PROPHYLAXIS; INDICATIONS AND

DIFFICULTIES

Dr. Suha ÖZKAN

•

CONGRESS COURSE

RECENT ADVANCES IN TUBERCULOSIS CONTROL AND PROPHYLAXIS

No conflict of interest

Presentation flow

• What is “Prophylactic therapy”?

• World experience about prophylaxis

• Prophylaxis in “Turkey National TB Guidelines”

• Practices and experiences from our country

• Problems of prophylaxis

Chemoprophylaxis

Latent tuberculosis infection treatment

Preventive treatment of TB

Prophylactic Therapy

Protection from Tuberculosis

1. Treatment of infectious patients

2. Prophylaxis

3. BCG vaccination

4. Prevent the transmission of TB bacillus

Iseman MD. Klinisyenler için Tüberküloz Kılavuzu. Çeviren: Ş. Özkara. (Tüberkülozun koruyucu tedavisi).Nobel Tıp Kitabevleri, İstanbul. 2002: s. 355-398.

Aim of Prophylaxis

Contact of TB patient prevent the development of infection

(No randomised studies)

TB infected person prevent the development of TB disease

(numerous double blind, randomised plasebo-controlled studies)

PROPHYLACTIC THERAPY

Target person for prophylaxis:

All TB infected person in the community

Is it possible?

NO

Let us then, prophylaxis for whom?

Groups with a high risk of developing TB disease

Benefits?

To avoid development of disease from Latent TB infection

To prevent the emergence of a new bacillis source

Epidemiological importance in TB Control

High risk of developing active disease groups

HIV infection, AIDS 113, 170 Silicosis 30 Tranplantation of kidney 37 Terminal stage renal disease 10 - 25.3 Newly infected person< 2 years 15 Iatrogenic immunosuppression 4 - 16 Age (< 5 or >60) 3 - 5 Diabetes 2 - 3.6

Dose Isoniazid, daily in adults; 5 mg/kg (max. 300 mg) For children; 10 mg/kg/day (max. 300 mg)

Period At least for 6 months. 9 months treatment recommended for the these groups; HIV positives, with silicosis, anti TNF treatment or other immunosuppression teatments.

Details of preventive drug therapy

If the source patient is resistant to INH or the person can not use isoniazid; rifampicin 10 mg/kg/day, maximum 600 mg/day (4 months)

Details of preventive drug therapy

If the source patient is resistant to H and R (MDR)

Pyrazinamide + ethambutol or Pyrazinamide + quinolone can be used.

But there is no large studies for efficacy and safety

In case of the six month preventive therapy within 9 months, the nine month preventive therapy within 12 months completed, treatment can be considered OK.

A Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000; 161(4 Pt 2):S221-47.

In prophylaxis:

• Medications should be used regularly and completed the period

• To educate and support is important

• Uninterrupted therapy is essential

• Short term intervals, the time is added to the end of treatment

Snider DE Jr. Pyridoxine supplementation during isoniazid therapy. Tubercle 1980; 61:191-196.

Pyridoxine (vitamin B6) in prophylaxis

• Diabetes Mellitus• Renal failure, dialysis• Malnutrition• Alcoholism• Pregnancy• Pyridoxine deficiency epileptic seizures

10 mg. Pyridoxine (Vitamin B6) daily used with isoniazid

• Whether or not symptoms transaminase values exceed 5 times the upper limit of normal• Upper limit of normal in a patient with symptoms of hepatitis, transaminase values exceeding 3 times• Without apparent cause other than bilirubin 1.5 mg / dL rise above.

Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006; 174: 935-952.

Hepatitis due to Isoniazid

Normally during the use of H may be temporary transaminase heights.

STOP “H”

After stopping Isoniazid (H), if the person used

lower drug doses then planned, prophylaxis can

be continued with rifampicin (R).

H is contraindicated in the presence of H allergy or a history of liver disease formed by H.

Patients with chronic liver disease, and regular alcohol use, not to use H would be more appropriate.

If the patient carries a high risk of side-effects are evaluated.

People had to informed about the side effects of drugs.

Be sure that the person has not TB disease• Medical history of patient• Physical examination and findings• Chest x-ray must be evaluated

If you think TB disease

Bacteriological examination is done

Before starting prophylaxis

If the person has TB disease and is not detected, the result of preventive treatment may be drug

resistance

Preventive treatment may be as effective as 19 years.

At the end of preventive therapy, alteration of the tuberculin skin test is not expected.

Comstock GW, Baum C, Snider DE Jr. Isoniazid prophylaxis among Alaskan Eskimos: a final report of the Bethel studies. Am Rev Respir Dis 1979; 119:827-830.

World experience in preventive therapy

Preventive treatment studies-USPHS*1) Household contacts of new diagnosed patients: 25.033 contacts of 5677 source cases, Randomised, double-blind, placebo controlled, H for 12 months, daily 5-6 mg/kg.

ACTIVITY: Reduction of 70% in pulmonary TB, 72% in extrapulmonary TB

in two years. *USPHS = United States Public Health Service

2) mental health institutions Total 25.210 people Randomised, double-blind, placebo controlled, H for 12 months, daily 4,2-5,0 mg/kg, watching for 10 years.

ACTIVITY: Reduction of 63% in two years, >60% prevention in long-term

follow-upM.D. Iseman, Klinisyenler İçin Tüberküloz Kılavuzu. Çev: Özkara Ş.

3) People in Alaska: Total of 6054 people, Age distribution: 0-14age (49%), 15-34 age (30%), 35-54 age

(16%), 55 age and upper (5%).

RESULTS:

59% decrease in morbidity for 6 years, preventive effect has seen for 19 years.

4) Inaktive lesions: Total 4575 people, People with inactive TB lesions in chest x-ray.

RESULTS: The rate of developing TB disease in placebo group 6.86%, H

preventive group 2.57% within two years. Total prevention is 63% in five years.

M.D. Iseman, Klinisyenler İçin Tüberküloz Kılavuzu. Çev: Özkara Ş.

Studies in Europe about Prophylaxis - IUAT*

Compatible with pulmonary tuberculosis cured films were studied nearly 28,000 people.

Divided into groups of placebo, 3 months H, 6 months H, 12 months H and ve radiological abnormalities were graded.

RESULTS: Compared to placebo, the incidence of TB had decreased

65% with 6 months regime, 75% with 12 months regime in 5 years.

If the radiological abnormalities are smaller than 2 cm, the preventive activity of 6 months regime and 12 months regime were similar.

*IUAT = International Union Against Tuberculosis

M.D. Iseman, Klinisyenler İçin Tüberküloz Kılavuzu. Çev: Özkara Ş.

Prophylaxis in TB Control

Every year, people infected with infectious tuberculosis patients will result in a new society, along with other infected people, and also similar numbers of patients will be seen again a year later.

Whether early treatment of TB patients effectively, reduce the number of those who are newly infected. However, the large population of people who have been infected previously not treated, the disease will be limited to a reduction in the number of those arrested.

* Ferebee and friends (USPHS)

Especially those who are at risk for the disease and contacts, chemoprophylaxis is given within the program, assuming the protection efficiency of 60%, less patient will be seen in the next year.

More than 50% decrease in the incidence of the disease in the United States within 15 years, largely because widespread drug preventive program run (2 million people each year, the drug was intended to protect). *

* Ferebee and friends (USPHS)

Prophylaxis in TB Control

The model of Ferebee and friends from USPHS

INH:INH:Placebo-Controlled Trials of Isoniazid for Placebo-Controlled Trials of Isoniazid for Treatment of Latent TB Infection, 1955-Treatment of Latent TB Infection, 1955-

1965196519 controlled trials in 11 countries:

United States Canada

GreenlandMexico

JapanNetherlands

France

Over 100,000 participants

25%-92% protection

HEPATITIS NOT REPORTED OR NOT RECOGNIZED

TunisiaKenyaIndia

Philippines

Dick Menzies MD, MSc, Tuberculosis Contact Investigations; TTS Meeting 2011

Prophylaxis in ATS- CDC Guideline- 2000

HIV +

Contacts of TB patient

TB liked inactive lesions in chest x-ray

Solid organ transplantations and immunosupressed people

Tuberculin Skin Test >5mm

Immigrants from high-prevalence countries in the last 5 years

IV drug users Poeple working or living in high risk institutions Mycobactery laboratory staff Co-morbid situtations: silicosis, CRF, DM, hematological

diseases, malignencies, gastrectomy, 10% weight loss Children under age of 4 years who are Contact in high-risk

adults

Tuberculin skin test >10mm

Prophylaxis in ATS- CDC Guideline- 2000

Person who has not any risk factor

Tuberculin skin test >15mm

Prophylaxis in ATS- CDC Guideline- 2000

Dr. Feridun Kunak’tan VEREM için özel karışım – 2 Ocak 2013 (Kanal 7)

Verem hastaları için Feridun Kunak, kendi show programında vereme iyi gelecek ve verem hastalığını tedavi edecek özel bir kür tarifi vererek, verem hastalarının yaşam kalitelerin yükseltmelerine muavenet ediyor. Verem için Feridun Kunak’ın vermiş olduğu bu kürü düzenli olarak uyguladığınız zaman hem kısa sürede bu rahatsızlığınızı geride bırakacak hem de veremden dolayı yaşadığınız bir takım sıkıntılardan kurtularak sağlıklı bir bünyeye sahip olmanın keyfini süreceksiniz. www.sagliksiteniz.com

Is it really difficult to treat and prevent TB?

??

PREVENTIVE THERAPY IN

“TURKEY NATIONAL GUIDELINE FOR TB CONTROL”

Conversion of TST

Immunosuppressed people with positive

TST

TST positive smaller then age 15

Contacts of infectious TB patient, age <35

The risk groups for preventive therapy in Turkey

It is necessary to screen house-hold contacts

before prophylaxis.

If there are suspected contact people outside

home, they are suitable for screening.

Doğrudan Gözetimli Tedavi ya da Koruyucu Tedavi Fotoğrafları (Bu Fotoğrafların bilimsel amaçlı sunularda kullanılması için hastalardan onay alınmıştır.) 

verem.org.tr

Prophylaxis with DOT in a school

yearsNumber

of TB patients

Contact examination

Number of preventive

therapy

Contact examination per patient

Preventive therapy per

patient

Registered TB patients in TB dispansaries, 2002-2009

TB patients, contact examinations, prophylaxis, 2002-2009

Due to preventive treatment practices in our country, the rate

of completion treatment is high.

In 2008, 75% of the people who started preventive treatment,

completed their regime in our country.*

It is shown that prophylaxis is effective in the age groups 0-14,

15-34, and over 35. In the recent years, some studies have

shown to be effective in immunocompromised patients.**

*Bozkurt H ve ark. Tüberkülozda koruyucu tedavi alanların değerlendirmesi. XXVI. Ulusal Tüberküloz ve Göğüs Hastalıkları Kongresi Bildiri Özetleri Kitabı, 2011.

**Sayıcı Ş ve ark. Akciğer tüberkülozu temaslılarında hastalanma ve koruyucu tedavinin etkinliği. XXVI. Ulusal Tüberküloz ve Göğüs Hastalıkları Kongresi Bildiri Özetleri Kitabı, 2011.

A Critical Approach to Preventive treatment; Doubts and Problems

Error in the determination of latent infection (TST?)

The risk of treatment-related hepatitis

The possible presence of resistance to Isoniazid

Treatment compliance problems

Being TB patient before prophylaxis or TB disease during preventive treatment

Efficacy of preventive treatment

Recurrent infection

Priorities in planning resource and health staff

Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection ATS/CDC Statement Committee on Latent Tuberculosis Infection Membership List, June 2000, MMWR, June 09, 2000 / 49(RR06);1-54

The evidence of treatment regimes

TB Patient

Progressive symptoms

Infectious

Radiological findings

Positive TST

Latent infection

No symptoms

Not infectious

No radiological findings

Positive TST

Treatment period

6 months9 months (evidence A)

6 months (evidence B)

“ Evaluation of tolerance and cost-benefit, 6 months treatment is optimal”

LAST WORDS: Studies show the effect of preventive therapy in

the prevention of TB disease. Preventive treatment is a main component of TB

Control Program in some countries. The discussion is whether preventive therapy

has priority according to the situation in the country.

The insidence of TB has reduced in Turkey, recent years.

Preventive treatment has been used widely.

Kaynaklar• Tüberküloz Tanı ve Tedavi Rehberi

Sağlık Bakanlığı, 2011

• Türkiye’de Tüberkülozun Kontrolü için Başvuru Kitabı,

Sağlık Bakanlığı Verem Savaşı Daire Başkanlığı, 2003

• Klinisyenler İçin Tüberküloz Kılavuzu,Michael D. Iseman, Çeviri: Şeref Özkara Nobel Tıp Kitabevi,

2002

• Tüberkülozdan Korunma,

G. Kıter, E. S. Uçan, Toraks Dergisi, 2001:2(1):85-90

• Tüberkülozda İlaçla Koruma,

E, Erdinç, Tüberküloz Kliniği ve Kontrolü, 391-397