Clinical Aspects of Tuberculosis

Name: Clinical Aspects of Tuberculosis
Uploaded: 2017-07-19T03:06:38+00:00
Duration: PTM27S47
Channel: Barnard Flynn
Description: Clinical Aspects of Tuberculosis

Clinical Aspects of Tuberculosis
Professor Mike McKendrick Lead Physician Department of Infection and Tropical Medicine Royal Hallamshire Hospital Sheffield Honorary Professor Division of Genomic Medicine University of Sheffield Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals
Clinical aspects of TB Pathogenisis Clinical diagnosis Treatment and monitoring and control New issues Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical Aspects of Tuberculosis
Pathogenesis of tuberculosis Infection versus disease Host factors Pathogen factors Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Pathogenesis Host factors include Social e.g. Poverty alcoholism Age e.g. Baby Teenage girl Old age Immunity e.g. HIV Gamma interferon SCID Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Pathogenesis Organism factors e.g. Virulence factors [Drug resistance] Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Pathogenesis MTB into lungs (or to cervical nodes or abdo. nodes) Replication of organisms Primary complex (lung and mediastinal lymph nodes) Mycobacteraemia with potential for ‘seeding’ Consequence of tuberculous infection Symptomatic illness – disease (minority) immunological control (majority) with Ghon focus on Xray. Infection is ‘contained’ by granuloma but not eliminated Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Pathogenesis Tuberculous disease is a consequence of: Primary infection e.g. in baby Reactivation ‘natural’ Associated with immunosupression Re infection Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical features Clinical illness Pulmonary Extrapulmonary Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical illness Chest Pulmonary Pleural Mediastinal nodes pericardium Extra pulmonary skin and soft tissues (including lymph nodes) Bone Abdominal Intra cranial other Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical clues for TB Clinical symptoms – usually ‘chronic’ rather than acute Fever Sweats Weight loss Focal symptoms Epidemiology History of TB, HIV Country of origin, recent travel/work Contact with TB [England, Wales & NI 2004 7,176 notifications, 414 children 70% foreign born population groups] Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

TB – guidelines for the clinician
Great mimicker Low index of suspicion Pulmonary TB usually easy to consider Non pulmonary often requires ‘lateral thinking’ Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical TB Laboratory samples In the current era every effort must be made to obtain adequate samples likely to lead to a microbiological diagnosis before treatment is started (sometimes difficult with surgical specimens!) Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

What can the laboratory do to help the clinician?
Awareness of TB e.g. in the patient with recurrent sputum samples for ‘chronic bronchitis’ ‘Rapid’ diagnosis of infection and resistance Culture and sensitivities – the clinician wants answers immediately if possible PCR – further opportunities for development Gamma interferon based tests?? other Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

What samples? Depends on clinical scenario
Chest Sputum – if productive Induced sputum Bronchoscopic alveolar lavage (BAL) Pleural biopsy Pleural fluid Other E.g. Lymph node, aspiration of abscess, mesenteric biopsy, stool, bone marrow etc. What about EMSU? - should be done selectively where it is likely to be helpful Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Induced sputum Hypertonic saline nebuliser in negative pressure room with HEPA filter and well trained physiotherapist Study of 27 confirmed positive patients 13 +ve induced sputum only 1 +ve bronchoscopy only 13 +ve induced sputum and bronchoscopy McWilliams T et al Thorax 2002: 57; Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Audit of induced sputum in Department of Infection in Sheffield
Criteria for procedure Past history TB or contact with TB in last year Respiratory symptoms of one or more of: Non-productive cough Fever, Night sweats, weight loss Haemoptysis 114 procedures, 12 positive for TB Cohort followed up for 12 months, no cases missed - Bell et al. J Infection 2003: 47; Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical cases Cases of pulmonary infection Non pulmonary infection Examples of spectrum of disease produced by TB Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Pulmonary and non pulmonary TB disease – Sheffield 2005
Equal numbers of patients with pulmonary and non pulmonary tuberculosis Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical presentation 1
35 year old African lady with fever and dry cough for 3 weeks. Mildly unwell Night sweats Weight loss 4 pounds No history of contact with TB CXR Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Case 1 – miliary tuberculosis
Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Pulmonary TB typically affects the upper zones of the lung

Case 1 Investigation FBC normal ESR 53 U and E normal LFT – albumen 31 CRP 40 Induced sputum – smear negative Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Case 1 Progress Clinical diagnosis of TB 4 drug treatment Clinical improvement TB culture positive at week 3 fully sensitive (week 5) Modified anti TB drug regime in light of lab results Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Case 1 What about HIV testing? – who to test? Strong association between HIV and TB Universal testing or selective testing? What about testing for vitamin D? Vitamin D has role in activating macrophages to destroy mycobacteria Vitamin D deficiency in ethnic populations in UK often low Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Case 1 Cured after standard 6 months therapy Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical presentation 2
28 year old African lady with backache for 6 weeks Diagnosed initially as non specific Developed fever – no obvious cause ID opinion sought Investigation with MRI scan Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical case 2 Diagnosis Vertebral osteomyelitis with soft tissue mass impinging on the cord Investigation Biopsy and culture Treatment 4 anti TB drugs and antibiotic therapy Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical case 2 What will happen if diagnosis or treatment for TB spinal osteomyelitis is delayed? Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

What will happen if treatment delayed? – gibbus formation (acute angulation of spine with or without neurological damage) Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

The physical appearance – Potts disease of spine - gibbus

Clinical case 2 Progress Increasing back pain and neurological symptoms – mild leg weakness Repeat MRI – changes similar Treatment Continue therapy consider surgical decompression Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical case 2 Further progress Weakness of legs Neurosurgery and internal splinting Other considerations - clinical Has she got HIV? Is her vitamin D level normal? Other considerations - epidemiological From where has she got infection? To whom might she have given it? Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

TB may affect any tissue of the body including: Skin and soft tissue Lymph nodes Bones and joints Intra abdominal structures including peritoneum Kidneys Adrenal glands Central nervous system Tuberculoma meningitis Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Skin and soft tissue Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

25 male African. Expanding non painful lesion in neck - Cervical lymph node TB progressing to abscess (beware deep extension – collar stud abscess) Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

TB node in neck with deep extension

35 female African – systemically well - hand and foot lesions present for 6 months – MTB grown on biopsy by plastic surgeons (HIV neg) Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Bony tuberculosis Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Astute radiologist should enable the appropriate further investigation

Often associated with delay in diagnosis – any chronic discharging lesion must be considered possibly TB Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Abdominal Tuberculosis

Renal tuberculosis (may have few or no symptoms) leading to autonephrectomy Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

30 middle eastern asylum seeker - abdo pain, fever, sweats – CT scan - peritoneal TB confirmed on biopsy – may mimic malignancy Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Intracranial TB Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

miliary TB on MRI scan tuberclomas on CT scan

meningitis – diagnosis usually made on clinical grounds
Acute or subacute Prognosis related to severity of disease at onset of treatment Commonly delay between presentation and diagnosis Common in children c100 cases per year in England CSF Cell count (50% lymphs, 50% polys) High protein ++ Low glucose Micro often negative (PCR/culture important) Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Treatment of TB Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

BTS guidelines – Thorax 2000: 55; NICE guidelines – 2006 Sensitive TB – 4 drugs for 2 months drugs for 4 months Resistant TB - 6 drugs for 24 months (second line drugs are not so effective) [Eng, Wales & NI 2004, 6.8% Isoniazid resistant, 1% MDR TB (R to Isoniazid and rifampicin)] Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Problems of TB therapy Toxicity e.g. liver Multiple therapy Prolonged treatment Drug interactions e.g. anti HIV drugs Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Compliance Treatment will not work if not taken DOTS (Directly Observed Therapy) if: Likely poor compliance MDRTB Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Outcome WHO target (1991) detect 70% infectious cases of TB and cure at least 85% by 2005 Eng, Wales and NI Probably detect 70% cases infectious TB Cure rate uncertain Among all TB patients with a known outcome the proportion of cases that have completed treatment 79% in 2003 78% in 2002 79% in CDR 23 March 2006 Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Why failure? Patient non compliance Deliberate Failure to understand e.g. language, culture Social e.g. alcohol Patient movement e.g. ‘lost to follow up’ Lack of medical/nursing support others Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

public health - avoiding transmission
TB is statutorily notifiable disease Multidisciplinary approach – medical, TB nurses, CCDC etc. Identify and manage possible sources of infection and contacts Considerations treat as OP where possible multi occupancy housing, social deprivation negative pressure rooms in hospitals (limited facility) beware transmission in OP setting e.g. waiting area Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

New challenges in TB Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Challenges in TB Anti TNF therapy (Eg infliximab, etanercept) May promote breakdown of granulomas and reactivation of TB How to screen Clinical history CXR (? With induced sputum) Skin testing ?? Value of gamma interferon tests Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Challenges in TB What will be the place of Quantiferon and Elispot type tests in clinical practice? Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical need for new and better anti TB drugs

Objective - to lead to more effective shorter course regimen Better pharmacokinetics longer half life better penetration to cavities Better activity kill TB in dormant phase Active against resistant strains Safer and easier Lack of interaction with anti HIV therapy Less toxic Low cost Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Will there be new affordable therapy for TB?
Global Alliance for TB Drug Development TB development drug discovery research unit Astra Zenica Glaxo SmithKline Novartis WHO links with pharma TB trials consortium (US CDC) Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Will there be new affordable therapy for TB?
Moxifloxacin TMC 207 OPC-67683 PA-824 LL3858 Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Summary TB is a challenging disease for the clinician Must have microbiology before starting treatment – more rapid lab tests? Need to encourage compliance Need for multidisciplinary approach to diagnosis and management and control Need shorter, better, cheap anti TB regimes Dpt. Infection and Tropical Medicine, Sheffield Teaching Hospitals

Clinical Aspects of Tuberculosis

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