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

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

3. Right lateral cervical mass
CHIEF COMPLAINT:
Right lateral cervical mass

4. 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

5. 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

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

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

8. 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

9. 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

10. 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: z = 0

11. 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

12. 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

13. 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

14. 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

15. Not patient’s plate

16. RIGHT LATERAL Cervical Mass
Presenting Manifestation
RIGHT LATERAL Cervical Mass

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

19. 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

20. 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] :
      

21. 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] :

22. 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

23. 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

24. 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

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

26. (+) 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 PPS, Inc. p.123

27. 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 PPS, Inc. p.123

28. WORK UPS AND MANAGEMENT

29. 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

30. 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

31. 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)

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

33. 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

34. Management of Tuberculosis

35. 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.

36. 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

37. 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.

38. 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

39. 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

40. 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

41. 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

42. 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

43. Supportive Management
Multivitamins 5 mL once a day
Anticipatory Guidance

44. Tuberculosis

45. 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.

46. 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.

47. 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

48. 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

49. 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.

50. 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

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

52. 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?

53. 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,
Close
Percent infected
Close
Casual
Casual
Grzybowski S, et al. Bull Int Union Tuberc 1975;50:90-106

54. 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.

55. 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.

56. 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.

57. 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 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 This proportion has remained stable over time in the US.

58. 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:

59. 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 population)
400
400
200
200
0.1
0.1
0.2
0.2
0.3
0.3
0.4
0.4
HIV prevalence adults years

60. 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

61. 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

63. 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

64. Transmission and Pathogenesis

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

66. 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

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

68. Classification System for TB

70. Risk Factors for the Development of TB Disease

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

72. 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

73. 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

74. 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

75. Sputum AFB Smear

76. AFB Smear: Tubercle bacilli

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

78. Drug Susceptibility Testing
Upper left contains no drugs