Molecular surveillance of global infectious disease

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Surveillance is key

Infectious diseases, caused by pathogens such as bacteria, viruses, fungi or parasites, may be tackled by a number of strategies. These include vaccines to provide protection against disease and drugs to kill the infectious agent. However, interventions such as these may impact on the circulating pool of pathogens by driving evolution through natural selection, potentially removing specific sub-populations or through acquiring drug resistance. Therefore, monitoring which pathogens are circulating, and any response to prevention or treatment programmes, is essential for cost-efficient and effective delivery of new or existing vaccines and drugs.

Streptococcus pneumoniae is just one example of a bacterium that causes vaccine preventable disease. The pneumococcus is the leading cause of child pneumonia deaths and kills more than 1.6 million people each year, including between 700,000 and 1 million children under five. Vaccines are available, or in development, for preventing life-threatening pneumococcal disease, such as pneumonia, meningitis and septicaemia. A global alliance of organisations, including NGOs, charitable foundations, vaccine companies and national governments are supporting coordinated vaccine programmes in order to deliver more widely the benefits of childhood immunisation taken for granted in the developed world. However there are over 90 different serotypes of Streptococcus pneumoniae, and current multi-valent polysaccharide conjugate vaccines cover only a limited number of serotypes, mainly associated with disease in the developed world. Therefore, detecting which serotypes are circulating in the target population and monitoring changes in response to large scale vaccination programmes is critical if these efforts are to be successful.

Inside information

Pathogens have evolved many ways to cause infectious diseases, avoid the body’s natural defences and overcome interventions, such as vaccines or drugs that aim to prevent or treat disease. The record of this evolution is encoded in the DNA inside each pathogen, incorporated within the genes and mutations of the genome. By using the latest genomics technologies to determine the DNA content of the pathogen, a comprehensive and detailed analysis of the genetic information is possible. Assessing the genetic make-up of the pathogen may reveal evidence of known mechanisms, or clues to novel adaptations, associated with vaccine escape or antibiotic resistance.

Some bacteria, such as Streptococcus pneumoniae, are coated in a polysaccharide capsule whose properties are linked to virulence, immune response and hence disease. The precise structure of this polysaccharide determines the serotype of the pneumococcus, due to cross-reactivity with typing antisera. Current pneumococcal conjugate vaccines are based on the capsule polysaccharide of a limited number of serotypes, so monitoring the pneumococcal serotypes present in the population is important to assess vaccine coverage and impact. Conventional serotyping methods use staining or agglutination methods to identify the serotype by visual inspection down a microscope or by eye. Elucidating the genetic basis of capsule biosynthesis for each serotype has enabled molecular serotyping approaches to be developed, which are based on detection of the DNA content inside the pathogen. BUGS Bioscience technology detects the combination of capsule biosynthesis genes present within the pneumococcus to predict the serotype from the DNA.

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Clinical insights

Clinical samples, such as nasal swabs, typically contain a huge variety of human cells, other colonizing commensal microbes, and even different strains of the same pathogen. Analysis of DNA extracted from these highly complex mixtures can be challenging, as the pathogen DNA of interest represents only a small proportion of the total DNA present. Extracting clarity from the complexity of these samples is important, to monitor the impact of any vaccine or drug interventions on the wider microbial population and also to gain further insights into the biology underlying any changes detected in specific pathogens.

The BUGS Bioscience technology platform for molecular serotyping of Streptococcus pneumoniae combines high throughput, molecular methods and genomics technologies with advanced mathematical algorithms and cutting edge software to predict the pneumococcal serotype based on the gene content of the DNA. The combined sequence capture and specific detection, facilitated by the microarray-based method for molecular serotyping, allows highly complex samples to be successfully dissected for results of interest. This approach has enabled detection of multiple pneumococcal serotypes in samples combined with estimation of the relative abundance of each serotype present. Furthermore, our technology may also indicate potential novel serotypes, detect the presence of antibiotic resistance genes, identify co-colonizing pathogens and determine the genetic relatedness of individual samples. In numerous studies worldwide, this has proven to be a robust approach, with high sensitivity and high specificity, and suitable for application to either cultured isolates or directly on clinical samples. BUGS Bioscience has developed an integrated technology and software platform to dissect these complex genomic data and report clear, intuitive results to inform future action.

A new vision

BUGS Bioscience was created as a joint spin-out venture between St George’s, University of London and private donors with the common aim of delivering a global platform for molecular surveillance of infectious diseases. We operate as a technology start-up comprising a creative and motivated team of molecular biologists, mathematicians and software engineers. We are committed to providing organisations involved in vaccine development and roll out, both commercial and NGO, with the highest levels of customer service with the not-for-profit ethos that any surpluses are reinvested in further development of our platform.

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BUGS Bioscience combines the latest developments in molecular biology with advanced mathematics and software in order to deliver a new vision for molecular surveillance.