Tuberculosis

This presentation is a detail discussion on different forms of TB and management.

1. TUBERCULOSIS Oct. 10,2017 Dep’t of Internal Medicine Melaku Yitbarek(M.D.)

2. OUTLINE: Epidemiology Pathogenesis Clinical pictures TB-HIV Co-infection Diagnosis Treatment ,Prevention& Follow up

3. Epidemiology More than 5.7 million new cases of TB (all forms, both pulmonary And extrapulmonary)Were reported to WHO in 2013; 95% of cases were reported from developing countries. It is further estimated that 1.49 million (range, 1.32–1.67 million) deaths from TB, including 0.36 million among people living with HIV infection

4. Epidemiology M. tuberculosis is most commonly transmitted from a person with infectious pulmonary TB by droplet nuclei, which are aerosolized by coughing, sneezing, or speaking Important determinants of likelihood of transmission: The probabilityof contact with a person who has an infectious form of TB, the intimacy and duration of that contact The degree of infectiousness of the case and the shared environment in which the contact takes place.

5. Epi. Cont’d TB patients whose sputum contains AFB visible by microscopy (sputum smear–positive cases) are the most likely to transmit the infection. The most infectious patients have cavitary pulmonary disease Patients with sputum smear–negative/culture-positive TB are less infectious, Crowding in poorly ventilated rooms is one of the most important factors in the transmission of tubercle bacilli because it increases the intensity of contact with a case

6. Epi. Cont’d Unlike the risk of acquiring infection with M. tuberculosis, the risk of developing disease after being infected depends largely on endogenous factors, such as the individual’s innate immunologic and non immunologic defenses and the level at which the individual’s cell-mediated immunity(CMI) is functioning.

7. Epi. Cont’d Clinical illness directly following infection is classified as primary TB and is common among children in the first few years of life and among immunocompromised persons. Although primary TB may be severe and disseminated, it generally is not associated with high-level transmissibility. When infection is acquired later in life, the chance is greater that the mature immune system will contain it at least temporarily. Bacilli, however, may persist for years before reactivating to produce secondary (or postprimary) TB,which, because of frequent cavitation, is more often infectious than is primary disease.

8. Epi . Cont’d Overall, it is estimated that up to 10% of infected persons will eventually develop active TB in their lifetime The risk is much higher among HIV-infected persons. Reinfection of a previously infected individual, which is common in areas with high rates of TB transmission,may also favor the development of disease

9. Natural HX of the disease untreated TB is often fatal About one-third of patients died within 1 year after diagnosis, and more than 50% died within 5 years. The 5-year mortality rate among sputum smear–positive cases was 65%. Of the survivors at 5 years, ~60% had undergone spontaneous remission, while the remainder were still excreting tubercle bacilli. With effective, timely, and proper chemotherapy, patients have a very high chance of being cured However, improper use of anti-TB drugs, while reducing mortality rates, may also result in large numbers of chronic infectious cases, often with drug-resistant bacilli

10. Etiology &Pathogenesis Mycobacteria:belongto the family Mycobacteriaceae and orderActinomycetales M. tuberculosiscomplex, which comprises eight distinct subgroups, the most common and important agent of human disease is M.tuberculosis M .tuberculosis complex includes M.bovis, M.caprea, M.africanum, M.microti, M.pennipeddi, M.canneti

11. Etiology M. tuberculosis is a rod-shaped, non-spore- forming, thin aerobic Bacterium measuring 0.5µm by 3µm Mycobacteria, including M. tuberculosis, are often neutral on Gram’s staining However, once stained, the bacilli cannot be decolorized by acid alcohol; this characteristic justifies their classification as acid-fast bacilli

12. AFB stain-rods in chain

13. Schematic diagram of Mycobacterial cell wall. 1.outer lipids 2.mycolic acid 3.polysaccharides ( arabinogalactan ) 4.peptidoglycan 5.plasma membrane 6.lipoarabinomannan (LAM) 7.phosphatidylinositol mannoside 8.cell wall skeleton

14. Pathogenesis The interaction of M. tuberculosis with the human host begins when droplet nuclei containing viable microorganisms propelled into the air by infectious patients are inhaled by a close bystander Although the majority of inhaled bacilli are trapped in the upper airways and expelled by ciliated mucosal cells, a fraction (usually <10%) reach the alveoli There, alveolar macrophages that have not yet been activated phagocytose the bacilli

15. Pathogenesis

16. Patho . Cont’d In the initial stage of host–bacterium interaction, prior to the onset of an acquired CMI response, M. tuberculosis disseminates widely through the lymph vessels, spreading to other sites in the lungs and other organs, and undergoes a period of extensive growth within naïve unactivated macrophages additional naïve macrophages are recruited to the early granuloma

17. Patho . Cont’d Ultimately,the chemo-attractants and bacterial products released during the repeated rounds of cell lysis and infection of newly arriving macrophages enable dendritice cells to access bacilli these cells migrate to the draining lymph nodes and present mycobacterial antigens to T lymphocytes At this point,the development of CMI and humoral immunity begins. These initial stages of infection are usually asymptomatic

18. Patho.Cont’d About 2–4 weeks after infection, two host responses to M. tuberculosis develop: a macrophage-activating CMI response T cell–mediated phenomenon resulting in the activation of macrophages that are capable of killing and digesting tubercle bacilli and a tissue-damaging response the result of delayed type hypersensitivity (DTH) reaction various to bacillary antigens; it destroys unactivated macrophages that contain multiplying bacilli but also causes caseous necrosis of the involved tissues

19. Patho.Cont’d Although both of these responses can inhibit mycobacterial growth, it is the balance between the two that determines the forms of TB that will develop subsequently With the development of specific immunityand the accumulation of large numbers of activated macrophages at the site of the primary lesion, granulomatous lesions (tubercles) are formed These lesions consist of accumulations of lymphocytes and activated macrophages that evolve toward epithelioid and giant cell morphologies

20. Clinical Manifestations TB is classified as pulmonary, extrapulmonary, or both. Dependingon several factors linked to different populations and bacterial strains, extrapulmonary TB may occur in 10–40% of patients. Furthermore, upto two-thirds of HIV-infected patients with TB may have both pulmonary and extrapulmonary TB or extrapulmonary TB alone.

21. Clinical.Cont’d Pulmonary TB: Pulmonary TB is conventionally categorized as primary or postprimary(adult-type, secondary) a large percentage of cases of adult pulmonary TB result from recent infection (either primary infection or reinfection) and not from reactivation

22. Clinical.Cont’d Primary Pulmonary TB: Primary pulmonary TB occurs soon after the initial infection with tubercle bacilli It may be asymptomatic or may present with fever and occasionally pleuritic chest pain. In areas of high TB transmission, this form of disease is often seen in children In the majority of cases, the lesion heals spontaneously and becomes evident only as a small calcified nodule TheGhon focus , with or without overlying pleural reaction, thickening, and regional lymphadenopathy, is referred to as the Ghon complex .

23. Clinical.Cont’d Primary Pulmonary TB: In young children with immature CMI and in persons with impaired immunity (e.g., those with malnutrition or HIV infection),primary pulmonary TB may progress rapidly to clinical illness Pleural effusion, which is found in up to two-thirds of cases, results from the penetration of bacilli into the pleural space from an adjacent subpleural focus. In severe cases, the primary site rapidly enlarges, its central portion undergoes necrosis, and cavitation develops (progressive primary TB) TB in young children is almost invariably accompanied by hilar or paratracheal lymphadenopathy due to the spread of bacilli from the lung parenchyma through lymphatic vessels

24. Pleural effusion…

25. Clinicla.Cont’d Primary Pulmonary TB: Enlarged lymph nodes may compress bronchi, causing total obstruction with distal collapse partial obstruction with large-airway wheezing or a ball-valve effect with segmental/lobar hyperinflation. Occult hematogenous dissemination commonly follows primary infection However, in the absence of a sufficient acquired immune response, which usually contains the infection,disseminated or miliary disease may result

26. Chest radiograph showing rt hilar LN enlargement and

27. Chest X-ray showing bilateral Miliary infiltrates

28. Clinical.Cont’d Postprimary (Adult-Type) Disease : also referred to as reactivation or secondary TB, It is usually localized to the apical and posterior segments of the upper lobes, where the substantially higher mean oxygen tension (compared with that in the lower zones) favors mycobacterial growth The extent of lung parenchymal involvement varies greatly, from small infiltrates to extensive cavitary disease

29. Clinical.Cont’d Postprimary (Adult-Type) Disease : Early in the course of disease, symptoms and signs are often non specific and insidious, consisting mainly of diurnal fever and nightsweats due to defervescence, weight loss, anorexia, general malaise,and weakness. However, in up to 90% of cases, cough eventually develops—often initially nonproductive and limited to the morning and subsequently accompanied by the production of purulent sputum,sometimes with blood streaking Hemoptysis develops in 20–30% of cases, and massive hemoptysis may ensue as a consequence of the erosion of a blood vessel in the wall of a cavity. Pleuritic chest pain,dyspnea

30. Clinical.Cont’d Post primary (Adult-Type) Disease: P/E: Many patients have no abnormalities detectable by chest examination whereas others have detectable rales in the involved areas during inspiration, especially after coughing. Occasionally, rhonchi due to partial bronchial obstruction and classic amphoric breath sounds in areas with large cavities maybe heard

31. Clinical.Cont’d Post primary (Adult-Type) Disease: P/E: Systemic features include fever (often low-grade and intermittent) in up to 80% of cases and wasting absence of fever,however,notexclude TB. In some cases, pallor and finger clubbing develop The most common hematologic findings are mild anemia,leukocytosis, and thrombocytosis with a slightly elevated erythrocyte sedimentation rate and/or C-reactive protein level None of these findings is consistent or sufficiently accurate for diagnostic purposes.

32. Extrapulmonary Tuberculosis In order of frequency, the extrapulmonary sites most commonly involved in TB are the lymph nodes, pleura, genitourinary tract, bones and joints, meninges, peritoneum, and pericardium However, virtually all organ systems may be affected As a result of hematogenous dissemination in HIV-infected individuals,extrapulmonaryTB is seen more commonly today than in the past in settings of high HIV prevalence.

33. Extrapul.TB Lymph Node TB (Tuberculous Lymphadenitis): The most common presentation of extrapulmonary TB in both HIV- sero-negative and HIV-infected patients (35% of cases worldwide and more than 40%ofcases in the United States in recent series) lymph node disease is particularly frequent among HIV-infected patients and among children Lymph node TB presents as painless swelling of the lymph nodes, most commonly at posterior cervical and Supraclavicular sites (a condition historically referred to as scrofula)

34. Extrapul.TB Lymph nodes are usually discrete in early disease but develop into a matted non tender mass over time and may result in a fistulous tract draining caseous material Associated pulmonary disease is present in fewer than 50% of cases, and systemic symptoms are uncommon except in HIV infected patients The diagnosis is established by fine-needle aspiration biopsy (with a yield of up to 80%) or surgical excision biopsy. cultures are positive in 70–80% of cases

35. Extrapul.TB Pleural TB: Involvement of the pleura accounts for ~20% of extrapulmonary cases in the United States and elsewhere Isolated pleural effusion usually reflects recent primary infection, and the collection of fluid in the pleural space represents a hypersensitivity response to mycobacterial antigens Depending on the extent of reactivity, the effusion may be small, remain unnoticed, and resolve spontaneously or may be sufficiently large to cause symptoms such as fever, pleuritic chest pain,and dyspnea

36. Extrapul.TB Pleural TB : Physical findings are those of pleural effusion: dullness to percussion and absence of breath sounds A chest radiograph reveals the effusion and, in up to one-third of cases,also shows parenchymal lesion. Thoracentesis is required to ascertain the nature of the effusion and to differentiate it from manifestations of other etiologies The fluid is straw colored and at times hemorrhagic; It is an exudate with a protein concentration >50% of that in serum Neutrophils may predominate in the early stage, but lymphocyte predominance is the typical finding later

37. Extrapul.TB TB of the upper Airways : Nearly always a complication of advanced cavitary pulmonary TB TB of the upper airways may involve the larynx, pharynx, and epiglottis Symptoms include hoarseness, dysphonia, and dysphagia in addition to chronic productive cough Acid-fast smear of the sputum is often positive, but biopsy maybe necessary in some cases to establish the diagnosis

38. Extrapul.TB Genitourinary TB : accounts for ~10–15% of all extrapulmonary cases Local symptoms predominate, and up to 75% of patients have chest radiographic abnormalities suggesting previous or concomitant pulmonary disease. Urinary frequency, dysuria, nocturia, hematuria, and flank or abdominal pain are common presentations Urinalysis gives abnormal results in 90% of cases, revealing pyuria and hematuria The documentation of culture-negative pyuria in acidic urine should raise the suspicion of TB Culture of three morning urine specimens yields a definitive diagnosis in nearly 90% of cases

39. Extrapul.TB Genitourinary TB: Genital TB diagnosed more commonly in female than in male patients In female patients, it affects the fallopian tubes and the endometrium and may cause infertility, pelvic pain, and menstrual abnormalities. In male patients, genital TB preferentially affects the epididymis, producing a slightly tender mass that may drain externally through a fistulous tract; orchitis and prostatitis may also develop

40. Extrapul.TB Skeletal TB: In the United States, TB of the bones and joints is responsible for ~10% of extrapulmonary cases In bone and joint disease,pathogenesis is related to reactivation of hematogenous foci or to spread from adjacent paravertebral lymph nodes. Weight-bearing joints (the spine in 40% of cases, the hips in 13%, and the knees in 10%) are most commonly affected Spinal TB ( Pott’s disease or tuberculous spondylitis; often involves two or more adjacent vertebral bodies With advanced disease, collapse of vertebral bodies results in kyphosis (gibbus) A catastrophic complication of Pott’s disease is paraplegia , which is usually due to an abscess or a lesion compressing the spinal cord.

41. Extrapul.TB Tuberculous Meningitis and Tuberculoma : TB of the central nervous system accounts for~5%of extrapulmonary cases in the United States It is seen most often in young children but also develops in adults, especially those infected with HIV. Tuberculous meningitis results from the hematogenous spread of primary or postprimary pulmonary TB or from the rupture of a subependymal tubercle into the subarachnoid space The disease often presents subtly as headache and slight mental changes after a prodrome of weeks of low-grade fever, malaise, anorexia, and irritability.

42. Extrapul.TB Tuberculous Meningitis and Tuberculoma : If not recognized, tuberculous meningitis may evolve acutely with severe headache, confusion, lethargy, altered sensorium , and neck rigidity Typically, the disease evolves over 1–2 weeks, a course longer than that of bacterial meningitis Lumbar puncture is the cornerstone of diagnosis. In general, examination of cerebrospinal fluid (CSF) reveals a high leukocyte count (upto1000/µL), usually with a predominance of lymphocytes but sometimes with a predominance of neutrophils in the early stage Culture of CSF is diagnostic in up to 80% of cases and remains the gold standard If unrecognized, tuberculous meningitis is uniformly fatal

43. Extrapul.TB Tuberculous Meningitis and Tuberculoma : Tuberculoma, an uncommon manifestation of central nervous systemTB, presents as one or more space-occupying lesions and usually causes seizures and focal signs. CT or MRI reveals contrast-enhanced Ring lesions, but biopsy is necessary to establish the diagnosis.

44. Extrapul.TB Gastrointestinal TB: Gastrointestinal TB is uncommon, making up 3.5% of extrapulmonary cases in the United States. Various pathogenetic mechanisms areinvolved:swallowing of sputum with direct seeding,hematogenous spread, or (largely in developing areas) ingestion of milk from cows affected by bovine TB. Although any portion of the gastrointestinal tract may be affected, the terminal ileum and the cecum are the sites most commonly involved Abdominal pain (at times similar to that associated with appendicitis) and swelling,obstruction, hematochezia, and a palpable mass in the abdomen are common findings at presentation.

45. Extrapul.TB Gastrointestinal TB: Fever, weight loss, anorexia, and night sweats are also common. Tuberculous peritonitis follows either the direct spread of tubercle bacilli from ruptured lymph nodes and intraabdominal organs (e.g.,genital TB in women) or hematogenous seeding Nonspecific abdominal pain, fever, and ascites should raise the suspicion tuberculous peritonitis In tuberculous peritonitis, paracentesis reveals an exudative fluid with a high protein content and leukocytosis that is usually lymphocytic (although neutrophils occasionally predominate) peritoneal biopsy (with a specimen best obtained by laparoscopy) is often needed to establish the diagnosis

46. Extrapul.TB Pericardial TB (Tuberculous Pericarditis ): pericardial TB has often been a disease of the elderly in countriesWith low TB prevalence However,it also develops frequently in HIV-infected patients. The onset may be subacute, although an acute presentation, with dyspnea, fever, dull retrosternal pain, and a pericardial friction rub, is possible An effusion eventually develops in many cases; cardiovascular symptoms and signs of cardiac tamponade may ultimately appear

47. Extrapul.TB Miliary or Disseminated TB: Miliary TB is due to hematogenous spread of tubercle bacilli. Although in children it is often the consequence of primary infection, in adults it may be due to either recent infection or reactivation of old disseminated foci Clinical manifestations are nonspecific and protean, depending on the predominant site of involvement. fever, night sweats, anorexia, weakness, and weight loss are presenting symptoms in the majority of cases Physical findings include hepatomegaly,splenomegaly, and lymphadenopathy

48. Extrapul.TB A high index of suspicion is required for the diagnosis of miliary TB. Frequently, chest radiography reveals a miliary reticulonodular pattern ,although no radiographic abnormality may be evident early in the course and among HIV-infected patients Sputum-smear microscopy is negative in most cases If it goes unrecognized,miliary TB is lethal; with proper early treatment, however, it is amenable to cure

49. TB-HIV Co-infection TB is one of the most common diseases among HIV-infected persons worldwide and a major Cause of death in this population more specifically, it is responsible for an estimated 24% of all HIV-related mortality A new TB infection acquired by an HIV-infected individual may evolve to active disease in a matter of weeks rather than months or years TB can appear at any stage of HIV infection, and its presentation varies with the stage.

50. TB-HIV Co-infection When CMI is only partially compromised, pulmonary TB presents in a typical manner with upper-lobe infiltrates and cavitations and without significant lymphadenopathy or pleural effusion In late stages of HIV infection, when the CD4+ Tcell count is <200/µL, a primary TB–like pattern, with diffuse interstitial and subtle infiltrates , little or no cavitations, pleural effusion, and intrathoracicl ymphadenopathy, is more common Overall, sputum smears are less frequently positive among TB patients with HIV infection than among those without; thus, the diagnosis of TB may be difficult Extrapulmonary TB is common among HIV-infected patients

51. TB-HIV Co-infection The diagnosis of TB in HIV-infected patients may be complicated not only by the increased frequency of sputum-smear negativity (up to 40% in culture proven pulmonary cases) but also by atypical radiographic findings, a lackof classic granuloma formation in the late stages The Xpert MTB/RIF assay (see “Nucleic Acid Amplification Technology,” below) is the preferred initial diagnostic option, and therapy should be started on the basis of a positive result because treatment delays may be fatal A negative Xpert MTB/RIF result does not exclude a diagnosis of TB, and culture remains the gold standard

52. TB-HIV Co-infection Immune reconstitution inflammatory syndrome (IRIS): Exacerbations in systemic (lymphadenopathy) or respiratory symptoms, signs, and laboratory or radiographic manifestations of TB have been associated with the administration of ART and occur in ~10% of HIV-infected TB patients Usually developing 1–3 months after initiation of ART, IRIS is more common among patients with advanced immuno suppression and extrapulmonary TB The earlier ART is started and the lower the baseline CD4+ T cell count, the greater the risk of IRIS Death due to IRIS is relatively infrequent and occurs mainly among patients who have a high preexisting mortality risk

53. Diagnosis The key to the diagnosis of TB remains a high index of suspicion Sputum Direct light Smear Microscopy mainstay of diagnostic methods to test for the presence of acid fast bacilli(AFB). Light emitting diode (LED) microscopy a newly introduced diagnostic tool to complement the conventional microscopy It is recommended for centers with high case load as it saves time and improves sensitivity. Sputum culture and medicine susceptibility test a highly sensitive diagnostic method Culture remains the gold standard in mycobacterial detection

54. Diagnosis Line Probe Assay a new test to identify the presence of specific mutations on the genes of TB bacilli which are responsible for Isoniazid and Rifampicin resistance It is a rapid and accura te test to identify cases with MDR-TB. Gene Xpert MTB/RIF a new, rapid and fully automated DNA/molecular diagnostic test to detect TB and Rifampicin medicine resistance simultaneously It is indicated for the diagnosis of TB in high MDR-TB and TB/HIV settings.

55. Diagnosis Fine needle aspiration from accessible mass like peripheral enlarged lymph nodes and histopathological examination. Tissue biopsy from any body tissues such as serous membranes, skin, endometrium, bronchial, pleural, gastric or liver tissue for histophatological examination Chest x-ray Other investigation: HIV test, ESR, CSF analysis

56. Treatment of TB Objectives Cure the TB patient and restore quality of life and productivity Prevent death from active TB or its late effects Prevent TB relapse Prevent the development and transmission of medicine resistance Decrease transmission.

57. Treatment of TB Non pharmacologic Counselling Good nutrition Adequate rest Admission for severely ill patients

58. Treatment of TB Pharmacologic: Treatment of TB is with a combination of 4 or more anti-TB medicines the treatment is standardized by putting patients into different treatment groups based on smear status and previous history of treatment for TB standardized treatment means that all patients in a defined group receive the same treatment regimen TB treatment strategy is referred to as DOT indicating that treatment is given under direct observation of a health worker or treatment supporter daily throughout the course of treatment

59. Treatment of TB Treatment with 1st line anti-TB Medicines: TB Patients with strains susceptible to first line anti-TB medicines are treated with standardized first line treatment regimen for 6 or 8 months, depending on the history of previous TB treatment The first line anti-TB medicines available for TB treatment in Ethiopia are: Rifampicin(R) Ethambutol (E) Isoniazid (H) Pyrazinamide (Z) and Streptomycin (S)

60. Treatment of TB 1.TB treatment regimen with first line anti-TB medicines Treatment regimen for new patients : newly diagnosed smear positive, smear negative and extrapulmonary TB patients who have never had treatment for TB,or have taken anti-TB medicines for less than 1 month This regimen consists of 8 weeks (2 months) treatment with Rifampicin, Isoniazid, Pyrazinamide and Ethambutol during the intensive phase , followed by four months with Rifampicin and Isoniazid in the continuation phase (2RHZE/4RH). Other Previously treated Smear Negative PTB and EPTB cases (Case definition ‘Other’) who were previously cured or treatment completed will be treated with New TB patient regimen

61. Treatment of TB 1.Treatment regimen for previously treated patients (Re-treatment Regimen) Patients who have previously received 1 month or more of anti-TB medicines. This regimen consists of an eight week (2 month) treatment with Streptomycin, Rifampicin, Isoniazid, Pyrazinamide and Ethambutol followed by a four week (1 month ) treatment with Rifampicin, Isoniazid, Pyrazinamide and Ethambutol during the intensive phase, followed by five months on Rifampicin, Isoniazid and Ethambutol: 2SRHZE/1RHZE/5(RH)E

62. Treatment of TB Common drug Side effects: Isoniazide : hepatitis, peripheral neuropathy Rifampicine: GI reaction, hepatitis Pyrazinamide : hepatitis,arthralgia Streptomycine: hypersensitivity, vestibular/ fetal auditory damage Ethambutol: optic neuritis

63. Treatment of TB Precautions during treatment with 1St line anti-TB medicines Treatment of patients with renal failure Consult expert. If not possible to consult then avoid Streptomycin & Ethambutol; therefore the recommended regimen is 2RHZ/4RH. Treatment of patients with (previously known) liver disorder (e.g. hepatitis, cirrhosis) Most anti-TB medicines can cause liver damage. Do not give Pyrazinamide because this is the most hepatotoxic anti-TB medicine. Isoniazid & Rifampicin plus one or two non-hepatotoxic medicines, such as Streptomycin and Ethambutol, can be used for a total treatment duration of eight months.

64. Treatment of TB Pericardial tuberculosis: For patients with pericardial tuberculosis, the same regimen (as pulmonary) of antiTB treatment is recommended (need expert opinion in diagnosis and treatment Corticosteroids are recommended as adjunctive therapy for 11 weeks during the first period of anti-tuberculosis therapy.

65. Treatment of TB Pleural tuberculosis Tuberculous empyema, a chronic, active infection of the pleural space containing a large number of tubercle bacilli, usually occurs when a cavity ruptures into the pleural space. Treatment consists of drainage (often requiring a surgical procedure) and anti-TB medicines.

66. Treatment of TB Tuberculous meningitis : Patients presenting with more severe brain impairment such as drowsiness neurological signs, or coma have a greater risk of neurological sequelae and higher mortality. Chemotherapy should be initiated with RHZS in an initial phase for 2 months and RH should be continued for 7 to 10 months in the continuation phase Adjunctive corticosteroid therapy is recommended for all patients

67. Treatment of TB Treatment during pregnancy and breast-feeding: Avoid Streptomycin because of the risk of toxic effects on the fetus. Chemotherapy should not be discontinued during breast-feeding. When a breast-feeding mother has PTB, the infant should, regardless of prior vaccination with BCG, be given chemo-prophylaxis and then be vaccinated with BCG if not previously vaccinated.

68. Treatment of TB Treatment of patients also infected with HIV HIV infection and Active TB disease should be started on HAART irrespective of CD4 cell count Patients infected with HIV usually respond equally well to TB treatment as those without HIV infection, with a few exceptions: They should always be treated with short course chemotherapy. Initiation of ART in the course of treatment for tuberculosis should follow the WHO guidelines

69. Treatment of TB Treatment monitoring : Health worker or a community TB treatment supporter must observe and ensure each patient swallows every single dose of the medicines; this is called directly observed treatment or DOT. During treatment follow-up, monitoring of patient’s progress involves: clinical assessment of signs and symptoms, weight measurement and follow-up AFB sputum examination. Follow-up sputum examination is done for all new smear positive TB cases at the 2nd, 5th and 6th month If smear result is positive at 2 nd sputum smear examination is done at the 3rd month, and if it is still positive, the sample must be sent for DST. If smear result is positive at 5th month or later, it is declared that treatment has failed and patient will be started on re treatment regimen and sputum is examined for DST. If smear is negative at 5month of follow-up, patient is declared cured

70. Treatment of TB Follow-up sputum examination is done for all previously treated smear positive TB cases at 3rd, 5th and 8th month If smear result is positive at the 3 rd month, sample must be sent for DST. If smear result is positive at the 5th month or later, it is declared that treatment has failed and patient must be started on 2nd line treatment regimen pending the DST result. If smear is negative at 5th and 8th month of follow-up, patient is declared cured.

71. Treatment of TB Medicine resistant TB: TB is considered medicine-resistant (DR) when the TB causative agent (mycobacterium tuberculosis) is not killed by one or more of the available anti-TB medicines. Mono-resistance: Rresistance to one anti-tuberculosis medicine. Poly-resistance: Resistance to more than one anti-tuberculosis medicine, other than Isoniazid and Rifampicin. Multimedicine-resistance (MDR)-TB: Resistance to at least isoniazid and rifampicin.

72. Treatment of TB Extensive medicine-resistance (XDR-TB): Resistance to any of the fluoroquinolones, and at least one of the three injectable Second Line Medicines (capreomycin, kanamycin and Amikacin), in addition to resistance to INH and rifampicin Total medicine-resistance (TDR-TB): resistance to all anti TB medicines. The clinical features of medicine susceptible and medicine resistant TB are the same.

73. References: Harrison’s Principles of Internal Medicine19 th ,Edition. Standard Treatment Guideline,2014 Uptodate 21.6

74. Thank You…