Pulmonary Tuberculosis

Introduction

Tuberculosis (TB) is one of the oldest diseases known to affect humans.
It is caused by bacteria of mycotuberculosis complex which includes M. tuberculosis, M. bovis, and M. africanum.
M. tuberculosis is the most common cause of tuberclosis worldwide.
Transmission is by droplet infection.
Nigeria ranks 11^th among the high burden countries of TB in the world.
Federal government of Nigeria established the National Tuberculosis and Leprosy Control Program (NTBLCS) in 1993 with the objective to reduce the prevalence of TB and Leprosy to a level at which they no longer constitute public health problem in the country.
Almost every organ can be affected. The lung parenchyma are affected in more than 80% of the cases. This can be either as primary pulmonary disease (occurs mainly in childhood) or post primary pulmonary disease.

Those at risk of acquiring tuberculosis are:

Contacts of patients with smear positive pulmonary disease
Immunocompromised individuals, health works and people living in overcrowded conditions.

Clinical Features

Common symptoms of pulmonary tuberculosis:-

Persistent cough
Weight loss
Drenching night sweats
Chest pain (dull or pleuritic)
Haemoptysis
Anorexia

Signs

Physical examination may be normal

Crepitations usually in the upper zone (earliest physical sign)
Physical signs of consolidation, cavitation and fibrosis develop later

Other signs:- palor and finger clubbing, Erythema nodusum and phlynctenular conjuctivitis (Primary PTB)

Differential Diagnosis

Pneumonia
Carcinoma of the bronchus
Lung abscess (especially due to Klebsiella pnenmoniae)
Pulmonary infarction

Complications

Lung collapse
Bronchiectasis
Chronic Obstructive Pulmonary Disease
Pleural effusion
Corpulmonale
- Destructive lung syndrome
- Lung abscess
Acute Respiratory Distress Syndrome
Spontaneous Pneumothorax
Haemorrhage/Mycetoma

Extrapulmonary TB:

Lymph node TB:

Painless swelling of lymph nodes (usually cervical and supracervical sites
Usually discrete in early disease; may become inflamed and have a fistulous tract draining caseous material)

Pleural TB:

Fever
Pleuritic chest pain
Dyspnoea
Dullness to percussion
Absence of breath sounds

TB of the upper airways:

Nearly always a complication of advanced cavitatory pulmonary TB
May involve the laynx, pharynx and epiglottis:
- Hoarseness
- Dysphagia
- Dysphonia
Chronic productive cough

Genitourinary TB:

Urinary frequency Dysuria Haematuria Flank pain

Skeletal TB:

Weight bearing joints are affected: spine, hips and knees

Spinal TB (Pott's disease):

Paraparesis Paraplegia

TB meningitis:

Headache
Mental changes
Confusion
Lethargy
Altered sensorium
Neck rigidity
Ocular nerve paresis
Hydrocephalus

Gastrointestinal TB:

Commonly affects the terminal ileum and caecum
Abdominal pain (may be similar to that of appendicitis)
Diarrhoea
Intestinal obstruction
Haematochezia
Palpable mass Fever
Weight loss
Night sweats
TB peritonitis

Pericardial TB:

Fever
Dull retrosternal pain
Friction rub
Cardiac tamponade

Military TB:

Fever
Night sweats
Anorexia
Weakness
Weight loss
Cough
Hepatomegaly
Splenomegaly
Lymphadenopathy
Choroidal tubercles (pathognomonic)
Meningitis

There are no clinical findings specific for a diagnosis of pulmonary TB; a history of contact with a smear positive pulmonary TB case, respiratory symptoms for more than 2-3 weeks not responding to broad spectrum antibiotics, and weight loss, failure to thrive may suggest TB

Investigations

Bacteriologic examination:

Sputum AFB X 3 (spot, morning, spot)
Sputum mycobacterial culture and drug susceptibility testing/Gene xpert-Xpert MTB-RIF Assay

Radiologic Examination

Chest X-ray

Other tests:-

Tuberculin skin test (low sensitivity and low specificity)
Hematologic - Full blood count and ESR

In cases of diagnostic difficulties one may need High Resolution CT and fibre-optic bronchoscopy with bronchoalveolar lavage and trans-bronchial biopsy

Treatment goals

Cure the disease
Prevent death from active TB or its late effects
Prevent relapse of TB
Decrease transmission of TB
Prevent the development of acquired drug resistance

NTBLCP recommends that all TB cases and TB suspects should be managed in DOTs centres. This programme provides good quality drugs free of charge to all patients. It also implements international standards for tuberculosis care

Drug treatment

Chemotherapy

Standard drug regimens for Adults

6 months regimen

Initial Intensive Phase:- This is for 2 months using Rifampicin, Isoniazid, Pyrazinamide and Ethambutol.
Continuation Phase:- 4 months using Isoniazid and Rifampicin.

In this regimen, there is fully supervised administration of drugs in both intensive and continuation phases.

Drugs	Daily dose	Adverse drug reactions
Rifampicin taken 30 mins before breakfast	10 mg/kg (maximum dose) 600mg	Drug interactions, hypersensitivity hepatitis fever
Isoniazid	5-10mg/kg (maximum dose) 300mg	Hypersensitivity, polyneuropathy.
Ethambutol	15-20mg/kg (maximum dose) 1.6g	Optic neuritis hypersensitivity
Pyrazinamide	20-35mg/kg (maximum dose) 2.5g	Hepatitis, gout, hypersensitivity

Pyridoxine 10mg is usually added to prevent peripheral neuropathy
These drugs can be provided as fixed dose combinations to enhance adherence to therapy or loose tablets.

Other aspects of management include:

Contact tracing
Health education of the patient

Standard drug regimens for Children

Two standardized treatment regimen adopted for the treatment of all children diagnosed with susceptible TB in Nigeria:

Standard six month treatment Regimen for all children with newly diagnosed or previously treated PTB disease.
- Regimen 1 for Children: 2(RHZ+E)/4(RH)
Standard six month treatment Regimen for all children with newly diagnosed or previously treated EPTB disease.
- Regimen 2 for children with EPTB: 2(RHZ+E)/10(RH)

Tb Paediatric drugs and dosages

Drug	Dosage(mg/kg)	Range(mg/kg)	Maximum dose (mg/day)
Isoniazide (H)	10	7-15	300
Rifampicin (R)	15	10-20	600
Pyrazinamide (Z)	35	30-40	2000
Ethambutol (E)	20	15-25	1200

Use of Pyridoxine (Vitamin B6) in children

Pyridoxine (vitamin B6) protects against isoniazid-induced peripheral neuropathy

Not routinely given but is recommended for severely malnourished and HIV-infected children

The recommended dose is 25 mg/ day until treatment is completed

Monitoring of PTB Treatment

Monitoring for response to therapy (clinical improvement and bacteriologic clearance in sputum) and adverse drug reactions.

Routine laboratory monitoring for drug toxicity may not be necessary when there are no symptoms, signs or co-morbid factors like hepatic and renal disease.

Multidrug Resistant Tuberculosis (MDR-TB)

Drug resistance in mycobacteria comes about through random spontaneous mutation.
Emergence of this is creating additional barriers to effective tuberculosis control.
MDR-TB is caused by an organism resistance to at least isoniazid and rifampicin.
XDR-TB is MDR-TB plus resistance to any of the fluroquinolones and one of the second line injectables.

MDR-TB Suspects

Failure of treatment with first line anti-tuberculosis drugs
Symptomatic contacts to a known MDR-TB case

Diagnosis

Send sputum samples to specialized facility for culture, molecular line probe and drug susceptibility
Treatment – refer to designated treatment centres

HIV Associated Pulmonary Tuberculosis

Tuberculosis is an important opportunistic among HIV infected persons and commonest cause of death in such patients.
It directly attacks the critical immune mechanism involved in protection against Tuberculosis.
Its presentation depends on the stage of HIV infection.
Diagnosis of tuberculosis in HIV patients may be difficult when the immunity is highly compromised (low CD4 count) because of atypical presentation, increase frequency of sputum smear negativity and atypical radiographic features.
All TB patients should be offered HIV counselling and testing; also all HIV patients should be screened for TB.

Treatment

Commence anti-tuberculosis treatment.
Offer Co-trimoxazole preventive therapy
Commence anti-retroviral therapy