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

Bacille Calmette-Guerin Vaccine-Induced Disease in Children with HIV/AIDSHAIVNHarvard Medical School AIDS Initiatives in VietnamLearning ObjectivesBy the end of this session, participants should be able to:Recognize clinical signs/symptoms suspicious for BCG disease in HIV-infected childrenIdentify different forms of BCG-related complications in HIV-infected childrenPropose the appropriate work-ups and treatment for BCGBCG Vaccine: Overview (1)M. bovis is part of the Mycobacterium tuberculosis complexBCG (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 INHIn 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 childrenThe rate of adverse effects due to the vaccine:Before HIV: 0.19-2 cases/million vaccinated infantsBCG Vaccine: Overview (2)Prompt treatment with both anti-mycobacterial and ARV therapies increases chance of survivalHealthy infants and children usually only develop:injection site ulcerationor lymphadenitisBecause 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 complicationsDisseminated disease:only occurs in severely immunocompromised individuals, andcarries an extremely high mortality rate above 80%BCG Vaccine RecommendationGive BCG vaccine to all HIV-exposed childrenPostpone vaccination until HIV infection is excluded in the following situations:High risk of HIV infection: mother and infant did not receive PMTCT, orThe infant presents with signs or symptoms suggestive of HIV infection, orLow birth weight (under 2500 g) and pre-termed infantsBCG-related ComplicationsSuppurative Axillary Lymphadenitis (Regional Disease)Ipsilateral to vaccine injection siteCan become extremely inflamed and painfulTake several months to subsideNeedle drainage or lymph node excision may be necessaryIf there are signs of dissemination, anti-TB treatment recommendedLeft Axillary LymphadenitisDisseminated BCG DiseaseUsually in young children with advanced HIV Median age at onset is 8 months Most common signs/symptoms:Wasting, failure to thriveAnemia, usually severeHepatosplenomegalyAxillary, cervical adenitisOsteomyelitisInfiltrates on CXRExtensive bilateral infiltrates in a patient with disseminated BCGWork-upAny child with left axillary lymph node adenitis:CBC, AST/ALT, CD4CXRGastric aspirate, needle aspiration of lymph node:send for AFB stain and culture with strain identification, drug susceptibilityTreatment (1)Local or regional disease:RHEPZA for 2 months or until TB excludedNeedle aspiration or FNA if node fluctuantConsider LN excisionStart ARTTreatment (2)Case StudyCase Study (1)3 year-old boy, HIV+, presented with:A left axillary lymph node and a left cervical LNAlso hepatosplenomegalyWhat do you want to do about the lymph nodes?Case Study (2)Aspiration of lymph node was positive for AFB Do you want to do anything further with the aspirates?Case Study (3)Patient was placed on TB therapy with 2RHZ/4RHCD4 3 cells/mm3Started on AZT/3TC/EFVOver 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 areasWhat do you think is going on?Case Study (4)Case Study (5)After 3 months of ART, CD4 increased from 3 to 8 cells/mm3, no weight gainWhat do you want to do?Given poor clinical progression, he was switched to second line with LPV/r + 3TC + TDF6 months after, all LN resolved. Case Study (6) After 3 months on TB therapy and ARVKey PointsBCG can cause severe complications in HIV-infected childrenBCG vaccine should not be given to infants at high risk of HIV infection or symptomatic infantsAnti-TB treatment and ARV should be started promptly for disseminated disease to improve chance of survivalThank you!Questions?