Bryan J. Marsh

Fish Tank Exposure and Cutaneous Infections Due to Mycobacterium marinum: Tuberculin Skin Testing, Treatment, and Prevention

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.

Revisiting Rates of Reactivation Tuberculosis: A Population-based Approach

RATIONALE 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. OBJECTIVES To calculate the rate of reactivation TB in a U.S. community. METHODS 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. MEASUREMENTS AND MAIN RESULTS 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). CONCLUSIONS 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.

Hepatitis C virus and HIV co-infection in people with severe mental illness and substance use disorders.

Objectives:The 5–7% of adults in the United States with severe mental illness (SMI), especially the 50% who are ‘dually diagnosed’ with co-occurring substance use disorders (SUD), are at an elevated risk of HIV and hepatitis C virus (HCV). However, little is known about HIV/HCV co-infection in this population. This paper examines the prevalence and correlates of HIV, hepatitis C, and HIV/HCV co-infection in a large, multisite sample of SMI clients. Design:We conducted a re-analysis of data on prevalence and correlates of blood-borne infections in a multisite sample of SMI clients. Methods:In 1997–1998, 755 SMI clients were tested for HIV, hepatitis B virus and HCV, and assessed for demographic, illness-related and other behavioral risk factors for blood-borne infections. The prevalence and correlates of co-infection were examined, as well as the knowledge, attitudes and risk behaviors of individuals with HCV mono-infection. Results:Of the 755 participants, 623 (82.5%) were negative for both HIV and HCV, 23 (3.0%) were positive for HIV, 109 (14.4%) were positive for HCV, and 13 (1.7%) were co-infected with HIV and HCV. Overall, 2.5% of dually diagnosed participants were co-infected, whereas only 0.6% of SMI participants without a comorbid SUD diagnosis were co-infected. Co-infection was associated with psychiatric illness severity, ongoing drug abuse, poverty, homelessness, incarceration, urban residence and minority status. HCV-mono-infected clients continued to engage in high levels of risk behavior for HIV. Conclusion:In addition to efforts to identify and treat SMI patients with HIV/HCV co-infection, HCV-mono-infected clients should be targeted for prevention interventions.

Dual Skin Testing with Mycobacterium avium Sensitin and Purified Protein Derivative to Discriminate Pulmonary Disease Due to M. avium Complex from Pulmonary Disease Due to Mycobacterium tuberculosis

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 risks and benefits of childhood bacille Calmette-Guerin immunization among adults with AIDS

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.

Cellular Immune Responses to Mycobacteria in Healthy and Human Immunodeficiency Virus-Positive Subjects in the United States After a Five-Dose Schedule of Mycobacterium vaccae Vaccine

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.

Immunization of HIV-Infected Adults With a Three-Dose Series of Inactivated Mycobacterium vaccae

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.

Utility of dual skin tests to evaluate tuberculin skin test reactions of 10 to 14 mm in healthcare workers.

OBJECTIVE To define the utility of 10- to 14-mm reactions to a Mycobacterium tuberculosis purified protein derivative (PPD) skin test for healthcare workers (HCWs). DESIGN 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. SETTING A single tertiary-care academic medical center. PARTICIPANTS 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. RESULTS 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. CONCLUSION 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.

Sustained reduction in tuberculosis incidence following a community-based participatory intervention.

BACKGROUND Rates of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease are elevated in the rural southeastern United States and among US- and foreign-born Black residents. To prevent TB and reduce TB transmission, community-based strategies are essential. OBJECTIVE To describe a community-based participatory intervention for improving the detection and treatment of LTBI and TB and reducing TB incidence. DESIGN In rural Florida, we carried out a community educational TB campaign from 1997 to 2000, including presentations at community events, a media campaign and working with local community groups to develop culturally appropriate prevention messages. The campaign was implemented concurrently with a population-based LTBI survey. RESULTS The annual TB incidence rate in the intervention area decreased from 81 per 100 000 in 1994-1997, to 42/ 100 000 in 1998-2001, and to 25/100 000 in 2002-2005 (P = 0.001). This decrease was not observed in communities where the intervention was not implemented. There was no decrease in the TB incidence rate ratio between Blacks and non-Blacks in either region during the study period. CONCLUSIONS We conclude that community participation in LTBI screening and TB education was associated with a substantial reduction in TB rates. Although the TB incidence rate ratio did not decrease between Blacks and non-Blacks, TB incidence fell in all racial groups.

Timing Is Everything

Tulula P. made her first visit to our AIDS clinic in January 2000. She tested HIV positive in late 1999 only after she had experienced several episodes