1 Bacille Calmette-Guerin Vaccine-Induced Disease in Children with HIV/AIDS HAIVN Harvard Medical School AIDS Initiatives in Vietnam

2 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

3 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: 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 ulceration or 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%

5 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 Injection site ulcerationRegional disease Regional lymph nodes ipsilateral to injection site (axillary, supraclavicular, cervical) Disseminated disease A local or regional process plus a distant site (lungs, CNS, bone, skin, etc) BCG cultured from a distant site

7 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

9 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

10 Extensive bilateral infiltrates in a patient with disseminated BCG

11 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

12 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) RHEZ, plus Ofloxacin 15mg/kg/day or Ciprofloxacin 30mg/kg/day Start ART as soon as possible Disseminated disease Observe for progression Rule out treatment failure, non-adherence, or relapse BCG IRIS

14 Case Study

15 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?

16 Case Study (2) Aspiration of lymph node was positive for AFB Do you want to do anything further with the aspirates?

17 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?

18 Case Study (4)

19 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

21 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

22 Thank you! Questions?