B J Marsh

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

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Publications (9)57.49 Total impact

  • 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. · 9.37 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. · 5.85 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. · 1.33 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. · 9.37 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. · 6.41 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. · 6.41 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. · 9.37 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. · 9.37 Impact Factor