Tuberculosis and pregnancy

Tuberculosis and Pregnancy :Changes & Challenges in Management by
Dr. Md. Khairul Hassan Jessy
Associate Professor
Respiratory Medicine,NIDCH

1. Tuberculosis and Pregnancy : Changes & Challenges in Management Dr. Md. Khairul Hassan Jessy Associate Professor Respiratory Medicine,NIDCH

2. Outline of Presentation Facts in relation to tuberculosis and the changes made over time The impact of pregnancy on TB and TB on pregnancy Screening and diagnosis Treatment Congenital / neonatal TB Key messages

3. Introduction TB is an ancient disease and pathological evidence was found in Egyptian mummies It is the 2 nd leading cause of death from an infectious disease

4. Introduction Charles Dickens ( 1812 – 1870 ) labeled TB as “ the disease which medicine never cured ”

5. Introduction Still today physicians are constantly being challenged by the same disease in different forms Many changes have been made & many changes are likely to come

6. Introduction It is one of the leading non-obstetric causes of maternal mortality The number of pregnant women with TB is increasing along with resurgence of TB In March 1993 WHO declared TB a global public health emergency

7. Historical Perspective Hippocratic view : Pregnancy had a beneficial effect on TB. This view persisted up to the early part of the 19 th century.

8. Historical Perspective As late as the 1835 : Ramadge , a German physician, believed – the enlarging uterus helps to collapse the open cavities and improve the clinical condition. & he recommended marriage and pregnancy in unmarried women with TB.

9. Historical Perspective In about the mid 19 th century : Grissole concluded that – TB was harmful during pregnancy and termination was recommended. The view persisted up to the 1 st half of the 20 th century.

10. Historical Perspective In 1953, the view changed showing no apparent relationship except higher risk of activation during puerperium and 1 st postpartum year.

11. Impact of Pregnancy on TB The pendulum swung from one extreme to the other and now has taken an intermediate position

12. Impact of Pregnancy on TB CURRENT OPINION IS Pregnancy does not predispose to the progression of TB

13. Impact of Pregnancy on TB Untreated TB is associated with higher risk of - abortion - IUGR - LBW babies - prematurity - congenital TB - neonatal TB

14. WHO Report 2014 – Global Picture In 2014, an estimated 3.2 million women fell ill with TB TB is one of the top five killers of women among adult women aged 20–59 years. 480 000 women died from TB in 2014, including 140 000 deaths among women who were HIV-positive. Of the 330,000 HIV-related TB deaths among adults (age ≥15) globally in 2014, just over 40% were among women, accounting for about a third of all AIDS-related deaths among female adults. Almost 90% of these HIV-associated TB deaths among women were in Africa.

15. Millennium Development Goal (MDG) In September 2000, at the United Nations millennium summit, Heads of States of 189 countries adopted a declaration The declaration was translated into 8 Goals (MDG) to be achieved by 2015 There were 8 goals, 18 targets and 48 indicators MDG 6 is linked to TB Bangladesh Govt. is committed to reduce the prevalence and mortality from TB along with others

16. Millennium Development Goal (MDG) Combat HIV/AIDS, malaria and other diseases Target 6.c Halt and begin to reverse the incidence of TB by 2015 Indicator 6.9 Incidence, prevalence and death rates associated with TB Indicator 6.10 Proportion of TB cases detected and cured under DOTS

17. Presentation The presentation of TB in pregnancy is similar to that in non pregnant women Diagnosis is often delayed in pregnancy due to non specific nature of early symptoms A high index of clinical suspicion is often needed

18. Presentation… Common symptoms are Cough Weight loss Fever Malaise Fatigue

19. Screening Routine screening – important in HIV prevalent setting Screening is indicated in women who are HIV positive immuno -compromised having symptoms of TB recently exposed to active TB immigrants from high prevalent countries

20. Screening… Recommended tests: Sputum microscopy TST/MT Chest radiograph if MT positive Interferon gamma release assays ( IGRAs ) ~ quantiferon gold TB Gold In Tube test/ T- spot. TB test

21. Screening… Mantoux Test/Tuberculin Test

22. Screening… CHEST RADIOGRAPH Routine screening with X-ray chest is not indicated If possible, X – ray chest should be avoided in first trimester If indicated strongly it should be done with proper abdominal shielding Last test to be done in pregnancy

23. Screening… Sputum Microscopy ( AFB )

24. Evidence Based Medicine EBM can be defined as systematic, scientific and explicit use of current best evidence in making decisions about the care of individual patients. EBM is graded as – Grade A : Based on RCT, meta-analysis or systematic review Grade B : Based on well designed cohort/case control studies Grade C : Based on uncontrolled studies/expert opinion

25. Pregnancy Category of Drugs Category A : Controlled studies show no risk ( large sample size ) Category B : No evidence of risk in humans ( limited sample size ) B 1 : No evidence of risk in animals B 2 : Inadequate information regarding risk in animals B 3 : Evidence of fetal damage in animal studies ( uncertain in humans) Category C : May cause reversible harmful effects on foetus / neonate no risk of malformations Category D : Risk of malformation or reversible damage Category X : Contraindicated, as there is high risk of Damage

26. Treatment TB in pregnancy should be treated as for non pregnant patients regardless of gestational age. If possible Fetotoxic drugs should be avoided in pregnancy The safety of the first line drugs has been established except streptomycin. Experience with 2 nd line drugs in pregnancy is limited.

27. Treatment WHO recommends Treatment of Active TB (new cases) 2HRZE/4HR Ethambutal (E), Isoniazid (H), Rifampicin (R) and Pyrazinamide (Z) for 2 months (intensive phase) followed by INH & RMP for 4 months (continuation phase)

28. Treatment Initial Phase 2m Continuation Phase 7 m INH INH Rifampicin Rifampicin Ethambutal If pyrazinamide is not used the regimen will be 2HRE / 7HR

29. Treatment SPECIAL CONSIDERATIONS Streptomycin (S) Streptomycin is hazardous throughout pregnancy ( independent of critical period of organogenesis) 1 in 6 foetuses can develop ototoxicity

30. Treatment PZA WHO recommends the use of PZA in pregnancy Extensive clinical trials have proved that it is safe in pregnancy

31. Treatment Rifampicin As there is risk of hypo- prothrombinaemia , Vit K should be given to both mother and infant postpartum

32. Treatment INH Increased risk of hepatotoxicity in pregnancy . So, periodic evaluation of LFT is recommended. Pyridoxine supplementation is recommended for all pregnant women taking INH.

33. MDR-TB

34. XDR-TB

35. Pregnancy and MDR-TB Treatment of gestational MDR-TB is controversial Routine termination of pregnancy is not recommended by many An approved treatment regimen does not exist Insignificant studies regarding the safety of 2 nd line drugs - an important contributory factor

36. Pregnancy and MDR-TB.. There are some case studies / cohort studies showing successful outcomes with aggressive treatment of gestational MDR-TB patient ( Studies with larger sample size are needed )

37. Pregnancy and MDR-TB.. MODERN OPINION: Aggressive treatment should be initiated without delay to prevent ~ congenital / neonatal TB ~ adverse pregnancy outcome ~ maternal progression of disease

38. Pregnancy and MDR-TB.. Severity of the disease & maturity of the foetus Important determining factors in managing a pregnant women with MDR-TB

39. Pregnancy and MDR-TB.. There are some case studies / cohort studies showing successful outcomes with aggressive treatment of gestational MDR-TB patient ( Studies with larger sample size are needed )

40. Pregnancy and MDR-TB.. In Clinically Stable Patients Therapy may be delayed until the second trimester Aminoglycosides and ethionamide should be avoided in pregnancy Capreomycin may be used if an injectable is unavoidable

41. Pregnancy and MDR-TB.. In Advanced Disease Despite teratogenic potential aggressive treatment should be continued with effective drugs Risks should be fully discussed Option should be given whether to continue/terminate the pregnancy

42. Pregnancy and MDR-TB.. Potential Risk of Anti MDR-TB Drugs Intra uterine exposure to Aminoglycosides - ototoxicity Ethionamide - CNS defect Fluoroquinolones - cartilage defects

43. Review of Literature 3 Studies in Lima Peru & 1 case report in Iran show/reveal immediate and no long term or late presentation toxicities associated with in – utero exposure to second line drugs

44. Reference Number 1: Shin S, Guerra D, Rich M, Seung KJ, Mukherjee J, Joseph K, et al. Treatment of multidrug-resistant tuberculosis during pregnancy: a report of 7 cases. Clin Infect Dis 2003;36:996–1003.. 7 pregnant women with advanced MDR-TB disease were treated with 2 nd line agents ( Ethionamide , Prothionamide , Co- Amoxiclav Capreomycin , Kanamycin ) . All of them carried their pregnancies successfully to term & delivered healthy babies. 6 out of 7 babies were evaluated postnataly .

45. Reference Number 2: Drobac PC, del Castillo H, Sweetland A, Anca G, Joseph JK, Furin J, et al. Treatment of multidrug-resistant tuberculosis during pregnancy: long-term follow-up of 6 children with intrauterine exposure to second-line agents. Clin Infect Dis 2005;40:1689–92. Long term ( 15m-6.5 yrs ) follow up of 6 children having intrauterine exposure to 2 nd line agents revealed no congenital / neonatal TB and no neurological / developmental defect except mild ototoxicity in one ( exposed to Capreomycin in 1 st trimester)

46. Contd.. In the 1 st trimester 2 babies were exposed to Capreomycin 4 “ “ “ “ Cycloserine 4 “ “ “ “ Amoxi – CA 2 “ “ “ “ Ethionamide 1 “ baby “ “ Prothionamide 1 “ “ “ “ KM 1 baby was exposed to Streptomycin in 2 nd trimester

47. Reference Number 3: Palacios E, Dallman R, Munoz M, Hurtado R, Chalco K, Guerra D, et al. Drug-resistant tuberculosis and pregnancy: treatment outcomes of 38 cases in Lima, Peru. Clin Infect Dis 2009;48:1413–9. 38 patients were treated during pregnancy with 2 nd line TB drugs 61% of patients were cured, 13 % had died, 5% remained in treatment and 5% experienced treatment failure 5 of the pregnancies terminated in abortion, 1 baby was stillborn, 3 babies were born with LBW, 1 was premature and 1 had foetal distress

48. Reference Number 4: Tabarsi P, Baghaei P, Mirsaedi M et al. Multidrug Resistant TB in Pregnancy: Need for more intensive treatment. Infection 2007 ; 35: 477-478 An 18 year old Afgan lady (Cat I and II failure) was on Ofloxacin , Amikacin , Clofazimin , Pyrazinamide , INH & B6 became pregnant Co- Amoxiclave , Prothionamide was given in the 2 nd trimester. She was given the option to terminate the pregnancy, but she desired to continue She delivered a term healthy baby vaginally & the baby was followed up for 18m having no complications

49. Pregnancy with TB/HIV Co-Infection WHO recommends TB treatment should be initiated first, followed by ART as soon as possible in the first 8 weeks of starting treatment (irrespective of CD 4 count)

50. Pregnancy with TB/HIV Co-Infection.. Treatment Early initiation may result in adverse side effects like Immune reconstitution inflammatory syndrome ( IRIS ) Efavirenz (EFV) containing regimens should be avoided in first trimester of pregnancy Rifabutin is preferred to Rifampicin when ART is used ( to avoid drug interaction )

51. Contraception A non hormonal method of contraception is recommended for patients taking Rifampicin containing regimen OCP with higher dose oestrogen (50 micrograms) may be given e.g. LYNES, MAYA Low dose pill

52. Latent Tuberculosis Infection (LTBI) Diagnosed by - MT or Interferon gamma release assays ( IGRAs ) Indications of treatment recent convertors recent exposure to infected TB immunocompromised women(e.g. HIV + ve ) Managed by - 6 - 9 months of INH therapy with pyridoxine

53. Baby Management

54. Congenital TB Very rare Occurs when the foetus is infected via Umbilical vein or by aspiration / ingestion of infected amniotic fluid For diagnosis – Cantwell’s criteria is followed

55. Congenital TB.. Clinical Presentation Symptoms and signs begin within 2 nd and 3 rd week Symptoms are often non specific Hepato-splenomegaly , respiratory distress, fever & lymphadenopathy – common Abdominal distension, irritability & lethargy – may be present

56. Congenital TB.. Diagnosis From clinical suspicion Demonstration of AFB in tissue / fluids Chest radiograph Histopathology of placenta if possible

57. Congenital TB.. Once diagnosed baby should be treated by 6 m course ( 2 HRZE/4 HR ) as in adult But the dose should be strictly weight based INH (10-15 mg/kg/day) Rifampicin (10-20mg/kg/day) Pyrazinamide (15-30 kg/day) Ethambutal (15-25 mg/kg/day) for the first 2 months followed by INH and Rifampicin for 4 months 6m. Course have shown good results

58. Baby Management… Mother with open TB can continue breast feeding But INH prophylaxis (5mg/kg) with Pyridoxine should be given to the baby

59. Baby Management… After 6 weeks – TST should be performed If negative - BCG vaccine given - Chemoprophylaxis stopped If positive - Active TB in the baby should be excluded - INH prophylaxis continued for 6 months

60. Breast Feeding Breast feeding is encouraged in most cases Contraindications are - Mother with tuberculous mastitis - Maternal non-compliance with treatment - MDR-TB with prolonged infectivity

61. Summary of Changes The name changes from consumption, through pthisis , the white plague, wasting disease to TB over time. New diagnosis tests are developing e.g. PCR, IGRAs

62. Summary of Changes.. Regarding treatment - Rifampicin - recommended throughout therapy -Use of DST/DOTs – intensified -Category I to IV – no longer used -PZA – more extensively used. -ART - recommended within 8 weeks of Anti-TB treatment irrespective of CD4 count.

63. Key messages

64. Key Messages Breast feeding is encouraged in most cases BCG vaccination is contraindicated in pregnancy & HIV positive children

65. Key Messages.. First line Anti-TB drugs are safe except streptomycin More research is needed with Second line drugs Routine therapeutic termination – not recommended (even in MDR-TB cases)

66. Conclusion With proper medical management a happy conclusion is expected in most cases.

67. Thank You