TUBERCULOSIS LATENTE: ESTRATEGIAS DE DIAGNÓSTICO Y MANEJO

Añadido: 2026-05-15

[00:02:14]Hello, how are you? Very, very good morning, good afternoon, or good evening to you, wherever you are viewing from, on whatever continent or continents you are looking at. And we are making this clarification because we are in the first webinar of the year of the Latin American Alliance of Infectious Diseases and Clinical Microbiology, Ale. Secondly, since this conglomerate of scientific associations was formed, it is always a great joy that this type of content can be disseminated, especially at such massive levels as the activity of this alliance presupposes. Today, latent tuberculosis, diagnostic strategies and management will be the topic to be addressed. I don't want to take up too much time because there are many guests and many people who will be participating, so I want to welcome Dr. Alfonso Rodríguez to the stage on behalf of Aleín. Doctor, thank you for being there. Uh, it's a pleasure for us as SAD to simply be guests at this Aleín gathering. We only lent you the little house, nothing more, everything is yours, this powerful alliance that we are also sure will benefit the community of our towns in health care. It's all yours.

[00:03:42]Next, we will give the floor to Dr. Fla Amalfa, who will be strictly coordinating the webinar. Alfonso, go ahead.

[00:03:51]Well, good afternoon everyone. I am Dr. Alfonso Rodríguez Morales, vice president of the Latin American Alliance of Infectious Diseases and Clinical Microbiology, Aleín. As already mentioned, I greet you from Colombia. It is a great pleasure to welcome you on behalf of Aleín and its 15 current member societies, which include the Argentine Society of Infectology, the Argentine Association of Microbiology, the Paraguayan Society of Infectology, and the Latin American Society of Travel Medicine, among others. This last one of which I am president, uh, and welcome you then to this webinar on latent tuberculosis, a silent but fundamental issue in the global control of tuberculosis. Although the main focus has been on active disease, latent infection still constitutes a huge problem. It is estimated that around a quarter of the world's population, according to WHO data, has been infected with mycobacterium tuberculosis. Moving towards the elimination of tuberculosis requires not only diagnosing active cases, but also strengthening strategies for diagnosing and managing latent tuberculosis, especially in vulnerable populations. Today we have highly experienced experts from the Aleaín society who will address key, pathophysiological, diagnostic and therapeutic aspects of this important problem. Many thanks to the organizing societies, especially SADI, which as already mentioned is contributing especially, among other things, to the platform issue, and of course to the other societies involved that I have already mentioned, and to everyone for joining us. Welcome, and now I give you the floor. Have a great afternoon and we hope you enjoy this very interesting webinar.

[00:05:44]Dr. Rodrigo Morales, thank you very much. Hey, we took him out of here, but I know he'll stay behind the scenes enjoying it with all of us. I welcome Dr. Flavia Amalfa, but not before reminding the 100 people connected on the other side that you can leave your questions on the social network where you are watching us. Wherever you are located, you can leave your questions or comments, which the doctors will surely answer when they finish their presentations. Now then, Dr. Malfa, it's all yours.

[00:06:17]Well, welcome everyone to this day, to this talk. Thank you all for the space. Uh, I'm Flavia Malfa, I'm a biochemist, a specialist in microbiology and president of SADEBAC, the Argentine Association of Microbiology. So I'm going to start by introducing Dr. Fernando Viasuti. He is a medical specialist in infectious diseases and a member of the provincial program for HIV/AIDS, STIs, viral hepatitis, and leprosy in Santa Fe. He is also a member of the HIV/AIDS unit at the Centenario Hospital in Rosario. She teaches in the postgraduate program specializing in general and family medicine. He is an infectious disease specialist at AHF Rosario. Member of the Sadi Management Committee for the tuberculosis area.

[00:06:59]Member of the board of directors of the SIR, the Rosario Society of Infectious Diseases, author of the book Latent Tuberculosis Infection, the basis of the Corpus publishing house published in 2022.

[00:07:11]Thank you Fernando for participating in this talk and we give you the space to begin. Thank you all and enjoy the talks.

[00:07:23]Well, thank you very much for the presentation and for the invitation. I'm going to begin. with the presentation.

[00:07:33]Those are my conflicts of interest.

[00:07:39]Well, the presentation was ruined. Actually, let's define it.

[00:07:49]Initially, we could say that the interaction between the host and the tuberculosis mycobacterium could be likened to a football match where there are three possible outcomes. One is to win, one is to draw, and one is to lose.

[00:08:05]From the host's perspective, we could say that there are people who, when mycobacteria tuberculosis enters the lung, present a first line of defense called the innate immune system, which has a particularity that it is trained, and this is a definition of Netea, the trained immunity. These people have this trained innate immune system and are able to eradicate or eliminate mycobacterium tuberculosis at the site of entry, which would be the lung, obviously without a TH1 type response, interferon gamma mediated in the lymph node.

[00:08:49]These people who have this immune system are called resisters and not only do they not get sick from tuberculosis, but they also do not develop a positive PPD test, which as you remember is generated in the lymph node, is TH1 and medium gamma interferon. It is estimated that roughly 8 to 12% of the world's population behave as resisters.

[00:09:15]Obviously, this would be the ideal defense mechanism against Mycobacterium tuberculosis, but 90% of mortals do not have it.

[00:09:27]The second situation, the second result, would be the complete opposite, that is, the mycobacterium in tuberculosis enters the site in the lung. The immune system presents its initial defense mechanism, innate immunity, which is nothing special. 90% of mortals have no innate immunity to anything.

[00:09:50]The immune system needs to generate an adaptive response in the lymph node, and whether due to immunosuppression, immunosuppression in essence, or in children who have a very underdeveloped immune system, that immune response does not arrive in time to contain the focus, and the tuberculosis disease occurs, either locally or disseminated.

[00:10:21]But what happens most often is that the game is tied, that is, mycobacterium tuberculosis enters the lung, the immune system presents an untrained innate immunity, it needs to mount an adaptive immune response in the lymph node and that adaptive immune response arrives in time to generate the granuloma and there the game is tied and the second half is played in the granuloma and in many cases it is played throughout life.

[00:10:51]However, we know that there are two situations in which the playing field is tilted in favor of Mycobacterium tuberculosis. One is in recently infected individuals, when the granuloma is not yet sufficiently structured, and others are in older infected individuals who experience a comorbid process of immunosuppression.

[00:11:14]Uh, this is what we define as a high-risk group for disease: recently infected and previously infected with immunosuppression.

[00:11:24]So far, the classical theory, and to review it in some points we could say that the granuloma is a defensive structure that contains the bacillus like a box of chocolates, but does not manage to eliminate it, which is why the bacillus persists in a latent or dormant form throughout its living life.

[00:11:48]Thus, the individual remains infected throughout their life and there is a permanent risk of reactivation, obviously increased with immunosuppression, and PPD and igra are interpreted as indirect evidence of viable mycobacteria, tuberculosis. This leads to the dogma that a quarter of the world's population has a latent infection with Mycobacterium tuberculosis and that they all constitute a potential reservoir. So far, this is 100% classical theory.

[00:12:25]However, there are modern hypotheses that somewhat call into question these dogmas of classical theory. There are two authors that I like to bring up. One is Marcel Bert. Uh, what Marcel maintains is the following. He says that many people eliminate the infection, that is, they destroy the mycobacterial cligene and retain the immune response as if it were a scar.

[00:12:54]Therefore, a positive PPD or Igra test is not synonymous with having live mycobacterium tuberculosis. It also says that the risk of getting sick decreases over time. In the first two years the risk is higher and then the risk falls and that many late cases are not actually true reactivations, but are reinfections especially in places or regions with high endemicity and that therefore a quarter of the world's population has been infected with mycobacterium tuberculosis and is not infected with Bicobacter tuberculosis.

[00:13:34]The WHO has taken this into account and in fact the verb tense has changed in the papers. I remember when we read articles that identified Mycobacterium tuberculosis as the single infectious agent that causes the most death in the world. One-quarter of the world's population is infected with bicobactylus tubercles. Many modern papers actually say that it has been infected or has had contact with, that is, the weather has changed. And what is Marcelber's basis for saying this, for making this theory available to us?

[00:14:10]Basically, one of the strongest points of the theory of seeing is, look at the graphs. In the graph on my left are people with positive PPD, one group was given a placebo and another isothiazide, and 10 years later they went to see what the rate of tuberculosis patients was in these groups and clearly what we observe is what one would expect, right? Patients who received insoniazid treatment have significantly less tuberculosis, almost 63% less than patients who did not receive it. Nobody is surprised by that.

[00:14:51]However, these patients who were successfully treated had their PPD measured again after 10 years and the PPD remained the same, positive. This means that despite having had successful treatment, the PPD remained positive.

[00:15:11]Another observation to note is the following. Look, these are two graphs, each one shows all patients with positive PPD, with some degree of immunocompromise. The graph on the left shows people who used Dalimumap, an anti-TNF. The graph on the right shows people who were post-transplant of solid or hematopoietic organs. Each of the eh columns A, B, C and D are cuts. Hm.

[00:15:45]And what Marcelber observed is that after 3 years, patients who had not been treated with preventive treatment and who had a positive PPD test, developed very few cases of tuberculosis. Note that the time free of tuberculosis is practically almost 100% in both groups. And what was striking was that when they developed tuberculosis, they did so very early on, thanks to the use of adalimumap and transplantation. And this was indirectly telling us that those people who developed tuberculosis were indeed infected, but if everyone had been truly infected, the number of tuberculosis cases would have been much higher.

[00:16:35]What are the criticisms of the viewing model? Well, the argument is epidemiological and inferential, and just as the classic model cannot demonstrate that there are live tuberculosis mycobacteria with the potential to reactivate, it also cannot show the sterilization of the tuberculosis mycobacteria in those people.

[00:16:59]Another author I like to bring up, but no longer from a clinical and epidemiological perspective, but from the perspective of granuloma, is Laita Rama Crisna. She says in her theory of granulomas that the granuloma is not the best defense mechanism. And we already saw that when I initially stated that the best defense mechanism was to be a resister. Hm. But she also adds that the granuloma should be interpreted as a battlefield and she uses the phrase " dynamic immunological ecosystems".

[00:17:37]Hm. Uh, the granuloma for ramacrine is not a watertight structure, is it? And that Mycobacterium tuberculosis is not a mere spectator of granuloma construction, but manipulates the immune system to build it. And this is important in the early stages. I do n't like to get involved with the molecular biology aspect, but I ca n't avoid it in order to explain Ramacrina's theory in somewhat rudimentary and basic terms.

[00:18:09]Ramacrina says that when mycobacterium tuberculosis enters macrophages, it secretes, as if from a syringe, through elxat 6. The STA 6, which we will surely see in the colleagues who support me when they talk about Igras, is one of the antigens it uses to stimulate the release of interferon. The SAS basically has two functions, one is to attract more macrophages. And why would mycobacterium tuberculosis want to attract more macrophages? Well, simply because the macrophages that are going to come to the site initially are naí macrophages. These are macrophages that are not adapted or trained and can easily be infected and replicate within the macrophage.

[00:19:02]Then, it calls many macrophages to the focus and in turn uses the human epithelial cells to generate a large amount of mm P9, which is a metalloproteinase that destroys the extracellular matrix and makes the granuloma more permeable. Hm.

[00:19:21]So, the granuloma would function as a host defense mechanism.

[00:19:26]Initially, in the early phase, it would help the amplification and spread of the tuberculosis mycobacterium. In the late phase, when the TH1 response is established and T lymphocytes arrive at the focus, the granuloma becomes much more robust, and the tuberculosis mycobacterium uses it as a survival niche. The tuberculosis mycobacterium will live inside the granuloma, but it will have to relinquish the ability to divide, multiply, and cause disease.

[00:19:56]Therefore, for Ramacrisna there is no single granuloma, but rather multiple granulomas, and she says, some progress, others are contained, and some sterilize. The theory of the ramacrine wing is criticized because the evidence is in a zebrafish model and the mycobacterium is marine.

[00:20:19]What are the points of contact between Ver and Rama Krigman, which have in fact led him to write a rather disruptive article that is cited there? It's about latent tuberculosis, two cycles of confusion, and of course, Ver says, "The risk of becoming ill decreases over time," while Rama says, "The early granuloma favors expansion, and obviously the risk of becoming ill is much higher at the beginning with a recent infection."

[00:20:50]Ver, for his part, says, "Some patients achieve the Mycobacterium tuberculosis cycle, preserving immunological memory," and Rama says, "There are granulomas that progress, others that are contained, and some that sterilize." These are the points of connection between both theories.

[00:21:08]And then, to what we saw previously, we add with the green arrow that while there are two moments in which the playing field tilts in favor of the mycobacterium in tuberculosis—we said, recently infected and previously infected with immunosuppression—there are two events in which the playing field tilts in favor of the host. One is time, and the other is the use of the TPT (tetrapulmonary agglutination test).

[00:21:34]These are the discotomies. between the classical and modern models. In summary, we could say that in the classical model, the granuloma is an immunological mechanism that the host builds to contain the bacillus. It is stable and protective. The modern model tells us that the granuloma is a mixed construct.

[00:21:54]Here, Mycobacterium tuberculosis actively intervenes. It is not at all stable or protective, especially in the early phase.

[00:22:03]The classical model states that dormant bacilli exist, but are alive and remain so for life. While the modern model states that many people eliminate the infection through spontaneous clearance. The classical model states that both PPD and IGRA are synonymous with current infection and live Mycobacterium tuberculosis. And the modern model states that both PPD and HIGA are equivalent to immunological memory. The classical model states that a quarter of the world's population is infected with Mycobacterium tuberculosis, and the modern model states that a quarter of the world's population has been infected with Mycobacterium tuberculosis.

[00:22:39]And finally, the classical model speaks of frequent late reactivations, and the modern model says that Late reactivations are less frequent, and the later cases are more likely due to reinfections, especially in regions with high endemicity.

[00:23:00]But of course, the problem is latency— latency is a word, a label, but it actually defines very different biological phenomena.

[00:23:09]I don't want to delve too deeply into history, but in the 19th century, latency was like a postmortem anatomopathological term, that is, referring to patients who had died from any other cause.

[00:23:19]Autopsies revealed tubercles, and it was thought that these tubercles didn't cause disease and were dormant. At the end of the 19th and beginning of the 20th centuries, latency was studied in terms of finding dormant, empty germs. So, autopsies were performed on people who had died from any other cause, macroscopically normal tissues, mainly lymph nodes, were taken and injected into animal models to see if they would develop the disease, searching for these dormant bacilli. And in the 20th and early 21st centuries, that's when the issue really started to get more complicated. Latency with an immunological finding, especially with a positive PPD test and subsequently with the acronyms. Therefore, latency is not a single state, but rather a dynamic spectrum. As you can see in the graph on the left, it is a dynamic spectrum where the common denominator is always a positive PPD or IGRA test, but the numerator includes different people with different risks of developing the disease, to the point that the numerator can range from people who are only immunoreactive—that is, those who have spontaneous or active prothrombin time (PTT) clearance of the mycobacterium—to clinically subclinical forms of tuberculosis, which from 2024 onward will be called asymptomatic tuberculosis.

[00:24:45]What does the WHO tell us about all this?

[00:24:48]Well, it defines latent tuberculosis infection as a state of immunoreactivity against Mycobacterium tuberculosis antigens, which is obviously determined by a positive PPD or IGRA test in the absence of signs and symptoms of disease and without radiographic abnormalities. Clearly, it is a clinical-immunological definition, but it is Ambiguous, it has certain limitations. Hmm.

[00:25:11]Positive tests don't indicate live Mycobacterium tuberculosis. The absence of symptoms can be a method, it's a very subjective finding. Patients may even deny having symptoms, and the changes on X-ray are also subjective; small lesions can go unnoticed.

[00:25:33]Why is it an ambiguous definition?

[00:25:35]Because it has a fundamental limitation. There is no standard goal to define Mycobacterium tuberculosis infection.

[00:25:41]So, what is needed?

[00:25:43]Clearly, we need new biomarkers. Perhaps transcriptomics and proteomics, using RNA signatures and protein biomarker panels, may not provide the answer.

[00:25:56]There are several studies where they are very promising. Why? Because these genomic sciences show the result of that real-time interaction between Mycobacterium tuberculosis and the host. That is, they show what is happening on the battlefield, and this would allow us to first define the exact place where our patient is on the spectrum, and intervene early in cases of disease. Tuberculosis, especially early intervention in symptomatic tuberculosis. And finally, optimizing preventive treatment in patients who are actually infected.

[00:26:36]In closing, I'd like to leave you with a question that is precisely the title of one of Marcelber's most iconic articles: Is mycobacterium tuberculosis a lifelong infection? Thank you very much.

[00:27:01]Well, excellent, excellent, Fernando, your talk. So, we'll leave the questions for last, and we'll give the floor to Dr. Roxana Paul.

[00:27:18]Dr. Roxana Paul is head of the Mycobacterium service in the tuberculosis laboratory at Piñero Hospital and is the coordinator of the mycobacteria subcommittee of Sadbac AM. Well, thank you, Roxana, for being with us.

[00:27:44]Well, thank you very much for the invitation, and we'll begin with the presentation, which in this case I'll be covering, the diagnostic aspect: how to detect the invisible, what the key elements are. Diagnostic methods that we have available at the moment, and to see what is being researched to diagnose this latent tuberculosis infection.

[00:28:11]To begin, we generally focus on the sick person, and it's good that we focus on the sick person, because here we have the active bacillus that is transmitting the disease to potential carriers of this new infectious process, which are all those susceptible people. But this would be just the tip of the iceberg.

[00:28:33]Below it, we have a whole mass of ice that will feed this tip, that is, that will generate more sick people, those who have a latent infection, or as the doctor said earlier, those who have been infected. A quarter of the world's population has been infected by Mycobacterium tuberculosis. And to meet the goals that the WHO has set in the End TB Strategy, which in my opinion are too ambitious, because, for example, by 2025 it was proposed that there would be To reduce the incidence of tuberculosis by 90%, for example, and here in the Americas region, the number of cases and deaths has actually been increasing.

[00:29:24]So, to achieve these goals, it is very important that we address the diagnosis and treatment of latent tuberculosis infection. This was just explained very well by the doctor.

[00:29:39]We are now going to focus on the diagnosis of latent tuberculosis infection, which, as you will see, has no clinical symptoms, no radiological abnormalities, and no way to isolate the bacillus in the microbiological laboratory.

[00:29:58]So, we are going to see what diagnostic techniques we have to make a diagnosis in this period of this spectrum that we have from exposure, from being uninfected to becoming ill. Yes? Why? To prevent the patient from developing the disease. That is, we have to try to be one step ahead to make a diagnosis in these patients who have been infected. And in cases where it is necessary, that We'll see this in the next talk. We've already discussed it, right? The diagnosis of latent infection needs to be directed at those patients who require some intervention.

[00:30:40]So, we're going to meet in this space where we have latently infected individuals, right?, who could become ill at some point in their lives.

[00:30:56]What tests do we have? The first tests we had were skin tests, the tuberculin test or the intradermal Mantu reaction, which has been with us for over 100 years. And now, in 2022, the WHO approved new skin tests that are more specific than the first test, the PPD, because they use specific antigens of Mycobacterium tuberculosis. Let's start by looking at the tuberculin test. Here, TPD is used, which is a proton pump inhibitor derived from Mycobacterium tuberculosis that has approximately 200 antigens. Yes. It's administered as an intradermal injection. On the forearm, on the ventral side of this PPD test.

[00:31:40]What this will lead to is that the PPD antigens will stimulate my immune system, the specific T cells, which will begin to release cytokines and will trigger an inflammatory response that will become visible and palpable through induration. What I'm going to measure is the induration, not the erythema. Yes? This induration is read at 48 or 72 hours.

[00:32:08]It's an indirect test that measures the delayed hypersensitivity response to the tuberculosis antigen. Yes, the cutoff point, let's say, to say it's positive is 10 mm, at least here in Argentina, and for people living with HIV, 5 mm or greater. But this positivity, these cutoff points, will depend on the patient's clinical status. Not only that, but also on the epidemiological context in which I 'm evaluating this test. Working with this skin test. Yes. Here in Argentina, we consider a skin test positive in immunocompetent individuals with a skinfold thickness of 10 mm or greater, and in people with HIV, a skinfold thickness of 5 mm or greater.

[00:32:56]This test, which has been in use for over a year, as we mentioned, has several limitations. First, it requires the patient to visit the testing site twice: once for the injection and again 48 to 72 hours later for the reading. This test requires trained personnel, not only for administration but also for interpretation, because the results are highly variable.

[00:33:25]This test is prone to errors. It uses a type of antigen that is biological and has low specificity.

[00:33:32]Why? Because it reacts with the BCG vaccine strain and with environmental mycobacteria. Right? On the other hand, the tuberculin skin test, which is administered in two steps to assess the booster effect, is generally more common in patients over 55 years of age. In these patients, the initial PPD test is negative, and the second test is used to assess the booster effect. I have to do a second dose after about three weeks, and if it's positive, I can say it's a booster effect and I have an old, latent infection, not a recent one. If the first and second PPD tests are negative, I can say the person isn't infected.

[00:34:18]And when the first PPD test is positive, obviously the second PPD test isn't positive, right? I already have a pre-existing infection based on the clinical context, right?

[00:34:28]Well, this test has false positives, as we already mentioned with those vaccinated with BCG, right? So when the PPD test is greater than 15 mm, then the interference of the vaccine strain is ruled out, right? It also gives false positives with infections from environmental mycobacteria or from local trauma or a ruptured blood vessel, or infection at the injection site.

[00:34:54]On the other hand, it has false negatives.

[00:34:56]People with allergies, for example, those at the extremes of age, in older adults or infants, those with immunosuppression, or those with recent infections, can give false positives. False negatives. Also in severely ill patients, 10 to 20% may have negative PPD tests before the expected period, if administered before the 8- to 12-week window period. And false negatives can also occur, as we mentioned earlier, when the operator is not trained in both application and interpretation. There are new skin tests; three were approved by the WHO in 2020. They use the same technique: an intradermal reaction is applied and read at 28 to 72 hours, but they use specific antigens of the tuberculosis microagent. They use ESAT 6 and CFP10, which are the antigens also used, as we will see later, by [unspecified group]. This gives it greater specificity; therefore, its diagnostic accuracy is similar to IGRAs, but greater than the MAND dextrose reaction because it eliminates cross-reactivity with the BCG vaccine strain and is a test It's safer because it doesn't use a biological antigen like PPD.

[00:36:14]The second type of test we have is the interferon gamma release assay. Interferon gamma is the most potent cytokine we have in our body's fight against tuberculosis, our immune system's defense against the virus.

[00:36:27]These interferon release assays were approved by the ONS in 2011. The classic assays are the Quadron TV Gold and the T Sport TV.

[00:36:39]In 2022, some alternatives were tested: the Quadron TV Gold Plus, which is an improvement on the one approved in 2011, and the One TV Igra. There are other Igra assays that are already available, but more experience is needed to validate them for use, so that their results are validated when one writes a report.

[00:37:03]But well, it's just a matter of time; most likely, in a couple of years, they will also be approved by the ONS. One of them is the Tiveron F, The Vidas test is from BioMérieta. I know it's in Argentina, it 's already available, but well, it still needs a little more evaluation.

[00:37:24]Okay, this acronym, for its English acronym, is an immunological test, an alternative to the PPD, for the detection of latent tuberculosis infection.

[00:37:33]It consists of measuring the in vitro immune response of memory T cells against these specific Mycovactin tuberculosis antigens.

[00:37:43]Skin tests are in vitro tests.

[00:37:46]These are IGRAs, they are in vitro tests. So, very simply put, the specific antigens ESAT 6, SFP10, and TB 7.7 are presented to macrophages. Phagocytosis occurs, antigen presentation takes place. And some parts of the slide aren't visible here.

[00:38:10]Unfortunately. Well, these antigen-presenting cells present them to the memory T cells. Yes. And once the antigen is recognized, this recognition occurs between the T lymphocytes and this antigen trigger the release of cytokines, primarily interferon gamma. These immunoglobulins have greater specificity because they utilize specific antigens that are absent in the vaccine strain. They are absent because they are encoded in a region called the differentiation region one, where antigens 6, FP10, and PV7.7 are encoded. Since vaccine strains lack this region, they do not produce these antigens, therefore there is no cross-reaction with the vaccine strain. However, false positives can still occur with some mycobacteria, including Mycobacterium avium, which actually causes skin infections in patients who work with aquariums or whose activity is fishing. There is an epidemiological factor that can lead to a false positive. The remaining mycobacteria, Ulcerative colitis, Clavis, and Senopus, cause pulmonary infections. Here in Argentina, for example, our largest The problem would be the cansas test because, in terms of frequency, it's the one that most often isolates these patients who come in with pulmonary infections caused by mycobacteria, not tuberculosis.

[00:39:39]The two most commonly used tests are the Conferon TB Gold and the T Sport TV PV. Let's see here, in very broad terms, the differences between them.

[00:39:50]Both require a blood sample.

[00:39:53]The Conferon TB Gold uses whole blood.

[00:39:58]Yes. In contrast, the IBspot requires a preliminary step, which is the separation of mononuclear cells.

[00:40:07]Both the mononuclear cells and the whole blood in these kits are exposed or incubated with specific tuberculosis antigens, and then the interferon-gamma is quantified. In the TV spot test, the technique is a spot test, and the result obtained is the number of interferon- and gamma-secreting T cells, that is, the number of activated T cells. And the cutoff point—there are two cutoff points. The United States uses one that is greater than or equal to eight spots. In the well, we have to see those colored dots; those are the Activated T cells. Uh, if it's greater than eight, we say it's positive. Uh, and yet the international consensus uh considers it greater than or equal to six. However, in the Tibigol quadrant, uh, which only works with whole blood, it doesn't have that preliminary step; it's incubated with the antigens, and the interferon gamma measurement is done by the Lisa method, and the results are expressed as interferon gamma concentration. And the cutoff point is 0.35.

[00:41:18]Yes, for the tube that has the antigens. There are also uh, these techniques have, excuse me, uh, a negative control and a positive control.

[00:41:30]Well, the Quantiferon uh is, let's say, the kit that has been most widely used and is the one that has evolved over the years. The first kits came out in 2001, and it has been improving its performance in terms of diagnostic accuracy. Uh, we just saw what the Tibigol quadrant is, the one with the three tubes. There's a new kit Which is the Quantiferon Tibigol Plus, which adds a fourth tube, so, in addition to measuring the response of CD4-positive T cells, yes, of the patient, it also includes the response of C8-positive T cells. And these T8-positive cells are taken as a predictor of progression from infection to disease. Why? Because their response would be greater in these cases.

[00:42:27]Hmm. So, with the addition of this new tube, this test becomes much more precise, increasing its specificity and sensitivity.

[00:42:39]In turn, this company has also designed a kit for peripheral use, which is the Kia RIP, which eliminates the positive and negative controls; it only works with one tube. That is, instead of drawing 5 ml to perform, for example, the Tibigol Gold Plus test with four tubes, here I only need 1 ml of blood because I am working only with the tube containing the specific antigens for tuberculosis.

[00:43:13]And also, the region is done in less time and the method changes, it is not an ELISA, but it is through lateral flow immunofluorescence, which are these little caps. blue. There is a device that allows us to perform eight tests at once, and it is for peripheral use, to bring these tests closer to the patient.

[00:43:36]Yeah?

[00:43:39]Well, between these two most commonly used, the Gold Plus quantiferon and the Tib Spot, there are several differences, but the most important thing to point out here is that the TIB Spot is a much more laborious technique than the quantiferon.

[00:43:55]And in turn, it has, for example, that the time required from when the sample is taken until it has to be processed is less for the TV Spot, which is 8 hours, and greater in the TV Gold Plus, which is 16 hours and at the hour it is a little more flexible even that by keeping it in the refrigerator at two between 2 and 8 gr the sample can be kept before carrying out the test 48 hours. Yes, the TB Spot is more reliable in some oppressed individuals than the quantiferon, but well, the quantiferon is actually more widely disseminated, it is all automated, whereas the TV spot is more technical, it is more laborious.

[00:44:37]Here's the difference between skin tests versus IGRAs: one is an in vivo test and the other is an in vitro test. One uses the PD which is a biological antigen. In exchange, the specific antigens of coacto and tuberculosis are used. This increases the diagnostic accuracy of the test, which for skin tests requires the patient to go twice for application and reading. In contrast, for livers it is a single visit by the patient to have blood drawn. The PPD, the reading is subjective. We had already said that the application and the reading are a key point. This is where the greatest number of errors occur, so we need to have trained personnel to perform it. In contrast, the acronym is an automatic reading; there is no subjectivity in those results. The skin test takes two to three days. In contrast, we have the cigars in 24 hours. Uh, the skin tests have the reactions used with the DCG vaccine strain, whereas the cidras do not. And one thing that is no less important is the cost.

[00:45:45]Titan tests are more accessible than hras. Well, implementation, one of the main obstacles in implementing these tests is their cost.

[00:45:56]And well, these new tools have come to optimize laboratory time, decrease operator-dependent variability, and facilitate implementation and access to testing. Well, even more evidence is needed in immunocompromised patients, pregnant women, and children, especially with these new kits that are simpler and faster, without positive and negative controls. And through these immunofluorescence methods, these lateral flow immunofluorescence cartridges, which actually give qualitative and not quantitative results.

[00:46:31]Uh, when we do a report on these IGRAs it must be as accurate and clear as possible. We need to specify what techniques are being used, what the results are, whether they are qualitative or quantitative, and how many have been used, so that it is easier to interpret them. And globally there is a priority in the development of new tests that allow us to predict the progression of infection to disease, not only to diagnose that they are infected or have been infected, sorry, but to see those patients who have a higher risk of progressing to the disease. That would be the greatest achievement. And currently, among others, the Igra test free of the ESAT 6 antigen is being investigated because it has been used as one of the components of the new vaccines. So they are investigating replacing this SAT 6 with other antigens.

[00:47:31]Okay, to summarize then, we don't have a standard Go test available. Hm.

[00:47:36]Both cutaneous PRAS and SIGRAS are indirect and require a competent immune response for a valid result. We had already said that more evidence is needed in immunocompromised people, pregnant women, and children. We currently do not have a test that allows us to differentiate between patients who have an infection or have been infected and those who have an active infection, the viability of the mycobacteria, the duration of the infection, and, most importantly, those infected who will progress to disease. They have a higher risk of progressing to disease. And these tests are only recommended for those individuals who will benefit from preventive tuberculosis treatment, not for mass testing, but for those patients who deserve preventive treatment.

[00:48:32]Well, for example, recent infections by mycobacterial tuberculosis or those people at higher risk who will be discussed in the subsequent talk, everything that is preventive treatment for latent tuberculosis.

[00:48:47]Okay, which of these two tests should I choose?

[00:48:50]Which one do I choose, depending on the population clinical context? For example, if I have people vaccinated with BCG, it is preferable to use a Higra because I am already ruling out what I am going to have, I am not going to have the cross-reaction with the vaccine strain. Hm.

[00:49:06]I also use the HIGRA test in immunocompromised patients, but if I have the option of using both tests, I can use both tests.

[00:49:11]Because? Because they are not the same size. Uh, so they complement each other in the diagnosis by approximately 10, 20%. Therefore, in high- risk tuberculosis groups, it is recommended to do both tests if the first test I do is negative. Hm. Because status, clinical context, and population context greatly influence the results. Yes.

[00:49:41]Well, this is what we have, but there are some reviews, but there are many research studies to have different tests that mainly identify these patients who have been infected and who are going to progress to the disease. One of them is molecular testing that involves RNA sequencing.

[00:50:06]I am detecting RNA, especially of bacillus antigens, which implies that the bacillus is beginning to replicate and that the patient will progress to disease.

[00:50:19]Proteomic tests are being used to detect and identify specific proteins at this latency stage, and research is also being done on cytokines as biomarkers, not only of interferon gamma, but also interloctin 6, 4, and 2. Yes, this is a paper that reviews all the ongoing work being evaluated to see if we can develop another test that allows us to make these diagnoses. And I didn't want to leave out Diacos TV, which we call the Argentine book. This is a development by CONISET, by Dr. Verónica García and her team. They started doing all these studies in 2015, in which they confronted different antigens of microacterium tuberculosis and saw which ones had a greater or lesser response from the C4 cell. And what they did was devise a Higra that has the specific antigens, SAT6, CFT10 and RB2626C, which is a late hypoxia antigen, which has high levels in the latency stage, but is detected in the active disease stage.

[00:51:38]So this Hra would be giving us a greater discernment or differentiation between what is latent and active infection that had not been achieved with the previous Ibras that we were mentioning. Yes, this development was done at the Faculty of Biological Chemistry of Exact Sciences.

[00:52:03]They do it; they have their kit that is approved by Almart.

[00:52:07]And well, here are some presentations of many publications from this group, which have been recounting this entire stage of antigen research up to the discovery of this RB 2626C and how it works in discerning what is latent infection, active infection.

[00:52:29]Thank you so much.

[00:52:33]Thank you so much.

[00:52:37]Well, Roxana, excellent, excellent.

[00:52:41]Wow, your talk was very interesting, so thank you a lot. And now we're going to give the floor to Dr. Ronald Bentos. He is a member of the Paraguayan Society of Infectology, a consulting physician at the Hospital de Clínicas and the National Institute of Respiratory and Environmental Diseases, and a ward and office physician at the Institute of Tropical Medicine. Ronald, this is your space.

[00:53:08]Presentation. Good afternoon everyone.

[00:53:11]Well, it's truly an honor to be here talking about such an interesting topic with so many facets and points to discuss regarding the types of latency. I'm going to try to give a look from the perspective of how much we do, whether it's in the office, through interconsultation, and the decisions we make precisely to indicate the preventive treatment of tuberculosis, clearly from a practical perspective, not as a mere formality or as an interpretation of a PPD or as a clinical decision. Clinical decision that has the main objective of identifying a person who is not yet sick, but who has a preventable risk of progressing to active tuberculosis.

[00:53:56]One question we always ask ourselves is, how many cases of active tuberculosis actually begin as a preventative opportunity to progress to an idea of ​​reviewing cases to answer specific questions such as, for example, who to look for? How to rule out an active disease? When to treat?

[00:54:17]When to defer? When should you not treat? The message that accompanies us throughout all the presentations that we do not properly address is that we do not address a preventable risk.

[00:54:31]And we're going to start with this first case.

[00:54:34]In this case we can see a young patient of 37 years, a smoker, a crack user, and a consultation with a one-month history of marked weight loss. Asthenia, pertina and nocturnal sweating.

[00:54:49]In the case of this patient, we have advanced pulmonary tuberculosis, as we can see in the tomographic images, but the main and central point is not to describe the current disease, but to look back a little further. A key piece of information is precisely the contact history. Your sister had active pulmonary tuberculosis 3 years ago and unfortunately this patient did not undergo any contact tracing or preventive treatment. The first case puts into practice the initial idea that many active tuberculosis cases may have started as an unrecognized preventive opportunity.

[00:55:37]Let's move on to the second case. Uh, this second case also shows a missed preventive opportunity.

[00:55:57]Dear Ronald, we kindly ask that your image and presentation look very good, but perhaps we can improve your audio if possible. I think so. Okay, fine, go ahead. Thank you.

[00:56:17]Yes. Uh, let me know if it sounds better here in the chat.

[00:56:21]Yes, yes, it sounds much better, much better. Well, continuing with the presentation here, in this case I wanted to show you another missed preventive opportunity, in this case an HIV patient adhering to antiretroviral treatment who comes to the consultation with a typical and characteristic picture of pleural tuberculosis.

[00:56:46]The key and interesting fact about this patient is that he was diagnosed 10 years ago and is adherent to antiretroviral treatment, but at no time is there any record of screening, nor even prophylactic preventive treatment in this patient. And this is precisely something we see a lot in our practice, we doctors who work in HIV clinics, that we have opportunities to treat these patients and prevent the progression to tuberculosis, and sometimes due to lack of knowledge, lack of time, or other variables, we don't do that screening properly because something we all know is that tuberculosis, even when controlled with antiretroviral treatment, does n't mean the patient is out of risk of developing active tuberculosis. HIV always requires active screening, as does latent tuberculosis infection because adherence to ART reduces the risk, but does not eliminate it completely.

[00:57:49]Here in this third case we completely change the point of focus, right?

[00:57:55]It leads to a completely different scenario.

[00:57:58]a patient who is going to start immunosuppression that can completely change their risk.

[00:58:03]We have a 22-year-old patient with inflammatory bowel disease, treated with corticosteroids, but without an adequate response, since he was probably evaluated by the appropriate specialist and prescribed treatment with antifungals, in this case Infisimón, which we know greatly increases the risk of progression and activation of tuberculosis, making this the scenario of a patient with latent tuberculosis.

[00:58:28]Interestingly, in this case the patient underwent a logical prior evaluation, an IGRA test was performed, which returned negative. In some situations this may reassure us, but proper questioning of the patient and correct evaluation of risk factors are always important, because a negative result alone cannot change our behavior. Even in this patient, a key piece of information in the logical pre-assessment was that he too was a patient who had been exposed to tuberculosis, living at home with a relative with tuberculosis for a year. Therefore, the risk changes completely despite a negative IGR. Therefore, the clinical reading and the main message of this slide is that the test does not replace clinical judgment.

[00:59:18]Before initiating any immunological treatment, in this case primarily anti-TNF therapy, active tuberculosis must be ruled out and it must be determined whether or not prophylactic treatment is appropriate. It must be based solely on the thesis. Sometimes we can err on the side of thinking, "We have a negative test result and everything is fine, we can start treatment," but if the patient has a relevant contact in a relevant epidemiological context, they are also a patient who should receive prophylactic treatment precisely to avoid reducing the risk of active tuberculosis after starting this treatment.

[00:59:54]And the fourth case that I'm going to show you completes the reasoning with an opposite situation, right? The key is always to try. Sometimes the right decision is also not to treat, even with a positive Igra result. So far we have seen scenarios where the problem was not missing preventive opportunities.

[01:00:13]The challenge here is not to turn a positive test into an automatic indication.

[01:00:18]That's a very interesting and relevant point that we can discuss at length.

[01:00:22]The patient has a positive Libra test, but the exposure, as we can see here, is a remote exposure; there is no recent contact, she does not live with an active case, and immunosuppression is not being considered. In that context, the first thing to note is that the current risk of progression seems low. In addition, another important fact is the primary filial cirrhosis that the patient has with a persistent alteration of liver enzymes. So, the question changes even here, right? It's not just whether the treatment could benefit the patient, but whether even the benefit of this treatment outweighs the expected risk of toxicity. In this case, remember that a positive IR (immune response) does not always obligate us to treat when the epidemiological risk is low; the risk and the risk of harm are high, as we see in this case. Not treating today when it is well-founded is also an active decision, and that is something very interesting that we have to keep in mind. Sometimes we can make a decision automatically, whether with a negative or a positive test, but we always have to assess the patient's clinical context, conduct an appropriate interview, and review any additional tests that can help us make that decision.

[01:01:28]And here, apart from the explanation after seeing the four cases, we can organize a little more how we decide the treatment, and the first thing we decide is precisely who we actively look for latent tuberculosis in. As we saw in the previous talk, we don't look for it in all patients, we don't look for it in all people, we look for it where preventive treatment can mainly prevent an active disease. And here we have two important paths towards precisely indicating who to look for. Patients who have a higher risk of progression and patients who have a higher probability of infection. When we talk about patients who are at higher risk of progression, we know very well that HIV/AIDS patients, patients who are receiving or will receive immunotherapy, patients who are on dialysis, patients with silicosis, those who are going to undergo an organ transplant, or patients who are going to undergo a hematological transplant.

[01:02:25]These are the patients who have a higher risk of progression. In these cases, we will always look for latent tuberculosis in order to provide prophylactic treatment if required. And also in patients with a higher probability of infection. In these cases we have patients with contacts of, patients with confirmed pulmonary tuberculosis, close contacts at work, school, institution, other closed spaces and population where systematic screening may be considered according to the context. In our country in Paraguay, for example, prisons and the indigenous population are places where we routinely actively search for latent tuberculosis to prevent its progression into active tuberculosis. I can decide which patient I am going to look for latent tuberculosis in. Our next step before directly treating the patient is to demonstrate that we are not dealing with active tuberculosis, and this is usually a step that has some complications and is a very important point that we have to keep in mind. Because?

[01:03:26]One of the most important points I want to share with you all is that we cannot start prophylactic treatment if the patient has a clinical, radiological, or microbiological suspicion of active tuberculosis. Because? Because in this patient, evidently, the patient needs a complete treatment before prophylactic treatment. So here I've left a clinical exclusion checklist that we can use in the office precisely for this decision, right?

[01:03:56]Always start with the interrogation. The questioning will help us a lot in making decisions.

[01:04:01]Obviously, if the patient has a cough, fever, night sweats, weight loss, hemoptysis, or any manifestation that we can take as a presentation of extrapulmonary tuberculosis, that patient should undergo studies first before deciding on a prophylactic treatment.

[01:04:19]Images help us a lot, a chest x-ray and if compatible results have been found, we can even expand the study with other complementary imaging methods and the samples that obviously, depending on the context and the patient's symptoms, will be necessary to rule out active tuberculosis.

[01:04:37]What is the first thing we should do before starting? We need to be absolutely sure that the patient does not have active tuberculosis.

[01:04:46]See later, and also as we saw in the previous talk, right? The hygra and PPD tests will not distinguish whether the patient has active tuberculosis or lactic tuberculosis. Therefore, the clinical decision is always based, first and foremost, on ruling out active tuberculosis. If it is ruled out, we can make a predictive indication and choose an appropriate scheme.

[01:05:06]The goal here is not to treat quickly, but to treat correctly to avoid resistance, toxicity, and diagnostic delay. So, the next question that comes to mind is precisely what we use and how we interpret the result. We saw with the previous clinical cases that the interpretation of the result is quite important precisely for our decision. And here we see precisely what the PPDI and the Liga tell us and what they don't tell us: both tests detect an immune response, neither test differentiates between infection and disease, and as we saw earlier, there is no test that has become the standard for diagnosing a latent infection.

[01:05:47]The most important thing is not deciding which test I am going to use, but how I am going to interpret the result of that test. And the most important thing is precisely to interpret in the appropriate clinical risk context, in the context of the patient, obviously a patient with contact, a relevant exposure of IH, with immunosuppression, the probability of re-completing the treatment is what will help us to interpret these tests. Because?

[01:06:15]Because a positive result will never directly force us to treat, it will not open the window to determine whether this patient will benefit from the treatment or not, and if they will benefit, whether they will tolerate said treatment or not. The key message I want to convey in this slide is that we don't directly treat the number three; we treat a person with a probable infection and a risk of developing a disease later on. Whether it's the PPD or the Igra, they open up a clinical decision for us, they don't directly close us off to a diagnosis.

[01:06:49]All of this must always be integrated, whether it's the relevant exposure, the host, or the safety of the treatment.

[01:06:55]Taking all of that into account, we will be able to say which patients we will treat and which patients we can expect or monitor clinically. If we decide to treat, another question arises: what scheme can we use to carry out an appropriate preventive therapy?

[01:07:12]We have the decision to treat, defer, or not treat. This is probably the most important slide of all the talks. The decision must always integrate the risk of progression, safety, and the real possibility of completing the scheme. We don't treat an isolated positive test, we treat a preventable risk. And here we have a timeline of how we should decide on the treatment. First, the probable infection, whether it's a patient with basilar contact, a relevant exposure, the risk of progression that an HIV patient may have, will receive antifungal, a biologic, a transplant, and we have already ruled out active tuberculosis, there are no compatible images, the patient has no symptoms, we must have a viable scheme to review first the interactions, whether or not it will present pathologicality, the availability and the adherence. And here we have three possible exits. The first decision would be the decision to treat. Which patients are we most likely to decide to treat? a patient who is at high risk of progression, who no longer has one, for whom we have ruled out active tuberculosis, and for whom we have a safe and available regimen. The second decision would be to defer. In the different case.

[01:08:32]First, as we saw earlier, if we still cannot completely rule out active tuberculosis, in this case we will first study the patient and then the prophylactic treatment. If there is any contraindication for the use of the medications we will see above, if there is a critical interaction of these medications, and if there is no complete certainty that the patient will receive adequate treatment. And the third point, which is the decision not to treat, will mainly be based on whether the patient has a low risk of progression and active tuberculosis, predictive value, balance, harm, unfavorable benefit in the patient.

[01:09:14]situations where prophylactic treatment may end up causing more complications than benefits to the patient. Therefore, the decision to treat, defer, or not treat is always based on the patient's total clinical context, not just on one test and not just on one study, but rather on integrating all of this so that the patient receives appropriate treatment and can successfully complete the treatment.

[01:09:44]If we decide to treat the patient, we will always choose what is safe and what is possible. depending on our availability.

[01:09:55]A practical principle: we will always prefer short schemes if they are safe and available. The short schemes are exemplified here in the slide, isoniazid rifacentin, eh rifar piscina sola o isoniazid con rifan piscina. These are the short regimens used, as you can see, based mainly on rifamysins. And that's something we need to keep in mind right before using it. We need to assess whether the patient is taking other medication, and if there are any contraindications between this medication and the other medications the patient may be taking, which could explain the need to use another type of prophylactic treatment.

[01:10:35]We'll choose in practice. If rifapentine is compatible, the patient has no contraindication to it, and there is no interaction with other medications the patient may be receiving, it would be our first treatment option. If we don't have a pool raffle, we can use what is a raffle, a pool raffle with isoniazid, or a pool raffle alone, which are also usually practical options. Now, if these rifasinas, whether it's the pentina rifa or the pisina rifa, are not safe because the patient may not tolerate them properly or has medications that could interact with them, we can use other options. And this other option is a treatment that is a little longer, so adherence to this treatment is usually a little less viable, which is isoniazid. Those are precisely the therapeutic options we have. And something that I think is most important is that the best plan for the patient is precisely the plan that the patient can complete without unnecessary risk. Ideally, it should be short when possible, but the most important thing is that it is always safe.

[01:11:51]Regarding contraindications and smart pauses for this medication, when the risk of treating outweighs the benefit of preventing, we can defer some situations, mainly if the patient has hepatitis, tertian fever, liver symptoms, excessive alcohol consumption, or a serious unresolved interaction.

[01:12:08]In those cases, even if the patient has a specific indication, we can postpone the treatment, which is not, obviously, not treating, but postponing it until we can solve these complications that may affect the patient. And the patient should receive it, but somehow has, like here, a chronic pathology, uh, a complete, uh, complex polypharmacy, sorry. In that case, we should individualize the treatment. It's not just a matter of prescribing and that's it, but of doing the proper follow-up, scheduling a re-evaluation to see precisely if the patient tolerates the medication or not, and if they do, whether they are taking it correctly and whether they complete the treatment. That's the most important thing.

[01:12:57]Regarding adherence and safety, the best regimen is the one that the patient can understand, tolerate, and complete. And there are three actions that specifically increase the completion of prophylactic treatment for tuberculosis. First, simplify; ideally, use short outlines. The shorter the outline, the easier it is for the information to complete the treatment. Obviously, this also needs to be safe and available. Explaining this is a point that we sometimes struggle with in consultations, right? Because of the number of patients we have, but it is extremely necessary to explain to the patient and clarify that what we are trying to prevent is future tuberculosis, even if the patient feels well at that moment, because that is precisely something that patients often complain about: why should I take medication if I feel well? We need to explain to them the risks of not taking the medication, as well as the risks of taking it, because that is also a good practice.

[01:13:52]Explain to him that the preventive treatment is precisely that, to prevent the patient from developing tuberculosis later on, which could complicate his lifestyle and cause some complications.

[01:14:07]And the patient continues, not taking the medication properly or interrupting the treatment. The important thing is to tell the patient that they need to contact him quickly so as not to lose him, to take an early break, to reassess the interactions the medication may have, to improve tolerance so that the patient can complete the treatment, and also to identify the real issues we need to address in the patient.

[01:14:35]In third world countries, the cost of transportation for the patient to come and pick up the medication is quite important. Whether due to work schedules, distance, the center, adverse effects, self-medication that may also occur in patients who may complicate prophylactic treatment and low compression of the tuberculosis patient.

[01:15:01]Here, adherence doesn't just depend on the patient; it depends on the plan being feasible, being explained properly, and being fully supported.

[01:15:12]And here to wrap things up, we're going back to the cases, and I think the most important thing about this presentation is precisely the title of it, right?

[01:15:23]Deciding on prophylactic treatments for tuberculosis without automation. We here are not dealing with an isolated test, we are dealing with a preventable risk. In case one, a patient with active tuberculosis that could have been prevented. Here we have a missed opportunity. In case two, an IH patient with pleural tuberculosis.

[01:15:41]Here, an active investigation will likely help the patient avoid precisely this active tuberculosis that he presented.

[01:15:50]In case three, the relevant thing is precisely that a fig does not close the decision not to treat the patient. And case four, the opposite, that at a proactive level, a patient with a pathology, is not directly something I must treat, but we must follow up and build to assess later on if the patient's risk increases and we can, in this case, provide treatment.

[01:16:19]To treat or not to treat. The right decision depends on the risk, the safety, and the actual possibility of completing the treatment. We do not treat PPD, we do not treat Igra directly, we treat a person with a preventable risk of active tuberculosis, treat, defer not treat. And I want to leave you with this thought, right?

[01:16:44]Prophylactic treatment for tuberculosis is a preventive intervention.

[01:16:50]Well, a preventive intervention that is important precisely not to automate, it is necessary to select appropriately, rule out active tuberculosis before deciding on the treatment, choose well and accompany until it is completed.

[01:17:08]Thank you very much for your attention. Uh, we're open now to any questions you may have.

[01:17:20]Thank you, Ronald. Excellent dissertation. So here we all are again. Okay, if you don't mind, since we're running a little over time, let's ask two questions. So here I have a question: "I'd like to know if you have experience with the TV Fón SPP test, the Biosensor brand. Thank you.

[01:17:46]Hello. No, look, uh, here in Argentina, IGRAs haven't really been used much.

[01:17:53]The main obstacle is the cost, right? Especially in public health. So, the truth is, we don't have experience with that kit. At the reference laboratory here at the Malá Institute, we don't perform the test. But, well, I know that some private laboratories do, but with a quantitative test, the test that has been most evaluated and has had the greatest use, let's say, the greatest acceptance, is the quantitative test.

[01:18:25]Perfect. And the other question is, how would the IGRA result be affected if a PPD or a CG vaccine was recently administered?

[01:18:41]Because I didn't hear you well, Flavia, you got the vaccine, uh, you gave me a PPD, let's say, and then they do the IGRA. That was the Question.

[01:18:51]Yes, no, no, it doesn't specify what, but I do understand the BG. Yes.

[01:18:58]Ah, so, they get the BCG and then they do the Igra test. There's no interference, no cross-reaction with the vaccine strain. Why? Because what it looks for is the reaction against specific antigens, right? That aren't present in the BCG, in the BCG vaccine strain.

[01:19:19]Perfect.

[01:19:22]I wanted to clarify that it's been uploaded, so everyone will be able to listen to it again.

[01:19:30]Since we don't have much more time for questions, we wanted to thank all the speakers, everyone who organized this event, and well, just to thank them again and everyone who was on the other side, listening attentively to this very important and difficult topic, right, Diego? Very good. We are grateful as guests and proud to be part of this alliance, which we are sure is moving forward steadily and tirelessly, and that events like these will be repeated for the good of our entire community.

[01:20:10]As We always say, we are very grateful to all of you for sharing your knowledge with others. Besides being an act of teaching, it's also an act of love. So it makes us very happy.

[01:20:23]Until next time. Then, as Flavia rightly said, this session is recorded as soon as it ends, so you can copy the link for free access, watch it again, save it, and I think you should recommend it too.

[01:20:36]Good afternoon or good evening wherever you were. Thank you.

[01:20:40]Thank you.

[01:20:44]Look, an infection that doesn't cut