Influenza- Prevention & Therapy

In this episode, we take a deep dive into the clinical management of influenza, a viral respiratory infection that causes significant morbidity and mortality globally and in Australia every year. We explore why the routine annual flu vaccine remains our most critical intervention, and break down the circulating subtypes, including Influenza A (H1N1 and H3N2) and Influenza B.

Join us as we unpack the evolution of flu vaccines, explaining the shift from trivalent to quadrivalent formulations to improve protection. We also highlight targeted vaccine strategies for high-risk demographics, such as the safety and necessity of vaccinating pregnant women at any stage of pregnancy, and the introduction of high-dose and adjuvanted vaccines specifically designed to trigger a stronger immune response in adults over 65.

Finally, we navigate the complex role of antiviral drugs, primarily Neuraminidase Inhibitors (NAIs) like Oseltamivir and Zanamivir. We discuss the crucial 48-hour window for treatment, how these medications impact symptom duration and mortality, and why they should never be viewed as a substitute for vaccination. We wrap up with a look at the limitations of current antiviral prophylaxis and what novel therapies are on the horizon to combat emerging viral resistance.

Key Takeaways in this Episode:

The Power of Prevention: Why routine vaccination is the most important defense against severe flu complications.

Vaccine Innovations: Understanding the differences between standard quadrivalent vaccines and specialized high-dose or adjuvanted trivalent vaccines for older adults.

Antiviral Realities: How NAIs work, who needs them most, and their modest effects on symptom duration.

Outbreak Management: The role of post-exposure prophylaxis in high-risk households and residential care facilities.

Transcript

SPEAKER_00 0:00

Right now, scientists across the globe are placing this massive high-stakes gamble on what the world is gonna look like about nine months from now.

SPEAKER_01 0:10

Yeah. And the prize for winning that bet is literally the seasonal flu shot waiting for you at your local pharmacy.

SPEAKER_00 0:17

Exactly. I mean, you probably see the signs go up every year. You know, you you roll up your sleeve, get the shot, and just go about your day.

SPEAKER_01 0:22

Right. It feels totally mundane.

SPEAKER_00 0:24

Yeah. But behind that totally mundane errand is this sprawling global security dragnet. And the whole point of it is trying to predict the next move of what is essentially a microscopic master escape artist. So welcome to today's deep dive, everyone.

SPEAKER_01 0:39

Thanks for having me. The stakes of that gamble we just mentioned are actually enormous because you know, people so often dismiss the flu as just a bad cold.

SPEAKER_00 0:47

Oh, for sure. People say, Oh, I just have the flu.

SPEAKER_01 0:49

Right. But influenza is actually a primary driver of severe illness and death every single year. So managing this virus requires far more than just um advising people to wash their hands and stay home.

SPEAKER_00 1:01

Aaron Powell, which is why today we are unpacking a clinical source specifically on influenza management. And while it heavily references the Australian context, the pharmacological strategies here are universally applicable.

SPEAKER_01 1:14

Absolutely. The clinical guidelines reveal a strategy built on precision timing, really complex pharmacology, and, well, anticipating how a virus mutates under pressure.

SPEAKER_00 1:26

Aaron Powell So if influenza is this master escape artist, the most logical first step is trying to intercept it before it even enters the building, right?

SPEAKER_01 1:33

Yeah, exactly. Catching it at the door is always our most important intervention for preventing severe complications. But building that initial shield requires a pretty intricate understanding of time.

SPEAKER_00 1:42

Because you don't just get the shot and instantly have a force field.

SPEAKER_01 1:46

No, not at all. It takes the human body approximately two weeks to process the vaccine and mount a full antibody response.

SPEAKER_00 1:53

Okay, two weeks.

SPEAKER_01 1:54

Right. And once you reach that peak level of protection, that optimal efficacy only really lasts for about four months.

SPEAKER_00 2:00

Wow. So it is a very specific window. I know in Australia, for example, the guidelines pinpoint March or April as the absolute sweet spot to get the shot.

SPEAKER_01 2:09

Aaron Powell Yeah, because that deploys that four-month shield right as their winter season hits hardest.

SPEAKER_00 2:15

But let's go back to that nine-month gamble we mentioned right at the start. I mean, how do we even know what to put in the shot if we are designing it almost a year in advance?

SPEAKER_01 2:23

Well, because the massive scale of manufacturing distribution, the formulation for the seasonal vaccine has to be locked in about nine months before the winter season begins.

SPEAKER_00 2:32

That's wild. So what are they basing it on?

SPEAKER_01 2:34

Aaron Powell Public health scientists basically analyze the specific viral strains that are currently circulating during the winter in the opposite hemisphere.

SPEAKER_00 2:43

Okay, so they use that data to make these like highly educated predictions about which specific mutations will dominate the globe nearly a year later. Exactly. It's essentially trying to predict next winter's fashion trends based on what people were wearing last winter on a totally different continent. You know, you're just hoping you guessed the right colors and fabrics.

SPEAKER_01 3:04

That is a surprisingly accurate way to look at it, actually.

SPEAKER_00 3:07

But wait a minute. If the optimal protection drops off after just four months, why on earth are we only getting this shot once a year?

SPEAKER_01 3:14

I hear that question a lot.

SPEAKER_00 3:16

Right. Shouldn't we be constantly topping it up so you just stay protected year-round?

SPEAKER_01 3:20

You have to consider the logistics of public health alongside the actual nature of seasonal viral peaks. The virus does not circulate at high levels year-round.

SPEAKER_00 3:29

Okay, so it operates in a highly concentrated seasonal window.

SPEAKER_01 3:33

Precisely. The strategic goal is to time that four-month window of maximum efficacy so that it perfectly overlaps with the peak of viral transmission in the community.

SPEAKER_00 3:43

So rolling out a massive global vaccination campaign twice a year would just face, what, insurmountable logistical hurdles?

SPEAKER_01 3:52

Yeah, enormous costs and significant public fatigue, all for a really marginal benefit during the months when the virus is relatively dormant anyway.

SPEAKER_00 4:00

Got it. You want your shield at maximum strength, specifically when the arrows are flying the thickest.

SPEAKER_01 4:06

Exactly. And regarding that shield, for most children and adults, the standard issue is a single quadravalent vaccine.

SPEAKER_00 4:14

And the quad there obviously means four.

SPEAKER_01 4:16

Right. You are receiving protection against two A subtypes of the virus, specifically H1N1 and H3N2, and two B lineages, known as Yamagata and Victoria.

SPEAKER_00 4:28

So transitioning to that four-strain formulation significantly improved our baseline protection, right? Just by casting a wider net.

SPEAKER_01 4:36

Yes. And crucially, without increasing adverse reactions. But um there is a vital exception to that single-dose protocol that the guidelines highlight.

SPEAKER_00 4:45

Oh, right. The two-dose rule. This is for kids receiving the flu shot for the very first time.

SPEAKER_01 4:49

Correct. If a child between the ages of six months and nine years old is getting the shot for the first time, they require two doses spaced at least four weeks apart.

SPEAKER_00 4:57

And doesn't the same rule apply to patients who are in their first year following a solid organ or a stem cell transplant?

SPEAKER_01 5:02

It does, yeah, because in both of those cases, you are dealing with an immune system that is completely naive to the virus or heavily suppressed.

SPEAKER_00 5:10

So you have to introduce the immune system to the virus and then four weeks later remind it again so it truly commits the escape artist's face to memory.

SPEAKER_01 5:18

Yeah, it requires that secondary priming. Now, the standard core drivelant shot provides excellent coverage for the general population. But as the human body ages, the immune system naturally becomes more sluggish.

SPEAKER_00 5:30

It just doesn't respond to that standard viral introduction with the same vigor.

SPEAKER_01 5:35

Exactly. And the stakes for the over 65 population are significantly higher.

SPEAKER_00 5:40

Yeah, because if they contract influenza, we aren't just looking at a few days of a bad cough.

SPEAKER_01 5:45

No, not at all. We're looking at an escalated risk of life-threatening complications, things like heart attacks, decompensated cardiac failure, and severe pneumonia.

SPEAKER_00 5:55

So to counteract that sluggish immune response, the pharmacological strategy just completely shifts for them.

SPEAKER_01 6:00

It does. For the over 65 demographic, the guidelines recommend shifting back to trivalent vaccines.

SPEAKER_00 6:06

Wait, meaning they only cover three strains instead of four?

SPEAKER_01 6:09

Right. But these are highly specialized intensified formulations.

SPEAKER_00 6:12

Let's break down how we intensify them, because the source material goes into this. Starting with the high dose option, like flu zone I dose.

SPEAKER_01 6:19

So this vaccine contains 60 micrograms of antigen.

SPEAKER_00 6:22

And just for context, an antigen is essentially the biological mugshot of the virus that we show your immune system so it knows what to attack.

SPEAKER_01 6:29

Exactly. And 60 micrograms is literally four times the amount of antigen in a standard shot.

SPEAKER_00 6:35

That is a massive payload.

SPEAKER_01 6:37

It is. By flooding the system with that much viral protein, we basically force the older immune system to pay attention and mount a robust defense.

SPEAKER_00 6:46

And then the alternative to a high dose is an adjuvante vaccine, such as fluod. And this relies on an entirely different mechanism, right?

SPEAKER_01 6:54

Yes. It includes an ingredient called MF-59, which is a squalene-based emulsion.

SPEAKER_00 6:59

Okay. Squalene-based emulsion sounds a bit like a fancy anti-aging skincare product. What does that actually do inside the body?

SPEAKER_01 7:06

Well, in immunology, an adjuvant like MF-59 acts as a localized irritant.

SPEAKER_00 7:11

An irritant.

SPEAKER_01 7:12

Yeah. When injected, it creates a rapid, localized inflammatory response that acts as an alarm bell, basically drawing immune cells to the area.

SPEAKER_00 7:22

Oh, I see.

SPEAKER_01 7:23

It specifically induces CD4 responses. You can think of CD4 cells as the generals of the immune system army.

SPEAKER_00 7:29

Because they orchestrate the entire counterattack.

SPEAKER_01 7:32

Right, and they create incredibly strong lasting memory in your T cells and B cells.

SPEAKER_00 7:36

So if the high dose vaccine is just shouting four times louder, the MF59 adjuvant is like handing the immune system a megaphone.

SPEAKER_01 7:45

That's a great way to picture it. And the real world data on handing out that megaphone is staggering.

SPEAKER_00 7:50

Yeah, the guidelines mention that studies show fluod is 51% more effective at preventing hospitalization from flu or pneumonia in older people compared to the standard shot.

SPEAKER_01 8:00

Aaron Powell It provides a really profound host response and it allows for what we call dose sparing, meaning we achieve superior protection without needing to manufacture that massive four times antigen payload.

SPEAKER_00 8:12

But utilizing that megaphone does come with a biological trade-off, doesn't it?

SPEAKER_01 8:16

It does. Because you are intentionally triggering a stronger localized alarm, it increases injection site reactions. Right. Older patients experience about a 30% localized reaction rate, like soreness or redness, versus about 20% for the standard shot.

SPEAKER_00 8:32

Okay, hold on though. I want to circle back to something. We just established earlier that the quadravalent vaccine is the gold standard because it covers two B strains instead of one. Right. So if we intentionally give the most vulnerable elderly population a trivalent vaccine, aren't we leaving them totally exposed to an entire lineage of the B virus?

SPEAKER_01 8:52

It definitely seems counterintuitive, but the clinical data resolves that concern. First, the AH3N2 strain is the primary driver behind the vast majority of severe infections, hospitalizations, and deaths in older patients.

SPEAKER_00 9:04

Okay, so that specific strain is the enemy we absolutely must suppress at all costs.

SPEAKER_01 9:09

Exactly. And second, the human immune system is incredibly adaptable. Vaccinating against a single B strain actually confers up to 50% cross protection against mismatched B strains.

SPEAKER_00 9:19

Oh, so the immune system kind of recognizes the family resemblance.

SPEAKER_01 9:23

Exactly. It sees the similarities. So the overwhelming benefit of using a high dose or a javanted vaccine to neutralize the most dangerous lethal strains far outweighs the marginal loss of directly targeting that fourth B strain.

SPEAKER_00 9:38

Trevor Burrus, Jr. That makes total sense. So we build the strongest possible shield for the most vulnerable people. But what happens when that predictive nine-month gamble fails? Or, you know, the vaccine's four-month efficacy window starts to close.

SPEAKER_01 9:51

Well, then the virus slips past the shield and gets into the body.

SPEAKER_00 9:53

Which triggers a frantic race against the clock. And that brings us to the next trap in our deep dives antivirals and the 48-hour window.

SPEAKER_01 10:02

Right. So to understand how antivirals work, you have to understand how the virus operates once it's actually inside you.

SPEAKER_00 10:08

Okay, break it down for us.

SPEAKER_01 10:09

When influenza enters a host cell, it hijacks that cell's machinery to print thousands of copies of itself. But to actually leave that host cell and spread the infection to the rest of your respiratory tract, it relies on an enzyme on its surface called neuraminidase.

SPEAKER_00 10:23

And neuraminidase basically acts like a pair of chemical scissors, right?

SPEAKER_01 10:26

Exactly. It cuts the newly formed viral clones free from the host cell membrane.

SPEAKER_00 10:31

And that brings in our heavy pharmacological hitters. Neuraminidase inhibitors or NAIs?

SPEAKER_01 10:36

Yes, NAIs.

SPEAKER_00 10:38

We are essentially gluing those chemical scissors shut. The virus can replicate inside the cell, but it is physically trapped there.

SPEAKER_01 10:45

That's exactly what happens. And the big three registered for use in Australia are oceltomavir, which is an oral pill, xenomavir, an inhaled powder, and paramivir.

SPEAKER_00 10:54

And perimirir is a single dose IV for patients who are critically ill, right?

SPEAKER_01 10:59

Aaron Powell Correct. But the golden rule for all of them is speed. The guidelines dictate they must be started within 48 hours of symptoms appearing.

SPEAKER_00 11:06

Aaron Powell Why is that 48-hour window so strict?

SPEAKER_01 11:09

Aaron Powell Because viral replication peeps incredibly early in an influenza infection. The virus multiplies exponentially in those first couple of days.

SPEAKER_00 11:17

So if you wait past the 48-hour mark, the virus has already flooded your system.

SPEAKER_01 11:22

Exactly. Gluing the chemical scissors shut at that point is like um locking the barn door long after the horses have bolted. The damage is already done.

SPEAKER_00 11:29

Aaron Powell Okay, let's look at healthy adults for a second, because the trial results on this are kind of surprising. You feel terrible, you scramble to the doctor, you rush to the pharmacy to get a celtomivir before that 48-hour clock runs out. Right. And what does gluing those scissors shut actually achieve for an otherwise healthy person? It shortens symptoms by roughly one single day.

SPEAKER_01 11:48

Yeah, just one day.

SPEAKER_00 11:49

And the data shows absolutely no confirmed reduction in severe complications like pneumonia for healthy individuals. So why do we even bother prescribing this to the general public? It feels like an exhausting drill for a tiny reward.

SPEAKER_01 12:04

I get that. For a healthy outpatient dealing with uncomplicated influenza, the clinical guidelines explicitly acknowledge that the benefit is marginal. It is indeed a massive effort for one less day of feeling miserable.

SPEAKER_00 12:17

So why is it such a big deal?

SPEAKER_01 12:19

The reason these drugs are a cornerstone of public health is their impact on vulnerable populations. While the benefit for a healthy person is small, there is a verified absolute mortality benefit for severe cases, hospitalized patients, and high-risk groups.

SPEAKER_00 12:33

Wow. So for a healthy adult, it basically saves you a day of a runny nose. But for an elderly patient, a pregnant woman, or an immunosuppressed individual, osultomavir is literally preventing death.

SPEAKER_01 12:47

That is the critical distinction. Prompt commencement of NAIs is totally mandated for anyone requiring hospitalization or at high risk of complications.

SPEAKER_00 12:56

But we have to deploy them strategically, don't we? Because the virus constantly mutates to pick the locks we put on it.

SPEAKER_01 13:02

It does. Antiviral resistance is an ever-present threat. Historically, we relied on a class of drugs called adamantines, but the virus entirely bypassed them.

SPEAKER_00 13:12

Oh, really?

SPEAKER_01 13:12

Yeah, they're no longer recommended at all due to widespread global resistance.

SPEAKER_00 13:16

That's terrifying. And even with our current drugs, the guidelines say we are tracking resistance mutations. The most prominent is the H275Y mutation.

SPEAKER_01 13:24

Right, which alters the shape of the virus just enough that a saltomivir can no longer glue the scissors shut.

SPEAKER_00 13:29

And the data shows this resistance develops most frequently in young children and immunocompromised patients. Why them specifically?

SPEAKER_01 13:36

It basically comes down to viral burden and time. Because their immune systems are weaker or naive, they just cannot clear the virus quickly.

SPEAKER_00 13:44

Oh, so the virus replicates inside them for a much longer protracted period.

SPEAKER_01 13:49

Exactly. It has days or weeks of extra time to practice picking the lock. Every time it copies itself, there is a chance for a mutation.

SPEAKER_00 13:57

And eventually it stumbles on the exact genetic sequence that renders the drug useless.

SPEAKER_01 14:02

Yes. And once that resistant strain is born, it can spread. Since the virus is constantly mutating to bypass individual treatments like Oceltamever, we can't just rely on treating sick individuals one by one.

SPEAKER_00 14:14

We have to change the battlefield entirely.

SPEAKER_01 14:16

Precisely.

SPEAKER_00 14:17

Which brings us to prophylaxis, using drugs not just to treat the sick, but to put out the fire before it spreads through a community.

SPEAKER_01 14:23

When an influenza outbreak is detected in a high-risk closed environment, the strategy shifts to post-exposure prophylaxis. We stop treating just the individuals showing symptoms and we treat the entire environment.

SPEAKER_00 14:36

The protocol for residential care outbreaks, like an aged care facility or a correctional center, is just a massive logistical undertaking.

SPEAKER_01 14:43

It really is. If an outbreak is declared, local health authorities must move within 24 hours.

SPEAKER_00 14:49

They distribute NAIs to all asymptomatic residents, regardless of whether they have their flu shy, right?

SPEAKER_01 14:55

Right, along with all unvaccinated staff members. Yeah. And they keep that entire population on the antiviral drugs for a full 10 days or until the outbreak is officially over.

SPEAKER_00 15:04

They also utilize a strategy called ring prophylaxis in other closed high-density settings, don't they? Like cruise ships, boarding schools, or military barracks.

SPEAKER_01 15:13

Yes, ring prophylaxis. The goal there is to identify the infected individuals and then heavily medicate everyone in their immediate physical or social circle.

SPEAKER_00 15:22

It operates on the exact same logic as firefighters cutting a fire break in a forest. You know, you clear out the dry brush ahead of an advancing wildfire so it literally starves to death.

SPEAKER_01 15:32

That's a perfect analogy. By medicating the people surrounding the patient, you're starving the virus of vulnerable host cells.

SPEAKER_00 15:40

But there are significant limitations to building these chemical walls because as soon as you stop administering the drugs, everyone's susceptibility returns immediately.

SPEAKER_01 15:49

Exactly. Plus, even while on the drugs, people can still asymptomatically transmit the virus.

SPEAKER_00 15:55

And as we noted with the H275Y mutation, utilizing antivirals on a massive long-term scale breeds the very resistance we are trying to avoid in the first place.

SPEAKER_01 16:06

Which is why we are rapidly approaching the biological limits of what neurminidase inhibitors can achieve. That is why the future of influenza management hinges on novel therapies that target completely different stages of the virus's life cycle.

SPEAKER_00 16:20

Let's break down that future tech pipeline because scientists are looking at drugs that attack the virus in entirely new ways.

SPEAKER_01 16:26

Right now we focus on gluing the chemical scissors shut so the virus can't leave the cell.

SPEAKER_00 16:31

But drugs currently in development target every other phase of the invasion. Take a drug like DAS-181 F03.

SPEAKER_01 16:38

Yes. That one prevents the virus from even docking onto the human cell in the first place by stripping away the specific receptors the virus uses to attach itself.

SPEAKER_00 16:46

It's like changing the locks on the doors of your cells.

SPEAKER_01 16:49

Exactly. Then you have fusion inhibitors, like arbitol.

SPEAKER_00 16:52

Okay, how does that one work?

SPEAKER_01 16:54

Even if the virus manages to dock and enter the cell, it has to physically fuse its own membrane with the human cell's membrane to actually release its genetic material.

SPEAKER_00 17:04

So arbitol blocks that fusion process.

SPEAKER_01 17:07

Right. The virus is inside, but it is trapped in its coat, completely inert.

SPEAKER_00 17:12

That's amazing. And if it does manage to release its genetic material, we have drugs like Favipyravir and Pimodovir.

SPEAKER_01 17:19

Instead of trapping the virus, these drugs attack the virus's internal photocopier.

SPEAKER_00 17:24

They disrupt the transcription process, meaning the virus physically cannot print the blueprints it needs to multiply.

SPEAKER_01 17:30

Exactly. And finally, you have maturation inhibitors like nitozoxinide.

SPEAKER_00 17:34

Right. So even if the virus successfully copies its genetic material and builds new viral proteins, nitozoxinide prevents those proteins from maturing properly.

SPEAKER_01 17:43

Yeah, the host cell ends up assembling defective viruses. It is the biological equivalent of a car factory producing vehicles with square wheels.

SPEAKER_00 17:51

They look like a virus, but they cannot function or infect anything else.

SPEAKER_01 17:54

Exactly.

SPEAKER_00 17:54

Looking at this incredible pipeline drugs that change the locks, trap the virus in its coat, jam the photocopier, and build square wheels, it raises an obvious question for me.

SPEAKER_01 18:04

What's that?

SPEAKER_00 18:05

With all these different mechanisms, why don't we just hit the virus with a massive cocktail of everything at once? I mean, that is exactly how we treat HIV to prevent it from mutating around a single drug.

SPEAKER_01 18:16

It is a sound hypothesis, and clinical researchers absolutely tested it. They ran extensive trials utilizing a combination therapy of ocultamivir and adamantane and a broad spectrum antiviral called Rivavirin. The results were definitive. The cocktail approach offered zero clinical benefit over simply using oscillamivir on its own.

SPEAKER_00 18:38

That is fascinating. Why didn't it work?

SPEAKER_01 18:40

Because the underlying biology of an acute respiratory virus like influenza is fundamentally different from a chronic retrovirus like HIV.

SPEAKER_00 18:47

Oh, because HIV integrates into human DNA.

SPEAKER_01 18:50

Right. And it requires lifelong suppression, which makes combination therapy highly effective at preventing long-term resistance. But influenza is a hit-and-run virus.

SPEAKER_00 19:00

It replicates furiously over a few days and then is cleared by the immune system.

SPEAKER_01 19:05

Exactly. Combining multiple toxicological pressures simultaneously didn't yield the synergistic effects we hoped for. It really just proved that we still have a lot to learn about how this specific virus behaves under extreme pharmacological pressure.

SPEAKER_00 19:19

Man, the escape artist still has a few tricks up its sleeve. Let's step back for a second and look at the vast architecture of everything we've unpacked today from the guidelines.

SPEAKER_01 19:28

It's a lot to take in.

SPEAKER_00 19:29

It really is. We started with the immense nine-month predictive gamble of formulating the seasonal vaccine.

SPEAKER_01 19:34

Then we explored how we turbocharge those shots for the elderly, utilizing adjuvants as an inflammatory megaphone to basically wake up a sluggish immune system.

SPEAKER_00 19:44

Right. And we track the frantic 48-hour clock of using antivirals to glue the virus inside the host cell. And finally, we examine how public health officials cut epidemiological firebreaks through communities to stop outbreaks in their tracks.

SPEAKER_01 19:59

All while simultaneously developing new tech to jam the virus's photocopiers. It is a phenomenal multi-layered defense architecture. Absolutely. And the crucial takeaway here is that managing influenza is never a static solved equation. It is a dynamic, constant adaptation to an enemy that alters its genetic makeup every single year.

SPEAKER_00 20:20

So true. So to you listening, the next time you see that sign outside your pharmacy and you know you roll up your sleeve, remember, you aren't just getting some generic one-size-fits-all injection.

SPEAKER_01 20:29

Not at all.

SPEAKER_00 20:30

You are receiving the final highly engineered product of a massive global dragnet, custom tailored for your specific age and risk profile. But I want to leave you with a final thought to mull over. Our entire current system, the whole reason we require a new shot every single year, relies on predicting the future based on last winter's virus.

SPEAKER_01 20:48

It is an incredibly sophisticated guess, but at the end of the day, it is still a guess.

SPEAKER_00 20:52

Right. But as these novel therapies come to market, the ones that target the fundamental, unchangeable mechanics of the virus, like its ability to copy its blueprints or fuse its membrane, we might one day stop relying on seasonal predictions entirely. Could we be rapidly moving toward a future where we don't need to try and guess the master escape artist's next outfit because we have finally figured out how to just lock the closet door altogether? Something to think about the next time flu season rolls around.