World TB day 2007: "TB anywhere is TB everywhere"

Mycobacterium tuberculosis infection is as old as civilization. The bacterium infects approximately a third of the world's population--roughly 2 billion individuals. It's estimated that 8 million new cases are contracted each year--around a new infection every second. ~2 million individuals die as a result of TB every year. The bacterium also plays a prominent role in the history of microbiology: it was on March 24, 1882, that Robert Koch announced his discovery of the causative agent of the dread disease tuberculosis:

"If the importance of a disease for mankind is measured by the number of fatalities it causes, then tuberculosis must be considered much more important than those most feared infectious diseases, plague, cholera and the like. One in seven of all human beings dies from tuberculosis. If one only considers the productive middle-age groups, tuberculosis carries away one-third, and often more."

Unlike many other feared infectious diseases of Koch's time, TB still remains a significant killer worldwide, and its effect has only been exacerbated by the AIDS epidemic. However, a concentrated effort is being made to again attract attention to this bacterium.

The epicenter of new TB infections remains in Africa. However, India is also hard-hit: approximately a quarter of new TB cases today come from this country. Additionally, as mentioned, TB has surged due to the HIV epidemic. Typically, only approximately 10% of those infected will ever show clinical symptoms of disease; the rest are infected asymptomatically. One can transition from an asymptomatic to a symptomatic infection due to suppression of the immune system; therefore, clinical TB is common in carriers with HIV co-infection. Indeed, in some areas, the majority of their TB cases are in individuals who are HIV-positive.

What's worse is that in the country with the highest rate of HIV-positivity, South Africa, a deadly new strain of TB has been identified. I mentioned here an outbreak of highly drug-resistant TB (so-called "XDR-TB") that had caused an outbreak in the country. Now it's spreading, putting neighboring countries--and indeed, the world, as most of the TB diagnosed in the US was contracted elsewhere--at risk.

The whole situation is, admittedly, depressing. But there are some bright spots. For one, most TB is treatable. However, the bacterium is extremely slow-growing, so treatment regimens take many months (and a variety of drugs) to complete. Still, those who are symptomatic are just the tip of the iceberg--to really make inroads, we need more effective education and prevention. The current vaccine simply isn't effective enough, and while progress has been made on a novel vaccine, it's still not ready for prime-time. In some areas, a diagnosis of TB carries with it significant social stigma, to the extent that people flee rather than be treated when they're told they have TB.

Nevertheless, there are people working to reduce the impact of TB. StopTB.org has a wealth of resources about the bacterium, the disease, and policy aimed at reducing it, including this sheet that lays out 3 key areas where work is needed: 1) investment of funds; 2) research into new TB drugs, diagnostics and vaccines; and 3) education and empowerment in areas that are hard-hit by the bacterium. The page is necessarily simplistic, but it's a good place to start for an overview of what needs done. They also have a BBC-produced movie that may be of interest to readers: Kill or Cure:

The documentary's primary focus is on DOTS [Directly Observed Treatment Short-course] in Rajasthan, India and on TB/HIV in Malawi, with scientific commentary provided by Dr. Douglas Young, chairman of the Stop TB Working Group on New Vaccines. But a strong sub-theme running throughout the film, and which is explicitly articulated by Young as a final note, is the urgent need for new tools -- drugs, diagnostics and vaccines -- in order to turn the tide against the epidemic. The documentary therefore provides a true 360-degree view on the contemporary challenges of TB control, and can be a powerful advocacy tool for all Stop TB partners.

Finally, TB is relatively rare in the US (compared to worldwide figures, anyway). Still, "rare" for TB amounts to ~15,000 cases diagnosed in the US in 2003, and it's estimated that over 10 million carry the infection. Because of its low priority in the US, it has been highly vulnerable to cuts in funding from the government, even though it's been pointed out that's bad policy:

"Funding for TB control is like keeping the New Orleans levees in good repair to prevent flooding. When we let our guard down, the disease predictably moves in and quickly," said Norman H. Edelman, M.D., chief medical officer of the American Lung Association.

To counter this, Sen. Barbara Boxer of California (a state hit heavily by TB due to its large immigrant population) and Republican Gordon Smith of Oregon introduced the Stop TB bill this past week. It proposes funds to support StopTB's goals and 10-year TB plan. WIll its bipartisan introduction be enough to push it through? Politicians are notorious from not learning from history, and for being penny-wise and dollar-foolish, particularly when it comes to support for public health. As always, you can try to educate your own senators about the importance of this problem by finding their contact information here. With a problem this massive, every little bit helps.

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What's worse is that in the country with the highest rate of HIV-positivity, South Africa, a deadly new strain of TB has been identified. I mentioned here an outbreak of highly drug-resistant TB (so-called "XDR-TB") that had caused an outbreak in the country. Now it's spreading, putting neighboring countries--and indeed, the world, as most of the TB diagnosed in the US was contracted elsewhere--at risk.

It's not just in South Africa it has been found, though it's where they have done the most to uncover the spreading. From the linked article:

Such strains now have been reported in 28 countries, Nunn said, including the United States. However, the bulk of the resistant strains are found in China, India and Russia.

It makes sense that it's the countries with the biggest populations that have the most cases.

And the XDR-TB strains are not only bad for the fight against TB, they are also bad for the fight against AIDS, since they hit HIV-infected people very badly.

According to the article in the later link, no new TB drug has been approved for 40 years, which indicates a lack of research into this (probably due to the fact that the current drugs have been considered "good enough").

I wonder if there are TB denialists out there? Why not...they could use the same tactics as those other people.

Seriously though.

Still, "rare" for TB amounts to ~15,000 cases diagnosed in the US in 2003, and it's estimated that over 10 million carry the infection. Because of its low priority in the US, it has been highly vulnerable to cuts in funding from the government, even though it's been pointed out that's bad policy:

I found a repository of more recent data HERE. I wonder if its low priority has as much to do with demographics as it does raw quantity. From the report for 2005.

Total cases: 14,097

Hispanics = 29%
Asian = 23%
African American = 28%
White = 18%

Or this way...

Foreign Born = 55%

Hello Dave,

and no I do not believe there are any TB denialists out there. The TB mycobacterium is quite well isolated and quite properly fulfills all of kochs postulates!

Thank you Tara for highlighting TB. Actually it is very nice to see the focus put on solving a serious problem disease like TB. And one that we can do much to get a grip on to minimize the problem, although it will not be an easy one to solve.

Of course, I think it is crucial to realize the same lessons we yet need to learn from other diseases, and that is that 3rd world countries still need proper nutrition, clean water, hygiene, and basic education, to lessen the depression of peoples immune systems in the first place. We also need to provide proper care in these areas to be able to give people a fighting chance to recover from TB even with medications.

Stressed out poverty stricken populations are at highest risk from this devastating illness. The disease hits mostly those populations that are stricken with life-views of apathy with its associated emotional pain due to the perception by these people, of their lives as being hopeless and themselves as being helpless to change their dire life circumstances. Chances are fairly high that only by lessening the stress of poverty and poor nutrition and clean water will the developed nations be able to have peoples immune systems be strong enough to resist being overtaken by TB in the first place.

And a lot of this depends on the people themselves in these areas. They most always cannot lift themselves up out of their difficult life situations without assistance. And all of the assistance in the world won't lift someone who does not want to lift themselves. Nor will it be easy when so much of the funds directed at such efforts are wasted or stolen by officials and others that are in positions to take personal gain and advantage of any help offered. And it is never easy to teach such deprived people to help themselves instead of becoming eternal wards of the caregivers.

It is a long term problem any way you look at it. Basic education will go a long way, as well as microloans to assist people in building a financial base of well being, as well as investment in basic infrastructure in these countries.

Out here in California, most of the TB cases are right here in San Diego, but they are mostly comprised of Latino's coming up here from Mexico for better treatment.

I absolutely disagree with Tara's statement that "Additionally, as mentioned, TB has surged due to the HIV epidemic".

I believe this to be a common misperception. TB was 80 percent of the verifiable disease before HIV and it is still 80 percent of verifiable disease in a population that has now doubled in that 25 year time period since before HIV was even heard of.

Additionally, throughout Africa, the doubling of the population of the most stricken countries over 25 short years has also added to stressing out the populations and infrastructure of these third world countries. The same for parts of Asia and India.

I do not believe that TB has surged due to a perceived HIV epidemic. What has surged in the last 25 years is the populations and the stress caused by this, and what has surged is the number of people that are being tested for HIV, hence the number of people who are cross reacting even though most of them are presently healthy has also surged. The stress of being diagnosed as HIV and believing one will die of it will not help many of these now scared and frightened and mostly poor and uneducated people to stay in a healthy frame of mind or body to begin with. And their lives have more than enough stress to begin with.

But most importantly, the number of people testing false positive on HIV tests that are most likely cross reactions due to infection by TB is of considerable, but ignored, importance. TB is well known to cause false positive Elisa tests.

We also have to remember that the areas in the world that are testing highest for TB are also the poorest areas where usually only ONE single HIV test is even given to diagnose HIV. Any doctor doing such as this in the Western world would lose his license to practice medicine. This practice of ignoring cross reactions may bring lots of money for AIDS drugs and HIV researchers, but it is done at the expense of funding for the very treatable cases of TB and at the expense of perhaps better investing these funds in the root causes of poverty and infrastructure.

I also question whether TB patients benefit at all from the very toxic DNA Chain Terminators and other very toxic drugs that are given along with TB antibiotics for HIV. I think that a recovering TB patients' immune system needs all of the help it can get, and I do not believe these patients
will benefit from being pushed to take lifelong drugs that will suppress the fastest growing, and much needed cells in a human body from growing. These include the entire intestinal tract as well as parts of an immune system and any other cells that divide rapidly in a normal healthy human body.

I realize there are a lot of people who believe in additionally dosing TB patients with lifelong HIV drugs who test HIV positive, but I truly think it is a big mistake that diverts much needed funding from treating the basic causes of poverty.

So, although it may be convenient as a scapegoat and myopic view of the problems involved, I see several major problems with blaming TB on HIV:

1) TB is well proven to cause false positive HIV tests, especially on the Elisa test that is used as the only diagnostic tool for HIV in the poorest and hardest hit by TB areas, and is a basic but highly oversensitive screening test for HIV, well known for cross reactions.

2) The HIV drugs do not have any verified effect on TB mycobacterium, and quite often cause a multitude of other side effects for a large percentage of those given these drugs, including nausea, vomiting, weight loss, calcium loss, painful neuropathy, liver and kidney and heart damage and other long term damage.

3) increased stress of HIV diagnosis will lead to increased illness.

4) less funding and avoidance of dealing with the core roots of poverty when focusing as HIV as the core of the TB epidemic.

I hope that the low-priority nature of this disease hasn't sapped our basic competence in handling outbreaks. I got a latent case back in '98 (go Navy!), and the doctor at the VA clinic I was treated in was so unfamiliar with the drugs I was on that he had to look up their side effects in some big white binder. He said he'd gotten trained on the East Coast and had no experience in treating it. I don't know how many people who've had a potential health problem managed so poorly, but God help 'em.

Popped over from Mooney's blog after seeing a photo of people carousing, and got reminded of the most aggravating episodes of my life. Jesus.

Lincoln, I must comment on some of your observations:

(1)"The TB mycobacterium is quite well isolated and quite properly fulfills all of kochs postulates!"

Unfortunately it doesn't. Not by (HIV) denialist standards anyway. You see, Postulate number One says that in all cases of the disease you must find the bacterium. Well this is untrue. If you consider the "disease" to be "bronchopneumonia" then clearly because there are other causes of this than mycobacteria, they cannot fulfil this postulate. Even if you take what is clinically thought to be definite cases of clinical tuberculosis defined by radiological characteristics, you cannot find mycobacteria in a small proportion with traditional culture methods, even on BAL fluid. One may have to (horror of horrors) resort to molecular diagnostics (DNA probes etc) or indirect methods (T-spot etc) to make the diagnosis, and then not 100% of the time.

The third postulate is unfulfilled, also. Not everyone who is infected or who acquires M. tuberculosis will develop clinical tuberculosis - many cases will remain subclinical or latent. Koch remained blissfully unaware of this group of people when he devised his postulates.

So you are misguided in thinking Koch's postulates are some holy grail for TB. In reality, they are possibly more "fulfillable" in microbiological terms for HIV than for MTB!

(2) You are correct in saying TB can be a cause for false positivity in HIV assays. However this is rare and confirmatory testing algorithms readily identify that this is the case, so no-one who has only TB should be misdiagnosed as having HIV co-infection if they haven't. I admit this might be a problem in TB endemic countries with limited HIV testing facilities, but even so it is very unusual. The way you refer to the problem suggests you have been following denialist-politik where they imply everyone with TB will test positive for HIV (in the fashion of Lynn Margulis saying most pregnant women will test HIV positive).
http://cdli.asm.org/cgi/reprint/2/6/637

Don't tell me that, in order to recognize World TB Day, that i've got to contract it myself. I don't know many who have it, and those that do aren't willing to share! On top of that, i've no idea how it's transmitted, or what the symptoms might be once i got it. Geez. It's worse than DST.

Disclaimer:

This is humor. No Mycobacterium tuberculosis were hurt in the making of this comment.

Lincoln, I'm shocked. You say about people in Africa,
They most always cannot lift themselves up out of their difficult life situations without assistance. And all of the assistance in the world won't lift someone who does not want to lift themselves

Your buddy, Ueberpat, calls HIV scientists racist and genital-obsessed because they recognize the sexual transmission of HIV and want to reduce it. He calls me a neocon because he disagrees with me on scientific points he admits to not understanding. I wonder what Pat would say about your offensive broad-brushing of (in your view) poor, apathetic Africans?

"... because they recognize the sexual transmission"

you're having it both ways now. Maybe you should just state your position clearly. To what extent is sexual transmission responsable for AIDS in Africa? I didn't disagree on the science, I disagree with the politics it engenders. I called you a neocon because your powers of persuasion are non-existant. I also told you to go and clean the poop out of your cage because it seems that life inside the lab is the only thing you know

"I wonder what Pat would say about your offensive broad-brushing of (in your view) poor, apathetic Africans?"

Why didn't you ask me? Why do you wonder out loud? I'll pretend for a sec that you did ask me and that you indeed care for an answer. I believe you are a) misunderstanding his post or b) misrepresenting it. Ok Adele, poverty is the devil's circle, not race. You missed his point about the hopelessness of poverty. You do understand the psychology of hopelessness, don't you? It makes you not "want". Hopelessness is not an African institution, it is a colonial import.

PS: apologizing is pointless, check.

With asymptomatic case (x-ray is good but with pcr it's tb +), the doctor said it's better to leave it untreated. Is it true? It feels like waiting the bomb to explode, though..

By asymptomatic (not verified) on 26 Mar 2007 #permalink

Ah yes, my favorite disease - good to see you back in the epi public eye again my horrifying friend.

I haven't seen the DOTs video so I hope this isn't completely off the point. Paul Farmer shows, in his 2003 NEJM paper that DOTs alone is not the way to go with MDR TB in developing countries;

http://content.nejm.org/cgi/content/full/348/2/119

"However, the short-course chemotherapy on which DOTS is based usually fails to cure multidrug-resistant tuberculosis.Rates of cure of multidrug-resistant tuberculosis with standardized short-course chemotherapy range from 5 percent9 to 60 percent."

So he put in the time and money to culture they infection and use the correct therapy;

"We conducted a community-based project for the treatment of multidrug-resistant tuberculosis in a resource-poor setting. This DOTS-Plus project -- which entailed the addition of second-line drugs, monitoring by sputum culture, drug-susceptibility testing, and directly observed individualized therapy to the well-established Peruvian DOTS program -- treated a cohort of patients with long-standing disease due to highly resistant strains of M. tuberculosis"

and found that;

"Large-scale, standardized surveys have revealed the presence of patients with multidrug-resistant pulmonary tuberculosis in virtually every country studied, yet to date, specific therapy for this disease has been restricted to high- and middle-income countries where care is usually delivered within specialized referral centers. This project in Peru yielded more probable cures than expected in patients whose prognosis was poor because of chronic, highly resistant tuberculosis, extensive parenchymal damage, and previous exposure to repeated, standardized regimens that probably resulted in the amplification of drug resistance. The percentage with probable cures in our community-based, ambulatory program (83 percent) was as high as any reported in a hospital setting to date."

I don't worship at the alter of Dr Farmer but I sure as hell read what he writes because, over and over, his approach works, is more cost effective and saves lives. We can win against TB as public health professionals, but the work won't be easy and may require that we piss off a few large governmental entities.

By mycotropic (not verified) on 28 Mar 2007 #permalink

I think the form of "TB denialism" that's out there does not deny the TB mycobacterium itself but its connection to the AIDS epidemic. One-third of all people who die of AIDS-related illnesses actually die of TB. Africa will not be the endgame of the HIV-AIDS epidemic, as it is starting now to move into Asia, particularly China and India. The Chinese government has refused to acknowledge the spread of the disease. People in the U.S. think that AIDS in Africa will not affect them, when in fact (aside from the moral question of ignoring it anyway) its spread into Asia will precipitate an explosion of TB cases around the world, and no one knows how the social upheaval in African society will affect the whole world. Plus, people in the U.S. think that AIDS in "under control" when in fact it is now spreading at an alarming rate among poor heterosexual women.