NATURAL HISTORY OF TUBERCULOSIS CAUSATIVE AGENT M. tuberculosis is a facultative intracellular parasite, i.e., it is readily ingested by phagocytes and is resistant to intracellular killing of importance to man are the human and bovine strains. The human strain is responsible for the vast majority of cases. The bovine strain affects mainly cattle and other animals COMMUNICABILITY Patients are-infective as long as they remain untreated. Effective antimicrobial treatment reduces infectivity by 90 percent within 48 hours Host factors • AGE : Tuberculosis affects all ages. Developing countries show a sharp rise in infection rates from infancy to adolescence. In the developed countries, the disease is now more common in the elderly, • (b) SEX : More prevalent in males than in females, (fe) HEREDITY : Tuberculosis is not a hereditary disease. However, twin studies indicate that inherited susceptibility is an important risk factor. • d) NUTRITION : Malnutrition is widely believed to predispose to tuberculosis, but the available evidence on this point is only indirect • (e) IMMUNITY : Man has no inherited immunity against tuberculosis. It is acquired as a result of natural infection or BCG vaccination. Clinical Features • Systemic: Systemic or constitutional symptoms of tuberculosis are due to toxemia and include anorexia, weight loss, lassitude, evening pyrexia, night sweets, etc. these are common to all forms of tuberculosis. Complications 1. Pulmonary: Pulmonary complications include pleurisy, pneumothorax, emphysema, pleural effusion, tubercular laryngitis, haemoptysis, etc. 2. Extra pulmonary: Extra pulmonary complications are varied and wide spread affecting multiple organs. Extra pulmonary complications may present as military tuberculosis, intestinal tuberculosis, tuberculous peritonitis, tuberculous lymphadenitis, cutaneous tuberculosis, tuberculous otitis, tuberculoma, etc. Social factors • The social factors include many nonmedical factors such as poor quality of life, poor housing, and overcrowding, population explosion, undernutrition, lack of education, large families, early marriages, lack of awareness of causes of illness, etc. All these factors are interrelated and contribute to the occurrence and spread of TUBERCULIN TEST The tuberculin test was discovered by Von Pirquet in 1907. A positive reaction to the test is generally accepted as evidence of past or present infection by M tuberculosis. The tuberculin test is the only means of estimating the prevalence of infection in a population. • There are three main tests currently in use : the Mantoux intradermal test, the Heaf and the Tine multiple puncture tests. The Heaf test is usually preferred for testing large groups of people because it is quick and easy to perform, reliable and cheap. The Mantoux is favoured when a more precise measurement of tuberculin sensitivity is required. The Tine test is considered by some authorities as unreliable, and therefore not • Tuberculin : The test material or antigen is known as tuberculin. There are two major antigens - the old tuberculin (OT), and the purified protein derivative (PPD). Since PPD is a purer preparation, it gives fewer non-specific reactions and is easier to standardize, it has replaced the OT. PPD is standardized in terms of its biological reactivity as "tuberculin units" (TU). • An international standard is maintained by WHO against which the potency of other preparations is measured. This standard PPD (PPD-S) has been arbitrarily designated as containing 50,000 tuberculin units per milligram (28). One TU is equal to 0.01 ml of OT or 0.00002 mg PPD. The WHO advocates a PPD tuberculin known as "PPD-RT-23 with Tween 80". • Tuberculines for skin testing have also been prepared from atypical mycobacteria. Thus we have PPD-B from the Battey mycobacterium; PPD-Y from M. kansasii; scrofulin from M. scrofulaceum, etc. These antigens are used in epidemiological surveys. • DOSAGE : The dosages of PPD in vogue are : (a) first strength or 1 TU, (b) intermediate strength or 5 TU, and for routine testing, the vaccinating teams in use 1 TU; in some countries, 5 TU are used. Nearly all truly infected persons react to 1 to 5 tuberculin units. MANTOUX TEST : The Mantoux test is carried out by injecting intradermally on the flexor surface of the forearm 1 TU of PPD in 0.1 ml. • The result of the test is red after 72 hrs. the reaction exceeding 10mm are considered positive. MODE OF TRANSMISSION • Tuberculosis is transmitted mainly by droplet infection and droplet nuclei generated by sputum-positive patients with pulmonary tuberculosis. To transmit infection, the particles must be fresh enough to carry a viable organism Incubation period • The time from receipt of infection to the development of a positive tuberculin test ranges from 3 to 6 weeks, and thereafter, the development of disease depends upon the closeness of contact, extent of the disease and sputum positivity of the source case (dose of infection) and hostparasite relationship. Thus the incubation period may be weeks, months or years. THE CONTROL OF TUBERCULOSIS • Case finding : • CASE FINDING TOOLS : • (i) Sputum examination : Sputum smear examination by direct microscopy is now considered the method of choice. The reliability, cheapness and ease of direct microscopic examination has made it number one case-finding method all over the world. Symptoms • a. persistent cough of about 3 or 4 weeks duration • b. continuous fever • c. chest pain • d. haemoptysis • Sputum culture : Culture examination of sputum is only secondary Importance in a case-finding programme. It is not only difficult, tedious, lengthy (takes at least 6 weeks) and expensive but also needs special training and expertise. (ii) Mass miniature radiography : Mass miniature radiography examinations have been stopped as a general measure of case finding. Chest X-ray is helping to some extent. • Tuberculin test : As the diagnostic value of tuberculin test is invalidated, this test has little value as a case-finding tool. Control by Treatment • Chemotherapy: • ''Chemotherapy is indicated in every case of active tuberculosis. The objective of treatment is cure - that is, the elimination of both the fast and slowly multiplying bacilli (including the persisters) from the patient's body BACTERICIDAL DRUGS • • • • Rifampicin (RMP) INH Streptomycin Pyrazinamide BACTERIOSTATIC DRUGS • Ethambutol • Thioacetazone Two-phase chemotherapy : • It is well recognized that there are two phases in the effective treatment of tuberculosis : • (i) the first is a short, aggressive or intense phase, early in the course of treatment, lasting 1-3 months. During this intensive phase, three or more drugs are combined to kill off as many bacilli as possible. The more rapidly the bacilli are killed initially, the less likely are "persisters" to emerge. • The risk of relapse is also lessened, (ii) the second or "continuation" phase is aimed at sterilizing the smaller number of dormant or persisting bacilli. • With the introduction of rifampicin and pyrazinamide, this period is now successfully reduced to 6-9 months. LONG-COURSE REGIMENS • the combination of INH plus thioacetazone is inexpensive, easy to administer and convenient to the patient because he has to swallow only one tablet a day./Streptomycin is given initially for the first two or three months. The total duration of treatment is usually 18 months. SHORT-COURSE CHEMOTHERAPY • There are a number of advantages of short-course chemotherapy, viz. rapid bacteriological conversion, lower failure rates and a reduction in the frequency of emergence of drugresistant bacilli. Patient compliance is improved, they become noninfectious earlier. The disadvantage is that the high cost of short-term chemotherapy militates against its wider use in developing countries.