1. Tuberculosis and perinatal period Kai Kliiman Tartu University Lung Clinic Estonian NTP 15 September 2006 Tallinn

2. Tuberculosis Is a communicable disease caused by Mycobacterium tuberculosis It is spread primarily by tiny air bone particles (droplet nuclei) expelled when person with infectious TB disease (lung or throat TB) coughs, sneezes, speaks or sings Close contacts have highest risk of becoming infected

3. Distribution of tuberculosis in the world in 2003 Dye C. Lancet 2006; 367: 938–40

4. Estimated TB incidence in the WHO European region; 2002 TB case rate (per 100 000) < 10 10-24 25-49 50-99 100-149 > 150 World Health Organization. Global tuberculosis control: surveillance, planning, financing. WHO report 2004. Geneva: WHO, 2004 TB case rate (per 100 000) < 10 10-24 25-49 50-99 100-149 > 150

5. Notification rate of TB in Baltic States and in Finland 1990 – 2004 EuroTB, 2004

6. Trajectories of tuberculosis epidemic for nine epidemiologically different regions of the world Dye C. Lancet 2006 High HIV incidence- ≥4% in adults aged 15-49 years in 2003

7. TB and HIV HIV is strongest risk factor for development of TB if infected - risk of developing TB disease 7-10% each year the risk of developing TB rises with worsening immune status more common are disseminated and extra pulmonary diseases low cure rates high mortality rates

8. Opportunistic Infections in AIDS patients in Developing Countries Vietnam Camboya India Uganda Botswana Tuberculosis Bacterial infections P. carinii pneumonia Wasting syndrome Criptococcosis Toxoplasmosis MAC Herpes Zoster Pencilinosis Chronic diarrhea Candidiasis CMV retinitis Kaposi sarcoma 25% 5% 2% 13% -- 1% 3% 9% 4% -- 39% 14% 8% 3% 30% -- 39% -- 1% -- 2% 1% -- 4% -- 12% 9% -- 25% -- 13% -- 9% 13% -- 11% 14% -- 31% -- 29% <5% -- 20% -- <5% 10%

9. TB in AIDS Patients Spain (1994-2002) HAARTHAART 2329 29% 7378 42% No of cases

10. Notified TB and HIV co infection in Estonia (number of cases, proportion of all) Estonian TB register 2006 0,1% 0,3% 1% 2,6% 2,2% 3,9% 6,6% 1998 1999 2000 2001 2002 2003 2004 2005

11. Bacille Calmette Guerin (BCG) vaccine is the most widely used vaccination was developed in the 1930's and it remains the only vaccination available against tuberculosis today does not ensure against exposure to and development of tuberculoses disease, but offers significant protection against serious and widespread invasion the WHO recommends that asymptomatic HIV-infected infants receive BCG vaccine at birth or shortly thereafter

12. Infants may have acquired TB - by trans placental spread through the umbilical vein to the fetal liver - by aspiration or ingestion of infected amniotic fluid - via airborne inoculation from close contacts (family members or nursery personnel) About 50% of children born to mothers with active pulmonary TB develop the disease during first year of life if chemoprophylaxis or BCG vaccine is not given

13. Neonatal TB The clinical presentation nonspecific Multiple organ involvement Usually fever, lethargy, respiratory distress, hepatosplenomegaly, or failure to thrive may indicate TB in an infant with a history of TB exposure For diagnosis: culture and smear of tracheal aspirates, urine, gastric washings for acid-fast bacilli, chest x-ray (miliary infiltrates). Biopsy of the liver, lymph nodes, or lung and pleura may be needed. Skin test results may be negative

14. Pregnant women with active TB Duration of therapy- at least 6 mo, drug- resistant cases- to 18 mo Isoniazid (300 mg po), ethambutol (15 to 25 mg/kg po), and rifampin (600 mg po) in single daily doses- in recommended doses have not been shown to be teratogenic Streptomycin is potentially ototoxic The other antituberculous drugs should be avoided because of teratogenicity (ethionamide, fluoroquinolones) or lack of clinical experience during pregnancy

15. Asymptomatic infants of women with active TB (1) The infant usually should be separated from the mother until effective treatment is under way and her sputum become smear negative (usually 2 to 3 weeks) Family contacts should be investigated for undiagnosed TB All anti TB-drugs are compatible with breastfeeding The infant’s skin test negative  BCG vaccine  start on a regimen of INH (5mg/kg) and send home at usual time

16. Asymptomatic infants of women with active TB (2) Skin testing should be performed at ages 3 and 6 mo If the infant remains tuberculin negative, INH may be discontinued and the infant followed with skin tests at 12 mo with monthly or bimonthly clinical evaluations The infant has a positive skin test  exclude tuberculosis disease by a thorough examination INH should be continued for at least 6 mo HIV-infected children should be treated for 12 mo

17. Newborns with active TB (1) Treatment with INH (10 to 15 mg/kg po), rifampin (10 to 20 mg/kg po), pyrazinamide 820 to 40 mg/kg po), and streptomycin (20 to 40 mg/kg im) in single daily doses given for 2 mo, followed by INH and rifampin for another 10 mo. Drug-resistance- instead of streptomycin may be used kanamycin or capreomycin

18. Newborns with active TB (2) CNS is involved- the initial therapy should also include corticosteroids (prednisolone 1 mg/kg/day po for 6 to 8 wk, then gradually tapered), continue with INH and rifampin daily or twice weekly for another 10 mo. Not disseminated form, and CNS, bones and joints are not involved- 6-9 mo regimen