Transcript Tuberculosis

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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Cases Annually
99 million Cases
Annually
>1/3 in
in India
India and
>1/3
and China
China
< 1 000
1 000 to 9 999
10 000 to 99 999
100 000 to 999 999
1 000 000 or more
No Estimate
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Reported TB Cases*
United States, 1982–2006
No. of Cases
28,000
26,000
24,000
22,000
20,000
18,000
16,000
14,000
12,000
10,000
1982
1986
1990
1994
Year
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1998
2002
2006
TB Case Rates,* United States, 2006
D.C.
< 3.5 (year 2000 target)
3.6–4.6
> 4.6 (national average)
*Cases perClinic
100,000.
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TB Case Rates by Age Group
and Sex, United States, 2006
Cases per 100,000
12
10
8
6
4
2
0
<15 yrs
15–24 yrs
25–44 yrs
Male
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45–64 yrs
Female
>65 yrs
Trends in TB Cases in Foreign-born
Persons, United States, 1986–2006*
No. of Cases
Percentage
10,000
60
50
40
8,000
6,000
30
20
10
0
4,000
2,000
0
86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06
No. of Cases
*Updated Clinic
as of April 6, 2007.
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Percentage of Total Cases
Drug Resistant TB Counted Cases defined
†
on Initial DST by Year, 1993–2006*
*Reported incident cases as of 7/18/07
Case Count
†
Drug Susceptibility Test
12
10
8
6
4
2
Year of Diagnosis
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2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
0
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?
• 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 - NYCDOH
Ozuah et al. JAMA;285:451
Risk factor
Sens.
Contact to a case
Birth/travel to endemic area
Contact to HR adult
Age > 11 yr
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26
63
19
67
Spec.
PPV
NPV
OR
99.6
89.7
96.6
71.0
38.9
5.4
4.9
2.1
99.3
99.6
99.2
99.6
92
15
7
5
Epidemiologically-Defined Groups
with HIGH Prevalence of Tuberculosis Infection
• 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)
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Underlying Medical Conditions
Which Increase Risk for
Progression to Active TB Disease
–
–
–
–
–
–
–
–
–
HIV infection
Chronic renal failure
Immunosuppressive Rx
Diabetes mellitus
Malignancy
TNF Alpha blocker therapy
Transplant recipients
> 15 mg Prednisone/day
Silicosis
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Incidence of Tuberculosis by Selected Risk
Factors in Persons with a Positive TST
Risk Factor
TB Cases/1000 person-years
Recent TB Infection
Infection < 1 year past
Infection 1-7 years past
12.9
1.6
HIV/AIDS
35.0-162
Injection Drug Use
HIV-positive
HIV-negative or unknown
76.0
10.0
Silicosis
68.0
Radiographic findings consistent with old TB
2.0-13.6
Weight Deviation from Standard
(5% overweight  15% underweight)
0.7-2.6
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HOW TO TEST
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Tuberculin Skin Testing
Tuberculin Skin Testing
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Induration of >5mm Considered a
Positive TST
• 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
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Induration of >10mm Considered a
Positive TST
• Recent arrivals (<5 yrs) high prevalence
countries
• Intravenous Drug Users
• Residents/employees - high-risk
congregate facilities (health care,
prisons, shelters, etc.)
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Induration of >15mm Considered a
Positive TST
• TB lab personnel
• Persons with “high-risk” medical
conditions
• Children <4 yrs or exposed to adults at
risk
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Interferon Gamma Release Assays
• 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.
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Positive Skin Test
Now what?
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Before Treatment of LTBI: Exclude
Active Tuberculosis
•
•
•
•
Absence of symptoms
Negative CXR
Negative medical evaluation
Order and wait for sputum culture if
any question
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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 of LTBI
• 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
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ISONIAZID PREVENTIVE THERAPY
Worldwide Trials, 1955-1965
19 controlled trials in 11 countries:
United States
Japan
Canada
Netherlands
Greenland
France
Mexico
Tunisia
Kenya
India
Philippines
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)
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25-92% protection
How Much Isoniazid Is Needed for
the Prevention of Tuberculosis?
• 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
Community based study, Bethel Alaska
Comstock GW, 1999.
Int J Tuberc. Lung Dis 3:847-850
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IUATLD Study of INH Therapy for
LTBI
• Reduction in culture positive TB at 5 years all
participants
– 6 months therapy
– 12 months therapy
65%
75%
• Reduction in culture positive TB at 5 years in the
group of completer-compliers (took > 80% of
doses):
– 6 months therapy
– 12 months therapy
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69%
93%
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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Treatment of Latent TB Infection in
Special Situations
• 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)
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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
Colditz GA et al. JAMA 1994; 271: 698-702.
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