Emergence of macrolide-resistant Bordetella pertussis in France, 2024: out of China
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Objectives
Pertussis is a highly contagious, potentially fatal vaccine-preventable respiratory disease, primarily caused by Bordetella pertussis ( Bp ). Macrolides constitute the first-line treatment for pertussis, reducing bacterial carriage and transmission. Despite consistent surveillance, only one resistant isolate had ever been reported in France before 2024 (in 2011). Here, we report 14 macrolide-resistant Bp (MRBP) cases, collected in France between February and November 2024, during the largest whooping cough outbreak of the last 20 years. We aimed to investigate whether these MRBP arose from macrolide-susceptible Bp (MSBP) in France or were instead imported.
Methods
Illumina sequencing was performed for all French isolates from 2024 and in addition, long-read sequencing was performed for the MRBP isolates. We compared the 14 MRBP genomic sequences with 1,571 macrolide-susceptible cultivated B. pertussis isolates collected in France (1993-2024, including 331 from 2024), the MRBP isolate from 2011, and 824 Bp collected in China (2018-2024), including 596 MRBP (75.2%).
Results
Phylogenetic analysis based on whole-genome single nucleotide polymorphisms revealed that the French MRBP belong to three separate branches nested within the diversity of MRBP isolates from China, suggesting three independent introductions into France. Two of these branches comprised more than one isolate, detected across several French administrative regions, indicating forward transmission and spatial dissemination. The MRBP isolates from France and China belonged to a single clade of the ptxP 3 lineage corresponding to the previous genotype denomination MT28.
Conclusion
The rise of MRBP in France is driven by importation followed by local dissemination. This exceptional emergence is concerning, given the high expected fitness of PRN-negative ptxP3 MRBP isolates in acellular vaccination countries. Besides vaccination, effective control of MRBP will require enhanced surveillance, strict adherence to transmission control guidelines, and prudent use of macrolides to avoid selective pressure favouring MRBP.
