Case Series of HIV-infected children with Bacillus Calmette-Guérin Vaccine Related Lymphadenopathy in Lilongwe, Malawi John Midturi Kazembe, PN., Schutze, GE., Kline, MW

Background-Malawi Population of 13 million HIV prevalence 14% (15-49yr) 30,000 children infected with HIV 125,000 individuals have been started on ART (Sept 2007)  children 8%

Background-Malawi (2) BCG incorporated into EPI schedule in 1974  Administered within 1 st week of life  99% coverage  Danish 1331

Background-Baylor COE Baylor COE- established officially in November 2006 Provision of pediatric HIV care, treatment and training 3612 patients  2155 active patients  ~50% on ART  Enroll ~100 new clients/month Average age at enrolment  4.56 years

Background-BCG vaccine Live attenuated vaccine Adverse reactions  Injection site ulceration  Lymphadenitis  Disseminated disease  Dependent on strain, administration method, bacillary load, host immunity, and physical-chemical property  Incidence 0-17%

Adverse reactions to BCG in HIV infected infants True Incidence, unknown:  Under-reported  0% to 30%  Frequency similar to uninfected population Turnbull CID 2002  HIV-negative: 2.5% vaccine site abscess & 1.7% lymphadenitis  HIV-Infected: 2.7% vaccine site abscess & 0.7% lymphadenitis

Objective  Identify incidence of BCG Disease in children infected with HIV at Baylor COE  Determine clinical course of BCG disease

Methods Retrospective chart review  July 2005 through February 28 th, 2007  All children diagnosed as HIV-infected at the Baylor COE. Data gathering:  Computerized medical record chart  Diagnosis of axillary lymphadenopathy, axillary lymphadenitis, BCG reaction, TB lymphadenitis, or right axillary adenopathy

Methods Diagnosis:  BCG disease (EPI):  ipsilateral axillary lymph node enlargement of >15x15 mm, suppurative ipsilateral axillary lymphadenitis, injection site abscess of 10 mm, or a clinically significant or non- resolving BCG papule  BCG disease IRIS:  Temporal association of ARV initiation and development of right axillary adenopathy  CD4/CD4% increase >5%

Results 13 cases:13/958, prevalence of 1.46% in HIV- infected children  10 BCG Disease IRIS (1.04%) Age:  Range 4 months to 18 months  Median 9 months WHO Stage:  8 Stage III (PTB/thrush/diarrhea)  5 Stage IV (PCP/severe malnutrition) Follow-up time:  Range 2 weeks to 37 weeks  Median 20 weeks

Median CD4% 13%, (2.2%-23.4%)

Median 3.5 weeks, (1-11weeks)

69.2% Spontaneously ruptured Median time to rupture 9.2 weeks, (2-14 weeks)

Median 3 months, (1-4 months)

Management Treatments:  8 TB therapy, 6 started TB meds prior to BCG Disease  6 antibiotics  All Started ART  No surgical intervention Outcome:  11 alive  2 died  both had BCG disease prior to ART  1 on TB therapy  Mortality 3.2 per 100 weeks follow-up

Conclusions Prevalence of 1.46% in our HIV- infected pediatric population Most develop BCG Disease IRIS 3-4 weeks after ART ~70% of them rupture 9 weeks after ART Most cases resolved after 3 months Most of our patients were already on TB therapy when they developed BCG Disease

Future Complete analysis of our data Potentially will become a more significant issue with the proposed universal treatment for all HIV-positive children under 12 months of age Prospective study:  Role of INH prophylaxis to see if it decreases incidence of BCG disease Delaying BCG vaccination in HIV- infected infants

Acknowledgments Dr. Peter Kazembe BIPAI Dr. Mark Kline Dr. Gordon Schutze Dr. Mark Kabue All the patients and families from the Baylor COE-Malawi