Phantom Plague

From The Wall Street Journal:

In 1992, a blue-ribbon panel commissioned by the Institute of Medicine published “Emerging Infections: Microbial Threats to Human Health in the United States.” The report was a broadside aimed at the “complacency of the scientific and medical communities, the public, and the political leadership of the United States toward the danger of emerging infectious diseases and the potential for devastating epidemics.” A stream of like-minded books followed—Laurie Garrett’s “The Coming Plague,” David Quammen’s “Spillover.” But the risks were hard to calculate, and despite some near misses (including Ebola and SARS-1), the possibility of a new plague seemed remote from day-to-day life. The warnings went unheeded.

The Institute of Medicine report mentioned tuberculosis, which had started a resurgence by taking advantage of patients suffering from AIDS. In the years since, a chorus of voices has been gathering strength, warning us of a looming microbial threat that can seem as esoteric and far away as bat viruses once did: multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB).

Add Vidya Krishnan’s “Phantom Plague” to the chorus. Covid-19 is a new infectious disease, but old foes have not gone away. Antibiotic resistance by the tuberculosis bacterium represents a continuing evolutionary arms race between biomedical science and one of the great killers of all time. In the middle are millions of victims, mostly poor, caught in the ancient vice grip between destitution and disease.

Tuberculosis—“consumption,” the “white plague”—could rightfully claim to be the great infectious disease. Bubonic plague, smallpox and influenza were more explosive, but only malaria can contend with tuberculosis for the steady, relentless toll taken on our species. The keys to TB’s success are tenacity and stealth. Most of history’s notorious germs cause acute infection—short and dramatic. TB is one of a handful of really successful agents of chronic infection. It lurks inside the immune cells meant to protect us, then patiently grinds down its victims.

TB is primarily a disease of the lungs, spread via the respiratory route. It thrives where human hosts are crowded together in squalor. Probably no infectious disease has killed more humans throughout history, but as Ms. Krishnan vividly reminds us, TB is not a disease of the past. Up to one quarter of the global population carries the bacterium in a latent state. Every year, some 10 million people fall sick, and in 2020 more than 1.5 million died of a disease that is preventable and treatable. Indeed, the TB bacterium was the deadliest microbe on the planet before it was dethroned by SARS-CoV-2. It is a safe bet that TB will soon resume its place atop the rankings.

. . . .

As we have recently learned, the bacterium that causes TB has not existed time out of mind. Both ancient bacterial DNA recovered from archaeological skeletons and massive data sets of modern DNA are allowing us to piece together the hidden back story of TB (and so many other human pathogens). The TB bacterium is only 4,000 to 5,000 years old, a product of the Bronze Age. It emerged when humans first built cities and long-distance trade networks, and it has opportunistically thrived on human progress ever since.

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When bubonic plague, smallpox and typhus were brought under control, TB was left to claim a larger share of the victims. Children, especially of the working classes, suffered most. Thomas Malthus gave voice to the widespread recognition that the “closeness and foulness of the air” in places like London was especially “unfavourable to the tender lungs of children.” In the early 19th century, TB came to account for upward of one third of all deaths in industrial cities, an almost unfathomable share.

The decline of TB in the West was late but miraculous; accomplished between about 1870 and 1940, it has been the subject of one of the most resonant debates in the history of health. Mortality from TB was reduced thanks to a combination of three factors: improved living standards that liberated people from desperate poverty; public health measures (such as bans on spitting, a government-driven behavioral change that Ms. Krishnan colorfully narrates); and biomedical interventions (from the BCG vaccine to antibiotics).

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What makes Ms. Krishnan’s book worth the price of admission is the tableau she paints of the current plague. She writes with authority about the current state of TB globally, especially in her native India, which is the epicenter of the disease today. A 20-year veteran of medical journalism, Ms. Krishnan is a powerful storyteller, and her accounts of frustration, suffering, grief and resilience are moving.

There is the case of 11-year-old Piya, whose ankle bone was infected with an extensively drug-resistant form of tuberculosis. Her disease presented as a limp, which eventually led to a diagnosis that upended the lives of everyone in her family. For Piya, it meant a daunting regimen of ineffective pills that turned her teeth yellow and her face flush red. The side effects only added to the stigma and shame of the disease itself. Meanwhile, she had to undergo excruciating debridement surgeries, in which infected tissue is scooped out. Fortunately for Piya, her plucky father flew to Tokyo and managed to arrange an audience with Otsuka, the Japanese pharmaceutical company that sells delamanid, one of the two relatively new drugs used to treat the hardest cases. Against the odds, he was able to have his daughter qualified for a compassionate-use case, and she has recovered.

Link to the rest at The Wall Street Journal (PG apologizes for the paywall, but hasn’t figured out a way around it.)