Tuberculosis

Etiology

• Mycobacterium tuberculosis

• Aerobic• Slow-Growing(24-36 hr.

Doubling time)• Complex cell wall• Acid fast• Resistant to drying

EPIDEMIOLOGY

• Susceptibility to infection with M. tuberclosis disease depends on exposure and person's immune system

• Without treatment, tuberculosis disease develops in 5% to 10% of immunologically normal adults with tuberculosis infection at some time during their lives

• An estimated 8 million new cases of tuberculosis occur each year among adults, and 3 million deaths are attributedto the disease annually.

• In developing countries, 1.3 million new cases of the disease occur in children younger than 15 years of age, and 450,000 children die

each year of tuberculosis• Most children with tubercolusis infection and

disease acquire M. tuberculosis from an adult with tuberculosis.

• Transmission:person to person

• Children with primary pulmonary tuberculosis disease rarely, if ever, infect other children or adults.

• Most initially infectious patients become noninfectious within 2 weeks of starting effective treatment, and many become noninfectious within

several days.

CLINICAL MANIFESTATIONS

• Tuberculosis infection (latent tuberculosis)• Tuberculosis disease(tuberculosis)

Primary pulmonary tuberculosis• in older infants and children is usually an

asymptomatic infection• positive TST with minimal abnormalities on the

chest radiograph, such as an infiltrate with hilar lymphadenopathy or Ghon complex

• Malaise, low-grade fever, erythema nodosum,or symptoms resulting from lymph node enlargement

may occur after the development of delayed hypersensitivity,

Progressive primary disease• is characterized by a primary pneumonia that

develops shortly after initial infection• Progression of the primary complex to pulmonary disease or disseminated miliary disease or progression of CNS granulomas to meningitis

occurs most commonly in the first year of life

Tuberculous pleural effusion

• accompany primary infection, generally represents the immune response to the organisms

• Pleurocentesis reveals lymphocytes and an increased protein level

• pleural biopsy may be necessary

Reactivation pulmonary tuberculosis

• Common in adolescents and typical in adults with tuberculosis

• usually is confined to apical segments of upper lobes or superior segments of lower lobes.

• There is usually little lymphadenopathy and no extrathoracic infection as a result of established hypersensitivity

• This is a manifestation of a secondary expansion of infection at a site seeded years previously during primary infection

• Advanced disease is associated with cavitation and endobronchial spread of bacilli. • Symptoms include fever, night sweats, malaise, and

weight loss. • A productive cough and hemoptysis often herald

cavitation and bronchial erosion.

Lymphadenopathy

• is common in primary pulmonary disease• The most common extrathoracic sites of

lymphadenitis are the cervical, supraclavicular, and submandibular areas (scrofula)

• Enlargement may cause compression of adjacent structures.

Miliarytuberculosis

• widespread hematogenous dissemination with infection of multiple organs

• characterized by fever, general malaise,weight loss, lymphadenopathy, night sweats, and

hepatosplenomegaly• Diffuse bilateral pneumonitis is common, and

meningitis may be present• The chest radiograph reveals bilateral miliary

infiltrates, showing overwhelming infection

• The TST may be nonreactive as a result of anergy

• Liver or bone marrow biopsy is useful for the dagnosis.

Tuberculous meningitis

• most commonly occurs in children younger than 5 years old and often within 6 months of primary infection.

• Tubercle bacilli that seed the meninges during the primary infection replicate,triggering an inflammatory response.

• This condition may have an insidious onset, initially characterized by low-grade fever, headache, and subtle personality change.

• Progression of the infection results in basilar meningitis with impingement of the cranial nerves and is manifested by meningeal irritation and eventually increased intracranial pressure, deterioration of mental status, and coma.

• CT scans show hydrocephalus, edema, periventricular lucencies, and infarctions

• CSF analysis reveals increased cell number (50 to 500/mm3 leukocytes), which early in the course of disease may be either lymphocytes or polymorphonuclear leukocytes

• Glucose is low, and protein is significantly elevated• Acid-fast bacilli are not detected frequently in the

CSF by either routine or fluorescent staining procedures.

• Although culture is the gold standard for dagnosis, PCR for M. tuberculosis is useful to make this diagnosis.

• Treatment regimens for tuberculous meningitis generally include four antituberculous drugs and

corticosteroids.

Skeletal tuberculosis

• from either hematogenous seeding or direct extension from a caseous lymph node.

• Radiographs reveal cortical destruction; biopsy and culture are essential for proper diagnosis

• Tuberculosis of the spine, Pott disease, is the most common skeletal site, followed by the hip and the fingers and toes (dactylitis).

Other forms

• Abdominal tuberculosis• Tuberculous peritonitis• Urogenital tuberculosis• Tuberculous pericarditis

LABORATORY AND IMAGING STUDIES

• Tuberculin Skin Test• Only persons at high risk should be offered a Mantoux test• Culture

Induration ≤5 mm•Children in dose contact with known or suspectedcontagious cases of tuberculosis disease•Children suspected to have tuberculosis diseaseFindings on chest radiograph consistent with active or previously active tuberculosis Clinical evidence of tuberculosis disease*•Children receiving immunosuppressive therapy orimmunosuppressive conditions, including HIVinfection

•Induration ≤l O mm•Children at increased risk of disseminated disease Children <4 years old Children with other medical conditions, including Hodgkin disease, lymphoma, diabetes mellitus, ihronl renal failure, or malnutrition•Children with increased exposure to tuberculosis disease Children born, or whose parents were born, in high prevalence regions of the world Children frequently exposed to adults who are Hiv infected, homeless, users of illicit drugs, residents of nursing homes, incarcerated or institutionalized, or migrant farm workers• Children who travel to high-prevalence region of the world

Induration ≤ 15 mmChildren ≤ 4 years old without any risk factors

Diagnostic Imaging

• The initial parenchymal inflammation that follows deposition of infected droplet nuclei in the alveoli of the lung usually is not visible radiographically.

• A localized, nonspecific infiltrate with an overlying pleural reaction may be seen, however. This lesion usually resolves within 1 to 2 weeks.

• All lobar segments of the lung are at equal risk of being the focus of the initial infection.

• In 25% of cases, two or more lobes of the lungs are involved, although disease usually occurs at only one site.

• Spread of infection to regional lymph nodes occurs early.

• The hallmark of childhood pulmonary tuberculosis is the relatively large size and importance of the hilar lymphadenitis compared with the less significant size of the initial parenchymal focus, together historically referred to as the Ghon complex (with or without calcification of the lymph nodes).

Diagnostic Imaging

• Hilar lymphadenopathy • Partial bronchial obstruction(air trapping,

hyperinflation, and lobar emphysema)• lobar pneumonia without impressive hilar

lymphadenopathy.• thin-walled primary tuberculous cavity

tuberculous spine

• usually show collapse and destruction of the vertebral body with narrowing of the involved disc spaces.

• Radiographic findings in bone and joint tuberculosis range from mild joint effusions and small lytic lesions to massive destruction of the bone.

DIFFERENTIAL DIAGNOSIS

• in early disease the symptoms and signs may be nonspecific.

• In pulmonary disease, tuberculosis may appear similar to pneumonia, malignancy, and any systemic disease in which generalized lymphadenopathy occurs.

• The diagnosis of tuberculosis should be suspected if the TST is positive or if there is history of tuberculosis in a contact.

• The differential diagnosis of tuberculous lymphadenopathy includes infections caused by:

• atypical mycobacteria,• catscratch disease, • fungal infection, • viral or bacterial disease,• toxoplasmosis, • sarcoidosis, • drug reactions, • and malignancy.

TREATMENT

• For patients with large populations of bacilli, such as adults with cavities or extensive infiltrates, at least two antituberculous drugs must be given

• For patients with tuberculosis infection but no disease, the bacterial population is small, and a single drug, such as isoniazid, can be given

• Isoniazid and rifampin are bactericidal Along with pyrazinamide

• Ethambutol, ethionamide, streptomycin, and cycloserine are bacteriostatic• A 9-month regimen of isoniazid and refampin cures

more than 98% of cases of drug-susceptible pulmonary• The addition of pyrazinamide and another drug

(ethambutol or an aminoglycoside at the beginning of the regimen reduces the duration of necessary treatment to 6 months.

• Meningitis, bone/joint:2 mo of isoniazid, rifampin,pyrazinamide, and an aminoglycoside or ethionamide,once a day, followed by 7-10 mo of isoniazid and rifampin, once a day or twice a week (9-12 mo total)

• Pulmonary and extrapulmonary(except meningitis and bone joint) :2 mo of isoniazid, rifampin, and

pyrazinamide daily, followed by 4 mo of isoniazid and rifampin twice weekly under DOT

COMPLICATIONS

• Tuberculosis of the spine may result in angulation or gibbus formation that requires surgical correction after the infection is cured

• With extrapulmonary tuberculosis, the major problem is often delayed recognition of the cause of disease and delayed