Abstract
Shigella spp. are the leading bacterial cause of severe childhood diarrhoea in low- and middle-income countries (LMICs), are increasingly antimicrobial resistant and have no widely available licenced vaccine. We performed genomic analyses of 1,246 systematically collected shigellae sampled from seven countries in sub-Saharan Africa and South Asia as part of the Global Enteric Multicenter Study (GEMS) between 2007 and 2011, to inform control and identify factors that could limit the effectiveness of current approaches. Through contemporaneous comparison among major subgroups, we found that S. sonnei contributes ≥6-fold more disease than other Shigella species relative to its genomic diversity, and highlight existing diversity and adaptative capacity among S. flexneri that may generate vaccine escape variants in <6 months. Furthermore, we show convergent evolution of resistance against ciprofloxacin, the current WHO-recommended antimicrobial for the treatment of shigellosis, among Shigella isolates. This demonstrates the urgent need to integrate existing genomic diversity into vaccine and treatment plans for Shigella, providing a framework for the focused application of comparative genomics to guide vaccine development, and the optimization of control and prevention strategies for other pathogens relevant to public health policy considerations.
Highlights
Shigella spp. are the leading bacterial cause of severe childhood diarrhoea in low- and middle-income countries (LMICs), are increasingly antimicrobial resistant and have no widely available licenced vaccine
The high level of reduced susceptibility, together with marked convergent evolution towards resistance, suggests that management of shigellosis with fluroquinolones at these sites may soon be ineffective and regional antimicrobial treatment guidelines may require updating. These results indicate the value of antimicrobial resistance (AMR) and genomic surveillance in LMICs for the control and management of shigellosis, and will be improved by initiatives such as the Africa Pathogen Genomics Initiative[51] and the World Health Organization (WHO) Global Antimicrobial Resistance Surveillance System[52]
The genomic diversity in Shigella presents a major hurdle in controlling the disease and we have demonstrated the anticipated pitfalls of current vaccination approaches, emphasizing the importance of considering the local and global diversity of the pathogens in vaccine design and implementation
Summary
Single (gyrA S83A) Single (gyrA S83L) Single (gyrA D87G) Single (gyrA D87N) Single (gyrA D87Y). To examine AMR prevalence among GEMS isolates for evaluating treatment recommendations, we screened for known genetic determinants (horizontally acquired genes and point mutations) conferring resistance or reduced susceptibility to antimicrobials. The high level of reduced susceptibility, together with marked convergent evolution towards resistance, suggests that management of shigellosis with fluroquinolones at these sites may soon be ineffective and regional antimicrobial treatment guidelines may require updating. These results indicate the value of AMR and genomic surveillance in LMICs for the control and management of shigellosis, and will be improved by initiatives such as the Africa Pathogen Genomics Initiative[51] and the WHO Global Antimicrobial Resistance Surveillance System[52]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
