Archive for the ‘tuberculosis’ Category

Tuberculosis Part two: Treatment options, Old, New or None

Monday, June 25th, 2012

Robert Koch discovered the bacillus that causes TB

In the era before antibiotics, especially in the late 19th century, tuberculosis, often called the "white plague," was a leading cause of death in the United States. Eastern patients were urged by their physicians to travel to Colorado where the fresh mountain air was supposedly curative. Hundreds of those stricken with TB went to Denver which was sometimes called "the world's sanatorium." Hospital beds were scare and a Jewish woman, Frances Wisebart Jacobs, recognized as the founder of what is today's United Way, spearheaded a movement to fund a TB hospital which eventually became National Jewish Hospital and served patents of any creed with free care for the indigent.

Prior to the advent of antibiotics, TB continued to treated in sanatoriums, where rest, fresh air (and sometimes surgical collapse of a lung or removal of a cavity) were all the therapy available. Extracts from one such patient's diary, begun in April of 1944 and continued through early June of 1946, are available online having been published in the British Journal of the Royal Society of Medicine in 2004. 

Latent TB is usually treated for nine months with a single antibiotic, usually INH like I was given in the late 1970s. Active TB is quite a different matter and for those with drug-susceptible infection, usually requires a four-drug combination given for six months. This may be given as directly observed therapy with a healthcare worker meeting the patent at their home or workplace.

If the patent stops taking the antibiotics too early or if the particular TB bacteria involved are drug resistant (this occurs more frequently in people with HIV/AIDS and those who have had previous TB therapy), or the medications used are of poor quality, multi-drug resistant TB can develop.

A 2002 paper titled "Tuberculosis therapy: past, present and future," while detailing the history of TB treatment, mentions that George Bernard Shaw, in his 1911 play, The Doctor's Dilemma, talked about the early attempts to cure the disease as a "huge commercial system of quackery and poisons." Elsewhere in the play, Shaw mentions "stimulating the phagocytes," referring to white blood cells that can engulf invading bacteria. The modern take on this 1911 quote would be a TB vaccine.

The only one I'm aware of is BCG, an attenuated live viral vaccine produced from the bovine strain of tuberculosis. It's been around since the 1930s and has been given to at least 5 million people globally, but its major benefit has been to prevent spread of TB to sites other than the lungs. At this stage we really need an effective immunizing agent, as our pharmacologic attempts to keep TB in check are becoming less and less effective.

We all need to support efforts to stamp it out.

Workers at the CDC published a 2007 paper titled "Worldwide Emergence of Extensively Drug-Resistant Tuberculosis" (XDR-TB) mentioning that nearly 90 countries have had multi-drug resistant TB (MDR-TB) requiring usage of so-called second-line drugs for at least two years. Now we've gone beyond that as nearly 10% of the 3,520 samples from an international MDR-TB pool were also untreatable with a majority of those drugs.

So we're up to 2012 and The Wall Street Journal's article, "India in Race to Contain Untreatable Tuberculosis." TB already kills more people than any other infectious disease except for HIV. But since the first cases of XDR-TB were reported in Italy in 2007, Iran and now India have also been struck by the strain.

There's an urgent need for an effective vaccine or a totally new approach to TB treatment.


Tuberculosis Part one: How long has it plagued us?

Saturday, June 23rd, 2012

I was reading an article in The Wall Street Journal this morning about "Untreatable tuberculosis in India" and decided to explore the background data before writing about what we're facing now.

I have a personal acquaintance with TB; when I returned to Air Force Active Duty status in 1977, I got a TB skin test. Much to my surprise it was positive.

I'm glad my chest x-ray didn't look like this

My chest x-ray was normal; I had none of the symptoms of active TB: chronic cough with blood-tinged sputum, night sweats, fever and weight loss. So I didn't have active disease and could be treated with only one drug; the infectious disease specialist told me I would take a medicine called isoniazid (INH) for a year.

I found out that about a third of the entire world population has been infected with the human variant of TB, Mycobacterium tuberculosis. In the US, 5-10% of the population will have a positive skin test; in other parts of the world, especially in some Asian and African countries, up to 80% will test positive.

Around the world new TB infection are estimated to occur at the rate of one per second, nine million cases a year with 95% of those living in developing countries. The vast majority of those remain asymptomatic. Of those who have a normal immune system, roughly 5-10% will ever develop active disease. But if you have HIV you have at least a 30% chance of moving on to symptomatic disease & x-ray-positive TB; other studies place the risk even higher, at 10% per year.

Now that milk is pasteurized, most of us in the US don't have to worry about the bovine strain of TB. But that isn't true everywhere, so beware of drinking unpasteaurized milk when you travel abroad.

A detailed online history of TB from the New Jersey Medical School commented that 2-3 million people die of the infection every year; the vast majority of those lived in developing countries. The ancient Greeks called the disease phthisis. It's been with us for millennia; ~4,500-year-old spinal column bits and pieces from mummies in Egypt  were the earliest evidence of human infection that I had been familiar with, but I found an article that doubled that estimate. Bones from an ancient site off the coast of Israel, estimated to be 9,000 years old, not only had the characteristic signs of TB, but also had DNA and bacterial cell wall lipids that could be analyzed by modern techniques.

One of his ancestors had evidence of the earliest TB we're aware of

Researchers from England commented that the tuberculosis we see today came from a human strain of the bacteria, not from a bovine origin. They also said that the DNA was subtly different from that of TB organisms today and felt this meant there has been a very long linkage between this infection and people. But the very earliest animal to have clearcut evidence of TB was a long-horned 17,000-year-old bison with skeletal remains showing the disease.

TB outbreaks still occur in the US. The June 20, 2012 edition of JAMA has a CDC report of cases which occurred in a homeless shelter in Illinois. The majority of the 28 patents involved (82%) had a history of excess alcohol use  and many had longer stays in the men's section of the shelter and socialized in two bars in the area.

The risk factors seen in developing countries: lower socio-economic status and overcrowding, seem to me to have played a role in this US series of patients. Alcohol over-usage has been implicated as a risk factor for TB,  perhaps from repeated prolong close contacts in bars and perhaps from effects on the immune system.

I'll get back to the current issues with TB in my next post.