Parasite evolution is making it harder to detect and treat malaria

By Michael Le Page

Cheap rapid tests for malaria have helped drive down the prevalence of the disease in many parts of Africa. But just 15 years or so after their introduction, “stealthy” malaria parasites have evolved that can no longer be detected by the standard rapid tests.

“This is a major threat to malaria control,” says Jane Cunningham at the World Health Organization Global Malaria Programme in Geneva.

In many African countries, only people whose rapid test results are positive get treated. But in Eritrea around 2016, health workers noticed that many children who appeared to be really sick with malaria were testing negative. When medics looked at blood samples under a microscope, they could see many of the children were indeed infected.

“It was a crisis situation,” says Cunningham. “They thought there was something wrong with the test.”

Instead, her team found that up to 80 per cent of the malaria parasites in the area have mutations that mean they no longer produce the two proteins – called pfhrp2 and pfhrp3 – detected by the rapid tests.

“Continued use of these rapid tests is selecting for [parasites without the two marker proteins] to proliferate,” says Cunningham.

Her team then did a survey in neighbouring Ethiopia. “We didn’t find as high a prevalence as in Eritrea, but we found really concerning levels,” she says.

Evolution is often a trade-off, with mutations that provide an advantage in one way being a disadvantage in another. But the parasites seem to thrive without the pfhrp proteins, whose function isn’t known.

Areas with the mutant malaria parasite are switching to tests that detect another protein, but these tests aren’t yet as reliable – they are less heat stable, for instance. Switching to microscope detection isn’t an option in most places as it requires expensive equipment and skilled technicians.

Ideally, says Cunningham, rapid tests would look for several biomolecular targets in the parasites at once, and ones that play a key role in the biology of the organisms, so it is hard for them to mutate. But this makes tests more complex and expensive.

It is common for viruses, bacteria, parasites and cancers to evolve resistance to treatments, but evolving to evade a test is much more unusual – this might be the first clear example. Some hepatitis B viruses have mutations that mean they are missed by tests, Cunningham says, but it isn’t clear if this is due to selection as a consequence of testing.

Some countries are now using rapid tests to detect the coronavirus, SARS-CoV-2, which in theory could evolve to evade them.

Journal reference: Nature Microbiology, DOI: 10.1038/s41564-021-00962-4