The epidemic of Q fever in 2018 to 2019 in Zhuhai city of China determined by metagenomic next-generation sequencing

Author summary Generally, the clinical diagnosis of acute Q fever, which is caused by Coxiella burnetii, is based on serologic methods that detect the presence antibodies produced by the body to fight the infection. However, the lag time between becoming infected and production of antibodies limits early diagnosis using this method. Here, we confirmed an epidemic of human Q fever in Zhuhai, a contemporary city in China, using clinical metagenomic next-generation sequencing (mNGS) and cell phone location data. Our results indicate that Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai were the likely infection source for the Q fever epidemic. More importantly, we demonstrate that mNGS is a useful tool for rapid and effective public health responses to acute bacterial infections. Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018-2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.