Preface Why Tubeculosis is important ? new cases increased world wide during last decade of 20 th century due to AIDS, poverty, lack of medical resources. one third of the world's population—2 billion people—are infected with M. tuberculosis 95% of cases in developing countries. 8 million/year new cases 3 million/year die Children: Children: 1.3 million/year new cases 450,000 /year die 450,000 /year die

Risk Factors RISK FOR TUBERCULOSIS INFECTION exposure to high-risk adults. Poor and homeless persons. age less than 5 years severe malnutrition. HIV infection RISK FOR PROGRESSION TO TUBERCULOSIS DISEASE Infants and children <4 yr of age, especially those <2 yr of age Adolescents and young adults Persons with skin test conversion in the past 1–2 yr Persons who are immunocompromised Chronic malabsorption syndromes Persons co-infected with HIV

Transmission Transmission of M. tuberculosis is person to person but young children with tuberculosis rarely infect other children or adults. Tubercle bacilli are sparse in the endobronchial secretions. cough is often absent.

Pathogenesis The lung is the portal of entry in over 98% of cases >>primary complex >>blood born dissemination. Meningeal TB 2-6 mo Lymph node or endobronchial TB 3-9 mo Bones and joints TB several years Renal TB decades 25–35% of children develop extrapulmonary TB 10% of adults develop extrapulmonary TB PREGNANCY AND THE NEWBORN fetal growth retardation low birthweight and perinatal mortality Congenital tuberculosis is rare

Clinical Manifestations PRIMARY PULMONARY DISEASE: 50% of infants and children with radiographically moderate to severe pulmonary tuberculosis have no physical findings and are discovered only by contact tracing 70% of lung foci are subpleural 25% of cases have Two or more primary foci large size of the regional lymphadenitis which lead to tuberculous bronchial obstruction Children may have lobar pneumonia without impressive hilar lymphadenopathy. Arrow points to cavity in patient's right upper lobe.

PRIMARY PULMONARY DISEASE cont. Progressive primary pulmonary disease is rare but serious complication Reactivation is rare below 2 years of age but more after 7 years of age Tuberculous pleural effusion is infrequent in children <6 yr of age and rare in children <2 yr of age pericarditis is rare, occurring in 0.5–4%

Lymphohematogenous (disseminated) Disease Tubercle bacilli are disseminated to distant sites, including liver, spleen, skin, bone and lung apices. it is usually asymptomatic. Miliary Tuberculosis: is most common in infants and young children and malnourished. 50% develop generalized lymphadenopathy and hepatosplenomegaly, fever become higher. Within several weeks, the lungs may become filled with tubercles, dyspnea and cough occurs, as the disease progress pneumothorax, pneumomediastinum, meningitis or peritonitis may occure, Cutaneous lesions include papulonecrotic tuberculids, nodules, Choroid tubercles occur in 13–87% of patients and are highly specific for the diagnosis of miliary tuberculosis. Unfortunately, the tuberculin skin test is nonreactive in up to 40% of patients

tuberculous lesions in the choroidPapulonecrotic tuberculide

miliary tuberculosis

diagnosisSite Lymph node biopsy Chest Xray and lumbar puncture Chest Xray, pleural tap Lumbar puncture Abdominal ultrasound and ascitic tap Xray, joint tap or synovial biopsy Ultrasound and pericardial tap Peripheral lymph nodes Miliary TB Pleural effusion TB meningitis Abdominal TB Osteoarticular Pericardial TB Extrathoracic Tuberculosis in childhood

tuberculous lymphadenitis

TB of the nervous system. Young children, especially those under two years, are particularly at risk for meningitis

Extensive calification in abdominal nodes due to tuberculosis

any bone can be affected by TB

n This child has a 'gibbus' deformity due to TB of the thoracic spine.

erythema nodosum, a phenomenon of hypersensitivity

Lupus vulgaris

Diagnosis of TB in children Guidance for National Tuberculosis Program on the Management of Tuberculosis in Children by WHO. Key features suggestive of TB The presence of three or more of the following should strongly suggest a diagnosis of TB:   chronic symptoms suggestive of TB   physical signs highly suggestive of TB   a positive tuberculin skin test   chest Xray suggestive of TB

Pulmonary TB, sputum smear positive The criteria are:   two or more initial sputum smear examinations positive for acid fast bacilli; or   one sputum smear examination positive for acidfast plus CXR of active pulmonary TB, as determined by a clinician; or   one sputum smear examination positive for acidfast bacilli plus sputum culture positive for M. tuberculosis.

Pulmonary TB, sputum smear negative The criteria are:   at least three sputum specimens negative for acidfast bacilli; and   radiological abnormalities consistent with active pulmonary TB; and   no response to a course of broadspectrum antibiotics; and   decision by a clinician to treat with a full course of antiTB chemotherapy.

Administering the Tuberculin Skin Test Inject intradermally 0.1 ml of 5 TU PPD tuberculin Produce wheal 6 mm to 10 mm in diameter (do not place control) Do not recap, bend, or break needles, or remove needles from syringes Follow universal precautions for infection control

Reading the Tuberculin Skin Test Read reaction hours after injection Measure only induration Record reaction in millimeters

PPD Diameter of induration Ballpoint Pen Method

Classifying the Tuberculin Reaction  5 mm is classified as positive in Recent contacts of known or suspected TB case Persons clinical or radiographic findings consistent with active or previously active TB Immunosuppressed patients: HIV

Classifying the Tuberculin Reaction (cont.)  10 mm is classified as positive in Risk for disseminated disease Concomitant medical conditions: DM, malnutrition, CRF, lymphoma Those < 4 years old Risk for exposure to TB Born or travel to a country with high prevalence of TB Frequent exposure to cases with risk factors for TB HIV, homeless, illegal drug use, immigrants

Classifying the Tuberculin Reaction (cont.)  15 mm is classified as positive in Persons with no known risk factors for TB

PPD Cutoff value 5 mm immunocompromised host recent exposure to infectious case high probability of infection (abnormal CXR) 15 mm low risk of TB 10 mm others

Factors that May Affect the Skin Test Reaction Type of Reaction Possible Cause False-positive Nontuberculous mycobacteria BCG vaccination Anergy False-negative Recent TB infection Very young age (< 6 months old) Live-virus vaccination Overwhelming TB disease Sensitivity of PPD: 80-96%

AntiTB treatment in children Treatment recommended by the CDC and AAP, is a 6 mo regimen of INH and RIF supplemented in the first 2 mo of treatment by PZA. success rate approaching 100%. Most experts recommend that all drug administration be directly observed, intermittent (twice-weekly) administration of drugs after an initial period as short as 2 wk of daily therapy is effective in children. If INH resistance is greater than 5–10%, or when the adult source case has drug-resistant tuberculosis, fourth drug is added—usually STM, EMB, or ETH—to the initial regimen.

Most Commonly Used Antituberculosis Drugs