Introduction and Background of the Project

Introduction

Chagas disease, caused by the parasite Trypanosoma cruzi, affects >7 million people in Latin America, and >0.5 million elsewhere. While vector-borne infections are on the way of being controlled, mother-to-child transmission remains a public health challenge. The two available drugs - benznidazole and nifurtimox - are highly efficacious and well tolerated by newborns, hence the importance of an early diagnosis for timely access to treatment. However, the current algorithm to detect vertical infections takes months, involves multiple tests, and suffers from poor sensitivity.

G2025-121 main goal is the registration as product of T. cruzi-LAMP for timely detecting congenital Chagas disease. LAMP is a near point-of-care molecular tool that parallels the standard PCR in sensitivity and specificity, being simpler to perform, quicker in the turnaround of results, at a lower expected market cost.

Project objective

To license the T. cruzi-LAMP in Argentina and Bolivia, respectively in front of ANMAT and AGEMED regulatory agencies. Additionally, both industrial partners involved (EIKEN and WIENER) will reach a Memorandum of Understanding (MOU) that provides the context for the subsequent commercialization of the technology. At the same time, we will promote the use of the LAMP for improved diagnosis of congenital Chagas disease. Enabling the adoption of this tool will increase access, aligning to the WHO 2030 roadmap for Neglected Tropical Diseases, and contributing to the PAHO Elimination of Mother-To-Child Transmission (EMTCT) of infections initiative.

Project design

In G2025-121, coordinated again by ISGlobal, we will extend the data of former project G2020-203 on the use of heparinized and dried blood spots (DBS) newborns samples in the study site of Yacuiba (Gran Chaco province, department of Tarija, Bolivia) operated by SANIT. These new data will complement the existing body of evidence, including prior analytical performance results generated by Eiken and CONICET-INGEBI, as well as the G2020–2023 clinical validation studies. In addition, performance data produced by Wiener using the T. cruzi-LAMP kits assembled at its manufacturing facility in Argentina will be incorporated. Together, this comprehensive dataset will underpin the preparation of the regulatory dossier and facilitate formal interactions with ANMAT and AGEMED, advancing the licensing and market authorization of the T. cruzi-LAMP diagnostic prototype in Argentina and Bolivia. The newly generated results will play a key role to respond the regulatory agencies requests, which include the analytical validation work conducted within the T. cruzi-LAMP verification studies led by Wiener.

Moreover, with the goal of recommending a change in the diagnosis policy to generalize a timely access to diagnosis (and treatment), we will advocate towards the adoptability of the technology through regular meetings with the competent health care authorities at both regional and national levels, as well as internationally to the PAHO and WHO.

How can your partnership (project) address global health challenges?

The lack of a sensitive timely diagnosis of mother-to-child T. cruzi infection precludes early treatment of infants. This is particularly dramatic considering that available anti-parasitic drugs (benznidazole and nifurtimox) yield an almost 100% cure rate when provided during the first year of life. Current diagnostic algorithms rely on direct microscopy-based observation of circulating parasites at birth and/or a few months later; but, since its performance is poor, if negative, a serological study is mandatory several months later when maternally derived antibodies wane. Such proceeding entails two major disadvantages: (i) the delay in achieving the serological diagnosis compromises drugs´ efficacy; and (ii) the algorithm is so cumbersome that the majority of children are lost in the course of the evaluation procedure, and will eventually be diagnosed as adults. By then, the efficacy of drug interventions will have dropped.

The findings of former GHIT Fund project (G2020-203) pointed out that T. cruzi-LAMP is able to anticipate >50% of positive cases versus the currently used microscopy-based technique, with a level of performance similar to that of the standard real time PCR, which we used as a comparator molecular test. Being much easier to perform than the PCR, and with an expected market cost that will be a fraction of that, the T. cruzi-LAMP is the technological solution to obtain a detection of vertically acquired T. cruzi infections on time. 

What sort of innovation are you bringing in your project?

We will be working to license the T. cruzi-LAMP prototype in Argentina and Bolivia. This molecular amplification point-of-care technology has been shown to provide a highly sensitive detection of congenitally acquired T. cruzi infections, which would greatly facilitate access to treatment when this is most efficacious.

Role and Responsibility of Each Partner

ISGlobal will coordinate. WIENER and EIKEN will lead the preparation and submission of the dossier to apply for licensing of the T. cruzi-LAMP to the regulatory agencies of Argentina (ANMAT), and Bolivia (AGEMED). The project also encompass the achievement of a MOU between the two industrial partners. INGEBI and SANIT will provide support to WIENER and EIKEN in each country, respectively. Besides, INGEBI will provide sample panels for the external quality control and will perform the PCR tests over the clinical samples collected in the Hospital Rubén Zelaya (Yacuiba, Bolivia). SANIT will be responsible for the activities in that site.

Others (including references if necessary)

For further information on the T. cruzi-LAMP technology, please see the following scientific articles:

https://pubmed.ncbi.nlm.nih.gov/39357671/

https://pubmed.ncbi.nlm.nih.gov/37058542/

https://pubmed.ncbi.nlm.nih.gov/38971173/