Dip Obs

1. TUBERCULOSIS (TB) IN
PREGNANCY
Themba Hospital DipObs Tutorials
By Dr N.E Manana

2. Intro
• Non-pregnancy related infections remain the most common cause of maternal mortality in South
Africa.
• TB is the single most common cause. The national consolidated guidelines strongly emphasise that
screening for TB is an essential component of antenatal care.
• Deaths from TB also occur in HIV negative women.
• All pregnant and lactating women should be screened for TB at every contact session during antenatal
care, at delivery, and during the breastfeeding period.
• Early detection and prompt initiation of TB treatment are essential.
• All HIV positive pregnant women who are acutely or chronically unwell need investigating for TB.
• New evidence has shown that TB symptom screening may have lower sensitivity in pregnant women
and any client newly diagnosed with HIV.
For this reason, a TB GXP should be done for the following women, regardless of TB symptoms:
• Any pregnant women with a new HIV diagnosis
• Any known positive women (whether on ART or not on ART) with a new pregnancy diagnosis
• TB screening at all subsequent contact sessions should be done using the TB symptom screen, with
subsequent investigation with TB GXP only if the symptom screen is positive

3. Symptom screening for TB
At all antenatal visits and other contacts with maternity services – ask the
following:
• Cough of any duration
• Fever
• Night sweats
• Loss of weight, or not gaining weight in pregnancy

4. TB GeneXpert
Indicated for:
• Any pregnant women with a new HIV diagnosis regardless of symptoms
• Any known positive women (whether on ART or not on ART) with a new pregnancy diagnosis,
regardless of symptoms
• Investigation of TB at subsequent contact sessions, if a woman has TB symptoms
• Collect two sputum samples (ask the patient to cough outside), and send to the laboratory for
GeneXpert and microscopy and culture, as per National TB guidelines
• Sputum collection should happen at the antenatal clinic
• Ensure the patient has a follow-up appointment for the results
If TB GXP and symptom screen are negative:
• HIV positive pregnant women are eligible for TB Preventative Therapy (TPT) if her CD4 cell count is <
350 c/uL (see below).
• HIV positive breastfeeding women are eligible for TPT regardless of her CD4 cell count
• If the sputum sample shows drug-sensitive TB, Start TB treatment as per national guidelines.
• All oral TB drugs are safe to use in pregnancy

5. TB GeneXpert
If the sputum sample shows rifampicin-resistant TB:
• Drug-resistant TB should be confirmed by culture and sensitivity
• Ensure that INH sensitivity and second-line sensitivities are requested
• Discuss with local infectious diseases (ID) specialists or senior doctors at local TB hospital for advice on
Regimen
• Drug-resistant TB has a high mortality, particularly without an aminoglycoside as part of the regimen.
• For this reason, ID specialists would generally recommend that an aminoglycoside should be included as part of
the regimen in pregnancy despite any potential risk to the foetus.
If the sputum sample is negative and there are ongoing symptoms of TB
• HIV positive patients with TB and low CD4 counts more frequently have negative sputum smears, may have normal
CXR, and more often have disseminated TB.
• Remember that a negative TB GXP test in the presence of TB symptoms does not exclude
Extra-pulmonary TB must be excluded.
• Refer promptly to an HIV/TB experienced doctor for inpatient or outpatient investigation which should include a
chest x-ray, a 2nd sputum for culture/line probe assay (LPA), antibiotics as per National TB Guidelines, and any
other investigations as indicated. If CD4 <100, do a urine LAM.
• Empiric TB treatment may be necessary

6. TB and ART Initiation
• In the absence of any abnormalities on history taking or clinical examination, or in the presence of mild
TB symptoms in an otherwise well woman, ART can be initiated before the GXP results become
available.
• If a woman is unwell with TB or other symptoms, discuss with a doctor or refer for further assessment
as a matter of urgency.
• If TB is suspected, do not start ART until TB is excluded/diagnosed, as these women may be at a higher
risk of developing IRIS.
• Do not start AZT monotherapy in situations where triple therapy ART is contra-indicated. AZT
monotherapy has been associated with a risk of IRIS and does therefore not give any benefits over
starting triple therapy A
• If TB is diagnosed, first initiate TB treatment. Review in 2 weeks. If stable and tolerating TB treatment,
initiate ART. If TB meningitis is diagnosed, defer ART for 4 to 6 weeks.
• Remember that DTG requires boosting with TB treatment to 50 mg twice daily.
• Women taking lopinavir/ritonavir (Aluvia®) based ART need to double the dose if they are taking
rifampicin: increase to four tablets twice a day.
• If TB symptoms worsen after ART initiation, consider TB IRIS and refer/discuss with an expert or the HIV
hotline (0800 212 506).

7. TPT for pregnant and breastfeeding women
• TB Preventive Therapy (TPT) was previously known as Isoniazid (INH) Preventive Therapy (IPT). TPT has been
shown to reduce the incidence of TB in all people living with HIV, including those on ART and pregnant women.
• However, the TB APRISE study, a randomised controlled trial, showed adverse pregnancy outcomes for women
who received INH during pregnancy.
• To balance the risk of TB for the mother and the impact of INH on the outcomes for the infant, TPT should only be
given to pregnant women who have a CD4 ≤ 350 cells/mm3. TPT should be deferred until six weeks post-delivery
for all women with a CD4 > 350 cells/mm3.
• Breastfeeding mothers can receive TPT regardless of CD4 cell count.
Who is NOT eligible for TPT:
• Pregnant women with CD4 < 350 cells/mm3
• People with confirmed or unconfirmed active TB
• Active liver disease, acute or chronic
• Excessive alcohol use, more than 21 units/week for women
• People who have completed treatment for MDR or XDR TB
• History of adverse reaction to isoniazid

8. TPT for pregnant and breastfeeding women
TPT regimen:
• Isoniazid 5mg/kg daily to a maximum of 300mg daily
• Pyridoxine 25mg daily
Duration of treatment:
• TPT should be given for 12 months
• No tuberculin skin test is required before initiating TPT
Symptom screening for TB should continue at all visits to maternity services:
• If symptom screen is positive, discontinue TPT and send sputum samples for TB GXP and LPA.
Adverse effects of isoniazid:
• Discontinue TPT and refer if any of the following occur: drug-induced liver injury: symptoms
are jaundice, right upper quadrant pain or tenderness, nausea and vomiting
• skin rash, peripheral neuropathy (numbness and/or tingling of the feet)

10. Management of infants born to mothers with
TB
• If the mother has active TB, the infant should be screened for congenital
TB.
• The outcome of the screening process will determine if the infant should
receive isoniazid prophylaxis (TPT) or TB treatment.
• BCG vaccination at birth should not be given until two weeks after
completion of either TPT or TB treatment.
• The mother should be educated on standard infection control practices,
including cough etiquette

12. OTHER OPPORTUNISTIC INFECTIONS (OIs) IN
HIV POSITIVE PREGNANT WOMEN
• HIV positive pregnant women with low CD4 counts are at risk of other
opportunistic infections in addition to TB.
• Stage four defining opportunistic infections have high mortality. The most
common are Pneumocystis jirovecii pneumonia, and cryptococcal meningitis
and both are significant causes of maternal mortality.
• Pregnant women who are unwell need prompt and intensive investigation for
opportunistic infections.
• Starting ART in pregnant women with OIs
• In general, start ART two weeks after initiation of treatment for OIs.
• However, for cryptococcal meningitis, it is recommended that ART is delayed for
four to six weeks after initiation of treatment because early ART leads to
increased mortality.

13. Screening for Cryptococcal disease
• HIV-positive adults, adolescents and pregnant women with a CD4 count < 100 cells/mm3, should be screened for
cryptococcal disease before initiating ART.
• A cryptococcal antigen (CrAg) assay is used to detect cryptococcal antigenaemia.
• All clients, including pregnant women, with a positive cryptococcal antigen (CrAg) blood test have disseminated
cryptococcal disease and should be referred for lumbar puncture (LP) to exclude cryptococcal meningitis.
• Women with a prior diagnosis of cryptococcal meningitis do not need to be screened.
If lumbar puncture shows a positive cryptococcal antigen test:
• If cryptococcal meningitis is confirmed on LP, patients should be managed in hospital (for at least two weeks), and
ART deferred for four weeks.
• Admit and treat with intravenous amphotericin B, oral fluconazole 1200mg daily, and regular therapeutic lumbar
punctures to reduce intracranial pressure.
• It is recommended that pregnant women with cryptococcal meningitis are managed on medical wards by
experienced doctors and not obstetric wards.
If lumbar puncture shows a negative cryptococcal antigen test:
• For CrAg-positive patients without suspected meningitis, oral fluconazole (1200 mg for two weeks, followed by
standard consolidation and maintenance treatment) is recommended, as well as for patients with an LP that is
cryptococcal test-negative.
• For patients without signs or evidence of meningitis, ART is recommended to be started two weeks after anti-fungal
therapy is initiated.

14. Teratogenicity of fluconazole
• Fluconazole should generally be avoided in the 1st trimester,
• But pregnant women should be counselled on the high risk of severe
morbidity and mortality, and that the benefits of fluconazole may
outweigh the risks in the management of cryptococcosis.
• All pregnant women < 20 weeks gestation exposed to fluconazole should
have an ultrasound scan to detect congenital abnormalities.
• For the management of breastfeeding mothers, consult a specialist, as
fluconazole is present at concentrations similar to maternal plasma
concentrations in breast milk that will be transmitted to the breastfed
infant.

16. Pneumonia in pregnant women
• Respiratory disease is a significant cause of maternal mortality.
• Respiratory symptoms or signs need prompt investigation: a raised
respiratory rate (>24 per minute) is indication of underlying respiratory
disease, and further investigation is indicated.
• Treatment of pneumonia is the same as in non-pregnant patients.

17. Thank you