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Dr. SERİR AKTOĞU ÖZKAN I zmir Göğüs Hastalıkları ve Cerrahisi Eğitim ve Araştırma Hastanesi [email protected] THE TRIALS RELATED TO TREATMENT OF LTB INFECTION. THE CONTROL OF T UBERCULOSIS. to detect of patients with active tuberculosis to cure the patients with active TB

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Dr. SERİR AKTOĞU ÖZKAN

Izmir Göğüs Hastalıkları ve CerrahisiEğitim ve Araştırma Hastanesi

[email protected]

THE TRIALS RELATED TO TREATMENT OF LTB INFECTION


The control of t uberculosis
THE CONTROLOF TUBERCULOSIS

  • to detect of patients with active tuberculosis

  • to cure the patients with active TB

  • to detect and treatment of persons with LTBI at high risk for developing to active TB


Treatment of latent tb infection
TREATMENT OF LATENT TB INFECTION

  • to detect LTBI with high risk for

    developing TB

  • to start standart treatment of LTBI

  • to complete of standart treatment of LTBI


Persons with increased risk for developing tb
Persons with increased risk for developing TB

  • Recent infection with M. tuberculosis

  • Clinical conditions that are associated with an increased risk for progression of LTBI to active TB (several factors that are associated with decreased cell-based immunity).


Several factors associated with impaired cell based immunity
Several factors associated with impaired cell-based immunity

  • Younger than 5 yr of age, adolescents and

    young adults

  • HIV infection, who are receiving immunosuppressive theapy (anti-TNF-α drugs, systemic corticosteroids, solid organ transplantation),

  • chronic renal failure, leukemias, lymphomas, carcinoma of the head or neck and lung v.s


Treatment of ltb i
TREATMENT OF LTBI

  • Isoniazid has been the mainstay of LTBI treatment

    for >40 years.

  • The preferred treatment for LTBI is 9 months of

    daily H

    Effectiveness of the drug 25- 93 %

  • Disadvantages: hepatotoxicity, poor completion

    rate, high H resistance


Randomized treatment trials in hiv infected subjects
RANDOMIZED TREATMENT TRIALS IN HIV INFECTED SUBJECTS

2 months of R (600mg) and Z (15-20mg/kg) in

combination (RZ) proved to be as effective as 6

months of (H) treatment for prevention of TB

Disease and was well tolerated.

Halsey NA, Coberly JS, Desormeaux J et al. Randomized trials of isoniazid

Versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1

İnfection. Lancet 1998; 351: 786-92.


Ltbi treatment in hiv infected subjects
LTBI TREATMENT IN HIV INFECTED SUBJECTS

2-3 months of RZ for LTBI treatment in HIV

infected patients was recommended by The

Centers for Disease Control and Prevention (CDC)

in 1998.


The person with positive tuberculin reaction who

are considerd to be at high risk for developing for

active TB should be offered treatment of LTBI


Treatment regimens for ltbi
TREATMENT REGIMENS FOR LTBI

ATS, CDC, AM J Respir Crit Care Med 2000;161: S221-S247


Severe or fatal hepatotoxicity in patients taking rz for ltbi
Severe or fatal hepatotoxicity in patients taking RZ for LTBI

  • 21 hepatotoxicity between 12 Feb- 24 Ağust 2001

  • 5 of whom died

  • The preferred treatment is 9 months of daily H

  • The regimen of 2RZ should generally not be

    offered for treatment of LTBI and intensive

    monitoring is required

    MMWR 2001; 50: 733-735

    JAMA; 2001: 286: 1445-1446.


  • High risk of hepatotoxicity

  • Intensive monitoring is required

  • 2RZ is not cost-effective for tuberculosis control

    programs

  • Standart therapy for LTBI is 9 months H


A meta analysis r plus z versus h for treating ltbi
A Meta-analysis : R plus Z versus H for treating LTBI

6 trials: Haiti, Mexico, USA, Brazil, Spain, Zambia, Hong-Kong

2-3 months RZ versus standart 6-12 ay H regimens

randomizedcontrolledtrials.

Incidence of TB:

0% 2RZ

0.4% 6H

Severe hepatotoxicity

8.2% 2RZ

1.7% 6H

Severe advers events

11.4% 2RZ

2.9% 6H Gao et al. Int. J Tuberc Lung Dis 2006; 10: 1-11


Recommendations and Reports

July 7, 2006 / 55(RR09);1-44

Prevention and Control of Tuberculosis in Correctional and Detention Facilities: Recommendations from CDC

Endorsed by the Advisory Council for the Elimination of Tuberculosis, the National Commission on Correctional Health Care, and the American Correctional Association

The material in this report originated in the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed), Kevin Fenton, MD, PhD, Director, and the Division of Tuberculosis Elimination, Kenneth G. Castro, MD, Director.

Corresponding address: Division of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed), CDC, 1600 Clifton Road, NE, MS E-10, Atlanta, GA 30333. Telephone: 404-639-8120; Fax: 404-639-8604.

Summary


Drugs

Dura

tion

Interval

No of doses

RatingEvidence

HIV- HIV+

H

H

R

9

6

4

Daily

Twicewkly

Daily

Twice wkly

Daily

270

78

180

52

120

A(II) A(II)

B(II) B(II)

B(I) C(I)

B(II) C(I)

B(II) B(III)

TREATMENT REGIMENS FOR LTBI

L

www.cdc.gov/mmvr/preview/mmwrhtml/ 2006


  • Retrospective design

  • Treatment completion 9H (62 %), 4R (86 %)

  • Hepatotoxicity 9H (1.4 %), 4R (0 %)

  • Side effects and drug reactions 9H (6.1 %),

    4R (3.1%)

  • Conclusions: Patients receiving 4R were

    significantly more likely to complete therapy than

    those receiving 9H


Efitorial comment consider rifampin but be cautious
Efitorial CommentConsider Rifampin BUT be cautious

  • Rifampin must be used with caution

  • Rifampin monotherapy can relaese

    Rifampin resistance

  • Randomized controlled trials is required for

    medical and public health recommendations.

    Chest 2006; 130: 1638-1639


Treatment for LTBI in people who exposed to MDR-TB

  • Z plus E or Z ve Quinolone 6-12 months ,if M. Tuberculosis strain isolated from the index case is susceptible to these drugs )


Preventing TB in people at risk of MDR

  • No randomized controlled trials

  • The balance of benefits and harms

    associated with treatment for LTBI in

    people exposed to MDR-TB is far from

    clear.


Anti tnf alfa treatment and tb infliximab etanercept adalimumab
Anti TNF- alfa Treatment and TB(infliximab, etanercept, adalimumab)

  • RA patients is at incresed risk of TB versus the

    general population

  • RA patients treated with TNF antagonists has a

    4-20-fold incresed risk of TB versus RA patients not

    treated withTNF antagonists

    Arthritis and Rheumatism 2005; 52: 1986-1992

    Arthritis and Rheumatism 2003; 48: 2122-2127


  • The increase in TB is associated with Anti-TNF-alfa.

  • Prior of commencing of anti-TNF-alfa, all patients

    should have their risk of TB assessed: history of TB

    infection and treatment, a clinical examination, a

    chest x-ray, Tuberculin testing

  • It is important to exclude of active TB

  • If the patient has active TB, full course of standart

    chemotherapy is required.



  • For patients with normal chest x-ray and BCG, no

    history of TB, no immunosuppressant thrapy,

    Tuberculin testing of 0-14, no further action is

    needed and anti-TNF-alfa theray can be

    commenced.

  • No BCG, and tuberculin testing of 0-5, no further

    action is needed and anti-TNF-alfa therapy can be

    commenced.


Ii raed the statement of consensus meeting 7 may 2005 zmir
II. RAED The Statement of ConsensusMeeting 7 May 2005 / İzmir

  • Anti TB therapy must be completed prior to

    commencing anti TNF-alfa therapy.

  • Prior of commencing of anti-TNF-alfa, all patients

    should have their risk of TB assessed: history of

    TB infection and treatment, chest x-ray and,

    tuberculin skin testing.


Ii raed the statement of consensus meeting 7 may 2005 zmir1
II. RAED The Statement of ConsensusMeeting 7 May 2005 / İzmir

  • If the patient with tuberculin testing of 1-4 mm

    (negative), no fibrocalcific lesions in chest x ray,

    and no contact with TB within last year, it is

    recommended to repeat tuberculin testing

    If the second tuberculin testinf is 1-4 mm, there is

    no need for LTBI treatment

  • However, the risk of TB outweighs the risk of

    chemoprophylaxis, therapy for LTBI may be

    started.


Ii raed the statement of consensus meeting 7 may 2005 zmir2
II. RAED The Statement of ConsensusMeeting 7 May 2005 / İzmir

Following conditions are required standart

treatment with H 9 month:

  • The patients with normal chest x-ray but

    tuberculin test of ≥ 5 mm

  • The patient with abnormal chest x-ray

    (fibrocalcific lesions and/or tuberculin

    testing ≥ 5 mm and excluding active TB

  • The patient who contact with active TB patients

    within last year

  • Health care workers with high risk ofTB


Turkish thoracic society 10 th annual congress mini symposia 2007 tuberculosis and anti tnf therapy
Turkish Thoracic Society 10 th Annual CongressMini Symposia 2007 Tuberculosis and anti-TNF-α Therapy

  • Most of patients (72%) had BCG mark

  • Most of patients (69%) were currently taking ≥1

    immunosuppressive drug other than anti TNF-α

    at the initiation of treatment.

  • %9 had taken none of them


Conclusions
CONCLUSIONS

  • It is important to detect of persons with LTBI at

    high risk for developing to active TB

  • Standart treatment for LTBI is 9 months of H daily

  • Treatment completion is of paramount importance

    to the success of LTBI therapy

  • No standart treatment for close contacts of

    MDR-TB cases


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