Molecular diagnostics for predicting Chagas disease in newborns

According to the World Health Organization (WHO), there are between six and seven million people worldwide, most of whom live in Latin America, infected with Trypanosoma cruzi, the parasite that causes Chagas disease.

20% of new cases are due to vertical (or congenital) transmission, that is, when an infected mother passes the parasite to her baby during pregnancy. Early detection is therefore a public health priority.

The problem is the lack of simple, fast and reliable tests. In high-income countries such as Spain, newborns can be diagnosed using PCR, but this is an expensive method that requires trained personnel.

Now, a new test that combines a DNA extraction system based on a modified 3D printer (PrintrLab) with loop-mediated isothermal molecular amplification (LAMP) can be used to detect parasitic infection in newborns.

This is the conclusion of a proof-of-concept study conducted in the Bolivian Chaco, an endemic region for the disease. The study, published in the journal Lancet Microbe, is coordinated by the Barcelona Institute for Global Health (ISGlobal).

In endemic areas, up to two microscopic examinations are performed (at birth and at two months of age), which, due to their low sensitivity, must be followed up a few months later by a serological test to detect antibodies against the parasite. The multiple tests and the time that elapses between them increase the risk that children will not receive the necessary treatment.

“In these areas, it would be very useful to have a simple, rapid and sensitive test to detect the parasite in a newborn, when treatment works best,” explains Julio Alonso Padilla, a researcher at ISGlobal.

Lower cost and infrastructure

In this study, a team led by Alonso Padilla evaluated a diagnostic test that combines a simple molecular amplification method (LAMP) developed by the Japanese company Eiken with a 3D printer modified to extract DNA from a small blood sample (PrintrLab). The results were compared with those of PCR and standard diagnostic methods (microscopy and serology).

The study included 224 neonates born to T. cruzi seropositive mothers and followed them for eight months. A total of 23 cases of congenital transmission were identified (nine neonates were identified by microscopy and 14 by serologic testing at eight months).

LAMP was able to detect 13 of 23 cases at baseline (i.e., four additional cases to those detected by microscopy), and PCR 14 of 23 (five additional cases).

“This shows that the sensitivity of PrintrLab-LAMP is higher than that of microscopic analysis and is almost equal to that of PCR,” says Alonso Padilla. The advantage is that PrintrLab should be cheaper than PCR and requires minimal infrastructure.

The importance of early detection

Following national guidelines for diagnosis and treatment of congenital chagas, all infected neonates were treated, highlighting the importance of identifying and treating neonates as early as possible.

The research team explains that this was a proof of concept to show the viability of the PrintrLab-LAMP test, and that it now needs to be tested on a larger scale and in more centres.

If its potential is confirmed, it could also be very useful for detecting acute infections in adults or for assessing the effectiveness of treatment.

Link:

Rojas L, et al., “Evaluation and validation of a PrintrLab-based LAMP assay for the detection of Trypanosoma cruzi in neonates in Bolivia: a proof-of-concept study.” Lancet Microbe, 2024.