Rapid Detection of Pandemics

A Coronavirus — like severe acute respiratory syndrome (SARS) — is back in the headlines. On returning from a trip to Saudi Arabia in summer 2012, a Qatari national was struck down by a mystery respiratory illness. Because of inadequate diagnostic capabilities, the patient was transferred from Qatar to London for intensive-care treatment and diagnosis. The UK Health Protection Agency (HPA) confirmed infection with the same Coronavirus strain discovered by a Dutch team following the death of a Saudi national earlier in 2012. Further investigations have confirmed nine cases by laboratory analysis, with five fatalities, all originating in Jordan, Qatar, and Saudi Arabia between April and October 2012 (1).

SARS first became known to the world in late 2002 and quickly spread from south China through Asia and North America. Ultimately it affected >8,000 people, with ∼800 related deaths. Are health authorities now better prepared to deal with the emergence and diagnosis of new infectious diseases? The answer is a cautious yes.

Identifying the Unknown

Since 2003, the field of molecular diagnostics has encompassed new technological developments. Although laboratory diagnostic capabilities have greatly improved, point-of-care diagnostics are more hit-and-miss. Correct diagnosis early on (when a patient first presents to a doctor or emergency room) is critical to managing the spread of disease.

Soon after the Qatari patient arrived in London, the HPA published a partial genomic sequence of the new Coronavirus variant, revealing that it is related to a virus associated with bats (unlike SARS, which is thought to have originated in civet cats). For now, health authorities are downplaying fears due to the disease’s low incidence and transmission among humans.

The speed of that genome-sequencing work underlines both the improved technical capabilities of existing DNA sequencing instruments since 2003 and a dramatic fall in the price of sequencing (outstripping Moore’s law). According to 2011 research at the National Human Genome Research Institute, the cost of sequencing 1,000,000 base pairs has fallen from ∼US$10,000 in 2001 to ∼$0.10 in 2012 (2). Such rapid progress in establishing a clinical molecular test will greatly help with future identification of affected individuals. And that will go some way toward developing faster point-of-care tests.

In the past decade, rapid advances were made in genome-sequencing technology, the “gold dash; standard” of identifying emerging biological threats. But for point-of-care or first-responder testing, progress is mixed. Despite advances in biosensing, many field identification instruments are based on technologies from 10 years ago — e.g., immunochemical techniques and polymerase chain reaction (PCR). Advances in such techniques have brought only modest improvements in performance or cost.

Few dedicated devices are commercially available for rapid, direct detection of Coronaviruses, probably because the SARS outbreak was relatively short-lived. Biofire Diagnostics released a respiratory pathogen panel for its FilmArray device that identifies SARS-like Coronavirus targets by targeting RNA-dependent polymerase or nucleoprotein genes. The respiratory panel includes tests for HKU1, NL63, 229E, and OC43 variants of Coronavirus, with a claimed sensitivity of 4–600 viruses/mL. The bench-top device uses nested multiplex PCR, reducing the reaction from a typical 30–40 cycles to 10–20 for a total hands-on time of four minutes and automatic processing of several sample types.

The HPA has very quickly analyzed the new viral genome, publishing a partial sequence in September (along with preliminary diagnostic PCR advice) followed by a full sequence in November indicating that assays for 229E and NL63 would not detect the new virus but that other previously developed pan-Coronavirus PCR primers “should work” (3, 4). Jordanian cases were identified only retrospectively by applying the HPA-developed assay to stored samples after the original Coronavirus-specific assays failed to identify the pathogen.

Biofire Diagnostics also makes RAZOR EX portable PCR instruments for first responders and the Joint Biological Agent Identification System (JBAIDS) fielded by the US military. So that company could incorporate new technology into portable instruments. Similar integrated laboratory diagnostic instruments include 3M’s Integrated Cycler and Cepheid’s GeneXpert systems. Neither yet offers an FDA-approved Coronavirus-identification panel. Only the FilmArray and Integrated Cycler systems fulfill the Edgewood Chemical and Biological Center’s criteria for use in a mobile setting (5), given their compact size, but the latter’s frozen reagents significantly reduce its utility outside laboratories.

The next major disease outbreak or pandemic will be a new and unknown disease. Thanks to phenomenal advances in nucleic-acid sequencing technology, the nature that disease will be identified quickly. But it is less certain how healthcare systems will perform without targeted infectious-disease screening tools that are suitable for use at the point of care. The Star Trek–style universal “Tricorder” demanded by the first-responder community is still some way from becoming a reality.

About the Author

Author Details
Dr. Andrew S. Thompson is a senior analyst covering in vitro diagnostics at GlobalData, 40-42 Hatton Garden, London, EC1N 8EB United Kingdom.

REFERENCES

1.) WHO Novel Coronavirus Update, 30 November 2012; www.who.int/csr/don/2012_11_30/en/index.html .

2.) DNA Sequencing Costs, National Human Genome Research Institute.

3.) Press release, September 2012; http://crofsblogs.typepad.com/h5n1/2012/09/hpa-partial-genetic-sequence-information-for-scientists-about-the-novel-coronavirus-2012.html .

4.) HPA Genetic Sequence Information for Scientists About the Novel Coronavirus.

5.) Emanuel, P, and M Caples. 2011. Chemical, Biological, Radiological Technology Survey.