Tuberculosis Richard Moriarty, MD UMass Medical School

“Yet the captain of all these men of death that came against him to take him away was consumption, for it was that that brought him down to the grave.” John Bunyan 1680

Tuberculosis 1/3 of world’s population is infected 2 nd most common ID cause of death 8 million new cases every year 2 million deaths annually Sub-Saharan Africa highest rate 290/100, Liberia incidence 310/100,000

Tuberculosis in Children 500,000 children die annually from TB Children more likely to develop TB once infected and are more vulnerable to disseminated TB Children get infected from adults Children with TB / latent TB infection (LTBI) indicate recent TB transmission Report 2 groups: 0-4 and 5-14

TB – The Bacterium Mycobacterium tuberculosis Aerobic, non-motile, non-spore forming Persists for long periods of time Waxy fatty capsule Slow-growing

TB Transmission Droplet nuclei 1-5 um Aerosolized by talking, singing, sighing, coughing, sneezing, yelling Inhaled into alveoli Only 1-5 bacilli needed to cause infection

TB – Primary Infection Multiply in macrophages Lyse macrophages and spread to surrounding cells and regional lymph nodes (Ghon complex) Initial CMI and DHS response prevents spread but takes 6 weeks to develop Residual bacilli persist 5-10% will develop disease later in life

TB - Symptoms Many children are asymptomatic Low grade fevers Weight loss or poor weight gain Primary focus usually in the lungs Chronic cough, wheezing 25-35% present with lymphadenitis 13% present with meningitis Miliary

TB Findings in Non-pulmonary foci gibbus, especially of recent onset non-painful enlarged cervical lymphadenopathy with with or without fistula formation; meningitis not responding to antibiotic treatment, with a subacute onset or raised intracranial pressure pleural effusion distended abdomen with ascites non-painful enlarged joint signs of tuberculin hypersensitivity (e.g. phlyctenular conjunctivitis, erythema nodosum)

TB SUSPICION INDICATOR TABLE Feature Score Cough > 4 weeks (not whooping cough) OR Pneumonia that does not improve after 3 weeks of treatment 1111 Fever lasting 2 weeks or more without explained cause1 Not recovering from measles after 2 months2 Child < 3 years old not gaining weight appropriately for 3 months OR Child > 3 years old with a regression of the general condition (not gaining weight appropriately or losing weight) 1212 No recovering from malnutrition on treatment OR No recovering from a severe malnutrition (hospitalised) 1212 Co-dweller with sputum (afb+) OR Mother (or caregiver) sputum (afb+) 2424 BCG done during the last 2 years If you get: 0-2 = TB less likely 3-4 = TB more likely 5 or more = TB likely

TB - Diagnosis Careful history Clinical examination with growth assessment Tuberculin skin testing Bacteriological confirmation whenever possible HIV testing (in high HIV prevalence areas)

Tuberculin Skin Test Mantoux test Intradermal Delayed hypersensitivity False negatives: time, malnutrition, measles, False positives

Bacteriologic confirmation whenever possible Sputum Gastric aspirate

Auramine O fluorescent stain for TB

HIV counselling and testing is indicated for all TB patients as part of their routine management.

TB – Goals of Treatment Kill actively growing and semi-dormant bacilli Eliminate residual bacilli Insure cure without relapse Prevent death Stop transmission Prevent emergence of drug resistance

TB – Treatment of Children Children tolerate meds well Directly observed therapy (DOT) is the gold standard Extended treatment necessary for slow- growing organism Irregular or incomplete treatment leads to multi-drug-resistant TB Contact tracing is key

TB - Treatment Isoniazid Rifampin Pyrazinamide Ethambutol

Advanced Search First-Line Treatment of Tuberculosis (TB) for Drug-sensitive TB

TB - Treatment DrugDaily dose mg/kg Max dose 3X weekly mg/kg Max dose Isoniazid 5 (4-6)30010 rifampin 10 (8-12)60010 (8-12)600 pyrazinamid e 25 (20-30)35 (30-40) ethambutol 20 (15-25)30 (25-35)

TB – Duration of Therapy Type of infection Intensive phase Continuation phase New – smear negative 2 HRZ4 HR or 4 HE New – smear positive 2 HRZE4 HR or 6 HE TB meningitis2 HRZS4 HR Relapse or rx after interruption 2 HRZES / 1 HRZE 5 HRE

BCG Vaccine M. bovis – 13 years of serial passage Different strains around the globe 50% efficacy; better against miliary and meningeal TB No protective effect after 10 years Complications: adenitis, drainage, disseminated disease No additional protection from revaccination May cause positive skin test

TB-HIV Coinfection PPD skin test may be negative Be sure of diagnosis – rule out other causes of pneumonia: bacterial, viral, PCP, LIP Begin TB treatment first Start ART therapy 2-8 weeks after TB rx INH preventive therapy if exposed to TB

References WHO 2006 Guidance for national tuberculosis programmes on the management of tuberculosis in children