Scientific Basis of DOTS

Scientific Basis of DOTS

In vitro experiments demonstrated that, after a culture of M. tuberculosis is exposed to certain drugs for some time, it takes several days before new growth occurs (the 'lag' phase). All the commonly used anti-TB drugs induce lag phases ranging from two days to forty days. Therefore these drugs can be given intermittently. Intermittent regimens make treatment observation more feasible and convenient for DOT providers and patients. They achieve high levels of treatment success with low relapse rates. As the quantity of drugs consumed is less, adverse reactions and costs are also lowered. In addition, intermittent dosing increases the efficacy of treatment by allowing organisms to re-enter the active metabolic phase in which the bactericidal drugs are more effective. Direct observation of treatment (DOT) ensures the best possible results in treatment of TB. Here an observer watches and assists the patient in swallowing the tablets, thereby ensuring that the patient receives the medication. Hence, by observing the patients during the entire course of treatment, one ensures that they receive the right drugs, in the right doses, at the right intervals and for the right duration. The bacillary sub-population in TB is of four kinds and different drugs act on different kind of bacteria. These are tabled below:
The phenomenon of 'persisters' explains to some extent why all bacilli are not killed during treatment. Relapse with drug-susceptible organisms after the end of treatment or endogenous reactivation may be due to bacilli that have persisted in residual lesions for a long time in a semi-dormant / dormant state.

Currently recommended treatment regimens aim to: Cure the patient

Type of TB Bacilli and Effective Drugs

• Extra-cellular rapidly multiplying :- Rifampicin,Isoniazid Streptomycin,Ethambutol
• Extra-cellular intermittently multiplying /semi- dormant:- Rifampicin
• Intra- and extra-cellular acidic environments intermittently multiplying/semi-dormant: -Pyrazina mide
• Dormant No drug

DOTS

• Prevent death from active disease or from its late effects
• Prevent the emergence and spread of drug-resistant organisms
• Minimise relapse
• Protect the community from continued transmission of infection

All treatment regimens consist of two phases:

Intensive Phase (IP) aims for a rapid killing of bacilli. This means a shorter duration of infectiousness ( 2 weeks), usually with rapid smear conversion (80% — 90%) after 2 to 3 months of treatment. Each dose in this phase should be directly observed to ensure adherence and involves 3 to 5 drugs depending on the category into which the patient has been placed.

Continuation Phase (CP) eliminates most residual bacilli and reduces failures and relapses. At the start of the CP, there are low numbers of bacilli and less chance of drug resistant mutants. Therefore fewer drugs are needed during this phase.


Dr Marwah