NTDs disproportionately affect people in tropical and sub-tropical regions.
While large-scale whole genome sequencing has the potential to grow our knowledge about NTD biology and inform control efforts, for most of these diseases, we still lack real-world proof-of-principle studies to demonstrate how genomic data can add value to existing control efforts. The global genomic surveillance of SARS-CoV-2 seen during the pandemic may now help to provide impetus to undertake such studies. Awareness of the potential benefits of large-scale genomic surveillance is now far greater among funders and policymakers, which can be capitalised upon to boost the genomics of NTDs.
More attention and money will certainly help, but there are many other challenges to be overcome if NTD genomics is to catch up with better-studied pathogens. Both Mat and Stephen highlight access to samples as a primary challenge for the field. Access is hampered by a lack of active surveillance or collection of samples as part of existing clinical studies or public health campaigns. It is also restricted by the difficulties in recovering DNA from samples to sequence. For Yaws, swabs of skin lesions yield low levels of DNA for sequencing, and that which is present is a mixture of DNA from humans and a whole range of skin-dwelling microbes, meaning that less than 1 per cent of it comes from Treponema pallidum. Mat and his colleagues use a special technique to ‘enrich’ Treponema DNA, however, this technique is expensive and difficult to perform, requiring specialist expertise and equipment not found in most sequencing laboratories. The picture is similar for soil-transmitted helminths, whose eggs are sampled from faeces which is densely packed with other microbes, while the eggs can be tough to crack open to access the DNA. Furthermore, people are often infected with more than one species of helminth, so obtaining sufficient DNA can be challenging.
In addition, there are often legal and regulatory issues that can complicate genomic surveillance efforts. International agreements about sharing of samples between countries, such as the Nagoya Protocol, are quite rightly in place to ensure equitable sharing of benefits arising from the use of genetic resources and support the conservation of biodiversity. However, such agreements also add a degree of complexity that can delay or prevent vital infectious disease research. Increasing sequencing capacity in endemic countries can help to address this issue, although, at present, limitations in terms of facilities, adequate reagent supply chains and expertise in genomics and bioinformatics often make it more cost-effective to sequence at institutes like Sanger, despite the additional logistical challenges associated with transporting samples around the world.
Stopping the neglect
Supporting partners in establishing or expanding their sequencing capacity and helping to train a new generation of genomic scientists and bioinformaticians is going to be key to using these technologies to tackle NTDs. However, the market forces that have led these diseases to be neglected up to now are not simply going to evaporate overnight. As such, perhaps it is worth reframing the building of genomic capabilities in the NTD field as part of the insurance policy that wealthy nations now realise must be invested in to prepare for, and prevent, the catastrophic impact of future global pandemics. Adoption of genomics proliferated during COVID-19 and building on this by further training and resourcing scientists to be capable of ongoing genomic surveillance of endemic neglected diseases will not only benefit efforts to study and control those diseases, but will provide a highly trained workforce that could be rapidly redeployed to track and study future emerging pandemic threats as part of a resilient healthcare system.
With continued hard work and commitment by individuals and organisations worldwide committed to NTD control, and a bit of luck, some of these diseases will hopefully not only stop being neglected but rather become eliminated as a public health problem in the coming years. Genomics will have an important role in realising this vision.