Tb and pregnancy

1. TB and PREGNANCY
Narendra Malhotra
Jaideep Malhotra
Global Rainbow Health Care,India
www.rianbowhospitals.org
Prerna Keshan,MB Bellad,Parag Biniwala

2. Charlotte Brontë (1816-1855)
novelist who died at 38 TB in PREGNNACY

3. INTRODUCTION
Tuberculosis (TB) and pregnancy are two
different types of stresses experienced by women.
Their simultaneous presence affects them both
physically and mentally. To the concerned physicians,
genital tuberculosis presents a diagnostic challenge
and management of the underlying disease in a
pregnant woman requires great care. Management
of such cases in the context of the Revised National
Tuberculosis Programme and the adoption of the
Directly Observed Treatment-Short Course (DOTS)
needs a strategy.

4. Incidence of TB in pregnancy
• In 2012 out of the estimated Global annual incidence of 8.6
million
• Not many studies have been done in this field. In one study
done in some ethnic groups in London it was found to be 1%.
• Tuberculosis cases 2.3 million were estimated to have
occurred in India.(India accounts for 30% of the burden of all
TB cases in the world.)
• 80% of the patients are in the economically productive age-
group of 15– 54 years.
• In Belgaum District of Karnataka during 2014 till October, 8
out of 3624 Tuberculosis patients a diagnosed are pregnant
women.
• Similar figures from UP/BIHAR/JHARKAND(may be more)
• In India Tuberculosis is a notifiable Disease

5. Introduction
• Tuberculosis continues to be a major health issue in a country like
India with a large population.
• Management of Tuberculosis in pregnancy continues to be one of
the challenges even to the experienced persons as pregnancy adds
many challenges for effective diagnosis and treatment because of
the altered situations .
• One third of the world population and approximately 50% of the
Indian adults are infected with Mycobacterium Tuberculosis .
• In India two deaths occur every three minutes due to Tuberculosis
- almost 1000 deaths/day
The disease is responsible for killing more
women of reproductive age than all the combined
causes of maternal mortality

6. TB is a major cause of mortality in
pregnancy
• •Johannesburg: 51% of deaths in HIV positive
pregnant women were attributable to TB.
• •TB was the third leading infectious cause of
maternal deaths in Durban at 14.0% and
Lusaka at 25% Botswana
Grange et al. Tuberculosis in association with HIV/AIDS emerges as a major non-obstetric cause
of maternal mortality in Sub-Saharan Africa. IntJ GynaecolObstet. 2010;108:181-183.
Black et al. Effect of HIV treatment on maternal mortality at a tertiary center in South Africa: a 5-
year audit. ObstetGynecol,. 2009; 114:292-299,
Khan et al. Maternal mortality associated with tuberculosis-HIV-1 co-infection in Durban, South
Africa. AIDS. 2001:14:1857-1863

7. Who is at risk of TB?
• Anyone can catch TB, but it is possible that pregnant
women have a slightly higher risk of TB.
• Some people are more at risk than others. These
include people who:
• • Have lived in the same household – or been in
prolonged contact –
• with someone with TB involving the lung/s
• • Have lived, worked or stayed for a long time in a
country with a high
• rate of TB
• • Are unable to fight off infection
(immunosuppressed) due to illness
• (such as HIV infection) or treatment (such as therapy
for cancer)
• • Are notably underweight
• • Are dependent on drugs and alcohol

8. What are the symptoms of TB during
pregnancy?
• The symptoms of tuberculosis in pregnant women
can be non-specific.
• Those that may suggest active
TB disease and require further assessment are:
• • Cough which persists for more than a few weeks
• • Persistent fever (a high temperature)
• • Heavy sweating at night
• • Loss of appetite
• • Unexplained weight loss
• • General & unusual sense of tiredness and feeling
unwell
• • Coughing up blood
• • Persistent swellings in the neck glands (or
sometimes other glands)

9. How might TB affect the mother and
her baby?
• Low birth weight
• Prematurity
• Congenital TB
• Increased neonatal and
maternal mortality
• Increased pregnancy
complications
• Abortion
• Post partum haemorrhage
• Pre-eclampsia

10. Consequences of TB in pregnancy
• Pregnant women with pulmonary TB who access
early appropriate TB treatment do not have an
increase in maternal or neonatal complications
Therefore it is important to:
• Prevent TB in pregnancy
• Diagnose and treat TB in pregnancy

11. Mother & new born
A neonate having congenital TB may
present with respiratory distress, fever, poor feeding,
lethargy, irritability, abdominal distention,
lymphadenopathy and hepato-splenomegaly
A fetus can get TB infection either by
haematogenous spread through
umbilical vein to fetal liver or by
ingestion or aspiration of infected
amniotic fluid.
True congenital TB is believed to be
rare.
The risk to neonate of getting TB
infection shortly after the birth is
greater

12. Can the mother infect the baby with
tuberculosis?
• A mother can infect her
newborn baby if she is
infectious; usually this
is only the case if she has a
cough and is not on treatment.
• It is very rare for the baby to
be born with active TB if their
mother has TB.
• Breastfeeding is encouraged
and TB drugs don’t harm the
neonate.

13. Diagnosis of TB in
pregnancy

14. Suspect
• Pregnant Woman with cough of ≥2 weeks duration
with or without other symptoms.
• Cough of any duration:
– If she is a contact of a sputum smear positive case in the
family.
– If she is having haemoptysis.
– If she is a suspected or confirmed extra pulmonary
Tuberculosis case.
– If she is also infected with HIV.
MBB

15. Diagnosis
• Two samples of sputum (one spot and one in
the early morning) are to be collected and
examined for Acid Fast Bacilli (AFB) with Zeil-
Neelson (ZN) stain
• Follow RNTCP* diagnostic algorithm
mentioned in the next slide
• Precaution: To cover the abdomen of the
pregnant woman with lead apron while taking
chest X-ray (if required)
*Revised National TB Control Program
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16. MBB
If cough persists after 10-14 days
If one or both +ve
Sputum smear +ve TB start ATT
X-ray suggestive of active TB
Smear –ve TB start ATT
If both samples –ve, treat with antibiotics for 10-14 days
2 more samples
If One or Both +ve
Refer For chest X-ray
X- Ray negative
No TB, refer for evaluation
Two Sputum Samples
If both -ve

17. Diagnosis dilema
• Under RNTCP, sputum examination done as per an algorithim is the preferred method for
diagnosis of pulmonary TB
• A chest skiagram (performed after shielding the abdomen) is done if all the 3 sputum
smears are negative and symptoms persist despite giving antibiotics for 1-2 weeks.
• The presence of suggestive radiographic abnormalities
• and a medical officer’s decision to treat with ATT labels the patient as a ‘smear-negative’ TB
case.
• A pregnant woman with extra-pulmonary TB has constitutional and organ-affection
symptoms.
• Routine haematology and Mantoux test ( not commonly
• advocated in programme) along with investigations specific for the site are carried out for
the
establishment of specific diagnosis.
• Co-existence of HIV infection should specially lead to a thorough search for any extra-
pulmonary tuberculous focus.
• A mediastinal or retro-peritoneal adenopathy, pleural effusion or parenchymal infiltrate
may be detectedin chest skiagram in late course of disease, whereas cavitary lesions could
exist in early HIV co-infection.

18. <5
>100
PCR
Culture
HPE
AFB Stain
Bacterial Load Method
>1000
The reason genital tuberculosis has such a poor prognosis is our
reliance on methods having low sensitivity

19. Sensitivity
Mantoux Test ? 50%
Laparoscopy 50%
AFB-Stain < 5%
HPE < 10%
Culture <30%
PCR > 80%

20. Diagnosis
• Diagnosis of extra
pulmonary Tuberculosis is
done by histopathology or
FNAC depending upon the
site involved.
• Loss of weight or no weight
gain corresponding to the
gestational age also is a
symptom for screening for
Tuberculosis in pregnancy.
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21. management

22. Categorization TB Cases
• Tuberculosis patients are categorized as per
RNTCP guidelines as category I (New cases) or
category II (Retreatment cases) depending
upon the history of previous Anti-tuberculosis
treatment received.
• Pregnant women with Tuberculosis who are
taking Anti-tuberculosis treatment for the first
time or who have taken Anti-tuberculosis
treatment for less than 1 month previously
are categorized as new cases
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23. Guideline
Treatment of tuberculosis in
pregnant women and newborn
infants

24. KET CRITICAL POINTS
• The decision to treat tuberculosis (TB) in pregnancy
must consider the potential risks to mother and fetus
from medication, and the benefits to mother, foetus
and the community. The benefits of treating TB in
pregnancy are widely considered to outweigh any risk
of treatment.
• Although small concentrations of anti-TB drugs are
excreted in breast milk, treatment for TB is generally
not considered a contra-indication to breastfeeding,
and is not associated with toxicity to the baby.

25. First-line treatment
• This guideline endorses the recommendation
of the use of standard first-line drug regimens
in pregnant women with TB. Isoniazid,
rifampicin, pyrazinamide and ethambutol are
not contra-indicated in pregnancy, but
treatment during pregnancy requires close
clinical follow-up, with the monitoring of at
least monthly liver function tests due to the
higher risk of hepatotoxicity.

26. International guidelines
• The International Union Against Tuberculosis and
Lung Disease (www.theunion.org) and the World
Health Organization (www.who.int) support the
use of standard first-line drug regimens in
pregnant women with TB.
• The CDC (www.cdc.gov) does not specifically
endorse the use of pyrazinamide in pregnancy,
citing the absence of detailed teratogenicity data,
but states that it can ‘probably be used safely’
during pregnancy. An alternative 9(E)HR regimen
is endorsed by the CDC.

27. treatment
• ATT should be started promptly as untreated disease
presents a hazard to the mother and foetus.
• The same regimens are recommended for use in
pregnancy as for the non-pregnant state except for
witholding of Streptomycin.
• Doubts about the use of Pyrazinamide in pregnancy
have
since been set as rest.
• Currently, an intermittent regimen (thrice weekly on
alternate days) under the DOTS strategy of RNTCP
is being increasingly used world-wide for the pregnant
women having TB.

28. Case of tb in pregnancy
Minimal streaky infiltrate RUL
Sputum was smear positive - rare
Regimen: Isoniazid, Rifampin, Ethambutol and
B6
Pyrazinamide deleted due to pregnancy

29. Treatment of drug-sensitive TB during
pregnancy
• •WHO and International Union against
Tuberculosis and Lung Disease support the use
of the standard regimen in pregnant women:
• –rifampicin, isoniazid for six months and
ethambutol and pyrazinamide for the first two
months (“rifafour”)

30. Isoniazid
• •Pyridoxine (vitamin B6) should be used during
pregnancy
• •Safe in pregnancy: no excess of birth defects
have been noted in the babies of pregnant
mothers taking rifampicin
• •Safe in breastfeeding
• •Hepatitis: some studies suggest higher
incidence of drug-induced hepatitis during
pregnancy
• •Isoniazid is considered safe as preventative
therapy in the form of IPT

31. Rifampicin
• •Cytochrome P450 induction can result in
clearance of contraceptive hormones and
unplanned pregnancy
• •Safe in pregnancy: no excess of birth defects
have been noted in the babies of pregnant
mothers taking rifampicin
• •Safe in breastfeeding

32. Ethambutol
• •Safe in pregnancy: no excess of birth defects
have been noted in the babies of pregnant
mothers taking rifampicin.
• •Safe in breastfeeding

33. Pyrazinamide
• •No studies of safety in pregnancy:
• –Extensive clinical experiencesupporting it’s
safety
• –WHO recommends the routine use of PZA in
pregnancy

34. Treatment
• Category I-Needs DOTS regimen
(Directly Observed Treatment and short course)
2H3R3Z3E3 / 4H3R3
Where numbers 2 and 4 are the months of
treatment and prefex 3 denotes the number of the
doses in a week.
H-INH (Isoniazid) R- Refampicin, Z- pyrazinamide,
E- Ethambutol S- Streptomycin.
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35. Treatment
• For first two months (intensive phase) four antibiotic are given.
They are ----
• Rifampicin 450 mg
• INH 600 mg
• Pyrazinamide 1500 mg
• Ethambutal 1200 mg
• If the weight of the patient at the time of initiation of the
treatment is 60 kg or more, or increases to 60 kg or more, during
the course of the treatment an additional dose of Rifampicin of
150 mg is to be added.
• The Doses are given on three days in a week; (on Monday,
Wednesday, Friday or Tuesday, Thursday, Saturday as the DOT*
days.)
*Directly Observed Treatment
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36. Side/adverse effects of ATT drugs
• Rifampicin: Red/orange coloured urine and tears, nausea,
vomiting, Jaundice
• INH: Burning in the hands and feet, nausea, vomiting,
jaundice, pruritis ( Peripheral neuritis)
• Ethambutal: Retrobulbar neuritis may occur.
• Pyrazinamide: May produce G. I upset, arthralgia,
Hypperuraecimia and hepatitis.
• Streptomycin: may cause vertigo, ototoxiaty and
nephrotoxicity (Contraindicated in Pregnancy)
Note:In all cases of jaundice anti Tuberculosis drugs should be
stopped immediately and the patients should be referred for
evaluation.
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37. Treatment
• The treatment is domiciliary based where, the doses are
given at the DOT centre by a DOT provider who keeps the
drug box reserved for the patient.
• The serious patients are admitted in the hospital till they
are recovered and become fit to take treatment in the
home.
• During the intensive Phase all the 3 doses in a week are
directly observed by the DOT provider,
• Whereas in the continuation phase first dose of the
weekly doses is directly observed and the remaining 2
doses are given to the patient for consumption in her
house.
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38. Treatment- regimen for cat II patients
2H3R3Z3E3S3 / 1 H3R3Z3E3/ 5H3R3 E3 :
• Category II patients (retreatment cases who have taken
Anti-tuberculosis treatment earlier for at least 1 month)
the pregnant woman with tuberculosis is treated with
the same regimen of RNTCP as for the non-pregnant
woman with Tuberculosis,
(except that Injection streptomycin is withheld till the
woman delivers)
• The intensive phase treatment is of 3 months duration
and the continuation phase is of 5 months.
In the intensive phase of 3 months streptomycin is given for the
first two months only( non-pregnant).
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39. Please note
• The intensive phase of treatment in both cat I and cat II patients
can be extended for one more month if the follow up sputum
after intensive phase is positive for AFB.
• While treating Tuberculous meningitis (TBM), streptomycin is to
be used in place of ethambutol after delivery in new cases during
the intensive phase (H3R3Z3S3 instead of H3R3Z3E3).
• The continuation phase of treatment for patients with
Tuberculosis meningitis or spinal Tuberculosis is for 7 months -
total duration of treatment will be of 9 months.
• Steroids as adjunctive therapy may be useful in patients with
Tuberculosis pericarditis and meningeal Tuberculosis, with an
initial high dose tapered down gradually over 6 - 8 weeks.

40. Also Note
• The patient is regularly followed up by the treating doctor
– In pulmonary - follow up sputum smear examinations are
done regularly
– Extra Pulmonary - assessed by regular clinical examination.
• A woman under Anti Tuberculosis treatment can breast feed her
infant taking the precaution of cough hygiene i.e she should
cover her mouth and nose with a cloth while breast feeding.
Practitioners who undertake to treat a patient with tuberculosis
must not only prescribe standard regimen but also have the means
to assess adherence to regimen and address poor adherence in
order to ensure that treatment is completed.

41. TB,HIV and Pregnanacy
• HIV and Tuberculosis are inextricably linked.
• Their effect is even more deadly in pregnancy; when they may
contribute significantly to maternal morbidity and mortality.
• Over 50% of maternal mortality occurring in mothers with
Tuberculosis in pregnancy is due to co-infection with HIV
• The treatment is also complicated by the challenges of
adherence, polypharmacy and overlapping side effects of anti-
Tuberculosis and Anti-Retroviral Treatment (ART) drugs.
Follow NACO guidelines 2013
(NATIONAL AIDS CONTROL ORGANISATION)

42. TB,HIV and Pregnanacy
• Effavirenz is contraindicated before the 13th week of gestational
age
• While the risk of toxicity due to the use of didanozine and
stavudine is significantly increased in pregnancy.
• Rifampicin may cause a reduction in the serum concentration of
effavirenz. Neverepin which is alternative to the use of effavirenz
also exhibits some drug interaction with rifampicin.
• Rifampicin may lead to the reduction of serum concentration of
neverepin by as much as 50%.
• To circumvent this problem rifabutin another rifampicin that is as
effective as rifampicin may be used.

43. TB,HIV and Pregnanacy
• The pregnant women with Tuberculosis and HIV should receive
Tuberculosis treatment as per RNTCP regimen along with ART
• ART should be initiated as soon as possible within 8 weeks of
initiation of Tuberculosis treatment irrespective of their CD4 cell
count.
• The drugs used in ART for pregnant women are Tenofovir (TDF),
Lamivudile (3TC) single pill (300 Mg + 300 Mg) and Effavirenz
(600 Mg) per day. The treatment is lifelong.
• For HIV exposed infant Neverepin 25ml (10 mg per ml), 3 bottles
per child up to 6 weeks should be given and may be extended to
12 weeks if the mother has received ART later than 24 weeks of
gestational age.

44. Multi Drug Resistant Tuberculosis
• Definition: Multi Drug Resistant (MDR) TB :
defined as resistance to isoniazid and rifampicin
with or without resistance to other anti-tuberculosis
drugs.
• Extensively Drug Resistant (XDR) TB: defined as
resistance to isoniazid and rifampicin ( i.e MDR
Tuberculosis) + resistance to any of the
fluoroquinolones and any one of the second line
injectable drugs (Amikacin, Kanamycin or
Capreomycin)
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45. MDR TB into 3 categories:A,B&C
Criteria-A
 All treatment failures of new Tuberculosis cases .
 Smear positive previously treated cases who remain smear positive at 4th
month of treatment.
 All pulmonary Tuberculosis cases who are contacts of known MDR
Tuberculosis case.
Criteria-B, in addition to criteria A;
 All smear positive previously treated pulmonary Tuberculosis cases at
diagnosis.
 Any smear positive follow up result in new or previously treated cases.
Criteria-c, in addition to criteria B;
 All smear Negative previously treated pulmonary Tuberculosis cases at diagnosis.
 HIV Tuberculosis co-infected cases at diagnosis.
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46. Options for treatment of DR-TB
during pregnancy
Need to consider risks and benefits for the
mother and fetus.
• –Option 1: Stop or delay MDR-TB treatment
• –Option 2: Terminate the pregnancy
• –Option 3: Continue treatment while pregnant

47. Show of hands
• Option 1: Stop or delay MDR-TB
treatment
• Option 2: Terminate the
pregnancy
• Option 3: Continue treatment
while pregnant

48. Recommendations
• •Provide individualized care based on risks
and benefits to the patient and foetus
• •The patient should be involved in therapeutic
decisions
• •Pregnancy should not be terminated because
of DR-TB infection

49. MDR- TB
• The treatment of MDR Tuberculosis in India has
been started from 2009 there is limited experience
in treating pregnant women with MDR
Tuberculosis.
• During 2013 in India 23289 MDR cases were
diagnosed. The death rate among MDR Tuberculosis
is around 20% as compared to drug sensitive
Tuberculosis which is around 5%.
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50. MDR- TB
• All women of child bearing age who are receiving
MDR Tuberculosis therapy should be advised to use
birth control measures because of potential risk to
both mother and the fetus.
• Use of barrier methods, Intra Uterine Device, or
DMPA (Depot Medroxy progesterone Acetate) are
recommended
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51. Basic RNTCP regimen for MDR TB
• 6(9) Km Lvx Eto CS Z E /18 Lvx Eto CS E [Reserve /
substitute drugs: PAS, Mfx, Cm]
(Km – Kanamycin, Lvx- Levofloxacin, Eto- Ethionamide, Cs
– Cycloserine, Z- Pyrazinamide, E- Ethambutol, PAS- Para
amino salicylic acid, Mfx –Moxifloxacin, Cm-
Capreomycin)
The figures denote the number of months of treatment
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52. Special adjustments to the standard MDR TB Regimen
• In case of intolerance to Kanamycin substitute with
capreomycin or PAS.
• In case of intolerance to any oral drugs PAS is the substitute.
• Baseline Levofloxacin and Kanamycin resistance (i.e XDR
Tuberculosis) should lead to referral for diagnosis of XDR
Tuberculosis.
• All drugs should be given as single daily doses under directly
observed treatment (DOT)
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53. Management of MDR TB during Pregnancy
• The gestational age (GA).
• If GA is <20 weeks, the women is advised MTP,
• For not willing for MTP or if GA is >20 weeks the risk to the mother and the
Fetus needs to be explained before starting the treatment.
• For patients with GA <12 weeks, Km and Ethionamide are omitted & PAS is
added.
• For patients with GA >12 weeks, Km is replaced with PAS, and after delivery,
PAS may be replaced with Km and continued until the end of Intensive
phase.
• Duration of treatment: At least 6 months of intensive phase treatment (IP)
may be extended up to 9 months in patients who have a positive culture
result at 4th month of treatment.
• Minimum 18 months of continuation phase treatment (CP) should be given
following IP.
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54. Regimen for XDR Tuberculosis
• Intensive phase IP: (6 – 12 months) consists of 7 drugs-
Capreomycin, PAS, Moxifloxacin, High dose INH,
Clofazimine, Linezolid and Amoxyclav.
• Continuation phase CP: (18 months) Consist of 6 drugs -
PAS, Moxifloxacin, High dose INH, Clofazimine,
Linezolid and Amoxyclav.
• Duration of treatment: 24- 30 months, with 6-12
months of IP and 18months of CP.
• RNTCP has a policy against empirical treatment of
MDR/XDR Tuberculosis without microbiological
confirmation from an RNTCP certified laboratory.
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55. Recommendations
• •There is limited evidence, but clinical experience
has shown that terizidone, moxifloxacin, and PAS
may be used safely in pregnant patients
• •During the first 20 weeks of pregnancy, avoid
the injectable if possible.
• –Exception: if the risk of mortality is high, an
injectable agent should be used.
• –Which injectable: Capreomycin or Kanamycin?
• •Ethionamide: Not enough data to confirm the
safety or risk

56. Conclusion MDR / XDR
• •The best way to deal with DR-TB and pregnancy
is to prevent it.
• •DR-TB treatment programs must provide
integrated contraceptive services
• –Depo-Provera can be provided at 3 month
intervals during clinic visits
• •Pregnancies should not be terminated because
of DR-TB
• •We need more data! Especially in the
management of HIV and DR-TB co-infection

57. Adverse effect of ATT on Fetus
• First line anti-tuberculosis drugs except
streptomycin are safe.
• Streptomycin and Kanamycin may produce
congenital deafness in the fetus.
• Ethionamide and PAS may cause various types of
congenital defects.
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58. Side effects of second line ATT drugs
• Ethionamide and PAS may cause G.I. disturbances.
• Kanamycin may cause nephrotoxicity.
• Use of Cycloserine may induce suicidal tendency,
psychosis and increase in the number of seizures.
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59. Warning
• It is well known that poor treatment practices breed drug
resistance.
• Good treatment is a pre-requisite to the prevention of
emergence of MDR Tuberculosis.
• Implementation of a good quality DOTS programme is the
first priority for Tuberculosis control.
• And prevention of emergence of MDR Tuberculosis in the
community is more imperative rather than its treatment.
• Each MDR case costs more than 20 times the cost of a drug
susceptible Tuberculosis case.
• Therefore basic Tuberculosis diagnostic and treatment
services should be prioritized implemented and adhered
strictly.
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60. Summary
• Diagnosis and treatment of Tuberculosis during pregnancy is
a real challenge.
• Pregnancy is not a contraindication for treatment of
tuberculosis.
• Good quality treatment is a prerequisite to the prevention of
emergence of drug resistance.
• Treatment must be adhered/ensured.
• Special precautions are essential in extra pulmonary,
recurrent and other types of Tuberculosis (MDR and XDR).
• Co-morbid conditions (like HIV) really affect the success of
treatment.
• Proper counselling, supervision and reassurance play a key
role in the success of the treatment.
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61. Conclusion
• In spite of the side effects mentioned above
the pregnant women tolerate the primary
anti Tuberculosis drugs reasonably well.
• And drugs (except streptomycin) under
RNTCP DOTS can be safely given to pregnant
women with tuberculosis
• Proper Counseling, reassurrance, supervision
are key to the successful treatment
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62. LET’S FIGHT T.B. TOGETHER
AND SAVE MOTHERS FROM DIEING
24TH MARCH WORLD T.B. DAY
Thank you for giving me this oppurtunity