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Transmission of Antimicrobial Resistant Yersinia pestis During a Pneumonic Plague Outbreak
Voahangy Andrianaivoarimanana1, David M Wagner2, Dawn N Birdsell2
1Institut Pasteur de Madagascar, Antananarivo, Madagascar.
Background:
Pneumonic plague (PP), caused by Yersinia pestis, is the most feared clinical form of plague due to its rapid lethality and potential to cause outbreaks. PP outbreaks are now rare due to antimicrobial therapy.
Methods:
A PP outbreak in Madagascar involving transmission of a Y. pestis strain resistant to streptomycin, the current recommended first-line treatment in Madagascar, was retrospectively characterized using epidemiology, clinical diagnostics, molecular characterization, and animal studies.
Results:
The outbreak occurred in February 2013 in the Faratsiho district of Madagascar and involved 22 cases, including 3 untreated fatalities. The 19 other cases participated in funeral practices for the fatal cases and fully recovered after combination antimicrobial therapy: intramuscular streptomycin followed by oral co-trimoxazole. The Y. pestis strain that circulated during this outbreak is resistant to streptomycin resulting from a spontaneous point mutation in the 30S ribosomal protein S12 (rpsL) gene. This same mutation causes streptomycin resistance in 2 unrelated Y. pestis strains, one isolated from a fatal PP case in a different region of Madagascar in 1987 and another isolated from a fatal PP case in China in 1996, documenting this mutation has occurred independently at least 3 times in Y. pestis. Laboratory experiments revealed this mutation has no detectable impact on fitness or virulence, and revertants to wild-type are rare in other species containing it, suggesting Y. pestis strains containing it could persist in the environment.
Conclusions:
Unique antimicrobial resistant (AMR) strains of Y. pestis continue to arise in Madagascar and can be transmitted during PP outbreaks.
Insights
Pneumonic plague outbreaks caused by Yersinia pestis are rare due to antibiotics. A Madagascar outbreak involved a streptomycin-resistant strain, highlighting the emergence of antimicrobial resistance (AMR) in plague bacteria.
Area of Science:
- Microbiology
- Epidemiology
- Genetics
Background:
- Pneumonic plague (PP), caused by Yersinia pestis, is a severe and potentially epidemic form of plague.
- Antimicrobial therapy has significantly reduced the incidence of PP outbreaks.
Purpose of the Study:
- To characterize a Yersinia pestis outbreak in Madagascar involving a streptomycin-resistant strain.
- To investigate the genetic basis and implications of antimicrobial resistance in Yersinia pestis.
Main Methods:
- Retrospective epidemiological analysis of 22 cases in Madagascar.
- Clinical diagnostics and molecular characterization of the Yersinia pestis strain.
- Laboratory experiments to assess the fitness and virulence of the resistant strain.
Main Results:
- The outbreak involved a Yersinia pestis strain resistant to streptomycin, a first-line treatment in Madagascar.
- The resistance stemmed from a point mutation in the rpsL gene, independently occurring at least three times globally.
- This mutation showed no significant impact on bacterial fitness or virulence in laboratory studies.
Conclusions:
- Antimicrobial-resistant Yersinia pestis strains are emerging in Madagascar.
- These resistant strains can be transmitted during pneumonic plague outbreaks, posing a public health threat.
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