Tuberculosis

tuberculosis : definition, epidemology, transmission of tuberculosis, stages of tuberculosis, types of tuberculosis,etiology, pathogenesis, pathophysiology, clinical presentations, diagnosis, treatment of tuberculosis, treatment of tuberculosis in breastfeeding, pregnancy, HIV/AIDS, oral contraceptives, renal failure, liver failure conditions and multi-drug resistance tuberculosis : types , diagnosis, and treatment

1. TUBERCULOSIS Presented by: Venu priya Boyapati

2. TUBERCULOSIS Chronic airborne infection caused by Mycobacterium tuberculosis . Mycobacterium tuberculosis is also known as acid fast bacilli . It can also caused by Mycobacterium avium & Mycobacterium africanus .

3. EPIDEMOLOGY Tuberculosis (TB) is one of the top 10 causes of death worldwide. In 2016, 10.4 million people fell ill with TB, and 1.7 million died from the disease (including 0.4 million among people with HIV). Over 95% of TB deaths occur in low- and middle-income countries. Seven countries account for 64% of the total, with India leading the count, followed by Indonesia, China, Philippines, Pakistan, Nigeria, and South Africa. In 2016, an estimated 1 million children became ill with TB and 250 000 children died of TB (including children with HIV associated TB). TB is a leading killer of HIV-positive people: in 2016, 40% of HIV deaths were due to TB.

4. Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. WHO estimates that there were 600 000 new cases with resistance to rifampicin – the most effective first-line drug, of which 490 000 had MDR-TB. Globally, TB incidence is falling at about 2% per year. This needs to accelerate to a 4–5% annual decline to reach the 2020 milestones of the End TB Strategy. An estimated 53 million lives were saved through TB diagnosis and treatment between 2000 and 2016. Ending the TB epidemic by 2030 is among the health targets of the sustainable development goals.

5. TRANSMISSION OF TUBERCULOSIS Active TB INFECTIOUS

6. TYPES OF TUBERCULOSIS

7. STAGES OF TUBERCULOSIS Latent TB Active TB TB lives but does not grow in the body. TB is active and grows in the body. Does not make a person feel sick or have symptoms . Makes a person feel sick and have symptoms. Cannot spread from person to person. Can spread from person to person. Can advance to TB disease. Can cause death if not treated.

8. ETIOLOGY Close contact . Having close contact with someone who has an active TB. Low immunity . Immunocompromised status like those with HIV, cancer, or transplanted organs increases the risk of acquiring tuberculosis. Substance abuse . People who are IV/injection drug users and alcoholics have a greater chance of acquiring tuberculosis. Inadequate health care . Any person without adequate health care like the homeless, impoverished, and the minorities often develop active TB. Immigration . Immigration from countries with a high prevalence of TB could affect the patient. Overcrowding . Living in an overcrowded, substandard housing increases the spreading of the infection.

9. PATHOGENESIS Droplet nuclei containing tubercle bacilli are inhaled enter the lungs , and travel into alveoli Tubercle bacilli multiply in the alveoli A small number of tubercle bacilli enter the blood stream and spread throughout the body 1 2 3 4 Macrophages form a hard shell & keeps bacilli under control 5 Hard shell breaks down and tubercle bacilli escape and multiply

10. PATHO- PHYSIOLOGY Inhalation .  Tuberculosis begins when a susceptible person inhales mycobacteria and becomes infected. Transmission .  The bacteria are transmitted through the airways to the alveoli, and are also transported via  lymph  system and bloodstream to other parts of the body. Defence .  The body’s immune system responds by initiating an inflammatory reaction and phagocytes engulf many of the bacteria, and TB-specific  lymphocytes  lyse the bacilli and normal tissue. Protection .  Granulomas new tissue masses of live and dead bacilli, are surrounded by  macrophages , which form a protective wall.

11. Ghon’s tubercle .  They are then transformed to a fibrous tissue mass, the central portion of which is called a Ghon’s tubercle. Scarring .  The bacteria and  macrophages  turns into a cheesy mass that may become calcified and form a collagenous scar. Dormancy .  At this point, the bacteria become dormant, and there is no further progression of active disease. Activation .  After initial exposure and  infection , active disease may develop because of a compromised or inadequate immune system response.

12. CLINICAL MANIFESTATIONS After an incubation period of 4 to 8 weeks , TB is usually asymptomatic in primary infection. Nonspecific symptoms . Nonspecific symptoms may be produced such as fatigue, weakness, anorexia, weight loss, night sweats, and low-grade fever, with fever and night sweats as the typical hallmarks of tuberculosis. Cough . The patient may experience cough with mucopurulent sputum. Hemoptysis . Occasional hemoptysis or blood on the saliva is common in TB patients. Chest pain . The patient may also complain of chest pain as a part of discomfort.

13. DIAGNOSIS Sputum culture : Positive for Mycobacterium tuberculosis in the active stage of the disease. Ziehl-Neilsen (acid-fast stain applied to a smear of body fluid): Positive for acid-fast bacilli (AFB). Skin tests (purified protein derivative [PPD] or Old tuberculin [OT] administered by intradermal injection [Mantoux]): A positive reaction (area of induration 10 mm or greater, occurring 48–72 hr after inter dermal injection of the antigen) indicates past infection and the presence of antibodies but is not necessarily indicative of active disease. Factors associated with a decreased response to tuberculin include underlying viral or bacterial infection, malnutrition, lymphadenopathy, overwhelming TB infection, insufficient antigen injection, and conscious or unconscious bias. A significant reaction in a patient who is clinically ill means that active TB cannot be dismissed as a diagnostic possibility. A significant reaction in healthy persons usually signifies dormant TB or an infection caused by a different mycobacterium.

14. Enzyme-linked immunosorbent assay (ELISA)/Western blot : May reveal presence of HIV. Chest x-ray : May show small, patchy infiltrations of early lesions in the upper-lung field, calcium deposits of healed primary lesions, or fluid of an effusion. Changes indicating more advanced TB may include cavitation, scar tissue/fibrotic areas. CT or MRI scan : Determines degree of lung damage and may confirm a difficult diagnosis. Bronchoscopy : Shows inflammation and altered lung tissue. May also be performed to obtain sputum if patient is unable to produce an adequate specimen. Histologic or tissue cultures (including gastric washings; urine and cerebrospinal fluid [CSF]; skin biopsy): Positive for Myco­bacterium tuberculosis and may indicate extrapulmonary involvement. Needle biopsy of lung tissue : Positive for granulomas of TB; presence of giant cells indicating necrosis.

15. Electrolytes : May be abnormal depending on the location and severity of infection; e.g., hyponatremia caused by abnormal water retention may be found in extensive chronic pulmonary TB. ABGs : May be abnormal depending on location, severity, and residual damage to the lungs. Pulmonary function studies : Decreased vital capacity, increased dead space, increased ratio of residual air to total lung capacity, and decreased oxygen saturation are secondary to parenchymal infiltration/fibrosis, loss of lung tissue, and pleural disease (extensive chronic pulmonary TB).

16. TREATMENT Treatment goals Promote airway clearance. Adhere to treatment regimen. Promote activity and adequate nutrition. Prevent spread of tuberculosis infection.

17. Pulmonary tuberculosis is treated primarily with anti tuberculosis agents for 6 to 12 months. First line treatment . First-line agents for the treatment of tuberculosis are isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide. Active TB . For most adults with active TB, the recommended dosing includes the administration of all four drugs daily for 2 months, followed by 4 months of INH and RIF. Latent TB . Latent TB is usually treated daily for 9 months.

18. Treatment guidelines . Recommended treatment guidelines for newly diagnosed cases of pulmonary TB have two parts: an initial treatment phase and a continuation phase. Initial phase . The initial phase consists of a multiple-medication regimen of INH, rifampin , pyrazinamide, and ethambutol and lasts for 8 weeks. Continuation phase . The continuation phase of treatment include INH and rifampin or INH and rifapentine, and lasts for an additional 4 or 7 months. Prophylactic isoniazid . Prophylactic INH treatment involves taking daily doses for 6 to 12 months. DOT . Directly observed therapy may be selected, wherein an assigned caregiver directly observes the administration of the drug

19. PHARMA- COLOGICAL THERAPY The first line anti-tuberculosis medications include: Isoniazid (INH). INH is a bactericidal agent that is used as prophylaxis for neuritis, and has side effects of peripheral neuritis, hepatic enzyme elevation, hepatitis, and hypersensitivity. Rifampin ( Rifadin ). Rifampin is a bactericidal agent that turns the urine and other body secretions into orange or red, and has common side effects of hepatitis, febrile reaction, purpura, nausea, and vomiting. Pyrazinamide . Pyrazinamide is a bactericidal agent which increases the uric acid in the blood and has common side effects of hyperuricemia, hepatotoxicity, skin rash, arthralgias, and GI distress. Ethambutol ( Myambutol ). Ethambutol is a bacteriostatic agent that should be used with caution with renal disease, and has common side effects of optic neuritis and skin rash.

20. TREATMENT OF TUBERCULOSIS IN SPECIAL CASES Pregnancy : Always ask a woman if she is pregnant before commencing treatment, most of anti-TB is safe during pregnancies except streptomycin, which causes permanent deafness in the foetus therefore it should be avoided during pregnancy Breastfeeding : Full TB treatments are safe and are best way to prevent tuberculosis in the baby mother and child can stay together for the entire duration of treatment. In the mothers with pulmonary tuberculosis, the baby should receive INH preventive (5mg/kg) for 6months followed BCG vaccination Oral contraceptives : Rifampicin interacts with oral contraceptives and reduces the efficacy of this contraception. Women using contraceptive should be advised to use pills with higher dose of oestrogen (50mcg) or change to another method

21. Liver disease : Most of anti-TB can cause liver damage. In case a patient develops jaundice, treatment should be stopped and restarted as soon as the jaundice resolves. In severely ill patients start streptomycin and ethambutol only. If the patient improves follow with a gradual step up introduction of isoniazid followed by rifampicin until full dose. Monitor liver functions and clinical picture. If the condition deteriorates stop the drug which was added. Patients with established chronic liver disease should not receive pyrazinamide Renal failure ; Isoniazid, Rifampicin and Pyrazinamide are almost entirely excreted by the liver and therefore safe to use. Streptomycin and Ethambutol are excreted by the kidneys and should either be avoided or given in a reduced dose. The safest regimen for patients with renal failure is 2 RHZ/4 RH combined with pyridoxine to prevent Isoniazid induced peripheral neuropathy

22. HIV/AIDS : There is a danger of interaction between Rifampicin and protease inhibitors in HIV positive patients receiving anti retroviral (ARV) treatments. Rifampicin stimulates the activity of the liver enzyme system, which metabolises protease inhibitors (PI) and Nucleoside Reverse Transcriptase Inhibitors (NRTIs). This can lead to decreased blood levels of PIs and NsRTIs . Of the NsRTIs the concentration of Nevirapine is significant reduced and hence Nevirapine and Rifampicin should not be used concomitantly. On other hand PIs enhance the liver enzyme system which influences the blood levels of rifampicin resulting in ineffective TB treatment or drug toxicity. NRTIs can cause peripheral neuropathy, which can result in an added toxicity caused by Isoniazid.

23. MDR-TB Multi drug resistance Tuberculosis : MDR TB is a laboratory diagnosis confirmed after culturing Mycobacterium tuberculosis strains and performing drug susceptibility tests (DST). Resistant strains will be identified because they will be able to survive exposure to anti TB drugs which were previously toxic to them. Four different categories of drug resistance have been identified: Mono-resistance : Resistance to one anti-tuberculosis drug Poly-resistance : Resistance to more than one anti-tuberculosis drug, other than both isoniazid and Rifampicin (e.g. against both pyrazinamide and isoniazid) Multidrug-resistance : Resistance to at least isoniazid and rifampicin Extensive drug resistance TB (XDR-TB): Multi drug resistance with additional resistance to any fluoroquinolone, and at least one of three injectable second-line drugs (capreomycin, kanamycin and amikacin

24. Diagnosis of MDR –TB : The required baseline investigations of any DR -TB suspect include: • Comprehensive medical history including outcomes of prior TB treatment • Physical examination • Collection of 2 sputum samples (spot – morning) for smear microscopy, culture and DST • Provider Initiated Testing and Counselling (PITC) for HIV • Chest X-ray examination DST confirmed MDR TB patients shall be referred and transported by a special ambulance to the MDR TB Hospital where they will be admitted

25. TREATMENT OF MDR-TB Standardized treatment : Regimens are designed according to representative Drug Resistance Well-defined patient populations. All patients in a patient group or category receive the same regimen . Suspected MDR TB should be confirmed by DST whenever possible. Intensive Phase (minimum 6 months, or 6 months post culture conversion) : Amikacin or Kanamycin Ofloxacin or Levofloxacin Pyrazinamide Ethionamide Cycloserine Ethambutol

26. Continuation Phase (minimum 12 months or 18 months post culture conversion) Ofloxacin or Levofloxacin Ethionamide Pyrazinamide Cycloserine Ethambutol

27. PATIENT EDUCATION Disposal of secretions.  Cough and sneeze into tissues and to dispose of all secretions in a separate trash can. Isolation.  Wear a mask when going outside of the room. Activity and nutrition.  Remind the patient to take a lot of rest and to eat balanced meals to aid recovery. Adverse effects.  Advise the patient to watch out for adverse effects of medications and to report them to the physician immediately

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