Question

Why combination therapy for tuberculosiswhy genetic yype of mutation develop in t.b?

Answer 1

The story of antituberculosis chemotherapy is a miniature of the history of anti-infective chemotherapy. In the first half of the 20th century the problem of tuberculosis appeared insoluble: the lipid-rich cell wall was believed to make chemotherapy impossible (21). This gloomy view seemed to be confirmed when the first antibiotics developed, sulfonamides and penicillin, had no useful activity against Mycobacterium tuberculosis. With this in mind it is easy to understand the early euphoria surrounding Albert Schatz and Selman Waksman’s discovery of streptomycin while working at Rutgers University in New Jersey (70) and Harold Lehmann’s discovery of para-aminosalicylic acid (PAS) shortly afterwards (47).

The clinical trials that followed the description of streptomycin rapidly dispersed the first hopes of a conquest of tuberculosis. Although patients improved compared with those patients not on therapy (the British Medical Research Council [BMRC] trial is widely considered to have been the first randomized controlled clinical trial), relapse occurred in many patients and the organisms were found to be resistant to streptomycin. Combined streptomycin and PAS trials proved that combination therapy prevented the emergence of resistance (14). The subsequent descriptions of isoniazid (19), pyrazinamide (52), rifampin (34), ethambutol (30), and other drugs gave the medical community the basic tools for tuberculosis control. The subsequent series of trials conducted under the auspices of the U.S. Public Health Service, the BMRC, and others produced data indicating that cure rates of over 95% with minimal relapse rates were possible in as little as 6 months, a reduction from the first regimens, which required treatment for 2 years (13, 22, 32, 33). Using these tools many countries have seen the virtual eradication of tuberculosis (82) and others, including some of the poorest, have seen a steady decline in the disease until the human immunodeficiency virus (HIV) epidemic caused the number of cases to spiral out of control (74). The tragedy of tuberculosis treatment is that, 50 years after the introduction of effective specific chemotherapy, the number of cases is higher worldwide and, more threateningly, there is an increasing number of cases of infections with organisms resistant to the major antituberculosis agents (25, 26, 62).

The circumstances in which drug resistance emerges are well known and have been so since shortly after the first clinical trials became available and their lessons were digested (51). In recent years the molecular basis for the mechanism of action of antituberculosis agents and the way in which the organisms become resistant have begun to be unraveled. In this review the clinical circumstances of resistance are described. The molecular mechanisms whereby resistance emerges are also outlined together with the insights that this brings to controlling the threat of an epidemic of multiple-drug resistance.

Answer 2

Explanation:

mutation and genetic drift are not same. 

• A mutation is defined as a heritable change in the genetic material of an organism.

• DNA sequence of the organism is altered and passed onto the daughter cells as the cell divides.

• Genetic drift is the change in the frequency of the alleles of a gene in a given population.

• Both of these are important mechanisms for evolution but are totally different.