Ebola Relapse; HPV Vaccine Success: It’s TTHealthWatch!

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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 helmet ventilation, Ebola reactivation, interfering RNAs, and success of HPV vaccination.

Program notes:

0:37 Helmet ventilation in COVID-19

1:37 No difference in respiratory support

2:35 Little more difficult to use

3:35 Continue with high flow nasal oxygen

4:12 Ebola virus relapse

5:15 Can detect some virus

6:10 Success of HPV vaccine

7:10 97% reduction in prevalence

8:10 Been recommended for anyone 11-12 years old

9:15 Treatment with interfering RNA

10:15 Stop liver from making oxalate

11:15 Attached to a sugar

12:40 End

Transcript:

Elizabeth Tracey: Should we use helmet ventilation for people with COVID-19?

Rick Lange, MD: Relapse of Ebola virus.

Elizabeth: The benefits of HPV vaccination.

Rick: And inhibiting RNA to cure a congenital metabolic abnormality.

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: Rick, how about if we start with this issue of helmet ventilation in folks with COVID-19? Unfortunately, of course, numbers on the rise again domestically. We know that on the heels of that are going to be hospitalizations and the development of more severe disease, and ultimately death for some of these people, so strategies for management, of course, still active areas of investigation.

This is a study that was conducted in Italy, where they have abundant experience, I’m just going to note, with this helmet ventilation. They compared that to high-flow nasal cannula. They got participants randomly assigned to receive one of those two treatments when they presented to the hospital and they had 109 patients who completed this trial. They had a couple of outcomes they were looking at and then a whole bunch of secondary outcomes that they also wanted to assess.

The upshot of this whole thing for me was that there basically was no difference in having to help somebody with their respiration at 28 days, whether you had high-flow nasal oxygen or whether you had the helmet. The big difference, though, that I think, and the authors and the editorialist believe deserves further investigation, is the fact that the folks who got the helmet ventilation required less mechanical ventilation. So they didn’t have to go on a respirator, which is, I think, a pretty wonderful outcome. There are some plus-minuses on either side, on both types of therapy, and it’s sounding to me like this is going to be something that’s going to be investigated more carefully.

Rick: For those that have a hard time visualizing, it looks like the old diving bells, the helmets they use with the glass things. Well, this is just plastic. We know that in individuals that have respiratory distress from COVID, the use of high-flow nasal oxygen — and that is giving 30 to 60 liters per minute — actually improves mortality, so this was a direct comparison of the helmet versus that.

Overall, it didn’t get people off of supplemental oxygen any quicker. It didn’t improve mortality. It was a little bit more difficult to use. It’s a little bit more uncomfortable for patients and the patients that were on it were less likely to be in a prone or face-down position, which we know is helpful.

So is there a net benefit? Well, it doesn’t appear to be. There was a lot of hope that this would really speed the recovery and it doesn’t look to be so, so I’m not sure that it’s going to gain widespread use.

Elizabeth: I think that the editorialists brought up some really excellent points about this also, that in the helmet group there was higher sedative use, 37%, compared with only 18% in the high-flow oxygen group and that is significant because when we’re looking at people who are in the ICU we know that that’s directly related to the development of ICU delirium and other sequelae.

Rick: Yep. The people that wore a helmet were more likely to be rebreathing carbon dioxide. They had more claustrophobia and issues with what’s called cycling dyssynchrony, that is kind of timing your breathing with how it’s delivered. It’s not a panacea and unfortunately there aren’t clear-cut benefits, so I think we’ll continue using high-flow nasal oxygen in most centers around the United States.

Elizabeth: I’ll counter with I think we’re going to see additional studies relative to this helmet. If these other secondary outcomes really pan out in greater numbers of patients, perhaps the rate of PTSD after an ICU stay will be declining if there’s helmet ventilation because of not having to have somebody paralyzed and all the rest of the stuff on the ventilator.

Rick: Okay. Well, we’ll stay tuned.

Elizabeth: Now we’re going to turn to the New England Journal of Medicine. Which of your two would you like to start with?

Rick: Let’s start with the Ebola virus and this is transmission of disease in somebody that had a relapse. We’ve not had reports where relapse has been associated with a lot of secondary infections, but this particular individual infected 91 people after the relapse, so a little bit of history.

It’s a 25-year-old person who worked as a motorcycle taxi driver in the Democratic Republic of Congo. It’s a person that had received the vaccine back in December of 2018, but then in June of 2019 actually developed their first infection. They got monoclonal antibody therapy and recovered, and then 149 days later developed recurrent symptoms.

It took them about a week before they got evaluated and then they had confirmation that, in fact, they had Ebola. They did some genetic and then also some epidemiologic analysis and determined that, in fact, it wasn’t a reinfection, not a secondary infection, but this person had had relapse. But by the time they figured it out, this person had been in contact with 29 patients who developed Ebola, and they infected another 62 people, through 91 individuals.

Why are we reporting on this? We know that in individuals that have had Ebola virus we can detect some virus in fluid inside the eye and in the semen as well, but very rarely has this resulted in a secondary transmission. This is a well-documented case of relapse in an individual that infected another 91 individuals. By the way, this individual subsequently died.

Elizabeth: Is it a cautionary tale? Is it a model for other circumstances where somebody could harbor a virus, infect plenty of other people, not be symptomatic? Oops, this is sounding an awful lot like COVID, isn’t it?

Rick: Yeah. One of the things that’s unique about this individual and the two others where there’s been persistent detection in body fluids is that they all seemed to be treated with the monoclonal antibody. Is that somehow interacting with their immune system that enables them not to be able to clear it totally? Around the world, when someone has recurrent symptoms, we need to be concerned.

Elizabeth: Let’s turn from here to Morbidity and Mortality Weekly Report. This is a success story, so it’s nice to turn to a success story, I think. This is taking a look at more long-term data since the HPV vaccine has been introduced and there’s been a little bit more uptake of it.

When the first HPV vaccine came out, it was against four subtypes of the virus. Now it’s against nine. That’s been since the end of 2016. This is NHANES data taking a look at, “Well, all right, how has HPV prevalence decreased under these circumstances?”

They grouped these females aged 14 to 19 years and 20 to 24 years. Since the pre-vaccine era there have been significant decreases in the HPV prevalence. Among 14-to-19-year-olds, it’s declined 88% and among 20-to-24-year-olds declined 81%. In sexually experienced females who received the 4-valent HPV vaccine, there has been a 97% reduction in those 14 to 19 years old and 86% among those 20 to 24 years old.

Then here’s the really important thing. Among those who reported no vaccination, there has been an 87% decline in the younger group and a 65% decline in the older group, the 20- to-24-year-olds, suggesting that this issue of herd immunity is really impacting on [them].

Rick: Human papillomavirus is first of all the most commonly sexually transmitted infection in the United States. Persistent HPV infection is associated with cervical cancer, anal-genital and oral-pharyngeal cancers, and also anal and genital warts. It’s the most common cause of cervical cancer. The use of the HPV vaccine, even in its infancy, has significantly decreased the rate of infection among both vaccinated and unvaccinated individuals. That’s incredibly good news.

As most listeners should be aware, it’s been recommended for anybody aged 11 to 12 for females, and since 2011, for males as well. But there’s also a catch-up vaccination that’s recommended through age 26, which is why we’re looking at the older age group.

Elizabeth: I think that the tables are really interesting, and what they reveal is that in that 14 to 19-year-old age group, in 2007 to 2010, only 34% of those folks were vaccinated. In the next interval, which is 2011 to 2014, it was almost 55%.

Now it’s slightly less than that, 54.3%, and the author suggests that could be because of COVID, that people aren’t getting these routine kinds of things going on. Then when you look at the next age group, that 20 to 24 [age], we see that almost 60% now in that group have been vaccinated. Wouldn’t it be great if it was close to 100%?

Rick: Our encouragement to our listeners is, for those in the particular age groups we talked about, aged 11 to 12, and even up to age 26, if people haven’t been vaccinated is to recommend that they do so.

Elizabeth: Let’s turn back to the New England Journal of Medicine, and to a hopeful treatment utilizing something we’ve been hearing an awful lot about, RNA technology.

Rick: We’re going to talk about a very rare genetic disease caused by liver overproduction of something called oxalate. It leads to kidney stones, it leads to calcification of the kidneys, it leads to kidney failure, and you can actually get oxalate deposited in the blood vessels around the body as well. It’s present since birth and these individuals oftentimes present very early on to be on dialysis and/or die even before they reach the age of 20.

So you say, “Well, this is so rare. Why are we talking about it?” Well, I’m actually more interested in the particular type of therapy. It’s called an RNA interference therapy. What happens in these individuals is they lack an enzyme. It’s a normal metabolic pathway that they would metabolize oxalate, so they can’t, so it continues to build up in the system. There’s no good treatment for it except to do a liver transplant if it’s discovered early. Once they’ve had kidney failure they go on dialysis, but inevitably they have a poor outcome.

If you could stop the liver from making oxalate, then you could potentially have a form of treatment and that’s exactly what RNA therapy does. It inhibits the protein that leads to the production of oxalate. In this particular circumstance, it decreased oxalate production substantially by about 65%. In fact, most individuals that have this condition that were treated with the RNA therapy, RNA interference therapy, had normal oxalate levels. They gave it as a monthly injection for the first 3 months and then every 3 months after that.

This is the third drug that’s approved for this particular type of therapy. It received a lot of enthusiasm 20 years ago, but then as we gave it, injected it into the body, it was degraded and it really wasn’t very successful. We just didn’t know how to package it, so we did two things. One is we put it in nanoparticles and the second thing is we attached sugars that would target a specific organ. The liver will attach certain sugars to it and internalize whatever those sugars are attached to, and that’s how it works.

Now that we have targeted specific liver abnormalities, this RNA therapy — we now have three FDA-approved RNA interference therapies, all directed towards congenital liver disease. Now, what the companies need to do next is direct it towards CNS [the central nervous system] or direct it toward the heart.

The downside is that it’s really expensive. This particular therapy costs a little bit less than $500,000 per patient per year currently. These therapies become less expensive as we develop more drugs that are RNA interference therapeutic agents.

Elizabeth: I’m finding it really fascinating, this predominance of RNA in all these investigations, in this case RNA interference, but certainly mRNA vaccines, and it kind of makes me wonder like, “What else is hiding in plain sight that we’re going to investigate next?”

Rick: Yeah. It gets from DNA to a protein. RNA is the messenger that transcribes it from the genetics into the protein and that’s what we’re particularly targeting here, and you’re right. We were familiar with the importance of RNA and RNA interference proteins. But how to package them so they could be vaccines or be therapy is really what’s come of age lately.

Elizabeth: On that positive note, that is 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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