Rapid Malaria Tests can be selected for species you cannot detect

Avoiding tests means avoiding treatment, and that means more infections. But in many parts of the world, rapid testing is a key feature of health care. If you do not have easy access to laboratory infrastructure - and many developing countries do not - a rapid test can provide a quick way to screen for common problems. In a number of countries, results of rapid trials determine whether people are treated for malaria.

But this may cause you problems. A new article suggests that the malaria parasite may be evolving beyond detection with the most common rapid tests. One or more proteins at the level of the pathogen. We can produce antibodies that detect this protein and attach it to a dye molecule. When there is no pathogen present, the antibodies remain scattered and the color is imperceptible. When the pathogen is present, the protein and antibodies build up, collecting enough of the dye molecule to be able to see it. The result is something like a red bar that appears in a certain place on the test device. But arguably the most effective test kit detects two types of proteins called histidine-rich proteins 2 and 3 (pfhrp2 and pfhrp3). Because the test produces consistent results, a number of countries have standardized it for malaria. People with symptoms are screened for this and take antimalarial medications if the test is positive.

One problem with this is that we don't really know what proteins usually do (this is referred to by their name, which tells you what the proteins look like. not what they do.) A number of malaria parasites have been isolated from where the genes have been lost, which Indicates that they are not necessary for infection. Therefore, it is possible to lose some breeds completely through routine testing. These medications usually kill the parasites, or at least prevent them from reproducing. In this way, they create a selective pressure that can stimulate evolution. This choice may lead to drug resistance. But it can also provide an option against the proteins that caused it to happen in the first place — proteins discovered by rapid testing. ad

gene deletion

Ethiopia is one of the countries using rapid tests to detect pfhrp2 and pfhrp3. Therefore, a team of Ethiopian researchers decided to find out if this test affects the development of malaria parasites in their country. To do this, they collaborated with a number of American researchers and formed a large international team.

They have recruited more than 12,500 people with symptoms of malaria and given them two different rapid tests: one that detects pfhrp2 and pfhrp3 and one that detects a different protein. A total of 2,714 of these participants tested positive in at least one of the trials. Among them, more than 350 (13%) tested negative for pfhrp2 and pfhrp3, indicating that they may have damaged genes encoding proteins. Examining the DNA, the researchers found that the genes had been completely destroyed - removed at some point in the parasite's past. However, as noted above, genes do not appear to be necessary for infection, so they may have been lost for reasons unrelated to the diagnostic test.

There are two reasons why we think this is not the case, the first is that the deletions are not specific to the genes encoding pfhrp2 and pfhrp3. It's large enough to remove nearby genes as well, and some of them appear to be very important. One is associated with red blood cells, a type of cell targeted by the parasite. Another is involved in allowing the parasite to enter the red blood cells. Thus, deletion of these genes appears to be detrimental to the parasite, indicating that the deletion will not occur until it is selected for them.

The second reason is related to the DNA deletion. If the deletions take too long, new mutations and recombination between chromosomes would be expected to create sequences in the vicinity that would make the DNA similar to the DNA in the lineages without the deletion. This was true in removing pfhrp3.

But removing pfhrp2 was different. Instead, the DNA near the deletions appeared to be the same, and significantly different from that found in the species without the deletions. This indicates that the pfhrp2 deletion was novel and did not have time to mutate and recombine to disrupt the nearby DNA sequence. Therefore, all parasites carrying the pfhrp2 deletion appear to have been inherited from an ancestor. This grandfather was very new. Selective pressure caused the spread of parasites that inherited the deletion.


All this is consistent with the so-called selective scanning, in which the evolution of a part of a chromosome leads to a high prevalence because it contains a desired mutation. Remember that these deletions also remove proteins that might help the parasite infect cells? Researchers suggest that eliminating these conditions can reduce the incidence of malaria so that it does not cause severe symptoms associated with infection that reaches the brain. If so, people with these deletions may not seek a diagnosis, so even a quick test is not done initially. Although none of this evidence is conclusive, it clearly shows that our ability to detect the presence of a pathogen influences the evolution of that pathogen. Given that diagnosis in this case leads to treatment, it is clear that there is a selective pressure consistent with this idea.

What does this mean for other rapid tests such as those used for coronavirus? ? Unfortunately, "that's complicated." If people change their behavior in response to the results of a rapid test, the test may reduce the rate of infection, thus creating selective pressure. Although there are obvious differences, the malaria parasite is a complex cell with a large amount of protein on its surface. Obviously, he could survive losing a number of them. SARS-CoV-2 is a virus that has a total of two proteins on its surface and can lose either of them and still function. Rapid tests against it rely on antibodies that detect the spike protein of the virus, so changes in test altitude are likely to be ineffective. But spike is also a protein that enables the virus to infect new cells, and there are limits to how much it can tolerate while performing this job. Plus, at the same time, it is under selective pressure to develop ways to avoid antibodies made by the immune systems of people who have already been vaccinated or infected. Given all this, it is unclear whether the diagnostic test will have a significant impact on the evolution of the virus. Therefore, even if this malaria risk is confirmed, it may not be used in tests for other pathogens. Cases must be evaluated on a case-by-case basis.

Nature Microbiology, 2021. DOI: 10.1038/s41564-021-00962-4 (about DOIs).

Rapid Malaria Tests can be selected for species you cannot detect
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