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News — Combining genomic data and human travel patterns in South Africa has revealed key insights into the spread, evolution, and resistance patterns of a major bacterium behind pneumonia and meningitis globally.

The approach combines a pathogen’s genomic data over 14 years with human travel patterns taken from anonymised mobile phone data during the period January 2020 to July 2021.

Researchers inferred the fitness (ability to survive and reproduce) of different pneumococcal strains using genomic data of the strains collected from both carriage and invasive disease.

Carriage data refers to asymptomatic infection while invasive disease means symptomatic infection.

The insight could inform vaccine development to target the most harmful strains and may be applicable to other pathogens.

Researchers from the University of the Witwatersrand, Johannesburg (), the National Institute for Communicable Diseases (NICD), the Wellcome Sanger Institute, the University of Cambridge, and partners across the Global Pneumococcal Sequencing project¹, integrated genomic data from nearly 7,000 Streptococcus pneumoniae(pneumococcus) strains collected in South Africa with detailed human mobility data².

This enabled researchers to see how these bacteria, which cause pneumonia and meningitis³, move between regions and evolve over time.

he findings, in Nature on 3 July, suggest that the 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.

All South African data

Co-author of the study Dr Anne von Gottberg is Associate Professor  in the , at , and joint staff at the NICD.

Von Gottberg said: “All the data are from South Africa. Our data for invasive disease were taken from the NICD’s national surveillance collaborating with multiple surveillance partners throughout the country. Carriage data were obtained from Wits VIDA studies during some years that overlapped the national surveillance. Our study used both the NICD and Wits VIDA datasets to explore carriage (asymptomatic infection) versus disease (symptomatic infection) isolates over time.”

is the Vaccines and Infectious Diseases Analytics Research Unit. , Professor of Vaccinology and Executive Director of Wits VIDA co-authored the study, for which Wits VIDA supplied carriage data.

Cebile Lekhuleni, a PhD student in the Division of Clinical Microbiology and Infectious Diseases at Wits and a researcher at the NICD, is one of the Global Pneumococcal Sequencing project partners under the leadership of Von Gottberg.

Also a co-author of the study, Lekhuleni says, "The genomic data and metadata contributed by the NICD’s national surveillance plays an important role in leveraging the power of pathogen genomics in tracking and monitoring diseases of public health concern. Through these data, collected in a systematic manner over a long period of time, we now have insights on the transmission dynamics of the pneumococcus in South Africa and supporting evidence of the fitness of important pneumococcal strains after vaccine introduction."

Why tracking pathogens matters

Many infectious diseases such as tuberculosis, HIV, and COVID-19 are caused by multiple strains or variants circulating simultaneously, making them difficult to study.

Pneumococcus, a bacterium that is a leading cause of pneumonia, meningitis, and sepsis worldwide⁴, is a prime example with over 100 types and 900 genetic strains globally. Pneumonia alone kills around 740,000 children under the age of five each year⁵, 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.

Madhi says, “The findings from this study on how the pneumococcus disseminates over time adds novel insight into the epidemiology of the pneumococcus. The recent work on pneumococcus adds to the body of knowledge on pneumococcus, of which scientists in South Africa have been at the forefront of research, dating back to the first ever studies of pneumococcal vaccines in the early 1900s. Pneumococcus remains a leading cause of death from pneumonia in children and adults, indicating the need for ongoing research on its evolution, and building on the success of current vaccines which protect against some – but not all – of the pneumococcal serotypes”.  

About the study

In the study, titled “Geographical migration and fitness dynamics of Streptococcus pneumoniae,” 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 Meta².

The team developed computational models which 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 types⁶, 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 may be short-lived.

Study finds vaccine-linked protection is short-lived and antimicrobial resistance increased

Lead author Dr Sophie Belman, a 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.”

Adapt vaccination strategies to counter rogue pathogens

Professor Stephen Bentley, senior author of the study at the Wellcome Sanger Institute, said: “The pneumococcus's 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.”

Von Gottberg concludes: “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.”

Notes: 

1. Partners from the Global Pneumococcal Sequencing project can be found here:
   
   
2. The human mobility data used in this study are Meta Data for Good baseline data, released during the 2020 SARS-CoV-2 pandemic. These data rely on personal consent for location sharing, and Data for Good ensures individual privacy by preventing re-identification in aggregated datasets.

For more information on the Movement Range Maps, access:

For more information on privacy matters, access:  

3. For more information on pneumococcal disease, visit:
   
   
4. 
   
   

Before these vaccines, 85 per cent of pneumococcal strains were those targeted by the vaccines. By 2014, this dropped to 33.2 per cent. This change was consistent across all nine provinces in South Africa. These data can be accessed here:

Publication:  Belman et al. (2024) ‘Geographic migration and vaccine-induced fitness changes of Streptococcus pneumoniae.’ Nature. DOI: 10.1038/s41586-024-07626-3

Funding: This research was supported by Wellcome, the Bill and Melinda Gates Foundation, NIH and the European Research Council. For full funding acknowledgements, please refer to the publication.