Search

Context: Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end-stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood.Objective: To assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use.Design and Setting: Community-based prospective cohort study with enrollment in 1988-1989 and a median follow-up of 8.8 years.Subjects: A total of 1667 persons aged 17 years or older with a history of injection drug use and an HCV antibody-positive test result during follow-up.Main Outcome Measures: Viral clearance was assessed in a subset of 919 patients and defined as failure to detect HCV RNA in at least 2 consecutive samples collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificates and defined by the presence of ascites, esophageal varices, or hepatic encephalopathy, or when ESLD was stated as a cause of death.Results: Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI], 2.60-10.17) and those not infected with human immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate model, risk of ESLD was higher for persons aged 38 years or older at enrollment (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95% CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis.Conclusions: Our results indicate that although HCV infection can be self-limited or associated with ESLD, the majority of adults have persistent viremia without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use. JAMA. 2000;284:450-456 [ABSTRACT FROM AUTHOR]

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 (P<.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.

Objective: To evaluate changes in T-cell subsets in prevalent human immunodeficiency virus type 1 (HIV-1) seronegative and seropositive intravenous drug users (IVDUs) and in HIV-1 seropositive IVDUs with known time of seroconversion., Design: Cohort study with a median 18-month follow-up., Setting: Community-based clinic established to study the natural history of HIV infection in IVDUs., Subjects: Eight hundred fifty-nine self-referred IVDUs aged 18 through 49 years who injected drugs within the last 10 years and who did not have an AIDS (acquired immunodeficiency syndrome)--defining illness; 152 were seronegative for HIV-1, 621 were seropositive, and 86 seroconverted during the study., Outcome Measures: Proportions and absolute numbers of lymphocytes and CD3, CD4, and CD8 T cells as determined at 6-month intervals by flow cytometry and complete blood cell counts with automated differential., Results: Median numbers of CD4 lymphocytes at enrollment were 1061/microL (1.06 x 10(9)/L) for seronegative IVDUs, 508/microL for seropositive IVDUs, and 733/microL for those who seroconverted (enrolled a median of 4.5 months after seroconversion); the corresponding figures for CD8 lymphocytes were 628, 894, and 889/microL, respectively. Median rates of decline in absolute numbers and percentages of CD4 lymphocytes per 6 months were 7.6/microL (0.0%) for seropositive IVDUs and 55.1/microL (1.9%) for IVDUs who seroconverted (median follow-up after seroconversion was 12 months). Multivariate regression analysis that incorporated the within-individual correlation of the CD4 lymphocyte counts showed no significant change in these cells over time and no change due to use of drugs., Conclusion: Our data suggest that progression of HIV-1 infection in IVDUs, as reflected in decline of CD4 cell counts, is no more rapid than that reported for other risk groups.

Objectives: --To identify differences in purified protein derivative (PPD) tuberculin positivity and skin test anergy rates by human immunodeficiency virus (HIV) serostatus, CD4+ lymphocyte count, and other risk factors in intravenous drug users (IVDUs); and to evaluate the appropriateness of the Centers for Disease Control (CDC)--recommended definition for a positive PPD tuberculin skin test result in HIV-1-seropositive patients., Design: --Nested case-control and cross-sectional analyses., Setting: --Community-based cohort of IVDUs., Patients: --Two hundred sixty HIV-1-seropositive and -seronegative IVDUs, drawn from an unselected cohort, were skin-tested for sensitivity to PPD tuberculin, mumps, and Candida antigens using the Mantoux method., Outcome Measures: --Positivity to PPD tuberculin, skin test anergy., Results: --Even using the CDC definition of an induration 5 mm or greater in diameter in HIV-1 seropositives, this group was substantially less likely to be PPD tuberculin positive than HIV-1 seronegatives (13.8% vs 25.2%; P = .02). In the HIV-1 seropositives the relative odds of being PPD positive varied depending on whether 10 mm or greater (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.2 to 0.7), 5 mm or greater (OR, 0.5; 95% CI, 0.2 to 0.9), or 2 mm or greater (OR, 0.7; 95% CI, 0.4 to 1.3) was used to define a positive test result. The mean diameter induration in the HIV-1-seropositive group was 2.6 mm vs 5.4 mm in the seronegative group (P = .005). Skin test anergy (to mumps and Candida) appeared to explain the differential. Anergy was substantially higher in the HIV-1 seropositive group and increased as the CD4+ lymphocyte count fell (chi 2 for linear trend, 24.5; P less than .0001). An inverse linear trend for PPD positivity and CD4+ lymphocyte count was also observed (chi 2 for trend, 6.1; P = .01). In multivariate analyses, being 35 years of age or older and being HIV-1 seronegative were significantly associated with PPD positivity, while history of previous police arrest was of borderline significance. Only HIV-1 seropositivity was significantly associated with anergy., Conclusions: --These findings show that CDC-recommended definition of an induration 5 mm or greater in diameter for PPD tuberculin positivity in HIV-1 seropositives significantly underestimates the "true" infection rate (using the PPD positivity rate in HIV-1 seronegatives as the criterion standard). A definition of 2 mm or greater would appear to be a better cutoff for reducing misclassification in HIV-1 seropositives. This study also confirms that delayed-type hypersensitivity is seriously depressed in HIV-1 seropositive IVDUs and that anergy testing is mandatory to properly assess a negative PPD test result.

Data from the Baltimore-Washington Infant Study of congenital cardiovascular malformations permitted detailed analysis of congenital cardiovascular malformations in 62 twins and 3 triplets and 2303 singleton cases. A probability sample of controls (n = 2793) included 43 twins. The case prevalence of multiple births was 28 of 1000, compared with a 15 of 1000 prevalence among controls (chi 2 = 5.7). There were more girls among case twins than among case singletons and controls (chi 2 = 9.0). Monozygosity was no more frequent in case twins than in controls. Looping defects occurred in 4 monozygotic twin pairs compared with only 1 dizygotic twin pair. The twinning process itself may be implicated in the development of congenital cardiovascular malformations in some of these infants, especially those with looping defects, but concordance of types of defects in 4 of 65 pairs implicates genetic factors in the determination of some forms of congenital cardiovascular malformations.