For the first time, researchers have been able to precisely quantify the ability of different pneumococcal strains to survive and reproduce, an insight that could inform vaccine development to target the most harmful strains, and may be applicable to other pathogens.
Their findings also suggest that the vaccine-linked protection against antibiotic resistance is short-lived.
The collaboration of scientists, from the University of the Witwatersrand, the National Institute for Communicable Diseases, the Wellcome Sanger Institute, the University of Cambridge and partners across the Global Pneumococcal Sequencing project, integrated genomic data from nearly 7 000 Streptococcus pneumoniae (pneumococcus) samples collected in South Africa with detailed human mobility data.
This enabled them to see how these bacteria, which cause pneumonia and meningitis, move between regions and evolve over time, reports MedicalXpress.
The findings, published in Nature, suggest initial reductions in antibiotic resistance linked to the 2009 pneumococcal vaccine may be only temporary, as non-targeted strains resistant to antibiotics such as penicillin gained a 68% competitive advantage.
Many infectious diseases, like tuberculosis, HIV and Covid-19, exist in multiple strains or variants circulating simultaneously, making them difficult to study. Pneumococcus, a bacterium that is a leading cause of pneumonia, meningitis and sepsis worldwide, is a prime example, with more than 100 types and 900 genetic strains globally.
Pneumonia alone kills around 740 000 children under five each year, making it the single largest infectious cause of death in children.
Pneumococcal diversity hampers control efforts, as vaccines targeting major strains leave room for others to fill the vacant niches.
How these bacteria spread, how vaccines affect their survival, and their resistance to antibiotics, remains poorly understood.
In this latest study, the researchers analysed genome sequences from 6 910 pneumococcus samples collected in South Africa between 2000 and 2014 to track the distribution of different strains over time. They combined these data with anonymised records of human travel patterns collected by Meta.
The team developed computational models that revealed pneumococcal strains take around 50 years to fully mix throughout South Africa’s population, largely due to localised human movement patterns.
They found that while introduction of a pneumococcal vaccine against certain types of these bacteria in 2009 reduced the number of cases caused by those types, it also made other non-targeted strains of these bacteria gain a 68% competitive advantage, with an increasing proportion of them becoming resistant to antibiotics such as penicillin.
This suggests that the vaccine-linked protection against antibiotic resistance is short-lived.
Dr Sophie Belman, first author of the study, former PhD student at the Wellcome Sanger Institute and now a Schmidt Science Fellow at the Barcelona Supercomputing Centre, Spain, said: “While we found that pneumococcal bacteria generally spread slowly, the use of vaccines and antimicrobials can quickly and significantly change these dynamics. Our models could be applied to other regions and pathogens to better understand and predict pathogen spread, in the context of drug resistance and vaccine effectiveness.”
Dr Anne von Gottberg, author of the study, at NICD, said: “Despite vaccination efforts, pneumonia remains one of the leading causes of death for children under five in South Africa. With continuous genomic surveillance and adaptable vaccination strategies to counter the remarkable adaptability of these pathogens, we may be able to better target interventions to limit the burden of disease.”
Professor Stephen Bentley, senior author of the study at the Wellcome Sanger Institute, said: “The pneumococcus' diversity has obscured our view on how any given strain spreads from one region to the next. This integrated approach using bacterial genome and human travel data finally allows us to cut through that complexity, uncovering hidden migratory paths in high-definition for the first time.
“This could allow researchers to anticipate where emerging high-risk strains may take hold next, putting us a step ahead of potential outbreaks.”
Study details
Geographic migration and fitness dynamics of Streptococcus pneumonia
Sophie Belman, Noémie Lefrancq, Shabir Madhi, Anne von Gottberg,
et al.
Published in Nature on 3 July 2024
Abstract
Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.
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