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Future Possibilities and Speculations about IPT
by Chris Duffield

Could IPT become a powerful new tool in the battle against tuberculosis (TB), one of the world's major killers?     by Chris Duffield, Ph.D.  May 24, 1999 (modified 5/23/2001)

        According to Dr. Perez Garcia 3, his father Dr. Perez Garcia y Bellon 2 had some experience treating TB patients with IPT.  This was apparently decades ago, before more effective medications were developed.  To my knowledge, no TB patients have been treated with IPT recently.  Dr. Perez Garcia 3 prefers not to treat such cases in his private practice, out of consideration for the safety and feelings of his other patients.  

         IPT's remarkable successes in treating other bacterial and viral diseases suggest that it might offer breakthrough advantages for TB as well.  A small research program could find out very quickly if insulin potentiation of standard TB drugs shows promise.  If it does, the benefits could be enormous. 

The TB epidemic             < How IPT could help>

        The statistics are overwhelming.  A third of all human beings, well over a billion, are infected with TB bacteria.  Each year there are  7 or 8 million new cases of active TB disease, and probably about 3 million people die of it.    Sixty percent of TB cases worldwide are in young men and women (while in rich countries most cases are among older men).  TB is the world's leading cause of death among girls and women of reproductive age (15 to 44 years).  900 million of them are infected, at least 2.5 million get sick with TB each year, and one million die.   HIV-infected people (a parallel epidemic) are 3 to 100 times more likely to develop the disease, contributing an estimated extra 3/4 million cases per year.    Currently, one person gets infected with TB every second, and one person develops the disease every four seconds.  (source: World Health Organization)

        TB is present in virtually all countries.  Its distribution is highly correlated with poverty.  The vast majority of cases are found in Asia, the western Pacific, and Africa.  Russia and eastern Europe are also hotspots.  TB has been around for thousands of years.  Yet, despite the existence of effective drugs and treatments, the epidemic seems to be out of control.  Regional financial troubles and wars and refugee situations (such as Kosova/o) will most likely make the situation worse.  Immigration, drug use, and HIV are leading to a resurgence of TB even in the rich countries.  So more people are dying of TB now than ever before.

        Besides potential side effects, and less than 100 percent cure rate, the main trouble with TB treatment is that it takes a long time for a cure -- 6 to 12 months.  Therefore it is very expensive and disruptive to patients' lives.   Drugs may not be readily available in poor countries due to high costs.  And poor and rural people are less likely to follow the entire long course of treatment, due to financial constraints on travel and lodging.  Patients may stop treatment prematurely when they feel well long before they are cured.  Such noncompliance leads to relapses, continuation of the infection cycle, and development of multiple-drug-resistant (MDR) TB bacteria.   MDR-TB may be present in up to 50 million people, and poses the threat of TB becoming an incurable plague.  The World Health Organization is pinning its hopes on a labor-intensive but more effective protocol called DOTS -- directly observed treatment short-course -- in which healthcare workers closely watch each patient take each dose, combined with a strict regimen of detection and monitoring.  Even though it is called short-course, DOTS treatment lasts 6 to 8 months.

How IPT could help

        Although an IPT treatment is more complicated, costly, and time consuming than just having a patient swallow some pills under supervision, it may have some overbalancing advantages:

Faster, lower-cost treatment?   TB treatment takes 6 to 12 months because it takes the bacteria so long to die.  I suspect that this is partly because it is hard for drugs to get to all the bacteria, which can be anywhere in the body, including lymph nodes, the joints, the brain, and cerebrospinal fluid.   IPT has been demonstrated to deliver drugs more effectively into these more difficult to reach compartments of the body, including across the blood-brain barrier.  If IPT could cut TB treatment time in half, it would be a great boon to humanity.  It could reduce the cost tremendously, and increase patient compliance.  I suspect that IPT could cut treatment time down more than that, maybe eventually down to as little as a few days.

Better cure rate?  It could be that some TB treatment failures, even after a full course of therapy, are due to bacteria emerging from hidden compartments of the body to reinfect the patient.  If IPT can more effectively deliver anti-TB drugs into these compartments, likelihood of a cure should increase.

Less multiple-drug-resistance?  If IPT helps increase the TB cure rate, treatment availability (due to lower cost), and patient compliance, it will more effectively and more often kill all the TB bacteria in a patient.  This will reduce the development of multiple drug resistance. 

Lower toxic side effects?   If IPT potentiates TB drugs as it does other drugs, it could result in a smaller dose being needed, resulting in fewer or eliminated toxic side effects.  Smaller dose also means less cost, important in poor countries.

Immune system boost?   If IPT indeed boosts the immune system, it will enable the patient's body to better work with the drugs to kill and eliminate TB bacteria.  

Faster recovery?  IPT could enhance absorption of nutrients taken during and after treatment, thereby helping patients recover from the disease.

Simultaneous HIV and TB treatment?  If it turns out that IPT enhances both HIV and TB treatment, both diseases could be treated at the same time.

Prevention of TB? It could be that a few IPT treatments with TB drugs could eliminate the bacteria from people who have been exposed.  This could be part of a general multi-pathogen IPT  (MP-IPT) treatment protocol.

Update on 4/11/00:   I have had some discussions in person and by email with two TB experts, Peter Small MD at Stanford and David N. McMurray of Texas A & M.  They both agree that even if IPT would work for TB, it would be impractical for large scale use in the developing world due to its requirement of too much skill and equipment and patient access time.  My impression is that nothing could happen on the IPT-TB front until a someone takes interest in sponsoring a preliminary clinical trial.  When IPTQ gets funded, I hope to support such a study.

        In the mean time, IPT is available to patients who can afford it, in the unlikely event that they become infected with TB.  I suspect that patients in the developed world, and richer patients in the developing world would find it to be a shorter and less toxic course of treatment.  

 

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