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Infection and Immunity, November 2002, p. 6188-6195, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6188-6195.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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 bovis BCG vaccination in areas of high tuberculosis prevalence. BCG's clinical and immune effects, not necessarily Mycobacterium tuberculosis specific, are unclear. BCG vaccine scarring often is used as a surrogate marker of vaccination or of effective vaccination. We evaluated BCG scarring status in relation to clinical findings and outcome in 700 hospitalized Malawians, of whom 32 had M. tuberculosis bloodstream infections (BSI) (10 of whom had cellular immune studies done) and of whom 48 were infants <6 months old and therefore recently vaccinated (19 of whom had immune studies). In the patients >=6 months old, scarring was not related to the presence of pulmonary symptoms (35 versus 30%), chronic cough or fever, mortality, or M. tuberculosis BSI. In M. tuberculosis BSI patients, scarring was unrelated to mortality, vital signs, or clinical symptoms but those with scarring had higher proportions of memory and activated T cells and more type 2-skewed cytokine profiles. Infants with either BCG scarring (n = 10) or BCG lesional inflammation (n = 5) had no symptoms of sepsis, but 18 of 33 infants without BCG vaccination lesions did. Those with BCG lesions had localized infections more often than did those without BCG lesions. These infants also had lower median percentages of lymphocytes spontaneously making interleukin-4 (IL-4) or tumor necrosis factor alpha (TNF-{alpha}) and lower ratios of T cells spontaneously making IL-4 to T cells making IL-6. Thus, we found that, in older patients, BCG vaccine scarring was not associated with M. tuberculosis-specific or nonspecific clinical protection. Those with M. tuberculosis BSI and scarring had immune findings suggesting previous M. tuberculosis antigen exposure and induction of a type 2 cytokine pattern with acute reexposure. It is unlikely that this type 2 pattern would be protective against mycobacteria, which require a type 1 response for effective containment. In infants <6 months old, recent BCG vaccination was associated with a non-M. tuberculosis-specific, anti-inflammatory cytokine profile. That the vaccinated infants had a greater frequency of localized infections and lesser frequency of sepsis symptoms suggests that this postvaccination cytokine pattern may provide some 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{at}cdc.gov.

Editor: S. H. E. Kaufmann

Infection and Immunity, November 2002, p. 6188-6195, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6188-6195.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Roth, A., Gustafson, P., Nhaga, A., Djana, Q., Poulsen, A., Garly, M.-L., Jensen, H., Sodemann, M., Rodriques, A., Aaby, P. (2005). BCG vaccination scar associated with better childhood survival in Guinea-Bissau. Int J Epidemiol 34: 540-547 [Abstract] [Full Text]  


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