Amboceptor

Microbiological, virological, bacteriological, immunological, medical, epidemiological, historical, anecdotal

Month: December, 2013

We have no fear of the coffee

If you’ve taken a microbiology class you probably learned how the bacterial pathogen known as “plague” still exists in the United States. It’s still virulent, but has degraded so far from its status as a civilization-toppling “black death” that it’s mostly associated with the undignified creatures known as prairie dogs.

Here’s something I didn’t know. Before the San Francisco Plague of 1900-04, plague was believed to be unknown in the Western Hemisphere. This was reviewed clearly and concisely by Elizabeth T. Anderson in an article called “Plague in the Continental United States, 1900-76”. (available here for free download (1))

From Anderson (1978), Plague in the Continental United States, 1900-76

From Anderson (1978), Plague in the Continental United States, 1900-76

The “Third Plague Pandemic” was largely an Asian phenomenon, killing millions in the Far East. In the 1890s the disease was ravaging Hong Kong, it reached India in 1896, and there was great concern in North and South America that it would arrive aboard a steamship. Anderson quotes the Surgeon General as saying at the time:

The appearance of the plague in Santos, Brazil, in October 1899 marks an important epoch in plague literature as furnishing the very first recorded instances of the occurrence of the disease in the Western Hemisphere.

In 1899 the inevitable happened. Ships with infected passengers arrived in Honolulu, New York City, and also Port Townsend, Washington. The latter two threats were eliminated via quarantine, but bubonic plague victims started to be seen in the Chinatown region of Honolulu. Authorities tried to control the illness by burning the houses of victims, which led to out-of-control fires that destroyed most of Chinatown.

So it was through San Francisco that the disease came to the mainland. The San Francisco plague was comprehensively mishandled in an effort to downplay the risks, including claims that it had been “eradicated” in 1904 which ignored the possibility that it had not been eradicated in rodents.

But it surely would have become endemic here at some point. Ever since then, there have been incidents of plague in North America, mostly in rural, dry areas. Like so many unfortunate things, it is now most common in Africa. See this review by Thomas Butler (2) for the present state of affairs.

The “plague-ship” that menaced New York was the J. W. Taylor, bringing a cargo of coffee from the previously-menaced Brazilian port of Santos. Here’s a Public Health Reports report (3) on how the threat was dealt with, written at the height of the crisis.

Immediately after the arrival of the ship in quarantine, and after the removal of the patients, the living apartments, cabin, and forecastle of the ship were most thoroughly disinfected by sulphur and corrosive sublimate solution, and all bedding, clothing, and textile fabrics, without exception, were subjected to the action of steam at a temperature of 230°F. for fifteen minutes, a perfectly safe and efficient process of disinfection.

The sacks have been so stowed upon the lighters as to admit abundant circulation of air and exposure to wind and sunlight during the day, and in addition have, during every night, been subjected to a temperature very near the freezing point, as there has been a heavy frost every night since the unloading was commenced. In addition to this thorough aëration, disinfection, and low temperature, it is the determination of Dr. Doty to keep these lighters in quarantine for a period of at least eight days before discharging them.

…The stevedores engaged in the unloading are kept in quarantine and are every night sent to Hoffman Island and brought back to their work in the morning. A careful watch has also been kept for rats, especially those dead; but 1 dead rat has been found and bacteriological examination so far would seem to indicate that he was a victim to the sulphur fumigation and not to plague. I should mention here that the hawsers securing the lighters to the ship are also guarded by large funnels of galvanized iron to prevent the passage of rats from the ship to the lighters.

From these passages, it becomes clear that the authorities had no desire to destroy the ship’s cargo. In fact, it was an insult to the brave people of New York to suggest that they were petrified of these sacks of coffee. Here’s an editorial from the New York Medical Journal, that concludes with an inspirational call to arms.

Let the cargo come to town!

plague-ship-1899

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1. Anderson ET (1978), Plague in the continental United States, 1900-76. Public Health Reports 93(3):297-301.

2. Butler T (2009), Plague into the 21st century. Clinical Infectious Diseases 49(5):736-742.

3. Geddings HD (1899). Plague on the steamship J. W. Taylor at New York quarantine. Public Health Reports XIV(49):2165-2167.

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The hygiene hypothesis, in fable form

Cleanliness and sterility are all well and good, and of course we don’t want to be surrounded by excrement and effluvia, but you know what? In this new century, when it’s all pasteurize this, and filter-sterilize that, and launder this, and have an inspector certify the soundness of that… well, you know, me and the old lady, we grew up on the farm, and we didn’t know from all this hygienic rigmarole the academic doctors endorse, and we just might have been healthier and heartier than youngsters today. A little dirt don’t hurt.

So here’s an odd little humor piece from Life magazine of February 25, 1904 (Volume XLIII, Number 1118, page 179), which medical men found so apt that it was re-printed in the Chicago Medical Journal, the Medical Fortnightly, the Mississippi Valley Medical Journal, the Indianapolis Medical Journal, the Eclectic Medical Journal, the Doctor’s Factotum, the St. Louis Clinique, the Cleveland Medical and Surgical Reporter, and the Philadelphia College of Pharmacy Alumni Report.

Happy New Year, symbolism of babies, and all that.

babies-life-hygiene

And while we’re at it, here’s an enlightening ad from the same issue of Life. Did you know that people who don’t drink beer seldom drink enough fluid of any kind? And that Schlitz is cooled in plate glass rooms? How has this wisdom been lost to the ages?

schlitz-beer-a-doctors-reasons

“But doctor, does my insurance cover Schlitz? Is there a generic available?”

Winter pandemic at the Winter Palace

From J. Lawrence-Hamilton (1893), Foul fish and fish fevers, Bulletin of the United States Fish Commission volume XIII: 311-334.

cholera-christmas-st-petersburg

Now that the long severe orthodox Russian church fast is almost over, I hope you’ve been careful at feast time when retrieving fish from your natural freezer sunk in the icy river. Remember, if you think the weather’s been mild enough to thaw the fish since you froze it, don’t take the chance. Stick with vegetables. No cholera outbreak has ever been traced to parsnips.

This epidemic in Russia lasted over a year and was reportedly the cause of death for the composer Tchaikovsky, among a hundred thousand others. Even in a frigid locale like Saint Petersburg, these things can happen with relatively warm conditions and no concern for the sanitary needs of the lower classes.

Christmas at the Winter Palace, 2011 (source: Xinhua)

Christmas at the Winter Palace, 2011 (source: Xinhua)

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For a PDF of the 1893 Bulletin of the United States Fish Commission, click here. J. Lawrence-Hamilton’s piece has also been encoded in HTML with a useful index, courtesy of Penobscot Bay Watch’s archive of New England- and Maritimes-related BUSFC reports.

The BUSFC has some interesting historical writing (“Notes on the History of the Fish-hook”; “The Fisheries of Japan”; “The Clam Problem and Clam Culture”), in addition to drier pieces such as “Vegetable Parasites of Codfish” and “The Propagation of Black Bass in Ponds”. This article, “Foul Fish and Fish Fevers”, merely mentions the St. Petersburg typhoid outbreak in passing, being quite an extensive collection of anecdotes about seafood-related disease of the past 1000 years, and the ways governments and guilds through the years have tried to enforce sanitary fishmongery.

Even the zoological pieces in the BUSFC can be quite readable, including “What We Know About the Lobster” (also 1893), by Fred Mather, Superintendent of the Cold Spring Harbor hatchery and editor of Forest and Stream magazine. This guy is hilarious.

A very natural question for a reader to ask … is: “Why don’t you retain the youthful lobster until it ceases to swim and settles down to crawling, and thereby stock a certain district in which your State, that pays for the work, is interested?” To this I should reply that in theory that would be the proper and most correct thing to do, but in practice we find that there is a factor that will not be left out of our calculations, and this factor is cannibalism.

There is, at present writing, no food for a larval lobster known to me that is as acceptable as another larval lobster that has just molted. I have tried to bribe them by hanging flesh of eel, clam, beef, lobster (adult), blue crab, and fiddler crab, but without avail; their love for their fellows which prompted them to take their brethren in out of the wet, lest they be devoured by small fishes, baffled my efforts… If each youngster could be placed in a tank or even a small compartment by itself, no doubt it would accept any, or all, of the foods named, but at present we are not prepared to feed a million or more individual lobsters in separate stalls for months before turning them out to shift for themselves. … They are fighters by nature, and when a lobsterman has a lot of adults in a floating car and a storm comes up each lobster blames his neighbor for any collision that may ensue and they engage in a general fight, which is not only disastrous to themselves but to the lobsterman, for lobsters are not marketable in fragments.

Merry Christmas!

christmas_lobster550

Data Update: Pox in rabbits, pox in mice

Here’s a paper by Frank Fenner (1914-2010), which compares quite a lot of different poxviruses to establish basic facts about their biology.

By 1958, when this was published, Fenner was already well known in Australia for his leadership role in releasing extremely deadly myxoma virus among the rabbit population. This was deemed to be worth the risk, as the creatures had for almost a century been locust-like in their consumption of Australia’s crops, only making themselves useful as a source of food during the Depression. In a prelude to fellow Australian Barry Marshall’s auto-experimentation with Helicobacter pylori, Fenner and two other experts infected themselves with myxoma to show that the risk to humanity was negligible.

Fenner F (1958). The biological characters of several strains of vaccinia, cowpox and rabbitpox virus. Virology 5(3):502-529. (abstract here: subscription required for full article)

This paper was an attempt to clear up the categorization of various poxvirus strains, mostly vaccinia virus. Fenner got colleagues around the world to provide samples of Mill Hill (V-MH), Williamsport (V-WILL), Pasteur Institute (V-PI), and other vaccinia isolates, which had been designated as either “dermal” or “neuro-” vaccinia based on whether they had been propagated in rabbit skin or rabbit brain. Were these categories practically useful? What strains of vaccinia, if any, were really typical of the virus?

The vaccinia strains were compared to the “Amsterdam” and “Brighton” variants of cowpox, and the “Utrecht” and “Rockefeller Institute” variants of rabbitpox. Rabbitpox is not the same as myxoma virus, by the way.

* * *

Frank Fenner inoculating eggs with virus in 1958. Source: Sydney Medical School

Frank Fenner infecting eggs. Source: Sydney Medical School

Also included in the comparison were “white variants” of certain virus strains. At this time culturing cell lines in vitro was not convenient. Lots of procedures, including growing virus, that we would now do with cellular monolayers in petri dishes were done in a system called the chorioallantoic membrane (CAM). The CAM is the membrane under the shell of an egg. Before doing any experiments on the various viruses, Fenner and associates made sure each virus was pure, by inoculating eggs and then extracting a single “pock” from the CAM for further propagation.

Often they would see that a virus that normally produced red, angry pocks had a few white pocks. Under further study, these “white variants” generally turned out to be milder than their parent strains, as a result of some genetic deletion. The white variants gave me some trouble in putting together the graphs based on Fenner’s data, because they are grouped with non-white strains that are far more virulent.

Sample chorioallantoic membrane pocks. 16a is the "white variant" of 16 (Rabbitpox Utrecht). 15a is the "white variant" of 15 (Cowpox Brighton).

Sample chorioallantoic membrane pocks. 16a is the “white variant” of 16 (Rabbitpox Utrecht). 15a is the “white variant” of 15 (Cowpox Brighton).

Let’s get to the data. After doing a bunch of CAM experiments, Fenner started infecting animals. He compared the viruses for their ability to kill mice and rabbits after brain infection, and induce skin lesions in rabbits after skin infection.

This table contains an immense amount of data, but it takes up two pages which is never a good thing. I think we can turn it into two good figures, one for mouse infection and one for rabbit infection.

fenner-table5

First of all, not all this data needs to be graphed. If you look at the last two columns, every rabbit skin lesion of more than 13 mm in diameter is considered “IPC”, and every smaller lesion is “N”. That’s all we need to know. Also, I don’t think it makes sense to list a mean survival time for experiments where almost every mouse survived. It’s a little sketchy to say that mice that never came close to dying had a “survival time” of 14 days, and then average that arbitrary number with actual survival times of mice that died. So I’ll drop the “mean survival time” data as well.

* * *

My mouse figure has two parts. I didn’t do any statistics on the data.

1A shows the relative virulence, which is a somewhat confusing metric that compares the LD50 (dose of virus at which half of infected animals die) with the virus’s ability to cause pocks on the egg membrane. All of the viruses grow pretty well in eggs, so this shows which viruses are particularly adapted to be dangerous to mice (or rabbits).

1B shows how many mice survived brain infection with each virus strain. Nowadays we would show survival curves for this – you know, the lines that always start out horizontal with 100% survival, and as the experiment goes on, the line goes down and down, stepwise, as mice succumb to mortality. But Fenner just shows the percent of mice that died during infection (probably this means the number that were dead after 14 days). I changed this to become a graph that shows the % of mice that survived infection.

Infect mice. (A)

Figure 1. Mice are more susceptible to neurovaccinia and rabbitpox than dermal vaccinia. (A) For each strain of virus, mice were infected intracranially with a range of doses, and the LD50 was calculated as the dose which was lethal to 50% of infected mice. LD50 values are normalized to the number of CAM pocks produced by the same dose of virus in eggs. Horizontal line represents the limit of detection. (B) For each strain of virus, mice were infected intracranially with 100,000 infectious particles. Here we show the percent of mice surviving to 14 days post-infection (sample size = 10). Bars with white stars represent “white variants”.

The rabbit figure has three parts.

2A is the relative virulence data again. This time it’s not the LD50, but the ID50. (Even though it says “LD50” in Fenner’s table, it says “ID50” in the legend and in the text.) “LD” means lethal dose, whereas “ID” means infectious dose. So this is the dose of virus at which half of infected animals show signs of infection. “Infection” in this case would be a skin lesion. He doesn’t say exactly how big a lesion needs to be before it’s considered “infection”.

2B is a similar graph showing the diameter of the lesions, in millimeters.

And then there’s a bunch of survival curves. 2D is too busy to be able to decipher each datapoint, with eight overlapping lines in a single graph, but what’s important is that there’s a huge difference between 2C and 2D.

rabbit

Figure 2. Rabbits are more susceptible to neurovaccinia and rabbitpox than dermal vaccinia. (A) For each strain of virus, rabbits were infected intradermally with a range of doses, and the ID50 was calculated as the dose which produced a lesion in 50% of infected mice. ID50 values are normalized as described in 1A. (B) For each strain of virus, rabbits were infected intradermally with 100,000 infectious particles. After 5 days of infection, the diameter of each skin lesion was measured with a ruler. (C-F) For each strain of virus, rabbits were infected intradermally with 100,000 infectious particles, and survival was monitored daily (sample size = 2-4).

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