Post on 15-Dec-2015
Continuity Clinic
Tuberculosis
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Objectives
• Know current epidemiologic trends in TB
• Know indications for testing for TB exposure and the tests available
• Be familiar with treatments for latent tuberculosis infections
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Background Epidemiology
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9 million Cases Annually>1/3 in India and China
10 000 to 99 999
100 000 to 999 999
1 000 000 or more
< 1 000
1 000 to 9 999
No Estimate
9 million Cases Annually>1/3 in India and China
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Reported TB Cases* United States, 1982–2006
10,000
12,000
14,000
16,000
18,000
20,000
22,000
24,000
26,000
28,000
1982 1986 1990 1994 1998 2002 2006
Year
No. of Cases
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TB Case Rates,* United States, 2006
< 3.5 (year 2000 target)
3.6–4.6
> 4.6 (national average)
D.C.
*Cases per 100,000.
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TB Case Rates by Age Group and Sex, United States, 2006
02468
1012
<15 yrs 15–24 yrs 25–44 yrs 45–64 yrs >65 yrs
Male Female
Cases per 100,000
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Trends in TB Cases in Foreign-born Persons, United States, 1986–2006*
0
2,000
4,000
6,000
8,000
10,000
8687888990919293949596979899000102030405060
10
20
30
40
50
60
No. of Cases Percentage of Total Cases
No. of Cases Percentage
*Updated as of April 6, 2007.
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Drug Resistant TB Counted Cases defined on Initial DST† by Year, 1993–2006*
0
2
4
6
8
10
12
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Case Count
Year of Diagnosis
*Reported incident cases as of 7/18/07†Drug Susceptibility Test
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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
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MAKING THE DECISION TO TEST FOR TB
The Initial “Test” for TB Infection is the History
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Who Should be Tested?Who Should be Tested?Who Should be Tested?Who Should be Tested?
• Those at epidemiological increased risk of having TB infection
• Those at increased individual risk of developing TB disease if infected
• ONLY test if you are going to treat the patient – a decision to test is a decision to treat
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Questionnaire Risk Assessment for TB Infection in Children - NYCDOHQuestionnaire Risk Assessment for TB Infection in Children - NYCDOH
Risk factor Sens. Spec. PPV NPV OR
Contact to a case 26 99.6 38.9 99.3 92
Birth/travel to endemic area 63 89.7 5.4 99.6 15
Contact to HR adult 19 96.6 4.9 99.2 7
Age > 11 yr 67 71.0 2.1 99.6 5
Ozuah et al. JAMA;285:451
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• Immigrants from areas of world with a high incidence of TB• Homeless persons, and other low income groups
with poor access to health care• Elderly persons
• Residents and employees in congregate living facilities serving persons at high risk of TB (correctional institutions, homeless shelters, health care facilities, nursing homes, assisted living facilities, AIDS housing)
Epidemiologically-Defined Groups
with HIGH Prevalence of Tuberculosis Infection
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– HIV infection – Chronic renal failure– Immunosuppressive Rx – Diabetes mellitus – Malignancy– TNF Alpha blocker therapy
– Transplant recipients– > 15 mg Prednisone/day– Silicosis
Underlying Medical Conditions Which Increase Risk for
Progression to Active TB Disease
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Risk Factor TB Cases/1000 person-years
Recent TB Infection Infection < 1 year past Infection 1-7 years past
HIV/AIDS
Injection Drug Use HIV-positive HIV-negative or unknown
Silicosis
Radiographic findings consistent with old TB
Weight Deviation from Standard (5% overweight 15% underweight)
12.91.6
35.0-162
76.010.0
68.0
2.0-13.6
0.7-2.6
Incidence of Tuberculosis by Selected Risk Factors in Persons with a Positive TST
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HOW TO TEST
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Tuberculin Skin TestingTuberculin Skin Testing
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• HIV positive persons
• Recent contacts of TB cases
• Fibrotic Changes on CXR c/w old (not treated) TB
• Patients with organ transplants or other immunosuppression
• Prednisone therapy 15 mg/day > 1 month
Induration of >5mm Considered a Positive TST
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• Recent arrivals (<5 yrs) high prevalence countries
• Intravenous Drug Users
• Residents/employees - high-risk congregate facilities (health care, prisons, shelters, etc.)
Induration of >10mm Considered a Positive TST
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• TB lab personnel
• Persons with “high-risk” medical conditions
• Children <4 yrs or exposed to adults at risk
Induration of >15mm Considered a Positive TST
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• Quantiferon – measure of interferon gamma in supernatant, currently at third generation test – Quantiferon Gold In-tube
• Elispot – measure of individual T-cells that produce interferon gamma.
Interferon Gamma Release Assays
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Positive Skin Test
Now what?
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• Absence of symptoms
• Negative CXR
• Negative medical evaluation
• Order and wait for sputum culture if any question
Before Treatment of LTBI: Exclude Active Tuberculosis
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Hilar adenopathy with infiltrate and collapse
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Miliary TB in a child
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Chest Radiograph “Pearls”
• Hilar nodes, pleural disease – extrapulmonary, few bacteria
• Cavitary disease – many bacteria• Parenchymal scars – NOT active, only
needs preventive therapy (LTBI) IF scar is > 2.5 cm
• Calcified node is functionally like a normal chest radiograph (very very few live AFB)
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Childhood TB diagnosed by:
Combination of : Contact with infectious adult case Symptoms and signs Positive tuberculin skin test Suspicious CXR or CT/MRI Bacteriological confirmation Serology?
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Treatment
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• Treatment regimens:– INH x 9 months– Alternative: Rifampin 600mg daily x 4 months
for adults, 6 months for children and HIV+– Possible:
• INH & Rifampin x 3 to 4 months• INH, Rifampin, EMB & PZA x 2 months
– No longer used: Rifampin/PZA x 2 months– New? Rifapentine & INH weekly x 12 weeks
Treatment of LTBI
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19 controlled trials in 11 countries:United States CanadaGreenlandMexico
JapanNetherlandsFrance
Over 100,000 participants
Household contacts (6), Entire communities (3), Inactive pulmonary lesions (5), Children with primary TB (2), School children (1) Railway workers (1), Mentally ill patients (1)
25-92% protection
TunisiaKenyaIndiaPhilippines
ISONIAZID PREVENTIVE THERAPYWorldwide Trials, 1955-1965
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• Longer durations of therapy corresponded to lower TB rates among those who took 0-9 mo
• No extra increase in protection among those who took >9 months
Comstock GW, 1999.Int J Tuberc. Lung Dis 3:847-850
Community based study, Bethel Alaska
How Much Isoniazid Is Needed for the Prevention of Tuberculosis?
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• Reduction in culture positive TB at 5 years all participants
– 6 months therapy 65%– 12 months therapy 75%
• Reduction in culture positive TB at 5 years in the group of completer-compliers (took > 80% of doses):
– 6 months therapy 69%– 12 months therapy 93%
IUATLD Study of INH Therapy for LTBI
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Contacts Of INH Resistant TB
• Four month regimen daily Rifampin for adults
• Six month regimen daily Rifampin for HIV infected
• Six month regimen daily Rifampin for children
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• For children and adolescents (<18 years old):- Isoniazid for 9 months
• For pregnant women:- Isoniazid for 9 or 6 months - may defer except for HIV- infected women and those recently infected with Mycobacterium tuberculosis
• For persons exposed to isoniazid resistant TB:- Rifampin for 4 months
• For persons likely infected with multidrug-resistant TB: - Pyrazinamide and ethambutol, or pyrazinamide and quinolone for 6-12 months (i.e., at least 2 drugs to which the organism is susceptible)
Treatment of Latent TB Infection in Special Situations
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• 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
Colditz GA et al. JAMA 1994; 271: 698-702.
TB and BCG Vaccination