Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the eradication of tuberculosis in domestic livestock. In Michigan, USA tuberculous white-tailed deer transmit M. bovis to cattle. One approach in dealing with this wildlife reservoir is to vaccinate deer in order to interrupt the cycle of deer to deer and deer to cattle transmission. Thirty-one white-tailed deer were assigned to one of three groups; 2 SC doses of 10 7 CFU of M. bovis BCG (n = 11); 1 SC dose of 10 7 CFU of M. bovis BCG (n = 10); or unvaccinated deer (n = 10). After vaccination, deer were inoculated intratonsilarly with 300 CFU of virulent M. bovis. Gross lesion severity scores of the medial retropharyngeal lymph node were significantly reduced in deer receiving 2 doses of BCG compared to unvaccinated deer. Vaccinated deer had fewer lymph node granulomas than unvaccinated deer, and most notably, fewer late stage granulomas characterized by coalescent caseonecrotic granulomas containing numerous acid-fast bacilli. BCG was isolated from 7/21 vaccinated deer as long as 249 days after vaccination. In one case BCG was transmitted from a vaccinated deer to an unvaccinated deer. In white-tailed deer BCG provides measurable protection against challenge with virulent M. bovis. However, persistence of vaccine within tissues as well as shedding of BCG from vaccinates remain areas for further investigation. Published by Elsevier Ltd.

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(48) and Zairians living in Belgium (35) compared to control individuals with less pigmented skin, presumably due to diminished synthesis. Tuberculosis, likewise, is common among individuals with heavily pigmented skin that relocate from equatorial regions to higher latitudes, in part due to deficiencies in vitamin D synthesis within the skin (65). In addition, patients with untreated tuberculosis often have lower concentrations of 25(OH)D 3 in plasma than do healthy subjects, and tuberculosis tends to occur during the winter when exposure to sunlight is reduced and production of cholecalciferol within the skin is diminished (16). Evidence for a clear correlation between vitamin D deficiency and susceptibility to tuberculosis, however, remains controversial. In vitro studies, however, provide more compelling evidence linking vitamin D status to susceptibility to tuberculosis.Addition of 1,25(OH) 2 D 3 to monocyte-macrophage cultures infected with Mycobacterium tuberculosis suppresses bacterial growth and viability (17,53,54). The mechanism of this suppression is mediated, at least partially, by nitric oxide (NO) (53). Induction of inducible NO synthase of macrophages and subsequent generation of reactive nitrogen intermediates (RNI) toxic to mycobacteria is a potent mechanism of killing (14,15,21,22,34). Cytokines (e.g., tumor necrosis factor alpha and gamma interferon [IFN-␥]) from antigen-specific T cells and/or from macrophages stimulated directly with mycobacterial antigens is responsible for RNI-mediated antimycobacterial defense (24,60). Production of RNI is crucial for controlling acute as well as latent infections in the mouse model of virulent M. tuberculosis infection (14,15,25,34). The role of RNI in mycobacterial killing within human macrophages is less clear. Alveolar macrophages of tuberculosis patients express high levels of inducible NO synthase, suggesting a role for RNI in disease pathogenesis and/or host defense (42). Nevertheless, recent evidence suggests that human but not mouse macro-* Corresponding author. Mailing address: United States Department