Certain lipids are altered in people infected with the parasite T. cruzi, and return to normal after treatment, shows a study led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by “la Caixa” Foundation. The findings highlight the role of lipid metabolism in the progression of Chagas disease, and suggest that these molecules could be used as biomarkers for the timely assessment of anti-parasitic treatment response in chronically infected individuals.
Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected tropical disease affecting an estimated seven million people worldwide. Most infections go undetected for years, but around 30% of chronically infected people eventually develop digestive and heart disorders, which can be fatal.
One of the biggest challenges in managing the disease is the difficulty in diagnosing it early and evaluating how well treatments are working. “Chagas disease is treatable, but the treatment is long and little progress has been made in identifying biomarkers that tell us if a patient is responding well to the treatment,” says ISGlobal researcher Julio Alonso-Padilla. Currently, the criterion for determining whether a person is cured is when antibodies against the parasite are no longer detectable in blood. But this ‘seronegativisation’ process can take up to 30 years.
Changes in lipid abundance
In this study, the research team led by Alonso-Padilla analysed blood samples from 28 patients enrolled at the Hospital Clinic (8 with symptoms and 20 without), before and after anti-parasitic treatment with benznidazole, in order to detect any changes. Fifteen healthy people served as controls. A large number of molecules related to the metabolism, including fats, or lipids, were measured using liquid chromatography and mass spectrometry.
The researchers identified three types of lipids, that helped distinguish between people who had symptoms and those who didn’t. Specifically, two types of phosphatidylethanolamine (PE) were more abundant in symptomatic patients, while levels of 10-hydroxydecanoic acid were reduced. PEs are an important component of the cell membrane and have been shown to increase in patients with heart failure and cardiovascular damage.
Remarkably, the analyses also revealed a number of molecules in the blood of treated patients that returned to levels similar to those in healthy people, including five types of sphingolipids. These molecules are known to modulate immune responses and are involved in the progression of several infectious diseases.
Implications
“Our results reinforce the idea that altered lipid metabolism plays an important role in the progression of Chagas disease, and that certain lipids could be used to monitor the progression and response of patients to treatment” says Juan Carlos Gabaldón, ISGlobal researcher and first author of the study. “The lipid signatures we identified may reflect damage to tissues infected by the parasite”, he adds.
The authors caution that the findings will need to be validated in other patient cohorts, and more research is required to understand the underlying mechanisms. Also, the technology to measure these molecules in blood must be simplified to make it accessible in low-resource settings, where Chagas disease is most prevalent.
Despite these challenges, the molecules identified in this study show potential as valuable tools to monitor Chagas disease progression and evaluate the effectiveness of both existing and new treatments.
Reference
Gabaldón-Figueira JC, Ros-Lucas A, Martínez-Peinado N et al. Changes in lipid abundance are associated with disease progression and treatment response in chronic Trypanosoma cruzi infection. Parasites and Vectors. 2024. https://doi.org/10.1186/s13071-024-06548-3
