Cai Jiehao, Liu Qiyi, Chen Biquan, Jiang Yue, Zeng Xiaoyan, Huang Jiebin, Lin Daojiong, Li Huanyou, Zhang Jinqiang, Zhuo Zhiqiang, Zhang Yanping, Lv Panpan, Wang Qiang, Zhang Wenhong, Chen Mingliang, Zeng Mei
Department of Infectious Diseases, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, PR China.
Department of Infectious Diseases, Anhui Children's Hospital, Anhui, PR China.
Lancet Reg Health West Pac. 2025 Jul 4;60:101628. doi: 10.1016/j.lanwpc.2025.101628. eCollection 2025 Jul.
In the spring and summer of 2024, an unexpected large outbreak of pertussis hit China, with the annual incidence of pertussis (34.03/100,000) more than 12-fold higher than that of 2023 (2.71/100,000). We aimed to assess clinical and molecular epidemiological patterns and unravel the reasons behind the 2024 pertussis outbreak.
PCR-confirmed pertussis cases were enrolled from five sentinel hospitals in Shanghai, Anhui, Hainan, Fujian, and Inner Mongolia between 1 January and 30 September 2024. The epidemiological data of PCR-confirmed cases, as well as the clinical data and vaccination history of hospitalized cases were collected. Nasopharyngeal swab samples were collected from partial pertussis cases and their household contacts for culture during the local peak months. Antimicrobial susceptibility testing and whole genome sequencing were performed on all 394 isolates to evaluate six antibiotic susceptibility and characterize the antigenic, virulent, and phylogenetic characteristics of the circulating isolates.
A total of 14,874 cases of pertussis were PCR-confirmed in the 5 sentinel hospitals, peaking in April to July. Infants represented 9.6% of cases and children aged 4-10 years represented 74.3% of cases in the five hospitals. Of the 7238 (48.7%) cases with vaccination data, 6563 (90.7%) were fully vaccinated. Breakthrough pertussis cases were mainly observed in fully vaccinated children since the age of 7 months. Among the 828 (5.6%) cases hospitalized for pertussis, 71.7% (594/828) cases had complications (pneumonia 69.7%, 577/828), 5.7% (47/828) were admitted to intensive care unit and 0.24% (2/828) cases died. Sixty-four per cent (403/630) of families had both the patient and at least one family member PCR-positive for . In total, 394 isolates were recovered from the 1921 nasopharyngeal swab samples. Ninety-nine point seven per cent (393/394) of isolates displayed high-level resistance to azithromycin (MIC range, 16-256 μg/ml), and 48.0% (189/394) isolates were susceptible to trimethoprim-sulfamethoxazole (MIC range, <0.008/0.152-0.5/9.5 μg/ml). All the isolates were susceptible to levofloxacin, doxycycline, ceftazidime, and cefoperazone/sulbactam. All the isolates were assigned to ST-2 and 99.5% (392/394) belonged to the MT28-Shanghai clone by SNP-based analysis, carrying AgST4, 23S rRNA-13 (with erythromycin resistance), and 150. 23.4% (92/394) of isolates were predicted to be PRN-deficient.
The waning vaccine-derived protection and the prevailing macrolide-resistant MT28 clone harboring non-vaccine type are responsible for the 2024 large outbreak of pertussis in China. Our findings highlight the urgent need for revising national pertussis vaccination strategies and traditional first-line antibiotic therapy. Booster vaccination for children aged 4-6 years is urgent to control the pertussis outbreak.
This work is supported by Shanghai Municipal Sixth Round Three-Year Action Plan for Strengthening the Construction of the Public Health System (GWVI-11.1-07, GWVI-2.1.2) and National Natural Science Foundation of China (82272381).
2024年春夏，中国意外出现百日咳大暴发，百日咳年发病率（34.03/10万）比2023年（2.71/10万）高出12倍多。我们旨在评估临床和分子流行病学模式，并揭示2024年百日咳暴发的原因。
2024年1月1日至9月30日期间，从上海、安徽、海南、福建和内蒙古的五家哨点医院纳入PCR确诊的百日咳病例。收集PCR确诊病例的流行病学数据以及住院病例的临床数据和疫苗接种史。在当地发病高峰月份，从部分百日咳病例及其家庭接触者中采集鼻咽拭子样本进行培养。对所有394株分离株进行药敏试验和全基因组测序，以评估六种抗生素敏感性，并鉴定流行株的抗原性、毒力和系统发育特征。
五家哨点医院共PCR确诊14874例百日咳病例，4月至7月达到高峰。婴儿占病例的9.6%，4至10岁儿童占病例的74.3%。在有疫苗接种数据的7238例（48.7%）病例中，6563例（90.7%）已全程接种疫苗。突破性百日咳病例主要见于7个月及以上的全程接种疫苗儿童。在828例（5.6%）因百日咳住院的病例中，71.7%（594/828）有并发症（肺炎69.7%，577/828），5.7%（47/828）入住重症监护病房，0.24%（2/828）死亡。64%（403/630）的家庭中患者及其至少一名家庭成员PCR检测呈阳性。从1921份鼻咽拭子样本中共分离出394株菌株。99.7%（393/394）的菌株对阿奇霉素表现出高水平耐药（MIC范围为16 - 256μg/ml），48.0%（189/394）的菌株对复方磺胺甲恶唑敏感（MIC范围为<0.008/0.152 - 0.5/9.5μg/ml）。所有菌株对左氧氟沙星、多西环素、头孢他啶和头孢哌酮/舒巴坦敏感。通过基于单核苷酸多态性的分析，所有菌株均归为ST-2型，9 ninety-nine point five%（392/394）属于MT28 - 上海克隆，携带AgST4、23S rRNA - 13（具有红霉素耐药性）和150。23.4%（92/394）的菌株预测为PRN缺陷型。
疫苗衍生保护作用减弱以及流行的携带非疫苗型的大环内酯耐药MT28克隆是2024年中国百日咳大暴发的原因。我们的研究结果凸显了修订国家百日咳疫苗接种策略和传统一线抗生素治疗方法的迫切需求。对4至6岁儿童进行加强免疫接种对于控制百日咳暴发至关重要。
本研究得到上海市第六轮加强公共卫生体系建设三年行动计划（GWVI - 11.1 - 07，GWVI - 2.1.2）和国家自然科学基金（82272381）的支持。
