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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. 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. [ABSTRACT FROM AUTHOR]

The emergence of severe cases of human influenza A (H7N9) viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine. In this study, a cold-adapted (ca), live attenuated monovalent reassortant influenza H7N9 virus (Ah01/AA ca) was generated using reverse genetics that contained hemagglutinin (HA) and neuraminidase (NA) genes from a 2013 pandemic A H7N9 isolate, A/Anhui/01/2013 virus (Ah01/H7N9); the remaining six backbone genes derived from the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AA virus). Ah01/AA ca virus exhibited temperature sensitivity (ts), ca, and attenuation (att) phenotypes. Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cell-mediated immune responses in a dose-dependent manner. Furthermore, the candidate Ah01/AA ca virus was immunogenic and offered partial or complete protection of mice against a lethal challenge by the live 2013 influenza A H7N9 (A/Anhui/01/2013). Protection was demonstrated by the inhibition of viral replication and the attenuation of histopathological changes in the challenged mouse lung. Taken together, these data support the further evaluation of this Ah01/AA ca candidate vaccine in primates. [ABSTRACT FROM AUTHOR]

In early spring 2013, the emergence of the influenza A (H7N9) virus in humans in Eastern China raised concerns of a new influenza pandemic. Development of a safe and effective H7N9 influenza vaccine is urgently needed. To this end, we first synthesized the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza A (H7N9) virus A/AnHui/1/2013. Using reverse genetics, we rescued a reassortant virus (H7N9/PR8) that contained the HA and NA genes from wild-type H7N9 and six genes encoding internal proteins from the A/Puerto Rico/8/34 (PR8) virus. Next, the pathogenicity of the reassortant virus was evaluated both in vivo and in vitro. We found that the virus was non-pathogenic in mice and was stable after serial passaging in eggs. Furthermore, we found that a monovalent influenza A (H7N9) split vaccine prepared from the virus was immunogenic in mice and ferrets. When given intramuscularly, the vaccine (two doses of at least 15-µg) completely protected mice from normally lethal wild-type H7N9 virus challenge. In summary, our H7N9 vaccine, developed over a short time, is a potential candidate for further clinical evaluation and human use. [ABSTRACT FROM AUTHOR]