Tuberculosis
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Tuberculosis. 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. Background Epidemiology. 9 million Cases Annually >1/3 in India and China.

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Objectives
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



9 million cases annually 1 3 in india and china

9 million Cases Annually

>1/3 in India and China

9 million Cases Annually>1/3 in India and 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


Reported tb cases united states 1982 2006
Reported TB Cases* United States, 1982–2006

No. of Cases

Year


Tb case rates united states 2006
TB Case Rates,* United States, 2006

D.C.

< 3.5 (year 2000 target)

3.6–4.6

> 4.6 (national average)

*Cases per 100,000.


Tb case rates by age group and sex united states 2006
TB Case Rates by Age Group and Sex, United States, 2006

Cases per 100,000


Trends in tb cases in foreign born persons united states 1986 2006
Trends in TB Cases in Foreign-born Persons, United States, 1986–2006*

No. of Cases

Percentage

*Updated as of April 6, 2007.


Drug resistant tb counted cases defined on initial dst by year 1993 2006
Drug Resistant TB Counted Cases defined on Initial DST 1986–2006*† by Year, 1993–2006*

*Reported incident cases as of 7/18/07

†Drug Susceptibility Test

Case Count

Year of Diagnosis


Tb in children
TB in Children 1986–2006*

  • 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


Making the decision to test for tb

MAKING THE DECISION TO TEST FOR TB 1986–2006*

The Initial “Test” for TB Infection is the History


Who should be tested
Who Should be Tested? 1986–2006*

  • 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


Questionnaire risk assessment for tb infection in children nycdoh
Questionnaire Risk Assessment for TB Infection in Children - NYCDOH

Ozuah et al. JAMA;285:451

Risk factorSens.Spec.PPVNPVOR

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


Epidemiologically-Defined Groups NYCDOH

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)


Underlying medical conditions which increase risk for progression to active tb disease
Underlying Medical Conditions Which Increase Risk for NYCDOHProgression 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


Incidence of tuberculosis by selected risk factors in persons with a positive tst
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

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)

12.9

1.6

35.0-162

76.0

10.0

68.0

2.0-13.6

0.7-2.6


How to test

HOW TO TEST Persons with a Positive TST


Tuberculin skin testing

Tuberculin Skin Testing Persons with a Positive TST

Tuberculin Skin Testing


Induration of 5mm considered a positive tst
Induration of >5mm Considered a Positive TST Persons with 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


Induration of 10mm considered a positive tst
Induration of >10mm Considered a Positive TST Persons with a Positive TST

  • Recent arrivals (<5 yrs) high prevalence countries

  • Intravenous Drug Users

  • Residents/employees - high-risk congregate facilities (health care, prisons, shelters, etc.)


Induration of 15mm considered a positive tst
Induration of >15mm Considered a Positive TST Persons with a Positive TST

  • TB lab personnel

  • Persons with “high-risk” medical conditions

  • Children <4 yrs or exposed to adults at risk


Interferon gamma release assays
Interferon Gamma Release Assays Persons with a Positive TST

  • 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.


Positive skin test

Positive Skin Test Persons with a Positive TST

Now what?


Before treatment of ltbi exclude active tuberculosis
Before Treatment of LTBI: Exclude Active Tuberculosis Persons with a Positive TST

  • Absence of symptoms

  • Negative CXR

  • Negative medical evaluation

  • Order and wait for sputum culture if

    any question



Miliary tb in a child
Miliary TB in a child Persons with a Positive TST


Chest radiograph pearls
Chest Radiograph “Pearls” Persons with a Positive TST

  • 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)


Childhood TB diagnosed by: Persons with a Positive TST

  • Combination of :

    • Contact with infectious adult case

    • Symptoms and signs

    • Positive tuberculin skin test

    • Suspicious CXR or CT/MRI

    • Bacteriological confirmation

    • Serology?


Treatment

Treatment Persons with a Positive TST


Treatment of ltbi
Treatment of LTBI Persons with a Positive TST

  • 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


Isoniazid preventive therapy worldwide trials 1955 1965

19 controlled trials in 11 countries: Persons with a Positive TST

United States

Canada

Greenland

Mexico

Japan

Netherlands

France

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

ISONIAZID PREVENTIVE THERAPYWorldwide Trials, 1955-1965

Tunisia

Kenya

India

Philippines


How much isoniazid is needed for the prevention of tuberculosis
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


Iuatld study of inh therapy for ltbi
IUATLD Study of INH Therapy for LTBI Tuberculosis?

  • 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%


Contacts Of INH Resistant TB Tuberculosis?

  • Four month regimen daily Rifampin for adults

  • Six month regimen daily Rifampin for HIV infected

  • Six month regimen daily Rifampin for children


Treatment of latent tb infection in special situations
Treatment of Latent TB Infection in Tuberculosis? 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)


Tb and bcg vaccination
TB and BCG Vaccination Tuberculosis?

  • 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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