (FAV) between December 2017 and March 2018. The collected data included ocular manifestations at examination, subsequent complications, management, and days of sick leave. Results: Out of 12,712 patients assisted at FAV from December 2017 to March 2018, 6,359 (50.0%) were diagnosed with conjunctivitis. The mean age of patients was 29.5 ± 14.1 years (range, 01–85 years), with similar distribution between sex (2,288 [50.1%] male; 2,282 [49.9%] female). The most common diagnosis was non-pseudomembranous conjunctivitis (5,645 cases [88.8%]). Conjunctival hyperemia (6,278 cases [98.7%]) and follicular reaction (6,255 cases [98.4%]) were the most frequent ocular findings. The most common complication was pseudomembrane in 1,062 cases (16.7%). Lubricants (4,308 [67.7%]) and antibiotic associated to corticosteroid eyedrops (2,033 [32.0%]) were the most prescribed medications. The average days of sick leave per patient was 4.8 ± 2.9 days (range, 1- 47 days) and the productivity loss estimated in R$1.159.329,14. Conclusion: The conjunctivitis outbreak in Pernambuco, Brazil was responsible for half of the consultations in an ophthalmic emergency room. Conjunctivitis outbreaks may cause an economic impact as it mostly affects young adults in their productive ages and take in average a 5-day sick leave. The clinical characteristics observed suggest an outbreak of conjunctivitis of viral etiology.


Outbreak of acute conjunctivitis in the period 2017-2018 in Recife, Brazil
IntRoductIon C onjunctivitis is the most prevalent Red Eye Syndrome diagnosis in primary eye care. (1) Conjunctivitis is a common infectious (bacterial, fungal or viral) toxin-induced or allergic disease; it is usually self-limiting. Although infectious conjunctivitis outbreaks are not unlikely, (2) this disease significantly affects basic daily activities of infected individuals and eye care institutes. (3) Conjunctivitis is defined as the extensive inflammatory process of the bulbar and/or tarsal conjunctiva, which leads to vessel dilation, hyperemia and chemosis. (4) This disease causes great socioeconomic impact, since its contagious and transmissible nature leads to the need of license from work during treatment. Accordingly, more than 377 million dollars are spent annually on conjunctivitis treatment in the US. (5) Brazil recorded an alarming increase in conjunctivitis cases from December 2017 to March 2018, mainly in the Northeastern region. Altino Ventura Foundation reported increase by 800% in conjunctivitis cases in Pernambuco State. (6) Thus, the aim of the present study was to assess the clinical, epidemiological and economic effects of this conjunctivitis outbreak from late 2017 to early 2018 in Recife City, Pernambuco, and to describe results on conjunctivitis management and complications.

methods
The present cross-sectional study assessed data from electronic health records of patients treated at the ophthalmology emergency room of Altino Ventura Foundation, from December 2017 to March 2018. Data was collected after the project's approval by the Research Ethics Committee of Altino Ventura Foundation (approval n. 3.008.774).
The keywords "conjunctivitis", "conj", "H10.3" and "H10" were entered into the foundation's electronic database. Only complete medical records were included in the study, from which the following data were collected for later analysis: demographic data, anamnesis, anterior segment biomicroscopy, diagnosis and management.
A single medical record was given to patients who visited the ophthalmologist more than once within 30 consecutive days. After this period, patients were given a new medical record.
Epidemiological data such as sex, age and residence city were collected and compared. The main common symptoms upon examination were also assessed, namely: periorbital edema, eye discharge, conjunctival hyperemia, follicular response, pupillary response, subconjunctival hemorrhage and chemosis. Complications secondary to these conjunctivitis types included: pseudomembranes; keratitis; corneal ulcers and abrasions; keratic precipitates; subepithelial infiltrates. Data on mean off-work time and mean sick-leave length based on number of ophthalmology visits were also collected.
Treatments for patients diagnosed with acute conjunctivitis during the outbreak period were based on the prescription of the following medications: topical antibiotics; topical and oral anti-inflammatory medication; eye drops; cold compresses, high--potency topical steroids; antibiotic-steroid eye drops. This treatment management was compared to that of the herein assessed ophthalmology institute.
Data were organized in Microsoft Office Excel ® (Microsoft Corporation, Albuquerque City, USA) spreadsheets. Keywords for each of the aforementioned variables were entered into a counter. The keywords contained at least two terms for each field.
Indirect production loss was calculated based on the human capital approach, which is based on the premise that license from work cannot be compensated by extra hours after the regular shift or by hiring other employees. Therefore, this method assumes that production losses can be estimated based on wage losses due to absence from work. (7) The following formula was used to estimate production loss (in R$): A x B x C x D, wherein, A -number of ophthalmology visits by patients at economically active age (≥ 14 years); B -mean nominal income/day; C -mean absence from work (sick-leave days); D -occupation level. Items B and D were based on the Continuous National Household Sample Survey (PNAD-C), which was published in the first quarter of 2018. (8)
Non-pseudomembranous conjunctivitis -described in the diagnostic hypothesis field of medical records -was diagnosed in 88.8% (n = 5645) of patients, whereas pseudomembranous conjunctivitis was diagnosed in 11.2% (n = 714) of them.  (Table 3).
Indirect costs with lost production throughout the study were estimated at R$ 1.159.329.14.

dIscussIon
Conjunctivitis is a common disease in Northeastern Brazil, whose hot and humid climate allows infectious agents (viruses and bacteria) to spread. Pernambuco State recorded increase by 800% in conjunctivitis cases from 2017 to 2018. (6) The herein presented data show that conjunctivitis accoun-    There was no significant sex distinction and most of the affected patients were economically--active young individuals. These findings corroborate those by Balasopoulou et al. (9) , who have demonstrated that sex does not significantly affect conjunctivitis diagnosis and that the young population is the most affected one. The highest conjunctivitis prevalence was recorded in March 2018, during school holidays and carnival celebration in Brazil. Since Carnival is one of the busiest events in Recife City, agglomeration may have contributed to the number of recorded cases.
The highest conjunctivitis prevalence during the outbreak was recorded in Cohab neighborhood (5.1%), which has the third-highest population density in Recife City (157.97 inhabitants/hectare). (10) Such a prevalence is assumingly associated with Cohab's large urban agglomeration, since conjunctivitis, as an infectious and contagious disease, can be easily transmitted through eye discharge, contaminated hands or even shared personal belongings.
The main clinical manifestations of Recife City's outbreak were conjunctival hyperemia and conjunctival follicles, which corroborate findings in the literature. Pinto et al. (11) found that follicular response, preauricular lymph nodes, epiphora, hyperemia, chemosis, periorbital hyperemia and pseudomembranes were the main viral conjunctivitis manifestations. Barbosa Júnior et al. (12) supported this diagnostic hypothesis by claiming that follicles, mainly those forming in the inferior fornix, are typical of adenoviral conjunctivitis -when it is accompanied by conjunctival hyperemia, photophobia, excessive tearing and foreign body sensation. Azari et al. (5) has also stated that viruses are the main etiological agents of conjunctivitis in adults. Symptoms such as chemosis and serous drainage may also be closely linked to this etiology. Therefore, the assessed outbreak was assumingly caused by a virus. This hypothesis could not be proven due to the following limitations: high costs of laboratory diagnosis and the Unified Health System's (SUS) lack of financial resources.
In 2005, Smith et al. (13) performed univariate sensitivity analysis to calculate the annual cost of conjunctivitis treatment and management in the US; they found that it ranged from 469 to 705 million dollars. Sick-leave length assessment is considered relevant because it provides a notion (estimate) of how conjunctivitis can be costly to society. Recife City's conjunctivitis outbreak led to production losses of more than R$ 1 million (≈ US$ 350 thousand), based only on the indirect costs of wage losses during the study period. Yet, this cost is underestimated, since it does not cover medical consultation, examination, medication and patient transportation expenses. Filleul et al. (14) estimated medical consultation and medication costs caused by the conjunctivitis outbreak on Réunion Island, France (2015), at $ 3.341.191.00 (≈ R$ 11 million). Such data demonstrate that acute conjunctivitis outbreaks can substantially affect the economy.
Several acute conjunctivitis treatments are recommended in the literature, since it can be caused by viral (most common etiology), bacterial and allergic infections. Viral conjunctivitis is usually self-limited and naturally healed within two to four weeks (11,15). Likewise, 60% of acute bacterial conjunctivitis cases are self-limited and naturally heals within 1 to 2 weeks. (5) However, conjunctivitis treatment is only effective in reducing one to two days of the condition's duration. Therefore, some authors do not recommend any conjunctivitis treatment. (5,11,15) Cold compresses, eye drops and topical antihistamine (for significant pruritus) are the most common medication prescribed for conjunctivitis symptom relief. (5,11,15) However, the most common medication prescribed for patients diagnosed with conjunctivitis in AVF were standard eye drops (67.7%), corticosteroid and topical antibiotic eye drops (32%); cold compress (18.6%). Such medications provided efficient symptom relief.
Topical antibiotic therapy is commonly indicated for patients susceptible to secondary bacterial infection or under high suspicion of bacterial conjunctivitis. (11,15) However, overuse of topical antibiotics can increase microbial resistance, drug toxicity and/or allergy. It also increases the risk of infecting the medication bottle, which can lead to infection of the contralateral eye. (5,15) Therefore, antibiotic therapy should be carried out with caution.
Another therapy alternative is topical corticosteroids, mainly dexamethasone, since it is a well-tolerated and potent steroid, which can be taken alone or in combination with other medication. They are widely used to reduce local inflammation and mitigate eye pain due to their effectiveness in alleviating patients' complaints, mainly conjunctivitis complications such as pseudomembranes and subepithelial infiltrates. (12) However, this therapy is not suitable for viral conjunctivitis, since even short-term therapy with low-potency medication can further viral replication and, consequently, aggravate the infection. (11,16) Topical antibiotics were empirically administered to 35.4% of patients diagnosed with conjunctivitis, based on the medical conduct of other ophthalmology centers. This conduct agreed with findings by Bro, (17) who has demonstrated that 1 in 3 patients receiving antibiotic therapy benefits from it; thus, 66% of non--purulent conjunctivitis patients received therapy even without formal indication. Risk factors of bacterial co-infection -such as the large gathering of acute conjunctivitis patients waiting too long for medical appointments at Altino Ventura Foundationwere also taken into consideration.
Erdin et al. (18) report that development of pseudomembranes and subepithelial corneal infiltrates are the most prevalent complications of conjunctivitis. This finding corroborates those of the present study, since the most common complications were pseudomembranes (16.7%), punctate keratitis (1.0%) and subepithelial infiltrates (0.6%). Pseudomembranes and subepithelial infiltrates are severe forms of acute conjunctivitis. (4) Yet, pseudomembranes were the most significant finding, since single urgent ophthalmology visits were more common than multiple visits -subepithelial infiltrates are usually formed between one and two weeks after the infectious episode. (11) Conjunctivitis duration varies according to its etiological agent, e.g., adenoviral conjunctivitis can last approximately 14 days. (12) Patients are forced to leave work during the symptomatic period of conjunctivitis due to its high infection rate. Sick-leave length ranged from 1 to 47 days (4.8 days, on average) during the outbreak period. Days off work were assumingly reduced because all diagnosed patients received therapy, which significantly reduced the disease's duration.
Since person-to-person contact is the main route of conjunctivitis transmission, both health education and guidelines are essential to raise population awareness and thereby reduce transmission. Accordingly, the following preventive measures were adopted: regular hand washing guidelines; not touching or scratching the eyes; not sharing personal objects; not sharing eye drops. This information was passed on verbally and through posters in intensive care units. Moreover, the large number of infected patients susceptible to conjunctivitis compelled Emergency Eye Care centers to take the following measures: using disposable gloves and daily changing eye drops to reduce iatrogenic transmission.

conclusIons
The conjunctivitis outbreak in Recife City was most prevalent among economically-active young adults. Accordingly, both days off work and decreased productivity due to this illness may have negatively affected the economy. The most common manifestations of this outbreak were conjunctival hyperemia, follicles, pseudomembranes and corneal subepithelial infiltrates. Although ophthalmic findings suggested that the etiologic agent is a virus, laboratory confirmation was not available. Nevertheless, educational measures and population awareness should be encouraged to prevent further outbreaks. In addition, protocols for widespread eye disease care should be made in order to ensure early diagnosis, therapy and data standardization.