Continuity Clinic

Tuberculosis

Continuity Clinic

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

Continuity Clinic

Background Epidemiology

Continuity Clinic

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

Continuity Clinic

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

Continuity Clinic

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.

Continuity Clinic

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

Continuity Clinic

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.

Continuity Clinic

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

Continuity Clinic

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

Continuity Clinic

MAKING THE DECISION TO TEST FOR TB

The Initial “Test” for TB Infection is the History

Continuity Clinic

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

Continuity Clinic

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

Continuity Clinic

• 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

Continuity Clinic

– 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

Continuity Clinic

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

Continuity Clinic

HOW TO TEST

Continuity Clinic

Tuberculin Skin TestingTuberculin Skin Testing

Continuity Clinic

• 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

Continuity Clinic

• 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

Continuity Clinic

• 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

Continuity Clinic

• 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

Continuity Clinic

Positive Skin Test

Now what?

Continuity Clinic

• Absence of symptoms

• Negative CXR

• Negative medical evaluation

• Order and wait for sputum culture if any question

Before Treatment of LTBI: Exclude Active Tuberculosis

Continuity Clinic

Hilar adenopathy with infiltrate and collapse

Continuity Clinic

Miliary TB in a child

Continuity Clinic

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)

Continuity Clinic

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?

Continuity Clinic

Treatment

Continuity Clinic

• 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

Continuity Clinic

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

Continuity Clinic

• 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?

Continuity Clinic

• 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

Continuity Clinic

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

Continuity Clinic

• 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

Continuity Clinic

• 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