Fight Dengue With Mosquitoes?; Flu Vax in Pregnant Women: It’s TTHealthWatch!

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week. A transcript of the podcast is below the summary.

This week’s topics include in-utero management of a congenital lung problem, infecting mosquitoes to control Dengue, flu vaccines in pregnant women, and hospital at home for those with chronic illness.

Program notes:

0:50 Flu vaccines in pregnant women

1:51 Not associated with any adverse outcomes

2:48 Can’t generalize to all vaccines

3:35 Hospital-at-home for people with chronic disease

4:33 No change in mortality

5:33 Presented to the ED

6:18 In-utero treatment of left diaphragmatic hernia

7:18 Those severely affected increased survival to 40%

8:18 More often undertaken

8:36 Dengue management

9:36 8,144 participants

10:36 Does the Wolbachia remain?

11:36 It’s labor-intensive

12:48 End


Elizabeth Tracey: Can infected mosquitoes help with dengue?

Rick Lange, MD: Treating a congenital problem for the child that’s still in the uterus.

Elizabeth: Can hospital-at-home work for people with chronic disease?

Rick: And when mothers get the flu vaccine when they’re pregnant, does it affect early childhood outcomes?

Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also the dean of the Paul L. Foster School of Medicine.

Elizabeth: In keeping with our declining COVID numbers, once again this week, we are not talking about COVID, although I will suggest that one of yours has a logical segue into COVID. So why don’t we start with that one in JAMA, a look at vaccination of pregnant women?

Rick: This falls on the recommendation from many organizations that women, during pregnancy, get the flu vaccine. If they get infected, it increases their risk and it also increases risk to the baby in terms of preterm labor and morbidity and mortality. But there have been concerns that when a woman gets the vaccine that it could potentially affect early childhood outcomes. To address that, these investigators looked at 28,000 women, of whom about 36% received the seasonal influenza vaccine during pregnancy, and they compared them to the women who did not have the vaccination. They followed the children for up to 3½ years.

They looked at immune-related outcomes — did the children born to mothers that had flu vaccine have an increased risk of asthma or infection? They looked at non-immune related complications like cancer or even sensory impairment, and then very nonspecific things: did they have an increased incidence of urgent or inpatient healthcare utilization? What they determined is that, in fact, maternal influenza vaccination during pregnancy was not associated with any increased adverse outcomes.

Elizabeth: Clearly, this is a population that we’re really interested in discerning whether there are specific risks, both to the mom and to the baby, with regard to these immunizations, and lots and lots of discussion, of course, as I suggested, that there is this concern about COVID vaccination in women who are pregnant. How germane would you say these findings are to concerns about other vaccines that are administered during pregnancy?

Rick: We’ve talked before about the fact that many of the people that are against vaccinations look back to data 20 years ago — and in fact, they were false or misleading data — and those studies have been refuted. Nevertheless, there is still this continued issue, so I think a study like this is very good. A large number of patients, it’s evidence-based, and it’s specific to this particular vaccine.

Now, we can’t generalize this to all vaccines, but what I can say is there’s no hint in any of the vaccines that are given to adults, especially to women during pregnancy, that it increases the risk of fetal adverse outcomes, either short-term or long-term. These vaccines provide antibodies to the baby in the first six months of life when their immune system is relatively naive and isn’t able to mount a response.

Elizabeth: And we know, and we are intensively studying, of course, those women who are pregnant and receiving the COVID vaccines and finding out that, in fact, this antibody transfer is really important there.

Rick: Right. As with flu, if women who are pregnant and get COVID infection, they’re much more likely to have a serious side effect or die. It not only protects the mother, but it protects the baby, certainly in the first 6 months of life.

Elizabeth: Let’s turn from here to JAMA Network Open. This is one that’s near and dear to my heart and also has a contemporary slant to it with COVID because there were a lot more people who were attempting to get these programs of hospital-at-home underway under the circumstances of COVID and concerns about contagion in the hospital.

This study is a meta-analysis. They searched all of the literature and they found out, really, after they did that — they only had nine studies that they included in this — 959 participants, about 64% of those were men, a median age of 71 years, and they had chronic conditions, they came to the ED, and the question that they were attempting to answer was, could we send them off to hospital-at-home? How did they do when that happened?

They took a look at could we avoid admissions to the hospital for COPD, heart failure, asthma, stroke, and neuromuscular disease. The outcomes of this was that there was no change in mortality and there was a reduced risk for readmission for hospital-at-home compared with inpatient care.

They did have an increased length of treatment at home, but a lower risk of long term care admission for the hospital-at-home folks, and they also showed improvements in depression and anxiety among those patients who were treated at home.

As you know, I’m a big fan of this particular strategy because we know very well that people are often uncomfortable being in the hospital and they dislike the whole change in routine, so I think it’s more evidence that this is the direction that we’re heading. That’s clearly underpinned by the fact that since CMS has said we’re going to have this acute hospital care at home program, more than 100 hospitals across the United States have applied for and received a CMS waiver to participate.

Rick: Elizabeth, as you mentioned, these are individuals with chronic conditions. They presented to the emergency department and the emergency department decided that the patients could be treated in a hospital-at-home situation rather than being admitted to the hospital.

When you do that, the interventions usually consist of treatment delivered to the patients involving monitoring or face-to-face clinical care from nurses and physicians. You have to be able to provide diagnostic testing and also a treatment.

We haven’t integrated it yet into our healthcare system, but it’s nice to know that in that setting, it doesn’t increase mortality. It can prevent readmissions, although it may require a longer treatment time. It does say for carefully selected patients and for properly resourced health systems it may be a viable alternative.

Elizabeth: Good news, and more coming, I’m sure. Let’s turn to your second one.

Rick: Elizabeth, I teed this up as “treating a congenital issue in utero.” Specifically, the condition that we’re talking about is what’s called a left diaphragmatic hernia, where the diaphragm doesn’t completely form, and it’s particularly on the left side where the intestines can move from the abdomen up into the thorax or into the chest wall. In moderate or severe conditions, the lung doesn’t adequately form. When the baby’s born, there is an increased risk of mortality — about 20% of fetuses with severe pulmonary hypoplasia and only 55% of those with moderate survive.

What this treatment is, it’s putting a small tube into the baby’s trachea through the abdomen — this is when the child’s still in the uterus — and blowing a balloon up in the trachea. What that does is it increases the pressure in the lungs and it stimulates the lung to actually form. That’s done at about 27 to 32 weeks of pregnancy, and then the balloon is released, and then the baby’s born.

Does it actually improve survival? These are two studies, one reported in infants that were moderately affected and in those that were severely. What they determined was in those that were severely affected, the use of this particular treatment, called fetal tracheal occlusion, increased survival from 15% to 40%. In those that had moderate hypoplasia of the lungs, there really wasn’t any significant improvement in mortality.

Elizabeth: Let’s just mention that this is in NEJM. Let’s talk about the larger picture of this in utero surgery strategy, which has been underway for quite a while.

Rick: You know, it has been, Elizabeth, and the reason why I think this is important is a lot of things that we do haven’t really been fully studied. These are the first randomized trials we’ve had looking at whether or not fetal tracheal occlusion actually helps in these individuals.

Elizabeth: Would it be your assertion that we’re going to be seeing a whole lot more of this kind of intervention just because with ultrasound now and with monitoring of fetuses so closely during development, we’re detecting these issues much more often?

Rick: Absolutely. We need to study to see whether the in utero procedure not only improved survival, but what are the long-term effects? These children obviously had an increased survival, which is great, but what happens later to their lungs and to their development afterwards? I think we are going to see additional studies with in utero procedures.

Elizabeth: Staying in the New England Journal of Medicine, let’s turn to this issue of dengue. Dengue, of course, is a viral disease that’s found all over the place where there are Aedes aegypti mosquitoes, which is also all over the place and increasingly, with climate change, this mosquito population is expanding the territory that it’s capable of living in. There are parts of the U.S., in fact, where we’ve had an issue.

This is a study that was done in Yogyakarta, Indonesia. What they did was infect Aedes aegypti mosquitoes with a really interesting type of bacterium, Wolbachia pipientis. I really love these words, how about you? The interesting thing about infecting these mosquitoes with this particular bug is that then they’re not susceptible so much to infection with the virus, so, okay, this is pretty interesting.

They looked at different communities where they released these infected mosquitoes. They had 12 geographic clusters. In toto, they had 8,144 participants, 3,700+ of whom lived in the intervention clusters, and 4,400+ who lived in the control clusters. What they wanted to find out was, gosh, how does it work? If we infect these mosquitoes, do you get dengue?

Sure enough, they found out that the protective efficacy of the intervention was 77.1%, which is pretty amazing, and also there are different serotypes of dengue, and so all four of them, it was similar, which is really great.

One of their secondary outcomes was, what about hospitalization for dengue? And sure enough, it was lower for those who lived in the intervention clusters. This is really good news, it sounds like. I don’t know if we know what the long-term impact of infecting these Aedes aegypti mosquitoes with this particular bug are and one of my questions is, “How long does it last?” They don’t really answer that question. They do monitor for a couple of years, but I want to know, “Hmm, does that Wolbachia stay in there?” It is a maternally-transmitted parasite, so maybe it does. I don’t know the answer to that.

Rick: A couple of things for our listeners that may not be familiar with dengue. It’s considered by the World Health Organization as one of the top 10 global health threats, with an estimated 50 to 100 million symptomatic cases globally each year. It can result in severe hematologic complications, neurologic complications, and death.

A human gets dengue, a mosquito bites the human, the mosquito becomes infected, then the mosquito lands on another person. So it’s transmitted from person to mosquito to person.

When these mosquitoes, these females mate with the male mosquitoes, the only viable mating outcomes are those in which the progeny are also infected with Wolbachia. Even though these were released in 2017, even up to 2020 — 3 years later — they could detect Wolbachia. This is a really novel way to decrease dengue infection.

Elizabeth: You know, in reading sort of some of the details of this study, I thought to myself, “It sounds so simple, and elegant, and beautiful.” Then you start reading some of the other stuff, right? I see this thing, it says, “Mosquito eggs are placed in intervention clusters,” and that it required between 9 and 14 rounds of deployments per place. It wasn’t like you turned ’em loose and said, “Okay, see you later.” You had to go back and do it multiple times. Then they also, to monitor this, had 348 adult mosquito traps where they were checking for this, so this is not without effort.

Rick: It did require some effort. I’m glad you picked that particular article. It’s a novel way. I never would have considered this as a possible way, but not only treating dengue, but it has other implications for other mosquito-borne viral illnesses as well. So stay tuned.

Elizabeth: Exactly. I mean, I really love that this has the potential to also attenuate transmission of Zika, chikungunya, and yellow fever. It could be very, very powerful. On that note, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.

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