No abstract

Context.-Recent studies suggest that one third of tuberculosis cases in urban areas result from recent transmission. Improved tuberculosis control measures such as uniform implementation of directly observed therapy might reduce the proportion of cases resulting from recent transmission. Objective.-To determine patterns of tuberculosis transmission in Baltimore, Md, after 15 years of community-based directly observed therapy. Design.-A 30-month (January 1994-June 1996), prospective, city-wide study of all cases of tuberculosis using traditional contact investigations, geographic information systems data, and molecular epidemiologic comparison of Mycobacterium tuberculosis isolates with 2 DNA probes. Patients.-One hundred eighty-two patients with culture-positive tuberculosis. Main Outcome Measures.-Proportion of disease defined as recently transmitted based on epidemiologic linkage by traditional contact tracing and molecular linkage by DNA fingerprint analysis of isolates; geographic foci of transmission based on linkage of residences by geographic information systems data. Results.-Of the 182 patients who had isolates of M tuberculosis available, 84 (46%) showed molecular clustering with 58 (32%) defined as being recently transmitted. Only 20 (24%) of 84 cases with clustered DNA fingerprints had epidemiologic evidence of recent contact. Geographic analysis showed significant spatial aggregation of the 20 clustered cases with epidemiologic links (PϽ.001), occurring in areas of low socioeconomic status and high drug use. The 64 cases with clustered DNA fingerprints but without epidemiologic links shared common risk factors and demographic features with the 20 clustered patients who did have epidemiologic links. Conclusions.-Recently transmitted tuberculosis accounts for a high proportion of tuberculosis cases in Baltimore. Recently transmitted cases occur in geographically distinct areas of Baltimore, and location-based control efforts may be more effective than contact tracing for the early identification of cases.

Hepatitis C virus (HCV) is an important human pathogen that represents a model for chronic infection given that the majority of infected individuals fail to clear the infection despite generation of virus-specific T cell responses during the period of acute infection. Although viral sequence evolution at targeted MHC class I-restricted epitopes represents one mechanism for immune escape in HCV, many targeted epitopes remain intact under circumstances of viral persistence. To explore alternative mechanisms of HCV immune evasion, we analyzed patterns of expression of a major inhibitory receptor on T cells, programmed death-1 (PD-1), from the time of initial infection and correlated these with HCV RNA levels, outcome of infection, and sequence escape within the targeted epitope. We show that the level of PD-1 expression in early HCV infection is significantly higher on HCV-specific T cells from subjects who progress to chronic HCV infection than from those who clear infection. This correlation is independent of HCV RNA levels, compatible with the notion that high PD-1 expression on HCV-specific CD8 T cells during acute infection inhibits viral clearance. Viral escape during persistent infection is associated with reduction in PD-1 levels on the surface of HCV-specific T cells, supporting the necessity of ongoing antigenic stimulation of T cells for maintenance of PD-1 expression. These results support the idea that PD-1 expression on T cells specific for nonescaped epitopes contributes to viral persistence and suggest that PD-1 blockade may alter the outcome of HCV infection.

Although efforts to reduce blood-borne infection incidence have had impact, this work will need to be intensified for the most transmissible viruses, such as HCV.

To determine the effect of human immunodeficiency virus (HIV) infection and other factors on infective endocarditis (IE) among injection drug users (IDUs), the incidence of IE was determined according to HIV status in a cohort of IDUs. A nested case-control study assessed IE risk factors. IE incidence (117 cases) was higher among HIV-seropositive than HIV-seronegative IDUs (13.8 vs. 3.3 cases/1000 person-years) during 1988-1998. Multivariate analysis of HIV-infected case patients revealed an inverse association between IE and CD4 lymphocyte count (odds ratio [OR] for 200-499 cells/mm(3), 2.01; OR for <200 cells/mm(3), 3.61) and with alcohol intake (OR for 1-21 drinks/week, 0.43; OR for >21 drinks/week, 0.32). Women had an increased risk of IE (OR, 3.26), as did persons with increasing injection drug use frequency (OR for less than daily use, 3.15; OR for at least daily use, 6.07). This study confirms that IE is more common among IDUs with advanced HIV immunosuppression even after accounting for injection drug use behaviors.