(ORDO NEWS) — Epidemiological analysis has shown that the indigenous peoples of the Amazon rainforest are practically free from American trypanosomiasis – Chagas disease.
Subsequent genomic analysis revealed several mutations in the tribes that protect them from infection with Trypanosoma cruzi, the causative agent of the disease.
According to the World Health Organization, Chagas disease, or American trypanosomiasis, affects six to seven million people worldwide.
Most people get sick from contact with triatomine bugs that carry the pathogen Trypanosoma cruzi, and South and North America are considered the main region of the disease, and the disease has begun to penetrate more and more cities.
Because of this, it has become more common in the US and Canada.
There is no vaccine against this disease, so all measures are aimed at preventing transmission of the infection – the fight against bedbugs, screening the blood of donors and women of childbearing age.
However, as a group of scientists led by Tábita Hünemeier from the University of São Paulo found out, some people have developed adaptive mechanisms that protect them from Chagas disease.
They examined the genome of 118 representatives of 19 tribes living in the Amazon region, in which the disease was practically not recorded.
Scientists have found that people from these tribes have mutations in the PPP3CA, DYNC1I1 and NOS1AP genes.
The most common “defender” turned out to be the PPP3CA gene, which encodes the catalytic subunit of alpha-protein phosphatase 3 and is involved in the G-βγ signaling pathway, one of the most important elements of intracellular G-protein signal transduction in immune cells.
In addition, the gene is responsible for calcineurin signaling, a key conduit for innate immunity against Trypanosoma cruzi. In disease-resistant people, this gene turned out to be inactive.
To test the role of this gene (and its knockdown) in the development of Chagas disease, the researchers infected cardiomyocytes derived from human induced pluripotent stem cells infected with T. cruzi.
The researchers chose cardiomyocytes as the infection model because the parasite often infects these cells in humans.
They found that in cells where PPP3CA gene expression was reduced by 65 percent compared to control, the parasite’s ability to infect cells was significantly reduced by about 25 percent (p < 0.0004).
In addition, when studying the geographical distribution of both Chagas disease and the mutation in the PPP3CA gene, scientists found that there are practically no cases of trypanosomiasis in the distribution area of the mutation, which also indirectly proves its protective effect.
The researchers believe that this natural selection of the mutation occurred for several reasons. First, the selection process began about seven thousand years ago, judging by the archaeological finds, which indicates a sufficient time for selection.
Secondly, the geographical features of the region under study make it possible to construct a model in which isolation led to the persistence of the mutation.
Thirdly, the fact that this mutation occurs in similar environmental conditions in Africa and southern Europe suggests that in the study region, environmental conditions are suitable for the survival of the mutation.
Back in 2020, the WHO announced that the African relative of trypanosomiasis, the causative agent of sleeping sickness, was practically defeated: by 2030, WHO plans to achieve zero infections while maintaining the current rate of decline in the incidence.
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