Overreliance on the results of PCR tests - A warning from the CDC, 2006

The M+G+R Foundation

Overreliance on the results of PCR tests (1)

In 2006, the CDC (2) warned against it regarding false diagnosis of a respiratory illness

but their warning is being ignored by all for the PCR testing on Covid-19

Originally published on July 21st, 2021

A guest document by Ricardo de Valencia

INTRODUCTION

During the outbreaks of respiratory illness mistakenly attributed to Pertussis (3) in 2004-2006 (4) -- a respiratory disease that, like Covid-19, is "complicated by nonspecific signs and symptoms" -- PCR testing produced near 100% false positives at two hospitals and one community when used on groups of symptomatic individuals. (5)

The false positives (cases interpreted as positive for Pertussis when tested by PCR) were confirmed as false cases of the disease when the samples were submitted for isolation analysis by culture (6). According to the CDC, "culture is a reference standard and 100% specific" (5) in the diagnosis of Pertussis.

As a result, the CDC concluded that there is an "overreliance on the results of PCR assays", pointing to "limitations of relying solely on PCR assays to confirm pertussis". (5)

Their acknowledgment of the problem, however, was only partial and the significance of the events were downplayed, by merely labeling as "limitations" those results that, taken together from the three hospitals involved, were a total predictive failure: 414 false cases out of 415 PCR-positive samples from symptomatic patients.

What significance or implications does this have for the Covid-19 PCR tests?

DETAILS

First of all, let us look at the specific figures. The episodes that, regarding the false Pertussis outbreaks of those years, demonstrated the resounding failure of PCR as a tool for predicting and confirming the disease, took place in the context of three different hospitals:

Hospital at New Hampshire, 2006.

Positive PCR: 98 cases. Confirmed when submitted for isolation by culture: 0 cases.

In May, a hospital in New Hampshire began PCR testing for pertussis on symptomatic health-care personnel. By June, of the 98 suspected pertussis cases identified by positive or equivocal PCR results, none yielded B. pertussis when submitted for isolation of B. pertussis by culture.

Hospital at Massachusetts, 2006.

Positive PCR: 32 cases. Confirmed when submitted for isolation by culture: 0 cases.

In October, a hospital initiated enhanced screening (8) of symptomatic health-care personnel with suspected pertussis. By December, of the 32 specimens which had tested positive for pertussis by PCR, none yielded B. pertussis when submitted for isolation of B. pertussis by culture.

Community around a hospital in Tennessee, 2004.

Positive PCR: 284 cases. Confirmed when submitted for isolation by culture: 1 case.

During a 2-month period, many people in the community who visited health-care providers with pertussis symptoms were evaluated for pertussis. Of the 284 symptomatic persons who where positive when tested by PCR, only the sample of a person (the infant whose case motivated the screening of the community) yielded B. pertussis when submitted for isolation of B. pertussis by culture.

The application of PCR tests to clinical diagnosis is something that the inventor of PCR technology himself had already denounced (7): it is a technology capable of detecting extremely small quantities of genetic material (from viruses, bacteria or other living organisms) that may not pose a risk to a person (in asymptomatic cases) or may not be the cause of the disease manifested in a patient (in symptomatic cases).

PCR tests, by giving YES/NO results for the presence of a molecule but not a precise and reliable measure of the amount found, cannot determine the probability of the risk of disease on a person, even less can they confirm the disease. In any case, these tests would serve to exclude one infectious agent among several possible in a sick person.

The false outbreaks of Pertussis described in the CDC's report (5) illustrate the real danger of using PCR tests for screening (8) or diagnosing a disease, a real danger which is not a mere accident caused by ill-designed tests. It is a problem inherent to the concept itself of PCR and comes with the interpretation of the results - as if positive results were a clinical confirmation of the disease when they are only a confirmation of the presence of some, maybe only traces of, genetic material.

Lessons allegedly learned and advice from the CDC...

The CDC, in their report evaluating those events of suspected Pertussis, concluded: (5)

The outbreaks described in this report illustrate the limitations of relying solely on PCR assays to confirm pertussis. PCR is an important tool for diagnosing individual cases of pertussis in persons for whom a high index of suspicion exists and for whom timely treatment and PEP are essential. However, the positive predictive value can be lower if PCR is used as a screening tool without culture confirmation during a suspected pertussis outbreak.

Overreliance on the results of PCR assays can lead to implementation of unnecessary and resource-intensive control measures (e.g., case identification, antimicrobial treatment, furlough of ill persons, and administration of PEP). In outbreak settings, positive PCR results should be interpreted in conjunction with epidemiologic investigation, evaluation of clinical symptoms, and confirmation by culture.

CDC recommends timely collection and testing (early in the course of illness and during the initial stages of the outbreak) of nasopharyngeal specimens for culture in at least a subset of persons who are symptomatic to confirm pertussis as the etiology of the outbreak. Absent or inconsistent supporting data and negative pertussis cultures in appropriately collected specimens should prompt testing for alternate pathogens.

... neglected for the Coronavirus Crisis:

It is very disturbing to see that each of these recommendations or lessons allegedly learned from the Pertussis pseudo-epidemics in 2004-2006 are being completely ignored in the massive testing on the population for the Covid-19 epidemic:

(a) There is an overreliance on the results of PCR assays, which leads to implementation of unnecessary and resource-intensive control measures.

(b) A massive number or PCR tests are being conducted on asymptomatic people. Testing for everyone is promoted, whether there is a "high index of suspicion" or not.

(c) Positive PCR results are taken as the sole basis for "confirmed cases", without evaluation of clinical symptoms and confirmation by culture.

Is the CDC a fair judge for PCR testing?

This particular statement by the CDC is very intriguing:

"PCR is an important tool for diagnosing individual cases of pertussis in persons for whom a high index of suspicion exists and for whom timely treatment and PEP are essential." (5)

Through the reported events in New Hampshire, Massachusetts and Tennessee in 2004-2006, it was demonstrated that PCR tests for Pertussis were not reliable at all for confirming symptomatic cases. But the CDC want us to believe that they still are useful for "some" symptomatic cases, those in which there is a "high index of suspicion".

When we read that, we wonder: If a physician has to determine that a patient has a "high index of suspicion" to know (before knowing) whether or not the PCR is going to be valid as a "diagnostic tool", then, what is the real predictive or diagnostic value of the PCR? To make a rough simile: this is like being sold a moisture detector and being told that "It is a great tool for detecting moisture, but you would better make sure, by other means, that the sample you want to test is full of water."

Now, regarding this statement:

"However, the positive predictive value can be lower if PCR is used as a screening tool without culture confirmation during a suspected pertussis outbreak." (5)

We can comment: In New Hampshire, Massachusetts and Tennessee, PCR tests were used for the systematic examination ("screening") of cases in symptomatic people. Out of a total of 415 PCR positives in the three scenarios, only the case of one person was confirmed as valid. This is the situation they describe by saying that "the predictive value of PCR positives can be lower". Only "can be lower"? Would it not be fairer to say that the predictive value of PCR tests for Pertussis was shown to be worthless?

CONCLUSION

If anyone still did not believe that PCR technology is inappropriate for the screening (8) and diagnosis of cases of infectious diseases, the failure in the false Pertussis crisis should serve as a practical demonstration.

Or, at least, for those reluctant to qualify it as a failure, this should be taken as an indication that something is wrong in the interpretation of PCR tests for diagnosis and screening. But, then, where is the concerted and systematic effort to assess the real clinical value of the Covid-19 PCR tests by systematically comparing them with the culture isolation test?

The CDC's attempt to downplay as mere "limitations" the failure of PCR testing in the 2004-2006 false Pertussis events - even with the numbers in the face of it - illustrates the CDC's lack of will to provide truthful conclusions regarding the dubious clinical value of PCR tests.

But the audacity is even greater when we see that the recommendations proposed by the CDC from that events are being completely neglected for the Covid-19 epidemic.

NOTES

(1) PCR: (Polymerase Chain Reaction) The technique and tests that is being used almost universally worldwide to define "confirmed cases" of Covid-19. For each disease, one or more specific PCR tests may be developed that are expected to detect certain points in the genetic material (RNA or DNA) of the infectious agent (virus, bacteria, etc.) to which the disease is attributed.

(2) U.S. CDC: Centers for Disease Control and Prevention, USA, is the national public health agency of United States.

(3) Pertussis: also known as whooping cough, caused by the bacterium Bordetella Pertussis.

(4) The 2004-2006 events, as narrated by The New York Times: Faith in quick test leads to epidemic that wasn't

(5) CDC Report: Outbreaks of Respiratory Illness Mistakenly Attributed to Pertussis -- New Hampshire, Massachusetts, and Tennessee, 2004-2006. Quotes reproduced here are with our highlithing.

(6) Isolation by culture / In vitro culture: It is a test in which a sample of material extracted from the patient is placed on a glass plate in the laboratory (or equivalent substrate) in conditions favoring that, if the sample contains the expected infectious agent (a particular virus, bacteria, or living organism), the suspected infectious agent will reproduce. If, after a specified time, it is observed that a characteristic chemical effect or signal has been produced in the culture, it is interpreted that the virus/bacteria/whatever has reproduced and it is "infectious". If it is a virus, it is said that the sample contains "active", "viable" or "infectious" virus, which are synonyms for "capable of reproducing".

(7) The real reason for the misuse of PCR tests

(8) Screening: (In reference to infectious diseases) The operation of systematically subjecting all or most members of a population (e.g., hospital health personnel) to a rapid medical evaluation, typically involving a rapid clinical test for signs of infection. The people tested may not exhibit previously any signs or symptoms of the disease, or they might exhibit only one or two symptoms, which by themselves do not indicate a definitive diagnosis.