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Pneumococcus Evolution, Spread Profiled With Genome Sequences, Mobile Phone Data

Streptococcus pneumoniae

NEW YORK – New research suggests vaccination has affected the spread and antimicrobial resistance features found in pneumonia- and meningitis-causing strains of Streptococcus pneumoniae (pneumococcus) in South Africa — patterns that investigators from the UK, Spain, and South Africa parsed using a combination of bacterial genomic and human mobility data.

"When a pathogen strain emerges in a specific location, it's crucial to understand where it might spread next and how its fitness — such as drug resistance or targeting by a vaccine — will affect this spread," first author Sophie Belman, a parasite and microbe researcher who was a Ph.D. student at the Wellcome Sanger Institute, said in an email.

As they reported in Nature on Wednesday, Belman and her colleagues performed whole-genome sequencing on 6,910 S. pneumoniae isolates collected from individuals in nine South African provinces during more than a decade, from 2000 to 2014, including isolates collected from 1,850 asymptomatic carriers and 5,060 individuals with invasive pneumococcal disease.

"Despite vaccination efforts, pneumonia remains one of the leading causes of death for children under five in South Africa," coauthor Anne von Gottberg, a clinical microbiology and infectious diseases researcher at the University of Witwatersrand, South Africa's National Institute for Communicable Diseases, and the University of Cape Town, said in a statement.

"With continuous genomic surveillance and adaptable vaccination strategies to counter the remarkable adaptability of these pathogens," von Gottberg added, "we may be able to better target interventions to limit the burden of disease."

Past studies have uncovered more than 1,000 strains of S. pneumoniae, falling in around 100 bacterial serotypes, the authors explained, including strains that have penicillin-resistance features and ones that don't, as well as strains that may or may not be targeted by existing vaccines.

The team noted that the current study was designed to overcome complexity related to the high genetic diversity known to exist in S. pneumoniae, coupled with the bug's ability to be carried by individuals who do not show symptoms of infection.

"This integrated approach using genomics and human mobility patterns allows us to cut through the massive diversity and actually get a clear view of the patterns of its ongoing spread," Belman, who is now at the Barcelona Supercomputing Center, said. "Ultimately, this could allow researchers to anticipate where emerging high-risk strains may take hold next, putting us a step ahead of potential outbreaks."

Together with human travel patterns gleaned from anonymized mobile phone records and social media data, the microbial sequence data made it possible to retrace the bug's transmission and evolution patterns and gauge the fitness effects of vaccines that target specific S. pneumoniae serotypes.

The team's analyses suggested that the bacterial serotypes not targeted by vaccines used in South Africa showed enhanced fitness and spread during the study time period. Those non-vaccine types were also more prone to developing penicillin resistance than the slower-spreading pneumococcus targeted by the vaccines.

"[I]n the years following vaccine implementation, the relative fitness of [non-vaccine type strains] compared with [vaccine type] strain increased … with an increasing proportion of these non-vaccine type] strains becoming resistant to penicillin," the authors reported. "Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient."