False positives and monkeypox
The same issue of false positives creating the illusion of serious outbreaks is very likely happening with monkeypox
I recently wrote to a professor and doctor at Johns Hopkins University warning about his advocacy of testing asymptomatic people for monkeypox. I’m copying my letter below because it highlights the potential for creating a totally illusory monkeypox epidemic if we do indeed engage in widespread testing for monkeypox in asymptomatic or pre-symptomatic people.
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Hi Dr. Mazer, I read with interest your recent piece in the Atlantic advocating for early and asymptomatic testing for monkeypox. I believe this would be a very imprudent policy because of the issue of false positives that arises in testing asymptomatic people for low prevalence diseases. The CDC’s recommendations for testing only on symptomatic lesions is correct.
This isn’t a small problem as false positives can easily constitute well over 90% of positive test results in screening for low prevalence diseases. FDA warned against false positives in the Covid-19 antigen testing context (and many other ailments such as the original SARS also) and quantified the risk as follows in their Nov. 2020 notice: at 0.1% disease prevalence a 98% specificity antigen test will yield fully 96% false positives with asymptomatic testing.
This is of course standard epidemiology and PPV statistics, as you are well acquainted with. The actual monkeypox prevalence in the population is surely far lower than 0.1% at this time, and even if the focus is on screening in the gay and bisexual population it is surely the case that the actual disease prevalence in this sub-population is also significantly less than 0.1%.
If we adopted widespread monkeypox testing with far less specific tests than Covid-19 antigen tests, and with significantly less background disease prevalence, we would likely see well over 96% false positive test results.
For example, if we employ the BMJ PPV calculator with 0.05% prevalence (prior probability) and a generous 95% specificity test, we get a 0.7% PPV and a 99.3% false positive rate:
I think you’d agree this would be a catastrophically high level of false positives and would create the false impression of a widespread illness that isn’t actually there.
It is likely that we are already seeing a high level of false positives even with a focus on symptomatic testing because of the media attention on monkeypox and a heightened alertness to disease at this time. There are dozens of causes of rashes that aren’t monkeypox, so simply testing anyone that has a rash and has had possible exposure to monkeypox will predictably also result in a significant number of false positives.