Tuberculosis

The CDC in 1989 made a commitment to eliminate TB from the US by something like the year 2015. At that time in the late 80s there were only about 22,000 cases a year. The bug won-out, however. TB staged a comeback in dramatic form. Tuberculosis kills some 2 million people a year worldwide. Approximately 1/3 of the world's population carries the infected. Areas of South America, Africa and Russia experience epidemic numbers of cases and now a new wrinkle, drug resistance.

In the two years I did the Health Festivals in Fiji, I experienced two cases that were clinically obvious TB without tests, visa vi: weight loss, night sweats, a sucussion splash and bloody sputum -- in one case, percussing the cracked pot sound of a cavity. These far advanced signs and symptoms rarely manifest themselves in the US

How can this resurgence occur with the scientific advances of the 21^st century? It's the same with malaria --- to answer the question simply: complacency, political correctness, ethnic conflict, AIDS, and the loss of education, sanitation and discipline, commensurate with the end of Empire which for better or for worse imposed all three.

When I was just a medical student at the University of Michigan Medical School in the mid 50s, I spent a month on what was then called a Med Chest Service, it amounted to open cavity, or highly active TB and some drug resistant staph. Later I rotated through Thoracic Surgery and Public Health. All were highly developed and highly respected. To a greater extent than one would like, all three have faded into obscurity, still present in the medical schools but hard to find beyond those cloistered halls.

Political correctness supposes that civil liberty contrary to the interests of public health, benefits the social order; it does not. None the less, the legislation of political correctness erodes the discipline of public health to an extent that defies logic. For example, when the AIDS epidemic first emerged, the population particularly at risk for the disease immediately promoted and caused legislation, prohibiting routine testing for the disease and specifically testing for the disease without written permission from the subject even in the hospital. Such restrictions caused a hospital policy of universal isolation, which predictably resulted in no isolation or precautions at all. With TB, the infected persons roam free with the assumption that drug therapy renders them non-communicable.

Isolation stood as the most powerful public health measure in controlling infectious disease prior to antibiotics. The developments of a wide array of effective antibiotics lead to complacency and the closing of sanitariums. That complacency contributes substantially to the spread of tuberculosis today particularly with the emergence of drug resistance. Furthermore, the reliance on patients taking the drug reliably and in necessary doses contributes to drug resistance; so does the use of inadequate treatment protocols and budgetary limitations of drug treatments. TB likes to lie dormant in the population, spreading from person to person with few if any symptoms. That does not negate the deadliness of the disease; it is just slow in doing so. Slow going too is the treatment. INH, iso-nicotenic acid hydrazide, so successfully treated TB as to justify the closing of sanitariums. INH required a year of treatment, however, a pill a day. The only serious side effect was a progressive neurological disorder, but that side effect was mitigated by precautionary vitamin B6. The real problem was patient compliance for a full year. Stopping the drug prematurely or frequent interruption in dosage, lead to drug resistance.

In the AIDS population, TB moves much faster and spreads more quickly. Next to pneumocystis carenaie, TB is the common opportunist in the immune deficient population. The more or less uninhibited spread of AIDS and TB as a common secondary infection, places us all at greater risk for TB, due to its increased prevalence, virulence and drug resistance.

Andrew Speaker, with a diagnosis of active TB traveled half way around the world twice, exposing unsuspecting airline passengers and his own family and friends out of a sense of entitlement (political correctness) but yet another shortcoming of the diagnostic and Public Health system was at play. The diagnosis of TB is not always obvious as in the cases I described in Fiji. The typical presentation may be subtle resembling a case of the flu or a stubborn case of bronchitis. A smear, called an acid fast, may lead to a presumptive diagnosis, but few are skilled in making the slides or interpreting what is seen. Greater certainty of diagnosis relies on a series of cultures. The cultures are slow growing, but what's worse: many practice guidelines, set to limit cost by both government and HMOs, limit the reimbursement for multiple cultures. (Political correctness, one is enough) In Andrew's case the cultures were positive but the extent of the drug resistance in his case was not fully appreciated when he left. The proof of extensive drug resistance, EDRTB came in after he left town creating a panic. When isolation is off the table, patients with suspected TB, or even certain TB with limited laboratory support, roam freely pending their treatment.

Skin testing helps to identify the presence of the infection and to some degree the extent of the disease. There too there are confusing aspects. Medical personnel are so commonly positive to skin testing and have so commonly contracted the disease that most medical personnel are given BCG vaccine. BCG is a bovine vaccine with limited specificity but it is enough to provide some limited protection. It renders skin tests positive thereafter, however.

All organisms, aside from immune systems, are endowed with certain mechanisms of expelling toxic environmental substances. The protection works on a cellular level with one or another kind of nano-pump, molecular mechanism, for expelling such substances. It is reasonable to imagine bacteria having some such capacity, giving them too the capability to survive, adapt and to evolve. The life-span of microorganisms runs to the order of 20 minutes, so within a few weeks or months of an infection there are many generations for microbes to adapt and evolve.

Until recently, many protocols in emerging economies were single drug protocols of specified sometimes insufficient duration. Economic limitations, poverty and lack of resolve or knowledge in the governance of these emerging regions feed the emergence of drug resistance.

Crowding feeds the spread of communicable disease. Many are forced to move to the city for jobs when their traditional rural agriculture fails or is displaced by war or globalization. In some prison populations with forced close quarters and limited ventilation the TB rate reaches 100%.

Combating drug resistance requires a return to the fundamentals of public health, sanitation, reducing poverty, education, and even isolation. Pharmacologically, the most effective way of overcoming drug resistance is with multi drug regimens and prolonged treatment.

Recent trends support a resurgence of public health and all that it implies. Currently there is a fear of biological agents used as terror weapons. That fear and the recognition of emerging drug resistance motivates enormous R&D, some financed by DARPA. (Defense Advanced Research Projects Agency) Legislators and bureaucratic interests seem willing to realization that privatization will not do it for us. The HMO and Hospital are interested in profit not in difficult labor intensive laboratory diagnostic challenges. The drug company would rather develop an expensive long slow cure, selling lots of pills, rather than a potent short term solution, but more to the point, big pharmacy would rather treat the disease of the affluent than that of the underdeveloped poverty areas of the world --- and TB is a World problem more prevalent where poverty prevails. State legislations, public health departments, the CDC and media, to a greater extent than ever, recognize these shortcomings. A few responsible drug companies make new investments in research, drug testing and vaccination.

There are technological breakthroughs in medicine that truly make a difference. One is a highly portable infectious disease detection unit that gives immediate, accurate identification of an organism and the particular strain of that organism even identifying its mechanism of resistance. Some of these devices were developed for real-time identification of weapons grade anthrax; one is in use in the post offices today.

In particular, one called "True Diagnosis," developed by Akonni, a small start-up, utilizes a small mass produced plastic card, the size of a credit card, to collect and amplify the specimen. The card inserted into a reader, which will also be miniaturized, then identifies any number of pathogenic microbes by fragments of their DNA. Various micro-dots are light-up by fluoresce from microscopic DNA sensors chips. The pattern of dots then identifies the organism by pattern recognition in the reader. The initial target for this device is for the various strains of TB and methacillin resistant staph. The card contains nano-pumps channeling fluids, micro-arrays with sensor chips in a technology calling itself, "molecular diagnostics." The device can identify MDR TB and XDR TB (Multi Drug Resistance & Extensively Drug Resistant TB –that's worse) with a 91% sensitivity and a 99% specificity, an unheard of level of accuracy, only a few false positives. The CEO Charles Daitch a research engineer hit a home run with this one. The licensing process will take a year. The product will be available in hospitals for research only, starting in 2008. I'm not sure the licensing delay is justified with a technique that offers so much immediate benefit, or is it a patenting delay?

Thomas Goetz "Wired" 15.08 Aug 07

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