Whole-Genome Sequencing and Epidemiological Investigation of Tuberculosis Outbreaks in High Schools in Hunan, China

Abstract

Background

Tuberculosis (TB) seriously threatens individual and public health. Recently, TB outbreaks in schools have been reported more frequently in China and have attracted widespread attention. We reported three TB outbreaks in high schools in Hunan Province, China.

Methods

When a tuberculosis patient was reported in a school, we carried out field epidemiological investigations, including tuberculin skin testing (TST), chest X-ray (CXR) and laboratory test for all close contacts, and whole-genome sequencing (WGS) analyses to understand the transmission patterns, the causes and the risk factors for the outbreaks, thereby providing a foundation for the control of TB epidemics in schools.

Results

A total of 49 students with TB patients were identified in the three schools where TB outbreaks occurred, including nine patients in School A, 14 patients in School B, and 26 patients in School C. In Schools A, B and C, the putative attack rates in the classes of the index case were 13.8% (8/58), 7.6% (5/66), and 40.4% (21/52), while the putative attack rates of expanding screening in the school were 0.3% (1/361), 0.2% (9/3955), and 0.2% (5/2080), respectively. Thirteen patients had patient delay, with a median delay interval of 69 days (IQR 30.5–113 days). Twelve patients had a healthcare diagnostic delay with a median delay interval of 32 days (IQR 24–82 days). Phylogenetic analysis of culture-positive patients revealed that most of them shared a small genetic distance (≤12 SNPs), with three separate genetic clusters (including one MDR-TB genomic cluster), indicating the recent transmission of Mycobacterium tuberculosis strains.

Conclusion

This combination of field investigation and WGS analysis revealed the transmission of three TB outbreaks in schools. Reinforced implementation is needed to improve timely case finding and reduce diagnosis delay in routine TB control in the school population.

Keywords:

• tuberculosis outbreak
• high school
• epidemiological investigation
• whole genome sequencing

Abbreviations

TB, tuberculosis; TST, tuberculin skin testing; CXR, chest X-ray; WGS, whole-genome sequencing; M. Tuberculosis, Mycobacterium tuberculosis; MIRU-VNTR, mycobacterial interspersed repetitive unit-variable number tandem repeat typing; CDC, Centers for Disease Control and Prevention; DST, drug susceptibility tests; RIF, rifampin; INH, isoniazid; AMK, amikacin; CPM, capreomycin; CIP, ciprofloxacin; EMB, ethambutol; KM, kanamycin; MFX, moxifloxacin; OFLX, ofloxacin; PZA, pyrazinamide; SM, streptomycin; BDQ, bedaquilin; IQR, interquartile range; M-L, maximum-likelihood; MDR-TB, multidrug-resistant tuberculosis; RR-TB, rifampin-resistant tuberculosis.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Acknowledgment

We thank all the investigators from the study sites for their contribution.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that there are no conflicts of interest.

Additional information

Funding

This research was supported by the Natural Science Foundation of Hunan Province, China (grant number: 2018JJ2215).