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Biomedical subjects

C Robert Horsburgh

Publications and source records attributed to C Robert Horsburgh.

At least 19 recordsLinked to original sources
PubMed2026

Tuberculosis in children who are HIV-exposed uninfected.

OBJECTIVES: 1.3 million children are born each year to mothers with HIV but remain HIV-uninfected; more than 70% of these children live in settings with high tuberculosis (TB) burden. Whether children who are HIV-exposed uninfected (cHEU) are at increased risk of TB infection and disease is debated. DESIGN: We performed a systematic review and meta-analysis of TB infection and disease in cHEU versus children who are HIV-unexposed uninfected (cHUU) and children with HIV (CWH). METHODS: We searched PubMed, Embase, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and publication bibliographies through October 2025, using terms related to gestational HIV exposure and TB. We performed a qualitative synthesis and a meta-analysis of TST/IGRA positivity prevalence and disease cumulative incidence in cHEU versus cHUU, and cHEU versus CWH. RESULTS: : We included 26 studies in a systematic review and 18 studies in meta-analyses; 21/26 (81%) studies were restricted to children less than 2 years of age. Prevalence of TST/IGRA positivity [RR 1.26; 95% confidence interval (CI) 0.92-1.72, I2  = 0.0%] and cumulative disease incidence (RR 0.72; 95% CI 0.48-1.08, I2  = 0.0%) were similar between cHEU and cHUU. Prevalence of TST/IGRA positivity (RR 0.24; 95% CI 0.02-3.91, I2  = 93.2%) was not significantly different between cHEU and CWH. cHEU had lower risk of TB disease cumulative incidence than CWH (RR 0.29; 95% CI 0.16-0.51, I2  = 71.5%). CONCLUSION: cHEU and cHUU experience similar risk of TB infection and disease, while cHEU experience lower risk of disease than CWH. Findings were limited by a lack of studies after infancy and a small number of studies.

Humans↗
PubMed2006

Baseline mycobacterial immune responses in HIV-infected adults primed with bacille Calmette-Guérin during childhood and entering a tuberculosis booster vaccine trial.

BACKGROUND: Most new tuberculosis vaccines will be administered as a booster to subjects primed with bacille Calmette-Guérin (BCG) during childhood. METHODS: We investigated in vivo and in vitro immune responses to mycobacteria in human immunodeficiency virus (HIV)-positive subjects in Tanzania primed with BCG during childhood and entering a tuberculosis booster vaccine trial. Tests included intradermal skin testing for Mycobacterium tuberculosis purified protein derivative (PPD) and Mycobacterium avium sensitin (MAS); lymphocyte proliferation assays and interferon (IFN)-gamma levels after stimulation with Mycobacterium vaccae sonicate (MVS), M. tuberculosis early secreted antigen (ESAT)-6, M. tuberculosis antigen 85 (Ag85), or M. tuberculosis whole-cell lysate (WCL); and determination of serum antibody to lipoarabinomannin (LAM). RESULTS: A total of 888 subjects with CD4 cell counts > or = 200 cells/mm3 were enrolled. PPD and MAS test results were positive in 34% and 30% of the subjects, respectively. Proliferative responses were detected as follows: MVS, 6%; Ag85, 24%; ESAT-6, 21%; and WCL, 59%. IFN-gamma responses were 2%, 6%, 12%, and 38%, respectively. LAM antibody was detected in 28% of the subjects. Subjects were more likely to have detectable proliferative and IFN-gamma responses if they had positive PPD test results or CD4 cell counts > or = 500 cells/mm3. Overall, 94% of the subjects had evidence of primed mycobacterial immune responses. CONCLUSION: Of HIV-positive BCG-immunized adults with CD4 cell counts > or = 200 cells/mm3 in Tanzania, 94% are primed for booster mycobacterial immunization.

Adult↗
PubMed2006

Factors associated with loss to follow-up in a large tuberculosis treatment trial (TBTC Study 22).

INTRODUCTION: Loss to follow-up in clinical trials compromises achievement of study goals. We evaluated factors associated with loss to follow-up after completion of treatment phase in a large tuberculosis treatment trial (TBTC/USPHS Study 22) in the U.S. and Canada. METHODS: Patients who were lost to follow-up were compared to those who reached a study end-point or successfully completed follow-up. A generalized estimating equation model was used to combine patient-specific and site-specific factors. RESULTS: Of 1075 patients enrolled, 965 (89.8%) reached a study end-point, died, or completed the 2 year post-treatment follow-up phase, and 110 (10.2%) did not. Multivariate analysis showed the following factors to be independently associated with loss to follow-up: birth outside USA/Canada (OR 2.07, 95% CI 1.25-3.40, p=0.005), history of homelessness (OR 1.94, 95% CI 1.00-3.80, p=0.05), enrollment at a health department (OR 2.71, 95% CI 1.27-5.79, p=0.010), and use of any kind of incentive (cash/cash equivalent) during treatment phase (OR 3.04, 95% CI 1.73-5.33 p=0.0001). CONCLUSIONS: Cultural or linguistic factors and lack of stable housing contribute to loss to follow-up. Attention to these factors could improve long-term retention in clinical trials. Enrollment at a health department and use of incentives during treatment phase may be markers for other factors leading to loss to follow-up.

Antibiotics, Antitubercular↗
PubMed2006

Predicting non-completion of treatment for latent tuberculous infection: a prospective survey.

UNLABELLED: Treatment of latent tuberculosis (TB) infection (LTBI) is essential for the elimination of TB in the United States, but treatment is often not completed. Little is known about patients' reasons for not completing treatment. We hypothesized that certain health beliefs, lifestyle, and clinic- and regimen-related barriers to provision of care could predict non-completion of LTBI treatment. METHODS: We administered a survey in English, Chinese, or Spanish to patients with LTBI at the first TB clinic visit. Using chi(2) and logistic regression analysis, we assessed demographics, TB risk factors, and survey responses as predictors of non-completion of 6 mo of isoniazid. RESULTS: 217 patients, 90% foreign-born, completed the survey, and 28.6% of which finished at least 6 mo of isoniazid under usual clinic conditions. Multivariate analysis identified two independent predictors of non-completion: low risk perception of progressing to active TB without LTBI treatment (odds ratio [OR], 0.31 [0.13-0.72], 95% confidence interval [CI]), p = 0.007, accounting for 20% of non-completers, and not wanting venipuncture (OR, 0.43 [0.22-0.85], 95% CI), p = 0.015, accounting for 37% of non-completers. Another 18% shared both predictors; thus these two predictors accounted for 75% of non-completers in total. CONCLUSIONS: Patients assess LTBI treatment risks and inconveniences relative to low perceived benefits at treatment outset. Predictors of LTBI treatment non-completion are identifiable at the first visit. Targeting TB high-risk individuals, minimizing inconveniences, further education, and use of diagnostic tests with improved specificity for TB may address these concerns.

Adult↗
PubMed2006

Predictors of failure to complete treatment for latent tuberculosis infection.

OBJECTIVE: Low rates of completion of treatment for latent tuberculosis infection (LTBI) limit its usefulness as a strategy for elimination of tuberculosis (TB) in the United States. This retrospective cohort study assessed predictors of completion of LTBI treatment among patients seen at an urban United States TB clinic in 1998. METHODS: A retrospective cohort study of acceptance and completion of LTBI treatment among patients first seen in a TB clinic in 1998 was performed. RESULTS: Of 2621 persons with a positive tuberculosis skin test (TST), 1723 were offered treatment and 1572 (91.2%) accepted. Of the 1572 who accepted, treatment was completed by 607 (38.6%). Of those persons who failed to complete treatment, 517/965 (54%) dropped out before the end of the first month of the course. Among 1375 persons under 35 years of age who initiated LTBI treatment, failure to complete was associated with birth in Haiti (OR=2.17, CI(95%) 1.49-3.17) or the Dominican Republic (OR=1.93, CI(95%) 1.08-3.43). CONCLUSION: These results suggest that country-specific cultural and behavioral factors may contribute to failure to complete LTBI treatment, and that interventions to increase completion should focus on the first month after initiation.

Adolescent↗
PubMed2006

Lack of weight gain and relapse risk in a large tuberculosis treatment trial.

BACKGROUND: Readily identified markers of tuberculosis relapse risk are needed, particularly in resource-limited settings. The association between weight gain or loss during antituberculosis therapy and relapse has not been well studied. METHODS: Subjects in the Tuberculosis Trials Consortium Study 22 were studied. Underweight was defined as 10% or more below ideal body weight at diagnosis. Weight change was assessed between (1) diagnosis and completion of induction phase therapy, (2) diagnosis and end of continuation phase therapy, and (3) completion of induction to completion of continuation phase therapy. RESULTS: A total of 857 subjects were monitored for 2 yr, and 61 of 857 (7.1%) relapsed. Relapse risk was high among persons who were underweight at diagnosis (19.1 vs. 4.8%; p < 0.001) or who had a body mass index of less than 18.5 kg/m(2) (19.5 vs. 5.8%; p < 0.001). Among persons who were underweight at diagnosis, weight gain of 5% or less between diagnosis and completion of 2-mo intensive phase therapy was moderately associated with an increased relapse risk (18.4 vs. 10.3%; relative risk, 1.79, 95% confidence interval, 0.96-3.32; p = 0.06). In a multivariate logistic regression model that was adjusted for other risk factors, a weight gain of 5% or less between diagnosis and completion of 2-mo intensive phase therapy among persons underweight at diagnosis was significantly associated with relapse risk (odds ratio, 2.4; p = 0.03). CONCLUSIONS: Among persons underweight at diagnosis, weight gain of 5% or less during the first 2 mo of treatment is associated with an increased relapse risk. Such high-risk patients can be easily identified, even in resource-poor settings. Additional studies are warranted to identify interventions to decrease risk of relapse in such patients.

Adult↗
PubMed2006

Environmental risk factors for infection with Mycobacterium avium complex.

Infection with Mycobacterium avium complex is acquired from the environment, but risk factors for M. avium complex infection and disease are poorly understood. To identify risk factors for infection, the authors performed a 1998-2000 cross-sectional study in western Palm Beach County, Florida, using a population-based random household survey. M. avium complex infection was identified by use of the M. avium sensitin skin test. Of 447 participants, 147 (32.9%) had a positive test reaction, 186 (41.6%) had a negative test reaction, and, for 114 (25.5%), test results were indeterminate. Among the 333 participants with positive or negative M. avium sensitin skin tests, age-adjusted independent predictors of M. avium complex infection in a multivariate model included Black race (odds ratio = 3.8, 95% confidence interval: 2.2, 6.6), birth outside the United States (odds ratio = 2.1, 95% confidence interval: 1.1, 3.9), and more than 6 years' cumulative occupational exposure to soil (odds ratio = 2.7, 95% confidence interval: 1.3, 6.0). Exposure to water, food, or pets was not associated with infection. Results indicate that soil is a reservoir for M. avium complex associated with human infection and that persons whose occupations involve prolonged soil exposure are at increased risk of M. avium complex infection.

AIDS-Related Opportunistic Infections↗
PubMed2006

Endothelial function in HIV-infected persons.

BACKGROUND: Several reports have suggested an increased risk of coronary disease in human immunodeficiency virus (HIV)-infected patients receiving protease inhibitors (PIs). Impaired endothelium-dependent vasodilation is a putative surrogate marker of coronary atherosclerotic disease. METHODS: The present study evaluated the effect of HIV infection and antiretroviral treatment on endothelial vasomotor function, by assessing brachial artery flow-mediated dilation (FMD). A total of 75 HIV-infected patients were compared with 223 control subjects who were presumed to be HIV uninfected. RESULTS: HIV-infected patients had significantly impaired FMD, compared with control subjects (mean +/- SD, 7.3% +/- 4.4% vs. 11.1% +/- 6.3%; P < .0001). When adjustments were made for smoking status, sex, and body mass index, the difference between the 2 groups remained statistically significant (P < .01). In a cross-sectional analysis of the HIV-infected patients, we found significant associations between FMD and current injection drug use, hazardous drinking, HIV load, and alpha-high-density lipoprotein triglyceride levels, but not PI therapy. In a multivariate analysis, only current injection drug use and a lower alpha-high-density lipoprotein triglyceride level were significantly associated with FMD. CONCLUSIONS: HIV-infected patients have significant impairment of endothelial function, and this impairment is worse among those with elevated levels of HIV replication, particularly injection drug users.

Adult↗
PubMed2006

The scope and impact of treatment of latent tuberculosis infection in the United States and Canada.

RATIONALE: The scope of treatment of latent tuberculosis infection (LTBI) in the United States and Canada is unknown. Identifying the types of clinics that administer such treatment and patients who receive it could guide resource utilization and improve treatment initiation and completion. OBJECTIVES: Estimate the number of persons started on LTBI treatment; describe the types of clinics that treat LTBI. METHODS: The Tuberculosis Epidemiologic Studies Consortium, consisting of 19 United States and 2 Canadian sites, conducted a survey among clinics that initiated LTBI treatment for>or=10 patients in 2002. RESULTS: Study catchment areas from the 19 United States sites represented 8.6% of the United States population and 12.7% of all tuberculosis cases in 2000. An estimated 37,857 patients started LTBI treatment during 2002 at 244 clinics surveyed. Of these treatment starts, 29,970 (79%) occurred at general public health clinics; immigrant/refugee clinics (2,409; 6.4%) and correctional/detention facilities (2,325; 6.1%) were the next most common sites. Based on these data, United States tuberculosis case rates, and United States population data, the estimated total number of LTBI treatment starts in the United States was 291,000-433,000. When the 37,145 persons who initiated LTBI treatment in the United States were extrapolated to the entire United States population, with a 5% lifetime risk of tuberculosis without treatment, and 20-60% treatment effectiveness, approximately 4,000-11,000 tuberculosis cases were prevented in the United States. CONCLUSIONS: LTBI treatment is initiated among a substantial number of persons in the United States and Canada, primarily in the public sector. Treatment of LTBI can significantly decrease the tuberculosis burden.

Adolescent↗
PubMed2005

HIV infection does not affect the performance of noninvasive markers of fibrosis for the diagnosis of hepatitis C virus-related liver disease.

BACKGROUND: Noninvasive markers of hepatic fibrosis hold great promise to stage liver fibrosis and to monitor disease progression. To date, few studies have assessed the performance of the currently available markers of hepatic fibrosis in HIV-infected cohorts. The aim of the current study was to compare the diagnostic performance and characteristics of a number of noninvasive markers of hepatic fibrosis in populations of hepatitis C virus (HCV)-infected patients with and without HIV infection. METHODS: A sample of 97 subjects (40 HCV/HIV-coinfected, 57 HCV-infected) undergoing liver biopsy as part of an ongoing prospective cohort study was evaluated. Liver biopsies were assessed by a single hepatopathologist and scored according to Ishak criteria. Noninvasive markers of fibrosis studied included international normalized ratio, platelet count, aspartate aminotransferase (AST)/alanine aminotransferase ratio, AST platelet ratio index (APRI), Forns index, procollagen III N peptide, hyaluronic acid, and YKL-40. RESULTS: The correlations between fibrosis markers with the stage of fibrosis and the diagnostic performance of each of the tests were similar in the groups with and without HIV infection. Although a trend to improved diagnostic performance in the HCV/HIV-coinfected group was observed, this may be related to the small sample size. CONCLUSIONS: The diagnostic performance of the evaluated noninvasive markers of liver fibrosis is equivalent in HCV/HIV-coinfected and HCV-infected subjects. These tests may be of value for the clinical evaluation of HCV/HIV-coinfected patients and warrant further study.

Adult↗
PubMed2005

High rates of clinical and subclinical tuberculosis among HIV-infected ambulatory subjects in Tanzania.

BACKGROUND: We sought to determine the prevalence of active tuberculosis among ambulatory HIV-infected persons in Tanzania with CD4 cell counts of > or =200 cells/mm3 and a bacille Calmette-Guerin vaccination scar. METHODS: Subjects who volunteered for a tuberculosis booster vaccine trial were screened for active tuberculosis by obtainment of a history, physical examination, chest radiography, sputum culture and acid fast bacillus (AFB) stain, and blood culture. All subjects underwent a tuberculin skin test (TST) and lymphocyte proliferation assays (LPAs) for detection of responses to mycobacterial antigens. RESULTS: Active tuberculosis was identified at baseline in 14 (15%) of the first 93 subjects who were enrolled: 10 (71%) had clinical tuberculosis (symptoms or chest radiograph findings), and 4 (29%) had subclinical tuberculosis (positive sputum AFB stain or culture results but no symptoms or chest radiograph findings). An additional 6 subjects with subclinical tuberculosis were identified subsequently. The 10 subjects with subclinical tuberculosis included 3 with positive sputum AFB stains results and 7 who were only identified by a positive sputum culture result. Compared with subjects who did not have tuberculosis, the 10 subjects with subclinical tuberculosis were more likely to have peripheral lymphadenopathy, positive TST results, and elevated LPA responses to early secreted antigenic target-6 (ESAT). Eight of 10 patients had received isoniazid because of a positive TST result before active tuberculosis was recognized. CONCLUSIONS: Clinical and subclinical tuberculosis are common among ambulatory HIV-infected persons, and some cases can only be identified by sputum culture. World Health Organization guidelines for screening for latent tuberculosis before treatment do not recommend sputum culture and, therefore, may fail to identify a substantial number of HIV-infected persons with subclinical, active tuberculosis.

Adult↗
PubMed2004

Human immunodeficiency virus infection in a rural community in the United States.

In 1986, a population-based survey of human immunodeficiency virus (HIV) infection in a rural Florida community showed that HIV prevalence was 28/877 (3.2%, 95% confidence interval (CI): 2.0, 4.4). In 1998-2000, the authors performed a second population-based survey in this community and a case-control study to determine whether HIV prevalence and risk factors had changed. After 609 addresses had been randomly selected for the survey, 516 (85%) residents were enrolled, and 447 (73%) were tested for HIV. HIV prevalence was 7/447 (1.6%, 95% CI: 0.4, 2.7) in western Palm Beach County and 5/286 (1.7%, 95% CI: 0.2, 3.3) in Belle Glade (p=0.2 in comparison with 1986). Independent predictors of HIV infection in both 1986 and 1998-2000 were having a history of sexually transmitted disease, number of sex partners, and exchanging money or drugs for sex. A history of having sex with men was a risk factor among men in 1986 but not in 1998-2000; residence in specific neighborhoods was a risk factor in 1998-2000 but not in 1986. The authors conclude that heterosexually acquired HIV infection did not spread throughout the community between 1986 and 1998 but persisted at a low level in discrete neighborhoods. Interventions targeting HIV-endemic neighborhoods will be needed to further reduce HIV prevalence in this area.

Adolescent↗
PubMed2004

Priorities for the treatment of latent tuberculosis infection in the United States.

BACKGROUND: The prevention of active tuberculosis through the treatment of latent tuberculosis infection is a major element of the national strategy for eliminating tuberculosis in the United States. Targeted treatment for persons who are at the highest risk for reactivation tuberculosis will be needed to achieve this goal. A more precise assessment of the lifetime risk of reactivation tuberculosis, usually estimated at 5 to 10 percent, could help to identify patients who are at the highest risk and motivate them to complete treatment. Currently, the rate of completion of treatment is low. METHODS: Published reports were reviewed to obtain estimates of the risk of tuberculosis among persons with a positive tuberculin skin test. Using these data, I constructed a model to estimate the lifetime risk of tuberculosis among persons with specific medical conditions. RESULTS: The lifetime risk of reactivation tuberculosis is 20 percent or more among most persons with induration of 10 mm or more on a tuberculin skin test and either human immunodeficiency virus infection or evidence of old, healed tuberculosis. The lifetime risk is 10 to 20 percent among persons with recent conversion of a tuberculin skin test and among most persons younger than 35 years of age who are receiving infliximab therapy and have induration of 15 mm or more on a tuberculin skin test. The risk is also 10 to 20 percent among children five years of age or younger who have induration of 10 mm or more on a tuberculin skin test. CONCLUSIONS: Persons with these characteristics should be targeted for intensive efforts to ensure full treatment of latent tuberculosis. Improved rates of completion of treatment among such persons could help to eliminate tuberculosis in the United States.

Adolescent↗
PubMed2004

Health-related quality of life of patients with HIV disease: impact of hepatitis C coinfection.

Health-related quality of life (HRQOL) is diminished in patients infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV), but the effect of HIV/HCV coinfection on HRQOL is unknown. We compared the HRQOL of urban HIV/HCV coinfected patients with that of patients infected with either HCV or HIV alone. We then compared the 3 groups with a US population sample, adjusting for demographic characteristics. HRQOL for the group of HIV/HCV coinfected patients was statistically similar to that of HRQOL in patients with either HCV or HIV alone, but the 3 groups had a significantly decreased HRQOL than did the adjusted US population. Using multivariate techniques, we determined that age, unemployment, injection drug use, and depression were associated with impaired HRQOL. These findings underscore the importance of a multidisciplinary approach to the treatment of these patient populations.

Adult↗
PubMed2003

Hospital water as a source of Mycobacterium avium complex isolates in respiratory specimens.

The clinical significance of recovery of Mycobacterium avium complex (MAC) organisms from respiratory specimens is poorly understood. One hundred sixty-one respiratory MAC isolates from 131 patients at Grady Memorial Hospital (Atlanta) and 13 MAC isolates from the hospital's hot water system were examined. Of the 131 patients, 35 (27%) had MAC disease, and 96 (73%) did not; 94 (72%) were human immunodeficiency virus infected. Ten different clusters were identified by pulsed-field gel electrophoresis. Patients without MAC disease were significantly more likely to have clustered isolates than were patients with MAC disease. Of 110 MAC isolates recovered from patients without MAC disease, 72 (65%) were part of a single large cluster that contained isolates recovered from the hospital's hot water system; 13 (25%) of 51 isolates from patients with MAC disease were also in this cluster. We conclude that acquisition of MAC from institutional water systems leads to substantial MAC disease but that most patients with MAC recovered from respiratory specimens have only transient colonization by MAC.

Carrier State↗
PubMed2003

Detection of latent tuberculosis among HIV-infected patients after initiation of highly active antiretroviral therapy.

This cross-sectional study of 110 individuals examined skin testing for latent tuberculosis infection (LTBI) after the initiation of highly active antiretroviral therapy. Skin test reactivity to one or more of four antigens was found in 98 out of 110 subjects (89%), and was maximal in those whose CD4 cell counts recovered to >= 100 cells/mm3. Skin testing is reliable for the identification or exclusion of LTBI once the CD4 cell count recovers to >= 100 cells/mm3.

AIDS-Related Opportunistic Infections↗
PubMed2003

Integration of a participatory research strategy into a rural health survey.

The Glades Health Survey, a population-based survey of tuberculosis and HIV infection, provides a model for building community-research partnerships with local health departments in ethnically diverse communities. The survey was initiated without broad community participation; a year and a half of organizing established community leadership of the project. Essential factors in the success of the project included a shared objective, direct confrontation of fears about research, inclusion of all socioeconomic and racial/ethnic groups, and community participation in performing the research. These activities led to establishment of a community-based organization that received funding for HIV counseling and testing and HIV prevention case management.

Community Health Planning↗