While there is debate and discussion about how genomics will be used in public health at a personalized medicine level, it is clear that rapid high-troughput DNA sequencing has immediate utility in epidemiological applications that seek to understand the origins of disease outbreaks.
In the most recent application, published this month, researchers at Pacific Biosciences (PacBio) used their PacBio RS sequencing system to identify the origins of the cholera outbreak in Haiti. According to the article, cholera as been present in Latin America since 1991, but is had not been epidemic in Haiti for at least 100 years. When the recent outbreak began in October this year, it was important to determine the origins of the disease, especially since it was concluded that Haiti had a low cholera risk following the earthquake. Understanding the origins of a disease can help define virulence and resistance mechanisms to guide therapeutic approaches.
Sequencing organisms to discover their origins in outbreaks is not new. What is new is the speed at which this can be done. For example, it took two months for the SARS virus to be sequenced after the epidemic started. In the recent work, the sequencing was completed in four days. And, it was not just one isolate that was sequenced, but two, with 40 times larger genomes.
When the Haiti sequences were compared to the sequences of 23 other V. cholera strains, the data indicated that the Haiti strain matched strains from South Asia more closely than the endemic strains from Latin America. This finding tells us that the stain was likely introduced, perhaps by aid workers. Additional sequence analysis of the colera toxin genes also confirmed that the strain causing the epidemic produces more severe disease. From a public health perspective this is important because the less virulent, easier to treat, endemic stains can be displaced by more aggressive strains. The good news is that the new strain is sensitive to tetracycline, a first line antibiotic.
The above work clearly demonstrates how powerful DNA sequencing is in strain identification. The authors favored single molecule sequencing on PacBio because its cycle time is shorter than second generation technologies like Illumina, SOLiD, and 454 and its long read lengths better handle repeats.While these points may be argued by the respective instrument vendors, it is clear is that we are entering an era where we can go very quickly from isolating infectious agents to classifying them at very high resolution in unprecedented ways. DNA sequencing will have a significant role in diagnosing infectious agents.
Further reading:
Scientists Trace Origin of Recent Cholera Epidemic in Haiti, HHMI News
The Origin of the Haitian Cholera Outbreak Strain, NEJM 2010
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