M5L8: Tuberculosis

TB is respiratory infection & India is highly vulnerable to it. The reason being is, India supports one of the highest population densities in the world.

As per Global Burden of Disease report published by WHO, India comes under the list of 14 countries that have a higher burden compared to the rest of the countries in the world, when calculated about the risks that it faces due to combined spread of human immunodeficiency virus (HIV) and TB.

The antibiotic widely used in the treatment of TB include Capreomycin, Gemifloxacin, Isoniazid, Levofloxacin, Moxifloxacin, Pyrazinamide, Rafampicin etc. and certain habit-forming drugs like psychotropic drugs. Of these, many including levofloxacin are also used to treat other infections other than TB since it is Broad Spectrum Antibiotic.

Drugs and Cosmetics Act (1945) differentiates prescription drugs, narcotic and psychotropic substances, over the counter drugs and medical devices, with a view to promote safety in public health. The scheduling system from A to Y helps law makers, law enforcers, and healthcare professionals identify the nature of existing as well as new drugs.

Stages of TB Inflection

The current first-line treatment for TB is a multidrug regimen consisting of rifampin, isoniazid, pyrazinamide, ethambutol and Streptomycin (RIPES). It must be taken for at least 6 months to achieve high cure rates (more than 95% in experimental settings).

The fluoroquinolones are registered as second-line anti-TB drugs to treat patients that have become rifampin resistant (also known as RR-TB). Moxifloxacin and gatifloxacin are candidates for it. In case the bacteria become resistant to even these drugs, then this phase is called Multi Drug Resistant Tuberculosis (MDR TB).

MDR-TB treatment should include a minimum of four active drugs: a later-generation fluoroquinolone (moxifloxacin, gatifloxacin or levofloxacin) plus an injectable aminoglycoside (amikacin, capreomycin or kanamycin) plus any first-line drug. In case the patient becomes resistant to these drugs as well, then such a condition is called extensively drug resistant Tuberculosis (XDR TB).

Broad spectrum & narrow spectrum is the classification of antibiotics according to spectrum of their activity. Narrow-spectrum antibiotics are active against a select group of bacterial types. Broad-spectrum antibiotics are active against a wider number of bacterial types and, thus, may be used to treat a variety of infectious diseases. Broad-spectrum antibiotics are particularly useful when the infecting agent (bacteria) is unknown. All new generation antibiotics are broad-spectrum preparations. They have high efficiency and minimal side effects. However, they are simultaneously increasing & aggravating the incidences of drug resistance Tuberculosis. Ideally, in order to prevent the incidence of XDR / MDR TB, doctors should prefer to use only narrow spectrum antibiotics. At the same time, the reckless use and over the counter sale of Broad-Spectrum Antibiotics, without the advice of Medical Practitioner is an equally contributing factor for MDR TB.

Factors responsible for Drug Resistance in India

1.    Improper solid waste management

2.    Non availability of DOTS center

3.    Overuse on antibiotics in aquaculture, poultry and veterinary drugs

4.    Mass bathing in Ganga

5.    Overuse of disinfectants in the form of hand sanitizers, Dettol/ Savlon soap that contain antiseptic

6.    Over the counter sale of drugs

7.    Loss of gut bacteria due to overmedicalization

8.    Non-completion of treatment due to unaffordable out of pocket expenditures

To restrict the over the development of resistance against drugs, the government has come out with a new Schedule known as H1. Schedule H Drugs contains a list of drugs that can be sold only against the prescription of a registered medical practitioner. Only the required amount of medications mentioned in the prescription can be dispensed. These drugs can be supplied only to the licensed parties. The drug label must exhibit the text “Rx” and Schedule H drug warning: To be sold by retails on the prescription of a Registered Medical Practitioner only. The newly allocated schedule type H1 is used to restrict the selling of antibiotics through over the counter (OTC) sales. These schedule H1 drug includes 3rd & 4th generation antibiotics, anti-tuberculosis drugs. The label for such drugs should also bear the following words in a box with a red border. "Schedule H1 Drug-Warning: It is dangerous to take this preparation except in accordance with the medical advice. Not to be sold by retail without the prescription of a Registered Medical Practitioner." To dispense these drugs two main criteria, have to be followed strictly. ·         The drug supplied under the schedule H1 specification should be recorded in a separate register at the time of supply, mentioning the name and address of the prescriber, name of the patient, and the name of the drug along with the quantity supplied. ·         This register has to be maintained confidentially up to three years and should be open for inspection. The schedule H1 drugs should be labeled with the symbol Rx in red, clearly displayed on the left top corner of the drug label. This will help in 1. Surveillance of OTC sales 2. Studying patterns of antibiotic sensitivity and resistance 3. Launching of appropriate antibiotic and psychotropic policies in a healthcare facility 4. Creating awareness about rational use of antibiotics in all levels of medical setups including teaching medical institutions 5. Conducting frequent pharmacy inspections 6. Conduct Frequent Pharmacy Inspections 7. Eliminate illegal drug trafficking activities.

Recently, two new anti-TB drugs were approved by the US Food and Drug Administration (US FDA), Bedaquiline and Delamanid to treat XDR TB.

1.    Bedaquiline belongs to diarylquinoline class of antibiotics & its bactericidal activity in the murine model is superior to that of that of isoniazid and rifampicin.

2.    Delamanid and pretomanid belong to the nitroimidazole class of antibiotics, & are presently undergoing clinical trials.

3.    Benzothiazinones (BTZs) have also been discovered as an extremely potent class of novel antimycobacterials & are undergoing pre-clinical trials.

Methods to treat TB

1.    Using a bacterio-phage (genetically modified killer bacteria to treat drug resistance TB

2.    Using Nano particles

3.    Developing non-antibiotics to treat TB

4.    Improving body immunity