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This question originally appeared on Quora. Answer by Drew Smith, former R&D director at MicroPhage and SomaLogic.

From a North American perspective, the threat of tuberculosis is grossly underappreciated.

TB was rampant in the United States in the 18th and 19th centuries, and was typically among the top three killers of the population at large — estimates range as high as 1 percent of the population per year[1].

TB began a steep decline in the middle of the 19th century, even before the discovery of the Tubercle bacillus.

Many other infectious diseases followed a similar trajectory through the 19th and 20th centuries as clean water reduced disease transmission; vaccines rendered populations immune; and antibiotics cured what clean water and vaccines did not prevent.

But TB is different. Unlike many other deadly infections, it is spread person-to-person, not through food or water (although Mycobacterium bovis can be spread through milk). Vaccines and antibiotics have played only a minor role in the control of TB in North America, as death rates dropped a hundred-fold before their availability.

The truth is that we do not really know why TB deaths declined so precipitously in the 19th and 20th centuries. Several theories have been advanced, of course: public health measures in the form of quarantines and milk pasteurization[2], general betterment of living conditions (the McKeown Thesis)[3], and — because death rates were so very, very high — natural selection[4].

If modern medicine has effective means to control TB incidence and mortality, then these discussions are principally of historical importance. But unfortunately, we still don’t know how to control the spread of TB except through effective treatment of active cases [5]. If treatment begins to fail, then we are left with no sure means of stopping TB.

For this reason, the spread of drug-resistance in TB is a much greater threat than the spread of drug-resistance in other bacteria. Even if completely untreatable strains of S. aureus, E. coli, Klebsiella, Pseudomonas and Acinetobacter arise and become more common, we can limit the damage with better public health measures and better hygiene in hospitals.

But if MDR TB continues to spread, we may reach a tipping point where it is completely uncontrollable. The treatment of MDR TB is expensive and arduous and completely beyond the capacities of the health systems in many limited-resource settings [6]. Unlike other antibiotic-resistant bacteria, MDR TB strains tend to be highly virulent and are quite capable of infecting otherwise healthy people. If large numbers of MDR TB patients are inadequately treated, these strains could spread rapidly through entire populations, particularly in mega-cities with high human densities.

And if this happens, there is no credible fallback plan. We cannot quarantine millions of people. Cleaner food and water will not stop TB. The efficacy of the BCG vaccine is only about 50 percent [7], well below the level required to create herd immunity.

We cannot expect TB to become less deadly over time. Most diseases tend to become less virulent in order to facilitate their spread. But there is a good argument that TB tends to become more virulent in crowded conditions [8].

I regard most warnings of the coming antibiotic apocalypse to be click-bait hype [9]. To be sure, the spread of resistance in S. aureus and various Gram-negative organisms is a serious concern. These bugs are already killing tens of thousands of Americans, and might conceivably kill hundreds of thousands if we are extraordinarily stupid and neglect to take the many feasible steps available to control them.

But these infections largely victimize old people. Few productive careers or young families are destroyed by MRSA or CRE infections. TB, by contrast, is a disease of young adults. A TB epidemic would have the capacity to disrupt society and civilization in ways that we have forgotten are even possible.

With only a few hundred deaths per year in the U.S., TB is not a trending health topic. MRSA, MCR-1, and Zika are seen as much greater threats. We may have forgotten TB, but it has not forgotten us, and we ignore it at our peril.

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