Clinical and Immune Impact of Mycobacterium bovis BCG Vaccination Scarring

http://iai.asm.org/cgi/content/abstract/70/11/6188

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Clinical and Immune Impact of Mycobacterium bovis BCG Vaccination Scarring

Janine Jason,^1* Lennox K. Archibald,² Okey C. Nwanyanwu,³ Peter N. Kazembe,⁴ Julie A. Chatt,¹ Elizabeth Norton,¹ Hamish Dobbie,⁴ and William R. Jarvis²

HIV Immunology and Diagnostics Branch, Division of AIDS, STD, and TB Laboratory Research,¹ Investigation and Prevention Branch, Hospital Infections Program, National Center for Infectious Diseases,² Office of Global Health, Centers for Disease Control and Prevention, U. S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 30333,³ Lilongwe Central Hospital and Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi⁴

Received 21 March 2002/ Returned for modification 21 May 2002/ Accepted 18 June 2002

The World Health Organization recommends Mycobacterium bovisBCG vaccination in areas of high tuberculosis prevalence. BCG's clinical and immune effects, not necessarily Mycobacterium tuberculosisspecific, are unclear. BCG vaccine scarring often is used asa surrogate marker of vaccination or of effective vaccination.We evaluated BCG scarring status in relation to clinical findingsand outcome in 700 hospitalized Malawians, of whom 32 had M. tuberculosis bloodstream infections (BSI) (10 of whom had cellularimmune studies done) and of whom 48 were infants <6 monthsold and therefore recently vaccinated (19 of whom had immunestudies). In the patients 6 months old, scarring was not relatedto the presence of pulmonary symptoms (35 versus 30%), chroniccough or fever, mortality, or M. tuberculosis BSI. In M. tuberculosisBSI patients, scarring was unrelated to mortality, vital signs,or clinical symptoms but those with scarring had higher proportionsof memory and activated T cells and more type 2-skewed cytokineprofiles. Infants with either BCG scarring (n = 10) or BCG lesionalinflammation (n = 5) had no symptoms of sepsis, but 18 of 33infants without BCG vaccination lesions did. Those with BCGlesions had localized infections more often than did those withoutBCG lesions. These infants also had lower median percentagesof lymphocytes spontaneously making interleukin-4 (IL-4) ortumor necrosis factor alpha (TNF-) and lower ratios of T cellsspontaneously making IL-4 to T cells making IL-6. Thus, we foundthat, in older patients, BCG vaccine scarring was not associatedwith M. tuberculosis-specific or nonspecific clinical protection.Those with M. tuberculosis BSI and scarring had immune findingssuggesting previous M. tuberculosis antigen exposure and inductionof a type 2 cytokine pattern with acute reexposure. It is unlikelythat this type 2 pattern would be protective against mycobacteria,which require a type 1 response for effective containment. Ininfants <6 months old, recent BCG vaccination was associatedwith a non-M. tuberculosis-specific, anti-inflammatory cytokineprofile. That the vaccinated infants had a greater frequencyof localized infections and lesser frequency of sepsis symptomssuggests that this postvaccination cytokine pattern may providesome non-M. tuberculosis-specific clinical benefits.

* Corresponding author. Mailing address: Mailstop A-25, DASTLR, NCID, CDC, 1600 Clifton Rd. N.E., Atlanta, GA 30333. Phone: (404) 639-3919. Fax: (404) 639-2108. E-mail: JMJ1@cdc.gov.

Editor: S. H. E. Kaufmann

J. Bacteriol.	J. Virol.	Eukaryot. Cell

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