TB_Patterson - TUBERCULOSIS... TUBERCULOSIS... the disease...

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Unformatted text preview: TUBERCULOSIS... TUBERCULOSIS... the disease in children and implications for the care of today’s child... from a clinician’s view. H. S. Patterson, M. D. H. TB IN CHILDREN OBJECTIVES • Understand, in simple terms, the pathophysiology and clinical course of TB in children. • Understand the difference between TB infection and TB disease. disease • Understand how to make the diagnosis of TB in a child. TB IN CHILDREN TB OUTLINE • • • • • • historical and epidemiologic perspectives historical diagnostic considerations natural course natural mortality/complications why prophylaxis? look alike TUBERCULOSIS... TUBERCULOSIS... The greatest killer of all time... The captain of all these men of death... ...during this century and the last, one billion people have died from tuberculosis TUBERCULOSIS... TUBERCULOSIS... “The White Plague” Oliver Wendell Holmes Sr, 1861 WHO is this famous Georgian who died of TB and how old was he when he died? he Leading causes of death in U.S. 1900 1900 CAUSE CAUSE Flu & Pneumonia Tuberculosis Diarrhea/Enteritis DEATH RATE 202/100,000 194/100,000 140/100,000 TB epidemiology in perspective TB • approximately 1/3 of the world’s approximately population is infected with m. tuberculosis m. • there are approximately 8 million new cases there of (active)TB per year, world wide (active) • 2.9 million deaths occur annually from TB • 1987-1991, in US, number of cases of 1987-1991, active TB in children less than 5 years of age, increased 49% age, 2000 1500 1000 500 0 1985 1986 1987 1988 1989 1990 1991 Annual number of cases of tuberculosis in children Annual less than 15 years of age in the United States less 2000 1900 1800 1700 1600 1981 1983 1985 1987 1989 Tuberculosis deaths by year, United States, 1980­1989 (National Health Statistics) TB RISK FACTORS RISK • • • • • crowding decreased access to health care lower socio-economic status HIV ? race Historical TB Historical 1000 100 50 MORTALITY rate per 100,000 10 Tb evidenced in 4,000 BC Tb evidenced in 4,000 BC 5 1 0.5 1700 1750 1800 1850 1900 1950 YEAR Mortality from tuberculosis in developed countries 2000 1000 100 1804 Laennec associates lesions, 1804 Laennec associates lesions, ddescribes“phthsis” escribes phthsis” describes ““phthsis” describes “phthsis” 50 MORTALITY rate per 100,000 10 Tb evidenced in 4,000 BC 5 1 0.5 1700 1750 1800 1850 1900 1950 YEAR Mortality from tuberculosis in developed countries 2000 11839,Shoenlein recognized “tubercle” as 839, 1839, Shoenlein recognized “tubercle” as 1839, fundamental lesion, ergo “tuberculosis”. . tuberculosis” fundamental lesion, ergo““tuberculosis” “tuberculosis” 1000 100 1804 Laennec associates lesions, describes “phthsis” 50 MORTALITY rate per 100,000 10 Tb evidenced in 4,000 BC 5 1 0.5 1700 1750 1800 1850 1900 1950 YEAR Mortality from tuberculosis in developed countries 2000 1839, Shoenlein recognized “tubercle” as fundamental lesion, ergo “tuberculosis”. 1000 11882,Koch discovers 882, 1882, Koch discovers 1882, mycobacterium tuberculosis mycobacterium tuberculosis mycobacterium mycobacterium 100 1804 Laennec associates lesions, describes “phthsis” 50 MORTALITY rate per 100,000 10 Tb evidenced in 4,000 BC 5 1 0.5 1700 1750 1800 1850 1900 1950 YEAR Mortality from tuberculosis in developed countries 2000 1839, Shoenlein recognized “tubercle” as fundamental lesion, ergo “tuberculosis”. 1000 1882, Koch discovers mycobacterium tuberculosis 100 1917 Flu pandemic 1917 Flu pandemic 1804 Laennec associates lesions, describes “phthsis” 50 MORTALITY rate per 100,000 10 Tb evidenced in 4,000 BC 5 1 0.5 1700 1750 1800 1850 1900 1950 YEAR Mortality from tuberculosis in developed countries 2000 1839, Shoenlein recognized “tubercle” as fundamental lesion, ergo “tuberculosis”. “tuberculosis” 1000 1882, Koch discovers mycobacterium tuberculosis mycobacterium 100 1917 Flu pandemic 1804 Laennec associates lesions, describes “phthsis” “phthsis” 50 MORTALITY rate per 100,000 10 Tb evidenced in 4,000 BC 5 1946, Streptomycin used as antibiotic 1946, Streptomycin used as antibiotic 1 0.5 1700 1750 1800 1850 1900 1950 YEAR Mortality from tuberculosis in developed countries 2000 Upstate New York Upstate 30000 26000 REPORTED TB CASES US actual 22000 18000 expected 1981 1983 1985 YEAR 1987 30000 26000 REPORTED TB CASES US actual 22000 HIV related 18000 expected 1981 1983 1985 YEAR 1987 Natural history of tuberculosis in a newly newly infected (adult) contact (infection is not necessarily disease) (infection NO INFECTION CONTACT Defenses NO DISEASE (90%) INFECTION Cell-mediated Cell-mediated immunity immunity EARLY DISEASE (5%) DISEASE LATE DISEASE (5%) DIAGNOSIS: CMI CMI NO INFECTION CONTACT Defenses INFECTION INFECTION cell-mediated cell-mediated immunity immunity NO DISEASE (90%) EARLY DISEASE (5%) DISEASE LATE DISEASE (5%) DIAGNOSIS: CMI CMI NO INFECTION CONTACT Defenses INFECTION INFECTION cell-mediated cell-mediated immunity immunity NO DISEASE (90%) EARLY DISEASE (5%) DISEASE LATE DISEASE PPD positive (5%) The TB Skin Test: MATERIALS The • OLD TUBERCULIN – culture of TB bacillus in glycol peptone broth – TB “tine” test • PURIFIED PROTEIN DERIVATIVE (PPD) – TB bacillus grown in Long’s media, filtered after TB heating heating – adopted by WHO as standard in 1950 – PPD-S 1952 – dose = 5 IU The TB (Mantoux) Skin Test The • Intra-dermal Intra-dermal – quality control important – trained practioner necessary • Delayed hypersensitivity – cell mediated – 48-72 hours • False negative – immuno-compromized conditions – measles/measles immunizations • Nonspecific reactions – increase >10 IU – cross reactions, atypical MB Factors causing decreased ability to respond to tuberculin respond • Factors related to the person being tested – Infections • Viral (measles, mumps, chickenpox) • Bacterial (typhoid fever, brucelosis, typhus, pertussis, overwhelming TB, • Fungal (South American blastomycosis) – Live virus vaccinations (MMR) – Metabolic derangements (chronic renal failure) – Nutritional factors (severe protein depletion) – Diseases affecting lymphid organs (Hodgkin’s lymphoma, chronic lymphocytic leukemia, sarcoidosis) – Drugs (corticosteroids, other immunosuppressive agents) – Age (newborn, elderly) – Recent overwhelming infection with M. tuberculosis – Stress (surgery, burns, mental illness, graft versus host reactions) • • • Factors related to the tuberculin used Factors related to the method of administration Factors related to reading the test and recording results Indications for skin test screening • • • • • • Persons with signs and/or symptoms suggestive of tuberculosis disease Recent contacts of persons known or suspected to have tuberculosis Persons with undiagnosed upper lobe fibrotic lesions Persons infected with HIV Alcoholics and intravenous drug abusers Persons with medical conditions known to increase the risk of disesase if infection has occurred: – silicosis, gastrectomy, jejunoileal bypasss, significant weight loss below IBW, chronic renal failure, diabetes mellitus, high dose corticosteroid treatment or other immunosuppressive therapy, leukemia, lymphoma, malignancy • Groups at high risk of infection: – Latin America, Oceana, medically underserved populations, residents of long term care facilities • Groups that would pose a significant risk to others if diseased: employees of health care facilities, schools, child care facilities ATS/CDC TB PATHOPHYSIOLOGY PATHOPHYSIOLOGY • • • • • • systemic infection primary infection/disease progressive primary disease miliary disease meningitis chronic TB (re-activation) Inhalation of Infected Inhalation Droplet Nuclei non-specific bronchopneumonia 1) skin test sensitization 2) resistance to exogenous reinfection 3) lympho-hematogenous spread complete resolution (rare) (rare) progression massive necrosis (rare) (rare) healing with granuloma formation breakdown with development of breakdown (re-activation)TB DIS EAS E DIS stable TB: PRIMARY Infection PRIMARY • 95% of cases begin 95% with pulmonary focus with • usually a SINGLE usually focus focus • hypersensitivity hypersensitivity develops 2 to 6 weeks develops – until then, focus may until grow larger grow – hypersensitivity brings hypersensitivity caseation caseation Tissue Specimens Obtained at Autopsy from the Patient Jha, A. K. et al. N Engl J Med 2004;350:2399-2404 PRIMARY Infection: Lympho-hematogenous spread Lympho-hematogenous • 8-14 weeks after onset of TB • usually occult • Mantoux positive during this Mantoux phase phase • body wide seeding occurs body during this phase during – bone, kidney, meninges etc. – 3% of children with nl CXR’s 3% develop calcifications in lung apices (SIMON FOCI) apices Jha, A. K. et al. N Engl J Med 2004;350:2399-2404 PRIMARY TB: TB: endo-bronchial consequences • lymph nodes draining primary infection site lymph become involved become • lymph node capsule becomes adherent to lymph bronchial wall bronchial – infection can progress to ulceration into the infection bronchial wall bronchial – bronchial compression occurs with more than bronchial one node at same level one – with healing, bronchial constriction/stenosis with can occur can INFECTION TO ENDO-BRONCHIAL DISEASE INFECTION DISEASE TO STENOSIS STENOSIS HEALED PRIMARY INFECTION HEALED SIMON FOCI CALCIFIED nodes CALCIFIED nodes and peripheral lesion and peripheral lesion (Ghon complex) (Ghon complex) other VISCERAL sites USUAL PROGRESSION OF PRIMARY INFECTION PRIMARY infection lympho-hematogenous lympho-hematogenous spread spread healed PRIMARY healed PRIMARY infection infection PROGRESSIVE PRIMARY TB(DIS EAS E) TB • occasional (3.7%) local progression, despite occasional hypersensitivity (more common in younger pt) (more • can be cavitary • can have endo-bronchial spread • similar in appearance to adult type, “reactivation” similar “reactivation” disease disease • 2/3 of cases progress to death in the untreated 2/3 PROGRESSIVE PRIMARY DISEASE DISEASE lymph node involvement cavitation pleural effusion Progressive Primary Disease Progressive ENDOBRONCHIAL SPREAD ENDOBRONCHIAL WITH SUBSEQUENT WITH BRONCHOPNEUMONIA BRONCHOPNEUMONIA Disseminated TB pneumonia Disseminated MILIARY Disease MILIARY Disease Generalized Hematogenous Tuberculosis • generalized dissemination through generalized bloodstream bloodstream – caseous focus ruptures into blood vessel – growth of tubercle within the blood vessel – may be acute, occult or chronic • • • uniformly fatal if not treated rare usually occurs in the first 4 months after usually primary infection MILIARY Disease MILIARY Disease • millet seed appearance on millet X-ray X-ray • Mantoux positive? • Most children still have Most active primary complex when miliary disease strikes strikes • most develop meningitis Major sites of extra-pulmonary tuberculosis among children in the United States among SITES lymphatics meninges pleura miliary skeletal other % 67 13 6 5 4 5 Avg. Age 5y 3y 16y 1y 5y Clin Chest Med 1989, Am. Rev. Resp. Dis, 1990 TB MENINGITIS TB • • • • • primary seeding caseous lesion adjacent meninges growth/discharge usually insidious prophylaxis is preventive TB MENINGITIS TB • 40% of cases ocur within 3 months of 40% estimated onset of TB estimated – rarely < 1 month • 90% with TB menningitis PPD positive – 94% of these have positive CXR’s • average duration from meningitis diagnosis average to death (untreated) 19.5 days to CHRONIC PULMONARY TB TB (re-activation/adult type) • occurs only after primary infection – 0.5-10 % incidence (7% by Lincoln) – usually not less than 1 year of age – most cases occur when primary infection most aquired after 7 years of age aquired • • • minute areas of bronchopneumonia tissue hypersensitivity - cavity formation few symptoms early on in disease 12 Rate per 1000 10 8 6 4 2 0 0 2 4 6 8 10 12 14 16 18 20 Age in years Annual risk of developing chronic pulmonary tuberculosis among survivors of pulmonary primary tuberculosis among (Dis Chest 38:473, 1960) Major sites of extrapulmonary tuberculosis among children in the United States SITES lymphatics meninges pleura miliary skeletal other % 67 13 6 5 4 5 Avg. Age 5y 3y 16y 1y 5y Clin Chest Med 1989, Am. Rev. Resp. Dis, 1990 DEATHS from TB in children DEATHS (natural course of the disease) • higher incidence in younger children • 25% of children will die in the untreated 25% state state • 90% of the deaths will occur in the first 90% year year INH PROPHYLAXIS PROPHYLAXIS • the best prophylaxis is AVOIDING exposure the • for patients with quiescent, uncomplicated, for non-active disease non-active • reduces antigen load, thereby decreasing reduces risk of (re)activation risk PULMONARY TUBERCULOSIS LOOK ALIKE... LOOK TB like manifestations TB TB IN CHILDREN SUMMARY SUMMARY • There is no such thing as a positive PPD from just There “being exposed” to the disease “being • primary vs reactivation disease • children with primary TB are rarely children “communicable” “communicable” • untreated, there is high morbidity and mortality • children with quiescent disease deserve prophylaxis children • prophylaxis is “essentially” curative ...
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This note was uploaded on 12/24/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

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