TUBERCULOSISnd

Epidemiology

Tuberculosis (TB) is the most common cause of death world-wide from a single infectious disease and is on the increase in most parts of the world. The reasons for this are primarily inadequate programmes for disease control, multiple drug resistance, immunosuppression associated with HIV infection (in whom the disease may present atypically) and a rapid rise in the world population of young adults, the group with the highest mortality from tuber-culosis. In the UK the incidence of tuberculosis is highest in Asian and West Indian immigrants, children of these immigrants, the homeless and those with HIV infection. Rates in the otherwise healthy indigenous white population have fallen to very low levels.

Pathology

The initial infection with M. tuberculosis is known as primary tuberculosis and usually occurs in the upper region of the lung producing a subpleural lesion called the Ghon focus (Fig. 11.7). The primary lesion may also occur in the gastrointestinal tract, particularly the ileocaecal region. The primary focus is characterized by exudation and infiltration with neutrophil granulo-cytes. These are replaced by macrophages which engulf the bacilli and result in the typical granulomatous lesions, which consist of Central areas of casea-tion surrounded by epithelioid cells and Langhans' giant cells (both derived from the macrophage). The primary focus is almost always accompanied by caseous lesions in the regional lymph nodes (mediastinal and cervical) -together these constitute the Ghon complex. In most people the primary infection and the lymph nodes heal completely and become calcified. However, they may harbour tubercle bacilli which may become reactivated if there is depression of the host defence system. Occasionally there is dis-semination of the primary infection, producing miliary tuberculosis.

Reactivation results in typical post-primary tuberculosis. Post-primary tuberculosis refers to all forms of tuberculosis that develop after the first few weeks of the primary infection when immunity to the mycobacteria has developed. Reinfection after successful treatment for TB is uncommon except in immunocompromised patients such as HIV-infected individuals.

Clinical features

Primary TB is usually symptomless; occasionally there may be erythema nodosum (p. 812), a small pleural effusion or pulmonary collapse caused by compression of a lobar bronchus by enlarged nodes (Fig. 11.7). Miliary TB is

Fig. 11.7 Manitestations of primary and post-primary tuberculosis.

the result of acute dissemination of tubercle bacilli via the bloodstream. Patients, especially the elderly, may present with non-specific ill-health, fever of unknown origin, weight loss and a few other localizing symptoms. Occa-sionally the disease presents as tuberculous meningitis, and in the later stages there may be enlargement of the liver and spleen. Choroidal tubercles (yellowy/white raised lesions about one-quarter the diameter of the optic disc) are occasionally seen in the eye. Most commonly clinical tuberculosis repre-sents delayed reactivation. Symptoms begin insidiously, with malaise, anorexia, weight loss, fever and cough. Sputum is mucoid purulent or blood-stained, but night sweats are uncommon. There are often no physical signs, although occasionally signs of a pneumonia or pleural effusion may be present.

Tuberculous disease (as above) must be differentiated from latent tuber-culous infection. Infection implies the presence of small numbers of tubercle bacilli in the body; the tuberculin test is positive (as with disease), but the chest X-ray is normal and the patient asymptomatic.

Investigations

In order to minimize the risk of transmission to other people, patients who are suspected of having pulmonary TB should be isolated in a ward side-room until sputum specimens are negative. This is to minimize the risk of transmis-sion to other patients in a confirmed case. Because of the rising incidence of drug-resistant TB, the diagnosis is confirmed bacteriologically whenever possible and to obtain drug sensitivities.

■ Chest X-ray typically shows patchy or nodular shadows in the upper zones, with loss of volume, and fibrosis with or without cavitation. With miliary tuberculosis the chest X-ray may be normal or show miliary shadows 1-2 mm in diameter throughout the lung.

■ Sputum is stained with an auramine-phenol fluorescent test or the less sensitive Ziehl-Neelsen (ZN) stain for acid- and alcohol-fast bacilli. Culture of sputum is more sensitive than microscopy and allows antibiotic sensitivity testing. Solid culture mediums (e.g. Lowenstein-Jensen) take 4-8 weeks for organism recovery and are gradually being replaced by liquid culture mediums (Bactec) which shorten the recovery time by 2-3 weeks. Sensitivity testing takes a further 3-4 weeks.

■ Bronchoscopy with washings of the affected lobes is useful if no sputum is available.

■ The diagnosis of extrapulmonary TB depends on a high index of clinical suspicion. Recovery of the organism from specimens is still necessary wherever possible. This may involve lymph node biopsy, bone biopsy, urine testing or aspiration of pericardial fluid.

■ Lumbar puncture and CSF examination for evidence of tuberculous infec-tion is indicated in all cases of miliary TB. This is due to the high rate of blood-borne spread to meninges, and positive CSF will alter the length of treatment.

■ Skin testing for TB (Mantoux test) is rarely of any value in the diagnosis or exclusion of active TB. It is neither sensitive nor specific.

■ Whole blood interferon-gamma assay detects interferon produced by T-cells after incubation with TB antigens in individuals who have been sensitized to TB.

■ HIV testing should be considered if risk assessment shows the patient to be from an area or background with increased risk of HIV co-infection. TB is an AIDS-defining illness.

Management

Tuberculosis should be treated by experienced physicians working closely with TB nurse specialists or TB health visitors. The latter are helpful in moni-toring patients' compliance with treatment and the accuracy and continuity of prescribing. It is a statutory requirement in the UK that all cases of TB must be notified to the local Public Health Authority so that contact tracing and screening can be arranged.

Patients who are ill, sputum-smear positive (patients with three negative smears are considered non-infectious), highly infectious patients (particularly multidrug-resistant TB), and those unlikely to be compliant with treatment should be initially treated in hospital.

A 6-month regimen comprising rifampicin, isoniazid, pyrazinamide and ethambutol for the initial 2 months followed by rifampicin and isoniazid for a further 4 months is standard treatment. Four drugs should be continued for longer than 2 months if susceptibility testing is still outstanding. Pyridoxine 10 mg daily is given to reduce the risk of isoniazid-induced peripheral neu-ropathy. Treatment time is extended in TB meningitis (to 12 months) and bone TB (to 9 months). Streptomycin is now rarely used in the UK, but it may be added if the organism is resistant to isoniazid. Significant side-effects are uncommon and are listed in Table 11.9. A transient asymptomatic rise in the serum aminotransferase level may occur with rifampicin, but treatment is only stopped if hepatitis develops. The major causes of treatment failure are incorrect prescribing by the doctor and inadequate compliance by the patient. Vagrants, alcoholics, homeless and the mentally ill are most likely to be non-compliant with therapy. In order to improve compliance special clinics are used to supervise treatment regimens where the ingestion of every drug dose is witnessed (directly observed therapy, DOTS). Incentives to attend include free meals and cash payments.

Multidrug-resistant (MDR, resistance to isoniazid and rifampicin) and extensively drug-resistant TB (EDR, resistance to first-line and some second-line treatment) is a world-wide major problem. It occurs mainly in HIV-infected patients who can then transmit the infection to healthcare workers and other patients. Treatment of MDR and EDR is difficult and uses

Table 11.9 Side-effects of the main antituberculous drugs

Rifampicin

Stains body secretions and urine pink

nduces liver enzymes - concomitant drug treatment may be less effective

Elevation of liver transferases and hepatitis

Thrombocytopenia (rarely)

Isoniazid

Polyneuropathy (rarely), prevented by co-administration of pyridoxine

Allergic reactions - skin rash and fever Hepatitis

Pyrazinamide

Hepatitis – rarely

Hyperuricaemia and gout

Rash and arthralgia

Ethambutol

Optic neuritis - testing of visual acuity (Snellen chart) and red-green colour perception performed before treatment. Patients asked to report visual changes (defects, colour blindness, acuity) during treatment

combination treatment (including capreomycin, clarithromycin, azithromycin and ciprofloxacin) to which the organism is sensitive for up to 2 years.

Prevention and chemoprophylaxis

Close contacts of a case are screened for evidence of disease with a chest X-ray and a Mantoux test (positive if area of induration > 10 mm 72 hours after intradermal injection of purified protein derivative of Mycobacterium TB) or whole blood interferon-gamma assay. Antituberculous treatment is given if the chest X-ray shows evidence of disease or if the Mantoux test is negative initially but becomes positive on repeat testing 6 weeks later. In adults, an initial positive tuberculin test with a normal chest X-ray is not usually taken as indication of disease.

Vaccination with BCG (Bacille Calmette-Guérin) reduces the risk of devel-oping tuberculosis. It is a bovine strain of M. tuberculosis which has lost its virulence after growth in the laboratory for many years. Immunization pro-duces cellular immunity and a positive Mantoux test. In the UK, BCG vaccina-tion is offered to infants living in areas with a high immigrant population, to previously unvaccinated new immigrants from high-prevalence countries for TB, to persons at occupational risk of TB (healthcare workers, veterinary staff, staff of prisons) and to contacts of known cases. BCG vaccination is given to all persons in developing countries where TB is more prevalent.

Targeted tuberculin testing for latent TB infection is an essential compo-nent of TB control and identifies people at high risk for developing clinical disease. High-risk groups for developing TB include recent immigrants from high-prevalence countries, injection drug users and HIV-positive patients. Patients with tuberculous infection identified by tuberculin testing are usually treated with one drug for 6 months (chemoprophylaxis) to prevent progres-sion to disease.

Patients with chest X-ray changes compatible with previous tuberculosis and who are about to undergo treatment with an immunosuppressive agent should also receive chemoprophylaxis with isoniazid.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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