Excerpt: The Phantom Plague by Vidya Krishnan

The HIV epidemic was a rude awakening.

Suddenly there was a realization that TB was a grave crisis. HIV, because it compromised immunity, liberated the latent TB. The logic was inescapable: any widespread epidemic that adversely affected immunity had the capacity to make latent TB into an active and deadly killer.

In Mumbai, TB is everywhere and nowhere. Spotting the bacteria is not unlike spotting a tiger in a jungle— while glimpses are uncommon or fleeting, there are fresh prints that show a predator is lurking nearby. You don’t have to walk into hospitals to find it. You see it in spit stains all over the city, in the unprotected coughing and sneezing in crowded buses, in tightly packed ghettos. Today, India is a moist “nation of spitters.”

The spread of TB is extensive. And it is extensively denied.

In India, these medieval tools are wielded by an army of science-deficient doctors for a government with scant respect for science, each piling errors on errors.

According to the WHO, the first case of extensively drug resistant tuberculosis was reported in 2006 in Italy.1 In 2009, fifteen TB patients in Iran were diagnosed with the same strain.2 In December 2011, Mumbai doctors reported four patients, and a few weeks later, the Times of India reported eight more cases in Mumbai. The WHO took a while, as is customary, before settling on calling it XDR TB. Meanwhile, scientists in different parts of the world were using new terms like “XXDR TB,” “super XDR TB,” and “totally drug-resistant TB” (“TDR TB”) interchangeably.

In Mumbai, Dr Udwadia was calling it TDR TB.

He had treated the four patients in 2011 and, methodical as he is, wrote a paper about the new, untreatable avatar of TB. He and his colleagues called the strain TDR TB, the term coined in 2009 by Iranian doctors who had treated the fifteen patients showing no response to the first- and second-line antibiotics. Dr Udwadia’s paper warned of an antibiotic apocalypse, when there will be no drugs known to modern medicine that could cure these emerging strains of the bacteria.

The Indian government did not like the prognosis.

It raided his lab, seized the patient samples, and pressured Dr. Udwadia to retract the paper. The NTEP did everything it could to sweep this piece of bad news under the rug. The tidal wave of bureaucracy rolled over the unimpeachable scientific evidence and once again drowned the science out in the twenty-first century as it had in the nineteenth. The Indian government’s response to new data on TDR TB had the same hallmarks of ignorance and arrogance that Ignaz Semmelweis dealt with.

Dr Udwadia has spent years speaking up to an increasingly unreasonable government.

He has a skeptical squint and a wry smile that redoubles the sense of skepticism. “They came down on us like a ton of bricks. Their first response was denial. Their second response was to take away our samples,” remembered Dr Udwadia, still surprised at the government’s reaction, years later.

He and his employers at the Hinduja Hospital were accused of spreading panic by using the term “totally drug resistant.” The Indian government argued that no such term had been approved by the WHO. Then, the NTEP dismissed his findings because the Hinduja Hospital’s laboratory — one of the finest in the country — had not been accredited by the government. So, their word could not be taken seriously. The government refused to investigate any further. But global media was starting to cover the story, so the ministry needed to be seen to run their own tests. “Literally, they seized culture from our laboratories. They took them for cross-checking,” says Dr Udwadia.

His epic struggle against TB and the Indian government’s vast labyrinth of bureaucracy was reported in the New York Times in September 2016.

***

The study in which actors were trained to walk into a doctor’s clinic with every red-flag symptom of TB has since been replicated in three other countries: South Africa, China, and Kenya. The “patients” all report a persistent fever and cough for two weeks, the first red flag. Then they follow a set script:

Regular Jane Doctor: Do you have cough with phlegm?

RJ Actor-Patient: Yes.

Fever?

Yes.

Weight loss?

Yes.

Loss of appetite?

Yes.

This is the textbook definition of a patient who should be screened for a TB test. In all the participating countries, the study discovered three alarming failures:

1. Most doctors could not correctly diagnose TB patients.

2. Even if they did, they did not correctly treat them.

3. Without proper medical guidance, the patients—all falling through the cracks of the health-care system — continued to infect their loved ones.

The number of undetected TB cases is genuinely alarming. Within global health, this problem has come to be known as “the missing millions.” According to the WHO, in 2019, 10 million people fell ill with TB. Only 7.1 million were picked up by national TB treatment programs. So 2.9 million were either undetected or unreported.

You cannot treat what you cannot diagnose.

The study found that across all four countries — India, South Africa, China, and Kenya — only 35 percent of the actor-patients were “correctly managed.” To begin with, researchers had set a low bar for the definition of “correctly managed.” “If the doctor referred the patient to another doctor or referred her to a government hospital — instead of screening her — we accepted it as a ‘correct diagnosis.’ We accepted any screening test they recommended as well — x-rays, sputum smears, and Gene Xpert. It was broadly defined,” Dr Pai told me in a Skype interview.

Even using this lenient definition, only one in five actorpatients was correctly managed. In Mumbai, 37 percent of patients were correctly managed, Nairobi 33 percent, rural China 28–38 percent, and South Africa, the “best” performer, 43 percent.

At this stage the study team was not looking at what was being prescribed but simply trying to see if doctors could diagnose TB correctly. The treatment, when it was recognized as necessary, often compounded the problem: “What they [doctors who’ve correctly diagnosed their patients] end up doing is, hit them with multiple rounds of broad-spectrum antibiotics.”

Basically, the few patients who are diagnosed correctly are carpet-bombed with powerful antibiotics, cough syrups, steroids, and antihistamines to see what “works.” Doctors, especially those in the private sector, were throwing a bunch of pills at the bacteria, found Dr Pai. “An average prescription has four to five pills, and the doctors say come back in two weeks if it doesn’t get better,” Dr Pai told me in 2019.

Only 10 percent of the actor-patients were referred to specialists, as they should have been immediately. “The job of the primary care doctor seems to be to retain the patient. At this stage, referral is practically dead,” the study concluded.

The hellish cycle of misdiagnosis can last for weeks as the patient is bounced from one doctor to another, feeling increasingly worse: “In most parts of the world, TB is only diagnosed after about three rounds of this. . . . Patients start with pharmacy, go to traditional medicine, switch to allopathy, change doctors,” Dr Pai told me.

Thanks to the study, we now know it takes a TB patient an average of sixty days and a minimum of three doctors to receive correct treatment. During this diagnostic delay, patients are actively infectious.

Government hospitals at least keep records.

India is, not coincidentally, home to one of the largest unregulated private sectors in the world, a vast and unregulated mess whose raison d’être has been to undercut the government-run, taxpayer-funded health system.

In April 2019, Dr Pai described the discrepant numbers regarding undetected or unreported TB to an audience at the London School of Hygiene and Tropical Medicines: “The missing could either be because they are walking around, undiagnosed. Or they are seeking care at pharmacies, or at private clinics. My hunch says that the missing patients are diagnosed but not reported. The countries with the most privatized health care are not only the ones with the largest patient burden but also the ones with the most missing patients. There is a clear correlation between private care seeking and the missing millions. That’s why working with the private sector is so critical, especially for India,” explained Dr Pai.

Global TB experts, including Dr Pai, reviewed thirty-two national tuberculosis surveys done in twenty-six countries between 2000 and 2016. All surveys revealed that, globally, everyone had underestimated the prevalence of TB.

It was a phantom plague.

In October 2016, the WHO said it had seriously underestimated the global TB epidemic because of inaccurate estimates of the tuberculosis burden in India between 2000 and 2015. The most alarming finding of the latest Global TB Report 2016 was that India had reported only 56 percent of its TB burden in 2014 and 59 percent in 2015. The massive underestimating resulted in the WHO revising the global TB burden upward by over four million cases.

The same problem occurred in all seven countries with the most TB patients in the world — India, Indonesia, China, the Philippines, Pakistan, Nigeria, and South Africa.

Speaking to me on the condition of anonymity, a senior bureaucrat in the health ministry was clear about the prospects of meeting Modi’s ambitious 2025 target to eliminate TB: “We did not give this target. This was set by nontechnical people. If you are asking me whether we will end TB by 2025, the answer is simple: we will not.”

To “end TB” by 2025, India would have to bring down new infections from the current 204 per one million people to 40. “This cannot even be done by 2040, if all hands were on deck, and the policy had no budget constraints,” the official added.

The HIV epidemic was a rude awakening.

Suddenly there was a realization that TB was a grave crisis. HIV, because it compromised immunity, liberated the latent TB. The logic was inescapable: any widespread epidemic that adversely affected immunity had the capacity to make latent TB into an active and deadly killer.

In Mumbai, TB is everywhere and nowhere. Spotting the bacteria is not unlike spotting a tiger in a jungle— while glimpses are uncommon or fleeting, there are fresh prints that show a predator is lurking nearby. You don’t have to walk into hospitals to find it. You see it in spit stains all over the city, in the unprotected coughing and sneezing in crowded buses, in tightly packed ghettos. Today, India is a moist “nation of spitters.”

The spread of TB is extensive. And it is extensively denied.

In India, these medieval tools are wielded by an army of science-deficient doctors for a government with scant respect for science, each piling errors on errors.

According to the WHO, the first case of extensively drug resistant tuberculosis was reported in 2006 in Italy.1 In 2009, fifteen TB patients in Iran were diagnosed with the same strain.2 In December 2011, Mumbai doctors reported four patients, and a few weeks later, the Times of India reported eight more cases in Mumbai. The WHO took a while, as is customary, before settling on calling it XDR TB. Meanwhile, scientists in different parts of the world were using new terms like “XXDR TB,” “super XDR TB,” and “totally drug-resistant TB” (“TDR TB”) interchangeably.

In Mumbai, Dr Udwadia was calling it TDR TB.

He had treated the four patients in 2011 and, methodical as he is, wrote a paper about the new, untreatable avatar of TB. He and his colleagues called the strain TDR TB, the term coined in 2009 by Iranian doctors who had treated the fifteen patients showing no response to the first- and second-line antibiotics. Dr Udwadia’s paper warned of an antibiotic apocalypse, when there will be no drugs known to modern medicine that could cure these emerging strains of the bacteria.

The Indian government did not like the prognosis.

It raided his lab, seized the patient samples, and pressured Dr. Udwadia to retract the paper. The NTEP did everything it could to sweep this piece of bad news under the rug. The tidal wave of bureaucracy rolled over the unimpeachable scientific evidence and once again drowned the science out in the twenty-first century as it had in the nineteenth. The Indian government’s response to new data on TDR TB had the same hallmarks of ignorance and arrogance that Ignaz Semmelweis dealt with.

Dr Udwadia has spent years speaking up to an increasingly unreasonable government.

He has a skeptical squint and a wry smile that redoubles the sense of skepticism. “They came down on us like a ton of bricks. Their first response was denial. Their second response was to take away our samples,” remembered Dr Udwadia, still surprised at the government’s reaction, years later.

He and his employers at the Hinduja Hospital were accused of spreading panic by using the term “totally drug resistant.” The Indian government argued that no such term had been approved by the WHO. Then, the NTEP dismissed his findings because the Hinduja Hospital’s laboratory — one of the finest in the country — had not been accredited by the government. So, their word could not be taken seriously. The government refused to investigate any further. But global media was starting to cover the story, so the ministry needed to be seen to run their own tests. “Literally, they seized culture from our laboratories. They took them for cross-checking,” says Dr Udwadia.

His epic struggle against TB and the Indian government’s vast labyrinth of bureaucracy was reported in the New York Times in September 2016.

***

The study in which actors were trained to walk into a doctor’s clinic with every red-flag symptom of TB has since been replicated in three other countries: South Africa, China, and Kenya. The “patients” all report a persistent fever and cough for two weeks, the first red flag. Then they follow a set script:

Regular Jane Doctor: Do you have cough with phlegm?

RJ Actor-Patient: Yes.

Fever?

Yes.

Weight loss?

Yes.

Loss of appetite?

Yes.

This is the textbook definition of a patient who should be screened for a TB test. In all the participating countries, the study discovered three alarming failures:

1. Most doctors could not correctly diagnose TB patients.

2. Even if they did, they did not correctly treat them.

3. Without proper medical guidance, the patients—all falling through the cracks of the health-care system — continued to infect their loved ones.

The number of undetected TB cases is genuinely alarming. Within global health, this problem has come to be known as “the missing millions.” According to the WHO, in 2019, 10 million people fell ill with TB. Only 7.1 million were picked up by national TB treatment programs. So 2.9 million were either undetected or unreported.

You cannot treat what you cannot diagnose.

The study found that across all four countries — India, South Africa, China, and Kenya — only 35 percent of the actor-patients were “correctly managed.” To begin with, researchers had set a low bar for the definition of “correctly managed.” “If the doctor referred the patient to another doctor or referred her to a government hospital — instead of screening her — we accepted it as a ‘correct diagnosis.’ We accepted any screening test they recommended as well — x-rays, sputum smears, and Gene Xpert. It was broadly defined,” Dr Pai told me in a Skype interview.

Even using this lenient definition, only one in five actorpatients was correctly managed. In Mumbai, 37 percent of patients were correctly managed, Nairobi 33 percent, rural China 28–38 percent, and South Africa, the “best” performer, 43 percent.

At this stage the study team was not looking at what was being prescribed but simply trying to see if doctors could diagnose TB correctly. The treatment, when it was recognized as necessary, often compounded the problem: “What they [doctors who’ve correctly diagnosed their patients] end up doing is, hit them with multiple rounds of broad-spectrum antibiotics.”

Basically, the few patients who are diagnosed correctly are carpet-bombed with powerful antibiotics, cough syrups, steroids, and antihistamines to see what “works.” Doctors, especially those in the private sector, were throwing a bunch of pills at the bacteria, found Dr Pai. “An average prescription has four to five pills, and the doctors say come back in two weeks if it doesn’t get better,” Dr Pai told me in 2019.

Only 10 percent of the actor-patients were referred to specialists, as they should have been immediately. “The job of the primary care doctor seems to be to retain the patient. At this stage, referral is practically dead,” the study concluded.

The hellish cycle of misdiagnosis can last for weeks as the patient is bounced from one doctor to another, feeling increasingly worse: “In most parts of the world, TB is only diagnosed after about three rounds of this. . . . Patients start with pharmacy, go to traditional medicine, switch to allopathy, change doctors,” Dr Pai told me.

Thanks to the study, we now know it takes a TB patient an average of sixty days and a minimum of three doctors to receive correct treatment. During this diagnostic delay, patients are actively infectious.

Government hospitals at least keep records.

India is, not coincidentally, home to one of the largest unregulated private sectors in the world, a vast and unregulated mess whose raison d’être has been to undercut the government-run, taxpayer-funded health system.

In April 2019, Dr Pai described the discrepant numbers regarding undetected or unreported TB to an audience at the London School of Hygiene and Tropical Medicines: “The missing could either be because they are walking around, undiagnosed. Or they are seeking care at pharmacies, or at private clinics. My hunch says that the missing patients are diagnosed but not reported. The countries with the most privatized health care are not only the ones with the largest patient burden but also the ones with the most missing patients. There is a clear correlation between private care seeking and the missing millions. That’s why working with the private sector is so critical, especially for India,” explained Dr Pai.

Global TB experts, including Dr Pai, reviewed thirty-two national tuberculosis surveys done in twenty-six countries between 2000 and 2016. All surveys revealed that, globally, everyone had underestimated the prevalence of TB.

It was a phantom plague.

In October 2016, the WHO said it had seriously underestimated the global TB epidemic because of inaccurate estimates of the tuberculosis burden in India between 2000 and 2015. The most alarming finding of the latest Global TB Report 2016 was that India had reported only 56 percent of its TB burden in 2014 and 59 percent in 2015. The massive underestimating resulted in the WHO revising the global TB burden upward by over four million cases.

The same problem occurred in all seven countries with the most TB patients in the world — India, Indonesia, China, the Philippines, Pakistan, Nigeria, and South Africa.

Speaking to me on the condition of anonymity, a senior bureaucrat in the health ministry was clear about the prospects of meeting Modi’s ambitious 2025 target to eliminate TB: “We did not give this target. This was set by nontechnical people. If you are asking me whether we will end TB by 2025, the answer is simple: we will not.”

To “end TB” by 2025, India would have to bring down new infections from the current 204 per one million people to 40. “This cannot even be done by 2040, if all hands were on deck, and the policy had no budget constraints,” the official added.