Risk Factors for TB
- Previous TB infection ( 10% chance and more in first 2 yrs)
- HIV infection
- Young children, the elderly, and other immunocompromised
- exposure to close contacts, and smoking.
transmission of TB
- TB is an airborne disease, spread in particles called droplet nuclei (contain 1-3 bacilli and are small enough to reach the alveolar space (1-5mm)
- These droplets may be passed by an infected person through coughing, sneezing, or shouting.
The progression to clinical disease depends on three factors:
- Infecting dose (the number of M. Tuberculosis organisms inhaled )
- The virulence of the organism
- host immune system
pathopysiology of tb
- tubercle bacilli inahled
- macrophage alveoli engulf and tries to kill the bacteria
- if it succed in kiiling infection aborted
- if didnt, bacteria replicate and rupture the macrophaes and relies
- the cycle will continue for weeks. primary infection
- after 3 weeks macrophages accumulate form granulomas. with nacrotic hardened tissue, and baciili domornate in it
- 90% of this sucessful and infection remaon in latent phase
- some percent of it will start replicating and remission and progession of active disease it will transfer to other organs:
N.B. M. tuberculosis can inhibit the fusion of lysosomes to phagosomes inside macrophages preventing their destruction inside macrophages.
patient assesment for tb
- fever, chills, night sweats, weight loss, and changes on chest radiograph.
- Hemoptysis (blood in sputum)
- HIV screening is recommended
- respiratory isolation.
Diagnosis of active disease of tb include ?
- Identification of acid-fast bacilli bacteria in sputum
- Chest radiography
- Tuberculin skin testing (PPD) – Mantoux Test
Culture Testing
- suptum smear on glass slide, to detect AFB
- M.T doesnt strain with gram strain so the Ziehl-Neelson strain with carbol fushin is used to strain microorganism.
- On culture, M. tuberculosis grows slowly doubling every 20 hours (other bacteria double every 30 mins)
Antimicrobial susceptibility testing
important for proper treatment but require 8 weeks to obtain until mt not detected emperical therpy started.
Rapid-identification tests include
1- NAAT( nuclie acid amplification test) using pcr
2- IGRAs ( interferon gamma rays assay)
Tuberculin Skin Test (TST) steps
- inject 0.1 ml of ppd on dorsal surface of arm 4cm below elbow. intradermly
- Mark the site with an indicator and wait for 48-72 hrs
- Measure the mm of induration (wheal – hard elevated area) - not the erythema
Interpretation of tst test
Induration of≥5 mm is considered positive in
HIV-infected persons
Recent contacts of TB case patients
Immunosuppressed patients
Interpretation of tst test
Induration of≥10 mm is considered positive in
- Recent immigrants (i.e., within the last 5 years)
- Injection drug users
- Residents and employees of the high-risk congregate settings like; prisons, hospitals and health care facilities, residential facilities for patients with AIDS and homeless shelters
- Mycobacteriology laboratory personnel
Induration of≥15 mm is considered positive in Persons with no known risk factors for TB
flase positive and false negative tst
FALSE POSITIVE
* Prior BCG vaccination
FALSE NEGATIVE
* Concurrent viral, bacterial or fungal infection
* Chronic renal failure
* Diseases affecting lymphoid organs (e.g., lymphoma, chronic leukemia)
* Immunosuppressive drugs (e.g., medical steroids)
* Children aged 6 months or less or elderly patients (i.e., immature or waning immunity)
* Stress (e.g., surgery)
* Recent TB infection (test needs 2 – 12 weeks to become positive
Interferon-gamma release assays (IGRAs)
Blood test the measures T-cell release of interferon-gamma following stimulation by antigens unique to Mycobacterium tuberculosis and a few other mycobacteria.
Unaffected by previous BCG vaccine
Treatment of Latent TB
first line: isoniazide
* 300mg daily ( 5-10 mg/kg) for 9 months (can be 6 mnth also)
* twice weekly (15mg/kg) for 6-9 mnths
* pyridoxine 25mg added to reduce risk of neuropathy peripheral
second line: rifampin
( 600mg) daily for 4 months
best drugs avalible for prevention drug resistance
isoniazid and rifampin
Treatment of Active Disease
the RIPE therapy for a total of 6 months of treatment:
- Rifampin, Isoniazid, Pyrazinamide + Ethambutol for 2 months, followed by
- Rifampin + Isoniazid for 4 months.
Extending treatment to 9 (or sometimes 12) months of isoniazid and rifampin treatment is recommended for:
- risk of failure and replase, cavity lesion on radiograph, sputum after 2 mnth of treatment,
- no pyrazinimide initially
- hiv patient without treatment
- cns involment 12mnths
- joint or bone involment 6-9mnths
extending treatment to 9mnths for culture test
positive cultures mean that bacteria causing TB were found in a sample (like sputum) even after the initial 2-month treatment phase.If both these conditions are present,extending treatment for at least 6 months after cultures become negative is recommended.This ensures all bacteria are eliminated.
when intermittent dosing can be considered:
Patients who have a low risk of relapse with non-cavitary TB and/or smear is negative at start of treatment
HIV negative patients
3 types of drug-resistant TB exist:
MDR-TB: resistance to both isoniazid and rifampin.
Extensive drug-resistant TB (XDR-TB): resistance to isoniazid & rifampin among first line agents, resistance to fluoroquinolones, and resistance to at least one second-line injectable drug.
Totally drug-resistant TB (TDR-TB): resistance to all first- and second-line agents.
Risk factors for drug-resistant TB
1- history of tb treatment
2- patient from area high prevelance of drug resisitance tb
3- children born from area high prebelance of drug resistance
4- hiv patient
5- patient with positive smaear after 2 mnth treatment
6- Tuberculosis in persons who are homeless, IV drug abusers, and HIV infected
Group A:
Levofloxacin OR Moxifloxacin
Bedaquiline
Linezolid
Group B:
Clofazimine
Cycloserine OR Terizidone
