Tuberculosis

Description
Tuberculosis, TB (short for tubercles bacillus) is a common and in some cases deadly infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis in humans. Tuberculosis usually attacks the lungs but can also affect other parts of the body. It is commonly associated with HIV.


Types

Active TB	Infection with mycobacteria of the M. tuberculosis complex, where mycobacteria  are growing and causing symptoms and signs of disease. Occurs in 10% of infected individuals without preventive therapy Risk increases with immunosuppression and is highest within the 1st 2 years 85% of cases are pulmonary, which are contagious
Latent TB	Positive TST or IGRA test no physical findings of TB disease the chest X-ray is normal or only reveals evidence of healed infection i.e. granulomas or calcification in the  lung, hilar lymph nodes or both. Asymptomatic and are not infectious
Primary	Disease resulting from initial infection
Recrudescent	Active disease occurring after period of latent, asymptomatic infection
Miliary	Disseminated disease

Epidemiology
1/3 of world's population infected with TB bacillus
Higher incidence in ethnic minorities and medically underserved populations
Worldwide: 140/100,000

Risk Factors
For infection:

• Demographics: Homeless, minority
• Institutionalization (e.g., prison, nursing home)
• Close contact with infected individual
• Immigrant within 5 years (from Asia, Africa, Latin America, former Soviet Union states)
• Health care workers (in hospitals, clinics, and medical laboratories)

For development of disease once infected:

• HIV; lymphoma; diabetes mellitus; chronic renal failure; cancer of head, neck, or lung
• Malnutrition
• Gastrectomy
• Steroids and other immunosuppressive drugs
• IV drug abuse

Pathophysiology

• Mycobacterium tuberculosis is spread by small airborne droplets
• Cell-mediated response by the body causes accumulation of activated T lymphocytes and macrophages to form a “granuloma” that limits replication of organism.
• Destruction of the macrophages produces early “solid necrosis.”
• In 2–3 weeks, this forms a soft cheesy necrotic environment; develops “caseous necrosis” establishing latency.
• In people with intact immunity, it generally undergoes “fibrosis” and calcification; in people with less effective immune systems, it progresses to primary progressive tuberculosis.

Aetiology
Mycobacterium tuberculosis
M. bovis
M. africanum

Presentation
Recent travel to or immigration from high-prevalence country
Exposure to high-risk populations (see Risk Factors) or to known infected person
HIV status/risk factors
Signs and symptoms: Cough, Hemoptysis, Fever and night sweats, Weight loss, Malaise, Painless adenopathy, Pleuritic chest pain
Physical Exam usually normal

• Specific findings vary based on organ involvement and might include adenopathy, rales on lung exam, or hepatosplenomegaly
• Late findings: Renal, bone, or CNS disease

Investigation
(Guidelines on The Prevention and Control of Tuberculosis in Ireland 2010)

TB screening	3 methods: Tuberculin skin test (TST) Interferon-Gamma Release Assays (IGRA) Chest X-ray
Tuberculin skin Test (TST)	1st line test for TB Description Intradermal injection of a small amount of purified protein derived from Mycobacterium tuberculosis bacteria (PPD). The local skin reaction to PPD is used to assess an individual’s sensitivity to the tuberculin protein. Media Result reaction(induration) will occur within 48 to 72 hours. PPD is positive if it is >5 mm and HIV infection (or suspected), immunosuppressed, recent TB contact, clinical evidence of disease on chest film >10 mm and age <5 years or other risk factors >15 mm and no risk factors Ireland use Mantoux 2TU/0.1ml tuberculin PPD False -ve in BCG, Steroids, HIV, gastrectomy, alcoholism, renal failure, lymphoreticular disorder,sarcoidosis, malnutrition, hematologic Those with positive TST results should be considered for IGRA testing
Interferon-Gamma Release Assays (IGRA)	May be considered on a case by case basis in adults and children Eg: QuantiFERON-TB Gold (QFT-G) is a new IFN-γ-release assay that measures the release of interferon after stimulation in vitro by M.tuberculosis antigens. Advantages It only requires one visit from the patient compared to two visits for a TST IGRA demonstrate improved specificity over the TST IGRA are at least as sensitive as the TST
CXR	Not gold-standard Primary TB: May show infiltrate with or without effusion, atelectasis, or adenopathy, A Ghon focus is a primary lesion caused bymycobacterium bacilli (tuberculosis) developed in the lung of a previously uninfected individual . If the Ghon focus also involves infection of adjacent lymphatics and hilar lymph nodes, it is known as the Ghon's complex.When it undergoes fibrosis and calcification it is called RANKE COMPLEX Recrudescent TB:  Cavitary lesions and upper-lobe disease with hilar adenopathy common HIV:  Atypical findings with primary infection, right upper-lobe atelectasis
Notification procedure	Once a diagnosis of TB is either laboratory confirmed or strongly suspected on clinical grounds, the MOH should be notified by the clinical director of a diagnostic laboratory and/or clinician as soon as possible and ideally at the time of diagnosis
Sputum collection	3 different morning sputum samples for acid-fast bacilli (AFB) stain and culture; use aerosol induction, gastric aspirate (children), or bronchoalveolar lavage if needed. If positive AFB, begin treatment immediately.
Others	Persons with TB should be tested for HIV; if positive, get CD4 count. Baseline CBC, creatinine, and liver enzymes, including bilirubin If using ethambutol: Baseline visual acuity and color discrimination If high risk: Test for hepatitis B and C If extrapulmonary suspected: Urine, cerebrospinal fluid, bone marrow, and liver biopsy for culture In case of pleural effusion- send for MC&S and Light’s Criteria

Management

Latent TB	Directly observed therapy (DOT) should be provided for those being treated for LTBI in immigrants from areas of high TB endemnicity, homeless persons and intravenous drug users The recommended treatment regimens for LTBI in adults are: Isoniazid for a minimum of six months with an optimum duration of nine months    (same in children) Rifampicin for four months (6 months in children) A combination of rifampicin and isoniazid for a duration of at least three months with an optimum of four months. (4 months in children)
Multidrug-Resistant or XDR LTBI	Consultation with a respiratory physician or infectious disease consultant Multidrug-resistant TB (MDR-TB) TB bacilli resistant to at least isoniazid and rifampicin with or without resistance to ethambutol and streptomycin Extensively drug-resistant TB (XDR-TB) is resistance to at least isoniazid and rifampicin (i.e. MDR-TB), plus resistance to any fluoroquinolone, and any one of the following second line anti-TB injectable drugs (capreomycin, amikacin or kanamycin).
Pre-treatment evaluation	Discuss with pt LFTs for all patients aged over 14 years before treatment
TB drugs	Drugs (MOA) Route Daily dose Major adverse reactions Isoniazid Bactericidal po/iv Children: 5-10mg/kg Adults: 5mg/ kg  [300mg] Hepatic enzyme elevations, hepatitis, rash, peripheral neuropathy, CNS effects, increased phenytoin levels, possible interaction with disulfiram Rifampicin Bactericidal po/iv Children: 10- 20mg/kg Adults:   8-12mg/kg [600mg] Hepatic enzyme elevations, hepatitis, rash, fever, thrombocytopaenia, influenza-like syndrome, reduced levels of many drugs (including methadone, warfarin, hormonal forms of contraception, oral hypoglycaemic agents, theophylline, dapsone, ketoconazole, Pyrazinamide Bacteriostatic po Children: 20-30mg/kg Adults: 20- 30mg/kg)[2.0g for both] Gastrointestinal (GI) upset, hepatotoxicity, hyperuricaemia, gout (rarely), arthalgias, rash Ethambutol Bacteriostatic po Children: 15-25mg/kg) [1.5g] Adults: 15- 25mg/kg [2.0g] Decreased red-green colour discrimination, decreased visual acuity, skin rash Streptomycin Bactericidal im/iv Children:n 15-30mg/kg Adults: 15mg/ kg [1.0g] Auditory toxicity, renal toxicity, hypokalaemia, hypomagnesaemia
Treatment regimen	Recommendation for patients with sensitive strains of tuberculosis and  where there are no contraindications. Intensive phase (2months) Isoniazid (H) and rifampicin (R), with pyrazinamide (Z) and ethambutol (E) Continuation phase (4months) isoniazid and rifampicin Selected patients have a higher rate of relapse with a six month regimen and may benefit from longer treatment. Extend to 9 months in the following cases: Drug-susceptible pulmonary TB with initial cavitation on CXR and  poxitive sputum after the intensive phase Persistent culture +ve at 2 months regardless of CXR Treatment regimen did not include pyrazinamide in the intensive phase or whose organism is resistant to pyrazinamide Patients being treated with once-weekly isoniazid and rifampicin whose sputum culture remains positive after the intensive phase
Pyridoxine	Used in conjunction with anti-TB drugs to prevent side effects in the peripheral and central nervous systems.   10mg daily
Monitoring	Before treatment: Baseline LFTs and a FBC including platelets and biochemistry panel, including creatinine Monthly testing not necerssary if baseline normal or asymptomatic
Directly observed therapy (DOT)	DOT is a way of helping patients to take their medicine for TB.   A person receiving DOT will take medication while being onserved by a healthcare worker/key worker everyday or several times a week at an agreed place e.g. the patient’s home, TB clinic.
hepatotoxicity Mgt	A consultant with expertise in TB should always be consulted when treating a patient with active TB disease with documented hepatotoxicity.
Follow up	After 6 months as relapse may occur
Pregnancy/ breastfeeding	Continue regimen in pregnancy unless contraindicated Breastfeeding is safe while taking TB regimen
Admin aspect	A high level of suspicion, education
Standard precautions	Occupational health programme Hand hygiene, Personal protective equipment Management of spillages of blood and body fluids, sharps, laundry Appropriate patient placement
Airborne precautions	airborne isolation room (negative pressure isolation room with an ante room or a neutral pressure design A respiratory protection programme for staff advised to wear respiratory masks Patients should wear a surgical mask while they are infectious,
BCG Vaccination	Def: Bacillus Calmette-Guerin (BCG) vaccine was derived by in-vitro attenuation of the bovine tubercle bacillus Dose: 0.05ml by intradermal (age <12m), 0.1ml by intradermal (age >12m)
Contact tracing	Conducted according to the concentric circle approach, whereby  contacts with greatest exposure to the index case are prioritised for screening.

Complications

• Cavitary lesions can be secondarily infected.
• Drug resistance declining in US. At risk for drug resistance if HIV+, or treatment taken improperly, or if from an area with high incidence of resistance

Prognosis
Generally few complications and full resolution of infection if drugs taken for full course as prescribed. If untreated, can lead to multiple complications, including death.