New insights into endometriosis, and mapping dengue in Latin America

First up on the podcast, Staff Writer Meredith Wadman joins host Sarah Crespi to discuss recent advances in understanding endometriosis—a disease where tissue that resembles the lining of the uterus grows outside the uterus, causing pain and other health effects. The pair talk about how investigating the role of the immune system in this disease is leading researchers to new potential diagnostic tools and treatments. Next on the show, why are there good dengue years and bad dengue years? This week in Science Translational Medicine, Talia Quandelacy and colleagues map the synchrony and spread of this mosquito-borne disease in Latin America. She joins the podcast to talk about how the seasons, rainfall, and even El Niño connect with dengue levels and how this understanding can help with prediction and preparation. Quandelacy is an assistant professor in the department of epidemiology at the University of Colorado School of Public Health. This week’s episode was produced with help from Podigy. Transcript Sarah Crespi: This is a Science Podcast for August 21st, 2025. I'm Sarah Crespi. First up, staff writer Meredith Wadman discusses recent advances in understanding endometriosis, a disease where tissue that resembles the lining of the uterus grows outside the uterus. We talk about how researchers are now investigating the role of the immune system in this disease and finding new paths to diagnosis and treatment. Next on the show, why are there good dengue years and bad dengue years? This week in Science Translational Medicine, Talia Quandelacy and colleagues map the synchrony and spread of this mosquito-borne disease in Latin America. She joins the podcast to talk about how seasons, rainfall, even El Nino connect with dengue levels. Endometriosis probably affects 10% of reproductive-aged women. It can be painful, it often takes years and years to diagnose, and the treatment options are not great. This week in Science, staff writer Meredith Wadman wrote about new insights into endometriosis and potential pathways to treatment, and these are often coming from researchers with the disease. Hi Meredith, welcome back to the podcast. Meredith Wadman: Glad to be here with you, Sarah. SC: Reading this story made me realize that I might need a refresher, I might have an old definition of endometriosis in my brain. What are the main characteristics of this illness? MW: Endometriosis is a disease where tissue like the lining of the uterus grows outside the uterus. That's most often in the pelvic cavity area, but it can occur further afield than that. That's the definition of the disease. SC: Why does it take so long to diagnose? MW: Well, a physicians don't have enough of an index of suspicion for it, and what is commonly called just period pain, normal, you're having cramps, sorry, that's part of life, girly, that too often is what happens, and it doesn't get properly investigated until women or young women or teenagers chronically come back and say, this isn't normal. And it takes a lot of agency to do that. So a lot of women, particularly less privileged ones, suffer in silence, and many of them are never diagnosed. SC: And if you do get diagnosed, what is the treatment like? We should mention that the pain, it does come often with the cycle of the period. So, when you're menstruating, you're going to have a lot more pain, for example. So, that's kind of why you can just, people might write it off as, oh, that's just extreme end of cramping during menstruation, but there can be more going on. MW: Just to flag before hitting treatments, chronic pelvic pain, not just during the menstrual time, is also associated with endometriosis. In fact, it can be a signal symptom of it because these areas of abnormal tissue growth become a little like mini centers of inflammation. And so, they're constantly grinding away. And then there's scar tissue that forms and it tethers the organs sometimes to each other, to the abdominal wall. There's lots of sources of pain. Oh, and by the way, these lesions also within themselves sprout their own nerves, which increases pain and activates pain pathways. SC: Just so they can do more shouting. MW: Yeah, right. SC: It takes a long time to figure out what's going on in people. And then what kind of treatment is on offer? MW: So first, there is no cure for endometriosis. The treatments such as they are, are intending to alleviate the pain of the disease. And they principally consist in giving hormones, whether that's combined oral contraception or sometimes synthetic copycats of the progesterone hormone made normally by the ovaries. And sometimes more serious drugs that shut down estrogen and progesterone production, the key reproductive hormones produced by the ovaries. So, those are the sort of medical take a pill or have an injection types of treatments. And then there's surgery, which by the way, is still the only way to get to an iron clad diagnosis of the disease. And that typically will both in the first instance, the surgeon will take biopsies to look at under the microscope. And yes, confirm this is endometriosis, but then they will try to excise the abnormal tissue growths, either with a laser, burn them off or remove them. And that works in some women for a while, but frequently the lesions will recur. And so surgery in itself is not always curative by any means. SC: How successful are surgeries when it comes to clearing the lesions and making people feel better? MW: Well, it depends on the surgeon. And this is a really important point. Ordinary gynecological surgeons who do not specialize in endometriosis, but take on a case here and there, the success rates are not great. These lesions are really tricky to spot sometimes and they can be overlooked. And the women close up and said, we didn't find anything or we found some lesions, but guess what? They missed some others that are hiding in certain spots. In the hands of a skilled endometriosis surgeon who does tons of these surgeries, like hundreds, the results are better. But even so, if you think about retrograde menstruation coming into the pelvis month after month, a surgeon can do a really fine cleanup and that doesn't necessarily eliminate the source of the problem. SC: So in the past, endometriosis was seen as hormone driven, which is evidenced by the treatments that you were talking about. That's the path that's been taken. But now scientists are looking at the immune system as a partner in this disease. What are some of the early indications that we're seeing that it might play a role in endometriosis? MW: Yeah, there's been this explosion of research in the immune system's role in endometriosis over the last 10 to 15 years, where if you search the medical literature, you just see this curve of papers. Just the graph is just practically climbing straight up because there's so many papers being published. And what they're learning is, is that the immune system fails to clear out this abnormal tissue. I mean, it should come running to the scene of the crime and say, "You're out of place. I'm going to hoover you up and get rid of you." And it's weak in that function. But also papers now are showing and have shown for quite some time that it's actively playing a role in allowing these lesions to get a foothold and persist. SC: Another area that's being explored right now is kind of looking at the root of this disease. Where do these cells come from? Why do they grow? How do they establish? What are we learning about that? MW: For really most of a century, it has been thought and theorized that the root of the disease is this what's called retrograde menstruation. That means backwards flow of menstrual blood. Instead of going out the vagina, going back up the fallopian tubes, which are open to the pelvic cavity and spilling out into the pelvis. And this indeed does happen in 90% of women. There's evidence that some degree of menstruation goes back into the pelvis. But there are obviously other systems at work in women with endometriosis or else 90% of women would have it. But that is historically and still today the dominant theory about how endometriosis establishes itself. But there are other theories as well because it's being learned that this is an incredibly varied and complicated disease and looks different in different places in the body and looks different in different women. So, it's not kind of a one size fits all causation probably. SC: So, sometimes people actually get endometriosis symptoms before they start menstruating, like at young age. MW: Right. There are girls who do, including the central character in this article, researcher Katie Burns, who began to have symptoms at the age of 10 or 11 well before she got her period. And there are a couple explanations for how this might happen. One of them is that these cells of the membrane that lines the pelvis called the peritoneal membrane, they share an ancestor in the early embryo with the cells that end up being endometrial cells. So, if you go back in time, they have this common progenitor. And it's postulated that ordinary cells of this membrane that lines the pelvic cavity convert spontaneously into endometrial cells. That's one example of how it might establish the disease, even in the absence of retrograde menstruation. SC: So, getting back to the immune system, kind of the research explosion there, what have we learned about the immune cells in endometriosis patients? MW: Well, number one, they have a lot more immune cells, highly elevated levels of these cells, including neutrophils and macrophages. These are sort of the earlier warriors of the immune system that come rushing to the scene and they are not behaving normally. For instance, Katie Burns, the central figure in this story again, has discovered that neutrophils collected from the menstrual fluid of women with endometriosis are a lot older than they should be. Neutrophils are normally very short-lived. They come and do their job, they're gone in hours. When they hang around and don't die off, they become very inflammatory and attract more of themselves to the scene as well. And so neutrophils are doing this, apparently, in women with endometriosis. And then you have macrophages. They're the ones that come and engulf, sort of surround and hoover up debris. But they're not doing that very vigorously in endometriosis. And what's more, they're ending to a behavior that actually restores and repairs and encourages these lesions to take root. And they're sending the cells that shouldn't be there survival signals that tell them don't die off. So, there's all this aberrant behavior by these immune cells that makes it look like the immune system is the real active participant in this disease and not simply a failed trash collector. SC: Well, the good news, though, is that the more we learn about how this disease might function, what the mechanisms are, we're going to get toeholds into diagnosis and into treatment. So, for example, you talk about there's some new diagnostic approaches that are coming out of our understanding of how the immune system might play a role in this. MW: Right. And there's both blood tests and tests of what's called menstrual effluent, which is collecting menstrual fluid in a cup and women mailing it in to be analyzed. A couple of groups actively doing this, and they are finding differences in what the immune cells are in number and in function in these menstrual fluid samples that are leading towards, hopefully, a diagnostic test. Because wouldn't it be wonderful if a woman could, in the privacy of her home, collect her menstrual fluid in a Diva cup, send it off and get a diagnosis without having to like persuade whatever doctor that this is not normal period pain and then push it along to finally get a surgery? It would be a quantum leap in the treatment of this disease if there were a rapid and accurate and non-invasive diagnostic test. SC: Meredith, how is this new intense focus on the immune system and its role in endometriosis? How is that playing into how we might treat it in the future? What are we looking at new targets? Are we looking at new approaches to combating this disease? MW: Well, I wish I could say that there's FDA approved therapies that are rolling out right and left, but I'm afraid we're not quite there. But there are several clinical trials, whether they're, for instance, against these chemicals put out by immune cells called interleukins, using antibodies to attack those. There's one against a certain receptor that pulls in various immune cells. And there's another that's simply targeting macrophages to improve their cell eating ability, although that trial is not yet off the ground. It's encouraging. At least there's clinical trials. There weren't 10 years ago. But the reality is that the approved approaches for this disease in terms of treatments are still hormone based decades after the discovery and well, the description of the disease and the naming of it, which was in 1921. SC: You mentioned kind of the central character here, Catherine Burns, has endometriosis herself. And several of the researchers you interview have this disease. Is that unusual when you're reporting that you find so many people are looking to better understand something they themselves are suffering from? MW: In my experience, it's fairly unusual. And there are really these women warriors out there. One of them didn't want to go public, but there are several who have the disease and are really high profile and who are very public about their own endometriosis. And with one in 10 women probably affected, there's a lot of women, everyone knows someone with endometriosis, whether they know it or not. But it's really it's heartwarming to see these women who are kind of running a race with leg weights on in terms of the pain and what they've had to cope with in their lives personally and still doing fantastic research. So, yeah, it's unusual in my experience, but I don't know. I mean, if you surveyed Alzheimer's researchers, I bet a lot of them have a parent with Alzheimer's or a sibling or something, even if they don't have it themselves. SC: All right, Meredith, this is your last feature story for science. You're leaving us for retirement. Are there any memories from, your work here, working on these stories? I think of you as someone who breaks big stories, writes with care about people suffering from various diseases or investigating things. What do you remember about your time? What's going to stick out? MW: Oh, I think the patients I've interviewed, whether they are a researcher with the disease like Tim Grenemyer, a Parkinson's researcher who has Parkinson's, or Michelle Dardengo, a courageous patient with Huntington's disease who was the first to receive a new therapy that unfortunately ended up not working. And then Katie Burns, who is just like, oh, my gosh, I have come to have so much admiration and respect for her. Getting to know her over these last couple of months while I've been working on this profile of her, because what she hasn't confronted without complaint, and she soldiers on where most of us might be lying at home in the fetal position. So, kudos to the patients and to the researchers who have been just an inspiration as I've reported these stories. SC: Thank you, Meredith. It's been wonderful working with you and speaking with you. MW: It's been wonderful working with you too, Sarah. Thanks for the opportunity. SC: Meredith Wadman is a staff writer for Science. You can find a link to the story we discussed at science.org/podcast. And if you click on the little icon that is Meredith on those pages, you can see everything that she's written for us here at Science. Up next, how the weather correlates with dengue outbreaks in Latin America. Dengue is an infectious disease transmitted by mosquitoes. Outbreaks are not easy to predict because there are so many factors that have to be taken into account. How much rain is there? What are the mosquitoes doing? What are the people doing? This week in Science Translational Medicine, Talia Quandelacy's team colleagues write about the synchrony of outbreaks of dengue in Latin America. Basically, the timing and spread in all these different countries. And how understanding these relationships across borders could help with prediction and preparation. Hi, Talia. Welcome to the show. Talia Quandelacy: Hey, thank you for having me. SC: Let's start out with the basics behind the scenes. What is dengue? I've heard it called dengue fever before. Is that still an accepted term? TQ: We typically refer to the disease as dengue, and we actually call infection with dengue, dengue virus infection. There has been a bit of a nomenclature change. I think historically people have heard it as dengue hemorrhagic fever. Those are the more severe forms of the disease, which we now kind of group a lot of those symptoms into a category called severe dengue. SC: What are some of the numbers here for dengue cases in this region or kind of more broadly? TQ: Yeah, so in 2023 and 2024, we've seen record numbers of dengue happening worldwide, particularly in the Americas have been hit especially hard. In 2023, they reported roughly 4.6 million cases. And in 2024, there was an estimated 13 million cases reported, which was a threefold increase. SC: How does this year look? TQ: Compared to those two years, this year is much quieter. Dengue has decreased globally with roughly 3.5 million suspected cases being reported in the Americas region. That actually is a 69% decrease from what we saw last year. SC: Oh, wow. Okay. So definitely a big public health impact. One oddity of dengue is that sometimes people, when they get it a second time, it can be much more severe. Can you talk a bit about what's behind that? TQ: Yeah, that is a really interesting phenomenon that we see in dengue epidemiology, and it's called antibody dependent enhancement. That's a case where you get infected with dengue the first time you might have maybe really mild symptoms. You might not even notice you're infected. The second time you're infected, then you have really bad symptoms. You might even go to the hospital because of it. And there's this really interesting feature of dengue where there are four types of dengue viruses. We usually call them dengue serotypes 1, 2, 3, and 4. And so, the first infection that you have actually matters with what type of virus serotype you were infected with because they have different immunological interactions. So, depending on if your first infection was with dengue 1, for example, and your second infection was with dengue 3, there's a recognition of your body's immune system that amplifies its response the second time. And that's when we can have dengue antibody dependent enhancement. SC: Now, I read this can complicate, for example, how vaccines work for dengue. We don't have to go into that in detail, but it did make it very complicated to generate a vaccine. Did it also affect kind of trying to understand how outbreaks happen and spread, like the different kinds that are in circulation and whether people have had a previous infection? TQ: Yeah, it really does. And with dengue, much like with Zika, there are a lot of asymptomatic infections. And so, usually when we're seeing outbreaks happening, we're only capturing a really small picture of how many people are actually being infected. Milder symptoms of dengue can feel like the flu, fever, a bit of achiness, but then you can also have really bad symptoms where we do see bleeding, encephalitis. And if we see new serotypes entering into a region or a new variation of a serotype that can also cause people to have more symptoms when they do become infected. But that is where we need to rely on public health surveillance to actually detect those changes in what's going on. SC: So, what were some of the other kind of factors that you wanted to take into account going into the study? What other possible variables might affect the size of an outbreak or the timing of it? TQ: One of the main questions we were trying to look at was a fairly simple one, which is historically, what have epidemics look like in the Americas region? Because the Americas is a really large geographical and climatically incredibly diverse area. It contains over 20 countries and all of them have their own ecosystems and populations and history with dengue. And so, one of the first simple questions we were trying to look at is just when there is an epidemic, what does that look like across the region? Do these epidemics occur all at once? Do they start in one particular place and move down? And then once we have a sense of the behavior of that epidemic, what are some of the factors that are causing that? And what we were able to look at with the data we had available are things like the environment. So, we were interested in seeing how does temperature play a role? What is the total rainfall in an area look like? And is there a timing between when we see a lot of rainfall and these epidemics happening, as well as patterns like El Nino, because El Nino does play a big role in the region and tends to occur when we see large epidemics of dengue. SC: It's kind of surprising that we don't have numbers on the dengue outbreaks in Latin America. TQ: There's been an analysis similar to this in Southeast Asia that has looked at similar things. And we have seen some historical papers looking at a country or two like Mexico, Puerto Rico and Brazil, but there hasn't been just an evaluation of what do these epidemics look like across the region. So, kind of stepping back and doing a very simple evaluation of just when we have the data, what does this look like? And we happen to see seasonally, yeah, a lot of these places, dengue peaks in the summer, which isn't news, but it's useful to see exactly when dengue peaks within a year for each country. That helps with planning, like you mentioned earlier. But also, what are the years that we see really large epidemics? And then once we saw that there were certain years where we have really big epidemics occurring across almost all of these countries, what is the timing of that? And yet what is the directionality of where these are occurring? SC: Let's talk a little bit about where you source your data from, and then we'll kind of get into some of your results. So, I saw you had data from over 14 countries over many decades. Where does this come from, and what exactly are you counting? TQ: We were really fortunate to be able to partner with a number of ministries of health from the countries that we've included in our study. So, this was a really big collaborative effort to collect the historical dengue data. So, what we did was look at data that was collected through routine surveillance, reported cases of dengue. So, when someone is sick and they seek care, that eventually gets reported to a public health system. And so, that's what we were looking at over time was monthly cases of reported dengue. SC: I mean, the disease is not constrained by borders, even if the data is, right? Definitely worth tracking down. So, when you get into the finer details based on this data, what are some of the patterns that you noticed? We talked about directionality or multi-year cycles. What were some of the things that popped out? TQ: So, one of the biggest things we saw, if we're just kind of thinking about what is a seasonal pattern is at least with dengue, it peaks in the summer. It tends to peak about two to three months after we see temperature peaking in a local area. And that isn't the newest finding, but it's really helpful to see kind of the movement in terms of timing when you move from the Southern Hemisphere to the Northern Hemisphere and how that timing actually differs based on your location. I think one of the really interesting findings we did see was when we have a major epidemic year, we tend to see these epidemics occurring across the region within six months of each other. So, from the start of when we first see it, we can expect to see epidemics happening everywhere else within about six months on average. And that's a really useful thing to understand for preparedness. SC: Do they move North? Do they move South? Do they move out from the Equator? What do we see there? TQ: With seasonal dengue patterns, that's a little clearer. We saw that a lot of dengue kind of seems to start in parts of Mexico or Central America and move outwards towards the Caribbean. And in the Southern Hemisphere, we see a lot of these epidemics in Brazil kind of starting first, and then you start to see other locations with their seasonal patterns having their seasonal dengue peaks. With these major epidemics, it's a little less clear. We saw that Central American region and Mexico seems to have a lot of similarity in terms of their timing and a lot of the directionality kind of moves through Mexico and out towards the Caribbean. And with the South American region, it's a little less clear. And I think that's also partly because there's so much geographic variability, which relates to climatic variability. SC: They're very long and skinny north-south. That's going to be very different, because when you talk about within country, you smear some of the facts on the ground, like elevation or humidity and that kind of thing. TQ: And at least with South America, we have colder regions like Chile and Argentina, but then we also have the Andes region, which goes through a number of countries. And so, when we look at some of those patterns, we see there's a little more local directionality that's kind of split by the Andes region. SC: And what did you see about this multi-year outbreak? Is that associated with multi-year weather like El Nino? TQ: For these multi-year patterns, it seems like local temperature and El Nino play a part. And with El Nino, that does affect local temperature. So, they're playing in concert, but the timing of them vary a little bit. We do see that when there's a big El Nino year, we have kind of the peak of its oscillation. We see that there's usually six months afterwards, we'll have a large epidemic. And similarly with temperature, we'll see big peaks, like maybe it's a really hot year, a bit hotter than other normal years. We'll see that there are also increases in dengue after about three months. SC: Now, does this give you some insight into the mechanisms at play here? If you can correlate weather, climate, and temperature with outbreaks, does that tell you, oh, this is a mosquito thing, or this is a person moving around thing, or this is a lots of water thing. TQ: A lot of times with dengue, unfortunately, it's a mixture of all of those things. And one of the things we weren't able to look at was the movement of people, and we do know that people move to different areas and if they're moving from places where dengue is, that's how we can get introductions. But we do know, at least with the timing of dengue and its relationship to things like temperature, rainfall, we have a better sense of the timing of that for this region now. And so, I think that does really help with being able to develop early warning systems and at least forecasting dengue, especially since it has such a strong biological relationship to things like temperature. SC: What other kinds of decisions about public health can you make based on this new understanding? TQ: I think the findings from our paper are helpful with preparedness. So, when we do see temperatures are peaking, then we can start planning at least vector control and trying to minimize mosquito breeding sites, human exposure to mosquitoes. And with El Nino, when we have a big El Nino year, at least there's some understanding of when we might expect to see a really large outbreak happening, which is about six months after we see an El Nino event. And that's useful. A lot of the focus of public health with dengue is on prevention. Since we don't have a cure for dengue, it's always really important to try to prevent mosquito bites and people getting infected. SC: What are some ways an analysis like this could be supplemented, like with a sampling of serotypes? What's your dream data set look like? TQ: Yeah, I think you hit the nail on the head. I think the dream data set would be having data dating back to our oldest data set, which is 1985, onward for every country in the region, along with having serotype data, because that really tells us something biologically about how the virus is changing and moving to different regions. And it lets us have some more insights into the immunological patterns we see at a population level for humans. And I think that's one of the bigger areas we would love to have included in this analysis. But for many places, serotyping isn't available. And so, it's something that we know is important, but are unable to evaluate. So, that would definitely be a dream data set. SC: Very cool. TQ: That and mobility. SC: Yes. Oh, yeah. And mobility. Absolutely. Thank you so much, Talia. TQ: Thank you for having me. SC: Talia Quandelacy is an assistant professor in the Department of Epidemiology at the Colorado School of Public Health. You can find a link to her Science Translational Medicine paper at science.org/podcast. And that concludes this edition of the Science Podcast. If you have any comments or suggestions, write to us at [email protected]. To find us on podcasting apps, search for Science Magazine or listen on our website, science.org/podcast. This show was edited by me, Sarah Crespi, and Kevin McLean. We had production help from Podigy. Our music is by Jeffrey Cook and Wynne Koi-Wen. On behalf of Science and its publisher, AAAS, thanks for joining us.