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Bacille Calmette-Guerin Vaccine-Induced Disease in Children with HIV/AIDS

HAIVNHarvard Medical School AIDS

Initiatives in Vietnam

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Learning Objectives

By the end of this session, participants should be able to:

Recognize clinical signs/symptoms suspicious for BCG disease in HIV-infected children

Identify different forms of BCG-related complications in HIV-infected children

Propose the appropriate work-ups and treatment for BCG

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BCG Vaccine: Overview (1)

M. bovis is part of the Mycobacterium tuberculosis complex

BCG (bacille Calmette-Guérin) is:• a live attenuated strain of M. bovis, developed as a

vaccine against TB disease • inherently resistant to PZA and may be resistant to INH

In TB-endemic countries including Vietnam, BCG is given at birth or shortly thereafter:• Although BCG does not provide 100% protection against

TB, it does reduce the risk of severe disease, namely meningeal and miliary TB, in children

The rate of adverse effects due to the vaccine:• Before HIV: 0.19-2 cases/million vaccinated infants

BCG Vaccine: Overview (2)

Prompt treatment with both anti-mycobacterial and ARV therapies increases chance of survival

Healthy infants and children usually only develop:

injection site ulcerationor lymphadenitis

Because BCG is a live attenuated vaccine, it can cause disease in susceptible individuals:

• HIV infected infants are at a much greater risk of BCG related complications

• Disseminated disease:only occurs in severely

immunocompromised individuals, and

carries an extremely high mortality rate above 80%

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BCG Vaccine Recommendation

Give BCG vaccine to all HIV-exposed children

Postpone vaccination until HIV infection is excluded in the following situations:• High risk of HIV infection: mother and infant

did not receive PMTCT, or• The infant presents with signs or symptoms

suggestive of HIV infection, or• Low birth weight (under 2500 g) and pre-

termed infants

BCG-related Complications

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Suppurative Axillary Lymphadenitis (Regional Disease)

Ipsilateral to vaccine injection site Can become extremely inflamed and

painful Take several months to subside Needle drainage or lymph node excision

may be necessary If there are signs of dissemination, anti-

TB treatment recommended

Left Axillary Lymphadenitis

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Disseminated BCG Disease

Usually in young children with advanced HIV

Median age at onset is 8 months Most common signs/symptoms:

• Wasting, failure to thrive• Anemia, usually severe• Hepatosplenomegaly• Axillary, cervical adenitis• Osteomyelitis• Infiltrates on CXR

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Extensive bilateral infiltrates in a patient with disseminated BCG

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Work-up

Any child with left axillary lymph node adenitis:• CBC, AST/ALT, CD4• CXR• Gastric aspirate, needle aspiration of

lymph node: send for AFB stain and culture with strain

identification, drug susceptibility

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Treatment (1)

Local or regional disease:• RHE• PZA for 2 months or until TB excluded• Needle aspiration or FNA if node

fluctuant• Consider LN excision• Start ART

Treatment (2)

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Case Study

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Case Study (1)

3 year-old boy, HIV+, presented with:• A left axillary lymph node and a left

cervical LN• Also hepatosplenomegaly

What do you want to do about the lymph nodes?

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Case Study (2)

Aspiration of lymph node was positive for AFB

Do you want to do anything further with the aspirates?

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Case Study (3)

Patient was placed on TB therapy with 2RHZ/4RH

CD4 3 cells/mm3 Started on AZT/3TC/EFV Over the next 3 months, a lymph node

drained and healed, and some other lymph nodes came up in the axilla. New lymph nodes appeared in cervical and supraclavicular areas

What do you think is going on?

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Case Study (4)

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Case Study (5)

After 3 months of ART, CD4 increased from 3 to 8 cells/mm3, no weight gain

What do you want to do? Given poor clinical progression, he was

switched to second line with LPV/r + 3TC + TDF

6 months after, all LN resolved.

Case Study (6)

After 3 months on TB therapy and ARV

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Key Points

BCG can cause severe complications in HIV-infected children

BCG vaccine should not be given to infants at high risk of HIV infection or symptomatic infants

Anti-TB treatment and ARV should be started promptly for disseminated disease to improve chance of survival

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Thank you!

Questions?