Tuberculosis

Tuberculosis

Dr Ghazi Farhan Haji
CARDIOLOGIST

Aetiology

Clssification
Clinical features
Investigation
Treatment
Adverse reaction of therapy
Prognosis

In TB ,the following true except;

1-(TB) is caused by infection with Mycobacterium tubercles
2- Erythema nodosum presented in post primary TB
3- The ascitic fluid is exudative and cellular with a predominance of lymphocytes
4-Nucleic acid amplification is use for the rapid confirmation of TB
5-The risk of peripheral neuropathy due to Isoniazid may reduced by prescribing pyridoxine
6-DOT . it is currently only recommended for patientswho are homeless


Aetiology
Tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis (MTB)
other types
M. bovis (reservoir cattle) and M. africanum (reservoir human). M. avium complex

The impact of TB on world health is significant; in 2006, there were an estimated 9.2 million new cases ,The majority of cases occur in the world's poorest nations

Factors increasing the risk of TB

Patient-related
Age (children > young adults < elderly) -immigrants from high-prevalence countries
Close contacts of patients with smear-positive pulmonary TB --Overcrowding (prisons, collective dormitories); homelessness (Chest radiographic evidence of self-healed TB)
Primary infection < 1 year previously –
Smoking
Associated diseases
Immunosuppression: HIV, high-dose corticosteroids, cytotoxic agents -Malignancy - diabetes mellitus -Chronic renal failure -Silicosis
Gastrointestinal disease associated with malnutrition

Timetable of TB

Time from infection Manifestations

3-8 weeks Primary complex, positive tuberculin skin test

3-6 months Meningeal, miliary and pleural disease


Up to 3 years Gastrointestinal, bone and joint, and lymph node

Around 8 years Renal tract disease

3 y Post-primary disease due to reactivation or reinfection

Clinical presentations of pulmonary TB

Chronic cough, often with haemoptysis
Pyrexia of unknown origin and night sweating
Unresolved pneumonia
Exudative pleural effusion
Asymptomatic (diagnosis on chest X-ray)
Weight loss, general debility
Spontaneous pneumothorax

Classification

Primary pulmonary TB
Miliary TB
Cryptic TB
Post-primary pulmonary TB


Clinical features: Primary pulmonary TB
(Primary TB refers to the infection of a previously uninfected (tuberculin-negative) individual).
self-limiting febrile ( Influenza-like) illness ,Primary complex &Skin test conversion but clinical disease only occurs if there is a hypersensitivity reaction or progressive infection
Lymphadenopathy: hilar (often unilateral), paratracheal or mediastinal -Collapse -Consolidation Obstructive emphysema -Cavitation (rare) -Pleural effusion -Meningitis -Pericarditis
Hypersensitivity
Erythema nodosum
Phlyctenular conjunctivitis
Dactylitis

Miliary TB

@Blood-borne dissemination gives rise to miliary TB, which may present acutely but more frequently is characterised by 2-3 weeks of fever, night sweats, anorexia, weight loss and a dry cough.
@Hepatosplenomegaly and tuberculous meningitis.

@Auscultation of the chest is frequently normal.

@Fundoscopy may show choroidal tubercles.

@The classical appearances on chest X-ray are of fine 1-2 mm lesions ('millet seed') distributed throughout the lung fields

@Anaemia and leucopenia reflect bone marrow involvement..

Cryptic TB
#Age over 60 years
#Intermittent low-grade pyrexia of unknown origin
#Unexplained weight loss, general debility (hepatosplenomegaly in 25-50%)
#Normal chest X-ray
#Blood dyscrasias; leukaemoid reaction,pancytopenia
#Negative tuberculin skin test
#Confirmation by biopsy (granulomas) of liver or bone marrow

Post-primary pulmonary TB

@Refers to exogenous ('new' infection) or endogenous (reactivation of a dormant primary lesion) ,The onset is usually insidious.
@ frequently pulmonary lesion in the apex of an upper lobe where the oxygen tension favours survival of the strictly aerobic organism.

@Systemic symptoms include fever, night sweats, malaise, and loss of appetite and weight, and are accompanied by progressive pulmonary symptoms.
@Radiological changes include ill-defined opacification in one or both of the upper lobes, consolidation, collapse and cavitation develop to varying degrees ..

Clinical features: Extrapulmonary disease

Extrapulmonary tuberculosis accounts for about 20% of cases in those who are HIV-negative but is more prevalent in HIV-positive individuals including :
CNS,Cardiac,skin.joint,abscess,LN enlargment .asciates. gastroentestinal , renal systems
And general finding like weight loss anoroxia ,night sweating
.


Lymphadenitis
#Lymph nodes are the most common extrapulmonary site of disease.

#The nodes are usually painless. and may discharge through the skin with the formation of a 'collar-stud' abscess and sinus formation.

#The tuberculin test is usually strongly positive.

#Rarely, surgical excision is necessary.

Gastrointestinal disease

@TB can affect any part of the bowel (Ileocaecal disease)

@Fever, night sweats, anorexia and weight loss are usually prominent and a right iliac fossa mass may be palpable.

@The main differential diagnosis is Crohn's disease

@Tuberculous peritonitis is characterised by abdominal distension,
The ascitic fluid is exudative and cellular with a predominance of lymphocytes..

Pericardial disease

@Disease occurs in two forms: pericardial effusion and constrictive pericarditis . associated with breathlessness and abdominal swelling.


@Pulsus paradoxus, a raised JVP(S3), hepatomegaly, prominent ascites and peripheral oedema are common to both types. chest X-ray (pericardial calcification occurs in around 25% of cases).

@The addition of corticosteroids to antituberculosis treatment has been shown to be beneficial for both forms of pericardial disease.

Central nervous system disease

@Meningeal disease represents the most important form of central nervous system TB .
@Cranial nerve palsy . Tuberculoma (SOL) Hydrocephalus

@If Un recognised and untreated, it is rapidly fatal.

@Even when appropriate treatment is prescribed, mortality rates of 30% have been reported and survivors may be left with neurological sequelae..

Bone and joint disease

#The spine is the most common site for bony TB (Pott's disease), which usually presents with chronic back pain and typically involves the lower thoracic and lumbar spine .

.
#CT and/or MRI are valuable in gauging the extent of disease, the amount of cord compression,

#Monoarthritis and polyarthritis might develope

Genitourinary disease
@Fever and night sweats are rare with renal tract TB . Haematuria, frequency and dysuria are often present, with sterile pyuria found on urine microscopy and culture.


@In women, infertility from endometritis, or from salpingitis

@In men, genitourinary TB may present as epididymitis or prostatitis.

Diagnosis of Pulmonary TB
@Sputum*
(positive when 5000-10 000 organisms are present)
@Fluid examination (cerebrospinal, ascitic, pleural, pericardial, joint):
@Tissue biopsy (from affected site); also bone marrow/liver

@Circumstantial (ESR, CRP, anaemia etc.)

@Tuberculin skin test (low sensitivity/specificity; useful only in primary or deep-seated infection) -----------Stain (Ziehl-Neelsen -Auramine fluorescence)

The presence of an otherwise unexplained cough for more than 2-3 weeks, particularly in an area where TB is highly prevalent, or typical chest X-ray changes should prompt further investigation .
@Culture (for definitive diagnosis if smear negative ) (Solid media (Löwenstein-Jensen) (Liquid media (1-3wk rapid confirm)) (only 10-100 viable organisms are required for sputum to be culture-positive).

@Nucleic acid amplification (New strategies for the rapid confirmation of TB at low cost and non invasive)

@CXR--

@Response to empirical antituberculous drugs (usually seen after 5-10 days

Management

TREATMENT

Category of TB

• Initial phase*

• Continuation phase

1
New cases of smear-positive pulmonary TB
2 months H3R3Z3E3 or 2 months H3R3Z3S3
4 months H3R3

Severe extrapulmonary TB
2 months HRZE or 2 months HRZS
4 months HR

Severe smear-negative pulmonary TB

6 months HE†

Severe concomitant HIV disease


2§
Previously treated smear-positive pulmonary TB
2 months H3R3Z3E3 or 1 month H3R3Z3E
5 months H3R3E3

Relapse
2 months HRZES or 1 month HRZE
5 months HRE

Treatment failure

Treatment after default

3‡
New cases of smear-negative pulmonary TB
2 months H3R3Z3E3
4 months H3R3

Less severe extrapulmonary TB
2 months HRZE
4 months HR


6 months HE†

Important notes

@Most patients can be treated at home.
@ isolation should be considered 1-uncertainty about the diagnosis, 2-intolerance of medication, 3-questionable compliance, 4-adverse social conditions or 5-a significant risk of multidrug-resistant TB (MDR-TB: culture-positive after 2 months on treatment, or contact with known MDR-TB). I
@In choosing a suitable drug regimen, underlying comorbidity (renal and hepatic dysfunction, eye disease, peripheral neuropathy and HIV status), as well as the potential for drug interactions, must be considered.

@Baseline liver function and regular monitoring are important for patients treated with standard therapy including rifampicin, isoniazid and pyrazinamide,.

Cont.

@Patients treated with rifampicin should be advised that their urine, tears and other secretions will develop a bright orange/red coloration, and women taking the oral contraceptive pill must be warned.

@Ethambutol should be used with caution in patients with renal failure,.

@indication of Corticosteroids 1-treating pericardial or meningeal disease, 2- children with endobronchial disease. 3- in TB of the ureter, 4-pleural effusions and extensive pulmonary disease, and 5- can suppress hypersensitivity drug reactions.

@Surgery is still occasionally required

Main adverse reactions of first-line antituberculous drugs

• Isoniazid

• Rifampicin
• Pyrazinamide
• Streptomycin
Ethambutol
Mode of action
Cell wall synthesis
DNA transcription
Unknown
Protein synthesis
Cell wall synthesis
Major adverse reactions
Peripheral neuropathy1Hepatitis2Rash
Febrile reactionsHepatitisRashGastrointestinal disturbance
HepatitisGastrointestinal disturbanceHyperuricaemia
8th nerve damageRash
Retrobulbar neuritis3Arthralgia
Less common adverse reactions
Lupoid reactionsSeizuresPsychoses
Interstitial nephritisThrombocytopeniaHaemolytic anaemia
RashPhotosensitisationGout
NephrotoxicityAgranulocytosis
Peripheral neuropathyRash


1The risk of peripheral neuropathy may be reduced by prescribing pyridoxine.
2Hepatitis is more common in patients with a slow acetylator status and in alcoholics.
3Reduced visual acuity and colour vision may be reported with higher doses and are usually reversible

The effectiveness of therapy for pulmonary TB may be judged by a further sputum smear at 2 months and at 5 months. A positive sputum smear at 5 months defines treatment failure.

2nd line therapy

quinolone

Control and prevention

Detection of latent TB Contact.Approximately 10-20%
Cases are commonly identified using the tuberculin skin test .
Asymptomatic contact with a positive tuberculin skin test but a normal chest X-ray may be treated with chemoprophylaxis
Chemoprophylaxis is also recommended for children aged less than 16 years identified during contact tracing to have a strongly positive tuberculin test, children aged less than 2 years in close contact with smear-positive pulmonary disease, those in whom recent tuberculin conversion has been confirmed, and babies of mothers with pulmonary TB. It should also be considered for HIV-infected close contacts of a patient with smear-positive disease.
Rifampicin plus isoniazid for 3 months or isoniazid for 6 months is effective.

Skin testing in TB : tests using purified protein derivative (PPD)

Heaf test( Read at 3-7 days)
Multipuncture method
Grade 1: 4-6 papules Grade 2: Confluent papules forming ring Grade 3: Central induration
Grade 4: > 10 mm induration
Mantoux test (Read at 2-4 days)


Using 10 tuberculin units
Positive when induration 5-14 mm (equivalent to Heaf grade 2) and > 15 mm (Heaf grade 3-4)

Directly observed therapy (DOT)

Poor adherence to therapy is a major factor in prolonged infectious illness, risk of relapse and the emergence of drug resistance.
DOT (direct observer therapy)involves the supervised administration of therapy thrice weekly and improves adherence.

it is currently only recommended for patients

1- unlikely to be adherent to therapy:
2- who are homeless, alcohol or drug users,
3- those with serious mental illness and those with a history of non-compliance.

Drug-resistant TB

Drug-resistant TB is defined by the presence of resistance to any first-line agent.

Multidrug-resistant (MDR) TB is defined by resistance to at least rifampicin and isoniazid,
.

The prevalence of MDR-TB is rising, It is more common in those with a prior history of TB, particularly if treatment has been inadequate, and those with HIV infection
.


Factors contributing to emergence of drug-resistant TB
Drug shortages
Poor-quality drugs
Lack of appropriate supervision
Transmission of drug-resistant strains
Prior anti-tuberculosis treatment
Treatment failure (smear-positive at 5 months)

Vaccines

BCG (the Calmette-Guérin bacillus), a live attenuated vaccine.
It is administered by intradermal injection.

Current vaccination policies vary world-wide according to incidence and health-care resources, but usually target children and other high-risk individuals.

BCG is very safe with the occasional complication of local abscess formation. It should not be administered to those who are immunocompromised (e.g. by HIV) or pregnant.

Prognosis

Following successful completion of chemotherapy, cure should be anticipated in the majority of patients.
.

In the absence of treatment, a patient with smear-positive TB will remain infectious for an average of 2 years;
..


In TB ,the following true except;
1-(TB) is caused by infection with Mycobacterium tubercles
2- Erythema nodosum presented in post primary TB
3- The ascitic fluid is exudative and cellular with a predominance of lymphocytes
4-Nucleic acid amplification is use for the rapid confirmation of TB
5-The risk of peripheral neuropathy due to Isoniazid may reduced by prescribing pyridoxine
6-DOT . it is currently only recommended for patientswho are homeless

Thank you