Ann Mosher

Prospective Multicenter Surveillance Study of Funguria in Hospitalized Patients

Although fungal urinary tract infections are an increasing nosocomial problem, the significance of funguria is still not clear. This multicenter prospective surveillance study of 861 patients was undertaken to define the epidemiology, management, and outcomes of funguria. Diabetes mellitus was present in 39% of patients, urinary tract abnormalities in 37.7%, and malignancy in 22.2%; only 10.9% had no underlying illnesses. Concomitant nonfungal infections were present in 85%, 90% had received antimicrobial agents, and 83.2% had urinary tract drainage devices. Candida albicans was found in 51.8% of patients and Candida glabrata in 15.6%. Microbiological and clinical outcomes were documented for 530 (61.6%) of the 861 patients. No specific therapy for funguria was given to 155 patients, and the yeast cleared from the urine of 117 (75.5%) of them. Of the 116 patients who had a catheter removed as the only treatment, the funguria cleared in 41 (35.3%). Antifungal therapy was given to 259 patients, eradicating funguria in 130 (50.2%). The rate of eradication with fluconazole was 45.5%, and with amphotericin B bladder irrigation it was 54.4%. Only 7 patients (1.3%) had documented candidemia. The mortality rate was 19.8%, reflecting the multiple serious underlying illnesses found in these patients with funguria.

Discriminating between latent and active tuberculosis with multiple biomarker responses

We sought to identify biomarker responses to tuberculosis specific antigens which could 1) improve the diagnosis of tuberculosis infection and 2) allow the differentiation of active and latent infections. Seventy subjects with active tuberculosis (N = 12), latent tuberculosis (N = 32), or no evidence of tuberculosis infection (N = 26) were evaluated. We used the Luminex Multiplexed Bead Array platform to simultaneously evaluate 25 biomarkers in the supernatant of whole blood samples following overnight stimulation using the Quantiferon(®) Gold In-Tube kit. We defined the response to stimulation as the difference (within an individual patient) between the response to the pooled tuberculosis antigens and the negative control. IP-10 response was significantly higher in tuberculosis-infected (active or latent) subjects compared to the uninfected group (p < 0.0001). Among the 25 parameters, expression levels of IL-15 and MCP-1 were found to be significantly higher in the active tuberculosis group compared to the latent tuberculosis group (p = 0.0006 and 0.0030, respectively). When combined, IL-15 and MCP-1 accurately identified 83% of active and 88% of latent infections. The combination of IL-15 and MCP-1 responses was accurate in distinguishing persons with active tuberculosis from persons with latent tuberculosis in this study.

Geographic Information System-based Screening for TB, HIV, and Syphilis (GIS-THIS): A Cross-Sectional Study

Objective To determine the feasibility and case detection rate of a geographic information systems (GIS)-based integrated community screening strategy for tuberculosis, syphilis, and human immunodeficiency virus (HIV). Design Prospective cross-sectional study of all participants presenting to geographic hot spot screenings in Wake County, North Carolina. Methods The residences of tuberculosis, HIV, and syphilis cases incident between 1/1/05–12/31/07 were mapped. Areas with high densities of all 3 diseases were designated “hot spots.” Combined screening for tuberculosis, HIV, and syphilis were conducted at the hot spots; participants with positive tests were referred to the health department. Results and Conclusions Participants (N = 247) reported high-risk characteristics: 67% previously incarcerated, 40% had lived in a homeless shelter, and 29% had a history of crack cocaine use. However, 34% reported never having been tested for HIV, and 41% did not recall prior tuberculin skin testing. Screening identified 3% (8/240) of participants with HIV infection, 1% (3/239) with untreated syphilis, and 15% (36/234) with latent tuberculosis infection. Of the eight persons with HIV, one was newly diagnosed and co-infected with latent tuberculosis; he was treated for latent TB and linked to an HIV provider. Two other HIV-positive persons had fallen out of care, and as a result of the study were linked back into HIV clinics. Of 27 persons with latent tuberculosis offered therapy, nine initiated and three completed treatment. GIS-based screening can effectively penetrate populations with high disease burden and poor healthcare access. Linkage to care remains challenging and will require creative interventions to impact morbidity.

Feasibility and willingness-to-pay for integrated community-based tuberculosis testing

BackgroundCommunity-based screening for TB, combined with HIV and syphilis testing, faces a number of barriers. One significant barrier is the value that target communities place on such screening.MethodsIntegrated testing for TB, HIV, and syphilis was performed in neighborhoods identified using geographic information systems-based disease mapping. TB testing included skin testing and interferon gamma release assays. Subjects completed a survey describing disease risk factors, healthcare access, healthcare utilization, and willingness to pay for integrated testing.ResultsBehavioral and social risk factors among the 113 subjects were prevalent (71% prior incarceration, 27% prior or current crack cocaine use, 35% homelessness), and only 38% had a regular healthcare provider. The initial 24 subjects reported that they would be willing to pay a median

Effect of Improving the Quality of Radiographic Interpretation on the Ability to Predict Pulmonary Tuberculosis Relapse

20 (IQR: 0-100) for HIV testing and

Moxifloxacin versus Ethambutol in the First 2 Months of Treatment for Pulmonary Tuberculosis

10 (IQR: 0-100) for TB testing when the question was asked in an open-ended fashion, but when the question was changed to a multiple-choice format, the next 89 subjects reported that they would pay a median

The value of end-of-treatment chest radiograph in predicting pulmonary tuberculosis relapse.

5 for testing, and 23% reported that they would either not pay anything to get tested or would need to be paid

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

5 to get tested for TB, HIV, or syphilis. Among persons who received tuberculin skin testing, only 14/78 (18%) participants returned to have their skin tests read. Only 14/109 (13%) persons who underwent HIV testing returned to receive their HIV results.ConclusionThe relatively high-risk persons screened in this community outreach study placed low value on testing. Reported willingness to pay for such testing, while low, likely overestimated the true willingness to pay. Successful TB, HIV, and syphilis integrated testing programs in high risk populations will likely require one-visit diagnostic testing and incentives.

Multi-cytokine Profiles After Tuberculosis Antigen Stimulation: A Search For New Biomarkers For Latent And Active Tuberculosis

RATIONALE AND OBJECTIVES Chest radiographic findings are important for diagnosis and management of tuberculosis. The reliability of these findings is therefore of interest. We sought to describe interobserver reliability of chest radiographic findings in pulmonary tuberculosis, and to understand how the reliability of these findings might affect the utility of radiographic findings in predicting tuberculosis relapse. MATERIALS AND METHODS Three blinded readers independently reviewed chest radiographs from a randomly selected group of 10% of HIV-seronegative subjects participating in a tuberculosis treatment trial. The three readers then arrived at a fourth, consensus radiographic interpretation. RESULTS A total of 241 films obtained from 99 patients were reviewed. Agreement among the independent readers was very good for the findings of bilateral disease (kappa = 0.71-0.86 among readers) and cavitation (kappa = 0.66-0.73). The original interpretation was reasonably sensitive and specific (compared to the consensus interpretation) for bilateral disease, but the sensitivity for cavity decreased from 81% for the 2-month film to 47% at end of treatment (P = 0.013). Substituting the consensus interpretation for the original interpretation increased the odds ratio for the association between cavitation on early chest radiograph and subsequent tuberculosis relapse from 4.97 to 8.97. CONCLUSION Radiographic findings were reasonably reliable between independent reviewers and the original interpretations. The original investigators, who knew the patients clinical course, were less likely to identify cavitation on the end of treatment chest radiograph. Improving the reliability of these findings could improve the utility of chest radiographs for predicting tuberculosis relapse.