On April 6, 2019, Zaoyang-County CDC in Hubei Province received an alert from the Automatic Early Warning Information System for Tuberculosis for a 16-year-old student in a secondary school that had been recently been diagnosed with a positive sputum smear for tuberculosis (TB). The Zaoyang-County CDC verified the case, screened all close contacts, and carried out epidemiological investigation immediately (1). In total, five multidrug-resistant tuberculosis (MDR-TB) cases and nine clinically diagnosed TB cases were identified and subsequently isolated from school to start a multi-drug regimen. This outbreak was defined as an MDR-TB public health emergency on May 6, and the response was in accordance with the Regulations on Responses to Public Health Emergencies.
The outbreak occurred at a public secondary school with 3 grade-levels, over 3,900 students, and over 300 staff members. The index case occurred in a 16-year-old student with positive TB sputum smear tests. An interview with the student revealed that in February 2019 he had an onset of coughing that was treated as a common cold. In late March, the student suffered from significant fatigue, more frequent coughing, and occasional left chest pain. On April 4, the student visited the county hospital for a diagnosis where chest computed tomography (CT) showed his lungs were infected with TB. A positive sputum smear test result confirmed the diagnosis, and the student was subsequently transferred to the Xiangyang Tuberculosis Control Hospital the following day. The student was further tested with GeneXpert testing and anti-TB drug sensitivity test (DST), and the student was shown to have resistance to rifampicin (R), isoniazid (H), and ethambutol (E).
All TB cases in this outbreak were diagnosed per the National Guidelines of Diagnosis for Pulmonary Tuberculosis (WS 288-2017) (2), which require TB cases to classified as bacteriological confirmed, clinically diagnosed, or presumptive cases and classify patients resistant to R and H to be diagnosed as multidrug-resistant tuberculosis (MDR-TB). According to these guidelines, this patient with MDR-TB was confirmed to be the index case of this outbreak in the secondary school.
According to the National Regulations for Tuberculosis Prevention and Control in Schools (1), the Zaoyang-County CDC screened all students’ regular classmates as they all had direct contact with the index case of MDR-TB. All close contacts were screened by symptom screening, purified protein derivative (PPD) skin test, chest X-ray, and sputum smear test. Following the results of these tests, some students were further examined with tests including GeneXpert testing and DST.
Out of the student’s regular classmates, 30 out of 60 students (50.00%, 30/60) had strongly positive PPD reactions. Chest X-rays showed that 13 out of these 30 students (43.33%, 13/30) had lesions of active TB in lung, which is consistent with imaging manifestations of TB (3). In the following days, GeneXpert testing and DST indicated that 4 of these 13 students had confirmed cases of MDR-TB (R, H, and E resistant) and 9 TB cases were clinically diagnosed.
The screening was then expanded to all teachers and students for the index-case patient’s grade. Among the remaining 1,144 students in other classes, 22 cases (1.92%, 22/1,144) had strongly positive PPD reaction but had normal chest X-ray results. Screening was ended as no more TB cases were found in the other classes. The rate of strongly positive PPD and incidence of TB in students in the index-case patient’s class is significantly higher than other classes (chi-square test, p<0.05; Table 1). This indicates that classmates of the index-case patient were more vulnerable due to close contact.
Class No. of students No. of strongly positive PPD reaction Rate of strongly positive PPD reaction (%) χ2 p value No. of TB patients Incidence (%) p value* Index-Case Patient’s Class 60 30 50.00 307.348 <0.05 13 21.67 0.000 Other Classes 1,144 22 1.92 0 0.00 *Using Fisher’s Exact Test.
Table 1. Rate of strongly positive PPD and TB incidence among contacts.
To explore the epidemiological linkage among patients, strains from those five bacteriologically-confirmed MDR-TB students were tested with whole genome sequencing. The results indicated infection by the same Mycobacterium tuberculosis (MTB) strain, which means that the index case acted as the source of transmission in this outbreak. Though no further epidemiological investigation was conducted between the index case and the nine clinically-diagnosed TB cases, the patients had close contact as classmates and the index-case patient was also considered as the source of transmission.
The results of an environmental hygiene survey indicated that the secondary school was in good condition. However, most of the doors and windows of classrooms were closed in the winter, which resulted in poor ventilation and encouraged MTB spread in the environment. In accordance with the Regulations on Response to Public Health Emergencies, this outbreak was defined as an MDR-TB public health emergency on May 6 and had been responded to appropriately.
The 14 students with TB were treated with a multi-drug regimen at a hospital for the first two months and then at home for the rest of the treatment course. While preventative treatment effectively lowers the risk of disease progression for contacts of individuals with drug-susceptible tuberculosis, the effectiveness of this strategy is not well understood for contacts of people with MDR-TB (4-5). Therefore, students with strongly positive PPD reactions and normal chest X-ray results were strongly encouraged to take chest X-rays and be monitored at regular intervals at 3, 6, and 12 months. The Zaoyang-County CDC provided health education on TB to enhance the awareness of TB control among students, to encourage students with suspected TB symptoms to prioritize visiting clinics, and for TB patients to be compliant to physician-supervised treatment. Presently, no new cases have been reported.
Further epidemiological investigation into the index case by the Zaoyang-County CDC revealed that a distant relative had dinner with the index-case patient towards the end of 2018 and also had MDR-TB. The distant relative’s TB drug resistance spectrum was the same as the index case (R, H, and E resistant). However, during the epidemiological investigation of the index case, this distant relative had negative sputum smear test results, and the reporting hospital did not retain the resistant strain during the initial diagnosis. Though a preliminary epidemiological association can be established, gene homology analysis cannot be done to fully confirm MDR-TB.