If there was a celebrity cause of death of the last millennium, it was probably tuberculosis. According to an unsigned, but rather exhaustive inventory, matter-of-factly entitled "List of tuberculosis victims" http://en.wikipedia.org/wiki/List_of_tuberculosis_victims, which I fact-checked for two dozen or so names, it does seem likely that all of the following died of TB or its complications: John Calvin, Cardinal & Regent of France Richelieu, Saint Theresa and Saint Bernadette Soubirous of Lourdes, all of the Bronte sisters, Elizabeth Barrett Browning, John Keats, Eugene O’Neill, William Somerset Maugham, D.H. Lawrence, George Orwell, Alexander Pope, Washington Irving, Moliere, Sir Walter Scott, Laurence Sterne, Henry David Thoreau, Robert Louis Stevenson, Jean-Jacques Rousseau, Frederic Chopin, Igor Stravinsky, Anton Chekhov, Maxim Gorky, Simon Bolivar, President James Monroe, Eleanor Roosevelt, Alexander Graham Bell, Louis Braille, Immanuel Kant, Florence Nightingale, Baruch Spinoza, Ho Chin Mihn & W.C. Fields. But TB is scarcely a “dead disease. ” Every year over 9,000,000 new cases are reported and 2,000,000 die from it. (Das & Horton 2010, Lonnroth et al. 2010). This is in contrast to the numbers who died during the recent, much more highly publicized H1N1 misnamed “swine flu and/or bird flu” epidemic: 14,286, according to the European Centers for Disease Control & Prevention.
Who Gets TB Today?
While anyone can conceivably get TB today, the following are among the most likely victims today. Poor urban dwellers (Cantwell et al 1998) with a history of alcoholism (see, for example Mathew et al 2010) and smoking (see for example Silva et al 2010)……although neither poverty nor alcohol nor tobacco use cause TB of themselves). Recent immigrants to developed Western countries from underdeveloped countries in Africa, the Middle East & Central Asia, or South East Asia (see for example Buu et al 2010, Menzies et al 2010), where TB is much more common. Certain isolated indigenous peoples, including some Native American Indian tribes (Breault & Hoffman 1997) . Dairy herdsmen and slaughterhouse workers, veterinarians, doctors, nurses, dentists (see for example Cadmus et al 2010) workers and the very people who fight TB the most: Public Health workers (Hanscheid & Grobusch 2010, Jong Lee et al 2010, Ling & Menzies 2010). And just about anyone with HIV, particularly in Sub-Saharan Africa. TB hits children (Marais & Schaff 2010) and the elderly (Mori & Leung 2010) much harder than adults.
From What, Where or Whom Do They Get TB?
Well over 90% of TB is transmitted from person-to-person. In other words if you have been exposed to people who are in their active stage of TB, people whose levels of Mycobacteria tuberculosis bacteria are such that they are abundant in their sputum which is sprayed about mostly through coughing and sneezing, long enough or in the right close circumstances, you can contract TB. Single digit percentages of TB are contracted from animals or animal products: most commonly through consuming unpasteurized dairy products and occasionally red meat. The causative agent is Mycobacterium bovis (so-called bovine or zoonotic TB). (Chickens can get their own form of TB, but transmission of that type to humans is not common, although chickens can give it to cows, where it causes Johne’s Disease).
However, TB is an equal opportunity disease: people can get it from their relatives, their cows, dairy products, and even from wildlife, and can give it right back to the sources they got it from or their uninfected herd or pack mates (Rock et al 2009)! Humans can infect cattle, whose excreta infects wildlife (in the US mostly deer, in the UK mostly badgers, in Africa wild buffalos and wildebeest, and anything that eat the wildlife or the cattle, so that wolves, lynxes, lions can get it and give it back too through saliva and excreta.) Humans can transmit the bovine form just as well as they can the more common M. tuberculosis form to other humans or to animals, and animals can give humans either type as well. Indeed, the best theory of TB origins have it arising from mutations of very tough soil-born versions which became capable of infecting livestock which in turn infected herdsmen. North Africa, Europe and Asia seemed to have developed both human and bovine types before the disease spread to Australia or the Americas. Indeed, traces of TB have been found in wooly mammoth and ancient musk oxen and bison frozen remains and bones on both sides of the Bering Strait, with a trail running down through the west coast of the US (Rothschild & Martin 2006).
Given that TB seems so infectious, why don’t more people have it?
The short answer in the western world of North America and most of Europe, is that more people used to have it, but three developments halted its more rapid spread, and knocked down its numbers dramatically. First, TB patients were very often quarantined in sanatoriums, cutting down on further person-to-person transmission, although health care workers at those facilities even now have elevated chances. Second, dairy products overwhelmingly became sold to the public only after pasteurization – a heating process which kills the bacteria. Cows that tested positive for TB in their milk were often put down or successfully treated with antibiotics until the infection cleared and even the antibiotics that cured them also cleared from appearance in the milk. Third, a number of drugs were developed that knocked down or completely eliminated the Mycobacteria in both humans and livestock. A fourth factor is now clear: some people and animals have an unusual genetic propensity for resisting the disease, while others have heightened genetic susceptibility (Allen et al 2010).
Can’t people be easily diagnosed, take their medicines, and get cured?
The diagnosis of TB is usual done by a tuberculin skin text (the PPD) and/or chest x-rays. While the PPD is still usually quite reliable, it does give out a small number of false negatives and false positives. One reason for the false positive, is that foreign-born patients may have received doses of BCG vaccine, which triggers this result. These vaccines are commonly used in an attempt to prevent TB in Europe, Africa and parts of Asia, but owing to limited effectiveness, are rarely used in the US. Chest x-rays however, seem to be even less useful on close examination than were previously thought (Eisenberg & Pollock 2010), although they are still frequently required as a condition of employment, of attending college, or joining the military, a practice going back to the times of WWII. More sophisticated tests are constantly being developed, but most are more expensive and less widely distributed than their predecessors (see for example Chen et al 2010, Graham 2010, Idh et al 2010).
The real problem with medications is two-fold: Many patients are non-compliant because the course of drug treatment can be months long, and they start feeling better sooner than the mycobacteria are totally eliminated. Patients with the quiescent “latent” form of TB often have no symptoms at all, and only know that they have TB owing to a PPD test, and resent having being forced to take medications, particularly after they are reassured that they are unlikely to be able to give anyone else TB while the disease is in its latent stage……the problem is that a number of other medical crises can precipitate the development of active TB disease, and that they become quite infectious to others and very sick themselves. While many governments subsidize the cost of these medications, they are not always free. Furthermore, in western societies, many immigrants of uncertain legality are leery about complying with government agencies for fear that they will be deported (see for example Kulane, Ahlberg & Berggren 2010).
Perhaps an even larger problem is the development of resistance to standard drugs of choice like Isoniazid (INH) and Rifampin (RIF) and a few other analogues that have served us well for several generations. Multiple Drug Resistance (MDR -----resistant to two standard drug types ) and Extensive Drug Resistance (XDR ----- resistant to all four standard drug types) are becoming a problem for hundreds of thousands (Dheda et al 2010, Hasan et al 2010, Metcalfe et al 2010). Most of these patients will either become stabilized for short periods of time on ever more exotic combinations of drugs taken on a trial basis, with the hope that their disease reverts to latency. But many more will die.
What can be done now?
- Immigrants from countries where TB is endemic need to be screened using more sophisticated tests such as the QuantiFERON®-TB Gold (QFT-G), QuantiFERON®-TB Gold In-Tube test (QFT-GIT); and T-Spot®.TB test. They are only moderately more expensive and show good results (Idh et al 2010). These test must be administered with scrupulous oversight and integrity of recordkeeping in settings that include modern instrumentation (Nkengasong et al 2010). Patients who test positive should be thoroughly treated before being allowed to immigrate. The developed world to which these unfortunate people wish to move must underwrite the higher cost of better diagnosis and treatment as being in its own enlightened self-interest.
- As suggested by practical trials in places like Taiwan (Tsai et al 2010), paying patients financial incentives for compliance with long term drug treatments for latent TB may be more effective and cheaper than police pursuit or treating full-blown TB cases that emerge from untreated latent TB.
- Drug research into new anti-TB agents must continue apace. (see for example Patel, Khani & Rajani 2010).
- Research into treatments for AIDS is in many cases also preventive or concurrent for dealing with TB, so that advances in one almost always aid the other (Pathak, Wentzel-Larsen & Asju 2010, VanZyl-Smit et al 2010.
- Continued vigilance concerning Mycobacterium bovis in farm animals, farm products and wildlife, is a relatively low-cost means of holding down to about 60,000 deaths annually this form of TB. Providing the means for immunizing and treating animals and/or absolute guarantees of compensation for putting down infected animals are at this time the best that can be done, and barring a foolish abandonment of pasteurization and a generalized return to raw milk products, likely to succeed (see for example Wee et all 2010) and perhaps even reduce those numbers. For an exhaustive overview of this story see the forthcoming Hardin, Crandall & Stankus (2010).
- Fundamental research into the cooption of the host immune system and the drug resistance bacterial genetics of Mycobacteria will likely give us the best long term outcome, while we fight on public health and pharmacological fronts for now (Behar, Devangai & Remold 2010).
Tony Stankus FSLA [email protected] Life Sciences Librarian, Science Coordinator & Professor
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