h2g2 The Hitchhiker's Guide to the Galaxy: Earth Edition

Hi

I'm currently writting a guide entry on syphilis, A2890235 and I want to include the microbiology of T pallidum, I've already done a little, but I would like some more, if you'd be able to help I'd be really gratful.

I'd also like to include Lyn Magilis theroy that eurkaryotic fagellae evolved from Treponema..

Heya Z,

Sorry I took so long to reply - I've been horribly busy (and am about to get even more so). Sure, how much do you need for the microbiology part of T. pallidum? I'll look up the Lynn Margulis thing... I *think* it's in Microcosmos, but it's been yonks since I touched the book.

Cheers,
Far.

Sorry it took so long to get back to you

Whatever you can write about this would be great, I'm looking for about two paragraphs on it.



Z

Hiya Z,

Sorry I took so long! But anyway...

Treponema pallidum

The bacteria Treponema is a spirochete, a long, slender, gram-negative bacteria whose cell is curled in a helix not unlike a spring. First detected in 1600 by Anton van Leeuwenhoek, the first man to ‘discover’ unicellular microorganisms, these special microbes are set apart from the rest of the bacterial world by their unique shape and unusual method of motility, relying on a number of flagella-like organelles called axial filaments (which wrap around the cell and are enclosed inside an outer sheath within the periplasmic space of the cell wall) anchored to each pole of the cell which rotate and propel the bacteria forward like a corkscrew.

There are 13 species of Treponema recognized by Bergey’s Manual of Systematic Bacteriology (Vol. 1). Ten are anaerobic (they live in non-oxygenated environments), and the remaining three are microaerophilic (require small amounts of oxygen to live) or aerobic. Of these, Treponema pallidum has the dubious honour of being the most famous, being the bacteria responsible for the most notorious sexually transmitted disease in the history of mankind.

Three subspecies of Treponema pallidum exist: Treponema pallidum subspecies pallidum, T. pallidum subspecies pertenue and T. pallidum subspecies endemicum, distinguishable by the manifestations of the diseases they cause. T. pallidum subspecies pallidum is generally the only one attributed to syphilis, although there are microbiology experts who assert that the yaws-causing subspecies pertenue is actually only a variant of subspecies palldium in that it is less virulent and causes different clinical symptoms, as these two subspecies are 100% similar in their DNA/DNA profile. Unfortunately for patients, the existing molecular diagnosis methods are unable to differentiate between these two subspecies, resulting in rather embarrassing problems and, among Muslims, a rather sticky mess.

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In addition, I compiled some other facts that you may or may not want to use for your article:

Historical timeline

1495: (you already have this)
1530: (you already have this)
1600: Anton van Leeuwenhoek, a Dutch merchant and minor city official, observes and draws cells seen through his 300x microscope, including one strange corkscrew shaped one taken from tooth scrapings (later identified as T. pallidum).
Mid-19th century: Mercury was introduced as a cure for syphilis.
Between 1905 and 1910: Schaudinn and Hoffman identify T. pallidum as the causative agent of syphilis.
1910: During the attempt to find a cure for sleeping sickness (caused by trypanosomes) Paul Ehrlich and Sahachiro Hata discover that compound number 606 (arsephenamine), while it was unable to eliminate Trypanosoma, was effective at destroying T. pallidum. Ehrlich named this arsenic-containing compound ‘Salvarsan’.
1913: Dermatologist Henry Pulsford discovers that salvarsan contains highly toxic levels of arsenic.
1914: Henry JF Wallhouser’s studies show that salvarsan is only effective at curing early-stage syphilis; in later stages it damages the patient’s organs and tissues.
1928: Alexander Fleming discovers penicillin, the Magic Bullet.
1945: Penicillin becomes the drug of choice for curing syphilis.
1998: The genome of T. pallidum is completely sequenced.

The clinical significance of syphilis

The number of syphilis cases in a large number of countries has been on the rise in recent years. In 1999 a total of 12 million new cases were reported worldwide, more than 90% of them occurring in developing countries, and with a rising trend in eastern Europe, most notably in the former Soviet Union where it has soared from 5-15 per 100,00 in 1990 to 120-170 per 100,00 in 1996. Hot spots in the Western Pacific include Cambodia, Papua New Guinea and the South Pacific. In stark contrast, the number of cases in Western Europe has declined over the last half of the 20th century to rates of 5 per 100,000 people in most of the countries.

Although the trend has been decreasing in the United States, nevertheless reports have shown that syphilis remains a significant venereal disease. There was an overall incidence increase of 75% from 1985 to 1990, the resurgence generally blamed on the increase of drug abuse associated with a trade of sex-for-drugs and concomitant infection with HIV. The number of cases in the US rose to 81,000 in 1994; this number dropped over the next 8 years to 32,000 cases in 2002. however, between 2001 and 2002 the number of primary and secondary syphilis cases increased 12.4% to 6,862 cases (most of these cases occurring in persons between 20 and 39 years of age; although the female age group is significantly lower than the male).

Diagnosis

Because Treponema pallidum cannot be cultured on artificial media, it both defies Koch’s postulates and prevents simple laboratory stain identification methods. The most common diagnostic method for syphilis is serological testing, which can be divided into non-treponemal tests (which cover a broad range of sexually transmitted diseases, and are targetted at antigens in the lipid layer of the microbes) and Treponema-specific tests. These tests are relatively inexpensive, simple to perform and generate rapid results, and are generally used to monitor disease activity; however, Treponema-specific tests are not completely specific because they can also detect other disease-causing spirochetes (such as Leptospira and Borellia burgdoferi), thus giving false positive results.

A direct examination for spirochetes in positive samples may also be carried out by means of a microscopic darkfield examination or by direct fluorescent antibody tests. However, oral cavity specimens cannot be used for this method because nonpathogenic species of Treponema are common flora of this region.

Other traditional laboratory tests include cerebro-spinal fluid analysis (as spirochetemia will cause Treponema to be seeded in the CNS of as many as 40% of patients) for evaluating seropositive patients displaying neurological signs and symptoms; and a complete blood count (which will detect anaemia, thrombocytopaenia and either leukopaenia or leukocytosis characteristic of syphilis).

Because congenital syphilis involves various bone sites including the joints, long bone radiography may be used to detect lesions in these bones.

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Alternative medication for penicillin-sensitive people:

Doxycycline and tetracycline for non-pregnant females with no evidence of neurosyphilis.

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References:

Shimeld, Lisa Anne. 1999. Chapter 22: Spirochetes. IN Essentials of Diagnostic Microbiology. Delmar Publishers, New York.

Wallhauser, Henry T. "The Introduction of "606" in New Jersey." IN New Jersey Medicine: The Journal of the Medical Society of New Jersey 94:7 (Jul. 1997), 43-46.

Disease Watch: Syphilis. http://www.who.int/tdr/dw/syphilis2004.htm

Global Prevalence and Incidence of Selected Curable Sexually Transmitted Infections: Syphilis. http://www.who.int/docstore/hiv/GRSTI/005.htm

Syphilis. http://www.emedicine.com/ped/topic2193.htm

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I'm fairly busy right now, but when I've the time I'll go hunting around to see if maybe there aren't any additional facts that you might want.

Crap! I just realised that I made a major blunder. In the 'Diagnostic section' the non-treponemal tests detect lipids released into the serum by cells *damaged* by syphilis infection. Sorry. Next time I should proof-read my own stuff. Anyway, aside from detecting other spirochetes, these serology tests may also generate false positive results for pregnant women, patients suffering from acute febrile illness, those using intravenous drugs and people following immunisation programs.

Addition to the History section: Because T. pallidum is an extremely sensitve microbe and can be easily killed off with heat, drying, and simple soap-and-water, there was a treatment introduced in the early 1900s called the 'fever box' whereby patients were placed in a closed box in the hot sun (with only the person's head out) to raise their body temperature (as the disease was found to be treatable by this method). Ghastly....

Thanks I'm just updating it now, and I'll co-credit you of course.

Why does the inability of a test to distingish bettween syphilis and other Treponomea infections mean that it's a sticky mess for Muslims

These serology tests may also generate false positive results for pregnant women, patients suffering from acute febrile illness, those using intravenous drugs and people following immunisation programs.

Is that both non-treponemal and treponemal tests?

Hi Z,

1. Because extramarital sex and nonmarital sex are punishable by their law, in their own special court (called the Syariah). Here's a story my lecturer told us: one of her friends was Muslim, and when he applied for this job (I can't remember what) he was required to take a series of health examinations. To his anguish he tested positive for syphilis, and was in danger of being reported. Then his doctor decided to do a little extra work and research this guy's medical history -- and found out that, as a child, the fellow had suffered from yaws! So much for test specificity.

2. The second set of false positives is for the nontreponemal tests.

*waves*

I've added the information you gave, and am busy adding other things that people have suggested in Peer Review.

And co-credited you, of course.



Z

Thanks! I'll pop over to have a read when time becomes available (right now I'm up to my eyebrows removing those bl**dy smart quotes from an article).

BTW I read that bit where Pinniped said, 'You seen Farlander's epic on the FP today? Now that's what I call the ideal length for a morbid Entry.' One day, if I should ever publish any of my non-fic, that will be a quote I shall include.

Hey, I just remembered that you wanted Lynn Margulis' theory that our common ancestor was the spirochaete. Now I don't know where on earth you're going to bung that in the article, but I thought you might want to read the original passage before incorporating it into the article, so I shall just quote the passage verbatim:

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Close study of undulipodia - tiny cell whips on many kinds of cells with nuclei - shows an amazing uniformity of structure across a vast array of organisms. These supple filaments have traditionally been called flagella if they are long and few like sperm tail, or cilia if they are short and many like hairs, but there is no basic difference between them. Nearly all algae, ciliates, and slime molds - that is to say, protists, the earliest organisms with nucleated cells to have evolved - have them. Their whipping or waving motion propels a free-swimming cell through its medium or, if the cell is fixed in place, moves particles past it. From the sperm of a male fern to the lining of a mouse's nostrils, many cells of complex organisms sport these undulating organelles.

No matter what cell or organism they adorn, undulipodia are all about a quarter of a micron in diameter, and in cross section show a telephone dial-like circle of nine pairs of minute microtubules surrounding another pair in the centre. This pattern, known as the 9+2 array (strangely, since 'nine' refers to the pairs in the outside circle while the 'two' refers to each individual tubule of the centre), is found in the sperm tails of bulls, of whales, and of ginkgo trees; in the cilia of our lungs, windpipes and oviducts and those of other mammals; in the antennules of lobsters; in the cilia that cover that familiar protist, the paramecium; and in those on zoospores of water molds. Indeed this is just a tiny sampling of the presence of these 9+2 patterns.

Further, an undulipodium invariably grows out of a structure called a kinetosome which is composed of nine triplets of microtubules arranged in a circle. The walls of all these microtubules contain two related proteins, alpha and beta tubulins. Nearly two hundred proteins, including an extremely complex one called dynein, make up the rest of the 9+2 structure. Many of the nontubulin proteins have not yet been isolated or named, but the combined evidence is so conclusive that all evolutionary biologists believe these 9+2 structures could not have evolved separately in protists, plants and animals. (Since fungi, although they always lack undulipodia, do have their component microtubules and tubulin proteins, it seems likely that their ancestors had cell whip but lost them). There was, rather, a common origin.

Our candidate for this common ancestor is the spiralling, motile, hairlike spirochaete, the fastest bacterium in the microcosm. In the sticky regions of their microworld of gelatinous muds and viscous fluids, spirochaetes are often the only bacteria capable of passing through a certain region. The spirochaete's metier is motion. Some spirochaetes even contain microtubules, although none, so far, have been found arranged in a telephone-dial array. To us the evidence strongly suggests that ancient pacts were made between the early bacterial confederacies that became cells with nuclei and spirochaetes or spirochaetelike bacteria. Spirochaetes hovered both inside and outside their nonspirochaete neighbours, and in the end they provided efficient movement for those who had never even requested it. Of course this is just a hypothesis, but it aids in the explanation of otherwise disparate data. As Darwin said in 1859 in The Origin of Species regarding his theory of natural selection:
Anyone whose disposition leads him to attach more weight to unexplained difficulties than to the eplanation of a certain number of facts will certainly reject my theory." The same holds true for the spirochaete hypothesis. It may seem bizarre, but it explains so many facts that the story of the microcosm, of the evolution of sex and meiosis in the so-called higher organisms, suffers without it.

- Lynn Margulis and Dorion Sagan. 1986. The Symbiotic Brain. IN Microcosmos: Four billion years of microbial evolution. University of California Press.