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The deal with ricin

So ricin is back in the news this week, but what is it, where does it come from, and why is anyone worried about it? Ricin is an extremely potent toxin derived from castor beans, and is a natural byproduct of castor oil production. It’s also long been a favorite of bioweaponeers, aspiring terrorists, and anti-government reactionaries.

We don’t know exactly how to derive ricin from castor beans (and wouldn’t tell you if we did), but it apparently isn’t that difficult. However, creating a ricin preparation that can be easily inhaled is considerably more difficult. This week’s ricin mailer apparently failed to overcome that obstacle, and we understand that the granular powder in the envelopes he sent was unlikely to be dangerous for this reason.

Ricin works by entering cells and binding to ribosomal subunits. This prevents cells from making new proteins and leads to cell death and, within 72 hours of exposure,  death of the poisoned individual. Fortunately, natural exposure to ricin is exceedingly rare, but successful and unsuccessful attempts to use it as a weapon are well documented.

Ricin is perhaps most famous for its role in one of the murkiest Cold War spy stories. In 1978 Bulgarian dissident Georgi Markov was walking over a bridge in London when he felt a sharp jab to the back of his leg, then turned to see a man behind him fumbling with an umbrella. Four days later he was dead. Investigators extracted a ricin-loaded pellet from the back of his leg, where the fumbling man had jabbed him with a spring-loaded umbrella.

Ricin has also popped up in other nefarious plots from time to time. In 2003 ricin-laced letters were detected in the White House mail, as one was this week. In 2006 a Virginia man was arrested for extracting ricin to use against his wife. Other cases involving ricin include elaborate plots to use ricin to assassinate public figures, but fortunately none have come to fruition.

The media isn’t wrong to treat these latest ricin letters as a serious matter; any time a dangerous toxin is sent to the President it’s important. However, they’re not making it very clear that you have nothing to worry about. That said, ricin poisoning is a life-threatening medical emergency, but if you’re concerned about it happening to you, the CDC FAQ page will hopefully persuade you otherwise, and will certainly tell you what to watch out for. Assuming you trust the people around you, don’t go on castor bean eating binges, and haven’t run afoul of Russian intelligence, ricin poisoning need not be high on your list of concerns.

-Steve

 

One Health & How Better Communication Can Help Limit West Nile Virus Outbreaks by Stephanie Porter

The One Health Initiative is the effort to increase communication and collaboration between disciplines such as human medicine, veterinary medicine, public health, environmental health, and other related fields 1. The hope is that by promoting collaboration, shared knowledge could improve the health of all species.

There are innumerable reasons why sharing knowledge between scientific disciplines is vital. Comparative medicine relies on the shared characteristics between the anatomy and physiology of humans and other animals, as well as similarities in disease pathogenesis. This knowledge is then used to establish animal models for biomedical research, which can help in the development of drugs, vaccines, medical devices, and increase understanding of infectious diseases and cancer. Identifying animal models that accurately reflect human disease is key, and requires input from those with knowledge of the physiology and pathology in both humans and potential animal models.

The large and increasing prevalence of zoonotic diseases is another reason why cooperation between human and veterinary medicine is of utmost importance. Of all the diseases which affect humans, ~60% are caused by pathogens which also infect non-human animals 2. Zoonotic diseases have become more problematic in recent decades, as ~75% of the infectious diseases that have emerged in the human population in the last 30 years have been zoonotic 2. Goals of the One Health initiative include improving surveillance, prevention, control, diagnosis, and treatment of zoonotic disease through joint efforts from various health disciplines, especially veterinary and human medicine.

The events surrounding the emergence of West Nile virus (WNV) in the United States in 1999 provide some of the best evidence that human and animal medicine have remained too distinct. WNV first entered the US in New York City during the summer of 1999. Crows, now known to be one of most highly susceptible North American WNV hosts, began dying in large quantities in June, but the New York state wildlife pathologist misdiagnosed 400 crow samples 3. Birds at the Bronx Zoo began dying on August 10th; by September 23, the zoo had lost a total of 27 birds 4. It was the zoo’s pathologist, Dr. Tracy McNamara, who started putting the puzzle pieces together when she realized that the encephalitis she was seeing in her birds may have something to do with the human disease outbreak that the city announced on Labor Day, which was misattributed to St. Louis encephalitis (SLE). She knew that her animals could not be dying from SLE, as it is generally asymptomatic in birds 3. Dr. McNamara appealed to both the USDA and the CDC to test her samples, and was met with resistance. One of the main problems she faced was jurisdictional, as neither government department wanted to claim responsibility for the health of wild and exotic species 5. People also did not want to believe that there was a link between the avian deaths and the human disease. Dr. McNamara finally got the Army to test her samples, and it was discovered that it was West Nile virus that was the causative agent. By that point it was September. In 1999, 62 individuals were infected with West Nile virus, 7 of whom died, statistics which may have been lower had there been more rapid identification of WNV 6.

Developing an effective surveillance program for West Nile virus activity took time, and retrospective analysis from avian samples collected during 2000 has revealed that WNV was evident in samples at least 2 weeks before the first human case 7. However, WNV birds were collected 3 months before the first human infection, so if laboratory testing had been conducted more swiftly there might have again been more advanced warning, and prevention of human disease 8. Today, WNV surveillance data is collected for human infections, sentinel chicken flocks, mosquitoes, veterinary cases, and dead birds (which rely on public reporting) 6. In 2012, there was a large WNV outbreak, resulting in increased avian and human deaths. The data has not yet been finalized, but the confirmed 5,387 human infections and 243 human deaths represent the most severe seasonal WNV epidemic since 2003 6.

Given the prevalence of zoonotic diseases, it would be impossible to have healthy people without also ensuring the health of other animals. That’s one of the reasons I get upset when I hear professors at JHSPH say things along the lines of “since this is a school of public health, obviously we’re going to focus more on human health.” We understand that multihost pathogens cannot be generally eliminated if you only focus on control in a single host, so I believe that public health is doing human health a disservice if it narrows its focus and ignores other species.

One Health is by no means a new concept, but one that has taken on increased importance given the globalization of our world, the growing prevalence of zoonotic infectious diseases, and the use of animal models in biomedical testing. Facing emerging medical problems as a collective force is perhaps the best way for all health professionals to ensure the well-being of all animal species, including humans.

1. One Health initiative. http://www.onehealthinitiative.com/.

2. King LJ, Anderson LR, Blackmore CG, et al. Executive summary of the AVMA One Health initiative task force report. J Am Vet Med Assoc. 2008;233(2):259-261.

3. Keynote by Dr. Tracey McNamara — 2012 Zoobiquity conference. http://www.youtube.com/watch?v=cBk9X4iwhmE. Updated 2012.

4. Steele KE, Linn MJ, Schoepp RJ, et al. Pathology of fatal West Nile virus infections in native and exotic birds during the 1999 outbreak in New York City, New York. Vet Pathol. 2000;37(3):208-224.

5. Microbeworld Video. One Health and the lessons learned from the 1999 West Nile virus outbreak (MWV46). http://www.microbeworld.org/podcasts/microbeworld-video/898-one-health-and-the-lessons-learned-from-the-1999-west-nile-virus-outbreak-mwv46-. Updated 2011.

6. CDC. West Nile virus. http://www.cdc.gov/ncidod/dvbid/westnile/index.htm. Updated 20122013.

7. Mostashari F, Kulldorff M, Hartman JJ, Miller JR, Kulasekera V. Dead bird clusters as an early warning system for West Nile virus activity. Emerg Infect Dis. 2003;9(6):641-646.

8. Eidson M. “Neon needles” in a haystack – the advantages of passive surveillance for West Nile virus. West Nile Virus: Detection, Surveillance, and Control. 2001;951:38-53.

 

Avian Flu Update

Since our first post the scale of the H7N9 avian flu outbreak in China has continued to increase. Authorities are now reporting 63 cases and 14 deaths (Update-now 77 cases, 16 deaths), and Beijing has also reported its first case. Additionally, thanks to the rapid work of Chinese researchers, we have learned a lot about this novel virus. Some of the information we have learned about this virus is certainly worrisome, but it’s extremely important to understand that neither the WHO nor the Chinese government have found any evidence of sustained person-to-person transmission. This means that while the number of cases is increasing, all cases are believed due to transmission from an infected bird to person, or perhaps limited transmission between people with extensive close contact, such as family members.

Researchers at the Chinese Centers for Disease Control and Prevention have published their initial, but extensive analysis of the H7N9 virus in The New England Journal of Medicine. Interpreting these findings requires knowledge of some basic virology, which we’ll try to keep to the basics. Those desiring a more technical explanation of influenza virus structure, lifecycle, and disease should look at Influenza 101 on Dr. Vincent Racaniello’s virology blog.

H7N9 denotes the subtype of influenza virus as defined by the two main proteins on the surface of the virus, HA and NA. Human influenza viruses are typically H1 or H3, whereas avian viruses include H5 and H7, among others. Unlike most viruses, which have a genome consisting of either one or two strands of RNA or DNA, the influenza virus genome consists of eight separate RNA segments, each of which directs the production of viral proteins. This segmented nature of the genome underlies the ability of influenza to mutate dramatically and cause pandemics, which is described in detail in Influenza 101.

The HA protein is particularly important. It is responsible for attachment of the virus to a target cell, and is also the protein against which our immune response produces protective antibodies. The structure of the HA protein also determines whether a virus is better suited to infecting avian or human cells, and therefore distinguishes between human and avian influenza viruses. When avian flu viruses do infect human cells, they normally do so deep in the respiratory tract, rather than in the upper respiratory tract. This makes them much less transmissible, or “contagious”, because they are less likely to be sneezed, coughed, or breathed out.

The Chinese researchers identified several troubling mutations in the HA protein of H7N9. Some of these mutations may make the virus better adapted to infecting human cells, especially cells in the upper respiratory tract. Other mutations are associated with an increased ability to infect cells outside the respiratory tract, and with increased virulence. Some of these mutations, as well as a mutations in a protein called PB2, are among those identified in last year’s controversial H5N1 research on avian flu transmission in ferrets. This underscores the critical important of continuing avian flu transmission research, despite the sensationalistic reporting in major media outlets such as The New York Times last year.

In the same issue of NEJM U.S. CDC flu researchers published a companion article detailing the pandemic risk posted by H7N9. The mutations identified by Chinese researchers make the risk very real. However, there is still no evidence of sustained person-to-person transmission, and little or no evidence for transmission even between very close contacts. The Chinese government is monitoring thousands of people who have been in contact with H7N9 patients, so any such transmission is likely to be quickly identified. Of course, the Chinese researchers as well as scientists in the U.S. and around the world are feverishly working to have a vaccine ready in the event H7N9 proves capable of causing a pandemic. Additionally, H7N9 is susceptible to Tamiflu, as demonstrated by the successful treatment of a young girl in Beijing along with laboratory testing.

Excellent resources for following new developments continue to be the CDC page on H7N9, the WHO disease outbreak and FAQ pages and the CDC Flu Twitter page. Additionally, feel free to leave comments or pose questions on our website or Facebook page.

-Steve

Big Azz Sodas. What’s The Big Whoop?

Welcome to my Sunday obsession. Since early March, I’ve heard many debates on The Soda War: is the banning of sodas greater than 16 oz an effective way to fight obesity? Here I will present a few of the issues in this debate and the great difficulty I’ve experienced in finding primary sources of information.

I listened last week to a Slate’s Table To Farm episode that debated about whether banning of extra-large sodas is an effective way to limit calorie intake and obesity. They had two guests on the show representing both sides of the debate. I personally found the anti-soda ban argument a bit weak—this guest said that policies are unfair because they are targeting low income people’s pleasure foods; you don’t see anyone limiting the intake of brie, chips, beer or wine, for example, which are also not particularly healthy. The failing of this argument is that one product is sold as a single serving (extra-large sodas) versus products that are meant to be multiple servings (though I suppose people do eat a whole bag of chips in a sitting)—but it’s not like you go to the movie theatre to buy a large wheel of cheese for yourself.

Their debate has stayed on my mind, so I started to look for good sources of information. After doing a preliminary Google search for “public health news,” I was lead to American Public Health Association’s website. At first glance, I was impressed by the breadth of topics covered: click on the “Topics” tab, you will see the broad range of public health news topics they are reporting on (Child Health, Environment, Funding, Health Reform, HIV, Nutrition, etc).

Once I got into the articles, however, I was disappointed by the lack of primary sources. On the “soda ban” page, it said in the first paragraph, “New research shows that prompting beverage makers to sell sodas in smaller packages and bundle them as a single unit actually encourages consumers to buy more soda — and gulp down more calories — than they would have consumed without the ban.”

It went to on to list how this topic was being portrayed in a couple of city newspapers, but it failed to cite the original paper it was talking about. I would like to see the article showing how it can encourage more soda drinking. It did have links to the Jon Stewart show and his mention of this topic (or rather heckling). Why not cite the original source so we can decide for ourselves if the research is good?

In trying to track down the original study, I discovered that many media sources had been referencing this study and using it as concrete evidence against the soda bans, ie “Study shows that limiting size makes us want to gulp more.” However, most of the articles I read, including a New York Times article, did not provide links to this study. Also, I could not find the original study on Pubmed (I searched for “Brent Wilson” “Limiting Sugary Drinks” “Wilson soda”). I could not easily find it by going to PLOS website. I finally found a link to it here (KPBS, affiliated with San Diego State University).

The author of the study is Brent Wilson, a psychology doctoral student at University of California San Diego. How many people were studied? 100 college students. Aren’t you glad that policy makers (and media sources and the public) are relying on this one study (by a student with undergraduate student participants) to make public health decisions? I haven’t personally decided yet what is the most effective way to fight obesity. But I won’t be making my decision based on this single, small study by a student.

Another part of this debate has to do with the ‘anti-Bloomberg laws.’ According to the New York Times, the State of Mississippi has passed a law mandating that any policy that restricts food or drink must be passed at the state level. This means that cities or counties cannot form their own policies on a large range of nutrition issues: limits to soda size, salt content, shortening in cookies, toys in fast-food meals for children, how a menu is written or just about any other daily dining experience. However, this has had an unexpected backlash. Local governments are upset, not because they wanted to ban large-sized drinks, but they see this as a limit on their local authority to decide what is right for their region. Others are upset, like restaurant owners, because they want the choice to be up to them. Because restaurants and other vendors are driven by consumer demand, more and more restaurants are taking up healthier options already, not because the government demands it of them, but because consumers want these options. Restaurants should therefore be able to cater to the demands of the consumers.  The ironic part of this, is that Mississippi, according to NPR, has the highest rate of obesity in the country (1 in 3). So if restaurants are catering to consumers, should we be focusing our efforts on educating these consumers and influencing them to want healthy options?

The biggest lesson from my weekend reading is that the major news providers seem to have a couple of pieces of knowledge that they are all reporting. They lack real evidence and, worse, make it difficult to track down the ‘real’ evidence they present. It took me a lot of motivation and time to track down the primary sources. There has to be a better way to access information that is cited in the top media sources. I want to be able to look at these primary sources, see what real evidence is out there for or against of proposed public health intervention, and decide for myself. If I had not taken the time to hunt the original sources down, I could easily have made important decisions based on very flimsy evidence.

What about you? What public health interventions do you think we should be focusing on to fight obesity? Policies? Education? And where can we go for reliable public health information on this?

-Nina

Functionally Cured: HIV cleared from child after receiving early drug therapy – by Nick Wohlgemuth

HIV causes a chronic viral infection, meaning that our bodies aren’t able to get rid of the virus like with cold or “flu” viruses. Thankfully for HIV patients, antiretroviral therapy is usually able to control viral replication, and patients are able to live long, healthy lives and drastically delay the onset of AIDS. However, antiretrovirals have bad side effects, and virus levels usually rise quickly once treatment is stopped.

In March, scientists presented a report of an infant that has been functionally cured of HIV. What the heck does that mean?

To be functionally cured of HIV, an individual has to have previously had a confirmed infection with the virus. Then, usually through the use of antiretroviral therapy, the virus is driven to such low levels that when the treatment is no longer administered, the virus levels don’t increase.

In this case, the baby was born to a mother with HIV and given antiretroviral therapy 30 hours after birth. Scientists confirmed that the child had virus in her blood and continued to monitor the virus levels. Soon, they couldn’t detect virus by using the normal clinical detection methods. The baby was taken off antiretroviral therapy when she was 18 months old, and virus levels remained undetectable up to the time of the report when she was 26 months old.

When scientists look with more sensitive methods, they can still detect virus in the child’s body, but the normal clinical screens are all negative. The child remains symptom free.

This is the first time there was been a well-documented case of a child being functionally cured of HIV. This case stresses the importance of starting antiretroviral therapy as soon as possible. The broader implications are limited at this time, but this seems to prove, in principle, that if we are able to get good antiretroviral drugs to infected individuals soon enough, then we might be able to functionally cure many more people with HIV.

-Nick Wohlgemuth

Conference Abstract

PHU News Analysis 1: Sources of News, H7N9, and West Nile Virus

News Analysis Episode 1 is now available!

Right click to download or click to stream

Nick, Nina, and guest Stephanie Porter discuss where they go for sources of information about science and health, the recent outbreak of avian influenza H7N9, West Nile Virus, and the One Health Initiative.

Links for the Episode:

H7N9 ProMED Mail Story

Steve’s H7N9 Blog Post

ProMED Mail

This Week in Virology

Virology Blog

Slate’s Political Gabfest

Science Friday

Ira Flatow

Center for a Livable Future

More information about the infant functionally cured of HIV

Recommended Twitter Follows

Why Snails Matter (a plea to Stephen Moore)

On a recent episode of “Real Time with Bill Maher”, Stephen Moore of the Wall Street Journal mockingly asserted that the government shouldn’t be funding research on snail mating habits. In response, fellow guest Zack Kopplin shot Moore down by telling him “you’re not a scientist!” The exchange got a big laugh, but it was a debacle for the advocacy of basic science research.

Kopplin is right, and wrong. There are extremely good reasons for funding snail research; we’ll get to those in a second. Kopplin’s answer to Moore, while good for laughs on a comedy show, is just as arrogant as Moore’s dismissive attitude towards basic science. Whether Moore knows why the government funds snail research or not is irrelevant. Most viewers probably don’t, and so Moore’s mocking of such research sounds right. Studying snail mating absolutely sounds ridiculous on its face. The fact is that this is taxpayer-funded research and the public deserves a better explanation than “but you’re not a scientist!!”

As a self-described science-education activist, Kopplin had an obligation to explain to Moore why he was wrong rather than shout him down. Since he didn’t, we will. Freshwater snails are the intermediate host of schistosomiasis, a parasitic worm that infects over 200 million people a year worldwide. The worms infect humans by burrowing their way out of the snails, and then into the skin of a nearby person. If you’re interested in where the worm goes from there, here’s a good depiction of the lifecycle.

Long-term infection with these worms causes severe liver damage and is a leading cause of bladder cancer in many parts of the world. Unfortunately, it’s also been an extremely difficult disease to control. One of the primary means of control is through killing the snail hosts. The snails are capable of reproducing extremely rapidly and to devise more effective control measures we need to better understand their lifecycle.

If you’re interested in learning more about schistosomiasis control research, the link for the study referenced by Stephen Moore is here. The CDC also has an extensive page on schistosomiasis, truly one of the world’s most important, and destructive parasites.

-Steve

The Future of Cancer Treatment

Talk of “curing cancer” is often overly simplistic. Every cancer is unique in terms of the location and the individual. This is highlighted by recent possible breakthroughs in cancer therapy designed around educating a particular patient’s immune system to attack the cancer, rather than using drugs that as we all unfortunately know, can be extremely toxic!

This past weekend University of Pennsylvania researchers announced very exciting Phase I clinical trial results for a new cancer vaccine that may save women with advanced ovarian cancer. Two weeks ago Episode 1 guest Steven Salzberg wrote on his blog, Fighting Pseudoscience, about an extremely promising experimental treatment for acute adult leukemia that uses similar principles. These therapies are still experimental, but are part of an exciting new type of cancer treatments that may offer hope in the future to people with very advanced cancers.

-Steve

A new bird flu? by Steve Goldstein

Yes, it does appear that a new type of bird flu has emerged in humans in southern China. What is meant by “bird flu” as opposed to our normal seasonal flu viruses or the pandemic H1N1 virus of 2009 fame? Avian flu viruses usually don’t infect people and when they do, transmission is almost always directly between birds and humans, as avian flu viruses typically don’t transmit well between people.

This H7N9 virus may be causing more severe disease than seasonal flu or similar avian flu viruses have caused in the past, and so has caught the attention of the World Health Organization, which is reporting 16 cases and 6 deaths so far. Fortunately for us, the virus does not seem to be transmitted from person-to-person. Therefore, measures already taken by the Chinese government, such as the culling of birds sold in local “wet markets”, have an excellent chance of stopping the outbreak.

The media has been kind enough to largely avoid the sensationalistic, inaccurate reporting that colored the debate about H5N1 research last year. Excellent articles about the current outbreak can be found here, here, and here.

The concern with avian flu viruses is that they might mutate and become more transmissible person-to-person. That’s certainly a possibility, which is why some of the world’s best scientists at the U.S. Centers for Disease Control and Prevention have already begun work on a vaccine to prevent H7N9 infection, just in case that happens.

The WHO FAQ page on H7N9 is an excellent resource, and you can also follow CDC Flu on Twitter. If you have questions for us feel free to post them in the comments, and if we can’t answer them ourselves we’ll get an answer for you from Dr. Andy Pekosz, who was featured in episode 1 of our podcast.

-Steve

Saving Lives With Better Science Communication