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Development of a non-invassive breath test for early diagnosis of tropical diseases

Periodic Reporting for period 2 - TROPSENSE (Development of a non-invassive breath test for early diagnosis of tropical diseases)

Reporting period: 2017-02-01 to 2019-01-31

Hydatidosis (cystic Echinococcosis), Leishmaniasis and Dengue are included in the list of 17 neglected tropical diseases elaborated by the World Health Organization (WHO), which are a group of tropical infections that are prevalent in the tropical and subtropical regions of Africa, Asia and the Americas, affecting especially the low-income populations in the developing areas.
All these neglected tropical diseases generally cause unspecific symptoms, and they cannot be easily identified when a patient arrives at the hospital. The failure of an early diagnosis and prescription of an adequate treatment can be extremely negative and even fatal for the patient.
The objective of our project is the development of a fast, inexpensive, and easy-to-operate diagnostics tool for on-site early detection of Hydatidosis, Leishmaniasis and Dengue, based on the analysis of exhaled breath composition.
We collected breath samples of patients affected by Hydatidosis, Leishmaniasis and Dengue, as well as from a group of control volunteers, in different hospitals from Colombia (Dengue and Controls), Tunisia (Hydatidosis, Leishmaniasis and Controls) and Poland (Hydatidosis and Controls).
We analysed the breath samples with an analytic equipment (QC-QTOF) that allows the identification of the compounds from the breath. By comparing the breath composition of the patients and of the control volunteers, we were able to identify the breath biomarkers of the diseases studied (the compounds that were statistically different between the patients and the controls):
- Dengue (Colombia): 6 breath biomarkers
- Leishmaniasis (Tunisia): 9 breath biomarkers
- Hydatidosis (Tunisia): 2 breath biomarkers
- Hydatidosis (Poland): 7 breath biomarkers
Based on these biomarkers identified by the analytical studies, we developed electronic nose devices based on organically-functionalized metal nanoparticles chemcial gas sensors, which achieved the following classification accuracy between patients and controls:
- Dengue (Colombia): 100%
- Leishmaniasis (Tunisia): 98.2%
- Hydatidosis (Tunisia): 100%
- Hydatidosis (Poland): 92.9%
A prototype was developed based on these results, and used for on-site validation tests in Poland. The results of these validation tests are currently carefully evaluated, and will constitute the basis for the further development of a reliable point-of-care prototype for the diagnosis of Dengue, Leishmaniasis and Hydatidosis.

The results obtained in this project led to the publication of 41 research articles and 2 book chapters, and participation at 91 international conferences and workshops. Moreover, five patent applications were submitted with the results derived from this Project.
We identified, for the first time ever, breath biomarkers for three different tropical diseases: Dengue, Hydatidosis and Leishmaniasis. This could be a cornerstone for new developments of small molecule drugs that specifically target the signatures of the pathologic changes of these diseases.
We demonstrated for the first time the possibility to diagnose different tropical diseases (Dengue, Leishmaniasis and Hydatidosis) through exhaled breath analysis with chemical gas sensors
We fabricated for the first time a portable prototype for the diagnosis of Dengue, Leishmaniasis and Hydatidosis via exhaled breath analysis
We designed and developed a novel sensor system combining cascade laser technology with a portable miniaturised dual channel mid-infrared hollow waveguide gas cells, and we demonstrated the real operation of this sensor system for online

Different seminars about the diagnosis methodology that we proposed in our project were presented to pupils, students, and the young people. After these seminars, it was evaluated the perception and social impact of volatile organic compounds (VOCs) detection techniques for diseases diagnostic by means of a fact sheet carefully prepared with the help of professional sociologists. The results collected are currently analysed in order to assess the social impact and the perception of this new emerging technology. The results will be published in a sociology journal.
Dengue transmission by mosquito byte
Image of Cutaneous Leishmaniasis lession