Lots of things make us sick. Right now, many of us are concerned about getting infected with pandemic flu. How do we know if this has happened? There are four basic approaches.
1. Rapid Tests.
These tests probe viral proteins for influenza signals.
- Fast. You can have an answer within 30 minutes.
- Easy to use. Very little training is necessary.
- Cheap. About $20.
- Can tell you if you have Flu A or Flu B.
- Can’t tell you which subtype of influenza A you have, ie, whether you have seasonal flu or pandemic flu.
- Fails to detect pandemic flu infection 50% of the time.
Given that the vast majority of Flu A cases are currently due to pandemic flu, someone with a positive result with a Flu A rapid test is almost certainly infected with pandemic flu. However, even if you have a negative result, you may be infected with pandemic flu. A negative result on a Flu A test is not a good reason to deny a patient antiviral treatment.
2. Real-time PCR (RT-PCR).
This assay uses nucleotide probes to examine the genetic material of the virus.
- Specific. This method can be used to determine subtype, ie, whether you have been infected with seasonal or pandemic flu.
- Sensitive. This method can detect very small amounts of virus and has been specifically designed to identify pandemic flu infections.
- Takes 24-72 hours to produce a result in most cases.
- Requires a high level of skill to set up the assay.
- Can be expensive if done manually.
- Can give false negatives if the virus develops mutations in the same regions the probes are directed towards.
RT-PCR is the most practical way to determine whether someone actually has pandemic flu. The first three disadvantages can be greatly mitigated if automated, high throughput protocols are put into place. Although this requires a substantial initial expense and considerable expertise to set up, once in place, large numbers of samples can be processed quickly and cheaply with little need for human involvement.
3. Seroprevalence studies.
This methods involves taking blood samples from individuals and determining whether they have made antibodies to the flu.
- Can be performed after a person has been infected.
- Can be done on large numbers of people relatively cheaply.
- Usually not clinically useful.
The primary utility of this approach is to determine how many people were infected in a particular outbreak. This type of study is essential when determining case fatality rate.
4. Unbiased sequencing.
With this approach, a sample is taken from a patient and everything within that sample is sequenced.
- Highest level of sensitivity. No infections will be missed.
- Can detect novel mutations. Mutations that might cause other methods to fail will not affect this technology.
- Can detect novel viruses. Even if an entirely new virus starts to circulate, this method will identify it.
- Very expensive, although the cost is dropping.
- Requires a very high level of skill to interpret the results. Relatively few laboratories have this capability.
Given the advantages and disadvantages of the different approaches, what is the most sensible strategy to utilise these methods?
Given the high failure rate for Rapid Tests, there is little justification for their use. Decisions on how to treat a patient should initially be guided by clinical judgment rather than this test.
High throughput RT-PCR should be used to test as many patients as possible. This is necessary to determine how many people are actually sick with pandemic flu as opposed to the many other infectious diseases which can cause similar symptoms. This information is critical to determine if the case fatality rate due to pandemic flu is starting to increase or if vaccines are failing.
Seroprevalence studies should be done (in fact, should already have been done) to calculate case fatality rates in different locations. Telephone surveys of influenza-like illness are not acceptable substitutes.
Unbiased sequencing should be reserved for cases of severe flu like illness but which are negative with RT-PCR assays. This would alert us to new strains or viruses.
The technology and expertise exists to put a sensible, 21st century diagnostic strategy in place that would guide correct treatment and inform policy-making. Unfortunately, the CDC seems to lack the necessary knowledge base and/or will to implement an up-to-date detection system.