Extrapulmonary Tuberculosis_SRP.....pptx

TB

1. Overview of Extrapulmonary Tuberculosis Dr Sundararajaperumal Anandakrishnan Associate Professor Department Of Thoracic Medicine Chengalpattu Medical College & Hospital Chengalpattu

2. Outline Overview of E xtrapulmonary Tuberculosis (EPTB) Clinical evaluation and treatment of EPTB

3. Extrapulmonary TB Worldwide, between 10-25% of TB infections occur in extrapulmonary sites (outside the lung)  TB can occur in any site, including: Pleura Lymph nodes Bones and joints CNS (usually meningitis, but can occur in brain or spine) Larynx Pericardial Abdominal sites Kidneys Genitourinary tract Disseminated ( miliary )

4. Extrapulmonary TB Especially common in children and people living with HIV, DM EPTB occurs ~10% in HIV(-) But in HIV(+), – 33% with extrapulmonary alone – 33% with pulmonary alone – 33% both pulmonary and extrapulmonary (many with negative CXRs)

5. Pathogenesis Same for Pulmonary and E xtrapulmonary TB Droplet nuclei containing tubercle bacilli are inhaled,enter the lungs, and travel to the alveoli.Tubercle bacilli multiply in the alveoli . A small number of tubercle bacilli enter the bloodstream and spread throughout the body. The tubercle bacilli may reach any part of the body, including areas where TB disease is more likely to develop (such as the brain, larynx, lymph node, lung, spine, bone, or kidney ).

6. Pathogenesis Within 2 to 8 weeks, special immune cells called macrophages ingest and surround the tubercle bacilli. The cells form a barrier shell, called a granuloma, that keeps the bacilli contained and under control (LTBI). If the immune system cannot keep the tubercle bacilli under control, the bacilli begin to multiply rapidly (TB disease). This process can occur in different areas in the body, such as the lungs, kidneys, brain, or bone.

7. Medical Evaluation of Extrapulmonary TB Symptoms of disease (what and how long) History of TB exposure, infection, or prior disease Past TB treatment Demographic risk factors for TB Medical conditions that increase risk for TB disease – HIV – Diabetes – Other immunosuppression – Under-nutrition

8. Extrapulmonary TB Symptoms Can have the same symptoms as people with P ulmonary TB: – fever, night sweats, fatigue, loss of appetite, weight loss. In addition, patients often develop complaints specific to the body site infected with TB. Examples: – Blood in the urine (TB of the kidney) – Headache/confusion (TB meningitis) – Back pain (TB of the spine) – Hoarseness (TB of the larynx) – Disseminated ( milliary ) TB may have no localizing signs, may present with anemia , or low platelets

9. Diagnosis of Extrapulmonary TB Physical Exam Specimens should be obtained from the suspected sites of involvement – AFB smear, culture – Drug-susceptibility testing – Nucleic acid amplification (NAA) testing – Histopathologic examination Always evaluate for pulmonary TB: symptom screen, CXR and sputum evaluation, especially in persons with HIV Provider-initiated HIV testing

10. Diagnostic Challenges Often more difficult to diagnose extrapulmonary TB Because EPTB is less common, we often first think of other causes for the patient’s symptoms – E.g., pain in the right ankle more likely a sprained ankle than TB of the joint Secondly, EPTB often occurs in body sites that are difficult to access (e.g., the liver, which cannot be touched, or examined easily). Resource-limited settings may not have diagnostic capability to obtain clinical specimen for testing EPTB

11. TB Lymphadenitis Epidemiology TB lymphadenitis represents 30% of EPTB; Represents reactivation at site seeded hematogenously during primary TB – Peak age from children, to 30-40 years old – Female to male ratio: 1.4 to 1 – HIV-infected Known historically as “scrofula” or the “ King’sEvil ”, this refers to TB of the superficial lymphatics usually of the neck

12. TB Lymphadenitis Typical Presentation Most often presents as isolated chronic, non tender unilateral mass in ant or post cervical triangles – Firm discrete mass or matted nodes fixed to surrounding structures – Multiple nodes may be involved – Overlying skin may be indurated – Uncommon: fluctuance , draining sinus; bilateral involvement Differential diagnosis Non- tuberculous mycobacteria, other infections, sarcoid , neoplasm

13. TB Lymphadenitis Primary Diagnostic Tests Fine needle aspirate is safer but less sensitive than biopsy – Combining both cytology and microbiology can increase sensitivity to 91% Nucleic acid amplification tests (NAAT) are underutilized – Automated NAAT ( Xpert ) active study

14. Pleural Tuberculosis Second most common site of extrapulmonary TB U p to 20% in countries where HIV common Rupture of sub-pleural focus into the pleural space with inflammatory response Symptoms: pleuritic chest pain, SOB, fever HIV-infected more likely to have +smear/culture and +pleural biopsy

15. Pleural Tuberculosis Pleural effusion:  Unilateral  Exudative, lymphocytic  pH 7.3-7.4  Smear positive <5%  Culture positive <50% Pleural biopsy  Pathology and microbiology combined sensitivity 65-95% Adenosine deaminase (ADA) level – Overall several meta- analyses show sensitivity of ADA around 91% and specificity 89% – Similar performance in HIV infected

16. Miliary TB Milliary TB occurs when tubercle bacilli enter the bloodstream and are carried to all parts of the body  Wide range of presentations  May include on one extreme ARDS and on the other extreme failure to thrive without fever  Symptoms may be dominated by whatever organ system is primarily involved  Typical patient has a febrile wasting syndrome of 2-4 months duration

17. Miliary TB: Diagnosis  The typical patient has an under lying disease that has lead to immunosuppression to some degree.  Non-specific symptoms are the rule  Rigors are present rarely  All organs can be involved  Many findings such as organomegaly are more common in children

18. CXR Findings in Miliary TB  CXR shows miliary pattern in more than half of cases  In those with an initial normal CXR, a miliary pattern will become apparent in days to weeks later  The size of nodules is generally 1-3 mm

19. Miliary TB: Diagnosis  Sputum smear is positive in about 25% of cases in both HIV and non- HIV patients  In sputum smear neg milliary TB, bronch led to an immediate diagnosis in 65% and this increased to 79% with culture  Nucleic acid amplification (NAAT) of Bronchial wash fluid can help.

20. Miliary TB: Prognosis  Prognosis is related to co-morbidity and those factors that lead to a delay in diagnosis.  HIV patients respond to treatment in a similar fashion to non-HIV patients  20% mortality is found and this has been stable for 30 years.  Delay in diagnosis is the key factor in mortality of miliary TB

21. Skeletal TB  Bone and joint disease due to TB affects all ages but the greatest risk appears to be in those >age of 65y  Spinal TB or Pott’s is the most common followed by hip and then knee  Diagnosis is ideally made with isolation of the organism from the affected area  The diagnosis is supported by – Mono articular disease – Cold abscesses – Positive PPD – Epidemiological risks – Chest x-ray with findings consistent with TB

22. Skeletal TB Skeletal TB is a haematogenous infection & affects almost all bones TB commonly affects spine & hip joint Constitutional symptoms generally occur before symptoms related to spine manifest Lower Thoracic & Lumbar vertebrae are most common sites of involvement followed by middle thoracic & cervical vertebrae

23. Spinal TB Infection generally begins with inflammation of the anterior aspect of the intervertebral joints; typically,it spreads behind the anterior ligament to involve the adjacent vertebral body. Once two adjacent vertebrae are involved, infection enters the adjoining intervertebral disc space. This tends to occur later in Pott's disease than in bacterial vertebral osteomyelitis and may have the radiographic appearance of relative disc sparing. Eventually , the avascular disc tissue dies; there is vertebral narrowing and subsequent vertebral collapse. Gibbus deformity, a form of structural kyphosis, distorts spinal canal anatomy Formation of a "cold abscess"(soft tissue mass) at the site is common. Noncontiguous spinal disease ( eg , disease at more than one level) is uncommon

24. Pott’s paraplegia Most serious complication of spinal TB Occurrence is reported to be as high as 30 % in patients with spinal TB Early onset paraplegia develops during active phase of infection Paraplegia of late onset can appear many years after disease has become quiescent even without any evidence of reactivation, occurs due to osteophytes and other chronic degenerative changes at a site of prior infection. Most commonly, paraplegia develops due to mechanical pressure on cord, but in a small number of patients cord dysfunction may occur due to non-mechanical cause

25. Bone & Joint TB Other sites Knee joint, foot bones, elbow joint and hand bones Rarely, it also affects the shoulder joint Two basic types of disease patterns have been observed: granular and exudative ( caseous ) Though both patterns have been observed, one form may predominate The caseous exudative type is characterized by bone destruction,local swelling, abscess formation, sinus formation, and constitutional symptoms; it occurs most often inchildren . The granular type is more insidious and less destructive than the caseous exudative type, andabscess formation is less common; it occurs most often in adults.

26. Central nervous system Tuberculosis Central nervous system (CNS) tuberculosis (TB) includes Three clinical categories : T uberculous meningitis, I ntracranial tuberculoma , and S pinal tuberculous arachnoiditis .

27. Neurological TB - TB Meningitis Accounts for 70-80 % of cases of neurological TB In bacteraemic phase of primary lung infection, metastatic foci can become established in any organ, which can become active after a variable period of clinical latency Rupture of a subependymally located tubercle (Rich focus) results in release of infectious material into subarachnoid space

28. Neurological TB - TB Meningitis Salient pathological features of TBM include Inflammatory meningeal exudate Ependymitis Vasculitis Encephalitis Disturbance of cerebrospinal fluid (CSF) circulation & absorption Focal neurological deficits & features of raised intracranial tension may precede signs of meningeal irritation Focal or generalised seizures are encountered in 20-30 % Cranial nerve palsies can occur in 20-30% 6 th nerve involvement being most common Complete or partial loss of vision is a major complication of TBM

29. Clinical manifestations - TB Meningitis The prodromal phase lasting two to three weeks, characterized by the insidious onset of malaise, lassitude , headache, lowgrade fever , and personality change. The meningitic phase with more pronounced neurologic features eg , meningismus , protracted headache , vomiting, lethargy, confusion, and varying degrees of cranial nerve and long tract signs. The paralytic phase in which the pace of illness accelerates rapidly; confusion gives way to stupor and coma, seizures, and often hemiparesis

30. Categorization - TB Meningitis B ased upon mental status and focal neurologic signs as follows: Stage I patients are lucid with no focal neurologic signs or evidence of hydrocephalus . Stage II patients exhibit lethargy, confusion; they may have mild focal signs, such as cranial nerve palsy or hemiparesis . Stage III represents advanced illness with delirium, stupor, coma, seizures, multiple cranial nerve palsies , and/or dense hemiplegia.

31. Neurological TB - TB Meningitis In untreated cases, progressive deterioration in level of consciousness, pupillary abnormalities & pyramidal signs may develop due to increasing hydrocephalus & tentorial herniation Terminal illness is characterised by deep coma & decerebrate or decorticate posturing Without treatment, death usually occurs in 5-8 weeks Atypical presentations include acute meningitic syndrome simulating pyogenic meningitis, progressive dementia, status epilepticus , psychosis, stroke syndrome, locked- in-state, trigeminal neuralgia, infantile spasm & movement disorders

32. Tuberculoma Tuberculomas are conglomerate granulomatous foci within the brain parenchyma ; that develop from deepseated tubercles acquired during a recent or remote hematogenous bacillemia . O bserved on histopathology or radiographic imaging Contrast enhanced MRI of brain (sagittal view, T1 weighted image) showing solitary enhancing ring lesion

33. Spinal Tuberculous Arachnoiditis A focal inflammatory disease at single or multiple levels producing gradual encasement of the spinal cord by a gelatinous or fibrous exudate . Symptoms develop and progress slowly over weeks to months and may culminate with a meningitis syndrome . Patients present with the subacute onset of nerve root and cord compression signs: spinal or radicular pain, hyperesthesia or paresthesias ; lower motor neuron paralysis; and bladder or rectal sphincterdysfunction

34. Differential diagnosis of central nervous system tuberculosis Fungal meningitis ( cryptococcosis , histoplasmosis , blastomycosis , coccidioidomycosis ) Viral meningoencephalitis (herpes simplex, mumps) Parameningeal infection (sphenoid sinusitis, brain abscess, spinal epidural abscess) Partially treated bacterial meningitis Neurosyphilis Neoplastic meningitis (lymphoma, carcinoma) Neurosarcoidosis

35. Abdominal TB Tuberculous enteritis is a form of extrapulmonary TB that can involve any aspect of the gastrointestinal tract.

36. Pathogenesis Swallowing infected sputum Hematogenous spread from active pulmonary or miliary tuberculosis (TB) Ingestion of contaminated milk or food Contiguous spread from adjacent organs

37. Abdominal TB - Gastrointestinal TB With widespread pasteurisation of milk, abdominal TB caused by M. bovis is now seldom Gastrointestinal TB can be ulcerative, hypertrophic, ulcerohypertrophic , diffuse colitis & sclerotic forms Gastrointestinal TB is a chronic illness with abdominal pain as most common symptom. Diarrhoea, anorexia, weight loss and fever are also common Other symptoms include a moving lump in abdomen, nausea, vomiting, malaena , & constipation Doughy feel of abdomen, mass in right iliac fossa due to hyperplastic caecal TB, lymph node enlargement & rolled up omentum Abdominal distension with increased peristaltic activity is generally associated with intestinal obstruction When intestinal perforation develops, signs of peritonitis is apparent

38. Abdominal TB - Peritoneal TB TB peritonitis have an acute onset & subjected to emergency surgery Ascitic Often insidious onset Abdominal distension, dilated veins and transverse solid mass in the abdomen Encysted or loculated form present with localised abdominal swelling Fibrous Widespread adhesions cause coils of intestine to be matted together & distended which may act as “blind-loop” Result in steatorrhoea , malabsorption syndrome & abdominal pain Adherent loops of intestine & thickened mesentery may felt as lump(s) in abdomen Purulent Rarely develops secondary to TB salpingitis Cold abscess, entero -cutaneous & entero -enteric fistulae can develop

39. Abdominal TB - Imaging Oral and intravenous contrast enhanced computed tomography CT finding is concentric mural thickening of the ileocecal region, with or without proximal intestinal dilatation Characteristic lymphadenopathy with hypodense centers , representing caseous liquefaction Colonoscopy — Colonoscopic findings of ileocecal TB may include ulcers, strictures, nodules, pseudopolyps,fibrous bands, fistulas, and/or deformed ileocecal valves

40. Abdominal TB - Gastrointestinal TB CT Abdomen - shows ascites, marked omental thickening in both flanks, and stranding in the mesentery Diffuse calcified mesenteric lymphadenopathy

41. Histopathology Granulomas associated with TB tend to be large and confluent, often with caseation necrosis . Ulcers are lined by aggregate epithelioid histiocytes , and disproportionate submucosal inflammation is seen. In contrast, granulomas associated with CD are infrequent, small, nonconfluent , and noncaseating . CD is also characterized by focally enhanced colitis and a high prevalence of chronic inflammation in endoscopically normal appearing areas

42. Other Gastrointestinal Sites Hepatobiliary & pancreatic TB are rare Associated with disseminated/ miliary TB (DTB/MTB) & more often in immune compromised Clinical manifestations are non-specific & depend on site & extent of disease Anorexia, malaise, low grade fever, weight loss, night sweats malena , pancreatic mass or abscess & obstructive jaundice Pancreatic TB may present as acute or chronic pancreatitis, or mimic malignancy Splenic TB presents as hypersplenism or splenic abscess, or as a solitary splenic lesion Multiple TB abscesses described in patients with HIV infection Pre-operative diagnosis is difficult & diagnosis is often confirmed on histopathological examination of excised specimen

43. Pericardial TB TB pericardial involvement present as Acute pericarditis Chronic pericardial effusion Cardiac tamponade Pericardial constriction Pericardial involvement most commonly results from direct extension of infection from adjacent mediastinal lymph nodes, or through lympho -haematogenous route from a focus elsewhere

44. Genitourinary TB Genitourinary TB (GUTB) complicate up to 3-4% with pulmonary TB Presents with dysuria , haematuria which may be painless, flank pain, renal mass, sterile pyuria , & recurrent urinary tract infection Rarely acute presentation mimicking pyelonephritis also described Other uncommon manifestations include nonhealing wounds, sinuses or fistulae & haemospermia Testicular tuberculosis. Computed tomographic scan of the pelvis showing a large, irregular, mixed solid and cystic left testicular mass  (arrow) .

45. Genitourinary Tuberculosis Often involves the fallopian tubes, also the endometrium Likely important cause of infertility worldwide (1-17%) Other symptoms include: chronic pelvic pain, menstrual irregularities, abdominal masses

46. Cutaneous TB Accounts for 0.1-2.5% of all with skin diseases Several clinical types of cutaneous TB In those not previously exposed to M.TB, TB of skin & TB chancre Previously sensitised hosts develop lupus vulgaris, scrofuloderma & TB verrucosa cutis Other lesions seen are tuberculids which includes lichen scrofulosorum , papulonecrotic tuberculid , erythema induratum & erythema nodosum Lupus vulgaris is most common variety seen in India, followed by TB verrucosa cutis & scrofuloderma Other types are distinctly rare Localised & generalised skin complications due to Bacille Calmette Guerin (BCG) vaccination Reddish brown plaques PAPULONECROTIC TUBERCULIDS VERRUCOSUS CUTIS

47. TB in Otorhinolaryngology Focus shifted on to otorhinolaryngological TB with advent of HIV infection & AIDS Patients with laryngeal TB present with hoarseness of voice Pain is also important feature which radiate to one or both ears & lead to odynophagia Occasionally, presentation can be similar to that encountered in acute viral laryngitis Laryngeal TB may co-exist with carcinoma

48. Ocular TB Choroid is most commonly affected Choroidal tubercles when present can provide valuable diagnostic clues to diagnosis of DTB/MTB Tuberculids & phlyctenulosis occur in post-primary TB Phlyctenulosis can involve conjunctiva, cornea or lid margin   Choroidal tuberculomas

49. More recently More recently, evidence has accumulated on the accuracy of CBNAAT MTB/RIF for various forms of EPTB . CBNAAT MTB/RIF should now be considered a central test in the work-up of EPTB, and may be used along with conventional tools, such as microscopy, liquid cultures (that are the most sensitive technologies for MTB detection), and histopathology (biopsy) to arrive at the final diagnosis .

50. M. Pai and R. Nathavitharana , Extrapulmonary Tuberculosis: New Diagnostics and New Policies , Indian J Chest Dis Allied Sci 2014;56:71-73 ]

51. Major Goals of EPTB Treatment 1.Cure patient, minimize risk of death/disability, prevent transmission to others 2. Provide safest, most effective therapy in shortest time 3. Prescribe multiple drugs to which the organisms are susceptible 4. Never treat with a single drug or add single drug to failing regimen 5. Ensure adherence and completion of therapy

52. Treatment of Extrapulmonary TB In most cases, treat with same 4 drug regimens used for pulmonary TB Culture-negative TB/ (culture not done) – Failure to isolate M. TB from person with clinical evidence does not exclude TB – If high likelihood of TB, initiate therapy with INH, RIF, PZA,and EMB

53. Treatment of Extrapulmonary TB Special considerations for therapy – Disseminated TB or TB meningitis in children: treat for 9–12 months – For bone and joint TB, 9 months favoured – Treat HIV+ patients with EPTB same as with pulmonary only TB, 6-9 months based on clinical factors (disseminated disease, cavitary pulmonary disease with slow response to therapy, etc.) – In tuberculous meningitis, ethambutol should be replaced by streptomycin / Fluroquinolones .

54. Treatment & outcome While 6 month treatment is sufficient for vast majority of patients, each patient should be individually assessed & , where appropriate, treatment duration may be extended for a given patient Patients receiving anti TB treatment should be carefully monitored for adverse drug reactions, especially drug induced hepatotoxicity Usefulness of corticosteroids in treatment of EPTB is controversial & not well established When diagnosis of TB is established with certainty, additional oral corticosteroid treatment may be helpful in selected patients with life-threatening forms of EPTB – TB meningitis and pericarditis

55. Treatment of Extra pulmonary TB Although sometimes required for diagnosis, surgery plays little role in the treatment of extrapulmonary TB. It is reserved for management of late complications of disease such as: – Hydrocephalus – Obstructive uropathy – Constrictive pericarditis – Neuro - logical involvement from Pott’s disease (spinal TB). For large, fluctuant lymph nodes that appear to be about to drain spontaneously, aspiration or incision and drainage appear beneficial

56. Use of other drugs in EPTB To address problem of drug interaction between Rifampicin & some of anti-retroviral (ARV) drugs, such as Nevirapine , antiretroviral treatment can be initiated after DOTS treatment is completed In HIV co-infected TB patients in later stages of immunosuppression, concomitant anti-retroviral & anti TB treatment may required & in such cases ARV regimen needs to be suitably modified, e.g. Nevirapine replaced with Efavirenz High index of clinical suspicion, timely & judicious use of invasive diagnostic methods & confirmation of diagnosis, early institution of DOTS & close clinical monitoring for adverse drug reactions, are key to successful management of EPTB

57. Conclusion TB remains a major cause of death worldwide New molecular diagnostics have made earlier and improved diagnosis of active disease possible Newer antiTB drugs offer the promise of shortened treatment regimens for drug-sensitive disease and more effective treatment for drug-resistant disease and latent infection New vaccines against TB in advanced clinical trials offer hope for future TB control Although these scientific developments are promising, the global economic crises continue to hinder TB-control programs Rise and spread of drug resistance and synergistic interaction with the HIV epidemic are posing difficult challenges and threatening global efforts at TB control Strong political and financial commitments will be required to achieve global control of TB and avert millions of unnecessary deaths

58. THANK YOU Feedbacks are solicited -- [email protected]

59. Lymphatic TB Treatment Treatment A six-month regimen including HRZE (two months HRZE, four months HR) is recommended Although the disease is pauci -bacillary, the development of nodes during therapy or at the end of therapy is common Usually there is no evidence of bacteriological relapse No role for steroids except perhaps in unusual circumstances of IRIS with HIV co-infection

60. Treatment of Bone and Joint Disease  Same therapy as for other forms of TB (RIPE)  Nine months is favoured  Myelopathy with or without functional impairment responds medically  A randomized trial of the Medical Research Council comparing surgical debridement with multi-drug regimens found no benefit to surgery  There are instances where surgery should be considered

61. Genitourinary TB – Treatment Treat with a standard regimen- INH, rifampin , PZA, ethambutol – Concerns for adverse effects of PZA on the fetus have not been supported by experience – PZA is recommended by the WHO and other international organizations 6 months usually sufficient Surgery usually only needed if large tubo -ovarian abscess

62. Extra-pulmonary TB and HIV  In PLHIV, their immune systems cannot respond as strongly to a TB infection so they are not able to contain the TB bacilli outside of the blood stream  Primary TB infection is still the lungs, but TB bacilli then access the blood stream and spread through the body, finding other sites to multiply and cause disease  Usually TB bacilli remain in the site where they first infected the body and do not gain access to the blood stream, however people living with HIV who are also infected with TB often have TB bacilli in their blood

63. Transmission of Extrapulmonary TB Outside the lungs ( extrapulmonary ) usually not infectious, unless person has: Concomitant pulmonary disease, Extrapulmonary disease in the oral cavity or larynx, or Extrapulmonary disease with open site, especially with aerosolized fluid.

64. Use of other drugs in EPTB In EPTB patients known to have co-existent HIV infection, Category I regimen is to be used under DOTS strategy / FDC All HIV co-infected TB patients should receive a Rifampicin -containing regimen

65. Tuberculosis of the Spine Infection begins in cancellous area of vertebral body, commonly in epiphyseal location & less commonly in central or anterior area of vertebral body Infection spreads & destroys epiphyseal cortex, intervertebral disc & adjacent vertebrae

66. Pott’s Disease

67. MRI scan A B B - MRI dorsolumbar spine of another patient (sagittal view, T2 weighted image) showing destruction of D10 & D11 vertebrae reduction in intervening disc with anterior granulation tissue & cord compression (arrow) A - MRI scan of dorsolumbar spine, (coronal view, T1 weighted image) showing central hypointense lesion (arrow) with reduced vertical height of vertebra & paraspinal cold abscess

68. Ocular TB Sclerokeratitis   TB uveitis can present as pan uveitis or as chronic granulomatous iridocyclitis Anterior chamber granuloma with granulomatous keratic precipitates and  hypopyon Recurrent sclerokeratitis resulting in corneal thinning and melt with adjacent active scleritis . ( B) Chest ( CT) revealed enlarged lymph nodes with necrosis involving pretracheal , paratracheal , and subcarinal groups

69. Use of Steroids in Extrapulmonary TB Unless drug resistance is suspected, adjuvant corticosteroid treatment is recommended for TB meningitis and pericarditis

70. Congenital TB Rare manifestation – Difficult to distinguish from infection acquired after birth Transmission in utero can occur 2 ways- – Hematogenous spread through the umbilical vein to the fetal liver – Ingestion/aspiration of infected amniotic fluid Mothers are often asymptomatic

71. Congenital TB Cantwell criteria: – Primary hepatic complex/ caseating granuloma on biopsy – TB infection of the placenta – Maternal genital tract TB and lesions in the infant in the first week of life Symptoms in infant can be nonspecific High mortality rate Treat infants with four drugs

72. Testing for TB in Pregnant Women When Should Testing for TB Occur in Pregnant Women?  As soon as possible if symptoms are present  For LTBI screening, should be done early in second trimester What Test Should be Used?  TST is valid and safe in pregnancy  IGRAs can be used but limited data on their accuracy in pregnant women

73. Chest X-Rays and Pregnancy  All TST/IGRA positive patients should have a CXR with abdominal shielding  Should not be delayed; identification of TB disease has implications for treatment and infection control  Radiation exposure for 2 view CXR = 0.1mGy – 10x lower than 9 month exposure to environmental background – This level of exposure considered negligible risk to fetus

74. TB and Pregnancy  Untreated TB is more of a risk to the mother and fetus than treating TB  Pregnant women should be assessed for their TB risk  TSTs and CXRs are safe during pregnancy  Treatment for LTBI can prevent development of TB disease and transmission of TB to the fetus or infant

75. Monitoring and Follow-up Assess patient’s response to treatment: – Clinical evaluation, bacteriological examination if possible,chest radiograph (if pulmonary as well) – As in pulmonary smear- negative disease, the weight of the patient is a useful indicator Conduct clinical evaluations at least monthly; after 2 months of therapy, if symptoms do not resolve, reevaluate for – Potential drug-resistant disease – Non-adherence to drug regimen – Other cause of clinical presentation if M. tuberculosis not confirmed

76. Extrapulmonary TB: Take home points  Not uncommon, especially in HIV-infected persons  Difficult to diagnose because can mimic many diseases, limited diagnostics in some countries  Respiratory isolation key until PTB ruled out  Always get HIV test in patients w/ EPTB.  Treat it like you would pulmonary TB, except: – Steroids in meningeal and pericardial disease