An Epidemic of Absence: A Book Review

An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases.
By Moises Velasquez-Manoff.
Scribner; 2012 ISBN 978-1-4391-9938-1

“No matter who we are, we evolved with many more parasites and commensals, both large and small, than we generally encounter today. The implication—and let's face it, the hope—is that reestablishing contact with some of these organisms can rebalance the immune system.”

If Moises Velasquez-Manoff were to sum up his latest book, An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases, in under fifty words, the quote above would be a good choice (p. 61). In recent years, a growing number of researchers have explored the relationships between humans and the species that live with us—both those that cause disease and those that do not—and found evidence that we may be better of with many of them than without. Framing the information within his own experience of allergy and autoimmune disease, Velasquez-Manoff comes at this body of evidence from every conceivable angle, and by the last page one cannot help but be thoroughly convinced.

Studies show that regularly swallowing pig whipworm eggs
can alleviate symptoms of autoimmune diseases.
Image Bobjgalindo (enhanced) CC BY-SA 3.0

This topic, in the hands of someone suffering from allergies and autoimmune disease, could easily have come across as pseudoscience, but Velasquez-Manoff is meticulous about pointing out what is actually known through scientific research, and what is still theory or speculation. He deftly balances anecdotes with comments from reputable scientists and medical specialists, and his obvious grasp of the difficulties of proving causation lends the work great credibility. Similarly, his exploration of the “hookworm underground,” where individuals who are not medical professionals sell worm infestations to ill and desperate people, might have appeared sensational, but instead seems appropriate in the context of the narrative.



The examination of similar evidence from many different directions, however, occasionally makes one feel that the point has been made again. And again. By the time the author writes “Enough! What to do about it?” in the last chapter, the reader who has stayed the course is bound to breathe a grateful “yes!” This is not to say that the narrative is boring; it is not. But brevity is not its greatest charm.

One discussion in particular stands out from the rest of the book in both tone and relevance, and that is the author's detailed character assassination of Jasper Lawrence, one of the “hookworm underground” operators he meets. It's unclear why Velasquez-Manoff feels it's necessary to aim a stream of accusations – which may or may not be justified - at Lawrence. At best, Lawrence is anecdotal; he operates outside of mainstream medicine and doesn't contribute to the scientific literature. At worst, he's irrelevant. If the intent is to warn off anyone considering buying parasites from one of these companies, a clear explanation of the risks would have been a better choice.

An Epidemic of Absence is a good book about a subject that's likely to become more mainstream, and more important, as the science progresses. If you read nothing else, read the last chapter for the essence of the book. Then, if you want to understand it all thoroughly, start at the beginning and read the whole thing.

CBC Ideas - Worthy Parasites

Have you ever found a tiny parasitic pea crab living
inside your oyster? Some folks like to eat these too.
Image: NOAA

My CBC Ideas documentary, Worthy Parasites: A Villain's Silver Lining, will air for the first time on Jan 8, 2013, at 9 PM.

Regular listeners of CBCs Ideas, hosted by Paul Kennedy, know that the program can explore virtually any topic in science, history, the arts, culture, religion or anything else you can think of. Interesting, provocative, and contemporary, it's been on the air for decades and it's always worth a listen.

That's why I'm thrilled and honored to be the contributor of an episode that explores how species almost everyone loathes - parasites - are actually beneficial in many ways, even essential in our world. If you think parasites have no worth, think again, and listen to my one-hour episode in January.

CBC Ideas, Worthy Parasites: A Villain's Silver Lining is available on CBC Radio One across Canada: Tuesday, January 8 at 9 p.m. (9:30 p.m. NT) and Monday, January 28 at 2 p.m. (2:30 p.m. NT). It will also be live streamed and streamed on demand on the CBC website, and available as a podcast.

You'll be surprised by all the good things parasites do for you.

Ivermectin for Bedbugs

Would you take a drug to make yourself poisonous to mosquitoes, or black flies, or wasps? How about taking Ivermectin for bedbugs? I'm not so sure about this - the most obvious problem is that one would have to be bitten before it could work!

Ivermectin for Bedbug Infestation

 

Bedbug bites can be very uncomfortable.
Taking Ivermectin for bed bugs would
only work if every bug bit at least
once more!

A recent article on Bloomberg.com suggested that giving people oral Ivermectin for bedbugs might be an effective way of dealing with a bedbug infestation. A very small study (three people) found that most bedbugs died if they fed on someone within a day of a dose of Ivermectin, and that 54 hours after the dose, 42% of bugs died after feeding.

Treating people who aren’t sick with drugs has precedent: it’s common for people traveling in places where mosquitoes carry malaria, for example, to take an anti-malarial drug to avoid infection. But while malaria can easily kill you, bedbugs have never been shown to transmit disease to humans.

Ivermectin is an antiparasitic and obviously an insecticide. Like all drugs, it comes with a risk of side effects, some of them quite serious. Would it really make sense to expose large numbers of people – people who aren’t infected with anything - to this drug? It seems to me that treating a dwelling with insecticides is one thing – sometimes not a very good thing – but turning people into insecticide laden bug traps is another.

Bedbug Feeding Habits

Would it even work? Past research has indicated that bedbugs don’t feed every day. A 2009 study indicated that they might feed every two to three days and that they might synchronize their feeding (in other words, the bugs in a colony all tend to feed at the same time). Ivermectin is typically given as a single dose; how would we determine when it’s feeding day for the bedbugs? If the first twenty-four hours is crucial, you’d want to make sure you took the drug on the right day. And what if some survived or didn’t feed that day? And you’d need 100% participation from people staying in the dwelling. Imagine trying to do this in an apartment building. How many doses of Ivermectin would it take?

Finally, I suspect resistance would arise fairly quickly. If 42% of bugs died after feeding at the 54 hour mark, that means 58% survived – and they’d all been exposed to the drug. If their survival was due to them having more natural resistance than the other bugs, and they passed that along to subsequent generations, we’d see more and more resistance.

Before very long, the days of using Ivermectin for bedbugs would be over.

 

Sources

Gale, J. (2012) “Bed Bugs Dying After Merck Drug Suggests Possible Weapon.” Bloomberg.com

Reinhardt, K., Isaac, D. and Naylor, R. (2010), Estimating the feeding rate of the bedbug Cimex lectularius in an infested room: an inexpensive method and a case study. Medical and Veterinary Entomology, 24: 46–54. doi: 10.1111/j.1365-2915.2009.00847.x

Thoughts on Naegleria fowleri, "Brain Eating Amoeba"

Naegleria fowleri: a protist that can be a cyst, an amoeba squelching along, or a whirling swimming flagellate; an organism found all over the world that loves warm water, a free living organism that can adopt a parasitic lifestyle; an organism that will almost certainly kill you if it gets into your brain. Beautiful. Fascinating. Deadly.

Naegleria fowleri takes various forms. When it invades a human central
nervous system, it is found as an amoeba or a flagellate.
 Image CDC Image library.

Annual Deaths Due to Naegleria fowleri

Every year during the sweltering days of summer we hear of deaths caused by the “brain eating amoeba.” This year a man died after teaching his daughter how to swim in an Indiana lake, and several children in other American states died after swimming in warm fresh water. Children have died after playing in bath water at home, and the use of neti pots to rinse the sinuses, or ritual inhalation of water into the sinuses, has resulted in deaths as well. The disease is called primary amoebic meningoencephalitis, or PAM.

How Does Naegleria flowleri Infect People?

Naegleria fowleri is just one of more than 20 Naegleria species found in the environment, but to date it is the only one found in human cases of PAM. What’s so special about N. fowleri? Perhaps it has something to do with N. fowleri being a thermophile – in other words it loves warmth. It can survive at temperatures as high as 45ºC, which would make it very comfortable at a normal human body temperature, and impervious to the highest fever. But many of the other species like high temperatures as well, so that’s not the whole answer.

Perhaps it’s important that N. fowleri adapts easily to axenic conditions – meaning that it doesn’t need a community of other organisms around to be happy; it can thrive all by itself. This does make it stand out from the other species, but living inside another organism isn’t exactly axenic, and strains of N. fowleri grown axenically in the lab lose their ability to produce disease. How this characteristic might help it invade the brain in the first place, then, and thrive there, is a tantalizing question – at least to me.

Studies have shown that N. fowleri isolated in the environment contain food vacuoles full of bacteria, whereas those isolated from cases of PAM contain vacuoles full of cell debris. So, when the organism is parasitic, it uses host cells as a food source instead of bacteria. It produces an enzyme that enables it to do this (Chang). This is clearly important, but do we know whether other Naegleria species produce a similar enzyme?

Hot Weather Means Water Sports and Naegleria fowleri

Perhaps it’s a combination of all these factors, and possibly others, that make N. fowleri uniquely equipped to be a “brain eating amoeba.” The question remains to be answered. What’s easier to understand is why it’s so rare, and yet so predictable. In order for N. Fowleri to get into a human brain, very warm water containing the organism must be inhaled into the nasal sinuses. This event is relatively uncommon, but can be expected to happen in the summer months when people – particularly young people – play in the water to cool off.

Sources

Chang SL. “Pathogenisis of Pathogenic Naegleria amoeba.” Folia Parasitol (Praha), 1979; (26)3:195-200.

De Jonckheere JF. “A Century of Reasearch on the Amoeboflagellate Genus Naegleria.” Acta Protozool, 2002; 41: 309-342.

MOLT: An Internet Game for Diagnosing Malaria

Twenty-four small images of red blood cells appear on the screen. Your job is to click on any that have a malarial parasite inside, removing the image. When you’ve removed all the infected cells, click on “Label all Negative” and another twenty-four cells appear. At the end, you’ll get a score and some information about how many correct choices you made.

You Can Help Diagnose Malaria

Blood films are used to diagnose malaria. The species of Plasmodium
present in the blood can be determined based on the appearance of the
parasites inside red blood cells.
Image: CDC - Public Health Image Library (PHIL) #5942

The game is called MOLT, and it was designed by the Ozcan Research Group at UCLA. Anyone can register and play. The idea is that anyone can be given some basic information about what malarial parasites look like in red blood cells and then be part of an accurate means of correctly diagnosing the disease without having to rely on experts in the field. This would be a huge improvement for malaria diagnosis in parts of the world where malaria kills millions each year and people skilled in diagnosis are rare.

A pilot study of the game using 20 gamers produced results that were within 1.25% of the accuracy of actual experts adept at recognizing malaria, which is pretty impressive. One can imagine an arrangement where someone puts a blood film on a microscope somewhere in Asia or Africa, the images are sent out electronically to potentially millions of gamers around the world, and the answer comes back, positive or negative, in a very short time. If the pilot is any indication, the answer would agree, most of the time, with what an expert would have said.

Crowd-sourcing Games Can Diagnose Malaria and Other Diseases

This has implications for lots of other things that are done by microscopy or other types of imagery: pap smears, fecal smears for parasites, pathology slides etc. It could be improved upon by adding automated scanning techniques and actual experts to the crowd of gamers. These things, plus a larger number of gamers would likely be even more accurate than the gamers used in the pilot. It’s exciting.

I’ve played the game – a number of times. I have lots of experience with reading blood films for malaria, and my biggest issue with the game is that the resolution – the sharpness – of the images is often not good enough

for me to feel completely comfortable with my choices. Platelets sitting on top of red blood cells can look like a parasite. So can debris on the slide. A red cell that’s damaged, or crunched up against another cell, or too darkly stained, or abnormal in some way, etc. etc., doesn’t look like it should to begin with.

I always want to look around a bit, see what the rest of the slide looks like, look for those particular features of a malarial parasite that leave no doubt. In other words, I have a very difficult time deciding whether something is positive or negative on the basis of only one cell (unless the resolution is very good).

My other complaint is with the scoring. I find it ambiguous. When they say “Correct Positive Diagnosis 91%” does that mean 91% of the cells marked as positive were actually positive (false positives), or 91% of positive cases were identified (false negatives). For anyone trying to improve at the game, clarification on this is important.

Play MOLT on BiioGames

Of course I understand that the point is that people who are not experts, and not demanding in terms of excellent microscope optics and parasite features, can still get the right answer if there are enough people providing input. From that perspective, I think the game is brilliant, and I hope it changes the world.

Play the game on Biogames

Read the paper:

Mavandadi S, Dimitrov S, Feng S, Yu F, Sikora U, et al. (2012) Distributed Medical Image Analysis and Diagnosis through Crowd-Sourced Games: A Malaria Case Study. PLoS ONE 7(5): e37245. doi:10.1371/journal.pone.0037245

Do Mosquitoes Transmit Lyme Disease?

While it takes a blood meal, a mosquitoe might
transmit a disease-causing organism. Thankfully,
mosquitoes are not known to transmit Lyme disease.
 Image: US Department of Agriculture

We’ve known for years that Lyme disease is transmitted to humans by ticks. In Europe, it’s usually I. ricinus, the sheep tick, and any of a group of closely related organisms: Borrelia burgdorferi, B. garinii, or B. afzelii; while in my area it’s the deer tick, Ixodes scapularis, and B. burgdorferi. This is enough to worry about as the woods are full of deer and the deer are full of ticks. In some areas more than 30% of deer ticks carry Borrelia, and the ticks are not fussy: they’ll jump onto deer, dogs, cats, and people without hesitation. One hates to think that other biting arthropods could also be transmitting Lyme.

But studies going back as far as the 1980s, and perhaps even farther have found Borrelia in the guts of mosquitoes. Websites devoted to Lyme disease state that mosquitoes are transmitting the disease to humans. Why, then, does the CDC website say “There is no credible evidence that Lyme disease can be transmitted… from the bites of mosquitoes, flies, fleas, or lice” (Lyme Disease Transmission)?

Lyme Disease Organisms (Borrelia) in Ticks

It’s not a matter of a mosquito or tick sucking Borrelia out of one host and then simply injecting it into another like a flying (or crawling) syringe, not like pouring liquid from one glass to another with no change in the contents. Here we are dealing with interactions between living things. Research has shown that things happen in the tick, things that are important in transmission.

In the tick’s gut, Borrelia produces a protein that enables it to persist there for long periods of time, likely aiding survival until the tick feeds again. When the tick is feeding, the spirochete cuts back on this protein and produces a different one instead, one that enables it to invade the tick’s salivary gland and then be transmitted to the new host in the tick’s saliva.

Similarly, Borrelia is able to enhance a tick protein that protects both tick and spirochete from attack by the host immune system: “Borrelia burgdorferi, the Lyme disease agent, is critically dependent on the presence of the tick protein Salp15 when infecting the host” (Schwalie and Schultz). The extended time that a tick spends feeding (days) provides plenty of time for this interaction to take place.

Lyme Disease Organisms (Borrelia) in Mosquitoes

In contrast, while Borrelia has been detected in mosquito guts and saliva, it doesn’t appear to survive there very long, probably because the proteins that support it in ticks don’t work in mosquitoes. Salp15, too, is a tick protein that won’t be available to help out in a mosquito, and mosquitoes take only minutes to obtain a blood meal, compared to days for a tick. Put simply, mosquitoes are not competent vectors of B. burgdorferi; they just don’t have the right stuff. While it’s not impossible that a mosquito bite could contain the spirochetes, it’s unlikely, and it’s even more unlikely Borrelia would succeed in setting up an infection. Mosquitoes are not significant vectors of Lyme disease.



References

Fontaine et al: Implication of haematophagous arthropod salivary proteins in host-vector interactions. Parasites & Vectors 2011 4:187 doi:10.1186/1756-3305-4-187

Hovius, JWR. Tick-host-pathogen interactions in Lyme borreliosis. Dissertation, Academic Medical Center, University of Amsterdam 2009

Kosik-Bogacka D, Bukowska K, Ku?na-Grygiel W. Detection of Borrelia burgdorferi sensu lato in mosquitoes (Culicidae) in recreational areas of the city of Szczecin. Annals of Agricultural and Environmental Medicine 2002, 9, 55–57

Schwalie PC, Schultz J.  Positive Selection in Tick Saliva Proteins of the Salp15 Family. Journal of Molecular Evolution Volume 68, Number 2 (2009), 186-191, DOI: 10.1007/s00239-008-9194-1

Magnarelli LA, Anderson JF. Ticks and Biting Insects Infected with the Etiologic Agent of Lyme Disease, Borrelia burgdorferi. Journal of Clinical Microbiology Aug. 1988, p. 1482-1486

Toola, Sea Otters, and Toxoplasma gondii

Reports in March 2012 of the death of Toola, a Toxoplasma gondii-infected sea otter who lived out her days at the Monterey Bay Aquarium, reminded me of the threat that T. gondii poses to marine mammals. Toola suffered from neurological damage thought to have been caused by the parasite and required daily anti-seizure medication. Among other things, she was the poster otter for legislation and other efforts to protect marine mammals from various health risks. And she was cute too.

Sea otters frequent the California coast, where they may
become infected with T. gondii. The consequences can be deadly.
Image by Mike Baird, Morro Bay, USA. CC BY 2.0

How do Sea Otters Get Toxoplasma gondii?

My impression has been that the risk of acquiring T. gondii has been rising in marine mammals, and that this is likely to be the result of runoff – oocysts being washed off the land into coastal waters. This made sense to me when considering the number of feral and roaming domestic cats, and the quantity of cat feces that must be carried into coastal waters by runoff (this has actually been studied: “domestic feline faecal deposition in communities adjacent to Estero Bay was conservatively estimated at 107 metric tonnes/year, or 26 kg/ha:” Miller et al.) I was surprised; therefore, to read that the majority of California sea otters tested in the 2008 study reported by Miller et al had a unique strain (dubbed Type X) that is not typically found in domestic cats.

Rather, the paper by Miller et al. reports that Type X T. gondii was found in wild felids (mountain lion, bobcat) and foxes. While foxes might be doing relatively well in urban areas, the number of wild felids is down from what it must have been before humans covered the west coast of North America with concrete and asphalt. So if domestic cats aren’t to blame, why are there more infected marine mammals now than before?

Humans and Mollusks Spread Toxoplasma to Marine Mammals

One answer apparently lies in all that concrete and asphalt. Hardscaping of the coast reduces the amount of runoff that’s absorbed into the ground before it spills into the sea. In addition:

• Human development has reduced wetlands, which provide natural filtration for runoff.


• Bivalves such as mussels flourish near storm sewers and have been shown to filter organisms, including T. gondii oocycts out of the water and concentrate them in tissue.


• Sea otters feed on mussels and other bivalves, consuming at least 76 mussels each day.

Studies done on land mammals have shown that a single oocyst can potentially be the source of chronic toxoplasmosis. Given those odds, its not surprising that Toola, and lots of other California sea otters (and other marine mammals) are infected with T. gondii.

Read the paper:

Miller, M.A., W. A. Miller, P. A. Conrad et al. "Type X Toxoplasma gondii in a wild mussel and terrestrial carnivores from coastal California: New linkages between terrestrial mammals, runoff and toxoplasmosis of sea otters." International Journal for Parasitology: 38(11), 2008