Drug treatment for TB

In the nineteen-thirties and forties a desperate search was conducted across the world to see whether any natural or synthetic antibiotics could be safely used on humans infected with TB. One by one new drugs emerged, each heralded by a fanfare of hope.

Even the safest and strongest of candidates, however, revealed the same consistently worrying weakness: given the smallest of opportunities, the TB bacillae managed to develop resistance which rendered each drug useless when administered on its own.

A solution was found, however - which was to use a regimen which used more than one single drug at a time - termed "combination therapy". First two were used, then three, and finally four - a combination which was found to be effective in almost all cases. These were termed the so-called "FIRST LINE DRUGS" (isoniazid, rifampicin, ethambutol and pyrazinamide). They need to be adminstered daily for a period of six to eight months. Unfortunately, however, they are not easily tolerated.

Drug Susceptible TB

This describes strains of TB which can be effectively treated by these four first line drugs.

Drug Resistant TB (DR-TB)

These come in a variety of classifications, some of which are still not totally accepted or classified.

Single Drug Resistance

This describes strains of TB which are resistant to one of the four first line drugs. Drug treatment should still be effective.

Multi Drug Resistance (MDR-TB)

This describes strains of TB which are resistant to the two most powerful of the four first line drugs (isoniazid and rifampicin). Drug treatment with first line drugs will not only almost certainly be inneffective, but it may well also promote further drug resistance to the other two active drugs (to XDR-TB). Second line treatment uses six drugs over a period of two years - a total of 8736 toxic pills and injections. Side-effects are often debilitating, and (according to MSF) survival in South Africa from this regime is as low as 52%.

Incidence rates of MDR-TB are quite clearly on the rise in Africa. No-one has any clear figures on this because no appropriate surveillance exists. What is quite clear, however, and is also most alarming, is that cases of MDR-TB are not just occurring in patients who have relapsed (possibly because of uncompleted first line drug treatment): they are also occurring inceasingly in new cases. This means that MDR-TB is effectively out of the bag.

No-one has any clear idea on what proportion of the existing pool of latent infection is already carrying drug-resistant strains. It is almost impossible, however, that this proportion isn't growing.

A further fundamental problem is one of drug cost.

Extensive Drug Resistance (XDR-TB)

This describes strains of MDR-TB which are also resistant to a second line drug (one of the floriquinolones) and also a second line injectable drug. These are extremely difficult to treat. The term XDR-TB was coined after an outbreak in South Africa in 2006. Thankfully, this type of TB is not common, but it is most definitely increasing.

Extreme Drug Resistance (XXDR-TB)

This describes strains of disease which are resistant to four or more of the drugs, more so than XDR-TB. This is a recent classification and is not official. (There are a total of around seventeen compounds which are recognised as being in some way effective for treating the disease, some of which are extremely toxic).

Poly-Drug Resistance (PDR-TB)

A general description of all strains that are resistant to more than one drug.

Total Drug Resistance (TDR-TB)

This describes strains of disease which are effectively pharmaceutcally untreatable. Patients infected with TDR-TB have been positively identified in India in 2012, and also possibly also in Iran and Italy. There is an understandable reluctance for the medical community to publicly accept that this strain actually exists. The announcement in Mumbai indicates the realisation of the nightmare that has been dreaded by the WHO.