Evolution and epidemic success of Mycobacterium tuberculosis in eastern China: evidence from a prospective study.

BACKGROUND: Lineage distribution of Mycobacterium tuberculosis (Mtb) isolates is strongly associated with geographically distinct human populations, and its transmission can be further impacted by the bacterial genome. However, the epidemic success of Mtb isolates at an individual level was unknown in eastern China. Knowledge regarding the emergence and transmission of Mtb isolates as well as relevant factors may offer a new solution to curb the spread of the disease. Thus, this study aims to reveal the evolution and epidemic success of Mtb isolates in eastern China. RESULTS: Of initial 1040 isolates, 997 were retained after removing duplicates and those with insufficient sequencing depth. Of the final samples, 733 (73.52%) were from Zhejiang Province, and 264 (26.48%) were from Shanghai City. Lineage 2 and lineage 4 accounted for 80.44% and 19.56%, with common ancestors dating around 7017 years ago and 6882 years ago, respectively. Sub-lineage L2.2 (80.34%) contributed the majority of total isolates, followed by L4.4 (8.93%) and L4.5 (8.43%). Additionally, 51 (5.12%) isolates were identified to be multidrug-resistant (MDR), of which 21 (29.17%) were pre-extensively drug-resistant (pre-XDR). One clade harboring katG S315T mutation may date back to 65 years ago and subsequently acquired mutations conferring resistance to another five antibiotic drugs. The prevalence of compensatory mutation was the highest in pre-XDR isolates (76.19%), followed by MDR isolates (47.06%) and other drug-resistant isolates (20.60%). Time-scaled haplotypic density analyses suggested comparable success indices between lineage 2 and lineage 4 (P = 0.306), and drug resistance did not significantly promote the transmission of Mtb isolates (P = 0.340). But for pre-XDR isolates, we found a higher success index in those with compensatory mutations (P = 0.025). Mutations under positive selection were found in genes associated with resistance to second-line injectables (whiB6) and drug tolerance (prpR) in both lineage 2 and lineage 4. CONCLUSIONS: Our study demonstrates the population expansion of lineage 2 and lineage 4 in eastern China, with comparable transmission capacity, while accumulation of resistance mutations does not necessarily facilitate the success of Mtb isolates. Compensatory mutations usually accompany drug resistance and significantly contribute to the epidemiological transmission of pre-XDR strains. Prospective molecular surveillance is required to further monitor the emergence and spread of pre-XDR/XDR strains in eastern China.

Genomic and spatial analysis reveal the transmission dynamics of tuberculosis in areas with high incidence of Zhejiang, China: A prospective cohort study.

In the mountainous, rural regions of eastern China, tuberculosis (TB) remains a formidable challenge; however, the long-term molecular epidemiological surveillance in these regions is limited. This study aimed to investigate molecular and spatial epidemiology of TB in two mountainous, rural counties of Zhejiang Province, China, from 2015 to 2021, to elucidate the recent transmission and drug-resistance profiles. The predominant Lineage 2 (L2) Beijing family accounted for 80.1% of total 532 sequenced Mycobacterium tuberculosis (Mtb) strains, showing consistent prevalence over seven years. Gene mutations associated with drug resistance were identified in 19.4% (103/532) of strains, including 47 rifampicin or isoniazid-resistant strains, eight multi-drug-resistant (MDR) strains, and five pre-extensively drug-resistant (pre-XDR) strains. Genomic clustering revealed 53 distinct clusters with an overall transmission clustering rate of 23.9% (127/532). Patients with a history of retreatment and those infected with L2 strains had a higher risk of recent transmission. Spatial and epidemiological analysis unveiled significant transmission hotspots, especially in densely populated urban areas, involving various public places such as medical institutions, farmlands, markets, and cardrooms. The study emphasizes the pivotal role of Beijing strains and urban-based TB transmission in the western mountainous regions in Zhejiang, highlighting the urgent requirement for specific interventions to mitigate the impact of TB in these unique communities.

Association of empty nest with depressive symptom in a Chinese elderly population: A cross-sectional study.

BACKGROUND: Empty nest has been becoming the main family pattern among old people, and influencing the traditional family providing for the aged in China. This study aimed to investigate the association of empty nest with depressive symptom in a Chinese elderly population. METHODS: Our study was based on the baseline investigation of Zhejiang Major Public Health Surveillance which was conducted in 2014. The final analyzed sample consisted of 9215 participants aged no less than 60 years. Subjects completed a questionnaire including demographic characteristics, living arrangements, behavioral risk factors, health status, subjective assessments, and Patient Health Questionnaire-9 scale. RESULTS: More than half of the participants were empty nest elders (57.4%). The overall prevalence of depressive symptom was 10.3%, while it was higher in empty nest group than in non-empty nest group (11.6% vs. 8.6%, P<0.001). A positive association was found between empty nest and depressive symptom, the OR (95%CI) was 1.223(1.045, 1.431). After stratified by gender/age/education level/employment status, this association was just prominent in participants of male, 70 years old and above, primary school education, and retirees. No matter living with spouse or living alone, empty nesters were more likely to have depressive symptoms than non-empty nesters. LIMITATIONS: Cross-sectional study could not make a causation conclusion. The social supports of participants were not been investigated in detail. CONCLUSIONS: Empty nest elders, especially those who are male, 70 years old and above, primary school education, and retired, are more vulnerable to depressive symptom.

Nosocomial transmission of avian influenza A (H7N9) virus in China: epidemiological investigation.

STUDY QUESTION: Can avian influenza A (H7N9) virus be transmitted between unrelated individuals in a hospital setting? METHODS: An epidemiological investigation looked at two patients who shared a hospital ward in February 2015, in Quzhou, Zhejiang Province, China. Samples from the patients, close contacts, and local environments were examined by real time reverse transcriptase (rRT) polymerase chain reaction (PCR) and viral culture. Haemagglutination inhibition and microneutralisation assays were used to detect specific antibodies to the viruses. Primary outcomes were clinical data, infection source tracing, phylogenetic tree analysis, and serological results. STUDY ANSWER AND LIMITATIONS: A 49 year old man (index patient) became ill seven days after visiting a live poultry market. A 57 year old man (second patient), with a history of chronic obstructive pulmonary disease, developed influenza-like symptoms after sharing the same hospital ward as the index patient for five days. The second patient had not visited any poultry markets nor had any contact with poultry or birds within 15 days before the onset of illness. H7N9 virus was identified in the two patients, who both later died. Genome sequences of the virus isolated from both patients were nearly identical, and genetically similar to the virus isolated from the live poultry market. No specific antibodies were detected among 38 close contacts. Transmission between the patients remains unclear, owing to the lack of samples collected from their shared hospital ward. Although several environmental swabs were positive for H7N9 by rRT-PCR, no virus was cultured. Owing to delayed diagnosis and frequent hospital transfers, no serum samples were collected from the patients, and antibodies to H7N9 viruses could not be tested. WHAT THIS STUDY ADDS: Nosocomial H7N9 transmission might be possible between two unrelated individuals. Surveillance on patients with influenza-like illness in hospitals as well as chickens in live poultry markets should be enhanced to monitor transmissibility and pathogenicity of the virus. FUNDING, COMPETING INTERESTS, DATA SHARING: Funding support from the Program of International Science and Technology Cooperation of China (2013DFA30800), Basic Work on Special Program for Science and Technology Research (2013FY114600), National Natural Science Foundation of China (81402730), Special Program for Prevention and Control of Infectious Diseases in China (2013ZX10004218), US National Institutes of Health (1R01-AI108993), Zhejiang Province Major Science and Technology Program (2014C03039), and Quzhou Science and Technology Program (20111084). The authors declare no other interests and have no additional data.