Childhood Tuberculosis (Dr. Getnet).pptx

Tuberculous

1. CHILDHOOD TUBERCULOSIS Getnet Aschale Ass.Professor of Pediatrics and Child Health 23-Jan-17 1

2. Out line Introduction Etiology Epidemiology Clinical manifestation Types of tuberculosis Diagnosis Treatment 23-Jan-17 2

3. Introduction During the last decade of the 20th century the number of new cases of tuberculosis increased worldwide. Currently, 95% of tuberculosis cases occur in developing countries because of the following HIV/AIDS epidemics (have had the greatest impact ) Lack of resource for proper identification and treatment of these diseases Poor social economic condition Over crowding living condition 23-Jan-17 3

4. Cont’d… Almost 1.3 million cases and 450,000 deaths occur in children each year. More than 1/3 rd of the world's population is infected with Mycobacterium tuberculosis According to the latest WHO Global TB Report 2011, there were an estimated 8.8 million incident cases of TB globally In 2010, of which 1.1 million were among people living with HIV MDR-TB is estimated to be 1.6% among all new TB cases and 12% among all previously treated TB cases 23-Jan-17 4

5. Etiology 53 different species of mycobacterium 3 species cause TB in humans M.tuberculosis M.bovis M. africanum M.microti M. canetti M. tuberculosis is the most important cause of tuberculosis disease in humans. 23-Jan-17 5

6. Mycobacterium tuberculosis ●an aerobic ●Slow growing ,curved rod with a generation time of 12-24 hr. A hallmark of all mycobacteria is acid fastness —the capacity to form stable mycolate complexes with arylmethane dyes such as crystal violet, carbolfuchsin , auramine , and rhodamine Once stained, they resist decoloration with ethanol and hydrochloric or other acids Isolation from clinical specimens on solid synthetic media usually takes 3-6 wk, and drug susceptibility testing requires an additional 4 wk. Cont’d… 23-Jan-17 6

7. AFB SLIDE 23-Jan-17 7

8. Transmission Inhalation Ingestion of milk Transplacental Increased risk with when the patient has : positive acid-fast smear of sputum an extensive upper lobe infiltrate or cavity copious production of thin sputum severe and forceful cough and sneezing (single cough can produce 3,000 bacilli. 23-Jan-17 8

9. Cont’d… Latent tuberculosis infection (LTBI) A reactive tuberculin skin test (TST) and the absence of clinical and radiographic manifestations are the hallmark of LTBI Untreated infants with LTBI have up to a 40% likelihood of developing tuberculosis, with the risk for progression decreasing gradually through childhood to adult lifetime rates of 5-10%. The greatest risk for progression occurs in the first 2 yr after infection 23-Jan-17 9

10. Risk factors for progression of latent tuberculosis infection to TB disease. Immunity status Nutritional status Intercurrent illness Length of time of exposure # of bacteria inhaled Age at infection Infants and children ≤4 yr of age, especially those <2 yr 23-Jan-17 10

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12. Pathogenesis The lung is the portal of entry in >98% of cases The tubercle bacilli multiply initially within alveoli and alveolar ducts Most of the bacilli are killed, but some survive within non activated macrophages, which carry them through lymphatic vessels to the regional lymph nodes Primary complex (Ghon complex), which is the combination of a parenchymal pulmonary lesion and a corresponding lymph node site, Tubercle bacilli are often carried to most tissues of the body through the blood and lymphatic vessels. 23-Jan-17 12

13. Cont’d… The parenchymal portion of the primary complex often heals completely by fibrosis or calcification after undergoing caseous necrosis and encapsulation If caseation is intense, the center of the lesion liquefies and empties into the associated bronchus, leaving a residual cavity Disseminated tuberculosis occurs if the number of circulating bacilli is large and the host's cellular immune response is inadequate 23-Jan-17 13

14. Natural history of TB In the great majority (90-95%) of infected persons the immunological defence either kills the inhaled or ingested bacilli or keeps them suppressed (silent focus) causing ‘ latent Tuberculosis infection’ Only 5-10% of such infected persons (primary infection) develop active disease Following primary infection, rapid progression to disease is more common in children less than 5 years of age. Patients with weakened immune systems, such as those with HIV infection, are at greater risk of developing TB disease. HIV positive people with latent TB infection have a 10% annual and 50% life time risk of developing active TB disease 23-Jan-17 14

15. Active TB disease arises from progression of the primary lesion as a continuous process within a year or so after infection, or from endogenous reactivation of latent foci, which remained dormant since the initial infection or exogenous re-infection. If untreated, TB leads to death within 5 years in at least 50 % of the patients. Without treatment, about 20 to 25% could have natural healing and 25 to 30% could remain chronically ill, thus continuing to spread the disease in the community. Cont’d… 23-Jan-17 15

16. Cont’d… The time between initial infection and clinically apparent disease is variable. Disseminated and meningeal tuberculosis are early manifestations, often occurring within 2-6 mo of acquisition. Significant lymph node or endobronchial tuberculosis usually appears within 3-9 mo. Lesions of the bones and joints take several years to develop, Renal lesions become evident decades after infection Extra pulmonary manifestations develop in 25-35% of children with tuberculosis, compared with about 10% of immuno competent adults with tuberculosis 23-Jan-17 16

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18. Immunity and tuberculosis infection Conditions that adversely affect cell-mediated immunity predispose to progression from tuberculosis infection to disease. Cell-mediated immunity develops 2-12 wk after infection, along with tissue hypersensitivity . Tuberculosis infection is associated with a humoral antibody response, which appears to play little role in host defense. In immunocompetent persons the response to the initial infection with M. tuberculosis usually provides protection against reinfection when a new exposure occurs. 23-Jan-17 18

19. Clinical manifestation Primary Pulmonary Disease Progressive Primary Pulmonary Disease Reactivation Tuberculosis Extrapulmonary tuberculosis 23-Jan-17 19

20. Primary Pulmonary Disease common type of TB in children The primary complex Parenchymal pulmonary focus + the regional LN is the hall mark. Partial obstruction of the bronchus caused by external compression can cause hyperinflation in the distal lung segment and complete obstruction results in atelectasis. Inflamed caseous nodes can attach to the bronchial wall and erode through it, causing endobronchial tuberculosis or a fistula tract The caseum causes complete obstruction of the bronchus. The resulting lesion is a combination of pneumonitis and atelectasis and has been called a collapse-consolidation or segmental lesion Erosion of a parenchymal focus of tuberculosis into a blood or lymphatic vessel can result in dissemination of the bacilli and a miliary pattern. 23-Jan-17 20

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22. Progressive primary pulmonary disease Rare Serious complications Primary focus expansion ↓ large caseous center ↓ liquefaction ↓ cavity (large number of bacilli) High fever, severe cough with sputum production, weight loss, and night sweats are common. Physical signs include diminished breath sounds, rales, and dullness or egophony over the cavity. 23-Jan-17 22

23. Reactivation Tuberculosis(2 TB) Reactivation TB results when the persistent bacteria in a host suddenly proliferate This form of tuberculosis is rare in childhood but can occur in adolescence Only 5 to 10 % of patients with no underlying medical problems who become infected develop active disease in their lifetime. The most common form is an infiltrate or cavity in the apex of the upper lobes, where oxygen tension and blood flow are great. The most common pulmonary sites are the original parenchymal focus, lymph nodes, or the apical seeding (Simon foci) established during the hematogenous phase of the early infection 23-Jan-17 23

24. Immunosuppressive conditions associated with reactivation TB HIV infection and AIDS End-stage renal disease Diabetes mellitus Malignant lymphoma Corticosteroid use Diminution in Cell Mediated Immunity associated with old age ,measles 23-Jan-17 24

25. Cont’d… In contrast to primary disease, the disease process in reactivation TB tends to be localized, because the established immune response prevents further extra pulmonary spread. there is little regional lymph node involvement and less caseation The lesion typically occurs at the lung apices, and disseminated disease is unusual, unless the host is severe immunosuppressed Children with a healed tuberculosis infection acquired at <2 yr of age rarely develop chronic reactivation pulmonary disease . More common in those who acquire the initial infection at >7 yr of age 23-Jan-17 25

26. Cont’d… Older children and adolescents with reactivation tuberculosis are more likely to experience fever, anorexia, malaise, weight loss, night sweats, productive cough, hemoptysis, and chest pain than children with primary pulmonary tuberculosis Most signs and symptoms improve within several weeks of starting effective treatment, although the cough can last for several months The most common radiographic presentations of this type of tuberculosis are extensive infiltrates or thick-walled cavities in the upper lobes. 23-Jan-17 26

27. The most common radiographic presentations of this type of tuberculosis are extensive infiltrates or thick-walled cavities in the upper lobes 23-Jan-17 27

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29. Extra Pulmonary Tuberculosis 23-Jan-17 29

30. Pleural Effusion Larger and clinically significant effusions occur months to years after the primary infection. Tuberculous pleural effusion is uncommon in children <6 yr of age and rare in children <2 yr of age. Effusions are usually unilateral but can be bilateral. They are rarely associated with a segmental pulmonary lesion and are uncommon in disseminated tuberculosis. 23-Jan-17 30

31. Cont’d… characterized by low to high fever shortness of breath, chest pain on deep inspiration, and diminished breath sounds. The fever and other symptoms can last for several weeks after the start of antituberculosis chemotherapy. The TST is positive in only 70-80% of cases. The prognosis is excellent, but radiographic resolution often takes months. Scoliosis is a rare complication from a long-standing effusion CXR 23-Jan-17 31

32. DX Pleural fluid analysis Color = yelow or straw color/rarely hemorrhagic. Cell =lymphocytic predominance Rarely TB empyema Culture <30% positive AFB microscopy is rarely +ve Pleural Biopsy demonstrate AFB /granulomatous change Protein level is usually 2-4 g/ dL , and the glucose concentration may be low (20-40  mg/ dL ) The specific gravity is usually 1.012-1.025, Biopsy of the pleural membrane is more likely to yield a positive acid-fast stain or culture, and granuloma formation usually can be demonstrated. 23-Jan-17 32

33. Pericardial Disease The most common form of cardiac tuberculosis is Pericarditis . rare, occurring in 0.5-4% of tuberculosis cases in children. usually arises from direct invasion or lymphatic drainage from subcarinal lymph nodes Symptoms are nonspecific, including low-grade fever, malaise, and weight loss. A pericardial friction rub or distant heart sounds with pulsus paradoxus may be present The pericardial fluid is typically serofibrinous or hemorrhagic. Acid-fast smear of the fluid rarely reveals the organism, but cultures are positive in 30-70% of cases. The culture yield from pericardial biopsy may be higher, and the presence of granulomas often suggests the diagnosis. Partial or complete pericardiectomy may be required when constrictive pericarditis develops. 23-Jan-17 33

34. Lymphohematogenous (Disseminated) Disease The most clinically significant form of disseminated tuberculosis is Miliary disease, which occurs when massive numbers of tubercle bacilli are released into the bloodstream, causing disease in 2 or more organs. The clinical picture may be acute, more often it is indolent and prolonged, with spiking fever accompanying the release of organisms into the bloodstream. Early pulmonary involvement is surprisingly mild, but diffuse involvement becomes apparent with prolonged infection Bones and joints or kidneys also can become involved. 23-Jan-17 34

35. Cont’d… Generalized lymphadenopathy and hepatosplenomegaly develop within several weeks in about 50% of cases. Meningitis or peritonitis are found in 20-40% of patients with advanced disease Cutaneous lesions include papulonecrotic tuberculids , nodules, or purpura Choroid tubercles occur in 13-87% of patients and are highly specific for the diagnosis of miliary tuberculosis Unfortunately, the TST is nonreactive in up to 40% of patients with disseminated tuberculosis. 23-Jan-17 35

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37. Upper Respiratory Tract Disease laryngeal tuberculosis have a croup-like cough, sore throat, hoarseness, and dysphagia. Most children with laryngeal tuberculosis have extensive upper lobe pulmonary disease Tuberculosis of the middle ear results from aspiration of infected pulmonary secretions into the middle ear or from hematogenous dissemination in older children. The most common signs and symptoms are painless unilateral otorrhea, tinnitus, decreased hearing, facial paralysis, and a perforated tympanic membrane. Diagnosis is difficult, because stains and cultures of ear fluid are often negative. 23-Jan-17 37

38. Lymph Node Disease TB of superficial lymph nodes ( scrofula) is the most common form of extra pulmonary tuberculosis in children . The nodes usually enlarge gradually in the early stages of lymph node disease. They are discrete, nontender, and firm but not hard. The nodes often feel fixed to underlying or overlying tissue. Disease is most often unilateral, but bilateral involvement can occur because of the crossover drainage patterns of lymphatic vessels in the chest and lower neck. 23-Jan-17 38

39. Cont’d… As infection progresses, multiple nodes are infected, resulting in a mass of matted nodes. Systemic signs and symptoms other than a low-grade fever are usually absent. The TST is usually reactive, but the chest radiograph is normal in 70% of cases. The onset of illness is occasionally more acute, with rapid enlargement, tenderness, and fluctuance of lymph nodes and with high fever. The initial presentation is rarely a fluctuant mass with overlying cellulitis or skin discoloration 23-Jan-17 39

40. Cont’d… Lymph node tuberculosis can resolve if left untreated but more often progresses to caseation and necrosis. The capsule of the node breaks down, resulting in the spread of infection to adjacent nodes. Rupture of the node usually results in a draining sinus tract that can require surgical removal. Dx - FNAC, Biopsy ,AFB ,Tissue culture(50%+ve) 23-Jan-17 40

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42. Central Nervous System Disease (CNS TB) Most serious complication in children and is fatal without prompt and appropriate treatment. The brain stem is often the site of greatest involvement, which accounts for the commonly associated dysfunction of cranial nerves III, VI, and VII. It is most common in children between 6 mo and 4 yr of age. The clinical progression of tuberculous meningitis may be rapid or gradual. 23-Jan-17 42

43. Cont’d… More commonly, the signs and symptoms progress slowly over several weeks and can be divided into 3 stages Stage 1 lasts 1-2 wk characterized by nonspecific symptoms such as fever, headache, irritability, drowsiness, and malaise. Focal neurologic signs are absent, but infants can experience a stagnation or loss of developmental milestones. 23-Jan-17 43

44. Cont’d… Stage 2 Usually begins more abruptly Common features are lethargy, nuchal rigidity, seizures positive Kernig and Brudzinski signs, hypertonia, vomiting, cranial nerve palsies, and other focal neurologic signs. The accelerating clinical illness usually correlates with the development of hydrocephalus, increased intracranial pressure, and vasculitis . Stage 3 is marked by coma, hemiplegia or paraplegia hypertension, decerebrate posturing, deterioration of vital signs, and eventually death 23-Jan-17 44

45. CNS –TB FORMS BRAIN Tb meningitis encephalopathy vasculopathy tuberculoma brain abscess Spinal cord arachidonitis Para spinal abscess pot’s disease Radiculopathy 23-Jan-17 45

46. Cont’d… DX The TST is nonreactive in up to 50% of cases, and 20-50% of children have a normal chest radiograph The CSF leukocyte count usually ranges from 10 to 500 cells/mm 3 . PNC leukocytes may be present initially, but lymphocytes predominate in the majority of cases. The CSF glucose is typically <40mg/ dL but rarely <20mg/ dL . The protein level is elevated and may be markedly high (400-5,000mg/ dL ) secondary to hydrocephalus and spinal block. MRI and CT scan , demonstrate basal enhancement with communicating hydrocephalus. 23-Jan-17 46

47. Tuberculoma a tumor-like mass resulting from aggregation of caseous tubercles that usually manifests clinically as a brain tumor In adults tuberculomas are most often supratentorial, but in children they are often infratentorial, located at the base of the brain near the cerebellum Tuberculomas account for up to 40% of brain tumors in some areas of the world. Lesions are most often singular but may be multiple. The most common symptoms are headache, fever, and convulsions On CT or MRI of the brain, tuberculomas usually appear as discrete lesions with a significant amount of surrounding edema. Contrast medium enhancement is often impressive and can result in a ring like lesion 23-Jan-17 47

48. Bone and Joint Disease TB usually affects weight bearing bones or joints, and most common sites are vertebrae, hip, knee and ankle The classic manifestation of tuberculous spondylitis is progression to Pott disease , in which destruction of the vertebral bodies leads to gibbus deformity and kyphosis . Tuberculous bone lesions can resemble pyogenic and fungal infections or bone tumors A catastrophic complication of Pott's disease is paraplegia, which is usually due to an abscess or a lesion compressing the spinal cord Multifocal bone involvement can occur A bone biopsy is essential to confirm the diagnosis 23-Jan-17 48

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50. Abdominal and Gastrointestinal Disease Any part of the GIT can be involved TB enteritis The pathogenesis of tuberculous enteritis has been attributed to four mechanisms Swallowing infected sputum Hematogenous spread from active pulmonary or miliary TB Ingestion of contaminated milk or food Contiguous spread from adjacent organs 23-Jan-17 50

51. Cont’d… The macroscopic appearance of the intestinal lesions can be categorized as follows Ulcerative type Hyper plastic type Skip lesion of the intestine Pan colitis form Hyperplasic type presented as intestinal obstruction Ulcerative forms usually have chronic dysentery with other symptoms The jejunum and ileum near Payers patches and the appendix are the most common sites of involvement. Biopsy, acid-fast stain, and culture of the lesions are usually necessary to confirm the diagnosis. 23-Jan-17 51

52. Tuberculous peritonitis Occurs most often in young men and is uncommon in adolescents and rare in children. Generalized peritonitis can arise from subclinical or miliary hematogenous dissemination. Localized peritonitis is caused by direct extension from an abdominal lymph node, intestinal focus, or genitourinary tuberculosis. Rarely, the lymph nodes, omentum, and peritoneum become matted and can be palpated as a doughy irregular non tender mass. Abdominal pain or tenderness, ascites, anorexia, and low-grade fever are typical manifestations. The TST is usually reactive. 23-Jan-17 52

53. Types of TB peritonitis 1)Dry peritonitis type 2)Hyper plastic type (mass) 3) ascetic form(fluid collection) 4)Acute abdomen Dx clinical suspicions CXR Abd us Ascitic fluid analysis Biopsy 23-Jan-17 53

54. Genitourinary Disease(Renal TB) Renal tuberculosis is rare in children, because the incubation period is several years or longer Usually during lymphohematogenous spread(miliary). In true renal tuberculosis, small caseous foci develop in the renal parenchyma and release M. tuberculosis into the tubules. Infection then spreads locally to the ureters , prostate, or epididymis . Often clinically silent in its early stages , (marked only by sterile pyuria and microscopic hematuria Dysuria, flank pain,gross hematuria ( late stage ) 23-Jan-17 54

55. Cont’d… Hydronephrosis or ureteral strictures can complicate the disease. Urine cultures for M. tuberculosis are positive in 80-90% of cases, and acid-fast stains of large volumes of urine sediment are positive in 50-70% of cases. An intravenous pyelogram or CT scan often reveals mass lesions, dilatation of the proximal ureters, multiple small filling defects, and hydronephrosis if ureteral stricture is present. Disease is most often unilateral 23-Jan-17 55

56. Genital TB In females of genital tract the fallopian tubes are most often involved (90-100% of cases), followed by the endometrium (50%), ovaries (25%), and cervix (5%). Genital tuberculosis in adolescent boys causes epididymitis or orchitis. 23-Jan-17 56

57. Disease in HIV-Infected Children Establishing the diagnosis of tuberculosis in an HIV-infected child may be difficult, because Skin test reactivity can be absent and culture confirmation is difficult Similar C/F to many other HIV-related infections and conditions Tuberculosis in HIV-infected children is often more severe, progressive, and likely to occur in extra pulmonary sites. Radiographic findings are similar to those in children with normal immune systems, but lobar disease and lung cavitations are more common. Nonspecific respiratory symptoms, fever, and weight loss are the most common complaints. Rates of drug-resistant tuberculosis tend to be higher in HIV-infected adults and probably are also higher in HIV-infected children. All children with tuberculosis disease should be tested for HIV co-infection 23-Jan-17 57

58. Perinatal Disease Associated with risk for prematurity, fetal growth retardation, low birthweight, and perinatal mortality. Congenital tuberculosis is rare because the most common result of female genital tract tuberculosis is infertility. Primary infection in the mother just before or during pregnancy is more likely to cause congenital infection than is reactivation of a previous infection. The tubercle bacilli first reach the fetal liver, where a primary focus with periportal lymph node involvement can occur. The bacilli in the lung usually remain dormant until after birth, when oxygenation and pulmonary circulation increase significantly. 23-Jan-17 58

59. Congenital tuberculosis can be caused through placenta ,aspiration or ingestion of infected amniotic fluid. However, the most common route of infection for the neonate is postnatal airborne transmission from an adult with infectious pulmonary tuberculosis . Symptoms of congenital tuberculosis may be present at birth but more commonly begin by the 2nd or 3rd wk of life. The most common signs and symptoms are Respiratory distress, fever, hepatic or spleen enlargement, Poor feeding, lethargy or irritability, lymphadenopathy, Abdominal distention, failure to thrive, ear drainage, and skin lesions. Many infants have an abnormal chest radiograph, most often with a miliary pattern. Cont’d… 23-Jan-17 59

60. Cont’d… Hilar and mediastinal lymphadenopathy and lung infiltrates are common. Generalized lymphadenopathy and meningitis occur in 30-50% of patients. Dx is often challenging can mimic sepsis or TORCHS The most important clue for rapid diagnosis of congenital tuberculosis is a maternal or family history of tuberculosis The infant's TST is negative initially but can become positive in 1-3 mo The mortality rate of congenital tuberculosis remains very high if not diagnosed and treated early CSF should be examined and cultured, although the yield for isolating M. tuberculosis is low 23-Jan-17 60

61. Cont’d… Prevention of perinatal TB Appropriate testing and treatment of the mother and other family members for TB High-risk pregnant women should be tested with a TST or IGRA, and those with a positive test result should receive a chest radiograph. If the mother’s chest radiograph or acid-fast sputum smear shows evidence of current tuberculosis disease,INH therapy is recommended for the newborn after ruling out active TB. 23-Jan-17 61

62. Diagnostic methods of TB X-rays Tuberculin skin test(TST) Culture Biopsy Molecular test - PCR GeneXpert MTB/RIF Line probe Assay AFB Stains Ziel Nielson Flourochrome T-cell based interferon-gamma assays QuantiFERON-TB gold T-SPOT.TB 23-Jan-17 62

63. Tuberculin Skin Testing The Mantoux TST is the intradermal injection of 0.1 mL purified protein derivative (PPD). Recruitment of sensitized T cells to the skin ↓ lymphokines ↓ Indurations( measure after 48-72hrs) Tuberculin sensitivity develops 3 wk to 3 mo (most often in 4-8 wk) after inhalation of organisms 23-Jan-17 63

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65. Cont’d… A TST should be regarded as positive: >5 mm diameter of induration: in children who are immunosuppressed including HIV-positive children and severely malnourished children, i.e. those with clinical evidence of marasmus or kwashiorkor >10mm diameter of induration: in all other children (whether they have received a BCG vaccination or not) 23-Jan-17 65

66. False negative PPD test Severe PEM Measles Overwhelming TB Wrong techniques HIV Steroids Cancer 23-Jan-17 66

67. False positive PPD test Atypical mycobacterial infections Hypersensitivity to constituents BCG vaccination 23-Jan-17 67

68. AFB MICROSCOPY Sputum(spot/morning /spot ) ;Induced sputum AFB/ Cultutre Gastric aspirate (three early morning sample) Early morning gastric aspirate(3x=50% positive culture) Any body fluid Urine…… etc(with centrifugation) 23-Jan-17 68

69. GeneXpert MTB/RIF For the diagnosis of pulmonary TB and rifampicin resistance Is new rapid test for TB Fully automated Provides accurate results in 100 minutes Indicated ( national guideline ) in : MDRTB TB/HIV Children Extra pulmonary TB 23-Jan-17 69

70. Line Probe Assay new test that use molecular technology identify presence or absence of specific mutation on genes of TB bacilli which are responsible for Isoniazid and Rifampcin resistance Rapid and accurate test MDR-TB can be proved on the same day 23-Jan-17 70

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72. # It can be difficult to clearly define what is “suggestive of PTB” on clinical or radiological findings in HIVinfected children because of clinical overlap between PTB and other forms of HIV-related lung disease. # CXR abnormalities of PTB in HIV-infected child are similar to those in HIV-uninfected child. 23-Jan-17 72

73. Any One Of The Following Is Suggestive of TB: i . Radiological picture of miliary pattern ii. Pathologic findings compatible with TB (Pathology) iii. Culture positive iv. Isolation of the organism by acid fast staining 23-Jan-17 73

74. Treatment Principles of TB Treatment 1.Chemotherapy 2.Adjuvant therapy 3.Nutritional therapy 4.Family screening 5.Follow up 23-Jan-17 74

75. 1.Chemotherapy 2 treatment phases A. Intensive phase 4 drugs for 2 month ( New cases) and 3months (Retreatment) It renders the patient non-infectious by rapidly reducing the load of bacilli in the sputum ,usually within 2-3 weeks B. Continuation phase 2drugs for 4mths ( new case) 3 drugs for 5 months (retreatment) It ensure cure, and prevents relapse after completion of treatment EXCEPTIONS In Children with TB meningitis and osteo-articular TB , the continuation phase should be 10 months 23-Jan-17 75

76. Commonly used drugs for the treatment of tuberculosis in infants, children, and adolescents DRUG DAILY DOSAGE, mg/kg MAXIMUM DOSE ADVERSE REACTIONS Ethambutol 20 1600mg Optic neuritis (usually reversible), decreased red-green color discrimination, gastrointestinal tract disturbances, hypersensitivity Isoniazid 10-15 300mg Mild hepatic enzyme elevation, hepatitis, peripheral neuritis, hypersensitivity Pyrazinamide 20-40 2gm Hepatotoxic effects, hyperuricemia, arthralgias, gastrointestinal tract upset Rifampicin 10-20 600 Orange discoloration of secretions or urine, vomiting, hepatitis, influenza-like reaction, thrombocytopenia, pruritus 23-Jan-17 76

77. A. FDC dosing regimen for new cases 23-Jan-17 77

78. B.FDC dosing regimens for Retreatment cases 23-Jan-17 78

79. 2.Adjuvant therapy Indication for steroid CNS Pericarditis Miliary TB with acute air blocking syndrome Tb adrenalitis The most commonly prescribed regimen is prednisone, 1-2 mg/kg/day in 1-2 divided doses orally for 4-6 wk, followed by gradual tapering. Indication for pyridoxine RVI pts Malnutrition Chronic diarrhea Breast feeding 23-Jan-17 79

80. 3.Family screening Those under five children Pregnant ladies Elders,age >65 yrs All HIV /AIDS pts at home 23-Jan-17 80

81. 4.Follow up Children, parents, and other close family members should be educated about TB Directly observed therapy(DOT) should be used for all children Asses two weeks after treatment initiation, after intensive phase and every 2 month until treatment completion assess treatment adherence, adverse events, weight A follow up sputum for AFB at 2months should be done for any child who was smear positive at diagnosis. A child who is not responding, should be assessed for drug resistant TB 23-Jan-17 81

82. Available approaches to prevent Tb in children 23-Jan-17 82

83. Treatment of Latent tuberculosis infection Indication All under 5 yrs that have household contacts of a case with sputum smear positive TB with no evidence of TB disease HIV infected children at all age Recommended dosage INH 10 mg/kg daily for 6 months 23-Jan-17 83

84. Drug-Resistant Tuberculosis The incidence of drug-resistant tuberculosis is increasing in many areas of the world There are two major types of drug resistance Primary resistance occurs when a person is infected with M. tuberculosis that is already resistant to a particular drug. Secondary resistance occurs when drug-resistant organisms emerge as the dominant population during treatment Most drug resistance in children is primary Secondary resistance is rare in children because of the small size of their mycobacterial population 23-Jan-17 84

85. Case definition of drug resistance TB Mono resistance : Resistance to only one first line drugs Poly-resistance : Resistance to more than one first line drugs, but not to both isoniazid and rifampicin Multidrug resistance (MDR ): Resistance to at least isoniazid and rifampicin Extensive drug resistance(XDR ): MDR as well as any fluoroquinolone, and any of the second line injectable anti TB drugs( capreomycin, kanamycin,and amikacin 23-Jan-17 85

86. Risk factors for drug-resistant tuberculosis  Personal or contact history of treatment for tuberculosis    Contacts of patients with drug-resistant tuberculosis    Birth or residence in a country with a high rate of drug resistance    Poor response to standard therapy    Positive sputum smears (acid-fast bacilli) or culture ≥2 month after initiating appropriate therapy 23-Jan-17 86

87. Less commonly used drugs for treating drug-resistant tuberculosis in infants, children, and adolescents Amikacin Am Capreomycin Cm Cycloserine Cs Ethionamide Eto Kanamycin Km Levofloxacin Lfx para -Aminosalicylic acid (PAS) Streptomycin S 23-Jan-17 87

88. MDR –TB treatment in Ethiopia Patients with MDR-TB confirmation, but no full DST result available yet Regimen E-Z-KM(Am)- Lfx - Eto -Cs MDR TB susceptible to kanamycin but not to quinolones Regimen E-Z-KM(Am)- Mfx - Eto -Cs-PAS MDR TB susceptible to quinolone but not to Kanamycin Regimen E-Z-Cm- Lfx – Eto -Cs XDR-TB (MDR-TB and resistace to quinolones and kanamycin Regimen E-Z-Cm- Mfx – Eto -Cs-PAS Duration of treatment Intensive phase- the injectable agents is used for a minimum of 8 months and at least 4 months after culture conversion Continuation phase- The total treatment is for a minimum of 18 months beyond culture conversion 23-Jan-17 88

89. SCREEN EVERY PATIENT FOR HIV SUSPECTED TO HAVE TB Many thanks 23-Jan-17 89