Prevalence of agr specificity groups among Staphylococcus aureus strains colonizing children and their guardians.

PCR-based assays were used to evaluate agr locus nucleotide polymorphism for the identification of agr autoinducer receptor specificity groups within a population of Staphylococcus aureus isolates colonizing children and their guardians. All isolates could be assigned to one of three major agr groups that had similar prevalences, regardless of whether isolates were implicated in transmission of S. aureus within families. Among healthy carriers, agr groups I to III appear to be equally fit, which may reflect selection for the coexistence of S. aureus strains in a population.

Increased incidence of multidrug-resistant tuberculosis in diabetic patients on the Bellevue Chest Service, 1987 to 1997.

STUDY OBJECTIVES: To investigate the characteristics of tuberculosis infection in diabetic patients at Bellevue Hospital. DESIGN: We conducted a case-control study retrospectively reviewing the records of patients at Bellevue Hospital Center from 1987 to 1997 with a discharge diagnosis of tuberculosis and diabetes mellitus. SETTING: Bellevue Hospital Center is a 1,200-bed, inner-city municipal hospital located in the Lower East Side of New York City. PATIENTS: Fifty-three identified patients had verified tuberculosis infection and diabetes; of these, 50 charts were available for review. One hundred five control cases were selected from nondiabetic patients with a discharge diagnosis of tuberculosis during the same time period. MEASUREMENTS AND RESULTS: Thirty-six percent (18 cases) of the patients with diabetes and tuberculosis had multidrug-resistant tuberculosis (MDR-TB) compared to only 10% (10 cases) in the control group (p < 0.01) Controlling for homelessness, HIV status, and directly observed therapy, the relative risk of MDR-TB was calculated to be 8.6 (confidence interval, 3.1 to 23.6) in the diabetic group compared to the control group. CONCLUSIONS: There was a significant association between diabetes and MDR-TB. Diabetes continues to be a risk factor for tuberculosis and was associated with MDR-TB in our patients.

Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of epidemic human immunodeficiency virus in Africa.

There is compelling evidence that both human immunodeficiency virus (HIV) types emerged from two dissimilar simian immunodeficiency viruses (SIVs) in separate geographical regions of Africa. Each of the two HIVs has its own simian progenitor and specific genetic precursor, and all of the primates that carry these SIVs have been in close contact with humans for thousands of years without the emergence of epidemic HIV. To date no plausible mechanism has been identified to account for the sudden emergence in the mid-20th century of these epidemic HIVs. In this study we examine the conditions needed for SIV to complete the genetic transition from individual human SIV infections to epidemic HIV in humans. The genetic distance from SIV to HIV and the mutational activity needed to achieve this degree of adaptation to human hosts is placed within a mathematical model to estimate the probabilities of SIV completing this transition within a single SIV-infected human host. We found that the emergence of even one epidemic HIV strain, following a single human exposure to SIV, was very unlikely. And the probability of four or more such transitions (i.e. HIV-1 groups M, O and HIV-2 subtypes A and B) occurring in a brief period is vanishingly small. We conclude that SIV cannot become a zoonosis, but requires adaptive mutations to become HIV. Some modern event must have aided in the transition of SIV to HIV. Our research indicates that serial passage of partially adapted SIV between humans could produce the series of cumulative mutations sufficient for the emergence of epidemic HIV strains. We examined the rapid growth of unsterile injections in Africa beginning in the 1950s as a biologically plausible event capable of greatly increasing serial human passage of SIV and generating HIV by a series of multiple genetic transitions. We conclude that increased unsterile injecting in Africa during the period 1950-1970 provided the agent for SIV human infections to emerge as epidemic HIV in the modern era.

Prevalence of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in the community.

Recent reports indicate that community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing and may now involve persons without risk factors predisposing for acquisition. To estimate the extent of community MRSA in New York City, the prevalence of S. aureus and MRSA nasal colonization in a well-patient population of 500 children and guardians was determined. The prevalence of S. aureus nasal carriage was 35% for children and 28% for guardians. One person with predisposing risk factors was colonized with an MRSA, which was identified as the predominant clone found in New York City hospitals. A high degree of methicillin-susceptible S. aureus strain diversity was noted, with no apparent selection for specific clonal types. Thus, MRSA colonization is not ubiquitous in persons without predisposing risk outside of the health care environment. Bacterial competition and a lack of strong selection may limit the community spread of MRSA and can account for its sporadic distribution.

The contribution of recently acquired Mycobacterium tuberculosis infection to the New York City tuberculosis epidemic, 1989-1993.

Current theory in the molecular epidemiology of tuberculosis holds that tuberculosis cases harboring Mycobacterium tuberculosis strains with a common deoxyribonucleic acid (DNA) fingerprint are the result of recent M. tuberculosis transmission. Here we propose a mathematical approach independent of DNA fingerprinting to estimating the percentage of recent transmissions responsible for current tuberculosis incidence. The "short-term reproductive number" of tuberculosis is defined as the average number of tuberculosis cases developing within 1 year of infection. Multiplying the short-term reproductive number by the number of tuberculosis cases in each year and dividing by the subsequent year's tuberculosis case burden equals the proportion of tuberculosis cases in the subsequent year that are due to recent transmission. We carried out separate calculations for human immunodeficiency virus (HIV)-negative and HIV-positive tuberculosis cases. We applied the model to pulmonary (infectious) tuberculosis cases diagnosed in New York City during 1989-1993, using tuberculosis and AIDS surveillance data. Model-based estimates of the proportion of tuberculosis due to recent transmission were lower than estimates based on DNA fingerprints. Reconciliation of these divergent estimates may require the re-estimation of model parameters from data collected de novo, additional model development, and further advances in DNA fingerprinting methods.

Identification of a W variant outbreak of Mycobacterium tuberculosis via population-based molecular epidemiology.

CONTEXT: Typing of Mycobacterium tuberculosis could provide a more sensitive means of identifying outbreaks than use of conventional surveillance techniques alone. Variants of the New York City W strain of M tuberculosis were identified in New Jersey. OBJECTIVE: To describe the spread of the W family of M tuberculosis strains in New Jersey identified by molecular typing and surveillance data. DESIGN: Population-based cross-sectional study. SETTING AND SUBJECTS: All incident culture-positive tuberculosis cases reported in New Jersey from January 1996 to September 1998, for which the W family was defined by insertion sequence (IS) IS6110 DNA fingerprinting, polymorphic GC-rich repetitive sequence (PGRS) typing, spacer oligotyping (spoligotyping), and variable number tandem repeat (VNTR) analysis. MAIN OUTCOME MEASURE: Identification and characterization of W family clones supplemented by surveillance data. RESULTS: Isolates from 1207 cases were analyzed, of which 68 isolates (6%) belonged to the W family based on IS6110 and spoligotype hybridization patterns. The IS6110 hybridization patterns or fingerprints revealed that43 patients (designated group A) shared a unique banding motif not present in other W family isolates. Strains collected from the remaining 25 patients (designated group B), while related to W, displayed a variety of IS6110 patterns and did not share this motif. The PGRS and VNTR typing confirmed the division of the W family into groups A and B and again showed group A strains to be closely related and group B strains to be more diverse. The demographic characteristics of individuals from groups A and B were specific and defined. Group A patients were more likely than group B patients to be US born (91 % vs 24%, P<.001), black (76% vs 16%, P<.001), human immunodeficiency virus positive (40% vs 0%, P = .007), and residents of urban northeast New Jersey counties (P<.001). Patients with group B strains were primarily non-US born, of Asian descent, and more dispersed throughout New Jersey. No outbreak had been detected using conventional surveillance alone. CONCLUSIONS: The implementation of multiple molecular techniques in conjunction with surveillance data enabled us to identify a previously undetected outbreak in a defined geographical setting. The outbreak isolates comprise members of a distinct branch of the W family phylogenetic lineage. The use of molecular strain typing provides a proactive approach that may be used to initiate, and not just augment, traditional surveillance outbreak investigations.

Cost-effectiveness of directly observed chemoprophylaxis of tuberculosis among drug users at high risk for tuberculosis.

SETTING: A methadone treatment program with on-site medical care in the Bronx, New York. OBJECTIVE: To define whether costs associated with directly observed preventive therapy (DOPT) of tuberculosis are justified by cases and costs of tuberculosis prevented among persons at high risk for active disease. DESIGN: Detailed data were collected on drug users in treatment regarding human immunodeficiency virus (HIV) and tuberculosis infection and disease, and costs of screening, chemoprophylaxis, direct observation and treatment of active disease. The cost-effectiveness of providing DOPT to this population was modeled. RESULTS: We assessed the impact of providing DOPT to 151 eligible persons. Assuming 65% isoniazid effectiveness, and incorporating costs of screening, observed chemoprophylaxis and clinical monitoring, a net savings in tuberculosis-related hospital costs of $285,284 ($563 per person screened) was associated with DOPT ($10,274 per case prevented). Direct observation of chemoprophylaxis proved cost-effective if associated with even a 10% increment in overall isoniazid effectiveness compared with self-administered chemoprophylaxis. DOPT costs per tuberculosis case averted remained below the in-patient costs of a single case of drug-sensitive disease across a range of parameter values. CONCLUSIONS: Providing DOPT is a highly cost-effective intervention for drug users in treatment. Commitment of additional resources required for DOPT should be given priority in this and other populations at high risk for tuberculosis.

Clinical predictors of Pneumocystis carinii pneumonia, bacterial pneumonia and tuberculosis in HIV-infected patients.

BACKGROUND: Clinicians are frequently faced with the differential diagnosis between Pneumocystis carinii pneumonia (PCP), bacterial pneumonia, and pulmonary tuberculosis in HIV-infected patients. OBJECTIVES: To identify features that could help differentiate these three pneumonia types at presentation by evaluating the clinical characteristics of the three diagnoses among patients at two urban teaching hospitals. DESIGN: Retrospective chart review. METHODS: Cases were HIV-infected patients with a verified hospital discharge diagnosis of PCP (n = 99), bacterial pneumonia (n = 94), or tuberculosis (n = 36). Admitting notes were reviewed in a standardized manner; univariate and multivariate analyses were used to determine clinical predictors of each diagnosis. RESULTS: Combinations of variables with the highest sensitivity, specificity, and odds ratios (OR) were as follows: for PCP, exertional dyspnea plus interstitial infiltrate (sensitivity 58%, specificity 92%; OR, 16.3); for bacterial pneumonia, lobar infiltrate plus fever < or = 7 days duration (sensitivity 48%, specificity 94%; OR, 14.6); and for tuberculosis, cough > 7 days plus night sweats (sensitivity 33%, specificity 86%; OR, 3.1). On regression analysis, independent predictors included interstitial infiltrate (OR, 10.2), exertional dyspnea (OR, 4.9), and oral thrush (OR, 2.9) for PCP; rhonchi on examination (OR, 12.4), a chart mention of 'toxic' appearance (OR, 9.1), fever < or = 7 days (OR, 6.6), and lobar infiltrate (OR, 5.8) for bacterial pneumonia; and cavitary infiltrate (OR, 21.1), fever > 7 days (OR, 3.9), and weight loss (OR, 3.6) for tuberculosis. CONCLUSIONS: Simple clinical variables, all readily available at the time of hospital admission, can help to differentiate these common pneumonia syndromes in HIV-infected patients. These findings can help to inform clinical decision-making regarding choice of therapy, use of invasive diagnostic procedures, and need for respiratory isolation.

Geographic diversity in tuberculosis trends and directly observed therapy, New York City, 1991 to 1994.

The New York City tuberculosis (TB) case rate declined from 1991 to 1994 following more than a decade of increases. The present study investigated TB trends in New York City neighborhoods and their association with neighborhood-specific rates of application of directly observed therapy (DOT). Using Poisson regression models, TB trends in each of New York City's 30 health districts were classified as increasing, decreasing, or stable, as indicated respectively by significant positive, negative, or nonsignificant regression coefficient. Case counts increased in four health districts, decreased in 10, and were stable in 16. Decreasing TB was associated with a higher rate of application of DOT. TB cases among foreign-born persons increased in 12 health districts and were stable in 18, whereas cases among persons born in the United States decreased in 19 and were stable in 11 districts. Among the foreign-born, increasing TB was not associated with a lesser rate of application of DOT. These data provide some support for the role of DOT in containing TB, but also suggest that the application of DOT among foreign-born residents is less effective than among United States-born residents. This may be due to a greater proportion of TB cases among the foreign-born being due to reactivation of TB rather than new infection.

Long-term perspective on the prevalent-cohort biases in studies of human immunodeficiency virus progression.

Because considerable information about progression of human immunodeficiency virus (HIV) infection has been provided by studies of cohorts of individuals with prevalent HIV infection, this study was designed to investigate bias due to onset confounding (differential time-since-infection distributions) and differential length-biased sampling in epidemiologic analyses of data from such cohorts. Subjects were participants in the Italian Seroconverters Study, a seroincident cohort of more than 1,200 adults seen at ambulatory care clinics in Italy, with observed HIV seroconversion in 1980-1988. Acquired immunodeficiency syndrome (AIDS) diagnoses, based on the 1987 Centers for Disease Control case definition, and mortality were ascertained through Italian national registries through 1994. To estimate bias in prevalent cohorts, a series of pseudoseroprevalent (PSP) cohorts were drawn by sampling, from among the total seroincident cohort, prevalent AIDS-free subjects in each calendar year. The relative AIDS risk associated with a given covariate was calculated in each PSP cohort and compared with the relative AIDS risk for that covariate in the seroincident cohort. Relative risks were estimated by both the ratio of AIDS incidence densities and the relative AIDS hazards from proportional hazards regression. Differential length bias was not evident, as assessed in the following way: Among 338 individuals with seroconversion dates in 1983-1986, the relative risk of AIDS for subjects born before 1951 compared with those born more recently was 1.67 (95% confidence interval (CI) 1.30-2.14). Although differential length-biased sampling was expected to bias this relative risk toward 1.0, the observed relative risk for earlier birth ranged from 1.79 to 2.86 in 1987-1992 PSP cohorts. Onset bias was observed: Among 644 subjects with seroconversion in 1980-1988, the AIDS relative risk for 1980-1985 seroconverters compared with 1986-1988 seroconverters was 1.09 (95% CI 0.76-1.55). Onset bias was seen in 1988-1990 PSP cohorts (relative risks for early seroconversion = 1.47, 1.46, and 1.34, respectively); in 1991-1992, relative risks were close to the expected value of 1.09, and CIs on relative risks from all PSP cohorts after 1989 included 1.0. Confounding attributable to differential length-biased sampling in prevalent cohorts does not necessarily bias estimates of the impact of covariates on rate of progression to AIDS. Bias can arise when a covariate suspected of affecting AIDS risk is closely linked to date of acquisition of HIV infection. However, onset bias appears to wane as subjects' dates of infection become more remote.

Low serum thiol levels predict shorter times-to-death among HIV-infected injecting drug users.

OBJECTIVES: To investigate whether serum thiol levels are altered by HIV disease, and whether low serum thiols predict time to death among HIV-infected injecting drug users (IDU). DESIGN: A cross-sectional study of serum thiol levels among 13 HIV-seronegative IDU, 116 HIV-seropositive IDU, and 17 HIV-seropositive IDU with a history of AIDS, and a cohort study of the 133 HIV-infected IDU who took part in the cross-sectional study. METHODS: Subjects were recruited from a methadone-maintenance treatment program during 1990-1991. Total serum thiols were determined spectrophotometrically at enrolment; low serum thiols were defined as those with an absorbance at 412 nm < or = 0.46. Deaths through 31 December 1993 were determined from the National Death Index (NDI). Twenty-six HIV-seropositive subjects died during follow up; death certificates, which were obtained for 23 subjects, indicated AIDS or HIV infection for 20. Product-limit estimation was used to calculate survival. Multivariate analyses employed Cox proportional-hazards regression. RESULTS: Analysis of cross-sectional data showed that serum thiols did not differ significantly among HIV-free subjects, HIV-infected subjects, and HIV-infected subjects with a history of AIDS. Cohort analysis, adjusted for age, revealed that persons with those with high serum thiols (relative hazard = 2.83; 95% confidence interval (CI), 1.15, 6.97); a significant interaction between low serum thiols and a history of AIDS was associated with a relative hazard of 5.65 (95% CI, 1.22-2.61). CONCLUSIONS: Among HIV-infected persons, low serum thiols, especially in concert with a history of AIDS, predict mortality risk. These findings support the hypothesis that oxidative stress is critical to the pathogenesis of HIV infection.

Social support for HIV-infected mothers: relation to HIV care seeking.

A cross-sectional survey was conducted to identify sources of social support for 92 HIV-seropositive mothers and to examine the relationship between social support and initiation of health care after a positive test for HIV antibody. Main outcome measures were self-reported source and amount of social support and length of time between the first positive HIV antibody test and the first visit for HIV care. Results indicated that HIV-infected mothers frequently delay seeking medical care and report attenuated social support networks. A limited program of HIV counseling and testing during pregnancy is unlikely to ensure that they will enter the healthcare system.

Use of a quantitative cytomegalovirus (CMV) antigenemia test in evaluating HIV+ patients with and without CMV disease.

Cytomegalovirus (CMV) infection remains a life-threatening infection in patients with HIV disease. A rapid, quantitative diagnostic technique is needed to adi in the diagnosis of CMV disease. This study was undertaken to evaluate the CMV antigenemia test in patients with HIV disease who are at risk for CMV disease. The study included 22 patients who underwent ophthalmologic exams or selected diagnostic techniques in whom CMV cultures and CMV antigenemia tests were performed. All of 11 patients with CMV disease had positive CMV antigenemia assays [range, 48-1,000 positive cells/2 x 10(5) peripheral blood leukocytes (PBL)], and 10 were also CMV viremic. There was no clinical evidence of CMV disease in 11 patients, including seven in whom the CMV antigenemia assay was negative and who remained without evidence of CMV disease after a median follow-up of 159 days. Four patients had low antigenemia levels. Of these four, two subsequently developed CMV retinitis. In conclusion, a positive CMV antigenemia result with > or = 48 positive cells/2 x 10(5) PBL correlated with concurrent CMV disease. The CMV antigenemia test appears to be a valuable tool for the rapid diagnosis of CMV disease in HIV-infected individuals.

Effect of stavudine on human immunodeficiency virus type 1 virus load as measured by quantitative mononuclear cell culture, plasma RNA, and immune complex-dissociated antigenemia.

The antiviral effect of stavudine (2', 3'-didehydro-3'-deoxythymidine) against human immunodeficiency virus (HIV) type 1 was measured in 15 HIV-infected patients at baseline and at weeks 4, 10, 22, 34, and 52 of therapy. Patients received 0.1, 0.5, 1.0, or 2.0 mg/kg/day of stavudine. At all time points examined during the 52 weeks of therapy, the median virus titers in peripheral blood mononuclear cells were decreased 1-2 logs, and median immune complex-dissociated antigen levels were reduced 37%-67% compared with baseline values. Plasma RNA content measured by polymerase chain reaction was reduced approximately 0.5 log from baseline median values at both time points examined (weeks 10 and 52). These data demonstrate that stavudine has a substantial and durable antiviral effect.

Injection drug use and human immunodeficiency virus infection.

In this paper we discuss the epidemiology and natural history of human immunodeficiency virus (HIV) infection in users of injection drugs. Use of injection drugs plays a central role in the HIV infection/AIDS epidemic in the United States, Europe, and many parts of the developing world. The significance of this role has been underappreciated until quite recently because of a number of factors. One factor has been systematic, albeit inadvertent, underreporting of cases of HIV disease and AIDS in drug injectors as a consequence of the initially narrow surveillance case definition for AIDS. A measure of this phenomenon has been the disproportionately larger increment of new cases in this population with each successive revision of the Centers for Disease Control and Prevention's surveillance case definition for AIDS. Other reasons for the underappreciation of the magnitude and consequences of HIV infection and AIDS in injection drug users include the lack of necessary diagnostic facilities in the institutions where drug users are often treated, high mortality rates among HIV-infected drug users for whom a diagnosis of AIDS has not yet been made, the severe marginalization of this population and its lack of advocates, and the localization of the initial epidemic in this population to certain geographic areas.

Childhood tuberculosis in the Bronx, New York.

The resurgence of tuberculosis (TB) in New York City in the period 1978-92 has been closely linked to the AIDS epidemic but the increase of active TB in areas of urban poverty also implies increased community exposure. We have examined the ecological relation between community rates of AIDS and residential crowding and cases of active TB in Bronx children under age 5. Residential crowding was defined as the percent of households with more than 1 person per room. All childhood TB cases reported between 1986 and 1992 for the Bronx (n = 75) were included. Cumulative AIDS mortality rates for adult females through 1990 represented community HIV burden. All data were coded by the 64 health areas of the borough. We examined trends in these data and used Poisson regression to model the effect of HIV burden and residential crowding on TB risk. For the Bronx as a whole the two variables of TB and residential crowding showed a clear temporal correspondence for the period 1970-90. Residential crowding was associated with poverty and greater dependence on public assistance, large household size, Hispanic ethnicity, and a higher proportion of young children. The overall TB case rate increased with the proportion of crowded households, with a rise from 1.47 to over 8 cases per 10,000 children as the proportion of crowded households increased. At both the lowest and highest levels of AIDS mortality in these areas, the childhood TB risk increased as crowding increased. Children living in areas of the Bronx in which over 12 percent of homes are severely overcrowded were 5.6-fold more likely to develop active TB, even after holding constant the presumed HIV burden in each local community. While HIV infection, the newest risk factor for TB, appears to play a critical role in the resurgent epidemic, our findings show that the earliest known TB risk factors, poverty and household crowding, are still potent forces.