Panton-Valentine Leukocidin–Encoding MRSA Outbreak in the Netherlands, 2023–2024

PVL-positive isolates of this CC398 lineage are increasingly observed in humans without livestock exposure and can harbor virulence determinants that may facilitate human-to-human spread.

• Investigation scope and setting:
• The report documents a community outbreak of Panton-Valentine leukocidin (PVL)–positive methicillin-resistant Staphylococcus aureus (MRSA) in the Netherlands, occurring from November 2023 through June 2024.
• The identified source of transmission was a massage center within the community, with transmission traced to both patients and environmental surfaces at the site.
• The investigation employed enhanced genomic surveillance, including whole-genome sequencing (WGS), to differentiate outbreak-related MRSA isolates and to characterize their relationships to previously reported strains.
• Public health framing and significance:
• The study highlights the importance of genomic surveillance to distinguish PVL-positive MRSA within the broader spectrum of CC398 lineages, a clonal complex sometimes described as livestock-associated MRSA.
• The outbreak underscores the emergence and potential community-based transmission of PVL-positive CC398 MRSA strains, reinforcing the need for rapid source tracing and tailored outbreak management in community settings.

A previously unknown employee tested positive on the fourth visit; this employee was removed from work and pursued MRSA eradication therapy, returning to work only after three consecutive negative tests.

• Case ascertainment and laboratory confirmation:
• Regional Public Health Service (PHS) was alerted by a microbiology hospital laboratory to a putative PVL-positive CC398 MRSA cluster in November 2023.
• Early cases were characterized by MRSA-positive abscesses requiring surgical drainage; five cases had this presentation within the first three weeks.
• Isolates underwent typing by multilocus variable-number tandem-repeat analysis (MLVA), yielding type MT2306 within complex MC0398, a configuration previously rarely seen.
• Surveillance incorporated enhanced genomic approaches, notably WGS, to resolve whether isolates represented a single clonal outbreak.
• Epidemiologic investigation and exposure assessment:
• The PHS conducted interviews with early cases to identify potential infection sources and contacts, guiding the search for a plausible center of transmission.
• A massage center emerged as the putative source location after initial interviewing and tracing.
• The PHS conducted serial site visits to the massage center (five visits), with screening of center employees across time points.
• Environmental sampling was performed on three occasions and yielded positive results in multiple samples.
• Microbiological workflow and surveillance outputs:
• Mechanisms for MRSA detection included screening for mecA/mecC genes via real-time PCR.
• An enrichment approach was used to culture nasal, throat, and rectal specimens.
• Environmental sampling leveraged two methods: gauze wipes with enrichment broth and PL agar contact plates, with both processing steps incorporating enrichment and subsequent testing.
• WGS analysis of the first 17 human isolates, the employee’s isolate, and environmental isolates was performed, with genomic relatedness evaluated via whole-genome MLST, applying a 15-allele difference cutoff.

The remaining three cases did not cooperate in source/contact investigation, but the outbreak was still included due to geographic and microbiologic linkage.

• Case demographics and clinical presentation:
• A total of 31 MRSA PVL-positive cases were identified during November 2023–June 2024.
• The median age was 42 years, with a range spanning from 3 to 69 years; nearly all cases were adults (only one case under 18).
• Sex distribution: 42% female, 58% male.
• Clinical presentation: the majority of cases experienced mild skin infections or abscesses; 27 of the 31 were symptomatic, 3 were asymptomatic, and 1 was of unknown status.
• Immune status: among the cases with available data, most were not immunocompromised; one case had type 2 diabetes mellitus; immune-status data were not available for all patients.
• Exposure pattern and transmission dynamics:
• A significant proportion of cases (22 of 31) reported visiting the massage center, supporting a link between the center and transmission.
• A subset (6 cases) did not report visiting the center; among these, one was a secondary case with household contact to a center-associated case.
• The distribution of cases underscores a clustered transmission pattern consistent with a point-source environment subsequently enabling human-to-human spread.

The primary emphasis of the report, however, centers on PVL status, clonal lineage, and transmission dynamics rather than a comprehensive resistance phenotype summary.

• Isolate lineage and clonal relationships:
• All MRSA isolates from the outbreak clustered as MLVA MT2306 within complex MC0398, a lineage aligned with CC398.
• WGS assigned these outbreak isolates to MLST ST1232 and Ridom core genome MLST complex type 35023.
• Within the genomic relatedness framework, the isolates differed by 0–12 alleles (mean 1 allele) on the core genome MLST comparison, supporting a single, tightly related outbreak cluster.
• Environmental isolates clustered with the human isolates, displaying only a 1-allele difference from human isolates, reinforcing environmental contamination as part of the outbreak milieu.
• Distinctions from a PVL-negative MC0398-MT2306 baseline strain from 2019 and from other historical isolates exceeded 200 alleles, indicating a distinct circulating PVL-positive cluster in this event.
• PVL status and comparative context:
• The outbreak centered on PVL-positive MRSA within a CC398-associated lineage, distinguishing it from prior PVL-negative CC398 records in this clade.
• Comparisons with international PVL-positive CC398 isolates and with a contemporaneous PVL-negative pig-associated lineage demonstrated substantial genomic divergence, supporting the interpretation of a distinct outbreak strain with PVL positivity rather than incidental importation of PVL-negative relatives.
• Antimicrobial resistance profile:
• The study included an assessment of antimicrobial resistance across the isolates, with data presented in supplementary tables (not reproduced here).

• Outbreak response architecture:
• Following initial notification, the region formed an outbreak management team comprising clinicians, infection prevention professionals from both the public health service and hospital settings, microbiologists, and communication specialists.
• The public health plan included guidance to general practitioners to culture non-responsive skin lesions to standard first-line therapy, thereby enabling earlier identification of additional cases.
• A public health alert disseminated via national surveillance channels and through an online European platform (EpiPulse) to alert other authorities and clinical laboratories.
• Source control and containment measures:
• Symptomatic and exposed contacts, including asymptomatic household contacts and those in occupations with close contact or physical touch (e.g., masseurs, skin therapists), were advised to undergo MRSA testing.
• All case-patients were advised to complete MRSA eradication therapy after lesion healing to mitigate reintroduction risk from the source setting.
• An infection prevention expert provided guidance to the massage center staff on MRSA transmission and hygiene practices.
• The massage center underwent thorough disinfection, led by a professional disinfection company in week 5 of the outbreak, with the removal of non-disinfectable items (e.g., fabric-covered tissue boxes and fabric decorations) recommended to reduce reservoir risk.
• Environmental and operational challenges:
• The setting posed unique management challenges typical of community outbreaks linked to small service settings, where privacy concerns limit comprehensive client screening and where environmental contamination contributes to ongoing transmission risk.
• The combination of confirmed human-to-human transmission and detectable viable MRSA on surfaces at the source reinforced the role of the environment in sustaining transmission dynamics and highlighted the necessity of multifaceted control measures.

• Temporal and geographic scope:
• The outbreak was confined to a defined period (November 2023–June 2024) and to a regional public health jurisdiction with participation from multiple stakeholders, including hospital laboratories, public health authorities, and a private service facility.
• Data completeness and uncertainties:
• Some patients had incomplete exposure data (e.g., three individuals with unknown exposure status or incomplete partner investigations), limiting full reconstruction of the transmission network.
• Immune status was not uniformly documented across all cases.
• Privacy constraints limited universal client screening at the massage center, constraining a complete accounting of all potential exposures within the facility.
• Genomic inference considerations:
• The genomic analyses utilized stringent allele-based relatedness thresholds (≤15 alleles difference as a criterion for clustering) and demonstrated minimal allelic variation within the cluster, reinforcing a single-source outbreak hypothesis.
• Comparisons with historical and international sequences provided a broader phylogenetic context, reinforcing the distinctiveness of the PVL-positive CC398 outbreak strain relative to prior PVL-negative CC398 isolates and to other PVL-positive MRSA strains.

• Surveillance implications:
• The outbreak underscores the feasibility and utility of whole-genome sequencing in outbreak investigations involving MRSA, particularly for delineating PVL-positive CC398 lineages within community settings.
• The authors emphasize heightened awareness of PVL-positive CC398 MRSA in community contexts and advocate for rapid genomic surveillance to distinguish strains and guide public health actions.
• Public health and infection prevention implications:
• The combination of patient lesions, environmental contamination, and a perturbed outbreak environment calls for integrated approaches combining clinical management, host-pathogen surveillance, and environmental hygiene measures.
• The case demonstrates how targeted interventions—screening of service-site staff, environmental remediation, and coordinated communication—can be employed to interrupt transmission chains in community facilities.
• Limitations in the evidence base:
• While the outbreak’s transmission linkage to the massage center is strongly supported, not all cases could be traced exhaustively due to privacy and participation constraints.
• The report centers on descriptive epidemiology and genomic clustering; it does not present quantitative estimates such as attack rates or comparative risk metrics that would require additional data.
• Open questions for future inquiry:
• What is the prevalence and regional distribution of PVL-positive CC398 MRSA in community settings beyond this outbreak, and what environmental reservoirs sustain transmission?
• Are there identifiable behavioral or procedural factors within massage or wellness centers that elevate risk for PVL-positive MRSA transmission, and how might targeted interventions reduce such risk?
• How does PVL positivity influence transmission dynamics in community settings compared with PVL-negative CC398 MRSA, and what are the implications for infection control policies?

• Data sharing and repository:
• All whole-genome sequencing data related to this outbreak has been deposited in the National Center for Biotechnology Information (NCBI) under BioProject PRJNA1254972, enabling access for further comparative analyses and verification.

The outbreak involved 31 cases, predominantly adults with mild skin infections, and demonstrated human-to-human transmission with corroborating environmental contamination at the source location.

Genomic analyses showed a tightly clustered outbreak strain across human and environmental isolates, distinguishing it from PVL-negative CC398 and from international PVL-positive MRSA strains.

Public health actions included an outbreak management team, targeted screening of exposed individuals, MRSA eradication strategies for cases, and comprehensive environmental disinfection of the source site.

The investigation illustrates the value of enhanced genomic surveillance in differentiating PVL-positive CC398 MRSA outbreaks in community settings and informs future preparedness for similar community-linked MRSA events.

Limitations include incomplete exposure data for some cases and privacy-driven constraints on exhaustive client screening.

• The Netherlands experienced a community outbreak of PVL-positive MRSA within the CC398 clade (MLST ST1232, Ridom cgMLST complex type 35023) from November 2023 to June 2024, with a massage center identified as the source.