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Interview with Pere Joan Cardona

This interview originally appeared on Planeta Salud’s website.

Pere Joan Cardona
Pere Joan Cardona

For 15 years, Dr. Cardona has focused his studies on infection with Mycobacterium tuberculosis (Mtb) has developed a hypothesis and dynamics of tuberculosis infection, which could explain why the Koch bacillus persists in the human body as implies a continuous reinfection of tissues. This may open the field to new health tools that provide an adequate response to the challenges of this ancient disease that kills 1.8 million people each year.

What are the main differences between the traditional theory of latent tuberculosis infection (TB) and has developed with his team?

Traditional theory considers a completely static scene in which the bacteria become dormant and remain for years within the injury, also static. Presumably, using an episode of immunosuppression of the infected individual, the bacillus is able to resurrect and destroy the injury that encapsulates, to generate a lesion cavitated * and thus active TB.

By contrast, the hypotheses put forward by our team integrates various physiological elements of both the host (humans) as the bacillus that have been able to carry on demonstrating. Is the tendency to healing of all lesions, the constant drainage of bacilli from lesions to the alveolar spaces, or the same mechanism of action isoniazid, The standard treatment of latent infection, which is only effective against actively growing bacilli and therefore would not work if the bacteria were encapsulated within a static lesion.

Briefly, our theory includes the fact that the immune response after the bacilli that become latent within the lesion Granulomatous *Are drained into the alveolar space before finally being evacuated to the alveolar fluid into the gastrointestinal tract. Interestingly, this process is a small loophole: the alveolar fluid is also the origin of aerosols generated by inhaling air from the outside. This process allows the latent bacilli reinfected again parenchyma * lung and therefore perpetuate the process. This cycle is fueled by the fact that the immune response generated against M. tuberculosis is basically cell type. This always leaves a loophole for the bacilli to multiply before the immune system to realize again that is invading the lung.

Finally, this theory also helps explain why a time-limited treatment (relatively, since it is nine months) is successful, given that isoniazid is only active against actively growing bacilli. If true the traditional theory, this drug would have no effectiveness: should be administered during the lifetime of the infected individual, just waiting for the bacillus boost growth. With the dynamic hypothesis, this treatment makes sense, since it allows drainage of the latent bacilli, preventing the process of economic growth, and therefore constantly induce further injury, which is the basis for persistence of bacteria in patients latently infected.

What suspicions led him to work on the development of a new hypothesis?

Ten years ago we observed in experimental TB model in mice after induction of immunity generated foamy macrophages * within the granulomas. These cells accumulated in the alveolar spaces, around the granulomas. The appearance of these cells is related to chronic inflammatory processes that generate cellular destruction. Entering new macrophages and phagocytose * cellular debris, lipids accumulate remnants of membranes, and thereby accumulate droplets of lipids in their cytoplasm. Thus, these cells gradually lose their phagocytic properties and are drained into the alveolar space. In short, they are true “sweepers” of the lung. Remember that in order to breathe, lung suffers the entry of many toxic filth lot! The cleaning action of macrophages is therefore very important.

But what struck us is the fact that within these cells, including lipid bodies, were also not multiplying bacilli that were in latent phase This was the great find! The granuloma was not the “fortress” that encapsulates the bacilli, as expected, unless there was a draining process constant, bacilli escape!

How has embraced the scientific community other proposal to change its model?

The truth is that from the beginning, the theory has been very well received. It incorporates many sound knowledge of both the human and bacterial physiology, which make it very robust. However, until proven in humans, it is final. In this we are!

How is research at this point? Are you expecting results soon?

The results that we currently have in minicerdo model – which has a lung structure very similar to human evolution-confirm the model predicted in mouse and guinea pig. These experiences have enabled a clinical trial in human beings, to assess the presence of these small lesions, not observed in chest radiographs and therefore go completely unnoticed and asymptomatic in infected patients. In this trial, conducted with high-resolution chest CT, confirmed the fact that these patients have small lesions that we observed in minicerdo model. Now it can be shown only on a great show that these lesions are disappearing and new ones are generated over time. This will be a very definitive!

Of being able to show, what would the dynamic theory in the development of new tools for TB?

The dynamic theory can already now have a clear therapeutic target. Considering the older theory, the treatment of latent infection would be impossible! How to attack a latent bacilli metabolically very active, and also locked in an old injury? Impossible! With our theory, the bacillus shows his vulnerability shows that can be destroyed.

In fact, this vulnerability was the origin of the vaccine therapy RUTI ® That combines a treatment chemotherapy * Short-term (one month) with the inoculation of the vaccine. The candidate is designed to generate a poliantigénica, which allow to identify the latent bacilli on their way to reinfection of the lung.

How do you think TB should be addressed now? What strategies do you think might be more efficient in the current context?

As I indicated, the future of both treatment of latent infection and active TB will pass through the combination of the use of chemotherapeutic agents capable of acting in bacillary growth phase-lag between the dormant and active growth-with the use of therapeutic vaccines that compensate local immunosuppression generated by the use of these chemotherapeutic agents.

Glossary:

  • Cavitated: Training pathological cavity in a tissue or organ.
  • Granulomatous: Having the appearance of a granuloma, ie set organized and compact mature mononuclear phagocytes (macrophages and epithelioid cells) that can be accompanied by necrosis or infiltration of other inflammatory leukocytes.
  • Parenchyma: Fabric of the glandular organs.
  • Macrophages sparkling wines: Connective tissue cell capable of phagocytosis (eating) larger particles.
  • Phagocytose: The term “phagocytic cell is a general term used to describe any white blood cell that can” phagocytose or ingest microorganisms. In general, there are two main categories of phagocytic cells, or phagocytes, 1) polymorphonuclear leukocytes (also called neutrophils or granulocytes) and 2) mononuclear phagocytes (also known as monocytes when in the blood and macrophages when they are in tissues).
  • Chemotherapy: Method healing of diseases, especially infectious, through chemicals.

Pere-Joan Cardona, Doctor of Medicine from the Autonomous University of Barcelona, Clinical Microbiologist, Associate Professor, Department of Genetics and Microbiology, Autonomous University of Barcelona and Head of Experimental Tuberculosis Unit of the Institut Germans Trias i Pujol.

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