April C. Pettit

The Index Case for the Fungal Meningitis Outbreak in the United States

Persistent neutrophilic meningitis presents a diagnostic challenge, because the differential diagnosis is broad and includes atypical infectious causes. We describe a case of persistent neutrophilic meningitis due to Aspergillus fumigatus in an immunocompetent man who had no evidence of sinopulmonary or cutaneous disease. An epidural glucocorticoid injection was identified as a potential route of entry for this organism into the central nervous system, and the case was reported to the state health department.

Herpes Simplex Encephalitis during Treatment with Tumor Necrosis Factor-α Inhibitors

We report 3 cases of herpes simplex virus encephalitis in patients receiving tumor necrosis factor-alpha (TNF-alpha) inhibitors for rheumatologic disorders. Although TNF-alpha inhibitors have been reported to increase the risk of other infectious diseases, to our knowledge, an association between anti-TNF-alpha drugs and herpes simplex virus encephalitis has not been previously described.

(1,3)-β-d-Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Meningitis Associated with Contaminated Methylprednisolone Injections

ABSTRACT Prompt diagnosis and treatment of fungal meningitis are critical, but culture is insensitive. (1,3)-β-d-Glucan (BDG) testing is FDA approved for serological diagnosis of invasive fungal disease; however, BDG testing is not approved for cerebrospinal fluid (CSF), and the appropriate cutoff value is unknown. We aimed to validate the diagnostic accuracy of CSF BDG measurements for fungal meningitis among patients exposed to contaminated methylprednisolone acetate (MPA). A retrospective observational study was conducted at St. Joseph Mercy Hospital and Vanderbilt University from November 2013 to February 2014. Patients were included if they had received a contaminated MPA injection. Cases were classified as probable or proven meningitis according to Centers for Disease Control and Prevention guidelines. CSF BDG testing was performed according to the package insert instructions for serum samples, and results were validated using Clinical and Laboratory Standards Institute procedures (MiraVista Diagnostics). Of 233 patients, 45 had meningitis (28 proven cases), 53 had spinal/paraspinal infections (19 proven cases), and 135 did not develop disease. Using the manufacturers cutoff value (≥80 pg/ml), the sensitivity and specificity were 96% and 95%, respectively, for proven meningitis and 84% and 95% for probable or proven meningitis. Receiver operating characteristic analysis identified the optimal cutoff value for proven meningitis to be 66 pg/ml (sensitivity, 100%; specificity, 94%) and that for probable or proven meningitis to be 66 pg/ml (sensitivity, 91%; specificity, 92%). Our results suggest that CSF BDG measurements are highly sensitive and specific for the diagnosis of fungal meningitis associated with contaminated MPA injections. Further study on the utility of CSF BDG testing for other types of fungal meningitis is needed.

Chronic lung disease and HIV infection are risk factors for recurrent tuberculosis in a low-incidence setting

SETTING Programmatic data from the United States on tuberculosis (TB) recurrence are limited. OBJECTIVES To determine the TB recurrence rate and to determine if chronic lung disease (CLD) and human immunodeficiency virus (HIV) infection are risk factors for recurrence in this population. DESIGN Nested case-control study among TB cases reported to the Tennessee Department of Health between 1 January 2000 and 31 December 2006. Time at risk for recurrence was through 31 December 2007. Multiple imputation accounted for missing data. RESULTS Of 1431 TB cases, 20 cases recurred (1.4%, 95%CI 0.9-2.1). Median time at risk for recurrence was 4.5 years (interquartile range 2.7-6.1). Initial and recurrent Mycobacterium tuberculosis isolates were available for genotyping for 15 patients; 12 were consistent with relapse (0.8%, 95%CI 0.4-1.5) and three with re-infection (0.2%, 95%CI 0.04-0.6). HIV infection (OR 5.01, P = 0.04) and CLD (OR 5.28, P = 0.03) were independently associated with recurrent TB, after adjusting for a disease risk score. HIV infection was a risk factor for TB re-infection (P < 0.001). CONCLUSIONS In this low-incidence US population, the TB recurrence rate was low, but CLD and HIV were independent risk factors for recurrence. HIV infection was also a risk factor for TB re-infection.

Tuberculosis risk before and after highly active antiretroviral therapy initiation: does HAART increase the short-term TB risk in a low incidence TB setting?

Objective:To evaluate the short-term and long-term effects of highly active antiretroviral therapy (HAART) on tuberculosis (TB) risk compared with risk without HAART in a low TB incidence setting. Design:An observational cohort study among HIV-infected persons in care at the Comprehensive Care Center (Nashville, TN) between January 1998 and December 2008. Methods:A marginal structural model was used to estimate the effect of HAART on short-term (≤180 days) and long-term (>180 days) TB risk, with CD4+ lymphocyte count incorporated as a time-updated covariate. Results:Of 4534 HIV-infected patients, 34 developed TB (165 per 100,000 person-years; 20,581 person-years of follow-up). Seventeen cases occurred among persons not on HAART or >30 days after HAART discontinuation (212 per 100,000 person-years; 8019 person-years of follow-up). Seventeen occurred among persons on HAART (135 per 100,000 person-years; 12,562 person-years of follow-up); 10 in the first 180 days (402 per 100,000 person-years; 2489 person-years of follow-up); and 7 after more than 180 days (69 per 100,000 person-years; 10,073 person-years of follow-up). After adjusting for the most recent CD4+ lymphocyte count, the risk of TB in the first 180 days of HAART exposure relative to no HAART was 0.68 (0.14-3.22, P = 0.63). Conclusions:In this low TB incidence setting, the TB rate in the first 180 days of HAART was almost twice as high as persons not on HAART. However, after adjusting for most recent CD4+ count, there was no significant difference in TB risk between these 2 groups. This suggests that low recent CD4+ lymphocyte count influences TB risk during the first 180 days of HAART.

Female sex and discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis

OBJECTIVES To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study. METHODS The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007-September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression. RESULTS Of 1306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5-50.0%) completed treatment and 196 (15.0%, 95% CI 13.1-17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32-2.10, p < 0.001) and current alcohol use (RR 1.41, 95% CI 1.13-1.77, p = 0.003) were independently associated with isoniazid discontinuation due to adverse effects. CONCLUSIONS The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects.

Diagnosis and treatment of latent tuberculosis infection: an update

It is estimated that more than two billion people have latent M. tuberculosis infection, and this population serves as an important reservoir for future tuberculosis cases. Prevalence estimates are limited by difficulties in diagnosing the infection, including the lack of an ideal test, and an incomplete understanding of latency. Current tests include the tuberculin skin test and two interferon-γ release assays: QuantiFERON Gold In-Tube and T-SPOT.TB. This update focuses on recent publications regarding the ability of these tests to predict tuberculosis disease, their reproducibility over serial tests, and discordance between tests. We also discuss recent advances in the treatment of latent M. tuberculosis infection, including the three-month regimen of once-weekly rifapentine plus isoniazid, and prolonged isoniazid therapy for HIV-infected persons living in high-tuberculosis-incidence settings. We provide an update on the tolerability of the three-month regimen.

Non-adherence and drug-related interruptions are risk factors for delays in completion of treatment for tuberculosis

SETTING A key program performance objective established by the Centers for Disease Control and Prevention (CDC) is that ≥93% of tuberculosis (TB) cases complete treatment within 12 months. OBJECTIVE To determine the rate of and risk factors for delay in anti-tuberculosis treatment completion. DESIGN Nested case-control study among TB cases reported to the Tennessee Department of Health between 1 January 2000 and 31 December 2010. Time to complete treatment was calculated using treatment start and stop dates documented in the Tuberculosis Information Management System (TIMS). RESULTS Of 2627 cases, 261 (9.9%) required >12 months to complete treatment. In adjusted conditional logistic regression analyses, cavitary disease and positive cultures after 2 months of therapy (OR 5.85, 95%CI 1.98-17.32, P = 0.001), non-adherence (OR 4.13, 95%CI 1.76-9.72, P < 0.001), and interruptions in treatment due to drug-related issues (OR 6.91, 95%CI 3.76-12.70, P < 0.001) were independently associated with delay in completion of TB treatment. CONCLUSION From 2000 to 2010, the proportion of TB cases completing treatment within 12 months increased from 84.6% to 94.9%, and remained above the CDC target during 2009-2010. Efforts to improve patient adherence and reduce interruptions in treatment due to anti-tuberculosis drug-related issues could improve the proportion of TB cases completing treatment within 12 months.

The 2013 HIV Continuum of Care in Tennessee Progress Made, but Disparities Persist

Objectives: We measured patient engagement in the human immunodeficiency virus (HIV) continuum of care in Tennessee after implementation of enhanced surveillance activities to assess progress toward 2015 statewide goals. We also examined subgroup disparities to identify groups at risk for poor outcomes. Methods: We estimated linkage to care, retention in care, and viral suppression among HIV-infected people in Tennessee in 2013, overall and by subgroup, after implementation of enhanced laboratory reporting, address verification, and death-matching procedures. Results: Of 792 people newly diagnosed with HIV infection in 2013, 632 (79.8%) were linked to care, close to the 2015 goal of ≥80%. Of 15 473 people living and diagnosed with HIV infection before 2013, 8458 (54.7%) were retained in care, approaching the 2015 goal of ≥64.0%. A total of 8640 (55.8%) were virally suppressed, surpassing the 2015 goal of ≥51.0%. Compared with people living and diagnosed with HIV infection before 2013, newly diagnosed people were more likely to be younger, male, non-Hispanic black, and men who have sex with men (MSM). For linkage to care, retention in care, and viral suppression, younger and non-Hispanic black people fared worse, whereas females and those enrolled in the Ryan White program fared better. For retention in care and viral suppression, Hispanic people, injection drug users, and East Tennessee residents fared worse than those in Memphis, whereas MSM fared better. Nashville residents fared worse in retention in care than Memphis residents. Conclusion: Tennessee’s HIV continuum of care in 2013 showed progress toward 2015 goals. Future efforts to improve the HIV continuum of care should be directed toward vulnerable groups and regions, particularly young, non-Hispanic black, and Hispanic people; injection drug users; and residents of the East Tennessee and Nashville regions.

Index case for the fungal meningitis outbreak, United States.

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