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Treatment

Until the discovery of antimicrobial drugs, there was no effective treatment for TB. Most of the drugs used to treat TB today are chemical antimicrobials rather than antibiotics. Antibiotics are gathered from micro-organisms, while chemical antimicrobials are produced in the chemistry lab. The two antibiotics are streptomycin and the rifamycins. The rest are chemical antimicrobials. Isoniazid is the most effective and seems to be the easiest to make. Pyridine is necessary to produce isoniazid. Today pyridine is produced with petrochemicals, while in the past it was produced from coal tar, which is available in the 1630s. There may not be enough pyridine produced for industrial users, but there should be enough for medical chemical production. While I was unable to find any references to whether chloramphenicol is effective in treating TB in people, the antibiotic can be tested on those with TB disease. Most anti-TB antimicrobials eventually produce resistant strains of bacilli when used alone in the treatment of diseased individuals. They don't cause resistance when used as a preventative or as a treatment for latent (inactive) infection. Luckily, isoniazid treatment takes much longer to produce resistant TB bacilli, so it can be used alone for a time. If chloramphenicol is effective against TB, it can be used in combination with isoniazid as the first line treatment of the disease. That will take some pressure off those trying to develop a second drug to use with isoniazid. Thioacetazone seems to me to be the most likely candidate as a second drug. It was produced by Bayer in post WWII Germany with limited production facilities. Other chemical antimicrobials are PAS, ethambutol, and pyrazinamide.

Discussion

Mitigation of the Great White Plague of Europe is not going to be easy. It is going to take decades, rather than months or years. The elimination of TB is going to take centuries if what has happened up-time is any consideration. I certainly don't presume to have all the answers. Smarter, more knowledgeable people than me are still trying to control TB in this century. Today up to one-third of the world's population has been infected with TB. The good news is the leaders in the fight against TB know what needs to be done. The bad news is that gaining compliance with control measures has been-and still is-an uphill battle. Our down-timers have an advantage over those left up-time: they have a huge head start in the fight against TB. They can see how others triumphed and how they failed, building on the past successes. They can build programs that are more likely to get local compliance which is absolutely essential for the programs to succeed. There are forward looking universities in Jena and Padua to work with them.

I am an optimist. I see control and prevention of TB moving outward in concentric rings from Grantville and places that accept help and knowledge from Grantville until the epidemic is finally controlled in a future decade or century. I see breakthroughs coming from downtime scientists in the coming decades and centuries. What will you do to help blunt the effects of the Great White Plague?

Bibliography and References

Daniel, Thomas M. Captain of Death: The Story of Tuberculosis.University of Rochester Press. 1997. ISBN 1-58046-070-4. Print.

Ryan, Frank, MD. The Forgotten Plague: How the Battle Against Tuberculosis Was Won – and Lost. Little, Brown and Company. First published in the UK as Tuberculosis: The Greatest Story Never Told. 1992. ISBN 03-316-76381-0. Print.

Dormandy, Thomas. The White Death: A History of Tubewrculosis. New YorkUniversity Press. 2000. ISBN 0-8147-1927-9. Print.

Kleeburg, H.H., DMV. "Tuberculosis and other Mycobacterioses." Diseases Transmitted from Animals to Man.Eds. William T. Hubbert, DVM, MPH, Ph.D. William F. McCulloch, DVM, MPH. Paul R. Schnurrenberger, DVM, MPH. Charles C. Thomas – Publisher. 1975. ISBN 0-398-03056-1. Print.

http://www.bikupan.se/tuberculosis/tuberc.html

Puranen, Bi. Tuberculosis: The Occurrence and Causes in Sweden 1750-2000. 2003. Web article.

http://hektoeninternational.org/Schwartz_TB.htm

Schwartz, Mindy A. "Tuberculosis – A Journey Across Time". Hektoen Internationaclass="underline" A Journal of Medical Humanities. Volume 1, Issue 4. August 2009. Web article.

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract amp;ProduktNr=224278 amp;Ausgabe=226544 amp;ArtikelNr=29220

Herzog, H. "History of Tuberculosis". Respiration: International Journal of Thoracic Medicine. Volume 65, No.1, 1998. Web article.

http://onlinelibrary.wiley.com/doi/10.1111/j.1863-2378.2009.01265.x/pdf

Fetene, T., Kebede, N., Alem, G. "Tuberculosis Infection in Animal and Human Populations in Three Districts of Western Gojam, Ethiopia". Zoonoses Public Health. 58. 2011. Web article.

http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.04.07_BOVINE_TB.pdf

"Bovine Tuberculosis". OIE Terrestrial Manual 2009. Web publication.

http://www.cdc.gov/tb/

Centers for Disease Controclass="underline" Tuberculosis. Web.

http://www.who.int/topics/tuberculosis/en/

WHO: Tuberculosis. Web.

http://www.nlm.nih.gov/medlineplus/tuberculosis.html

MedLine Plus: Tuberculosis. Web.

http://en.wikipedia.org/wiki/Tuberculosis

Wikipedia: Tuberculosis. Web.

http://en.wikipedia.org/wiki/History_of_tuberculosis

Wikipedia: History of Tuberculosis. Web.

http://en.wikipedia.org/wiki/Tuberculosis_treatment

Wikipedia: Tuberculosis Treatment. Web.

http://en.wikipedia.org/wiki/Isoniazid

Wikipedia: Isoniazid .Web.

http://en.wikipedia.org/wiki/Bacillus_Calmette-Gu%C3%A9rin

Wikipedia: Bacillus Calmette-Guerin. Web.

http://tuberculosis.emedtv.com/tuberculosis/tuberculosis.html

EmedTV: Tuberculosis. Web.

http://www.emedicinehealth.com/tuberculosis/article_em.htm

Emedicinehealth: Tuberculosis. Web.

The New Royal Touch: Synthesis of Anti-TB Drugs

Iver P. Cooper

This "mini-article" is intended to supplement Brad Banner's "The White Plague" article by providing some hopefully informed speculation as to how, and how soon, various anti-tuberculosis drugs might become available in the 1632 universe.

The chemists in Grantville have access to only a minute fraction of modern chemical literature. I have tried to reconstruct what can be figured out from "Grantville Literature" alone; sources that I deem to be so available are marked with *, and maybes with **.

Mycobacteria are nasty; a cure usually requires treating the subject for several months. If you try to eke out a limited supply by using a short drug course, you will be breeding drug-resistant strains, not curing your patients. Moreover, since the critters are quick to develop drug resistance, it's de rigeur to treat with a combination of two structurally unrelated pharmaceuticals.

My proposed availability is based on a subjective evaluation of synthetic difficulty relative to the canonical DDT (June 1633), chloramphenicol (September 1633), sulfanilamide (winter 1633-34), hexachlorobenzene (same), and coal tar dyes (1634), given the limitations of Grantville Literature. See Cooper, Industrial Alchemy, part 3 (Grantville Gazette 26).

Production of Selected Drugs

Isoniazid. This was first synthesized in 1912, by two young chemists pursing dissertation research (Ryan 359). Isoniazid is a derivative of pyridine. Pyridines make up about 0.01% of coal tar (KO 20:661) and the coal tar pyridine derivatives include the 2-, 3- and 4-methyl picolines (*M amp;B 1083). A chemist would know that pyridines are bases (*M amp;B 1087) and would therefore consider purifying them from coal tar by acid extraction, neutralization of the acid with inorganic base, and fractional distillation or crystallization. Limited characterizing data (melting point, boiling point, refractive index, optical rotation, solubility) is available (*MI, *CRC).