Risk factors for transmission of tuberculosis among United States-born African Americans and Whites.

SETTING: Tuberculosis (TB) patients and their contacts enrolled in nine states and the District of Columbia from 16 December 2009 to 31 March 2011. OBJECTIVE: To evaluate characteristics of TB patients that are predictive of tuberculous infection in their close contacts. DESIGN: The study population was enrolled from a list of eligible African-American and White TB patients from the TB registry at each site. Information about close contacts was abstracted from the standard reports of each site. RESULTS: Close contacts of African-American TB patients had twice the risk of infection of contacts of White patients (adjusted risk ratio [aRR] 2.1, 95%CI 1.3-3.4). Close contacts of patients whose sputum was positive for acid-fast bacilli on sputum smear microscopy had 1.6 times the risk of tuberculous infection compared to contacts of smear-negative patients (95%CI 1.1-2.3). TB patients with longer (>3 months) estimated times to diagnosis did not have higher proportions of infected contacts (aRR 1.2, 95%CI 0.9-1.6). CONCLUSION: African-American race and sputum smear positivity were predictive of tuberculous infection in close contacts. This study did not support previous findings that longer estimated time to diagnosis predicted tuberculous infection in contacts.

Immunological mechanisms controlling mycobacterial infections.

After a brief review of the present knowledge about cell mediated immunity mechanisms involved in controlling mycobacterial diseases, variations of the immune responses to mycobacterial diseases in man and in experimental animals models are described. Related factors involved in the variations of the BCG vaccination effectiveness against human tuberculosis are presented according to present hypotheses on varying potency of BCG strains and influence of previous sensitization with non tuberculous mycobacteria. Also new hypotheses concerning qualitative differences in immune responses to mycobacteria in humans are discussed in association with information suggesting that tuberculosis, as other granulomatous chronic infectious diseases, is a disease in which an immune spectrum can be described with a significant modulation of T and B lymphocyte mediated responses. Evidence obtained in murine experimental models, using BCG infection in inbred and recombinant mice, demonstrated the existence of at least two genes which are able to control the induction and expression of CMI after mycobacterial infection. One of them, being not linked with the major histocompatibility complex gene (non H2), controls the natural non specific activity of the mononuclear phagocytic system and the other, linked with H2 complex, is able to modulate the level of CMI in responsive mice. Collective or individual antituberculosis strategies must be reconsidered following this finding.

Delayed-type hypersensitivity to sheep red blood cells in selected lines of mice with high or low antibody responses.

Interline differences in DTH to SRBC which developed in high antibody producer (H/Ab) and low antibody producer (L/Ab) genetically selected lines of mice were observed after intravenous (IV) or subcutaneous (SC) sensitization. This interline difference was more marked in female that in male mice, and with the optimal dose for DTH sensitization. The kinetics of the local inflammatory reaction after local challenge, the development and decay of the 24-h DTH reaction tested at varying intervals after sensitization, were always statistically significantly higher in H/Ab than in L/Ab mice. This higher DTH was associated with a higher capacity of these mice to produce a secondary humoral response, and the more marked difference was observed for the production of 2-mercaptoethanol-resistant specific antibodies. Higher DTH reaction in H/Ab mice could not be explained by the participation of either B lymphocytes or humoral antibodies, since high dose (200 mg/kg) of CY injected before IV-SRBC, sensitization, in order to inhibit B-cell activation, did not alter the DTH-interline difference. Moreover, IV injection of specific antibodies from H/Ab immune mice did not enhance DTH in adoptively immunization L/Ab mice. Immune serum alone was not able to adoptively transfer DTH either in H/Ab or in L/Ab mice. Also, a low dose (40 mg/kg) known to inhibit T-cell suppression, injected before SC-SRBC sensitization, was not able to modify the DTH reaction in L/Ab mice. The persisting higher 48-h local inflammatory reaction in H/Ab mice after CY pretreatment was also related to a high blood monocyte rebound. When the afferent arc of the immune response to SRBC was studied in these mice, as tested by the lymphoproliferative response in draining popliteal node after footpad sensitization and by the evaluation of the ability of the T-activated cells located in these draining nodes to transfer locally an adoptively DTH reaction into naive recipients, it was shown that in immunized mice more specifically activated T cells were produced in H/Ab than in L/Ab mice. Moreover, the H/Ab recipients had a higher capacity to develop a local inflammatory reaction than the L/Ab recipients. The mechanisms of these observed interline differences are discussed.

Immunological behavior after mycobacterial infection in selected lines of mice with high or low antibody responses.

Resistance and susceptibility to mycobacterial infection in the Biozzi high and low lines of mice which were genetically selected for their responses to heterologous erythrocytes have been found to be related to the innate ability of nonimmune macrophages to kill or inhibit the growth of the organisms during the first two weeks after infection and to their ability to mount specific and nonspecific immune responses. High antibody-producer mice were more capable of expressing cell-mediated immune parameters than low antibody-producer mice. A direct relationship was observed between the ability of bacteria (BCG vaccine) to multiply inside the reticuloendothelial system and the development of cell-mediated immunity, as measured by the delayed local reaction at the injection site, the lymphoproliferative response in the draining nodes, the tuberculin delayed-type hypersensitivity, the acquired resistance, and the adjuvant effect after BCG inoculation. In high line mice, apart from the inability of their macrophages to inhibit the early growth of bacteria, their lymphocytes in spleen and thymus were more capable of being stimulated in vitro by varying concentrations of living BCG. The data presented in this report are compatible with the hypothesis that a group of genes segregated in each line during the selective breeding controls the innate microbicidal activity.

In vivo antitumor activity of various forms of delayed-type hypersensitivity in mice.

Relationships among various forms of delayed-type hypersensitivity (DTH) and nonspecific resistance to Lewis lung tumor were studied in syngeneic and semisyngeneic mice. Only the tuberculin type of DTH obviated a virulent inoculum of 10(6) tumor cells. The Jones-Mote type of DTH, even modified by cyclophosphamide pretreatment, produced a significant local inflammatory reaction which was unable to destroy tumor cells. The antitumor effect of the tuberculin type was observed in BCG-or in Corynbacterium parvum-immune mice and also in sheep red blood cell-immunized mice, but only after the modulating effect of BCG. The antitumor activity of the DTH reaction was anatomically restricted and time related, and it required local persistence of specific antigen. A minimal number of bacteria, 1 times 10(6) living or heat-killed BCG organisms, were equally able to eradicate 10(5) tumor cells in BCG-immune mice. Biphasic effects on tumor growth were observed when systemic specific inflammatory reactions were elicited in BCG-immune mice. However, tumor-specific immunity was never observed, inasmuch as BCG-immune mice surviving injection of a mixture of BCG and tumor cells did not resist a second tumor cell challenge.