B J Marsh

Dartmouth–Hitchcock Medical Center, Lebanon, New Hampshire, United States

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Publications (20)113.3 Total impact

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    ABSTRACT: A positive tuberculin skin test (TST) may indicate cross-reacting immunity to non-tuberculous mycobacteria (NTM) and not latent tuberculosis infection (LTBI). To assess misclassification of LTBI, as assessed by skin testing with Mycobacterium avium sensitin (MaS), and to determine how this misclassification affects the analysis of risk factors for LTBI. In a population-based survey, participants underwent skin testing with M. tuberculosis purified protein derivative (PPD) and MaS. A PPD-dominant skin test was a reaction that was ≥ 3 mm larger than the MaS reaction; a MaS-dominant skin test was a reaction that was ≥ 3 mm larger than the PPD reaction. Of 447 randomly selected persons, 135 (30%) had a positive PPD test. Of these, 21 (16%) were MaS- dominant, and were therefore attributable to NTM and misclassified as LTBI. PPD reactions of 5-14 mm were more likely to be misclassified than those ≥ 15 mm (OR = 5.0, 95%CI 1.9-13.2). Adjusting for misclassification had only a small impact on the analysis of risk factors for LTBI. A substantial number of individuals who are diagnosed with LTBI are actually sensitized to NTM. Using dual skin testing would reduce misdiagnosis and prevent unnecessary treatment.
    The International Journal of Tuberculosis and Lung Disease 11/2011; 15(11):1504-9, i. DOI:10.5588/ijtld.11.0015 · 2.76 Impact Factor
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    ABSTRACT: Reactivation tuberculosis (TB) occurs as a result of reactivation of latent TB infection (LTBI), and was reported to occur in the United States at a rate of 0.10 to 0.16 cases per 100 person-years in the 1950s; it has not been measured since. To calculate the rate of reactivation TB in a U.S. community. A population-based tuberculin skin test survey for LTBI was performed in western Palm Beach County, Florida, from 1998 to 2000 along with a cluster analysis of TB case isolates in the same area from 1997 to 2001. Reactivation (unclustered) TB was presumed to have arisen from the population with LTBI. The rate of reactivation TB among persons with LTBI without HIV infection was 0.040 cases per 100 person-years (95% confidence interval [CI], 0.024-0.067) using the n method and 0.058 cases per 100 person-years (95% CI, 0.038-0.089) using the n-1 method. HIV infection was the strongest risk factor for reactivation (rate ratio [RR], 57; 95% CI, 27-120; P < 0.001). Among persons without HIV infection, reactivation was increased among those older than 50 years (RR, 3.8; 95% CI, 1.3-11) and among those born in the United States (RR, 3.2; 95% CI, 1.1-9.3). Rates of reactivation TB in this area have declined substantially since the 1950s. The greatest part of this decline may be attributed to the disappearance of old, healed TB in the population. If similar declines are seen in other areas of the United States, the cost-effectiveness of screening and treatment of LTBI may be substantially less than previously estimated.
    American Journal of Respiratory and Critical Care Medicine 08/2010; 182(3):420-5. DOI:10.1164/rccm.200909-1355OC · 11.99 Impact Factor
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    ABSTRACT: A rural section of a county in central Florida. Racial disparities in tuberculosis disease (TB) are substantial in the United States. To determine if TB was attributable to primary infection, reactivation or both. A population-based survey of latent tuberculosis infection (LTBI), a case-control analysis of TB, and a cluster analysis of TB isolates were performed between 1997 and 2001. Of 447 survey participants, 135 (30%) had LTBI. Black race was strongly associated with LTBI among US-born (OR 2.6, 95%CI 1.3-5.5) and foreign-born subjects (OR 4.3, 95%CI 2.2-8.4). Risk factors for TB included human immunodeficiency virus (HIV; OR 27.4, 95%CI 10.1-74.1), drug use (OR 4.6, 95%CI 1.7-12.4) and Black race (OR 3.4, 95%CI 1.2-9.6). The population risk of TB attributable to Black race was 64%, while that attributable to HIV was 46%. Cluster analysis showed 67% of TB cases were clustered, but Blacks were not at a significantly increased risk of having a clustered isolate (OR 2.1, 95%CI 0.12-36.0). Both reactivation TB and recent TB transmission were increased among Blacks in this community. Therefore, LTBI screening and intensive contact tracing, both followed by LTBI treatment, will be needed to reduce TB in Blacks.
    The International Journal of Tuberculosis and Lung Disease 06/2010; 14(6):733-40. · 2.76 Impact Factor
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    ABSTRACT: SETTING: A rural section of a county in central Florida.BACKGROUND: Racial disparities in tuberculosis disease (TB) are substantial in the United States.OBJECTIVE: To determine if TB was attributable to primary infection, reactivation or both.DESIGN: A population-based survey of latent tuberculosis infection (LTBI), a case-control analysis of TB, and a cluster analysis of TB isolates were performed between 1997 and 2001.RESULTS: Of 447 survey participants, 135 (30%) had LTBI. Black race was strongly associated with LTBI among US-born (OR 2.6, 95%CI 1.3-5.5) and foreign-born subjects (OR 4.3, 95%CI 2.2-8.4). Risk factors for TB included human immunodeficiency virus (HIV; OR 27.4, 95%CI 10.1-74.1), drug use (OR 4.6, 95%CI 1.7-12.4) and Black race (OR 3.4, 95%CI 1.2-9.6). The population risk of TB attributable to Black race was 64%, while that attributable to HIV was 46%. Cluster analysis showed 67% of TB cases were clustered, but Blacks were not at a significantly increased risk of having a clustered isolate (OR 2.1, 95%CI 0.12-36.0).CONCLUSION: Both reactivation TB and recent TB transmission were increased among Blacks in this community. Therefore, LTBI screening and intensive contact tracing, both followed by LTBI treatment, will be needed to reduce TB in Blacks.
    The International Journal of Tuberculosis and Lung Disease 05/2010; 14(6):733-740. · 2.76 Impact Factor
  • American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California; 04/2009
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    ABSTRACT: Although patients with human immunodeficiency virus (HIV) infection who live in the rural United States receive less expert care and less antiretroviral treatment, the impact of living in rural areas on mortality from HIV infection is unstudied. We compared mortality rates in 327 rural and 317 urban patients with HIV infection in a retrospective cohort study using a multivariate logistic regression model. Rural patients with HIV infection were older at the end of follow-up (43.4 vs. 41.4 years, p = 0.002), and more likely white (93.0% vs. 77.9%, p < 0.001), and a greater proportion were men who have sex with men (55.5% vs. 36.1%, p < 0.001). While the mean year of diagnosis was 1994 in rural patients and 1995 in urban patients (p < 0.001), the mean CD4(+) T cell count at presentation was similar in the two groups: 376 vs. 351 cells/mul (p = 0.298). Rural patients in our cohort were more likely to receive antiretroviral medications at any CD4 count (73.7 vs. 62.1%, p =0.0016), and received PCP prophylaxis at comparable rates (23.5% vs. 25.6%,p =0.555). Mortality was higher in rural patients (10.4% vs. 6.0%, p = 0.028). The risk of mortality remained higher in rural patients when adjusting for age, sex, race, HIV risk factors, year of diagnosis, travel time, lack of insurance, and receipt of antiretroviral treatment or PCP prophylaxis in a logistic regression model (OR 2.11, 1.064 to 4.218, p = 0.047). Patients with HIV who live in rural areas have higher mortality rates than urban patients with HIV.
    AIDS Research and Human Retroviruses 05/2007; 23(5):693-8. DOI:10.1089/aid.2006.0206 · 2.46 Impact Factor
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    ABSTRACT: 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.
    American Journal of Epidemiology 08/2006; 164(1):32-40. DOI:10.1093/aje/kwj159 · 4.98 Impact Factor
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    ABSTRACT: 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.
    American Journal of Epidemiology 10/2004; 160(6):582-8. DOI:10.1093/aje/kwh262 · 4.98 Impact Factor
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    ABSTRACT: To define the utility of 10- to 14-mm reactions to a Mycobacterium tuberculosis purified protein derivative (PPD) skin test for healthcare workers (HCWs). Blinded dual skin testing, using PPD and M. avium sensitin, of HCWs at a single medical center who had a 10- to 14-mm reaction to PPD when tested by personnel from the Occupational Health Department as part of routine annual screening. A single tertiary-care academic medical center. Employees of the medical center who underwent routine annual PPD screening and were identified by the Occupational Health Department as having a reaction of 10 to 14 mm to PPD. Nineteen employees were identified as candidates and 11 underwent dual skin testing. Only 4 (36%) had repeat results for PPD in the 10- to 14-mm range, whether read by Occupational Health Department personnel or study investigators. For only 5 (45%) of the subjects did the Occupational Health Department personnel and study investigators concur (+/- 3 mm) on the size of the PPD reaction. Two of the 4 subjects with reactions of 10 to 14 mm as measured by the study investigators were M. avium sensitin dominant, 1 was PPD dominant, and 1 was nondominant. A reaction of 10 to 14 mm to PPD should not be used as an indication for the treatment of latent tuberculosis (TB) infection in healthy HCWs born in the United States with no known exposure to TB.
    Infection Control and Hospital Epidemiology 12/2003; 24(11):821-4. DOI:10.1086/502143 · 3.94 Impact Factor
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    ABSTRACT: In the present study, 8 patients with soft tissue infection due to Mycobacterium marinum are described, and contemporary data on treatment are reviewed. Six patients had positive cultures, all patients had cutaneous exposure to fish tanks, 7 had sporotrichoid lesions, and 2 had deep infection. All 7 tested patients had tuberculin skin test reactions > or =10 mm. Six patients with disease limited to the skin were successfully treated with 2-drug combination therapy, including clarithromycin, ethambutol, and rifampin. Optimal treatment should include 2 drugs for 1-2 months after resolution of lesions, typically 3-4 months in total. Deeper infections may require more prolonged treatment and surgical debridement. Positive tuberculin reactions may be due to infection with M. marinum. Persons with open skin lesions or immunosuppression should avoid cutaneous contact with fish tanks.
    Clinical Infectious Diseases 09/2003; 37(3):390-7. DOI:10.1086/376628 · 9.42 Impact Factor
  • The American Journal of Gastroenterology 09/2002; 97(9). DOI:10.1016/S0002-9270(02)05296-6 · 9.21 Impact Factor
  • AIDS clinical care 01/2001; 12(12):101-3.
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    ABSTRACT: The safety and immunogenicity of heat-killed Mycobacterium vaccae vaccine were investigated in a pilot study assessing the feasibility of immunization to prevent mycobacterial disease in patients with human immunodeficiency virus (HIV) infection. Fifteen (seven healthy and eight HIV-positive subjects) received five doses of M. vaccae vaccine. Lymphocyte proliferation assays (LPAs) were performed using Mycobacterium avium sensitin (MAS) and M. vaccae sonicate (MVS). Vaccine was well tolerated in all 15 subjects with minimal induration at the vaccine site. LPAs for four of seven healthy vaccines were positive for MAS after immunization. Median responses to MAS and MVS that were determined by LPAs were consistently higher for the eight HIV-positive vaccinees than for the seven healthy controls. A five-dose series of M. vaccae vaccine is safe for both healthy and HIV-positive subjects and deserves further evaluation as a vaccine to prevent HIV-associated mycobacterial disease.
    Clinical Infectious Diseases 01/1999; 27(6):1517-20. DOI:10.1086/515024 · 9.42 Impact Factor
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    ABSTRACT: Skin testing with Mycobacterium avium sensitin (MAS) RS 10/2 and purified protein derivative (PPD) was conducted on patients with pulmonary disease due to M. avium complex (MAC) or Mycobacterium tuberculosis (MTB) and no known immunodeficiency. Reactions > or = 5 mm to either MAS or PPD were present in 37 (84%) of 44 MAC patients and 28 (97%) of 29 MTB patients. MAC patients had a mean MAS reaction of 13.8 (+/-8.3) mm and a mean PPD reaction of 3.5 (+/-8.6) mm (P < .001). MTB patients had a mean MAS reaction of 17.9 (+/-9.4) mm and a mean PPD reaction of 22.9 (+/-11.4) mm (P < .001). MAS-dominant skin tests (MAS reaction > or = 5 mm larger than PPD reaction) were present in 32 (73%) of 44 MAC patients and 1 (3%) of 29 MTB patients. MAS-dominant skin tests had a specificity of 97% for discriminating MAC disease from MTB disease.
    The Journal of Infectious Diseases 04/1998; 177(3):730-6. DOI:10.1086/514225 · 5.78 Impact Factor
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    ABSTRACT: Heat-killed Mycobacterium vaccae vaccine was administered in a 3-dose schedule to 12 HIV-infected adults with CD4 cell counts > or = 300/mm3. Local and systemic side effects were monitored. Delayed-type hypersensitivity to purified protein derivative and Mycobacterium avium sensitin was measured at baseline and after the final dose. Antibody to aralipoarabinomannin, man-lipoarabinomannin, and a short-term culture filtrate of Mycobacterium tuberculosis were also measured. Lymphocyte proliferation responses to M avium sensitin and M vaccae sonicate were determined. Vaccine site induration was maximal at 2 days (median, 6 mm) and no systemic side effects were noted. Purified protein derivative skin test conversions did not occur. Changes in CD4 counts and HIV viral load were not significant. Three (27%) of 11 subjects who completed the trial showed either M avium skin test (n = 1) or short-term culture filtrate antibody (n = 2) responses. A three-dose schedule of M vaccae vaccine is safe and well tolerated in adults with early HIV infection and produces detectable immunologic responses in a subset of these subjects.
    The American Journal of the Medical Sciences 07/1997; 313(6):377-83. DOI:10.1097/00000441-199706000-00011 · 1.52 Impact Factor
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    ABSTRACT: Heat-killed Mycobacterium vaccae vaccine was administered in a three-dose intradermal schedule to 10 healthy adult volunteers at 0, 2, and 10 months. Local and systemic side effects were monitored and vaccine site reactions were measured and photographed at visits 2 days, 14 days, and 2 months after each dose. Reactions to skin tests with purified protein derivative (PPD) and Mycobacterium avium sensitin (MAS) and titers of antibody to arabinose lipoarabinomannin were determined at baseline and after each dose of vaccine. Lymphocyte proliferation responses to MAS were determined after the final dose of vaccine. Immunization was safe and well tolerated, with maximal induration (range, 6-25 mm) at 2 days. PPD skin test conversions did not occur. Seven subjects completed the three-dose schedule; preexisting immunologic responses to mycobacteria were boosted in three, and a new response was elicited in one. M. vaccae vaccine is safe and induces measurable immunologic responses to mycobacterial antigens in some healthy adults.
    Clinical Infectious Diseases 06/1997; 24(5):843-8. DOI:10.1093/clinids/24.5.843 · 9.42 Impact Factor
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    ABSTRACT: To define the risks of disseminated bacille Calmette-Guérin (BCG) or disseminated Mycobacterium tuberculosis in adults with AIDS who were immunized with BCG in childhood. HIV-infected patients with CD4 < 200 x 10(6)/l were enrolled from five study sites (New Hampshire, Boston, Finland, Trinidad and Kenya). Prior BCG immunization was determined and blood cultures for mycobacteria were obtained at study entry and at 6 months. Acid-fast bacilli were identified as Mycobacterium tuberculosis complex (MTBC) using DNA probes. MTBC isolates were then typed by both IS6110 restriction fragment length polymorphism and polymerase chain reaction/restriction enzyme analysis. Most patients in New Hampshire and Finland were outpatients; most patients in Trinidad were inpatients with terminal illness; and most patients in Kenya were outpatients, although 44 were inpatients with terminal illness. A total of 566 patients were enrolled, including 155 with childhood BCG immunization; 318 patients had a single study visit and culture, and 248 patients had two study visits and cultures. Isolation and identification of mycobacteria from blood cultures. Blood cultures were positive for MTBC in 21 patients; none were positive for M. bovis BCG, and 21 were M. tuberculosis-positive. In Trinidad, seven (87%) out of eight isolates of M. tuberculosis were indistinguishable by IS6110 typing; BCG immunization was associated with a decreased risk of bacteremic infection with M. tuberculosis (P = 0.05). The risk of disseminated BCG among adult AIDS patients with childhood BCG immunization is very low. Childhood BCG immunization is associated with protection against bacteremia with M. tuberculosis among adults with advanced AIDS in Trinidad.
    AIDS 05/1997; 11(5):669-72. · 6.56 Impact Factor
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    ABSTRACT: Objective: To define the risks of disseminated bacille Calmette-Guérin (BCG) or disseminated Mycobacterium tuberculosis in adults with AIDS who were immunized with BCG in childhood. Design: HIV-infected patients with CD4 < 200 × 106/l were enrolled from five study sites (New Hampshire, Boston, Finland, Trinidad and Kenya). Prior BCG immunization was determined and blood cultures for mycobacteria were obtained at study entry and at 6 months. Acid-fast bacilli were identified as Mycobacterium tuberculosis complex (MTBC) using DNA probes. MTBC isolates were then typed by both IS6110 restriction fragment length polymorphism and polymerase chain reaction/restriction enzyme analysis. Setting: Most patients in New Hampshire and Finland were outpatients; most patients in Trinidad were inpatients with terminal illness; and most patients in Kenya were outpatients, although 44 were inpatients with terminal illness. Participants: A total of 566 patients were enrolled, including 155 with childhood BCG immunization; 318 patients had a single study visit and culture, and 248 patients had two study visits and cultures. Main outcome measures: Isolation and identification of mycobacteria from blood cultures. Results: Blood cultures were positive for MTBC in 21 patients; none were positive for M. bovis BCG, and 21 were M. tuberculosis-positive. In Trinidad, seven (87%) out of eight isolates of M. tuberculosis were indistinguishable by IS6110 typing; BCG immunization was associated with a decreased risk of bacteremic infection with M. tuberculosis (P = 0.05). Conclusions: The risk of disseminated BCG among adult AIDS patients with childhood BCG immunization is very low. Childhood BCG immunization is associated with protection against bacteremia with M. tuberculosis among adults with advanced AIDS in Trinidad.
    AIDS 05/1997; 11(5):669-672. DOI:10.1097/00002030-199705000-00015 · 6.56 Impact Factor
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    ABSTRACT: We sought to determine if patients with cystic fibrosis and sputum cultures positive for Mycobacterium avium complex (MAC) have delayed-type hypersensitivity to an M. avium sensitin. Seventeen (33%) of 51 selected patients had MAC isolated from at least one sputum culture. Skin tests with purified protein derivative and M. avium sensitin demonstrated that five (10%) of 51 patients were anergic, and anergy was correlated with use of systemic steroids. Sixteen (35%) of 46 nonanergic patients had M. avium-dominant skin test reactions. Twelve (75%) of these 16 patients with cultures positive for MAC had M. avium-dominant skin tests; the specificity of skin testing was 87%. These data suggest that most patients with cystic fibrosis and sputum cultures positive for MAC have infection rather than colonization with MAC. Skin testing with M. avium sensitin is a sensitive and specific method for screening these infections.
    Clinical Infectious Diseases 04/1996; 22(3):560-2. DOI:10.1093/clinids/22.3.560 · 9.42 Impact Factor
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    ABSTRACT: The sensitivity and specificity of dual mycobacterial skin testing were assessed in an unblinded study of 22 patients with culture-confirmed Mycobacterium avium complex (MAC) infection and 20 patients with culture-confirmed Mycobacterium tuberculosis infection. Intradermal skin tests were performed with 0.1 mL of M. avium sensitin, 0.1 mL of PPD (purified protein derivative), and two control antigens (mumps and Candida). All patients with M. tuberculosis infection reacted to the skin tests; the mean reaction size was 19.7 +/- 1.4 mm when PPD was administered and 10.3 +/- 1.5 mm when M. avium sensitin was administered. Four patients with MAC were anergic; for the remaining 18, mean reactions of 15.2 +/- 1.4 mm to M. avium sensitin and 4.3 +/- 1.3 to PPD were noted. A skin test was defined as M. avium-dominant or PPD (M. tuberculosis)-dominant if there was a minimum reaction size of > or = 5 mm to the given species, and the reaction to the given species was > or = 3 mm greater than the reaction to the heterologous species. Dominant skin test reactions were present in 18 (90%) of 20 patients with M. tuberculosis and 15 (83%) of 18 nonanergic patients with MAC. The specificity of dominant skin tests was 100% for infection with M. tuberculosis and 100% for infection with MAC. M. avium-dominant skin tests identify subjects with prior MAC infection and distinguish them from patients with M. tuberculosis infection.
    Clinical Infectious Diseases 07/1994; 19(1):15-20. DOI:10.1093/clinids/19.1.15 · 9.42 Impact Factor