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As the title states, I'm wondering whether simply redoing a test is a valid means of eliminating the risk of a given result being false.

The question is specifically about repeating the same exact test, not using a different testing methodology. If relevant, I'm mostly interested in blood tests, more specifically for the diagnosis of brucellosis.

Or, put another way, what are the most common reasons for false results? There's obviously the risk of lab error and cross-contamination, but I assume there are also reasons intrinsic to the patient themselves.

I've read that some tests can generate false positives if the patient is infected with some other virus or bacteria (which may or may not be harmful) [1, p.2]. Is this the only cause or are there other problems which may interfere with the test (possibly including cases where the test doesn't work on this person for reasons unknown)?

External factors would likely be eliminated by repeating the test (if the lab is usually reliable). However, I assume the reasons intrinsic to the patient would not be affected, such that the second test would give the same false result if the "problem" is the patient.

Which raises the further question of whether there are any general statistics on the most likely causes of false results: are they usually due to user error (and therefore identifiable by redoing the test) or due to some underlying condition in the patient (and likely doomed to give the same mistaken result every time)?

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    The reasons a test result could be a FP/FN will vary substantially based on the specific test. For example a viral test might be FP because of insufficient sampling of the appropriate tissue where the virus is located. A lab test of enzyme activity might be abnormally low because the sample was heated so hot that it was inactivated. Whether repeating the test will fix the issue is therefore related to the cause. Thus, I fear that the question as asked is too broad. I recommend you edit the question to focus on a single specific question.
    – Ian Campbell
    Commented Feb 1, 2022 at 19:36
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    All this said, I have definitely seen papers in the medical literature listing most common reasons for a specific lab test failing. So if you have a particular test in mind, the question could probably be answered.
    – Ian Campbell
    Commented Feb 1, 2022 at 19:41
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    @IanCampbell I've edited the question to specify that I'm most interested in blood tests for the diagnosis of brucellosis (which I'd assume is similar enough to that of any other bacterial infection).
    – Wasabi
    Commented Feb 1, 2022 at 22:16
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    Great, that is a very specific and answerable question. The only issue now is prior research. Most of the biology SE sites require a link or two showing what you have found thus far to frame the question and resulting answers. This is much like the notable claim requirement you have experienced on Skeptics.SE.
    – Ian Campbell
    Commented Feb 1, 2022 at 22:19

1 Answer 1

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Although somewhat buried in the question, it appears you are interested in Brucellosis.

Brucellosis is an infectious disease caused by bacteria of the Brucella genus including B. melitensis, B. abortus, B. suis, and B. canis.

Diagnostic testing for Brucellosis can generally be placed into 4 categories¹:

  1. Bacterial culture: the causative bacteria are grown in a specialized medium outside of a host
  2. Agglutination test: antibodies from the patient are mixed with an antigen (such as Brucella bacteria) and cause visible clumping
  3. ELISA: antibodies themselves are identified (read more)
  4. Genetic studies: genetic material from the bacteria are identified in a patient sample

Bacterial Culture

Obviously, getting a bacterium to grow in the lab requires you actually collect the bacterium. Many pathogenic bacteria are surprisingly hard to grow outside a human. The sensitivity of culture for Brucellosis is often less than 50%². If the clinician has not actually collected the bacteria, repeating the test can potentially work.

Bacteremia (bacteria in the blood) can be low level as 1 to 5 bacteria per mL and occur intermittently³. Repeat culture can be particularly useful if testing a different body site, for example cerebral spinal fluid if there are neurologic symptoms.

Bacterial cultures can often grow many different types of organisms and laboratories have standard methods to identify what has grown. In resource rich areas, 16S ribosome sequencing has made this task relatively straightforward.

Agglutination test and ELISA

Both the agglutination type tests and ELISAs rely on detecting patient's antibodies in a sample. Antibody production is complex but generally follows a predictable pattern.

Antibody Curve Hypothetical antibody curves adapted from this WHO report.

Depending on when a sample is taken in this curve, antibodies may not have been produced in detectable quantities yet. Repeating a sample might be helpful.

However, the reality is that Brucella are endemic in many parts of the world, and so many people have pre-existing antibodies. It is for this reason that the US Centers for Disease Control recommends routinely taking two samples to observe the increase in antibody levels.

The agglutination tests are also susceptible to the prozone phenomenon where antibody levels are so high that they coat the bacteria in such a way that the do not cross link and clump. This can usually be overcome with diluting the sample rather than a repeat sample.

Sometimes, a patient's antibodies to another bacterium might also bind to the Brucella in the agglutination test. This would be a false positive and a second sample would be unlikely to change the result. Using an ELISA with a more specific antigen would be one possible alternative approach.

Genetic Testing

Molecular genetic testing for Brucella is not widely used in clinical practice, but detection of genetic material requires it be present in the sample at a reasonable level. The same principles as described in the bacterial culture section apply.

Of note, the 16S ribosome sequence of all Brucella species sequenced so far have been identical, so determination of the particular species is not possible.

Laboratory Error

In addition to all of the above considerations, there are obviously process problems that can occur. For example, a sample could be miss-labeled or inadvertently moved. A critical reagent in the process might also fail. In some of these cases, repeating the test, potentially at a different laboratory, might address the issue.

Conclusions

Thus, overall, for some types of false negative results, repeating a sample could be useful. However, for most false positive results, repeating a test may not be helpful, and so an orthogonal approach should be employed.

An experienced clinician with training in infectious disease practicing in a research rich setting will be familiar with the issues in their particular community and know how to address them.

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  • "An experienced clinician with training in infectious disease practicing in a research rich setting will be familiar with the issues in their particular community and know how to address them." You cannot know how much I wish this were true. People in ivory towers are blissfully unaware of what's going on in their own communities. Commented Feb 3, 2022 at 2:32

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