Macrolides such as erythromycin are the empirical treatment of Bordetella pertussis infections. China has experienced an increase in erythromycin-resistant B. pertussis isolates since they were first reported in 2013. Here, we undertook a genomic study on Chinese B. pertussis isolates from 2012 to 2015 to elucidate the origins and phylogenetic relationships of erythromycin-resistant B. pertussis isolates in China. A total of 167 Chinese B. pertussis isolates were used for antibiotic sensitivity testing and multiple locus variable-number tandem repeat (VNTR) analysis (MLVA). All except four isolates were erythromycin-resistant and of the four erythromycin-sensitive isolates, three were non-ptxP1 . MLVA types (MT), MT55, MT104 and MT195 were the predominant types. Fifty of those isolates were used for whole genome sequencing and phylogenetic analysis. Genome sequencing and phylogenetic analysis revealed three independent erythromycin-resistant lineages and all resistant isolates carried a mutation in the 23S rRNA gene. A novel fhaB3 allele was found uniquely in Chinese ptxP1 isolates and these Chinese ptxP1-ptxA1-fhaB3 had a 5-fold higher mutation rate than the global ptxP1-ptxA1 B. pertussis population. Our results suggest that the evolution of Chinese B. pertussis is likely to be driven by selection pressure from both vaccination and antibiotics. The emergence of the new non-vaccine fhaB3 allele in Chinese B. pertussis population may be a result of selection from vaccination, whereas the expansion of ptxP1-fhaB3 lineages was most likely to be the result of selection pressure from antibiotics. Further monitoring of B. pertussis in China is required to better understand the evolution of the pathogen.

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Purpose: The study aimed to quantify the global trends of the incidence rates of multidrug-resistant (MDR) tuberculosis (MDR-TB) and extensively drug-resistant (XDR) tuberculosis (XDR-TB).Methods: Cases, age-standardized rates (ASRs), and incidence rates of MDR-TB and XDR-TB during 2010–2019 were obtained from the Global Burden of Disease Study 2019. The incidence trends of MDR-TB and XDR-TB were evaluated using the estimated annual percentage changes (EAPCs) in ASRs. The relationships among the ASRs of MDR-TB and XDR-TB, the MDR rate, the XDR rate, and socio-demographic index (SDI) were assessed using locally weighted regression and Pearson’s correlation coefficient.Results: The global ASR of MDR-TB on average decreased by 1.36% (EAPC = −1.36, 95% confidence interval [CI] = −2.19 to −0.52) per year whereas that of XDR-TB was stable (EAPC = 0.69, 95% CI = −0.15–1.54) during 2010–2019. The incidence trends of MDR-TB in most regions and countries were decreasing, but those of XDR-TB were increasing. People aged 35–44 and 55–64 years had the highest incidence rates for MDR-TB and XDR-TB. The MDR and XDR rates both peaked in those aged 35–44 years. Areas with higher SDI tended to have lower ASRs of MDR-TB (p < 0.001, ρ = −0.43).Conclusion: The current achievements for the incidence trends of MDR-TB and XDR-TB are insufficient. More strategies and tools need to be developed to further curb MDR-TB and XDR-TB, especially in high-risk areas and age groups, and in low SDI regions.

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Background: The global prevalent ptxP3 strains varies from about 10% to about 50% of circulating B. pertussis population in different areas of China. Methods: To investigate the difference of vaccination status between different genotypes in the circulating B. pertussis after 10 years of acellular pertussis vaccine (aPV) used in China. The nasopharyngeal swabs and isolates of B. pertussis from these patients were used to perform genotyping of antigen genes. We use antibiotic susceptibility test against erythromycin and sequencing methods for site 2047 of 23S rRNA to determine the resistance status. Results: The ptxP1 allele with erythromycin resistant (ER) B. pertussis infection (total of 449 subjects) consisted of 84.70 to 96.70% from 2012 to 2016 in this study. Vaccinated with co-purified aPV was found in 133(133/403,33.0%), 1(1/9,11.1%) and 2(2/21,9.5%) in ptxP1/fhaB3-ER, ptxP1/fhaB2-ES and ptxP3/fhaB2-ES B. pertussis infected children each, which showed a significant difference (χ 2 = 6.87, P = 0.032). Conclusions: The ptxP3-ES B. pertussis was rare while the ptxP1-ER B. pertussis was steadily increased in Xi'an, China from 2012 to 2016, where co-purified aPV was prevalent used. This pose a hypothesis that the co-purified aPV might protect against ptxP3 strains more efficient, which generated a rare chance for ptxP3 strains to be under the antibiotic pressure and further developed to be erythromycin resistance. A further cohort study and the mechanisms of the additional antigen proteins of co-purified aPV protected against B. pertussis should be consideration.

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