TB by mwebaza victor 2021..pdf

1. M W E B A Z A® VICTOR BMS/9114/172/DU MBchB4.2 mwebazavictor1997@gmail.com Africa Uganda October/2021 TUBERCULOSIS Presentation . Internal medicine department mubende regional hospital Supervisor:- Dr Wabwona William (MRRH-H.O.D Medical department) Kampala international university western campus-mubende site(MUBENDE RRHosp) mubende Uganda. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

2. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. Introduction Epidemiology Definition Aetiology Transmission Pathogenesis Clinical presentation Case definition Classification of Tb Laboratory diagnosis Fixed drug combition Aim of treatment AntiTb medicine, side effects, route of administration,contraindications, and drug interactions Adjunctive treatment Tb Rx regimens Rx monitoring Rx out come IPT Latent Tb Treatment of Tb in special situations:- preg,BF, liver diseases, renal diseases, bone,jointandspinal Tb, Tb meningitis, and Tb/HIV co-infection IRIS Additional Resources on Tb Further reading on Tb References Outline 2022/3/24 MWEBAZA VICTOR MBchB TB presention

3. Introduction: Burden of Tuberculosis in uganda The National TB prevalence survey conducted in 2015 puts the incidence of TB at 234/100,000 population for all TB cases and prevalence of TB is 253/100,000 population. The survey further showed that about 24% of TB patients are HIV co-infected. Based on the 2015 global TB report, the mortality rate from TB (excluding HIV positive TB) in 2014 was estimated at 12/100,000 population. Multidrug resistant TB is an emerging problem with more than 1,040 estimated cases every year and the actual case ﬁnding is around 200 cases per year. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

4. Epidemiology of Tuberculosis worldwide on 24/march/2021 Report™ 2022/3/24 MWEBAZA VICTOR MBchB TB presention

5. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

6. Tuberculosis is a communicable chronic granulomatous disease caused by mycobacterium tuberculosis, it usually involve the lungs but can affect other organs or tissues in the body . Typically the center of tubercular granulomas undergo caseous Necrosis Deﬁnition 2022/3/24 MWEBAZA VICTOR MBchB TB presention

7. Aetiology Tuberculosis (TB) is usually caused by a bacterium, Mycobacterium tuberculosis (M.tb) complex (such as Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum and Mycobacterium microti). In clinical and laboratory settings, these bacteria are also referred to conventionally as tubercle bacilli (because they cause lesions in tissues called tubercles) or acid-fast bacilli (AFB), because they retain a red dye after washing with alcohol following staining. M.bovis infection arise from drinking non-sterilised milk from infected cows. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

8. In few cases mycobacterium bovis that causes TB in animals can cause TB among humans. However, the most common cause is myc. tuberculosis. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

9. Transmission Transmission of tubercle bacilli occurs when a patient suffering from pulmonary TB who is not on effective treatment expels into the environment air containing droplets with the bacilli (coughing, singing or sneezing). The liquid in the droplets evaporates leaving the droplet nuclei containing the bacilli. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

10. 1. 2. 3. 4. 5. The droplet nuclei are small enough to be inhaled into the lungs and deposited into the alveoli. Transmission is easier in the following situations: Closed environment where ventilation is poor. High number of TB bacilli in the sputum Close contact over a prolonged period with a pulmonary TB sputum smear-positive patient who is not yet on treatment increases the chance of becoming infected with M.tb. Duration of exposure to the infectious source High prevalence of TB in the community. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

11. On the other hand, the chance of getting infection is low if the contact is occasional or the patient has extra-pulmonary TB. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

12. Pathogenesis of TB infection 1. 2. 3. 4. 5. This occurs in ﬁve steps which are Entry into macrophages Replication in the macrophages The Th1 response Th1 mediated macrophages activation Granulomatous inﬂammation and tissue damage 2022/3/24 MWEBAZA VICTOR MBchB TB presention

13. 1. 2. Entry into the macrophages (0-3weeks) This is by phagocytosis mediated by protein molecules on both MTB and phagocyte ie the mannose and C3b on MTB bind with mannose receptor and CR3 respectively on the phagocytes Replication in macrophages (ﬁrst 3weeks) After being phagocytized The MTB multiply in the vesicle after inactivating the macrophages though blocking formation of phagolydosomal contents They block phagolysosomal formation by:- Inhibiting Ca++ signal Inhibiting of recruitment and assembly of the proteins that mediate phagolysosomal formation 2022/3/24 MWEBAZA VICTOR MBchB TB presention

14. After the multiplication phase some microbes get disseminated in blood circulation leading to bacteremia and ﬂu like illnesses in some pts. The Th1 response(3-4weeks) Th1 response is mounted roughly three weeks after infection and this involves activation of the macrophages. ®Innate immune receptors TLR2 recognize the multiple pathogen then the TLR2 become stimulated by the mycobacterial ligands thus this makes them activated The activated TLR2 stimulate the dendritic cells 2022/3/24 MWEBAZA VICTOR MBchB TB presention

15. Stimulated dendritic cells migrate to near by lymph node then produce IL12 The IL12 cause the Tcell to undergo differentiation producing Th1 cell Th1 mediated activation of macrophages and killing of the bacteria Th1 cell in the lymph node or lungs produce INF-gamma this cause classical activation of the macrophages Activated macrophages produces cytokines for example IL1,IL2,IL3,IL6,IL8,IL23,more IL12 on addition to maturation of phagolysosomes in the infected macrophages, activation off Nitric oxide synthesis All those proinﬂammatory mediates are produced to kill the microbes 2022/3/24 MWEBAZA VICTOR MBchB TB presention

16. Granulomatous inﬂammation and Tissue damage The activated macrophages aggregate around the microbes forming giant cells thus forming Ghan complexs, milliary consolidation due to the inﬂammatory mediates produced by the Activated macrophages affects the normal parenchymal cells of the lungs causing caseation necrosis of the tissues also erosion of lung blood vessels and tissues contributing to hemoptysis and thick sputum and formation of lung cavitations 2022/3/24 MWEBAZA VICTOR MBchB TB presention

17. 1. 2. 3. NOTE:- in primary TB Ghan focus are formed at the lower part of the upper lung lobe and upper part of the lower lobe close to the the lateral pleural border. In secondary TB granulation occurs /involves the apex of the upper lobe of one or both lung And these are seen on CXRay 2022/3/24 MWEBAZA VICTOR MBchB TB presention

18. Clinical presentation General signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and fatigue.Signiﬁcant nail clubbing may also occur. Pulmonary Symptoms may include chest pain and a prolonged cough >2weeks producing purulent sputum. About 25% of people may not have any symptoms (i.e. they remain "asymptomatic"). Occasionally, people may cough up blood in small amounts, and in very rare cases, the infection may erode into the pulmonary artery or a Rasmussen's aneurysm, resulting in massive bleeding. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

19. Extrapulmonary In 15–20% of active cases, contribute to EPTB Extrapulmonary TB occurs more commonly in immunosuppressed persons and young children. In those with HIV, this occurs in more than 50% of cases. Notable extrapulmonary infection sites include the pleura (in tuberculous pleurisy), the central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (in Pott disease of the spine), among others. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

20. When it spreads to the bones, it is also known as " osseous tuberculosis",a form of osteomyelitis. Sometimes, bursting of a tubercular abscess through skin results in tuberculous ulcer.An ulcer originating from nearby infected lymph nodes is painless, slowly enlarging and has an appearance of "wash leather". A potentially more serious, also TB of the intestines. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

22. Case defination 1. 2. 3. Presumptive TB refers to a patient who presents with symptoms or signs suggestive of TB (previously known as a TB suspect). A bacteriologically confirmed TB case is one from whom a biological specimen is positive by smear microscopy, culture or WRD (such as Xpert MTB/ RIF). All such cases should be notified, regardless of whether TB treatment has started. A clinically diagnosed TB case is one who does not fulfil the criteria for bacteriological confirmation but has been diagnosed with active TB by a clinician or other medical practitioner who has decided to give the patient a full course of TB treatment. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

24. Classification of TB Infection Classification based on Site of the disease Pulmonary tuberculosis (PTB); Refers to any bacteriologically confirmed or clinically diagnosed case of TB involving the lung parenchyma or the tracheobronchial tree. Tuberculous intra-thoracic lymphadenopathy (mediastinal and/or hilar) or tuberculous pleural effusion, without radiographic abnormalities in the lungs, constitutes a case of extra-pulmonary TB. Extra-pulmonary tuberculosis (EPTB); Refers to any bacteriologically confirmed or clinically diagnosed case of TB involving organs other than the lungs, e.g. pleura, lymph nodes, abdomen, genitourinary tract, skin, joints bones, and meninges. A patient with both pulmonary and extra-pulmonary TB should be classified as a case of PTB. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

26. Classiﬁcation based on History of treatment 1) New patients: These are patients who have never been treated for TB or have taken anti-TB drugs for less than one month. 2) Previously treated TB patients: These are patients who have received one month or more of anti TB drugs in the past. They are sub classiﬁed as follows:- i) Relapse patients have previously been treated for TB, completed treatment, were declared cured or treatment completed at the end of their most recent course of treatment, and are now diagnosed with a recurrent episode of TB (either a true relapse or a new episode of TB caused by reinfection). 2022/3/24 MWEBAZA VICTOR MBchB TB presention

27. ii) Treatment after failure patients: are those who have previously been treated for TB and whose treatment failed at the end of their most recent course of treatment. iii) Treatment after loss to follow-up patients: have previously been treated for TB and were declared lost to follow-up at the end of their most recent course of treatment. (These were previously known as treatment after default patients). iv) Other previously treated patients are those who have previously been treated for TB but whose Outcome after their most recent course of treatment is unknown or undocumented. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

28. Classification based on HIV infection status HIV-positive TB patient refers to any bacteriologically confirmed or clinically diagnosed case of TB who has a positive result from HIV testing conducted at the time of TB diagnosis or other documented evidence of enrolment in HIV care, such as enrolment in the pre-antiretroviral therapy (ART) register or in the ART register once ART has been started. HIV-negative TB patient refers to any bacteriologically confirmed or clinically diagnosed case of TB who has a negative result from HIV testing conducted at the time of TB diagnosis. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

29. Any HIV-negative TB patient subsequently found to be HIV-positive should be reclassified accordingly. HIV status unknown TB patient refers to any bacteriologically confirmed or clinically diagnosed case of TB who has no result of HIV testing and no other documented evidence of enrolment in HIV care. If the patient’s HIV status is subsequently determined, he or she should be reclassified accordingly. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

30. Classification based on Drug resistance Mono resistance: resistance to one first-line anti- TB drug only. Poly drug resistance: resistance to more than one first-line anti-TB drug (other than both Isoniazid and Rifampicin). Multidrug resistance: resistance to at least both Isoniazid and Rifampicin. Extensive drug resistance: resistance to any fluoroquinolone and to at least one of three second line injectable drugs (Capreomycin, Kanamycin and Amikacin), in addition to multidrug resistance. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

31. Rifampicin resistance: Resistance to Rifampicin detected using phenotypic (usual drug susceptibility testing, DST) or genotypic methods (commonly Xpert MTB/Rif), with or without resistance to other anti-TB drugs. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

32. Post TB patients A post TB patient is a patient who was successfully treated for TB who presents with respiratory symptoms. Many people who have been treated and cured of TB continue to present with respiratory symptoms long after their TB is cured. The common symptoms are chest pain, cough, shortness of breath and hemoptysis. The public health importance of these patients is just being recognized. There are no standard guidelines on how they can be evaluated and treated. Health workers should immediately repeat 2022/3/24 MWEBAZA VICTOR MBchB TB presention

33. Diagnosis of TB Microscopy It is the most commonly available test currently for diagnosis of TB. It can be either ZiehlNeelsen microscopy or Fluorescence microscopy . It can be used to examine sputum specimen or gastric aspiration ﬂuid or any other body material suspected to contain the TB bacilli. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

34. Xpert MTB/Rif is the most used NAAT(Nuclear Acid Amplification Test) in Uganda. Xpert MTB/Rif is an automated DNA test for mycobacteria and for the mutation that causes resistance to Rifampicin. The following body fluids or samples can be examined for TB using XpertMTB/Rif: Sputum, Lymph node tissue and aspirates, Pleural fluid, Cerebrospinal fluid and Gastric aspirates http://www.who.int/tb/areas-of-work/laboratory/ policy_statements/en/. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

36. Culture Culture is done using LJ media(Löwenstain-Jensen media) or DST media. culture of MTB is very sensitive and speﬁc but expensive as its a complex and sophisticated procedure. It require aspecilized laboratory setup and culture results are available only after 6 to 8 weeks for LJmedia, culture results of DSTmedia can take a very long period. If available, culture can be used for diagnosis or conﬁrmation of the diagnosis of TB in patients with PTB and EPTB. Since it is more sensitive than smear, culture may also have a role in the diagnosis of smear-negative, HIV-positive TB suspects who are likely to be paucibacillary. http://www.tbfacts.org/culture-tb/#sthash.YFcLUfu1.dpuf 2022/3/24 MWEBAZA VICTOR MBchB TB presention

37. TB LAM test is based on the detection of LAM in urine and has the potential to be point-of-care tests for TB. WHO recommends the test to assist the diagnosis of TB in HIV positive adult inpatients with signs and symptoms of TB (pulmonary and/or extra-pulmonary) with a CD4 cell count less than or equal to 100 cells/ μL, and people living with HIV who are deemed “seriously ill”. http://www.who.int/tb/areas-of-work/laboratory/ policy_statement_lam_web.pdf CSF Analysis. Those pt who present with CNS signs and symptoms on addition to chronic cough, B-syptoms. ℅ meningeal Tb.® how to analyse CSF Analysis results in line with Tb-meningititis. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

38. Radiology Radiology investigations such as chest X-ray: Features of chest X-ray consistent with TB disease include cavitation milliary picture, pleural effusion and mediastinal lymph gland enlargement with lung infiltration. Although the findings of radiology are nonspecific, abnormalities like any heterogeneous opacities and cavitation, if located in the upper parts of the lung, are more likely to be caused by TB 2022/3/24 MWEBAZA VICTOR MBchB TB presention

42. Ultrasound Diagnostic ultrasound is a useful test in the diagnosis of extra pulmonary TB. For example,ultrasound is useful in abdominal TB in which case you can see omental thickening, increase in mesenteric thickness and an increase in the mesenteric echogenicity (due to fat deposition), combined with retroperitoneal and mesenteric lymphadenopathy. Presence of dilated and matted small bowel loops and ascites further substantiate the diagnosis. Calciﬁcations within granulomas due to TB in the liver and spleen can also be picked by abdominal ultrasound scans 2022/3/24 MWEBAZA VICTOR MBchB TB presention

43. 1. 2. Histology Pathology can play a complementary role in confirming the diagnosis of EPTB, such as tuberculosis lymphadenitis. Multiplication of tubercle bacilli in any site of the human body causes a specific type of inflammation, with formation of characteristic granuloma that can be found on histological examination. Samples can be taken in the following ways: Fine needle aspiration of the lymph nodes: affected peripheral lymph nodes, particularly cervical nodes, can be aspirated. Tissue biopsy: serous membranes (pleura, pericardium and peritoneum), skin, lymph node, endometrium, bronchial mucosa or liver tissue can be taken. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

44. Management of Tuberculosis and FDC Early diagnosis and effective treatment is the key to stop the spread of TB and to improve treatment outcomes of patients suffering from TB. Individuals should start treatment as soon as possible after a diagnosis of TB is made and should be treated according to NTLP recommended regimens (for uganda)under Directly Observed Treatment (DOT) And the drugs are usually given as ﬁxed-dose combinations (FDC). The FDCs contain two or more drugs in a single tablet with known strength (mg) of the drugs in each table 2022/3/24 MWEBAZA VICTOR MBchB TB presention

45. 1. 2. 3. FDC tablets have the following advantages: Prescription errors are minimized. Dosage recommendations are more accurate and adjustment of the dose according to patient weight is easier. The patient has fewer tablets to swallow, which contributes to adherence. If the treatment is not supervised, patients cannot be selective about which the drugs to swallow 2022/3/24 MWEBAZA VICTOR MBchB TB presention

46. 1. 2. 3. 4. 5. The aims of treatment are to: Cure the TB patient Prevent complications and death from TB disease Prevent TB relapse Reduce TB transmission Prevent development of drug-resistant TB 2022/3/24 MWEBAZA VICTOR MBchB TB presention

47. Anti-TB medicines and there side effects, Route of administration, contraindications, and important drug interactions. Anti-TB medicines can be classified into first and second line. First-line anti-TB medicines are used for the treatment of susceptible TB while second line medicines are used for treatment of drug resistant TB. The first-line anti-TB medicines, together with their standard abbreviations, are shown below: Rifampicin (R) Isoniazid (H) Pyrazinamide (Z) Ethambutol (E) 2022/3/24 MWEBAZA VICTOR MBchB TB presention

49. Adjunctive treatment in TB 1. 2. Pyridoxine (vitamin B6). 25mg OD given concomitantly with Isonizid for the duration of treatment to prevent peripheral Neuropathy. ® isonizid interfere with vitamin B6 metabolism thus leading to vitB6 deficiency. Prednisolone in TB pt in whom complication of fibrosis are anticipated because of severe inflammation such as Tb meningitis 2022/3/24 MWEBAZA VICTOR MBchB TB presention

50. a. b. TB Treatment Regimens Anti-TB drugs are given in combinations called regimens. The regimens have the following characteristics; Contain at least one of the most effective anti-TB drugs (Rifampicin or Isoniazid) in both the initial and continuation phase of treatment Must be written in abbreviation that clearly identiﬁes the drugs in the initial and continuation phases of treatment 2022/3/24 MWEBAZA VICTOR MBchB TB presention

51. Initial phase: The initial phase is the ﬁrst two months of treatment. The combination of 4 drugs used during this phase is Isoniazid, Rifampicin, Pyrazinamide and Ethambutol (RHZE). Using these 4 drugs, results in rapid killing of the tubercle bacilli. Patients become non-infectious in about 2 weeks. Symptoms reduce, and most smear- positive cases become smear-negative within the ﬁrst 2 months. Continuation phase: The continuation phase is the second part of treatment which lasts 4 months. Here, two drugs are used in combination, usually Rifampicin and Isoniazid (RH). 2022/3/24 MWEBAZA VICTOR MBchB TB presention

56. Treatment monitoring Once a TB patient is started on treatment, it is important to ﬁnd out if the patient is getting better as a result of the treatment. This is called treatment monitoring. The following methods are used for treatment monitoring in order of importance: Laboratory monitoring– Sputum microscopy (or culture) must be used for monitoring all pulmonary TB patients. Sputum smears are performed at the end of the initial phase (2 months), at beginning of 5 months and beginning of 6th month of treatment. This should be done for both smear-positive and smear-negative pulmonary TB patients 2022/3/24 MWEBAZA VICTOR MBchB TB presention

58. Treatment out comes 2022/3/24 MWEBAZA VICTOR MBchB TB presention

60. Isoniazid preventive therapy (IPT) IPT is currently strongly advocated by NTLP for all HIV positive persons and under 5 child contacts of patients with active TB. NTLP has published an IPT health workers guide to assist health workers in initiating IPT. It is important that before IPT is initiated that active TB is excluded. This is done to avoid monotherapy for active TB because TB should always be treated with combination therapy. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

61. The following key points from the IPT guidelines need to always be remembered: 1. Adults and adolescents living with HIV should be screened for TB using the four symptom screening tool for TB in PLHIV(people Living with HIV and AIDS). Those who do not report any one of the symptoms of current cough, fever, weight loss, or night sweats are unlikely to have active TB. And those unlikely to have active TB upon screening should be offered Isoniazid preventive therapy. 2. Adults and adolescents living with HIV who report any one of the symptoms of current cough, fever, weight loss, or night sweats may have active TB. These individuals should be evaluated for TB and other diseases 2022/3/24 MWEBAZA VICTOR MBchB TB presention

62.    3. Adults and adolescents living with HIV who are unlikely to have active TB should receive at least six months of Isoniazid Preventive Therapy (IPT). This should be irrespective of: The degree of immune suppression, Whether the patient is on antiretroviral therapy or not, Whether the patient is pregnant or not. 4. A Tuberculin Skin Test (TST) is not a requirement for initiating IPT in PLHIV. 5. PLHIV who have a positive TST beneﬁt more from IPT. TST should be used where feasible to identify such individuals. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

63. 6. Providing IPT to PLHIV does not increase the risk of developing Isoniazid resistant TB. Therefore, concerns regarding the development of Isoniazid resistance should not be a barrier to providing IPT. 7. Children living with HIV who do not have any one of the following symptoms: poor weight gain, fever, or current cough are unlikely to have active TB. 8. Children living with HIV who have any one of the following symptoms: poor weight gain, fever, current cough or contact history with a TB case may have TB. These children should be evaluated for TB and other conditions. If the evaluation shows no TB, such children should be offered IPT except if they less than 1 year. Children less than 1 year can be offered IPT if they are active TB contacts. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

64. 9. Children living with HIV who are more than 12 months of age: For those who are unlikely to have active TB and have no contact with a TB case should receive six months of IPT (10 mg/kg/day). 10. Children living with HIV who less than 12 months are of age (infants) This group should only receive IPT if there is a history of contact with a TB case and they have no active TB. 11. All children under ﬁve years: Those who have a history of contact with a TB case should be screened for active TB using the Intensiﬁed TB Case Finding Guide. Those who have no symptoms and signs suggestive of active TB should receive six months of IPT 2022/3/24 MWEBAZA VICTOR MBchB TB presention

65. Latent TB Diagnosis of latent TB is conﬁrmed by positive Tuberculin skin test(TST) the commonest method for TST is the manotoux method. A standard dose of tuberculin units (TU - 0.1 ml) is injected intradermally and read 48 to 72 hours later. This intradermal injection is termed the Mantoux technique. A person who has been exposed to the bacteria is expected to mount an immune response in the skin containing the bacterial proteins. The reaction is read by measuring the diameter of induration across the forearm in millimeters. If there is no induration, the result should be recorded as "0 mm". Erythema (redness) should not be measured. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

66. >/=5mm high Risk group >/=10mm moderate risk group >/=15mm low risk group. TST has +ve when the TST has a diameter of 5mm and above in HIV +ve pt and 10mm and above for HIV -ve pt . Reactivation of latent TB to active TB occurs in:- Pt who are immunosuppressed or those with underlying pathological condition. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

67. Heaf test, a diagnostic skin test used in latent Tb was long performed to determine whether or not children had been exposed to tuberculosis infection. The gun injected tuberculin purified protein derivative (PPD) equivalent to 100,000 units per ml to the skin over the flexor surface of the left forearm in a circular pattern of six. The test was read between 3-7 days later. The injection could not be into sites containing superficial veins. The reading of the Heaf test was defined by a scale: Negative - No induration. Grade 1 - four to six papules (also considered negative) Grade 2 - Confluent papules form indurated ring (positive) Grade 3 - Central filling to form disc (positive) Grade 4 - Disc >10 mm with or without blistering (strongly positive) 2022/3/24 MWEBAZA VICTOR MBchB TB presention

68. Grades 1 and 2 could result from previous BCG or avian tuberculosis, rather than human TB infection. Children who were found to have a grade 3 or 4 reaction were referred for X-ray and follow-up 2022/3/24 MWEBAZA VICTOR MBchB TB presention

69.  TREATMENT OF TUBERCULOSIS IN SPECIAL SITUATIONS Pregnancy The number of pregnant women with TB has increased because of the current HIV epidemic. The clinical presentation of TB in pregnancy is like non- pregnant women. Once a diagnosis of TB is made, treatment should be promptly started because untreated The NTLP-recommended regimen of 2RHZE/4RH for susceptible TB is safe for use in pregnancy. All pregnant women diagnosed with TB should be screened for HIV and if positive managed according to national TB-HIV management guidelines. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

70. Breastfeeding A breastfeeding woman who has TB should be treated with a full course of a standard regimen recommended by the NTLP. The concern here is to ﬁnd out if the child already has TB disease or is just a contact likely to be infected by the mother. Concentrations of anti-TB drugs in breast milk are too low to prevent or treat TB in infants. The child should therefore be investigated for TB disease and, if found to have TB disease, must be given full course of anti-TB treatment. If the child does not have TB disease, give Isoniazid preventive therapy (10mg/kg body weight) for 6 months. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

71. Mother and child should stay together and breastfeeding should continue normally but standard TB infection prevention measures are recommended. BCG vaccination of the child should then be postponed until the end of Isoniazid preventive therapy. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

72. Treatment in Patients with Liver Disease Patient can have pre-existing liver disease or develop it as a toxicity of TB drugs. In patients with liver failure, a regimen without Rifampicin may be used. Streptomycin and Ethambutol may be used if treatment is necessary for patients with severe liver disease. These patients should be referred to higher level of care for specialised management 2022/3/24 MWEBAZA VICTOR MBchB TB presention

73. Treatment of patients with drug induced liver injury Suspect liver damage when a patient on anti-TB drugs has developed jaundice plus or minus other symptoms of liver injury such as abdominal pain, nausea and vomiting If the liver enzymes (ALT/AST) are elevated more than three times the normal upper limit, all medications including non-TB medications should be discontinued and the patient monitored until the enzymes normalise 2022/3/24 MWEBAZA VICTOR MBchB TB presention

75. Treatment of Patients with Renal Failure Isoniazid, Rifampicin, and Pyrazinamide may be given in normal dosage to patients with renal failure, since these drugs are eliminated almost entirely by biliary excretion or are metabolised into non-toxic compounds. Patients with severe renal failure who are receiving Isoniazid should also receive pyridoxine to prevent peripheral neuropathy. These patients should be referred to a higher level of care for further management. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

76. Bone, Joint, and Spinal Tuberculosis TB can virtually affect any tissue in the body. TB infects bone, joint tissues and the spine. TB of these tissues requires extended TB treatment durations longer than the standard six months.(12month) 2 RHZR/10RH There is additional beneﬁt of surgical debridement in combination with chemotherapy 2022/3/24 MWEBAZA VICTOR MBchB TB presention

77. TB Meningitis TB meningitis requires longer duration of treatment than TB in pulmonary site. The range of duration is 9-12 months. The usual regimens of TB treatment are used. However, a choice can be made between ethambutol and an injectable aminoglycoside. In adults, ethambutol is usually suﬃcient. In children, there is preference for an aminoglycoside. Adjunctive corticosteroid therapy recommended in the treatment of TB meningitis with dexamethasone or prednisolone tapered over 6–8 weeks for patients. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

78.  TB/HIV CO-INFECTION HIV is the strongest risk factor for developing tuberculosis (TB) disease in those with latent or new Mycobacterium tuberculosis infection. The risk of developing TB disease is between 20 and 37 times greater in people living with HIV (PLHIV) than among those who do not have HIV infection 2022/3/24 MWEBAZA VICTOR MBchB TB presention

79. TB prevention in HIV 1. 2. 3. 4. 5. 6. 7. Intensified TB case-finding:- All people living with HIV (children, adolescents & adults), wherever they receive care should be regularly screened for TB using the Intensified TB Case Finding too Isoniazid preventive therapy (IPT) Infection Control Co-trimoxazole preventive therapy (CPT) Provider Initiated HIV testing and counselling HIV prevention methods in the TB clinics Provision of antiretroviral treatment 2022/3/24 MWEBAZA VICTOR MBchB TB presention

80. After diagnosis of HIV/TB Co-infection before you iniate ARVs start with antiTBs for 8weeks then introduce the ARVs this helps to prevent IRIS 2022/3/24 MWEBAZA VICTOR MBchB TB presention

82. IRIS Immune reconstitution inﬂammatory syndrome (IRIS) is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inﬂammatory response that paradoxically makes the symptoms of infection worse. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

83. Infections most commonly associated with IRIS include Mycobacterium tuberculosis and cryptococcal meningitis. Persons living with AIDS are more at risk for IRIS if they are starting HAART for the ﬁrst time, or if they have recently been treated for an opportunistic infection 2022/3/24 MWEBAZA VICTOR MBchB TB presention

84. J • J 2022/3/24 MWEBAZA VICTOR MBchB TB presention

85. References 1. 2. 3. 4. World Health Organization. WHO consolidated guidelines on drug-resistant tuberculosis treatment. 2019. Xu P, Chen H, Xu J, Wu M, Zhu X, Wang F, et al. Moxiﬂoxacin is an effective and safe candidate agent for the tuberculosis treatment: a meta-analysis. Int J Infect Dis. 2015 Oct 16. NTLP(uganda) manual 3rd edition march 2017. Davidson's principles and practice of medicine 21st edition part 2 chapter 19 page 688 - 695. 2022/3/24 MWEBAZA VICTOR MBchB TB presention

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