Vaccine advocacy 101

I recently finished a 2-year stint as an American Society for Microbiology Distinguished Lecturer. It’s an excellent program–ASM pays all travel expenses for lecturers, who speak at ASM Branch meetings throughout the country. I was able to attend Branch meetings from California and Washington in the West, to Massachusetts in the east, and south as far as El Paso, Texas, with many in-between. Each Lecturer selects several topics to speak on, and the Branch chooses from those which they want to hear. Mine included basic research (zoonotic disease, antibiotic resistance) as well as science outreach and advocacy topics (zombies, vaccines).

My talk on vaccines covered vaccine hesitancy and denial, the concerns some parents have regarding vaccination, and the way social media and celebrities contributed to the spread of vaccine misinformation. Inevitably, someone would ask in the Q&A or speak to me afterward inquiring, “But what can I do? I don’t feel I know enough about why people reject vaccines, and feel helpless to combat the fears and misinformation that is out there.” These were audiences of microbiologists and other types of infectious disease specialists–people who are very likely to be educated about vaccines and vaccine-preventable diseases, but who may not have followed the saga of disgraced former physician Andrew Wakefield, or aren’t familiar with the claims of the current anti-vaccine documentary, Vaxxed, or other common anti-vaccine talking points.

To help fill this gap, I recently published a paper in Open Forum Infectious Diseases,” Vaccine Rejection and Hesitancy: a Review and Call to Action.” As the title suggests, in it I give a brief overview of some of the figures in the anti-vax movement and the arguments they commonly use. I don’t go into rebuttals directly within the paper, but the supplemental information includes a subset of both anti-vax literature as well as several published rebuttals to them that interested individuals can look up.

I also briefly review the literature on vaccine hesitancy. Who fears or rejects vaccines, why do they do so, and how might we reach them to change their minds? This is really an area where many individuals, even if they’re educated about vaccines and infectious disease, lack a lot of background. As I note in the paper, many science-minded people still think that it’s enough to just educate people about vaccines properly, and that will be enough. While accurate information is indeed important, for many individuals on the vaccine-hesitant spectrum, it’s not only about misinformation, but also about group identity, previous experience with the health care field, and much more.

Still, vaccine advocates can get involved in a number of way. One of the easiest is simply to discuss your own vaccine history in order to normalize it. I regularly post pictures of my own vaccinations on social media (including my public Facebook and Twitter accounts), and those of my kids*. In over 17 years of parenthood, their vaccinations have all been…boring. These “uneventful vaccination” stories are the ones which rarely get told, as the media focuses on “vaccine injury” stories, in which the injuries may or may not actually be caused by vaccines. Those interested in promoting vaccines can write letters to the editor, get involved with local physicians to speak with hesitant families, break out and be political about vaccine exemptions; there are a number of ways that we can work to encourage vaccination and keep our children and our communities healthy (again, explored in more detail in the manuscript).

Figure 1: Examples of photos posted to the author’s social media accounts. Panel A: The author (middle) and her older children after receipt of seasonal influenza vaccines. Panel B: The author’s youngest child at Walt Disney World, wearing a shirt saying “Fully Vaccinated. You’re Welcome.” Both techniques can serve as conversation-starters around vaccination.

 

I hope this paper will serve as a starting point for those who want to be a vaccine advocate, but just aren’t sure they know enough background, or know where or how to jump in. Whether you’re an expert in the area or not, everyone can do small things to encourage vaccines and demonstrate your trust in them. Those of us working in the area thank you in advance for your help.

Reference:

Smith TCVaccine Rejection and Hesitancy: a Review and Call to Action. Open Forum Infectious Diseases, 2017, in press.

 

*AKA, how to get your kids’ pictures into a scientific paper.

The Zika conspiracies have begun

Like cockroaches, the conspiracy theorists suggesting the Zika virus outbreak is anything but a normal, naturally-occurring event have begun to come out of the woodwork. To be expected, the theories they’re espousing make no sense scientifically, and each theory is incompatible with the others, but why should anyone expect that conspiracy theorists would actually use logic?

Claim One: the current Zika virus outbreak is due to the release of genetically-modified mosquitoes by British company Oxitec. The suggestion is that GMO mosquitoes were released in the same area of Brazil now experiencing Zika outbreaks, and somehow these mosquitoes caused the outbreak. The mosquitoes are engineered to require the antibiotic tetracycline in order to survive development in the wild, so when a wild female mosquito breeds with a male GMO mosquitoe, it’s essentially is a death sentence to the female’s offspring. Theorists argue that livestock use of tetracycline leaves this antibiotic in the environment, allowing some offspring to survive. Somehow, Zika is inserted into this.

Who’s claiming this? Stories at Natural News, the Daily Mirror, The Ecologist, and Antimedia, among others. Alex Jones brings in the Bill Gates connection.

What’s wrong with it? There’s absolutely nothing that makes sense to relate this to Zika. Even if these GMO mosquitoes can reproduce, that doesn’t mean they’re suddenly infected with the Zika virus. This article probably lays it out the best as far as a suggested mechanism, but even then it’s a convoluted mess, suggesting a transposon* (a “jumping gene”) moved from the mosquito into Zika virus (but where did the Zika come from in the first place though? was it already in Brazil?), then that transposon made Zika more virulent and gave the virus “an enhanced ability to enter and disrupt human DNA” (what??), which then leads to microcephaly. All without absolutely any citations from the scientific literature to back up this scenario, of course.

And that’s even assuming that the area where the testing occurred was the same as where the mosquitoes were released. It’s not, as both The Mad Virologist and Christie Wilcox point out. Both have many more details taking down this theory as well.

Claim Two: a program encouraging pregnant women to get the Tdap vaccine led to the presumed increase in microcephaly in Brazilian babies. Because, toxins?

Who’s claiming this? Really credible places, like Brazilian Shrunken Head Babies (not even joking).

What’s wrong with it? Pretty much everything. First, the vaccine isn’t recommended until relatively late in pregnancy; even one of the links cited by the “shrunken heads” page notes that it’s suggested in the 27th to 36th week of pregnancy. This is very late in pregnancy to have such a severe effect on brain/skull development. For other microbes that cause microcephaly (such as cytomegalovirus or rubella), infection occurring in the first half of the pregnancy (before 20 weeks) is usually associated with a higher likelihood of adverse developmental outcomes, not one very late like Tdap. And of course, this theory completely contradicts the “Zika-GMO mosquito” one, which suggests that Zika is the cause.

Biologically, this makes zero sense–and furthermore, why wouldn’t other countries be seeing this spike, if Tdap is truly the cause? Women in the U.S. and other countries also receive this vaccine during pregnancy, but we haven’t seen an increase in microcephaly cases. Furthermore, a recent study has demonstrated yet again that Tdap is very safe during pregnancy.

Claim Three: Rockefeller something something bioterrorism something, maybe. They’ve taken the fact that an organization, the American Type Culture Collection (ATCC), has Zika virus available on their website, and twisted that into apparently some kind of deliberate release, maybe? It’s all pretty shadowy. [Updated: this site very clearly says the Rockefellers invented it to kill people. If that were true, they did a pretty shitty job].

Who’s claiming this? Chemtrails Global Skywatch and The Freethought Project.

What’s wrong with it? Even the Freethought Project post basically unravels its own conspiracy theory, but still posted this for some reason, noting “It seems that while the virus is available online, it is not extremely easy to get, and would likely require some extremely creative fraud in order to make it happen,” but concluding that “…it definitely does seem that it would be possible for a group or individual that is determined enough to make their way through the website’s security measures.”

I seriously doubt that.

For those of you who don’t know, ATCC is basically a global clearinghouse for biological samples–they offer tissue culture lines, bacteria, viruses, etc. Researchers need these for a number of reasons, such as having positive controls for assays, or to be sure they’re using the same cells as another investigator whose work they want to replicate or expand upon. I’ve used them many times to get both bacteriophage as well as isolates of bacteria for my research projects. And they won’t ship to just some random person.

When I moved institutions and set up my new laboratory, on my first ATCC order, they contacted the director of biosafety at my institution to be sure my lab was equipped and ready to handle the organisms I had requested. When that was assured, we still had to establish a Material Transfer Agreement in order for the items to actually be shipped–a legal document between ATCC and my university, signed by an “authorized representative” of my institution. It was only after jumping through all of these hoops that I was finally able to get the requested samples.

Even if someone had chosen to order Zika, an obscure, mostly-asymptomatic virus that until this outbreak was not associated with any serious ill effects, and perpetuated the “extremely creative fraud” mentioned by the Freethought Project…why? They’d need to initially infect themselves or others in order for the mosquitoes to subsequently become competent vectors of the virus. The mosquitoes would feed on them when there was adequate virus in the blood, and presumably the insects would then be released–to what end? To spread a previously-thought-relatively-harmless virus into a new population? Again, nonsensical.

[Updated: this doesn’t mean that “Rockefeller owns the patent on Zika virus,” as sites like this are claiming. As far as I can ascertain, there are no patents involving Zika. What it means is that the virus was deposited by Jordi Casals, who was an eminent virologist and had a large collection of viruses that he accumulated throughout his career, including Zika (but many others, as a search of ATCC shows). Rockefeller makes no money on this–in fact, now some journals require deposition of strains to ATCC or similar banks as a condition for publishing.]

Claim four: Zika simply doesn’t exist and/or isn’t causing microcephaly, and the “outbreak” is a ploy to push the not-yet-extant Zika vaccine/get people to blindly obey the government. (hat tip to Mary Mangan for this one).

Who’s claiming this? HIV denier and anti-vax advocate Jon Rappoport, among others (another post of his here on the topic). A very common sentiment in the comments pages on anti-vaccine pages.

What’s wrong with it? Pretty much everything. Rappoport has made a meta-conspiracy theory, claiming the increase in microcephaly is caused not by Zika, but by a combination of pesticide use and manufacturing, the Tdap and GMO mosquitoes mentioned above, mosquito sprays, and poverty/sanitation/malnutrition (the boogeymen of every anti-vaccine advocate). While he’s correct that the link between Zika and microcephaly isn’t yet 100% confirmed (as I mentioned yesterday), he’s taking at face value the claim that there actually is an increase in microcephaly at all–something which is also not been confirmed. So like many science deniers, he’s taking the parts of the research that fit his biases (look at how toxic Brazil is! Of course it’s causing health problems in babies!) and ignoring the parts he doesn’t–that if there is an increase in microcephaly, Zika might be a driving force. In his mind, the virus is irrelevant and just a mechanism to make the public into “sheep” who will fall in line with government recommendations.

I’m sure this will not be the last of the conspiracy theories. Like those we saw with Ebola, these have the potential to cause real harm. Outcry over the GMO mosquito program can curtail use of another agent to control the Aedes aegypti mosquito–the primary vector not only of Zika, but also yellow fever, chikungunya, and dengue. I know those who benefit from these type of conspiracies will never stop churning them out (Mike Adams, I’m looking at you), but we need to bring them to the light and show just how little scientific support any of this has. It won’t inoculate everyone against these ideas, but hopefully it will provide enough community immunity that they’re unable to spread far and wide.

*Christie Wilcox pointed out another great observation on just how implausible this is–that the potential to insert a 8.4kb double-stranded DNA transposon into a 10.8kb single-stranded RNA virus is…not possible. So, yeah, just to add to the ridiculousness of that idea.

Preparing for the zombie apocalpyse

I have a paper out in the Christmas issue of BMJ on the coming zombie apocalypse.

You read that right. And yes, it was peer-reviewed.

I’ve discussed previously how I’ve used the attention paid to zombies to talk about infectious diseases with children and other audiences; and to bring some science to the Walking Dead and other zombie tales. I even include a zombie lecture as part of the talks I give in my position as an American Society for Microbiology distinguished lecturer.

Why?

Like them or hate them, zombies are part of the zeitgeist. The Walking Dead is still one of the highest-rated programs on television, and its spin-off, Fear the Walking Dead, has been renewed for a second season. Early 2016 will bring us Pride and Prejudice and Zombies on film. Even Aaaahnold Schwarzenegger did a zombie movie. The Girl with all the Gifts was a sleeper hit, and a movie version of the zombie fungus video game The Last of Us is supposedly on the way.

So that’s what the BMJ paper was all about. Of course, it’s ridiculous at its core–no one really expects a zombie outbreak. *But*, we do see new diseases emerging all the time. MERS. Zika virus. Chikungunya. Hendra. Nipah. Pandemic influenza. Other, novel influenzas. And of course, the Ebola virus disease outbreak that is still ongoing in Guinea and Liberia (though cases have finally slowed to a mere trickle).

And we’re still unprepared for them when they become explosive, as Ebola did in 2014. Analyses have showed that the delayed response to that outbreak cost lives. And that’s for a virus that is not particularly easy to transmit, as it’s only spread late in the illness via direct contact with infected bodily fluids. If that had been another virus that was airborne instead of bloodborne, the world could have been in a much worse situation. Now imagine that it was the Solanum virus of World War Z (the book version), slowly incubating in infected individuals as they move all over the globe. Definitely unprepared.

Furthermore, even with our handful of cases in the U.S., we saw that the hype and misinformation about Ebola was out of control. We saw this with H1N1 in 2009 as well, and H5N1 before that. We’re still, as a whole, pretty bad at communicating about infectious disease threats–striking that correct balance of assurance that we know what we’re doing, but acknowledging the gaps in our data and how we’re working to address those. It’s not an easy thing to do, but we need to continue improving. Because again, that’s how it always starts in zombie movies, right?

All-Im-saying-is-Zombie-movie

Ebola and zombies also lead to ethical dilemmas. As I noted in the paper, for a zombie outbreak, there would remain the question of quarantine (for those exposed/bitten but not yet sick), and isolation (for those who are ill)–how would those be handled? What if quarantining the healthy-but-exposed led to essentially a death sentence, as the bitten would inevitably “turn”, and possibly start chowing on the still-living who were quarantined with them? Again, ridiculous on its face, but it has parallels in real-life outbreaks and the legality and ethical quandaries of when to use such measures (and, of course, used with the assumption that they would be effective–which doesn’t always hold). There are accusations that these were violated last year, when individuals coming back from working the Ebola outbreak were quarantined–lacking in scientific justification for sure, and potentially illegal as well.

Using zombies in lieu of real diseases gives researchers, public health professionals, policy makers, and laypeople the ability to discuss these heavy issues without getting bogged down in one specific outbreak or pathogen, because many of the problems we’d face during the zombie apocalypse are similar to those that come up in any serious epidemic: coordination. Funding. Communication. Training. Access to treatment or prevention. Though I didn’t discuss it in this particular article, proper personal protective equipment (PPE) is another issue–both access to it (lacking in developing countries), and being sure to choose the right gear for the outbreak (“overprotection” is not always better). Further, it encourages individuals to put together their own zombie (disaster) preparedness plan, which is how the CDC has used the zombie phenomenon.

In short, it’s way more fun for the average person to shoot the shit about zombies than to have a more serious discussion about influenza, or Ebola, or whatever the infectious disease du jour may be–and maybe even learn a bit of science and policy along the way.

 

Is there such a thing as an “evolution-proof” drug?

Eleven years ago, two scientists made a bet. One scientist wagered that a new type of antimicrobial agent, called antimicrobial peptides, would not elicit resistance from bacterial populations which were treated with the drugs. Antimicrobial peptides are short proteins (typically 15-50 amino acids in length) that are often positively charged. They are also a part of our body’s own innate immune system, and present in other species from bacteria to plants. It is thought that these peptides work primarily by disrupting the integrity of the bacterial cell, often by poking holes in them. Sometimes they work with the host to ramp up the immune response and overwhelm the invading microbe. Because the peptides are frequently targeted at the bacterial cell wall structure, it was thought that resistance to these drugs would require a fundamental change in membrane structure, making it an exceedingly rare event. Therefore, these antimicrobial peptides might make an excellent weapon in the fight against multiply drug-resistant bacteria.

Additionally, the remarkable diversity of these peptides, combined with the presence of multiple types of peptides with different mechanisms of action present at the infection site, rendered unlikely the evolution of resistance to these molecules (or so some reasoning went). However, evolutionary biologists have pointed out that therapeutic use of these peptides would differ from natural exposure: concentration would be significantly higher, and a larger number of microbes would be exposed. Additionally, resistance to these peptides has been detailed in a few instances. For example, resistance to antimicrobial peptides has been shown to be essential for virulence in Staphylococcus aureus and Salmonella species, but we didn’t *witness* that resistance develop–therefore, it might simply be that those species have physiological properties that render them naturally resistant to many of these peptides, and were never susceptible in the first place.

The doubter of resistance, and the bet instigator, was Michael Zasloff of Georgetown University, who wrote in a 2002 review of antimicrobial peptides:

Studies both in the laboratory and in the clinic confirm that emergence of resistance against antimicrobial peptides is less probable than observed for conventional antibiotics, and provides the impetus to develop antimicrobial peptides, both natural and laboratory conceived, into therapeutically useful agents.

Certainly in the short term, resistance may be unlikely to evolve for reasons described above. However, if these peptides are used over an extended period of time, could the mutations necessary to confer resistance accumulate? This was the question asked in a new study by Dr. Zasloff along with colleagues Gabriel Perron and Graham Bell. Following publication of his 2002 paper where he called evolution of resistance to these peptides “improbable,” Bell challenged Zasloff to test this theory. Zasloff took him up on the offer, and they published their results in Proceedings of the Royal Society

The result?

Zasloff had egg on his face. Resistance not only evolved, but it evolved independently in almost every instance they tested (using E. coli and Pseudomonas species), taking only 600-700 generations–a relative blip in microbial time. Oops.

Well, everything old is new again. A very similar claim has been making the rounds recently, originating from the press release for a new paper claiming to have found bacteria’s “Achilles’ heel,” advancing the claim that “Because new drugs will not need to enter the bacteria itself, we hope that the bacteria will not be able to develop drug resistance in future.”  A grand claim, but history suggests otherwise. It was argued that bacteria could not evolve resistance to bacteriophage, as the ancient interaction between viruses and their bacterial hosts certainly must have already exploited and overcome any available defense. Now a plethora of resistance mechanisms are known.

Alexander Fleming, who won the 1945 Nobel Prize in Physiology or Medicine, tried to sound the warning that the usefulness of antibiotics would be short-lived as bacteria adapted, but his warnings were (and still are?) largely ignored. There is no “magic bullet;” there are only temporary solutions, and we should have learned by now not to underestimate our bacterial companions.

Part of this post previously published here.

“Spillover” by David Quammen

Regular readers don’t need to be told that I’m a bit obsessed with zoonotic disease. It’s what I study, and it’s a big part of what I teach. I run a Center devoted to the investigation of emerging diseases, and the vast majority of all emerging diseases are zoonotic. I have an ongoing series of posts collecting my writings on emerging diseases, and far too many papers in electronic or paper format in my office to count. Why the fascination? Zoonotic diseases have been responsible for many of mankind’s great plagues–the Black Death, the 1918 “Spanish” flu pandemic, or more recently, HIV/AIDS. So you can imagine my delight when I read about Spillover, a new book by David Quammen on zoonotic diseases.

I’ve previously highlighted some of Quammen’s work on this site. That link goes to a 2007 story he wrote for National Geographic on “infectious animals,” which really serves as a preview to “Spillover,” introducing some of the concepts and stories that Quammen elaborates on in the book.

“Spillover” is wide-ranging, tackling a number of different infectious agents, including viruses like Nipah, Hendra, and Ebola; bacteria including Coxiella burnetii and Chlamydia psittaci; and parasites such as Plasmodium knowlesi, a zoonotic cause of malaria. HIV is a big part of the story; Quammen devotes the last quarter or so of the book to tracing the discovery and transmission of HIV from primates to humans, and from 1900 to present-day. He even takes the time to explain the basic reproductive number–something that’s not always a page-turner, but Quammen manages to do it well and without being too tangential to the rest of the story; much more of a Kate-Winslet-in-Contagion than Ben-Stein-in-Ferris Bueller delivery.

Indeed, “Spillover” is somewhat unique in that it doesn’t read quite like your typical pop science book. It’s really part basic infectious disease, part history, part travelogue. Quammen has spent a number of years as a correspondent for National Geographic, and it shows. The book is filled with not only well-documented research findings and interviews with scientists, but also with Quammen’s own experience in the field, which gives the book a bit of an Indiana Jones quality. In one chapter, he details his adventure tagging along with a research team to capture bats in China, entering a cave that “felt a little like being swallowed through the multiple stomachs of a cow.” This was after an earlier dinner in which he describes his encounters with the an appetizer of the “world’s stinkiest fruit” (I’ll keep the description of the smell to myself) with congealed pig’s blood for a main dish (bringing to mind the scooping out of monkey’s brains in “Temple of Doom”–and the various zoonotic diseases that could be associated with those, come to think of it).

Quammen’s book is an excellent, and entertaining, overview of the issues of zoonotic disease–why do they emerge? Where have they come from? How do they spread? The only thing that’s missing is more of a cohesive discussion about what to do about them. However, that’s rather understandable, as we certainly have less of a grasp of this question than we do about the others (and even with some of those, our knowledge is spotty at best). I hope “Spillover” will inspire another generation of future germ-chasers, as “The Coming Plague” did almost 20 years ago.

Using zombies to teach science

With my colleague Greg Tinkler, I spent an afternoon last week at a local public library talking to kids about zombies:

The Zombie Apocalypse is coming. Will you be ready? University of Iowa epidemiologist Dr. Tara Smith will talk about how a zombie virus might spread and how you can prepare. Get a list of emergency supplies to go home and build your own zombie kit, just in case. Find out what to do when the zombies come from neuroscientist Dr. Greg Tinkler. As a last resort, if you can’t beat them, join them. Disguise yourself as a zombie and chow down on brrraaaaiiins, then go home and freak out your parents.

Why zombies? Obviously they’re a hot topic right now, particularly with the ascendance of The Walking Dead. They’re all over ComicCon. There are many different versions so the “rules” regarding zombies are flexible, and they can be used to teach all different kinds of scientific concepts–and more importantly, to teach kids how to *think* about translating some of this knowledge into practice (avoiding a zombie pandemic, surviving one, etc.) We ended up with about 30 people there: about 25 kids (using the term loosely, they ranged in age from maybe age 10 to 18 or so) and a smattering of adults. I covered the basics of disease transmission, then discussed how it applied to a potential “zombie germ,” while Greg explained how understanding the neurobiology of zombies can aid in fleeing from or killing them. The kids were involved, asked great questions, and even taught both of us a thing or two (and gave us additional zombie book recommendations!)

For infectious diseases, there are all kinds of literature-backed scenarios that can get kids discussing germs and epidemiology. People can die and reanimate as zombies, or they can just turn into infected “rage monsters” who try to eat you without actually dying first. They can have an extensive incubation period, or they can zombify almost immediately. Each situation calls for different types of responses–while the “living” zombies may be able to be killed in a number of different ways, for example, reanimated zombies typically can only be stopped by destroying the brains. Discussing these situations allows the kids to use critical thinking skills, to plan attacks and think through choice of weapons, escape routes and vehicles, and consider what they might need in a survival kit.

Likewise, zombie microbes can be spread through biting, through blood, through the air, by fomites or water, even by mosquitoes in some books. Agents can be viral, bacterial, fungal, prions or parasitic insect larvae (or combinations of those). Mulling on these different types of transmission issues and asking simple questions:

“How would you protect yourself if infection was spread through the air versus only spread by biting?”

“How well would isolation of infected people work if the incubation period is very long versus very short?”

“Why might you want to thoroughly wash your zombie-killing arrows before using them to kill squirrels, which you will then eat?” (ahem, Daryl)

can open up avenues of discussion into scientific issues that the kids don’t even realize they’re talking about (pandemic preparedness, for one). And the great thing is that these kids are *already experts* on the subject matter. They don’t have to learn about the epidemiology of a particular microbe to understand disease transmission and prevention, because they already know more than most of the adults do on the epidemiology of zombie diseases–the key is to get them to use that knowledge and broaden their thinking into various “what if” situations that they’re able to talk out and put pieces together.

It can be scary going to talk to kids. Since this was a new program, we didn’t know if anyone would even show up, or how it would go over. Greg brought a watermelon for some weapons demonstrations (household tools only–a screwdriver, hammer and a crowbar, no guns or Samurai swords) which was a big hit. Still, I realize many scientists are more comfortable talking with their peers than with 13-year-olds. Talking about something a bit ridiculous, like an impending zombie apocalypse, can lessen anxiety because it takes quite a lot of effort to be boring with that type of subject matter; it’s entertaining; and kids will listen. And after all, what you don’t know, might eat you.

Infectious disease epidemiology and zombies

Have two awesome announcements that I’ve been waiting to share. One will still have to wait a few more days as we’re finalizing some details, I can now let you know that I just started a new position as an Advisory Board member of the Zombie Research Society. It’s a pretty cool group, including THE George Romero (Zombie Godfather); Daniel Drezner, author of Theories of International Politics and Zombies, and Steven Schlozman, author of The Zombie Autopsies. Plus a bunch of other white guys.

So, why do something like this? Zombies obviously are huge in pop culture, and typically “zombieism” is caused by some kind of transmissible infectious agent. As such, it’s a good way to talk about infectious diseases in a more lighthearted and fun manner. The CDC already took advantage of this with their popular “Preparedness 101: Zombie Apocalypse” page, while Robert Smith? demonstrated the utility of using a zombie outbreak to model infectious diseases. I think there’s more to be explored and am looking forward to the journey.

Worms: Are they good or bad for us?

Student guest post by Shylo Wardyn

“Of all the parasites I’ve had over the years, these worms are among the… hell, they are the best”.

Was Fry from the animated show ‘Futurama’ right in his assessment of worms being good for him? Did he know something about parasitic worm infections that I was unaware of? Well, in the show, his parasites were doing remarkable things for his body, but does this translate to real life at all? Some people think so. Altman reviews the idea that over evolutionary time, our ancestors were infected with all sorts of parasites and this led to an interaction between the worm gene products and the immune system. These interactions led to modulation of dendritic cells and establishment of T-cell networks. It has been hypothesized that in an environment without these interactions, as is the case for most people living in “Westernized” countries, there is a loss of the ‘fine tuning’ of the adaptive immune system.

In another review, Jackson et al. discuss how this mechanism could have co-evolved. It is generally believed that the T helper cell type 2 (Th2) evolved to counter infections with parasitic worms. These cells are activated in response to parasitic worm infection, which leads to a large regulatory T cell response. Our response to worms seems to involve an immune response that is less inflammatory than our response to microbes, and it also takes much longer to reach the peak of effectiveness. This is due in large part to an initial systemic suppression of innate and adaptive immunity in the host. This is likely caused by regulatory CD4+ and CD25+ T cells producing suppressive cytokines or other suppressor T cell subsets. Anti-inflammatory responses are also caused by alternatively activated macrophages. These macrophages secrete anti-inflammatory cytokines and express genes whose functions relate to wound healing and repair. Therefore, being infected with parasitic worms leads to a down-regulation of proinflammatory responses, while allowing mechanisms for wound repair and a controlled development of the Th2 response. This Th2 and T regulatory response is beneficial for both the worm and the host. For us, the regulated Th2 response is less costly than the generation of a strong immune response, which often can be detrimental to our own cells. For the parasites, they are able to survive the initial immune response and therefore reproduce, while later parasites would not be able to survive the developed immune response.

The overall thought is that since parasitic worm infections are ubiquitous in mammals and have been since mammals first evolved, there would be a positive selective pressure for those individuals whose immune systems respond well to worm infections. Our immune systems may have been selected to anticipate a chronic exposure to Th2 and T regulator inducing pathogens. Since our ancestors were chronically infected by worms, their immune systems would have developed to work well in this context, while not necessarily working as well in the absence of worms. This scenario may explain why in some cases the immune system goes haywire in populations that are free from parasitic worms.

So is there any strong evidence linking parasites with populations free from allergies and autoimmune diseases? There have been many ecological studies which show an inverse correlation between the parasite load and allergy level for a particular region. Does this prove anything? Not really, the data is simply correlative. There have been other studies showing that treatment of worm infections is accompanied by an increase in skin test reactivity to allergens and IgE antibody levels. It appears that in the absence of worms, the immune system overreacts to allergens to which it normally wouldn’t mount a response in the presence of worms. This gives us a better idea about the link between parasitic worms and immune responses. While the evidence is still shaky, it is biologically plausible that the lack of worms in our environment has led to the massive increase in the amount of immune related diseases, such as asthma, multiple sclerosis, type 1 diabetes, and general allergies. However, the immune system is incredibly complex, as are those diseases, and I’ve barely scratched the surface of it for this topic. So while it seems being infected with worms may prevent immune system diseases, I doubt anyone would trade their asthma for a tapeworm. It does make for an interesting hypothesis (and Futurama episode) though and should be researched more thoroughly.

References

Altmann D. M. (2008). Review series on helminths, immune modulation and the hygiene hypothesis: Nematode coevolution with adaptive immunity, regulatory networks and the growth of inflammatory diseases. Immunology, 126(1); 1-2.

Jackson J. J., Friberg I.M., Little S. and Bradley J. E. (2008). Review series on helminths, immune modulation and the hygienehypothesis: Immunity against helminths and immunological phenomena in modern human populations: coevolutionary legacies? Immunology, 126(1); 18-27.

Weiss S.T. (2000). Parasites and asthma/allergy: What is the relationship? Journal of Allergy and Clinical Immunology, 105(2); 205-210.

The Uncertain Etiology of PMS and a Link to Infectious Disease

Student guest post by Anne Dressler

Ninety percent of menstruating women experience some kind of premenstrual symptoms during the luteal phase of the menstrual cycle, with 20-30% experiencing moderate to severe symptoms. With an even more severe collection of symptoms, is premenstrual dysphoric disorder (PMDD). 3-8% of menstruating women report symptoms severe enough to be considered suffering from PMDD. Yet another designation, premenstrual magnification (PMM), is used to describe women who are symptomatic the entire cycle but have a premenstrual exacerbation of a diagnosed psychiatric, medical, or gynecological condition.

With a large number of wide-ranging symptoms and the difficulty involved in making a diagnosis, it is not surprising that the various theories advanced to explain premenstrual syndrome (PMS) have yet to been proven. One problem is that PMS is a diagnosis of exclusion, meaning there could be a variety of poorly understood conditions responsible for these symptoms. Several theories attribute PMS to fluctuations in sex hormones and neurotransmitters. The observation that symptoms disappear when a women has a menstrual cycle during which she does not ovulate and a corpus luteum is not formed, led to the theory that sex steroids, estrogen and progesterone, produced by the corpus luteum are responsible. In addition, the neurotransmitters serotonin and gamma amino butyric acid (GABA) have been implicated in various pathways. The list of other hormones and their modes of action that are suspected to be involved is long and confusing, making it no wonder that there is still no known etiology.

One distinctly different hypothesis is that PMS is due to a broad set of persistent infectious illnesses that are exacerbated by cyclic changes in immunosuppression due to the fluctuating levels of progesterone and estrogen. In general, there have been studies looking at two major categories of causation- genetic and environmental and have found moderate correlations at the best. Infectious causation has been overlooked for the most part, with almost no empirical support in published literature. I don’t think this means there is no value to the theory, simply that it is a very hard one to test. One very convincing article by Doyle et. al explains how this possibility of infectious causation is integrated with the cyclic changes in hormone levels that have been observed and are generally thought to be involved in PMS.

As the article explains, immune function varies across the menstrual cycle. During the luteal phase, cell-mediated immunity is suppressed and humoral immunity is amplified. This appears to be related to higher levels of progesterone that enhances humoral immunity by promoting the development of type 2 helper T cells. In addition, progesterone is involved in suppressing type 1 helper T cells, which is associated with inhibition of natural killer cells and phagocytosis. This leads to less effective control of various fungi, viruses, and intracellular bacteria. Estrogen also seems to suppress cell-mediated immunity. These hormone driven changes to the immune system provide the possibility that persistent infections may be less well controlled during the luteal phase, leading to the symptoms that make up PMS.

Supporting evidence for this theory is a long list of infections, compiled by Doyle et. al, that are normally controlled by cell-mediated immunity but are exacerbated premenstrually. These include, increased proliferation of Candida albicans, increased proliferation of cytomegalovirus in the cervix, increased number of lesions from human herpes simplex virus-1, and exacerbated peptic ulcers from Helicobacter pylori among others. There are also chronic diseases that have infectious causes or are suspected to have infectious causes that are exacerbated premenstrually. A few examples are, Crohn’s disease, lupus, multiple sclerosis, rheumatoid arthritis, asthma, and chronic fatigue syndrome. The pathogens that are suspected causes for these diseases are also controlled by cellular immunity.

Finally, one group performed a double blind, randomized clinical trial to determine the effects of the antibiotic doxycycline on PMS. Compared to the placebo group, individuals taking the antibiotic had significantly decreased symptoms. Subsequently, the placebo group was also given the antibiotic and experienced similar symptom reduction. This reduction in symptoms was steady during a six-month follow-up period. The investigators also found a high percentage of endometrial biopsy cultures positive for Mycoplasma species, Chlamydia trachomatis, and anaerobic bacteria.

This theory seems to be strongly biologically plausible, but lacks any of the other criteria for causality due to the lack of published studies on the topic. It is not in disagreement with the currently accepted idea that sex hormones fluctuate during the menstrual cycle and are involved in symptom manifestation. However, Doyle et. al advance this idea by explaining how it is may not be the direct effects of the hormones, rather a hormone-driven suppression of cellular immunity that could lead to poor control of persistent infections causing symptoms. This is certainly an interesting theory, yet one that would be difficult to study. Practical applications of findings from studies on this subject could be to consider control of PMS symptoms with antibiotics.

References:

Backstrom, T., et al. The Role of Hormones and Hormonal Treatments in Premenstrual Syndrome.” CNS drugs 17.5 (2003): 325-42.

Doyle, C., H. A. Ewald, and P. W. Ewald. “Premenstrual Syndrome: An Evolutionary Perspective on its Causes and Treatment.” Perspectives in biology and medicine 50.2 (2007): 181-202.

Korzekwa, M. I., and M. Steiner. “Premenstrual Syndromes.” Clinical obstetrics and gynecology 40.3 (1997): 564-76.

Pinkerton, J. V., C. J. Guico-Pabia, and H. S. Taylor. “Menstrual Cycle-Related Exacerbation of Disease.” American Journal of Obstetrics and Gynecology 202.3 (2010): 221-31.

Silberstein, S. D., and G. R. Merriam. “Physiology of the Menstrual Cycle.” Cephalalgia : an international journal of headache 20.3 (2000): 148-54.

Toth, A., et al. “Effect of Doxycycline on Pre-Menstrual Syndrome: A Double-Blind Randomized Clinical Trial.” The Journal of international medical research 16.4 (1988): 270-9.