Tuberculosis in Pregnancy

This is a quick summary of the points taken from the TOG article which was published in July 2023. It is an important exam topic so must be covered thoroughly.

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Introduction

• Tuberculosis (TB) is one of the leading infectious causes of overall mortality
• Highest disease burden in low-resource countries 
• >2/3 cases in Africa and Southeast Asia
• Co-infection of TB & HIV in reproductive years is significant
• In UK — increasing due to immigration 
• Can have adverse effects on mother & fetus

Epidemiology

• Global incidence - 1990-2020 — 9.9 million with 1.3 million deaths worldwide 
• Major contributors to the resurging global TB epidemic — Poverty, HIV Coinfection, Drug resistance
• In 2020 UK had 4700 cases = 6.9 per 100 000
• Risk of new migrant women having active TB highest in first 5 years of migration
• Exact worldwide TB prevalence in pregnancy - Uncertain & depends on area
• Low-prevalence countries 0.06-0.25%
• High-prevalence countries 
• 0.07-0.5% (in HIV negative)
• 0.7-11% (in HIV-positive) 

Pathophysiology

• Causative organism — Mycobacterium tuberculosis (non-spore-forming, aerobic & non-motile bacteria)
• Primarily airborne infection
• Can also occur through ingestion of unpasteurised milk or direct implantation
• TB particles range from 1-5 microns in size, carried to terminal alveoli and multiply there
• Alveolar macrophages ingest & destroy most of the particles, but few survive and continue to multiply
• A granuloma is formed by macrophages around the bacilli
• Usually, the immune system clears the infection, but if it fails, it remains dormant without clinical manifestations or may cause symptoms.
• ~10% immunocompromised with latent TB will develop reactivation of TB
• ~10% healthy acquire infection during their life
• Most common form of clinical TB — Pulmonary disease
• 20% active TB can present as extrapulmonary TB with cervical nodes being most common site (31%). 
• Other sites are CNS, spinal cord, abdomen, pericardium (more common in immunocompromised & HIV-positive)

Outcomes of primary TB infection 

1. Latent TB
2. Primary TB (within 2 years)
3. Secondary TB

Clinical Presentation 

• Suspect TB if h/o exposure to patients with chronic cough or recent visits to endemic areas
• Symptoms except for Fever same as non-pregnant — weight loss, night sweats, chills, appetite loss, tiredness & weakness
• Latent disease will be asymptomatic & non-infectious but can have reactivation
• Four-symptom screening for TB suggested by WHO 

1. Fever
2. Night sweats
3. Cough
4. Weight loss

Investigations

Screening tests

• TB skin test (TBT)
• Interferon gamma release assay (IGRA)

Confirmatory tests

• Microscopy
• Culture and sensitivity 

Additional tests

• Imaging studies

Tuberculosis Skin Test (TST)

• Purified protein derivative (PPD) injected intradermally & delayed hypersensitivity reaction induration (5-15 m) measured at 48-72 hrs.
• No effect of pregnancy on results
• PPD safe for both mother & fetus
• Two types of TST : Tine (used rarely) and Mantoux (commonly used)
• False positive: with previous BCG vaccination, previous TB infection and infection with non-tuberculous mycobacterium
• False negative: due to technical issues, women with recent TB infection, immunocompromised, sarcoidosis, non-Hodgkin’s lymphoma, recent live vaccination with measles or chickenpox

Interferon-gamma release assay (IGRA)

• Detects interferon gamma 
• Not influenced by BCG vaccination
• Not validated for use in pregnancy but performed routinely
• Can not differentiate latent from active infection

Microscopy

• Most commonly used to detect acid-fast bacilli (AFB) - Ziegle-Neelsen staining of sputum 
• Sputum-positive detects 56 - 68% of pulmonary TB which means it may miss 1/3 of active cases

Culture and sensitivity

• Lowenstein-Jensen medium used traditionally
• Culture takes 4-8 wks Drug sensitivity a further 6-8 weeks
• Solid culture media now replaced by liquid culture media (BD-BACTEC & MGIT 960)

Imaging studies 

Chest X-ray (CXR)

• Good screening tool 
• Should be used in pregnancy when clinically indicated with proper shielding
• CXR can show healed lesions or a Ghon’s focus in treated cases
• 14% of culture-positive TB patients can have normal CXR

Ultrasound: Can be used safely

CT & MRI: Used if needed 

Effects of Pregnancy on TB

• Pregnancy makes the diagnosis challenging
• Increased risk of reactivation in postpartum period (highly susceptible time)
• Prognosis depends on severity of disease, response to medicines, organs involvement and individual susceptibility 
• HIV Coinfection more likely to progress the disease
• Timely diagnosis & prompt treatment improves outcomes 

Effect of TB on Pregnancy

• Outcomes depend on disease stage, gestation at diagnosis, treatment, if extrapulmonary spread, coinfection with HIV and comorbidities like DM
• TB increase risks during pregnancy & postpartum
• Aneamia 41% (active TB) vs 23% (no active TB)
• Prematurity 32% SGA 22% Increased Oligohydramnios

HIV-TB Coinfection

• Challenging to diagnose and treat
• Higher risk of multidrug-resistant TB and disease relapse
• Risk of TB 21 times higher in women with HIV as compared to general pregnant women.
• HIV-TB con infection can lead to increased anaemia, eclampsia, placenta accreta, drug abuse  and depression

Treatment of TB in pregnancy

• When treated earlier, associated risks almost eliminated
• Plan in collaboration with MDT
• Treatment initiated based on disease status

Ref: TOG

Active TB

• Start t/m as early as possible
• NICE: no difference in treatment, duration and dose in pregnant
• TB not involving CNS to be treated with 
• Isoniazid, Rifampicin, Pyranzimide, Ethambutol — 2 months (initial phase)
• Isoniazid, Rifampicin — 4 months (continuation phase)
• Total duration of treatment — 6 months 
• If CNS involved treatment for — 12 months (Same drugs 2 M + 10 M)
• Must give pyridoxine 10mg/day with isoniazid to avoid neurotoxicity to mother and baby
• Once treatment started, must have a follow-up to assess if converted to non-infectious
• NICE recommends fixed-dose daily dosing in all women
• If CNS involved, adjuvant corticosteroids with either dexamethasone or prednisolone recommended. Given over 4-8 wks with gradual dose tapering. Consider stress dose of steroids during labour.
• All first-line anti-TB drugs are FDA category C and are safe in pregnancy
• Avoid streptomycin which has 15% risk of neonatal irreversible deafness

Drug-resistant and multidrug-resistant TB

• Duration of initial t/m phase same 2 M but continuation phase varies 4-7 months

Latent TB

• Consider for prophylaxis if HIV positive, at high risk of acquiring recent TB or after investigations. 
• Do not delay treatment until 2nd trimester
• For latent TB give isoniazid 6 months or combination of Isoniazid + Rifampacin for 3 months
• Must give supplemental pyridoxine with isoniazid

Perinatal TB

• Included TB acquired congenitally & postnatal
• Both have same treatment and prognosis 
• Congenital TB — refers to acquiring TB by fetus in utero, either antenatal or intrapartum
• Neonatal TB — usually acquired in immediate postpartum period. 
• The primary focus in neonates is on liver and periportal lymph nodes
• Military pattern is the most common finding on CXR in neonates
• Diagnostic criteria for perinatal TB
• demonstration of lesions in the new-born in the first week of life  
• primary hepatic complex or caseating granuloma on percutaneous liver biopsy at birth  
• placental or maternal genital tract TB  
• excluding the likelihood of transmission by postnatal contacts
• Perinatal TB has high mortality rate for both treated 22% and non-treated 38%
• Treatment same as adults along with pyridoxine 
• If active maternal TB and no clinical or lab evidence of prenatal TB, isoniazid preventive therapy at 10 mg/kg/day recommended for 6 months along with pyridoxine
• Breastfeeding to be commenced after MDT
• Anti-TB drugs considered safe if mother completed at least 2 weeks of treatment
• Breastfeeding usually not recommended for breast TB, multidrug or extended drug-resistant TB or co-infection with HIV

BCG vaccination

• Currently the only approved vaccine by WHO
• Single dose given to all neonates as soon as possible after birth
• In UK — BCG vaccine recommended for neonates whose parents or grandparents were born in a country where annual incidence of TB is ≥40/100 000 or newborn lives in an area of UK with annual incidence of ≥40/100 000
• Avoid BCG vaccine in pregnancy
• Contraindicated in infants exposed to immunosuppressant t/m in utero or in breastfeeding children with an active TB case suspected or confirmed in their household. 
• HIV-positive mother — BCG to be given if child HIV negative at 12-14 wks & exclusively formula fed since birth 

Ref: TOG

Ref: TOG

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