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Singing the blues about tuberculosis

Jim deMaine, MD
Conditions
April 30, 2012
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Should we all have the TB Blues? I think you’d agree that we should after listening to this 1931 classic by Jimmie Rodgers who died from TB.

Tuberculosis is known to have existed in ancient Egypt and TB may have even been referenced in the Bible – “The Lord will smite you with consumption, and with fever, inflammation, and fiery heat …” Deuteronomy 28:22.

Many well known authors, artists, musicians, and others suffered or died from TB. Perhaps the most notable family severely affected was the Bronte family:

Maria Bronte (wife) dies of tuberculosis – age 38
Maria dies of tuberculosis – age 11
Elizabeth dies of tuberculosis – age 12
Bramwell – d. 1848 age 30
Emily dies of tuberculosis – age 29 (Wuthering Heights)
Anne dies of tuberculosis – age 27
Charlotte dies of tuberculosis and complications in pregnancy – age 39 (Jane Eyre)
Rev. Bronte dies 1861 – age 87 of “chronic bronchitis”

No one had a clue about the cause of tuberculosis, until the little known German physician, Robert Koch, astounded the scientific world with proof that he could stain the TB bacillus, that it was isolated from patients, and could be transmitted from animal to animal (guinea pigs).

After Koch’s discovery, patient isolation and TB Sanitariums began to open where bed rest was the primary treatment. Little progress was made until the era of drug treatment which began in the late 1940’s.

As a medical student on the East Coast, I was lined up at school in 1963 and given BCG, the TB vaccine which has had variable but limited use in TB prevention in the USA. Calmette and Guerin in France in the early 1900’s had painstakingly developed an altered strain of Bovine TB. Even thus vaccinated, after being exposed at an autopsy of a patient with far advanced TB, one of my classmates developed active tuberculosis, was sent to a TB San and missed a year of school. In 1943 Selman A. Waksman was successful in developing the first anit-TB drug, for which he received the Nobel Prize (as did Koch previously) . Streptomycin purified from Streptomyces griseus was first administered to a human on November 20, 1944. Other drugs like INH, PAS, Cycloserine, Ethambutol, Ethionamide, PZA, and Rifampin came along one at a time. That was a problem, because it was soon discovered with exposure to just one drug, the TB germ could fairly rapidly develop drug resistance.

I saw a few cases of TB while in medical school, but many more during my fellowship in infectious diseases and in heading the admitting TB Ward at Firland Sanatorium in Seattle for a year or so. This was a teaching and research institution with academic affiliation so anything unusual that might be TB was admitted there. In the 120 or so in-patients at that time, there were a few with what we now call MDR TB – multiple drug resistant organisms. This was inadvertently caused over the years by adding a new drug one by one as they came along. But lessons were learned and these patients subsequently had extensive drug sensitivity assays with tailored multiple drug regimens, sometimes four or five drugs plus the need for occasional surgery.

One night, a chronic patient woke up spouting blood from his mouth and nose. A bridging artery in a TB cavity in his lung had burst. He died within minutes. This is one of the “classical deaths” well described in TB literature as well as classical literature. A biography of Keats shows the unfortunate ignorance of physicians adding to the poet’s suffering with consumption, a fate of many other well known persons.

After TB Sans closed across the nation in the 1970’s there was unwarranted optimism that TB would be conquered in this country by 2025. TB care and control went to private physicians like me and to overworked health departments. Case tracking and medication adherence in populations was shockingly poor leading to outbreaks of MDR TB in large urban cities like New York. Subsequent strategies have developed to address the need for careful drug planning and directly observed therapy – both of which drain resources and budgets.

Then HIV came along in the 1980’s which proved to be an explosive situation for patients co-infected with tuberculosis. Both are treatable, but the treatment for TB remains complex usually with four drugs for two months, followed by at least two drugs for four additional months. MDR TB/HIV epidemics continue with newer reports of extensively drug resistant strains. In South Africa the journal Lancet reports a large number of XDR TB patients who, when also infected with HIV, rapidly died within a few weeks of diagnosis.

In the USA, we will continue to see sporadic cases of TB most often in those born in countries with a high TB incidence, the homeless and under-served, and in Native American populations. An Asian corporate executive with a fever, voice change, and cough was referred to me for evaluation. His chest X-Ray was suspicious for TB and on exam there was a bulging mass pushing the back of the throat forward and narrowing the airway. To make a long story short, this patient had TB of the cervical spine as well as pulmonary TB. He responded beautifully to modern TB drugs and is cured.

An African born high school patient was referred with fever and a pleural effusion. Fluid cultures, cancer checks and blood tests were all unrevealing. Finally I did a pleural biopsy and pleural culture (after two weeks of head scratching). Yes, it was TB. His skin test was only weakly positive at 5mm. Again, he was cured.

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A Caucasian patient was brought on a stretcher to the TB sans in 1971 with wasting, fatigue, pallor, cough, and a diffusely abnormal X-Ray. This 17 year old girl had been seen at her home off an on for six months for “pneumonia” by her MD uncle. Her TB was far advanced, oxygen levels low, and nutrition very poor. Basically she received standard drugs, vitamins, good food and classic bed rest. She spent two years recovering but permanently lost 60% of her lung function. A few of us attended her wedding several years later.

A diabetic patient had severe lower abdominal pain. A laparotomy (prior to the days of CT scans) was unrevealing. However review of her abdominal X-Rays showed destruction of two lumbar vertebrae from TB, causing the referred pain in the abdomen. Again, treatment and cure was straight forward.

A 70 year old woman from India, developed fever confusion, neck stiffness and went into coma. A spinal tap was suspicious for TB, but not proven. Aggressive treatment for TB allowed this woman to recover and ultimately return home.

The classic historical book about TB is by Jean Dubois: The White Plague: Tuberculosis, Man, and Society. But TB is still a modern plague and killer in much of the world particularly where there is poverty or social disruption. The astounding data from the CDC is as follows:

Tuberculosis (TB) is one of the world’s deadliest diseases:

  • One third of the world’s population are infected with TB.
  • Each year, over 9 million people around the world become sick with TB.
  • Each year, there are almost 2 million TB-related deaths worldwide.
  • TB is a leading killer of people who are HIV infected.

In total, 11,545 TB cases (a rate of 3.8 cases per 100,000 persons) were reported in the United States in 2009. Both the number of TB cases reported and the case rate decreased; this represents a 10.5% and 11.3% decline, respectively, compared to 2008.

So what’s being done. Paul Farmer’s book, “Mountains Beyond Mountains” gives a picture of his personal and academic attempts in Haiti and outlines the scope (and hope) for workable programs. The Bill and Melinda Gates Foundation supports multiple programs in Global Health and many medical schools now are focusing on “translational research” to focus on the needs. Organizations like Seattle Biomed, Infectious Disease Research Institute,and the Oxford-Emergent Tuberculosis Consortium are working toward TB prevention (vaccines) and novel identification and targeted drug management.

But TB control came to the USA largely by reducing crowding, improved case identification and control, better nutrition, and better housing. Seattle was designated a “TB swamp” by the government in the early 1900’s but all the above measures have probably had more impact than drug treatment per se. TB was well on the way to declining in the USA before the effective drugs were initiated in the 1950’s. So long term control and eradication will need both social and medical improvements to attack the very sad deaths of nearly 2 million people each year – each one preventable.

Jim deMaine is a pulmonary physician who blogs at End of Life – thoughts from an MD.

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