Epidemiological characteristics and clinical features
The outbreak occurred in a pharmaceutical factory of Wuxi, China. The factory has 238 employees in 13 departments, of which 7 departments are involved in this outbreak（Fig.1）. The first case A is in the DC workshop of the production department. On February 14, 2019, case A consciously developed fever, but did not measure body temperature. The next day around 23:00, the patient found a lot of rashes (no itching) on her arms and torso, accompanied by sore throat. On the third morning, the patient developed symptoms of dry mouth, ocular conjunctival hemorrhage and the rashes spread over her face and body. Then she went to the hospital for treatment. The blood test showed the value of white blood cells was low (2.92*109/L). The doctor gave her antiviral treatment. The symptoms of ocular conjunctival hemorrhage disappeared on the fourth day. On the fifth day, the rashes subsided and the body was itchy. According to the patient’s self-report, she and her family traveled to Suzhou, Shanghai and Zhoushan respectively from February 5 to February 7, with one day in each place. Zhoushan is a coastal city with abundance of seafood. The patient ate a large amount of seafood at street stands during the tour in Zhoushan on February 7, including oysters, scallops, fish, shrimp and so on. The food ingested by the patient in Shanghai and Suzhou was healthy, without eating at street stands, no history of aquatic products except fish and freshwater shrimp, no raw and cold food. During the travel, the patient felt a little tired and weak. The patient did not have a history of exposure to similar cases. She returned to work on the 11th until 15th.
The factory emerged patients with rash, fever, ocular conjunctival hemorrhage as the main symptoms in succession from the February 15. It has spread to other workshops and reached its peak on the 18th. After taking the control measures such as disinfection, window opening and ventilation, home isolation on 19th, the number of cases has decreased, but still had cases. In order to better control the outbreak, the factory was temporarily closed on the 23rd for 10 days. Eventually, the outbreak ended on March 6 (Fig.2).
The highest percentage (26.32%, respectively) for spatial distribution of cases was in the DC workshop where the first case was located and refining plant, followed by dissolution workshop, maintenance workshop, acylation workshop and office (10.53%, respectively) (Fig.1). According to epidemiological investigations, all employees involved in the production of the products all leave work after taking bath in the factory’s bathroom. Of the patients who developed the disease, 89.47% (17/19) used the bathroom. All patients had no history of exposure to similar cases outside the factory. All employees in the factory are dining in the same canteen and drinking the same batch of bottled water from the same brand.
A total of 19 workers had symptoms up to March 31, 2019, giving an attack rate of 8.26%. These patients with a male to female ratio of 1.11 to 1, were between 22 and 42 years old. The main symptoms were rash (19 cases, 100.00%), ocular conjunctival hemorrhage (19 cases, 100.00%), fever (total 11 cases, 57.89%. 4 cases below 38.5 °C, 5 cases of 38.5–40.5 °C, 2 cases of conscious fever, accounting for 21.05%, 26.32% and 10.53% respectively) and sore throat (6 cases, 31.58%). Except for one patient whose main symptom was ocular conjunctival hemorrhage, all other patients had systemic rashes, and some patients (7 cases, 36.84%) showed symptoms of fatigue and limb joint pain in the course of disease (Fig.3, Table 1). After symptomatic treatment by doctors (mainly antipyretic, antiallergic, antivirals), the patients experienced symptoms for an average of 8 days. Two patients (10.53%) felt itchy skin at the time of the eruption, and one patient presented with the debridement of the corners of the mouth. Five patients were not routinely examined for blood. Of the remaining 14 patients, except for 3 patients with low white blood cells, the rest was normal.
Analysis of the attack rates in different departments showed that there was no statistical difference in the attack rates among various departments (p>0.05) (Table 2).
We analyzed bathing in the bathroom as a risk factor for disease through the epidemiological investigations. The result showed that the risk of illness was 7.37 times higher taking bath in bathroom than that of not taking bath (95% CI 1.67, 32.79) (Table 3).
Six of 12 nasopharyngeal swabs were positive for enterovirus nucleic acid. Subsequently, the VP1 genes of the six samples were amplified, sequenced and identified by PCR. The sequencing results were analyzed by BLAST. It was found that Coxsackie A6 was the enterovirus type causing this outbreak.
The six samples became a cluster through comparison and analysis of the phylogenetic tree, which was the same branch as the original strain in the United States in 1949 (AY421764/USA1949). The homology was 91.5% (Fig.4).