De Vera, Dela Cruz, Dela Cruz, Dela Cruz, Dela Rosa, Dimalala Case Conference De Vera, Dela Cruz, Dela Cruz, Dela Cruz, Dela Rosa, Dimalala

General Data J.T. 6 years and 2 months old, Female 416 Hernandez 2nd St. Sampaloc Manila Roman Catholic Filipino Informant: Mother Reliability: Good

Right lateral cervical mass CHIEF COMPLAINT: Right lateral cervical mass

History of Present Illness 9 days PTC: patient had productive cough with whitish phlegm, no fever, no colds -no medications and consultations done -resolved after 2 days 7 days PTC: appearance of mass on the left lateral part of the neck. -progressed in size and became tender -sought consult = MUMPS no medications given -progression in size

REVIEW OF SYSTEMS No weight loss, no weight gain No rashes, no jaundice, no pruritus, alopecia No dizziness, no lacrimation, no hearing difficulties, no aural discharge, no toothache, no sore throat No chest pain, no difficulty of breathing No cyanosis, no easy fatigability No abdominal pain, change in bowel movements, melena, hematochezia No hematuria, no frequency, no discharge, no edema, anuria, oliguria, dysuria No tremors, no convulsions, no behavioral changes No polyuria, polydipsia, polyphagia, no heat/cold intolerance No weakness, no joint swellings, no limitation of motion No pallor, no bleeding, no easy bruisability

Family History (+) Hypertension – maternal and paternal grandparents (+) Diabetes – maternal aunt (+) Bronchial asthma – cousins (+) allergy – mother (fish) (-) tuberculosis, cancer, seizure, blood dyscrasia, renal, congenital anomalies

Past Medical History 2 years old: German measles No previous hospitalizations and operations

Family members Age Occupation Condition Father 30 years old Employee Healthy Mother 29 years old Housewife Sibling (Justine Richie) 7 years old Grade 1 Sibling (Jama Lian) 3 years old Sibling (Jermaine) 2 years old

Environmental History The patient lives with both parents and siblings in a concrete house, well-lit, and well ventilated. No factories are nearby. Pets: none Garbage is collected everyday by a garbage truck, not properly segregated

Physical Examination Conscious, coherent, alert, ambulatory, well looking, well hydrated, not in cardio-respiratory distress BP: 90/60 CR: 96, regular RR: 18, regular Temp: 36.5 C Ht: 115cm z = 0 Wt: 21.2 kg z = 0 BMI: 16.03 z = 0

Physical Examination Skin: warm, moist skin, no lesions Head: normocephalic, thick shinny hair, no hair nits, no hair lice, no tenderness, no palpable masses Eyes: no swelling, lids not matted, pink palpebral conjunctiva, anicteric sclera, pupils 2-3 mm ERTL Ears: no swelling, no tragal tenderness, nonhyperemic EAC, impacted cerumen AU Nose: no discharge, turbinates not congested, midline septum Mouth/ Throat: moist buccal mucosa, nonhyperemic posterior pharyngeal wall, tonsils not enlarged, no dental caries, no oral ulcers

Neck: supple neck, (+) 5cm x 3cm non movable, tender mass on the left retroauricular extending up to the angle of the mandible Lung/ Chest: no intercostal and supraclavicular retractions, symmetrical chest expansion, clear breath sounds, equal vocal fremiti Heart: adynamic precordium, apex beat at 4th Left ICS MCL, S1>S2 apex, S2>S1 base, no heaves, thrills, murmurs

Abdomen: flat abdomen, normoactive bowel sounds, soft, nontender, no palpable masses Extremities/ Pulses: pulses full and equal, no deformities, no cyanosis, no edema Neurologic examination: unremarkable

Salient Features: 6 years old Filipino Sampaloc, Manila (+) non productive cough (+) 5cm x 3cm non movable, tender mass on the left retroauricular extending up to the angle of the mandible (-) TB exposure

Not patient’s plate

RIGHT LATERAL Cervical Mass Presenting Manifestation RIGHT LATERAL Cervical Mass

Cervical Lymphadenopathy in children Infectious Non-infectious Bacterial Viral Connective tissue disorders Leukemia Lymphoma Kawasaki disease Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) Medications

Approach to Diagnosis History Duration and laterality of adenopathy and change in size over time Associated symptoms Ill contacts Ingestion of unpasteurized animal milk or undercooked meats Dental problems or mouth sores Skin lesions or trauma Animal exposures Immunization status Medications Geographic location and travel History Duration and laterality of adenopathy and change in size over time Associated symptoms (weight loss, fever, arthralgias, sore throat) Ill contacts (viral respiratory infections, cytomegalovirus [CMV], Epstein-Barr virus [EBV], Streptococcus pyogenes [group A streptococcus, GAS], tuberculosis [TB]) Ingestion of unpasteurized animal milk (brucellosis, Mycobacterium bovis) or undercooked meats (toxoplasmosis) Dental problems or mouth sores (anaerobes, actinomycosis, enteroviral herpangina, herpes simplex gingivostomatitis) Skin lesions or trauma (Staphylococcus aureus, GAS, herpes simplex virus [HSV], cat scratch disease, tularemia, plague) Animal exposures (cat scratch disease, toxoplasmosis [cats], brucellosis [especially goats], tularemia [especially rabbits], bubonic plague [especially prairie dogs]) Flea or tick bites (bubonic plague, tularemia) I mmunization status (diphtheria, measles) Medications (eg, phenytoin, carbamazepine) Geographic location and travel (tularemia, bubonic plague, TB

Approach to Diagnosis Physical examination Examination of the lymphatic system, including assessment of the liver, spleen, cervical lymph nodes, and noncervical lymph nodes should be performed. Hepatosplenomegaly with generalized adenitis indicates a possible infection with EBV, CMV, HIV, histoplasmosis, TB, or syphilis. These findings also may be signs of neoplastic disease, collagen vascular disease, or other noninfectious etiology Physical examination  Examination of the lymphatic system, including assessment of the liver, spleen, cervical lymph nodes, and noncervical lymph nodes should be performed. Hepatosplenomegaly with generalized adenitis indicates a possible infection with EBV, CMV, HIV, histoplasmosis, TB, or syphilis. These findings also may be signs of neoplastic disease, collagen vascular disease, or other noninfectious etiology The lymph node number, location, size, shape, consistency, tenderness, mobility, and color should be recorded.   "Reactive" lymph nodes are usually discrete, mobile, feel rubbery, and are minimally tender. Infected lymph nodes are usually isolated, asymmetric, tender, warm, and erythematous; they may be fluctuant; they are less mobile and discrete than reactive lymph nodes. Malignant lymph nodes often are hard, fixed or matted to the underlying structures; they are usually nontender. Oral cavity — The oral cavity should be examined for evidence of periodontal disease, herpangina, HSV gingivostomatitis, or pharyngitis. Eyes — Conjunctival injection may indicate Parinaud oculoglandular syndrome (associated with cat scratch disease) or Kawasaki disease (show picture 1). (See "Microbiology; epidemiology; clinical manifestations; and diagnosis of cat scratch disease" and see "Clinical manifestations and diagnosis of Kawasaki disease"). Skin — A generalized rash may suggest a viral illness, whereas a localized skin lesion may indicate a more specific etiology (eg, cat scratch disease (show picture 2A-2B), tularemia (show picture 3), S. aureus or GAS, HSV, etc). Less common infections in which a papular or pustular lesion is suggestive of an inoculation site include [1] :       

Approach to Diagnosis Physical examination The lymph node number, location, size, shape, consistency, tenderness, mobility, and color should be recorded.   "Reactive" lymph nodes are usually discrete, mobile, feel rubbery, and are minimally tender. Infected lymph nodes are usually isolated, asymmetric, tender, warm, and erythematous; they may be fluctuant; they are less mobile and discrete than reactive lymph nodes. Malignant lymph nodes often are hard, fixed or matted to the underlying structures; they are usually nontender. Oral cavity —periodontal disease, herpangina, gingivostomatitis, or pharyngitis Eyes — Conjunctival injection Skin — generalized rash, pustular or papular lesions Physical examination The lymph node number, location, size, shape, consistency, tenderness, mobility, and color should be recorded.   "Reactive" lymph nodes are usually discrete, mobile, feel rubbery, and are minimally tender. Infected lymph nodes are usually isolated, asymmetric, tender, warm, and erythematous; they may be fluctuant; they are less mobile and discrete than reactive lymph nodes. Malignant lymph nodes often are hard, fixed or matted to the underlying structures; they are usually nontender. Oral cavity —periodontal disease, herpangina, HSV gingivostomatitis, or pharyngitis Eyes — Conjunctival injection may indicate Parinaud oculoglandular syndrome (associated with cat scratch disease) or Kawasaki disease Skin — A generalized rash may suggest a viral illness, whereas a localized skin lesion may indicate a more specific etiology (eg, cat scratch disease (show picture 2A-2B), tularemia (show picture 3), S. aureus or GAS, HSV, etc). Less common infections in which a papular or pustular lesion is suggestive of an inoculation site include [1] :

Differentials Non-Infectious Causes Patient: 6y.o./ Female Collagen vascular diseases Malignancy (+) 5x3cm, unilateral, semi-solid, tender, cervical mass on the left retroauricular area, extending to the angle of the mandible 1 week duration nontender, firm, rubbery, and matted. Persistent or progressive lymphadenopathy that does not respond to antibiotic therapy suggests the need for more extensive evaluation Weeks to months (+) cough for 2 days (-) colds (-) fever (-) weight loss (-) failure of weight gain Prolonged fever, rash, and arthralgias Fever, weight loss, Musculoskeletal pain, headache, mediastinal mass, testicular enlargement, peripheral blood abnormalities We can remove this na

Differentials Infectious Causes Patient: 6y.o./ Female Bacterial Infection Viral Infection TB Infection (+) 5x3cm – progressive in size, unilateral, semi-solid, tender (initially non-tender), fixed, mass on the left retroauricular area, extending to the angle of the mandible 1 week duration Most often unilateral; but can be bilateral; usually is 3 to 6 cm in diameter, tender, warm, erythematous, nondiscrete, and poorly mobile variable most often bilateral some can be generalized; small, rubbery, mobile, discrete, minimally tender, and without erythema or warmth unilateral nontender firm discrete mass or matted nodes, fixed sometimes accompanied by overlying skin induration; submandibular and supraclavicular lymph node involvement also occurs Weeks to months

Differentials Infectious Causes Patient: 6y.o./ Female Bacterial Infection Viral Infection TB Infection (+) cough for 2 days (-) colds (-) fever (-) weight loss (-) failure to gain weight history of a recent URI or impetigo; fever, tachycardia, and malaise may be present, the patient usually does not appear toxic history of an ill contact and current or recent symptoms that may include sore throat, rhinorrhea, nasal congestion, and/or cough Cough/ wheezing of 2 or more weeks Unexplained fever of 2 or more weeks; loss of appetite, loss of weight, failure to gain weight; failure to regain previous state of health after infection; fatigue, reduced playfulness or activity

t/c Primary Tuberculosis Clinical Impression How can we rule out yung URTI? t/c Primary Tuberculosis

(+) signs/ symptoms of TB Close contact of a source case Approach to Diagnosing a TB symptomatic child who has no/unknown exposure (+) signs/ symptoms of TB TB Close contact of a source case No/Unknown 0-4 years old 5-9 years old Yes … Tuberculosis in Infency and Childhood 3rd ed. 2010 PPS, Inc. p.123

Evaluate further and refer 5-9 years old Can produce sputum? NO TST Negative Evaluate further and refer Positive TB Disease DSSM Tuberculosis in Infency and Childhood 3rd ed. 2010 PPS, Inc. p.123

WORK UPS AND MANAGEMENT

Traditional and New Diagnostic Approaches DIAGNOSTICS APPLICATIONS Traditional approaches - Symptom-based -TST TB Culture - AFB smear - Chest radiograph Probable active TB Evidence of MTB Infection Bacteriologic Confirmation of active TB Probable Active TB New Diagnostic Approaches ORGANISM BASED Colorimetric cultures systems - phage based test - Microscopic- based observation drug susceptibility (MODs) assay Bacteriological confirmation of active TB Probable active Tb and detection of rifampin resistance Probable active TB and detection of resistance

Traditional and New Diagnostic Approaches DIAGNOSTICS APPLICATIONS New Diagnostic Approaches ANTIGEN BASED ASSAYS LAM detection assay IMMUNE BASED ASSAY Antibody based assay -MPB-64 skin test - T- Cell assays SYMPTON BASED Symptom based screening Refined symptom based Diagnosis Probable active TB Diagnosis of Latent TB infection Screening child contacts of adult TB cases Probable Active TB Of the all the diagnostic approach , the traditional approaches as well as tyhe symptom based screening of child contcats have been the basis for arriving at apresumptive diagnosis of TB as agreed upon in the PPS national consensus on TB

Diagnosis of TB A positive culture with or without a positive smear for M. Tuberculosis is the gold standard for the diagnosis of TB In the absence of bacteriologic evidence , a child is presumed to have active TB if > 3 crteria are present: Exposure to an adult/Adolescence with active TB (EPIDEMIOLOGIC) Signs and symptoms suggestive of TB (CLINICAL) Positive tuberculin test (IMMUNOLOGIC) Abnormal chest radiograph suggestive of TB (RADIOLOGIC) Other lab findings suggestive of TB (LABORATORY)

OUR PATIENT TST – 12 mm induration Chest X –ray showed evidence of primary infection Signs and symptoms of TB

Chest X- ray of the patient 11/24/10 The heart is not enlarged. There is slight haziness over the right lung base and the retrocardiac region, with nodular densities over the retrocardiac region, which may be due to lymph nodes. This may represent primary infection. Both hemidiaphragm and sinuses are normal. The visualized osseous structures are unremarkable. 11/24/2010

Management of Tuberculosis

Objectives of Drug Therapy in TB: Cure the patient of TB Prevent death from active TB Prevent relapse of TB Prevent the development of drug resistance Decrease transmission By rapidly eliminating most of the bacilli Or its late effects By eliminating the dormant bacilli By using a combination of drugs to achieve these goals, is is necessary to have athorough understanding of the pathopysiology of the disease. The need for multiple drugs and prolonged duration of therapy can be explained by the fact that naturally occurring drug resistant mutants are present within large bacterial populations even before chemotherapy is started. iN addition mycobacteria replicate slowly , can remain dormant for long periods , and can be eradicated only during replication. Finally bacilli live in several sites within the host and each site contains organism with a different populationsize metabolic activity and replication rate.

Phases of Treatment Intensive Phase - efficient killing of actively dividing organisms - relief of symptoms - terminates transmision - prevents emergence of drug resistance Continuation Phase - kills irregularly dividing bacilli - sterilizes lesions and prevent relapse

Drug Administartion The optimal dosing frequency for new patients with pulmonary TB is daily throughout the course of therapy. Alternative Regimens: A daily intensive phase followed by tree times weekly continuation phase [2HRZE/4H3R3] , provided that each dose is directly observed Three times weekly dosing throughout the therapy [2H3R3Z3E3/4H3R3] , provided that every dose is directly observed. Sytematic reviews have not found much difference in failure or relapse rates for daily versus three times weekly regimens. However , rates of acquired drug resistance were highrer among patients receiving intermittent dosing throughout. Therapy. Patients on intermittent therapy should adhere strictly to the prescribed regimen , since any missed doses leads to a significant reduction of the total quantity of the drugs received by the patient thus can lead to treatment failure.

Essential Anti-Tuberculosis Drugs MOA DOSE RANGE Single daily dose mkd 3X weekly mkd INH Bactericidal agent -Acts on extracellular and intracellular bacillary populations - presumed to inhibit biosynthesis of mycolic acid (cell wall component ) and effects glycolysis , nucleic acid synthesis 10 -15 Max 300 mg 20-30 Max 900 mg Rifampicin - inhibits nucleic acid synthesis 10-20 Max 600 mg

Essential Anti-Tuberculosis Drugs MOA DOSE RANGE Single daily dose mkd 3X weekly mkd Pyrazinamide - weak bactericidal but with potent sterilizing activity within macrophages, areas of acute inflammation 20-40 Max 2 g 50 mg Streptomycin - Bactericidal max 1 g Ethambutol Bacteriostatic, but with some bactericidal action at higher doses - acts on intra and extracellular bacillary populations - presumed to inhibit synthesis of mycolic acid (cell wall component) 15- 25 Max 1.2 g 30-50 Max 2.5 g

Essential Anti-Tuberculosis Drugs ADVERSE REACTIONS INH - peripheral neuropathy Other neurological disturbance, optic neuritis, toxic psychosis, generalized convulsions - systematic or cutaneous hypersensitivity reactions during the first week of treatment - hepatotoxicity Rifampicin Gastrointestinal intolerance - if intermittent adminidtration: rash , fever, thrombocytopenia, flu like symptoms - increases risk of hepatotoxicity if used with INH Pyrazinamide - hypersensitivity reactions -moderate rise in trasaminase levels - Hyperuricemia - arthralgia, particularly of shoulders Hepatotoxicity – may need to discontinue INH if with symptoms of hepatitis or trans aminase levels increase greater than 3.5 X from upper limits of normal

Essential Anti-Tuberculosis Drugs ADVERSE REACTIONS Streptomycin - sterile abscess - vestibular, auditory function impairment - hemolytic anemia Ethambutol - retrobulbar neuritis ( reduced visual acuity, contraction of visual fields, green red color blindness) Hepatotoxicity – may need to discontinue INH if with symptoms of hepatitis or trans aminase levels increase greater than 3.5 X from upper limits of normal

TREATMENT 21 kg Isoniazid 200 mg/5mL (10 mkd) Give 5.5 mL once daily 30 minutes before breakfast Rifampicin 200mg/5mL (10 mkd)- Give 5.5 mL once daily, 30 minutes before breakfast Pyrazinamide 500 mg/5mL (20 mkd) Give 4.5 mL once daily, 30 minutes before breakfast Ethambutol 400 mg/tab (20 mkd) - 1 tab Give 1 tab once daily, 30 minutes before breakfast

Supportive Management Multivitamins 5 mL once a day Anticipatory Guidance

Tuberculosis

Tuberculosis A Global Emergency One third of the world’s population is infected TB kills 5,000 people a day – 2-3 million each year HIV and TB co-infection is producing explosive epidemics Hundreds of thousands of children will become TB orphans this year MDR threatens global TB control It is estimated that one-third of the world’s population is infected with Mycobacterium tuberculosis, and that TB kills 5000 people a day or between 2 and 3 million people each year. The combination of HIV and TB coinfection is producing explosive epidemics. Hundreds of thousands of children will be orphaned this year when their parents and caretakers die from TB. Finally, multi-drug resistant TB, or MDR, is threatening global TB control.

Background Tuberculosis (TB) is increasing among adults in many areas TB is major cause of childhood morbidity and mortality worldwide Limited information on epidemiology of TB in children There is ample evidence that TB among adults is increasing in many areas of the world. TB is an important cause of childhood morbidity and mortality worldwide, although it has been a lower public health priority in recent years. There is limited information on many aspects of TB in children, including the epidemiology of TB.

Childhood TB Why neglected? Why is it important? Not considered important in global program or contributing to immediate transmission Not regarded as public health risk Difficult to diagnose Why is it important? Health problem in children May later contribute to epidemic

Leading Infectious Disease Causes of Death, 1998 3.5 2.3 2.2 1.5 1.1 0.9 TB is among the leading causes of death for all ages worldwide. While infections with and deaths due to HIV/AIDS are on the rise in many countries, many of these individuals are coinfected with TB, and in fact also frequently die from TB. WHO Report 2000

TB in Children WHO estimate of TB in children 1.3 million annual cases 450,000 deaths 15% of TB in low-income countries children vs. 6% in United States In 1989, the World Health Organization, or WHO, estimated that there were 1.3 million annual cases, and 450,000 deaths due to tuberculosis among children less than 15 years of age. Unfortunately, these estimates have not been revised more recently. It is estimated that 15% of all TB in low-income countries occurs among children less that 15 years of age compared with only 6% in the United States, and even lower percentages in some European countries.

Childhood TB as Sentinel Event Indicates recent transmission in a community Rapid progression from infection to disease “A deterioration in the control of TB thus immediately hurts the youngest generation” (Rieder, 1997) Children are future reservoir of disease Despite the relative neglect of the subject, a case of childhood TB has been described as a sentinel event, because it indicates recent transmission of M. tuberculosis in a community. Because there can be rapid progression from infection to disease in young children, it has been said that “A deterioration in the control of TB thus immediately hurts the youngest generation.” Further, children represent the future reservoir of disease. Thus, any effort to control the burden of TB over the long term needs to consider the role of infection and disease in children. Rieder H. Anales Nestle, 1997

Childhood TB diagnosed by: Combination of : Contact with infectious adult case Symptoms and signs Positive tuberculin skin test Suspicious CXR Bacteriological confirmation Serology

Risk factors : infection to disease HIV Malnutrition Recent exposure Young age Short incubation period More severe Highest risk More difficult to diagnose Host factors Effect of HIV?

Grzybowski S, et al. Bull Int Union Tuberc 1975;50:90-106 Tuberculous Infection Among Children by Type of Contact and Bacteriologic Status of Index Case, British Columbia and Saskatchewan, 1966-1971 Close Percent infected Close Casual Casual Grzybowski S, et al. Bull Int Union Tuberc 1975;50:90-106

Challenges for Surveillance Difficult diagnosis of childhood TB Lack of standard case definition Increased extrapulmonary disease Low public health priority of childhood TB There are many challenges to the surveillance of childhood TB. They include the difficult diagnosis of TB in children which often relies on clinical algorithms or checklists instead of bacteriologic confirmation. In published studies and surveillance systems, there is not a standard case definition of childhood TB. Children, particularly young children, are more likely to have extrapulmonary disease which can also be more difficult to confirm bacteriologically. Finally, because many children are not smear-positive, and therefore not as infectious, childhood TB has been given a low public health priority in comparison with other aspects of TB control.

WHO Estimated Total Cases by Age, 2000 Country Total Cases Cases <15 yrs % in Children India 1,815,740 185,233 10.2 China 1,645,703 86,978 5.3 Indonesia 581,918 15,691 2.7 Bangladesh 325,110 33,166 Nigeria 261,404 32,310 12.4 Pakistan 244,736 61,905 25.3 Philippines 230,217 12,167 South Africa 220,486 35,449 16.1 Russian Fed. 183,373 7,778 4.2 Ethiopia 178,349 28,675 Dem. Rep. Congo 148,598 24,052 I have abstracted these estimates for the 22 high burden countries and calculated the percent of disease which occurs in children for each country. The results of these estimates are shown on this slide and the next one. I have listed the 22 high burden countries in order of descending total of TB burden. Estimates of cases less than 15 years of age vary from a low of 2,317 cases in Thailand to a high of more than 185,000 cases in India. TB in children accounts for a highly variable percentage of all TB in a given country ranging from a low of 2.7% in Indonesia and Thailand to more than 20% in Afghanistan, Brazil, and Pakistan. In most Sub-Saharan countries, TB in children represented more than 15% of all TB cases. Had approximately 16% of all TB in children.

WHO Estimated Total Cases by Age, 2000 Country Total Cases Cases < 15 yrs % in Children Viet Nam 143,023 7,559 5.3 Kenya 137,603 22,124 16.1 Tanzania 117,489 18,890 Brazil 113,528 23,520 20.7 Thailand 85,928 2,317 2.7 Myanmar 78,489 8,007 10.2 Zimbabwe 76,296 12,267 Uganda 75,250 12,099 Cambodia 75,045 3,966 Afghanistan 69,342 17,540 25.3 Mozambique 47,909 7,703 TOTAL 6,856,537 659,397 9.6 Using this method, there were nearly 7 million total TB cases worldwide in 2000 in the 22 high burden countries, of which nearly 660,000 or 9.6% occurred in children. Using total WHO estimates, there were a total of 884,011 cases in children. The 22 high burden countries accounted for 75% of all TB in children in 2000. While these estimates provide a bench mark, the large variability in the percent of childhod cases by country is surprising, and suggests some countries may significantly underreport childhood cases. These estimates are dependent on the number of smear-positive cases reported to WHO as well as a number of other assumptions which have not been tested.

Extrapulmonary TB in Children Proportion in a given country could be used as measure of case detection 25-44% of all childhood TB in Ugandan study 43% of children in Ethiopian study 21.3% of childhood TB using US surveillance data Several researchers have suggested that the proportion of extrapulmonary TB in children could be used as a measure of case detection. Thus, countries reporting a high proportion of extrapulmonary TB may in fact be underdiagnosing cases of childhood pulmonary TB. A study of TB among hospitalized children in Uganda found that extrapulmonary TB accounted for from 25 to 44% of all TB in children from 1985 to 1989. In a study of 412 cases of both inpatient and outpatient childhood TB in Ethiopia over two years, 43% of all cases were extrapulmonary. By way of comparison, extrapulmonary TB accounted for only 21.3% of all childhood TB in the United States from 1990 to 2000. This proportion has remained stable over time in the US.

TB and BCG Vaccination Efficacy for adult pulmonary TB 0-80% in randomized clinical trials Best efficacy against serious childhood disease 64% protection against TB meningitis 78% protection effect against disseminated TB BCG important for young children, inadequate as single strategy Finally, in the next section, I would like to briefly mention a few topics of importance in understanding the epidemiology of childhood TB: BCG vaccination, TB/HIV coinfection, and drug resistance. BCG has an important, but limited role in the control of TB, particularly childhood TB. While the efficacy of BCG in preventing adult pulmonary TB has varied from 0 to 80% in randomized clinical trials, it has shown the best efficacy against serious forms of childhood disease. In a published meta-analysis of BCG efficacy, it had a 64% protective effect in preventing TB meningitis in children and a 78% protective effect in preventing disseminated TB among children. Clearly, BCG has an important role in preventing serious disease in young children. However, BCG alone is insufficient to prevent children from TB. Colditz GA et al. JAMA 1994; 271: 698-702.

Estimated TB incidence HIV prevalence adults 15- 49 years Relationship between TB and HIV What about children? 800 800 600 600 Estimated TB incidence (per 100 000 population) 400 400 200 200 0.1 0.1 0.2 0.2 0.3 0.3 0.4 0.4 HIV prevalence adults 15- 49 years

History of M. tuberculosis Phthisis (Greek) known since ancient times Often thought of as a hereditary condition 1854 first sanatorium 1882 Koch demonstrated relationship between germ and disease 1895 Roentgen discovery of diagnostic x-ray 1940’s-1950’s chemotherapy

Around the World An estimated 1.58 million deaths occurred in 2005 from TB disease 8.8 million new TB cases estimated for 2005 1/3 of world population has TB infection

High Burden Countries (WHO) Afghanistan Myanmar Bangladesh Nigeria Brazil Pakistan Cambodia Philippines China Russian Federation Democratic Republic South Africa of the Congo Thailand Ethiopia Uganda India United Republic of Tanzania Indonesia Viet Nam Kenya Zimbabwe Mozambique

Transmission and Pathogenesis

Pathogenesis Inhale droplet nuclei Bacteria multiplies Macrophages consume bacteria, then die Travel through the bloodstream, lymph system Containment-infection Multiplication-disease

Generation of TB Droplet Nuclei One cough produces 500 droplets The average TB patient generates 75,000 droplets per day before therapy This drops to 25 infectious droplets per day within 2 weeks of effective therapy

Factors Affecting TB transmission Characteristics of source case Environment Factors increasing risk for contacts

Classification System for TB

Risk Factors for the Development of TB Disease

Signs/Symptoms Productive cough 3 weeks or longer Shortness of breath Chest pain Hemoptysis Night sweats/fever/chills Unexplained weight loss Fatigue

Suspect TB: Chest x-ray Location of the infiltrate Presence of a cavity Hollow areas, dense areas, fluid on the lung or at margins Normal x-ray = usually no infectious TB disease

Chest Radiograph Abnormalities often seen in apical or posterior segments of upper lobe or superior segments of lower obe May have unusual appearnce in HIV+ patients

Sputum Collection Sputum specimens are essential to confirm TB Sputum: mucus from within the lung, not Saliva 3 specimens on 3 different days Spontaneous morning sputum more desirable than induced specimens

Sputum AFB Smear

AFB Smear: Tubercle bacilli

Cultures Use to confirm dx of TB Culture all specimen Result in 4-14 days when liquid medium systems used Susceptibility testing

Drug Susceptibility Testing Upper left contains no drugs