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Doing Science

science communication

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Dear Tara,

If I am not mistaken, the part of the paper you quote refers to conventional semisynthetic vancomycin analogs which are already in the clinic (with their single effective mechanism of action against VRE) rather than the most promising compound 18 (with three effective mechanisms of action against VRE) that the authors synthesised.

Furthermore, the resistance experiments carried out by the authors (Figure 10) are done with VRE, meaning the vancomycin resistance genes are in fact already present?

I am intrigued to hear your thoughts on the paper considering these two points. Personally, I see the results from the paper as promising although I agree that the use of the term "resistance-proof" is seriously problematic.

Kind regards,
Sophie

This was a very interesting post! I have a question regarding Fleming's theory. Did he think that the use of antibiotics wouldn't be able to be used for a long period of time due to the bacterial resistance? Wouldn't that be congruent with the blog post about having temporary treatments since bacteria can always figure out how to become resistant? Thanks for your clarification.

In the future do you think we will ever come up with a "resistant proof" antibiotic or will the bacteria always adjust no matter what we find??

Baby on board--in a BSL4 lab

tsmith — Mon, 18 Aug 2014 11:28:41 +0000

Baby on board--in a BSL4 lab

I'm happy to welcome Dr. Heather Lander to the blogosphere and Twitterverse. She's a virologist who has done work with some of the world's deadliest pathogens in a high-security biosafety level 4 laboratory. This is the type of lab where one must wear "space suits" to work with organisms. You've probably seen in dramatized in various movies and TV shows (such as The Walking Dead). Heather describes what it's really like to work in one--even while pregnant.

Dr. Lander, 9 months pregnant in a BSL4 lab

TS: Can you tell readers a bit about your background and research? How did you get interested in studying viruses, especially some of the deadliest on earth that require BSL4 containment?

HL: I began my college career as a music major but I also loved science so I enrolled in many science classes, weighing my options. When I took a molecular cell bio class I was hooked. I changed majors and didn't look any farther ahead than my Bachelor's degree. But then the news exploded with tale of deadly virus outbreaks, and books and movies started coming out. I was fascinated, as are most people, so with permission from the professor I enrolled in a graduate level molecular virology course. Turns out viruses are beyond interesting. They blew my mind: microscopic, consist of hardly anything and can take us down in a matter of days. I wanted to know what was going on. At this point I thought all viruses were insanely interesting, but I found myself drawn to those that cause hemorrhagic fevers (HFV), and not only because of the media attention. I started reading the literature and these viruses were pretty different than the more familiar ones. They were confounding and I wanted to help figure them out.

Because I hadn't planned ahead, I wasn't ready to apply to grad school. So to improve my chances of working with these viruses, I got a job as a technician in a very highly regarded lab that worked on angiogenesis; basically the biology of blood vessels. Because HFVs either damage blood vessels or make them leaky, I thought it would be a good knowledge base. From there I got into the University of Texas Medical Branch as a PhD student and ended up working with CJ Peters, one of the premier experts in HFVs. Our interests aligned and he was great at listening to and encouraging the ideas of a neophyte.

We wanted to investigate viral infection of the cells that line the blood vessels, endothelial cells, and UTMB was getting ready to open their new BSL4 facility - The Robert E. Shope, MD Laboratory - the first of its kind at a U.S. university. In deciding which virus to work with, we took Ebola off the table because it was pretty clear that Ebola caused blood vessel leakiness through overt damage. Other HFVs did not, so the mechanisms of vessel leakiness were still unknown. Of these viruses, the arenaviruses were good options for me. One in particular, Junín virus, which causes Argentine hemorrhagic fever, was a nice model because we had access to virulent and attenuated strains. I could work with the attenuated BSL2 virus, to get my model and systems up and working, and then repeat the experiments with the virulent BSL4 virus. So I researched the effects of Junín virus infection on human endothelial cells.

TS: For readers who aren't familiar with what working in a BSL4 entails, can you describe what it's like to work in such a laboratory?

HL: Working in a BSL4 lab adds a lot of steps to any lab work so everything takes longer. Before you can even go inside you are required to have extensive training, health and psychological assessments and be granted Department of Justice security clearance - many BSL4 organisms are Select Agents. After training at all other levels: BSL2 and 3, you are required to complete 100 hours of mentored, supervised BSL4 training, and assessment by the mentor, before being granted independent access. So, BSL4 research is only done if you can't answer the scientific questions another way. Now, UTMB has the Galveston National Lab, a second BSL4 lab that is much larger, but the Shope lab is relatively small, only a few people can be in there at the same time. This means you have to plan ahead and schedule. Do you have all the supplies you need? You can only carry so much in at one time and you can't go in and out, it's too time consuming. So you have to make sure you know what you'll need and I would often go in a day ahead of time, just to take supplies and make sure I would be ready to go.

During training you do a lot of practice. One of the most important things to practice initially is how to safely hold and open cryovials while wearing bulky rubber gloves. You also learn all safety and decontamination protocols as well as some practical things like moving around the lab safely. Seems silly, but in the lab, you are connected to an air supply through a hose that is attached to the air supply system on the ceiling. Those hoses don't move with you. They stretch only so far and then you have to disconnect, move to where you need to be and connect a hose at that location. The suits are positive pressure with a constant inflow of air, with ports for air exhaust, otherwise they'd pop like a balloon. The air-flow is wonderful. The suits are cool and relatively comfortable, much more so than the stuff you wear for BSL3. Another important thing to learn and practice is how to enter and exit the lab. Seems simple but there are many steps involved. Here's a description of what is is like to enter and exit the UTMB Shope Lab. Other labs are different, so this description isn't meant to apply to all BSL4 labs in general, although the principles would be the same.

One of the best things about working in BSL4 is that, once you're inside no one bothers you, no one interrupts you. There is a phone, but you don't use it unless you have to. So there are no annoying deliveries, phone calls or bored people stopping by to chat. It's great. Though there was one very important thing I learned early: if you're disconnect from the air hose, don't bend over! When you do, you force the air that's in the suit, out through the exhaust valves, so when you stand back up, the suit is sucked to you like a vacuum sealed bag with no air. Yeah, I did it. They laughed. It only happened once.

TS: Did you or your husband have any reservations about you continuing to work while pregnant? What convinced you that it was safe?

HL: We never had any reservations, and I'll explain why. When I started working in the BSL4, I made sure I explained the work and the risks, to my family and my husband. So when I got pregnant, I had been working in the lab for a couple of years and he was very familiar with what I did. We had many long conversations about it and, as a couple, sat down with CJ and also our environmental health safety officer, the go-to person at UTMB for Select Agent biosafety, and member of the ASBA council. CJ had been head of USAMRIID's containment lab and then he was Chief of Special Pathogens at the CDC. CJ and out EHS officer both know their stuff and were very helpful. I never felt pressured to continue working in the BSL4. It was my decision, with input from my husband of course, but he let me make the call. He trusted me and knew I wouldn't be foolish. Aside from the obvious, the concern with Junín virus is that the case fatality rate is much higher than normal for pregnant women and fetuses, so it was not a cavalier decision by any means.

The bottom line, was that the entire time I worked in the BSL4, I valued my life and I was exacting and followed protocols to the letter. BSL4 protocols are designed to prevent any chance of contamination or infection and if they are followed, then the lab is clean. It's the cleanest lab I've ever been in. I think a big misconception is that there are viruses floating around everywhere in the BSL4 and that's why you wear the suit, but that's just not true. The BSL4 protocols prevent contamination and infection. The suits are back-up - meant more to prevent exposure in the event of an accident than as a first line of defense. If someone in the BSL4 goes into cardiac arrest, we would remove the suit and administer first aid. This of course depends completely on each scientist adhering to protocols, and they do. And they are watched to make sure they do. The director's office has cameras so he can see who is working and what they are doing. Every action is documented. And the people working in there are highly trained. I trusted those people and I trusted myself. I never deviated from the protocols, and I knew that. I was already being as careful and exacting as I could be, so there was no way for me to be more careful because I was pregnant. In addition, I wasn't working with animals at that point, so the risks were lower. I was never worried and neither was my husband.

TS: How did your superiors take it when you first met with them to discuss continuing to do such work while pregnant? Was there anything you had to sell them on to allow you to work in there during your pregnancy?

HL: This was hard. I was terrified that they would make me stop working. No pregnant woman had ever been knowingly allowed to work in a BSL4 lab in the U.S. prior to this. I say "knowingly" because CJ pointed out that it's possible that there were women at the CDC or USAMRIID who went into the BSL4 while pregnant and either didn't know it yet, or they knew but waited as long as they thought they could before telling their supervisor, because they knew they would be told to stop. And here I was, a student at a university.

I broke the news in a committee meeting, my last powerpoint slide was an ultrasound photo. The reactions were mixed, to say the least, but CJ was my advisor so they deferred to him. I didn't have to sell it to CJ, or to our EHS officer. They were very supportive and seemed to welcome the opportunity to advance the rights of pregnant women in biosafety, in a safe way. We discussed the risks and my work and when my husband and I decided to go ahead and push for me to be allowed to keep working, consulting with the Director of the Shope Lab, and the safety experts at USAMRIID and the CDC.

We also involved my physician, who really advocates to prevent unneeded limitations of pregnant women. It took about 3 months for these negotiations, during which time, I did not go into the BSL4. With the help of my doctor we came up with a plan that would allow me to work in the BSL4, with limitations designed specifically to mitigate any difficulties that the pregnancy itself might cause. We drafted a contract and everyone signed it and it went into my UTMB file along with my OBGYN medical records.

Because sometimes unexpected things can happen during pregnancy, some limitations imposed included that I would not be allowed to go into the BSL4 alone. We also decided I would not stay in the lab for more than 3 hours at a time. This was to prevent me from getting both too tired, or dehydrated. Turns out this one really didn't need to be written down, my bladder was always screaming at me before the three hours were up and that meant exiting the lab. I also couldn't work with animals, which wasn't something I was doing anyway. When all was said and done, USAMRIID, the CDC, my Physician and UTMB were all on board and I went back in. After I paved the way, others have done it. You're welcome. ;)

Dr. Lander displays her Junin Romero plaque assay.

TS: How was it, logistically, working in there while pregnant? I know I always felt huge and clumsy while pregnant and I wasn't working with anything above BSL2 level and wearing a normal lab coat.

HL: Because the suits are cool, it was still pretty comfortable. It slowed me down for sure, especially the last couple of months. Moving with deliberation was already ingrained in me so that didn't change, but I definitely moved more slowly. And I was huge, and the suit was definitely cumbersome. My belly pushed against the suit near the end but it wasn't painful or even uncomfortable, I just had to give myself enough clearance when moving around tables and things. I also had to ask for help when doing normal everyday housekeeping kinds of things in the lab like emptying a trash bin or lifting autoclave pans. Everyone I worked with was very helpful and kind, so it was not a problem. I had the normal aches and tiredness, but if I ever felt too tired to go in, and there were a few times I did, I would cancel my time for that day and reschedule. I knew my limits and respected them.

TS: Any good stories?

Oh boy do I. Unfortunately I can't share the best ones. When I was still in the 100-hours-of-mentored-training segment of my BSL4 experience, I was in the lab with a professor and we were working with Rift Valley Fever inmice. We had finished the work and had already put the animals away and cleaned up. We were just getting ready to exit the animal room, to go into the main section of the lab, and the air hose connection valve on my suit broke. Without the air hose, there's no air, not to mention the suit had a hole in it. The professor realized what happened before I did and grabbed the air hose and shoved it against the broken valve, allowing air to get inside the suit. He and I took turns holding air hoses in place while we showered and exited. Because of the incident we had to fill out paperwork and I had to go to the university hospital's BSL4 exposure unit for a potential exposure. Because we hadn't been working with anything when the valve broke, I wasn't actually exposed to anything, but it was standard protocol. I was released fairly quickly and have a story to tell. The experience taught me a lot about how to handle those situations and even though those kinds of things are REALLY rare, the BSL4 director made changes to specifically prevent anything like that from ever happening again, and it hasn't happened since.

TS: What are you working on now and what are your longer-term career goals?

HL: I want to put my expertise to good use and I've come to realize that I love writing so I'm hoping to find something that can incorporate that. In the meantime, I have a really interesting job doing grant development for faculty at UTMB. This involves high-level assessment of the science, grantsmanship and presentation/writing of proposals, in an effort to help make faculty more competitive. To get my pathogen fix and dispel some emerging disease misconceptions, I recently started the blog and I'm really enjoying it. I also have ideas for a novel (don't we all?), so...who knows?

Many thanks to Heather for participating! Be sure to check her out at Pathogen Perspectives or Twitter.

tsmith Mon, 08/18/2014 - 07:28

Tags

hemorrhagic fever virus

Categories

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

tsmith — Thu, 24 Jul 2014 11:20:08 +0000

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.

Part of this post previously published here.

tsmith Thu, 07/24/2014 - 07:20

Tags

antibiotics

Antimicrobial Peptides

bacteria

evolution

The doubters about resistance clearly did not read Darwin very well. In particular the sections about artificial selection. For that is what drug resistance is. We modify the environment and effectively select for organisms that can live in the presence of the drug. Essentially it is just survival of the fittest in a modified environment.

Guest post: Will new FDA guidelines reduce threat from superbugs?

tsmith — Wed, 01 Jan 2014 10:00:24 +0000

Guest post: Will new FDA guidelines reduce threat from superbugs?

Guest post by Tim Fothergill, Ph.D.

In January of this year the British Chief Medical Officer urged her government to add threat posed by superbugs to the official list of "Apocalypses to Worry About" along with catastrophic terrorist attacks and massive flooding. With typical British understatement, its actual name is the National Risk Register of Civil Emergencies but a very stark picture was painted of a post-antibiotic world in which routine operations, such as hip replacements, could prove fatal. In September, The Centers for Disease Control in the US issued a similar statement which estimated that 23,000 people die every year in the US from antibiotic resistant infections. So what is it that has Dame Sally Davies and so many others so worried?

"Superbug" is a term used to describe bacteria which are resistant to many common antibiotics which are used to treat infection. Resistance to these drugs makes treatment more difficult and has increased mortality rates. As resistance to individual antibiotics becomes more prevalent the number of deaths is only set to increase, especially because there is a dearth of research into new antibiotics. Antibiotics are used medically in the short term, so don't offer the same kind of return on investment for the pharmaceutical companies as drugs for chronic diseases or long-term treatments, such as anti-depressants or hypertension medications. Even more worryingly of all is that strains of potentially deadly infectious bacteria, such tuberculosis have already been identified that are resistant to every potential drug.

Against this background the FDA's announcement of a plan to phase out the agricultural use of antibiotics is very welcome. Many animals raised for human production are fed antibiotics as a matter of course to boost growth rates. The animals are not suffering from infection, but the drugs can help them grow faster, resulting in a more efficient production of meat for the market. For most drugs, there is a mandatory withdrawal period during which the animals are fed no antibiotics so that they will clear out of the meat prior to slaughter. However, the antibiotics can impact the food supply and human health in other ways. Not only is there concern about meat contaminated with resistant bacteria but the standard agricultural practice of using animal waste as fertilizer only increases the risk of releasing resistant bacteria into the environment contributes to the spread of resistance. This is of particular concern if the land fertilized in this manner is subsequently used to grow food crops that are typically consumed raw. Previous recalls due to bacterial contamination have included spinach and cantaloupe melons. The potential for harm would only have been greater if these cases had involved superbugs, but this possibility is becoming more and more likely. Resistant bacteria that are spread onto crops via animal manure fertilizer have been demonstrated to not only persist in the soil but to also pass the genes for antibiotic resistance onto other species. As we have no control over this genetic transfer it is quite possible that they spread to even more pathogenic species.

The FDA's proposal to limit antibiotics in cattle feed would seem like good news then. However, the most significant caveat with this plan is that it is voluntary and as such is dependent on the cooperation of the drug producers and farmers. Two of the largest antibiotic producers, Zoetis and Elanco, have indicated that they will no longer labelling their products as suitable for growth promotion. Any subsequent use of these antibiotics for growth promotion would be "off-label" and something that the FDA can and does regulate. However, as with all regulation the devil will be in the details. We do not know yet what the change in labelling will actually say. If their new label can be interpreted in such a way that cattle are still regularly fed antibiotics then nothing will have been achieved.

For example, in Denmark they found that after introducing a ban on antibiotic use for growth promotion in cattle that the quantities of antibiotics actually increased. Animals no longer fed a sub-therapeutic level of antibiotic became more susceptible to infection and thus need therapeutic treatment more often. At first glance this might seem as if little has changed but antibiotics taken at therapeutic levels for the prescribed duration will result in fewer occurrences of resistance to the antibiotic in question. Anybody who has been told by their doctor to ensure that they take the full course for an infection will know this. By reserving antibiotic use for therapeutic use only, where it is needed in greater quantities to fight infections, not only will there be fewer superbugs released into the environment, but the drug companies will stand to increase their sales. This might explain their willingness to cooperate with these proposals. Their other option would be to switch production to antibiotics which are not regarded as being important for human health (such as the ionophores) as these are not covered by these new proposals. However, this is something that would presumably involve some cost to them.

It is also worth comparing the timescale for voluntary phase-out (three years) with the length of time it would take the FDA (presumably in collaboration with the USDA) to implement a strategy for an obligatory regulatory framework, which might have more teeth in terms of enforcement, but which is not yet on the table. The FDA has many admirable qualities but turning on a dime is not one of them. This process would take at least that long if not longer. What we do not know at this point is whether there are plans for the FDA to pursue such mandatory regulation if this voluntary arrangement is found not to be working. Such efforts would presumably require specific budgeting and it seems unlikely that this will happen any time soon given the current state of Congressional deliberations on budget matters. Another possible mandatory option would be Louise Slaughter's PAMTA bill which is currently with the Health Subcommittee.

If our goal is to reduce the spread of antibiotic resistant bacteria from agriculture then the FDA plan may in fact be the best option, and it is certainly better than doing nothing. Mandatory regulation seems unlikely at this point. However, accountability is still vital to the success of this voluntary agreement. What form could this accountability take? The FDA must be prepared to state publicly if insufficient progress is being made. Also, it is to be hoped that increased demand from major chains like Chipotle, McDonalds and KFC will help. If they were to make this demand then cattle production would change at a much faster pace than that proposed currently. This means that consumers are in a position to contribute by choosing to support suppliers of meat produced in a way consistent with these new guidelines.

********************

Tim Fothergill, Ph.D. is a microbiologist with over a decade of experience in researching the mechanisms for the spread of antibiotic resistance. This interest has led him to the intersection of antibiotic resistance in bacteria and policy, where his is now looking at the implications and consequences of legislation and regulation around antibiotic use. As a result, he has become concerned that the threat posed by overuse of antibiotics needs to be taken more seriously. But it's not all doom and gloom: his interest in instrumentation and general microbiology extends to brewing his own beer.

tsmith Wed, 01/01/2014 - 05:00

Tags

antibiotic resistance; agriculture; policy; antibiotics; superbugs

http://www.ahi.org/wp-content/uploads/2011/06/Screen-shot-2011-06-08-at…

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It didn't take three years to strengthen airport security after 9.11.

If there was an overt terrorist threat in the mix here, you can be sure the gov would crack down on agricultural antibiotics and start insisting on proper agricultural sanitation again.

Meanwhile I'm just about to finish a course of metronizadole for a nasty C.Diff infection; hopefully this will clear it, but the possibility that it may not is cause for serious worry.

"We're living in the times we warned you about years ago."

There certainly does seem to be something of a problem in terms of communicating just how serious this is. I suspect part of the problem is that there are very few people that still remember a time before antibiotics.

There are just so many issues that need to be addressed that I could write a huge number of blog posts. Perhaps I need to start up my own on just this subject.

It is not correct to state that antibiotic use overall went up in Denmark after the ban. The 2009 Danmap report does not include information on the amounts of antimicrobials used for growth promotion before the ban. Danmap does not include this information in any report after 2006. If you add in the amount of antibiotics used before the ban 105,000 kg in 1996 the last year reported before ban started in 1998 you find a significant drop even though there was an increase in therapeutic use. Also over half of the growth use was macrolides a critically important drug.

Hi Steve

You're absolutely correct that 2009 report does not include numbers for growth promotion consumption (you can find them all here: http://www.danmap.org/Downloads/Reports.aspx). It certainly doesn't make sense to keep recording something after you've banned it and ascertained it isn't happening any more. However, there are previous records of growth promotion use though. These are all very nicely summarised in this figure (as a caveat I should say this is from an article by the Animal Health Institute who's conclusions I do not support but I believe the numbers used in the figure to be accurately copied from the reports):

If you look at the numbers for the last year of growth promotion use (1999), the total amount of antibiotics has indeed gone up quite significantly. The same could be said for 1998. Compared to previous years the total has not gone up so I suppose it depends what you want to use as your starting point. I think it's accurate to say that since the ban the totals have increased.

Also, I do think the figure amply shows the increase in therapeutic use though since the ban. This trend in the increase of antibiotic use has been consistent since the ban and I'm sure is one of the primary considerations of the major drug companies in this country when agreeing to these new FDA guidelines.

Apologies if my referencing wasn't extensive enough and that I didn't fully explore in the text the origin of all of this data. My aim was to inform rather than debate the sources.

Very nice article Tim. One concern is the statement "At first glance this might seem as if little has changed but antibiotics taken at therapeutic levels for the prescribed duration will result in fewer occurrences of resistance to the antibiotic in question." Are we absolutely sure about this? I have struggled to find good literature that convincingly demonstrates that this is true, particularly for the "superbugs" in question that spread their genes via plasmid transfer. If you have any relevant papers to support this please share!!
Thanks
Tim

Hi Tim

Very good question indeed. When I wrote that I was thinking of the standard medical advice about finishing a course of antibiotics, eg:

http://www.mayoclinic.org/antibiotics/ART-20045720

I'm not at all sure of the mechanism for preventing the occurrence of resistance though. Perhaps the antibiotics knock the population down to a size that your own immune system can handle, so you need to keep taking them until you've done so. If your immune system destroys bacteria carrying such plasmids and the drugs take care of the rest then I could see it working. That does of course presume that the proportion of the population already carrying these resistance genes is relatively small at the point of taking the antibiotics. If the majority of a bacterial population causing an infection are already resistant then that can only lead to trouble, as we're seeing.

I'm now going to be spending some considerable time searching pubmed, etc. for the basis of that medical advice. Thanks ;)

Hi Tim,

Thanks for this informative balanced approach. And thanks everyone else for the insightful comments. We're just putting the final touches on a new film that by all accounts does 'communicate just how serious this problem is'. not only in veterinary and agricultural practice, but in human medicine as well. We filmed all over the US, in Denmark and Canada. We even filmed some with this blog's very own Tara Smith. You can see a teaser and find out more about the film at resistancethefilm.com It would be great to connect at some point about getting you involved in a screening at some point.

Student guest post: New Study Finds that the Flu has Multiple Ways of Spreading

tsmith — Fri, 21 Jun 2013 07:00:15 +0000

Student guest post: New Study Finds that the Flu has Multiple Ways of Spreading

Student guest post by Sean McCaul

Image Source: http://www.cejournal.net/?p=1934

The next time somebody in your office or household has the flu, you might want to consider keeping your distance. A new study published this month in Nature Communications suggests that about half of the transmission of influenza A results from inhalation of microscopic infectious droplets created by the coughing and sneezing of people infected with the flu. The flu virus hitches a ride in these droplets, and may infect nearby susceptible people who breathe them in.¹

The influenza A virus generally causes fever, coughing, body aches, runny nose, sore throat, headache, and fatigue. Vomiting and diarrhea may occur, but are more common in children.³ Fever and most other clinical signs usually resolve within 5 to 7 days, but coughing may last two weeks or more.² Children under 2 years old and the elderly are at greatest risk for complications such as pneumonia, and over 90% of influenza deaths are in people over age 65.²

Seasonal outbreaks of influenza are common in the United States, and typically occur during winter months. During and average outbreak, 5% to 20% of the people in a community may become ill with the flu, and up to half of the people in environments like schools and nursing homes may get sick.²

In adults with healthy immune systems, the flu virus is shed in highest numbers during the first 3 to 5 days of illness, making spread of the flu most likely during this time. Children may shed the virus for up to 10 days, and people with weakened immune systems may shed the virus even longer.² In a typical outbreak, a person sick with the flu passes the illness on to an average of 1 to 2 other people.^1,2

Previously, influenza A viruses were thought to be transmitted primarily by direct contact and by larger (but still very tiny) droplets generated by coughing, sneezing, and talking.^1,2,3 These droplets are capable of travelling 1 to 2 meters, where they may come to rest in the eyes, nose, or mouth of a susceptible person and cause them to become sick with the flu. These droplets may also fall upon nearby surfaces and objects, where the flu virus can survive for hours. A person touching these surfaces or objects may get the flu virus on their hands, and then transfer the virus to their eyes, nose or mouth and become ill.^1,2

The recent study, published on June 4, 2013, used a mathematical model of influenza virus transmission to evaluate the data from two previously published studies of the effectiveness of hand hygiene and facemasks for the reduction of transmission of influenza A viruses. It suggests that the flu virus may survive in very tiny droplets created by coughing and sneezing that can remain suspended in the air as an aerosol long enough to be inhaled by nearby susceptible people. The study shows that aerosols are an important route of transmission of the virus, and may account for as much as 50% of the spread of the flu.¹

Image Source: http://www.livescience.com/32307-why-do-bright-lights-make-me-sneeze.html

How you get the flu may determine, in part, how ill you get. Influenza researchers have long suspected that inhalation of aerosols containing the flu virus can lead to more severe illness than exposure to the flu virus by direct contact or by the settling of larger droplets in the eyes, mouth or nose of susceptible people. This is thought to be because larger droplets are trapped by the defense mechanisms of the upper respiratory tract, such as the large surface area of the nasal turbinates and the mucus lining the nose, pharynx, and trachea. Smaller droplets, meanwhile, are capable of being inhaled deep into the lungs, resulting in infection in the lower respiratory tract which can cause more severe disease. The current study found that there was an increased risk for fever plus cough in people suspected to have contracted the flu by inhalation of infective aerosols, which is consistent with current ideas regarding the importance of the route of infection.¹

Understanding the routes of transmission of influenza is also important for designing control measures to reduce the spread of this disease. Interventions such as increased hand hygiene and facemasks help to limit transmission of influenza by larger droplets produced by coughing and sneezing, but may offer little protection from inhaled aerosols.¹ Additional methods for controlling the spread of influenza through aerosols, such as improved ventilation of enclosed spaces, ultraviolet lights (which are capable of killing the flu virus), and minimizing exposure to those infected with the flu could reduce the risk of becoming sick.¹

So, what can you do avoid getting the flu? The most effective way is to get vaccinated before flu season. In the United States, flu season can start as early as October, though the peak months for flu are January and February, and sometimes even later.³ Because the flu strains circulating through the population change from year to year, you should be vaccinated each year. The vaccine is developed to prevent illness caused by the flu strains likely to cause outbreaks during the flu season, but may not prevent illness from novel or unanticipated strains causing outbreaks. Some people, such as babies less than 6 months old and those with allergies to eggs should not receive the flu vaccine.³ So the CDC recommends that you take additional preventive measures, such as good hand hygiene, avoid close contact with people who are sick with the flu, avoid touching your eyes, nose, and mouth, and practice good health habits such as remaining well hydrated, eating a healthy diet, exercising, and getting plenty of rest.⁵

If you do get the flu, what can you do to avoid infecting your family, friends, and colleagues? First, avoid close contact with others. Stay home from school or work if at all possible, and don’t run errands while you are sick. In this way, you can avoid exposing others to your illness. Second, cover your nose and mouth when you cough or sneeze. Experts recommend that you cough and sneeze into a cloth or into your elbow, so that you don’t contaminate your hands, which are commonly implicated in the spread of the flu. This simple practice can reduce the amount of infectious material you spread into your environment. Practice good hand hygiene, particularly before touching doorknobs and other items that may leave the virus where others are likely to become exposed.⁵

References

Cowling, B.J., Dennis, K.M., Fang, V.J., Suntarattiwong, P., Olsen, S.J., Levy, J., Uyeki, T.M., Leung, G.M., Malik Peiris, J.S., Chotpitayasunondh, T., Nishiura, H., & Simmerman, J.M. (2013). Aerosol Transmission is an Important Mode of Influenza A Virus Spread. Nature Communications, DOI: 10.1038/ncomms2922 LINK
Bridges, C.B., Fry, A., Fukuda, Shindo, N., & Stohr, K. (2010). Influenza (Seasonal). In Heymann, D.L. (Ed.). Control of Communicable Diseases Manual. American Public Health Association, Unbound™ Mobile Platform
Centers for Disease Control (February 13, 2013), Key Facts About Influenza (Flu) and Flu Vaccine, accessed at http://www.cdc.gov/flu/keyfacts.htm , June 8, 2013
Centers for Disease Control (May 6, 2013), What You Should Know for the 2013-2014 Flu Season, accessed at http://www.cdc.gov/flu/about/season/flu-season-2013-2014.htm, June 8, 2013
Centers for Disease Control (January 11, 2013) Preventing the Flu: Good Health Habits Can Help Stop Germs, accessed at http://www.cdc.gov/flu/protect/habits.htm, June 8, 2013
Flu Virus Image: Tom Yulsman (May 26, 2009), U.S. and Other Countries Fail to Adequately Monitor Pigs for Flu, accessed at http://www.cejournal.net/?p=1934, June 8, 2013
Sneeze Image: Ben Mauk, photo credit Andrew Davidhazy/RIT (November 28, 2012), Why Do Bright Lights Make Me Sneeze?, accessed at http://www.livescience.com/32307-why-do-bright-lights-make-me-sneeze.html, June 8, 2013

tsmith Fri, 06/21/2013 - 03:00

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Eastern Equine Encephalitis: The Mosquito that bit the Snake

tsmith — Wed, 17 Oct 2012 12:15:29 +0000

Eastern Equine Encephalitis: The Mosquito that bit the Snake

Guest post by Hillary Craddock

Last week a new study regarding Eastern Equine Encephalitis (EEE) was published online (Bingham et.al.). EEE is a mosquito-borne virus that can cause serious, and sometimes deadly, disease in humans and equines. In warmer parts of North America, the virus is spread year-round, but in areas where mosquitoes get killed off in the winter it has been something of a mystery as to how the virus makes it from year to year. Humans and equines are both dead-end hosts, which means that a mosquito can not be infected from biting an infected person or horse. Researchers in Alabama found that wild snakes in the Tuskegee National Forest were positive for Eastern Equine Encephalitis virus (EEEV), which could explain how EEE was maintained after the first frosts killed off infected mosquitoes. Essentially, what would happen is that an infected mosquito bites a snake, probably during the summer or early fall, and the snake harbors the virus in its blood during the winter. Then, in the spring, an uninfected mosquito (which overwinters as a larva) bites the snake and acquires the virus. This now-infected mosquito can bite a horse or a human, who can then get sick. (I’m sensing a Chad Gadya theme here. Just me? Ok…)

Amphibians and/or reptiles as the winter reservoir of EEE is not a recent research question. A book, Reptiles as possible reservoir hosts for eastern encephalitis virus, (which I was unfortunately unable to get my hands on, since apparently only the University of Alberta has an available copy) was published in 1961, and another study in 1980 by Smith and Anderson stated that two New England species of turtles could be infected by the virus. Interestingly enough, a 2012 study by Graham et. al. (same research group as Bingham et.al.) found that, out of 27 species surveyed, only snakes showed high seropositivity (positive for virus antibodies in the blood), while amphibians, turtles, and lizards had low to no seropositivity. A 2004 study by Cupp et.al., also in Alabama, found that mosquitoes carrying EEEV had fed on amphibians and reptiles in addition to birds and mammals. Now, it’s all well and good to show that a reptile can act as a host, but just because something can be the host doesn’t mean that it is the host in the actual system. The crucial step was testing their hypothesis in a wild population.

And test they did. The researchers were careful to state that the question of snakes acting as reservoir hosts is “unresolved,” but there is “mounting evidence” that snakes are the winter hosts of the virus. Cottonmouths (Agkistrodon piscivorus) were the most common snake sampled, making up 41% of sampled reptiles. They were also frequently seropositive, with 35.4% testing positive for EEEV. Of the five species sampled, one other, the copperhead (Agkistrodon contortrix) was found to be positive. The researchers tested for active infection in addition to antibodies, and found that some snakes were actively infected. This means that, if a mosquito bit the snake, the mosquito could possibly acquire the virus and pass it on to other creatures.

So why am I so excited? When I took my first Emerging Infectious Diseases class in college, the professor explained to us that zoonotic infectious diseases were most likely to jump between closely related species. Granted, I’m using the word “close” loosely here. She meant that diseases were far more likely to jump mammal to mammal or bird to mammal than, say, fish to mammal or reptile to mammal. I was also taught that if you can understand how a disease is transmitted, you’re one step closer to controlling it.

Which answers the ultimate question – so what does this all mean? When we better understand how a disease is transmitted, it’s easier to control it. Further research in other parts of the country is needed to see if snakes are harboring the virus in the North East and Midwest regions, but the implications for disease control are there. If we understand where or when snakes congregate, we might be able to better predict disease dynamics, specifically outbreaks. If the first outbreaks in the summer originate from mosquitoes biting snakes, then it’s possible that scientists could conduct heavier surveillance in areas where snakes are known to congregate. In this case, we have two entire categories of experts – herpetologists (reptile specialists) and wildlife scientists – that public health practitioners can work with to try to control the disease. This paper is amazing because it unlocks a whole new cavalcade of questions and potential solutions.

______________________________________________________________________________________

This post was republished with permission by the author, and was originally published at Mind the Science Gap.

Hillary is a second year master's student in Epidemiology at the University of Michigan, and she is currently working in influenza research. Her primary interests include zoonotic, emerging, and vector-borne infectious diseases, disaster preparedness and response, and public health practice.

tsmith Wed, 10/17/2012 - 08:15

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ecology

General Epidemiology

Interesting post, Hillary. We have had an outbreak of equine West Nile in Iowa, with 21 cases reported by the USDA as of October 2, and by September, I am aware of at least two horses that had to be put down in eastern Iowa. I am unclear if Equine West Nile and EEE are carried by different mosquitos - the CDC has conflicting information - and I am very surprised to learn that any mosquitos bite reptiles. The thickness of reptile skutes/scales would seem to protect them. In considering prevention and further investigation, an appropriate train of thought would be to consider the typical equine environment along with snake environments .... snakes (in Iowa, the most likely is probably the black rat snake [elaph obsoleta obsoleta]). LIke horses, they live in barns, where they feed on rats and other rodents. One problem to consider in the Midwest is that many people have horses that live in pastures (of varying conditions, from muddy to grassy to dry) and I am constantly surprised at few of these horses are used much for work or pleasure. In well-kept stables where people keep dressage or hunter/jumper horses (or even western pleasure horses), the horses are well-cared for and well trained. The loose horses that seem to roam around many farms along the back roads are unlikely to be trained and, in my opinion, pose an injury risk to people, especially children. Untrained horses are big, dangerous animals. Those same horses are likely to live in the same environment as grass and other snakes, although (fortunately) Iowa is not home to cottonmouth snakes. Thinking about these linked environments, including the existence of standing water in puddles or ponds, may help us control the spread of EEE.

Scarlet fever--past and present

tsmith — Wed, 06 Jul 2011 07:00:00 +0000

Scarlet fever--past and present

While "flesh-eating infections" caused by the group A streptococcus (Streptococcus pyogenes) may grab more headlines today, one hundred and fifty years ago, the best known and most dreaded form of streptococcal infection was scarlet fever. Simply hearing the name of this disease, and knowing that it was present in the community, was enough to strike fear into the hearts of those living in Victorian-era United States and Europe. This disease, even when not deadly, caused large amounts of suffering to those infected. In the worst cases, all of a family's children were killed in a matter of a week or two. Indeed, up until early in the 20th century, scarlet fever was a common condition among children. The disease was so common that it was a central part of the popular children's tale, The Velveteen Rabbit, written by Margery Williams in 1922.

Luckily, scarlet fever is much more uncommon today in developed countries than it was when Williams' story was written, despite the fact that we still lack a vaccine for S. pyogenes. Is it gone for good, or is the current outbreak in Hong Kong and mainland China a harbinger of things to come? More below...

First, what are the symptoms of scarlet fever? Most often, this manifestation occurs during or following strep pharyngitis ("strep throat"). Rarely, scarlet fever occurs after the skin infection, impetigo. Children with scarlet fever develop chills, body aches, loss of appetite, nausea, and vomiting; these are symptoms may occur at the same time as or shortly following the onset of pharyngitis. When the rash emerges, it typically seems like an itchy sunburn with tiny bumps. After first becoming visible on the neck and face, it spreads to the chest and back, later spreading to the arms and the remainder of the body. Though initially consisting of separate bumps, these bumps tend to merge together, giving the entire torso a red appearance. Generally, the rash beings to fade by about the sixth day; and similarly to sunburn, the skin may peel afterwards. The tongue, typically very red and bumpy ("strawberry tongue") may also peel.

Scarlet fever is nothing new to humanity, though the earliest case definition of scarlet fever is a matter of contention. Some researchers attest that descriptions of disease which match scarlet fever date back almost 2,500 years, to Hippocrates. Others believe the first conclusive diagnosis is found in the tenth century writings of Rhazes, who also worked to distinguish measles and smallpox as separate diseases. It is generally agreed upon that the first sufficiently detailed paper identifying scarlet fever as a disease distinct from other rashes appears in 1553. In that paper, the Italian physician Giovanni Ingrassia describes the disease and refers to it as "rossalia." The term "febris scarlatina" appears in a 1676 publication by the British physician, Thomas Sydenham.

Historical data suggest at least three epidemiologic phases for scarlet fever. In the first, which appears to have begun in ancient times and lasted until the late eighteenth century, scarlet fever was either endemic (always present at a low level) or occurred in relatively benign outbreaks separated by long intervals. In the second phase (~1825-1885), scarlet fever suddenly began to recur in cyclic and often highly fatal urban epidemics. In the third phase (~1885 to the present), scarlet fever began to manifest as a milder disease in developed countries, with fatalities becoming quite rare by the middle of the 20th century. In both England and the United States, mortality from scarlet fever decreased beginning in the mid-1880s. By the middle of the twentieth century, the mortality rate from scarlet fever again fell to around 1%.

Fig. 1. Boston 1840-1940. Severe streptococcal infections in historical perspective. Depicted in the insert are the recorded deaths in the United States from 1900 to 1960. From Krause RM, citation below.

During Sydenham's life (1624-1689) and for more than a century afterwards, scarlet fever was considered by both parents and physicians to be a relatively mild childhood disease. Although several European cities experienced fatal epidemics of the disease, these epidemics were often short-lived, and it does not appear they were widespread.

In the early nineteenth century, the clinical presentation of the disease appears to have changed for the worse. Lethal epidemics were seen in Tours, France, in 1824; in Dublin, Ireland, in 1831; and in Augusta, Georgia, during 1832-33. Similarly, in Great Britain, the fatality rate from scarlet fever increased from between 1 and 2 % to more than 15% in 1834.

From 1840 until 1883, scarlet fever became one of the most common infectious childhood disease to cause death in most of the major metropolitan centers of Europe and the United States, with case fatality rates that reached or exceeded 30% in some areas--eclipsing even measles, diptheria, and pertussis.

Scarlet fever pandemics of this and other eras also had a profound effect on history, in addition to providing a plot device for a beloved children's story. Charles Darwin lost two of his children to scarlet fever. The first, his beloved daughter Annie, died at the age of 10 in 1851 (two sisters, also infected, recovered from this bout). In July 1858, Darwin also lost his 18-month-old son, Charles Waring, to scarlet fever. It is believed that a bout of scarlet fever at the age of 19 months caused Helen Keller to lose her senses of vision and hearing. Scarlet fever also led to the founding of The Rockefeller University by the world's first billionaire and the founder of Standard Oil, John D. Rockefeller, whose 3-year-old grandson died of scarlet fever. Rockefeller remains a leader in biomedical research today, including research investigating various aspects of the biology of the group A streptococcus.

Why did scarlet fever, once a scourge of childhood, end up as a relatively rare infection in developed countries? While some of this can be attributed to antibiotics (particularly from the 1950s on), both the incidence of scarlet fever and mortality from the illness started to decline well before the antibiotic era (seen on the graph above)--a phenomenon that may be attributable to the emergence of novel strains of S. pyogenes in the population which were less likely to cause scarlet fever, but more likely to spread in the population. (A similar strain replacement may have occurred in the late 1970s/early 1980s, leading to the increase in the aforementioned "flesh eating" strains of strep). Other biological factors such as herd immunity to epidemic strains, as well as social factors including decreased crowding, improved hygiene, and even milk pasteurization (milk was responsible for several large group A strep outbreaks) also probably contributed to this decrease.

Scarlet fever still remains a threat today, particularly in developing countries, but nowhere today is it as severe a disease as it was during that frightening time in the middle of the nineteenth century. However, the current outbreak in China shows how quickly this situation can change, as they've seen a quadrupling in the number of cases in 2011 compared to previous years and several fatalities. News stories have suggested this is some kind of "mutant" strain and has increased resistance to antibiotics, though I haven't seen much elaboration on either of those claims. (This story touts "the new strain has about 60 percent resistance to antibiotics used to treat it, compared with 10 percent to 30 percent in previous strains," which doesn't make much sense as written--maybe resistance to 60% of the antibiotics tested...?) Though still of relatively low mortality compared to Victorian era, the resurgence of this disease, and the potential for the emergence of a new strain shows how quickly this disease can make a comeback. Additionally, at least one article notes a simultaneous outbreak of chickenpox--and strep plus varicella zoster (the chickenpox virus) are a can be a nasty combination.

I also wonder if the current outbreak is really caused by a new strain as suggested, or by one that has been percolating throughout Asia for awhile and only recently hit the big time. I guess time--and hopefully sequencing data--will tell.

Further reading:

Katz SL, Morens DM. Severe streptococcal infections in historical perspective. Clin Infect
Dis 1992;14:298-307. Link.

Krause RM. Evolving microbes and re-emerging streptococcal disease. Clin Lab Med. 2002 Dec;22(4):835-48. Link.

tsmith Wed, 07/06/2011 - 03:00

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General Epidemiology

Streptococcus pyogenes

public health

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Medicine

HiÃ§bir Åey, Tayfun dÃ¼ÅÃ¼nÃ¼n. Bir fincan kahve ister misiniz?

My 20-something sister had scarlet fever right here in the US of A just last year. Her doctor was completely bowled over -- hadn't seen a case in ages. Lab confirmed, though. I think that was the first time I actually knew someone who had it in my lifetime.

Scarlet fever is uncommon in the US? Wow. My 2-year-old son has had it three times! I just figured everybody got it at some point. Then again, my fully immunized son also managed to catch a mild case of chicken pox recently.

Either my son's doctor has lousy diagnostic skills (although the positive strep tests back him up) or my son has a real talent. Lemme see, so far: croup from RSV, croup from parainfluenza x3, scarlet fever x3, chicken pox, various colds, molluscum contagiosum, coxsackie virus...

@Mara, I can't speak about most of those conditions, but I personally had chicken pox twice. A very good case both times. My doctor said that in about 10% of the population, the immune system effectively "doesn't remember" the first time, regardless of how bad you have it. The second time, I was 17 and they nearly hospitalized me (the doc wanted to, but my mom wouldn't let them, so the doc gave her explicit instructions to follow in giving me liquids, etc...I still hate ginger ale to this day). It was pretty horrible, had them in my mouth, hair, and eyelids. When I got older and had my daughter, I had her vaccinated for chicken pox at the correct age, and she still developed it a couple of years later (which frankly didn't surprise me a bit). The vaccine doesn't give a 100% guarantee of never catching it for one thing, and I'm of the opinion (not medically certified, just my opinion) that my daughter inherited my tendency for the immune system to "forget" it. My sister's son did the same thing.

Yeah, it's rare but can happen, and some kids tend to be more susceptible to various manifestations of strep infections than others. My daughter gets strep throat roughly twice/year like clockwork, and my son's never had it, despite being exposed and occasionally sharing drinks, utensils, etc. before we knew she was sick. No scarlet fever to date, though.

I'm in my mid 20s, and I had scarlet fever when I was 3 years old. I have vague memories of a really high fever, and being really uncomfortable. I'm the only one I've ever met to have had it. It impresses the heck out of people when I tell them.

We have friends whose son had scarlet fever back when I was pregnant with my older child. I had no idea what it was and got it confused with rubella, so I ran around like a chicken with its head cut off, convinced I'd been exposed to something that would kill my baby.

(Mind you, I'd had my immunity to rubella confirmed before I even got pregnant. But I'd be the last person to claim that pregnant women were rational.)

Now that I think about it, though, that's the only other case I can think of! My son is so talented :)

My dad had scarlet fever as a child ca. 1920, if I remember it correctly. He acquired a heart murmur as a result of some childhood illness, in any event, and it made him 4F during World War II. (He was also my grandma's sole means of support, so he probably would not have seen combat, anyway.) On the downside, it weakened one of his heart valves, which many years later had to be replaced with a porcine valve when his blood pressure got too high and damaged the valve further.

However, I could be confusing scarlet fever with rheumatic fever.

I got scarlet fever in about 1990. I was well enough in the morning to send into school, and after lunch I collapsed from a high fever. The next thing I remember was nearly a week later. Apparently, my grandmother, born in about 1918, had kittens when she saw me (she beat the doctor to the diagnosis); the teacher tried to treat it as an ordinary fainting fit (she'd never seen scarlet fever nor realised fevers could get high enough for loss of consciousness); my unfortunate mother had to deal with a procession of army medical personnel trooping up to my room to see the clinical case of something they'd only read about. Luckily I didn't spread it to anyone, and they didn't know where I'd managed to pick it up.

However, I could be confusing scarlet fever with rheumatic fever.

It's quite possible the latter came as a result of the former--rheumatic fever/rheumatic heart disease are sequelae of strep infections, so the scarlet fever could have led to RF/RHD. That was fairly common in the pre-antibiotic era.

Thanks, Tara.

@stripey_cat: my daughter, who's now 25, was sick with what we thought was a bad cold when she was around 4. Her fever suddenly spiked to 104, she passed out and started convulsing. Scared us shitless. After a trip to the ER and some meds, she was fine and recovered in a few days.

Maybe this kind of thing can run in families?

My son got scarlet fever at age two. He must have had the more benign "modern" type, since he never acted particularly sick, just turned some interesting colors and peeled like a post-it a week later. Of course taking the kid to the pediatrician as soon as he started resembling a boiled lobster may have had something to do with it!

I myself, had scarlet fever at age 5 in 1970 with a temp of 105. I don't remember any of it except what was told to me by my parents. During my teens, I suffered with mono and recently was diagnosed with EBV. I am now 45 and have been suffering with neurological problems and a heart murmer. Could Scarlet Fever cause this after 40+ years??

It is quite scary to think that scarlet fever can still strike at will. This is especially true in the case of developing countries as correctly stated as they do not have the mechanism to prevent it completely. The increases resistance to antibiotics is something to be worried about.

AraÅtÄ±rmalarÄ±nÄ±zÄ± takip ediyorum hizmetleriniz iÃ§in teÅekkÃ¼rler.

My brother had scarlet fever twice in the 1970s - I remember quite distinctly because we both had to have the nasty penicillin syrup for 10 days each time. I didn't have it until the early 80s, when I was a teenager: came home from a babysitting job and my fever went up around 103-104 F as soon as I got home. It stayed there for several days until my parents finally took me to the doctor for a diagnosis and some penicillin (pill form, fortunately).

Neither my brother nor I had long term consequences from this, but I certainly heard horror stories once I got back to high school about aunts and uncles who died or lost all their hair to scarlet fever.

Scarlet Fever makes one thank God for scientists and modern medicine. My son had the disease about 5 years ago, and I've never seen him so miserable. The doctor was unalarmed but fascinated, and called in every doctor and nurse in the clinic to observe an actual case and feel the sandpaper rash. Which, once I realized the disease wouldn't kill him, I was happy to allow. What floored me more was that all it took was a short course of antibiotics to knock it out.

I am profoundly grateful to all the scientists who turned this deadly and scarring disease into just another inconvenient childhood malady.

I am 50 years old and had Strep Throat which progressed into Scarlet Fever when I was 2, with my temperature reaching as high as 107.4 degrees. I was initially misdiagnosed, though my mother cannot recall what the wrong diagnoses were. I now have RA and Arrythmia and wonder if these might be related to having the disease as a child. I have heard they could be. I would love to hear from anyone with knowledge, especially medical knowledge about this. Thanks!

10 years ago, I had Strep that went undiagnosed even though I visited the Doctor. He lost my culture results. As a result Strep turned into Scarlet Fever and a week in the hospital. They told me to monitor for heart problems. . Just recently I have noticed waking up with a very high heartbeat multiple times each night. I initially thought this was my thyroid gone a little crazy. But now I realize this occurs primarily when I lay a certain way on my left side. Upon researching Scarlet Fever and heart valves, I realize I should get this checked out quickly. Thanks for scaring me into it!

I had Scarlet Fever in 1966...am now 50 yrs. old. I have never had a fever since then. Even with getting the normal flu and a few bouts of Strep throat over the years, my body just never fevers. My best friends mom is 80, and she's the only person I know who has said her body doesn't fever either. She too had Scarlet Fever as a child. Doctors look at me like I'm a nut when I tell them this. Has anyone experienced or heard of this?

@ Lisa..I had scarlet fever as a child with strep throat. I was about 6. I'm now 36 and have never had a fever since even with cold and flu symptoms.

I had Scarlet Fever when I was 5 in 1959. I remember being taken to hospital and seemed to be there for weeks but arnt sure how long exactly. It was over Christmas and my mum came to see me on Christmas day but wasnt allowed in my room. She had to look at me playing with my presents through the glass door. I had injections in my bottom every day and my skin peeled off on my hands. I have four brothers and it was expected that they would get it too but they didnt.

I am 64 and remember when I developed Scarlet Fever back in the 50's,. I was 4 or 5 and recall being sent to an isolation hospital. It must have about Christmas time, the nurses toured the wards with candles, singing carols round the christmas tree. Like Jean I remember seeing my parents through the window only. I also remember my fav toy, my hollowing, had to be sterilised and was returned to me, an awful grey colour, when he had been boiled I guess. That upset me more than anything else!

My fav toy was golliwog, sorry for mistake.

I have a mitral valve heart defect after surviving scarlet fever in 1958. I missed a month of school. It caused me to be a sickly child for years. I couldn't run or get upset or my heart would get out of rhythm. At age 51, I had a stroke from a blood clot in my brain that migrated from my heart. It took several years to be able to stand up on my own. I have permanent memory problems and I can't drive anymore. We should be very concerned that this blight on childhood ever takes a foothold again.

My daughter was just diagnosed today with scarlet fever. She was cold and tired 1st day, headache 2nd day , rash 3rd day. No other symptoms. Dr said 2nd case in her practice this week. She's seen it about 2 yrs ago. I was very surprised but she's ok thank goodness

If you have had scarlet fever as a child.. what can you expect as an adult? I am 27 years old, and had scarlet fever at 11 or 12. I don't remember much, however remember being carried to a few different doctor offices to get other opinions. My ankles were very swollen and I was very week. After taking a skin biopsy they confirmed that it was Scarlet Fever. Since then, I've only ever gotten sick (serious sick) a couple of times. I never catch a cold and I'm not an extremely healthy person. I did used to get horrible migraines a year or so after Scarlet Fever. And caffeine makes my heart race. I may sound naive, but could this be at all linked to Scarlet Fever?

My 18 year old daughter suffers from chronic strep throat, all last week high fever sore throat, by friday she was "feeling better" Saturday she came upstairs looking like a boiled lobster. Ran to the clinic yup SCARLET FEVER, which I happened to find hilarious, as I recognized it immediatly.. I had it when I was 20, my younger sister had it at 16... it is actually an allergic reaction to the poisinous toxins that Strep A passes through the body and only certain people are allergic... which is why not everyone who gets strep throat gets scarlet fever.

My four year old son was diagnosed with scarlett fever and strep throat yesterday. He had a fever with vomitting and diahhrea for three days. We thought he seemed to be doing better and the fourth day he woke up with almost all of his face except below the mouth and his upper chest and the back of his neck was pinkish red and part of his face slightly swollen. I took him straight to the dr where they tested and confirmed strep and scarlett fever. Hes been on amoxicillin since yesterday morning and he hasnt vommited once, his fever is slight

The doctor said theyd not seen a strep case get that bad.The day before he got sick he was fine, running around and playing with his cousins.

My daughter, who just turned one, got diagnosed with strep throat and scarlet fever today. I really thought scarlet fever was a thing of the past! How wrong was I! She does have a slight rash but nothing as bad as what it sounds like it could be. Yet......

I had Scarlet Fever at the age of 6 which turned out real bad and had to be rushed to hospital for weeks. My Mother asked the Doctor if I could get Heart problems later on in life and he replied no. This does worry me as most of you have pointed this out.. I am only 25 but do feel all stressed out sometimes and notice my heart does have a kind of dull ache at times but I hope this is nothing :/

My son is almost five and he had Scarlet Fever twice in the last year. He has had strep throat before but the Scarlet Fever only developed on his last 2 times. He did not complain about any symptoms but that red rash freaked me out the first time.

Just yesterday, my almost 4 year old daughter got Scarlet Fever for the first time (2 weeks after my son had finished his round of antibiotics). It may run in the family.

Although this might be a modern version of the Middle Ages Scarlet Fever because the children are definitively not suffering (thank God). And I do not think Scarlet Fever is so uncommon.

I'm 13 years of age and I have scarlet fever... It took the doctors about two months to figure out what was wrong. They had diagnosed me with so many different things before my mother demanded a blood test and it showed that it's in my blood stream... Out really sucks and is not something you want to get. The meds I have to take are super strong but might not work so I'm a bit on the scared side

I am 28 years of age and have had Scarlett fever when i was about 7 or 8? I don't remember a whole lot except for laying on my grand fathers couch with a high fever and pinkish red cheeks. Thank fully we have the technology today to help with this kind of stuff.

My two year old son has this right now it has caused a side effect not listed on any site. The roof of his mouth is bloody. Its a very scary diease i have only heard of in talks with my history teacher an my great grandma. Its something everyone told me was nothing more than a simple heat rash an sore throat. I trusted my gut an took him to the hospital good thing to because it could cause him to have kidney liver heart and breathing problems if left untreated. Hope the antibiotics do the trick. If not i was told he will be kept in the hospital in a completly setrial room untill they can figure out what to do.

My 7 year old daughter was diagnosed with Scarlet fever yesterday. Her temp got up to 104. She only threw up one time. Her rash has been really itchy. This really surprised me because i didnt think anyone got it anymore. My 2 older kids never had it, i just hope there arent any long term effects.

I had scarlet fever at about 6, and I remember being itchy... VERY ITCHY... With red bumps everywhere. It was very scary. But my brother, with his high immunity to infections, didn't catch it. He also evaded catching strep throat when I would get it every year like clockwork in January-February. I've been getting panic attacks lately and am wondering if the two might be related? Thanks.

my 11month son was diagnosed with scarlet fever/strep he has had it for about 4 days now he is feeling much better but it is a scary site seeing your lil boy spred it looks like he sat in straight sunlight for days he started with just a small fever then 30 min later a rash started the another 30 mins after that he was just as red as can be i took his temp it was 102.8 hurried and rushed him to the docs and by time we got there it was a 105.3 thise was all in a 20 min time spand is how high his fever got and was riseing the did test and when it came back they where stuned how his blood count was and they transported him to a childrens hospital it took untill the next day for the complete results to come back but iam glad and i think god i cought it in time

I had scarlet fever when I was five. I am 52 now. The only thing I remember is waking up feeling horrible and my parents taking me home and how happy I was to be going home. For the life of me, I cannot remember where I was apparently quarantined but I must have been because I distinctly remember the ride home. Now I suffer from psoriatic arthritis. I wonder if there is any link between the two.

My 12 year old son went to school Monday morning feeling fine. School nurse called at 10:30 with him in her office with sore throat but mild low fever. She gave him Tylenol and some mints. Within a few hours he was back again but fever was a little higher ...99.7. Came to get him and went to doctor. Confirmed it was strep throat and given amoxicillin. Tuesday afternoon he said that he had bites all over him, but when I looked I could tell it was a rash. I thought it was an allergy to the medicine. Took him back to doc and she said its no allergy.....it's scarlett fever. I nearly fainted! She calmed me down and told me that it's not like it used to be and that it's treated with normal antibiotics which he was already on. She said he should be better by Friday. I see a marked improvement today, in that he's not nauseous or running a high fever. It got up to over 103 Tuesday night. He was miserable. Labored breathing, high fever and nauseated. Plus, he complained about the top of his head being extremely sore. Aches and chills, night sweats too. The rash is still spreading today, but everything else is much better.

My daughter had Scarlet Fever when she was 9. She is now 59 and her hands started peeling recently, just like when she was ill at age 9. I have been searching for a reason for this peeling but cannot fine anything.

I had scarlet fever for several weeks when I was 14. My parents thought it was just the flu or something. We went on vacation instead of cancelling because I said I'd be fine and didn't want to ruin their trip. I wish I had. I have never been so miserable. I couldn't eat and my throat was so swollen I could barely swallow tylenol. We didn't know what it was but I got a red rash and my throat kept getting worse my grandmother kept saying it reminded her of when her uncle had scarlet fever but no one got that anymore so that couldn't be it. I went to the doctor when we got home even though I was feing better pretty much but sure enough that's what it was. They said I was lucky to have lived because it was really severe and my throat is still damaged from it. I never had any antibiotics for it though. My immune system hasn't been nearly as stable since then. I get sick at least once a month now.

My son had scarlet fever maybe 6 years ago; he was 5. Since then, he has complained of chest pains and shortness of breath with exertion. I'm kinda freaking out now. I'm certain the symptoms are related. Oh and my son showed no symptoms days before he got the rash. The morning of the "boiled lobster" rash he did complain of a sore throat and I made him an appointment at his Dr office. By the early afternoon he had developed the full red rash. Can't recall if he had a high fever, don't think so. But he always reacts runny when seriously ill.

My son has scarlet fever and strep throat which obviously the scarlet fever is due from the strep. It is only the 2nd day and his skin is so bad and they say that last for 6 or so days. My son has a weak immune system. He had the mouth foot and hand disease and it was horrible. He still has scars, which the doctor tells me can't be, but they been there since then in the same spit it was very bad. He just got over the flu last week and now this.
I or my family has never experienced a case of scarlet fever but then again my baby does this to us a lot of the time. I guess he wants to make sure we stay on our game.

My little boy has scarlet fever now it's so sad fever rash sore throat. I didn't even know scarlet fever even existed anymore

My poor younger brother got it when he was 15 (2012). My mother knew what it was and asked the pediatrician to do a strep test. Dr refused and sent my brother home. Over the course of the next two weeks she took him in 3 separate times and each time the Dr. told her he'd be fine, no strep test needed, obviously not scarlet fever. Then over the weekend he suddenly got a lot worse. My brother's temperature shot up to 106.7 degrees, he was unable to eat or drink or even sit up. My parents basically went "F-- the doctor" and took him to the local ER. They immediately took him back , hooked him up to a drip for dehydration, took a strep test, confirmed scarlet fever, got him his antibiotics, and sent him home. Not including the time he spent hooked up to the drip and other basic care, it took 15 minutes. One of the nurses at the ER told my mom that if he hadn't got to ER when he did he'd have been dead within a few days.

I had scarlet fever as a child and I still as an adult have bad immune system and every time I get sick I get the fever bumps and I'm wondering if that's normal to keep getting those rashes

I had scarlet fever when was two in Scotland. Back then (1950) they shaved my head, burned my toys and sent me to hospital where I was in isolation for more than a month.
This past year I had my aortic valve replaced (my second open heart surgery).

My son has this and I took him to Bolton hospital were they sat him in a room full of old people even though the rash was all over his body and they had to google symptoms and still didnt know it was Scarlett fever they gave him cream and said if it didnt go to come back the staff there just ain't qualified enough in my thoughts and to put old people at risk is diabolical

My daughter got scarlet fever around age 4 from a misdiagnosis of strep throat. She is now 16 and gets it anytime she comes down with a fever. A few years ago we went to a dermatologist because her hands and feet peel every few days. You can actually see the beads of sweat on the tips of her fingers. She has no fingerprints and never will as her skin peels off every few days. She is very athletic and hardly ever gets sick but when she does, it comes back. The dermatologist says this is something that will never go away. But this seems to be the only continually symptom that she has from it. Hope that helps someone.

I had scarlet fever when I was about seven.Every time I get sick I get a rash. .I am 58. For years I thought I was allergic to penicillin, but any illness such as bronchitis gall bladder removal etc I get rash all over my body. like scarlet fever think it might be related.

I had Scarlet Fever and Rheumatic Fever as a child not sure what year but I was young and I was born in 1963. I have recently been diagnosed with Sjogrens Syndrome and was wondering if this has something to do with these diseases as this should run in the family but seems to have started with me.

In the early 1960's I had Scarlet Fever, I'm sorry I do not remember the year. What I do remember is being very sick. My Mother put suppositories in my rectum for the high fever. She gave me 7-up to drink because of dehydration. My Mother slept with me because she was so concerned. In the middle of the night I started screaming that I wanted my Mom ( I remember that). The next day she called the Dr and he said my fever broke. I have read some of the remarks and some of them remind me of my expierances. How will Scarlet Fever effect me now that I'm older?

I had scarlet fever twice once in 2003 and again in 2005. i don't remember much except that the second time I was always really hot and puked everywhere. (I was 3 years old, not much to be said.)

My records are micro fished at Lincoln Memorial Hospital in Lincoln Ne, according to what my mother told me was when i was three that would be in 1945 i was taken to the doctor because i had blood blisters on both legs. the doctor looked up at my mom and said i had 48 hours to live. She said, the doctor that is, that i had scarlet fever that had gone into my blood and the veins were bursting in my legs. they put me in the hospital put cast on both of my legs and gave me blood transfusion because the blisters were breaking and blood was pouring through the skin of my legs. i am rh negative and they had given me what they called the universal blood. when they took the cast off of my legs they saw that from lack of oxygen i had developed gage green, there were two doctors on my case. one was a female and another was a doctor from the southern states that heard about my case according to my mom he got off the train to stay with my case. my mom was told that there was only one woman in the south that had the same complications from scarlet fever but they had to abutat both of her legs to the hips. the doctors would debate one wanted me to die with my legs on the other wanted me to live with my legs off. well still have my legs. i have the scars to this day where they scraped the infection from both legs. When i was older and pregnant with my third child my mom took me to see the Female doctor that took care of me. what a reunion that was. i have had no other complications like heart murmur as mentioned could happen. i do Praise God for healing me when i was three and allowing me almost 73 years of living.

I had Scarlet Fever when I was in the first grade, about 6 years old, in 1956. My memories are sort of cloudy, but some things I will never forget. I was in the hospital for several weeks, the nurses came around with Easter baskets for us, while they wore a little cotton ball taped to the back of their skirt uniform (yes, no scrub pants), bunny ears. The only thing I ate from the basket was a pack of chewing gum. My other strong memory is that I kept asking for my clothing, especially my Daniel Boone polo......And lastly, I remember the nurse being so "mean" to me when she forced me to eat..........me with the worst sore throat ever! Our neighbors from the block in Brooklyn chipped in and bought me dolls, (I remember the Ginny doll the best with her own little closet/box and so much clothing! I couldn't wait to take everything home to share with my siblings. I would have my first grade work brought to me, to keep my little brain sharp. When the big day came for my release, which seemed like years, my mother brought me some "new" clothes and the most horrible lace-up shoes I ever saw. "Why, mommy?" I asked, I want my clothes. I wanted my special polo. She explained the first reality check to me.....The clothing had to be burned because it was full of "Scarlet Fever germs".....no, I can't take my new dolls home, or my Easter basket with just the gum taken out of it.........no, these are full of germs and have to be destroyed. What?????? So I went home in horrible clothing, orthopedic type shoes and no toys! Then, I am told that I cannot go back to school yet....I have to sit in the sunlight across the street from the house we lived in, every day, to recuperate. What??? My classmates walked past me every day after school and called me a hooky player! Did I ever realize how sick I was? Not until my mother told me that they almost "lost me".....but didn't even tell her at the time because she was pregnant with my sister (born the following month). So......wow....I almost died? I didn't think I was THAT sick! Wow. My friends child had it in the 1980's......they gave her antibiotics and sent her home! The wonders and miracles of modern medicine will never cease to amaze me!

Hemolytic uremic syndrome (HUS) in history--part 4: the bigger picture

tsmith — Thu, 23 Jun 2011 07:00:00 +0000

Hemolytic uremic syndrome (HUS) in history--part 4: the bigger picture

As I've laid out this week (part 1, part 2, part 3), the realization that a fairly simple, toxin-carrying bacterium could cause a "complex" and mysterious disease like hemolytic uremic syndrome came only with 30 years' of scientific investigation and many false starts and misleading results. Like many of these investigations, the true cause was found due to a combination of hard work, novel ways of thinking, and simple serendipity--being able to connect the dots in a framework where the dots didn't necessarily line up as expected, and removing extraneous dots as necessary. It's not an easy task, particularly when we've had mostly culture-based methods to rely on since the dawn of microbiology.

If you read start digging around in the evolutionary medicine literature, you'll see that one oft-repeated tenet is that many more "chronic" and "lifestyle" diseases are actually caused by microbes than we currently realize. (I'll note that there is active disagreement here in the field--one reason noted is that many of these diseases would decrease one's fitness and thus they are unlikely to be genetic, but many of them also have onset later in life than the prime reproductive years, so--still controversial). But whether you agree on the evolutionary reasoning or not, I think it's safe to say that those who make this claim (like the Neese & Williams book I linked) are probably right on the overall assertion that more and more of these "lifestyle/genetics" diseases are going to be actually microbial in cause than we currently realize.

Why do I agree with this claim? History is a great indicator. Many infectious diseases were thought to be due to complex interactions of genetics (or "breeding," "lineage," etc.) with "lifestyle." Think of syphilis and tuberculosis in the Victorian era. Syphilis (and many other diseases which we know now to be sexually-transmitted infections) was considered a disease which affected mainly the lower social classes ("bad breeding"), and was thought to be rooted in both family history as well as an over-indulgence in sex or masturbation. Tuberculosis, because it affected those throughout the income spectrum, was still blamed on "poor constitution" in the lower classes, but was a disease of the "sensitive" and "artistic" in the upper classes. It was also thought to be due to influences of climate in combination with genetics. Or, look to more recent examples of Helicobacter pylori and gastric ulcers, which were also ascribed to dietary habits and stress for a good 30 years before their infectious nature was eventually proven. And from that same era, HIV/AIDS--which even today, some are still all too ready to write off as merely a behavioral disease, rather than an infectious one.

So, we still view many of these diseases of unknown etiology as multi-factorial, "complex" diseases. And undoubtedly, genetic predisposition does play a role in almost every infectious disease, so I'm not writing off any kind of host/pathogen interplay in the development of some of these more rare sequelae, such as HUS as a consequence of a STEC infection. But looking back over history, it's amazing how many diseases which we view now as having a documented infectious cause were studied for years by researchers thinking that the disease was the result of exposure to a toxin, or diet, or behavior, or a combination of all three.

I've mentioned the example of multiple sclerosis in previous posts. Multiple sclerosis is an autoimmune disease; the body produces antibodies that attack and eventually destroy parts of the myelin sheath covering our nerves. The cause of MS, like HUS 40 years ago, is unknown, though it's thought to be a combination of genetics and environmental influences. Going through the literature, it seems like almost everything has been implicated as playing a causal role at one point or another: pesticides, environmental mercury, hormones, various other "toxins," and a whole host of microbes, including Chlamydia pneumoniae, measles, mumps, Epstein-Barr virus, varicella zoster (chickenpox), herpes simplex viruses, other herpes families viruses (HHV-6 and HHV-8), even canine distemper virus. They've done this looking at both microbe culture (from blood, brain tissue, CNS, etc.) as well as using serology and DNA/RNA amplification in various body sites. None have shown any strong, repeatable links to the development of MS--much like the spurious associations that were seen with adenovirus and HUS.

Although no microbial agent has been convincingly implicated to date, there are tantalizing hints that MS is caused by an infectious agent. There have been "outbreaks" of MS; the most famous occurred in the Faroe Islands in the 1940s. Studies of migrants show that the risks of developing MS seem to be tied to exposures in childhood, suggesting a possible exposure to an infectious agent as a kid. And one of the most common mouse models used to study MS has the disease induced by infection with a virus called Theiler's murine encephalitis virus (TMEV). If it can happen in mice, why not humans?

It might seem implausible that infection with some microbe could lead to the eventual neurological outcomes of MS, but again, examples abound of weird connections between microbes and health outcomes. For STEC, it might not be intuitively obvious at first glance how a fecal organism could be a cause of kidney failure. The respiratory bacterium Streptococcus pyogenes usually causes throat infections ("strep throat"), but if left untreated, it can also cause kidney damage (glomerulonephritis) or even heart failure due to rheumatic heart disease. A microbial cause of MS could lie in a virus, bacterium, parasite, or fungus--maybe one that we haven't even discovered yet, but that perhaps will pop up as we learn more and more about our metagenome. Perhaps 30 years down the road, the way we view many of these "complex" diseases will look as short-sighted as it does looking back at old HUS papers from today's vantage point.

tsmith Thu, 06/23/2011 - 03:00

Tags

General Epidemiology