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Biomedical subjects

T R Sterling

Publications and source records attributed to T R Sterling.

At least 19 recordsLinked to original sources
PubMed2006

Mortality in a large tuberculosis treatment trial: modifiable and non-modifiable risk factors.

SETTING: North America. OBJECTIVES: Tuberculosis (TB) patients in North America often have characteristics that may increase overall mortality. Identifying modifiable risk factors would allow for improvements in outcome. DESIGN: We evaluated mortality in a large TB treatment trial conducted in the United States and Canada. Persons with culture-positive pulmonary TB were enrolled after 2 months of treatment, treated for 4 more months under direct observation, and followed for 2 years (total observation: 28 months). Cause of death was determined by death certificate, autopsy, and/or clinical observation. RESULTS: Of 1075 participants, 71 (6.6%) died: 15/71 (21.1%) HIV-infected persons, and 56/1004 (5.6%) non-HIV-infected persons (P < 0.001). Only one death was attributed to TB. Cox multivariate regression analysis identified four independent risk factors for death after controlling for age: malignancy (hazard ratio [HR] 5.28, P < 0.0001), HIV (HR 3.89, P < 0.0001), daily alcohol (HR 2.94, P < 0.0001), and being unemployed (HR 1.99, P = 0.01). The risk of death increased with the number of independent risk factors present (P < 0.0001). Extent of disease and treatment failure/relapse were not associated with an increased risk of death. CONCLUSIONS: Death due to TB was rare. Interventions to treat malignancy, HIV, and alcohol use in TB patients are needed to reduce mortality in this patient population.

Adult↗
PubMed2005

Impact of empiric antibiotics and chest radiograph on delays in the diagnosis of tuberculosis.

SETTING: Maryland Department of Health and Mental Hygiene, Division of Tuberculosis (TB) Control. OBJECTIVES: To assess the implications of antibiotic treatment of presumed community-acquired pneumonia (CAP) on delays in the diagnosis of TB, and to assess the frequency with which chest radiographs (CXRs) were utilized before a diagnosis of pneumonia or pulmonary TB was made. DESIGN: A nested case-control study within a prospective study conducted to assess factors associated with delays in the diagnosis of TB. RESULTS: Cases (n = 85; 54%) were patients who received antibiotics for non-TB diagnoses/indications prior to TB diagnosis, and controls (n = 73; 46%) were patients who had initially received TB therapy. Median health care delay for cases was 39 days vs. 15 days (P < 0.01) for controls. Median antibiotic delay was similar among all antibiotic classes. Of 54 patients who did not have a CXR at their first health care visit, 41 (79%) received empiric antibiotics, compared to 44/105 (42%) who had a CXR (P < 0.01). Only 31/54 (57%) patients initially diagnosed with CAP had a CXR at the time of diagnosis. CONCLUSION: More widespread use of CXR when diagnosing CAP should reduce delays in diagnosing TB, and the unnecessary use of antibiotics.

Adult↗
PubMed2004

The WHO/IUATLD diagnostic algorithm for tuberculosis and empiric fluoroquinolone use: potential pitfalls.

According to the current WHO/IUATLD diagnostic algorithm for tuberculosis, to establish the diagnosis of smear-negative pulmonary disease, patients should first demonstrate no clinical response to a course of broad-spectrum antibiotics. The fluoroquinolones have broad-spectrum activity against respiratory pathogens and are generally considered first-line therapy for the treatment of community-acquired pneumonia; they also have bactericidal activity against Mycobacterium tuberculosis. Of note, empiric fluoroquinolone monotherapy has been associated with delays in the initiation of appropriate anti-tuberculosis therapy, and also resistance in M. tuberculosis. Delays in the diagnosis and treatment of tuberculosis are associated with increased morbidity and mortality. Resistance to fluoroquinolones in M. tuberculosis could limit the use of this potentially first-line class of anti-tuberculosis agents. The WHO/IUATLD diagnostic criteria for smear-negative tuberculosis should be revised to ensure that fluoroquinolones are not used inappropriately and that the detrimental effects of empiric fluoroquinolone monotherapy in tuberculosis patients are avoided.

Algorithms↗
PubMed2003

Evaluation of an extensive tuberculosis contact investigation in an urban community and jail.

SETTING: Urban community and jail. OBJECTIVES/DESIGN: Evaluate outcome and process of an extensive tuberculosis contact investigation, including completion of treatment of latent TB infection (TLTBI). RESULTS: Between April 2000 and September 2001, 18 epidemiologically-linked tuberculosis cases were identified; 15 were culture-confirmed, all with a matching 14-band DNA fingerprint pattern. The source case had cavitary pulmonary disease and had been incarcerated 4 months prior to diagnosis. Sixty-six of 67 (99%) community contacts and 221/344 (64%) jail contacts were evaluated. The presumed new infection rate was 56% for community contacts (11 cases, 25 tuberculin skin test [TST] positive) and 20% for jail contacts (6 cases, 32 TST converters). Screening results for 113 (33%) jail contacts were obtained in the jail TST registry upon rearrest. All identified cases completed treatment. Of 22 community contacts initiating TLTBI, 11 completed (44% of infected, 50% of initiators). Of 32 infected jail contacts, 12 initiated TLTBI (all who remained incarcerated), and 10 completed (31% of infected, 83% of initiators). None of 20 additional in-fected jail contacts, all of whose TST conversions were identified with re-arrest data, were subsequently located. Two additional related cases have been identified as of October 2003. CONCLUSIONS: Close health department/corrections collaboration facilitated this extensive contact investigation, which identified high Mycobacterium tuberculosis transmission rates and controlled the outbreak. Numerous contacts were identified and screened, but rates of treatment completion for infected contacts were low. Novel strategies are needed to maximize the number of infected contacts who are not only identified and evaluated, but completely treated.

Adolescent↗
PubMed2002

A high tuberculosis case-fatality rate in a setting of effective tuberculosis control: implications for acceptable treatment success rates.

Worldwide, the case-fatality rate of smear-positive pulmonary tuberculosis among persons on treatment is 3.8%. We assessed the case-fatality rate among such patients in Baltimore between January 1993 and June 1998. Tuberculosis incidence was < 17/100 000 population, and 99% of patients received directly observed therapy. Of 174 patients, 42 (24%) died on treatment. Patients who died were older (mean age 62 vs. 47 years; P < 0.001) and were more likely to have underlying medical conditions. In multivariate analyses, older age, diabetes mellitus, and renal failure were independently associated with an increased risk of death. With effective control, tuberculosis may become concentrated in older persons with chronic diseases and be associated with high case-fatality rates. In such settings, acceptable treatment success rates may need to be revised.

Age Factors↗
PubMed2001

HIV-1 RNA, CD4 T-lymphocytes, and clinical response to highly active antiretroviral therapy.

OBJECTIVE: To determine if HIV-1 RNA and CD4 lymphocyte thresholds for the initiation of highly active antiretroviral therapy (HAART) are associated with clinical response to therapy. DESIGN: Observational cohort study. SETTING: Johns Hopkins Hospital HIV Clinic. PATIENTS: HIV-infected adults. INTERVENTION: Patients initiating HAART (n = 530) were compared with concurrent patients who did not receive HAART (n = 484). MAIN OUTCOME MEASURE: Progression to a new AIDS-defining illness or death. RESULTS: The average duration of follow-up for the cohort was 22 months. HAART resulted in decreased disease progression among persons with fewer than, but not more than, 200 x 10(6) CD4 lymphocytes/l prior to treatment. Among persons receiving HAART, plasma HIV-1 RNA level prior to therapy was not associated with HIV disease progression within CD4 T-lymphocyte count strata. In a Cox multivariate proportional hazards model that adjusted for age, sex, race, prior opportunistic infection, and CD4 T lymphocytes, < or = 200 x 10(6) CD4 lymphocytes/l was the strongest predictor of disease progression. HIV-1 RNA level prior to starting HAART of < 5000 copies/ml, 5001-55 000 copies/ml, or > 55 000 copies/ml was not associated with disease progression on therapy, particularly among persons with > 200 x 10(6) CD4 lymphocytes/l. There was no sex difference in disease progression on treatment. CONCLUSIONS: Our data suggest that current guidelines for initiating HAART should place greater emphasis on CD4 lymphocyte than HIV-1 RNA level for both men and women. Further longitudinal follow-up will be needed to better ascertain whether HAART initiated at > 200 x 10(6) CD4 lymphocytes/l is effective in slowing disease progression.

Adolescent↗
PubMed2001

Isoniazid preventive therapy, hepatitis C virus infection, and hepatotoxicity among injection drug users infected with Mycobacterium tuberculosis.

Treatment of latent Mycobacterium tuberculosis infection with isoniazid can cause hepatotoxicity, but the risk of isoniazid-associated hepatotoxicity among persons coinfected with hepatitis C virus (HCV) is unknown. We conducted a prospective study among 146 injection drug users with M. tuberculosis infection and normal baseline hepatic transaminase values who were treated with isoniazid. Of 146 participants, 138 (95%) were HCV-seropositive. Thirty-seven participants (25%) were human immunodeficiency virus (HIV)-seropositive. Thirty-two (22%; 95% confidence interval [CI], 16%-30%) of 146 participants developed transaminase value elevations to >3 times the upper limit of normal. Transaminase value elevation was associated with concurrent alcohol use but not with race, age, presence of hepatitis B surface antigen, HIV-1 infection, or current injection drug use. Isoniazid was withdrawn from 11 participants (8%; 95% CI, 4%-13%). Of 8 deaths during follow-up, none were attributed to isoniazid-associated hepatotoxicity. The risk of transaminase value elevation and drug discontinuation for HCV-infected persons receiving isoniazid was within the range reported for populations with lower HCV prevalence.

Adult↗
PubMed2001

Transmission of Mycobacterium tuberculosis through casual contact with an infectious case.

BACKGROUND: An ongoing restriction fragment length polymorphism study of Mycobacterium tuberculosis isolates from tuberculosis cases showed an identical 12-band IS6110 pattern unique to 3 unrelated patients (Patients A-C) diagnosed as having tuberculosis within a 9-month period. METHODS: In an attempt to identify epidemiologic links between the 3 patients, we performed site visits to the retail business work site of patient A and conducted detailed interviews with all 3 patients and their contacts. RESULTS: Patient B had visited patient A's work site 3 times during patient A's infectious period, spending no more than 15 minutes each time. Patient C visited patient A's work site on 6 to 10 occasions during this period for no more than 45 minutes at any one time. There were no other epidemiologic links between these 3 cases other than the contact at the store. Contact investigation identified 4 tuberculin skin test conversions among 8 (50%) of patient A's coworkers, 6 positive tests among 15 household contacts (40%), and 8 positive tests among 16 identified customers who were casual contacts (50%). Patient B and patient C were most likely infected by patient A during one of their brief visits to patient A's work site. CONCLUSIONS: These data demonstrate that some tuberculosis is spread through casual contact not normally pursued in traditional contact investigations and that, in certain situations, M tuberculosis can be transmitted despite minimal duration of exposure. In addition, this outbreak emphasizes the importance of DNA fingerprinting data for identifying unusual transmission in unexpected settings.

Adult↗
PubMed2001

Human immunodeficiency virus-seronegative adults with extrapulmonary tuberculosis have abnormal innate immune responses.

Extrapulmonary tuberculosis is presumably a marker of underlying immunodeficiency, but cytokine response pathways in these patients have not been well studied. Cytokine responses of peripheral blood mononuclear cells from human immunodeficiency virus-seronegative adults with prior culture-confirmed extrapulmonary tuberculosis were compared with those of persons with latent Mycobacterium tuberculosis infection. Mitogen-stimulated interferon (IFN)-gamma production, interleukin (IL)-12 production, and IFN-gamma receptor- and IL-12 receptor-mediated cytokine production did not differ between case patients and control patients. However, median resting IL-8 production was significantly lower in case patients than control patients (8051 vs. 19,290 pg/mL; P=.009). In addition, the median tumor necrosis factor (TNF)-alpha response was lower in case patients than control patients after stimulation with lipopolysaccharide (833 vs. 1149 pg/mL; P=.06) and lipopolysaccharide plus IFN-gamma (3301 vs. 4411 pg/mL; P=.04). These abnormalities in resting IL-8 and lipopolysaccharide-induced TNF-alpha production were not associated with IFN-gamma or IL-12 abnormalities and were detected up to several years after cure of disease, suggesting an abnormality in innate immunity.

Case-Control Studies↗
PubMed2001

Initial plasma HIV-1 RNA levels and progression to AIDS in women and men.

BACKGROUND: It is unclear whether there are differences between men and women with human immunodeficiency virus type 1 (HIV-1) infection in the plasma level of viral RNA (the viral load). In men, the initial viral load after seroconversion predicts the likelihood of progression to the acquired immunodeficiency syndrome (AIDS), but the relation between the two has not been assessed in women. Currently, the guidelines for initiating antiretroviral therapy are applied uniformly to women and men. METHODS: From 1988 through 1998, the viral load and the CD4+ lymphocyte count were measured approximately every six months in 156 male and 46 female injection-drug users who were followed prospectively after HIV-1 seroconversion. RESULTS: The median initial viral load was 50,766 copies of HIV-1 RNA per milliliter in the men but only 15,103 copies per milliliter in the women (P<0.001). The median initial CD4+ count did not differ significantly according to sex (659 and 672 cells per cubic millimeter, respectively). HIV-1 infection progressed to AIDS in 29 men and 15 women, and the risk of progression did not differ significantly according to sex. For each increase of 1 log in the viral load (on a base 10 scale), the hazard ratio for progression to AIDS was 1.55 (95 percent confidence interval, 0.97 to 2.47) among the men and 1.43 (95 percent confidence interval, 0.76 to 2.69) among the women. The median initial viral load was 77,822 HIV-1 RNA copies per milliliter in the men in whom AIDS developed and 40,634 copies per milliliter in the men in whom it did not; the corresponding values in the women were 17,149 and 12,043 copies per milliliter. Given the recommendation that treatment should be initiated when the viral load reaches 20,000 copies per milliliter, 74 percent of the men but only 37 percent of the women in our study would have been eligible for therapy at the first visit after seroconversion (P<0.001). CONCLUSIONS: Although the initial level of HIV-1 RNA was lower in women than in men, the rates of progression to AIDS were similar. Treatment guidelines that are based on the viral load, rather than the CD4+ lymphocyte count, will lead to differences in eligibility for antiretroviral treatment according to sex.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Paradoxical worsening of tuberculosis in HIV-infected persons.

OBJECTIVE: To determine the incidence of paradoxical worsening of tuberculosis (TB) in HIV-infected persons. DESIGN: Observational cohort study. SETTING: Public, urban TB clinic. PATIENTS: HIV-infected persons treated for TB between January 1, 1996, and December 31, 1999, and followed through June 30, 2000. INTERVENTION: Patients received standard anti-TB therapy. Antiretroviral therapy was provided by primary medical providers. Patients receiving antiretroviral therapy were given nucleoside reverse transcriptase inhibitors alone or highly active antiretroviral therapy (HAART; nucleoside reverse transcriptase inhibitors in combination with a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor). MAIN OUTCOME MEASURE: Paradoxical worsening of TB. RESULTS: There were 82 TB cases in 76 patients. Paradoxical worsening was identified in 6 of 82 cases (7%; 95% confidence interval, 3 to 15%). Paradoxical worsening occurred in 3 of 28 cases (11%) in patients receiving HAART and in 3 of 44 cases (7%) in patients not receiving antiretroviral therapy (p = 0.67). Cases complicated by paradoxical worsening were more likely to have both pulmonary and extrapulmonary disease at initial diagnosis than cases without paradoxical worsening (83% vs 24%; p = 0.006). TB relapse occurred in 2 of 6 cases (33%) in patients with paradoxical worsening and in 4 of 76 cases (5%) in patients without paradoxical worsening (p = 0.06). CONCLUSIONS: Paradoxical worsening of TB occurred less frequently than in previous reports and was not associated with HAART. Paradoxical worsening also appeared to be associated with an increased risk of TB relapse. Further studies are warranted to better characterize the risk factors for paradoxical worsening and the appropriate duration of anti-TB therapy in patients in whom it occurs.

AIDS-Related Opportunistic Infections↗
PubMed2000

A multi-state outbreak of tuberculosis among members of a highly mobile social network: implications for tuberculosis elimination.

SETTING: Baltimore, Maryland. OBJECTIVE: To describe a tuberculosis (TB) outbreak among a highly mobile population and the efforts required to control it. DESIGN: Epidemiologic outbreak investigation. RESULTS: Between June 1998 and January 2000, 20 TB outbreak cases were identified, of which 18 were culture-confirmed. Seventeen isolates of Mycobacterium tuberculosis had an identical 11-band DNA fingerprint; another isolate had one additional band and was considered a match. Two cases were diagnosed in New York City; another patient lived primarily in Atlanta, but was diagnosed in Baltimore. Persons in the outbreak were predominantly young (median age 24 years), black, male, infected with the human immunodeficiency virus (HIV), and gay, transvestite or transsexual. Activities common among many TB cases included attending two nightclubs, membership in one of three social 'Houses', attending balls or pageants in East Coast cities, marijuana use, and prostitution. Community outreach, extended contact tracing, DNA fingerprinting, directly-observed therapy, and expanded use of preventive therapy were utilized to assess and control the outbreak. During the outbreak period the Baltimore City TB rate declined by 10%. However, additional public health personnel were required to control the outbreak, resulting in a 17% increase in TB clinic staff. CONCLUSION: As TB rates decline, remaining cases are likely to occur in difficult-to-reach populations. Increased resources per case of TB treated will be required to eliminate TB.

AIDS-Related Opportunistic Infections↗