Gregory Huhn

Spectrum of Infection and Risk Factors for Human Monkeypox, United States, 2003

Infection is associated with proximity to virus-infected animals and their excretions and secretions.

Two outbreaks of occupationally acquired histoplasmosis: more than workers at risk.

Objective: The objective of this study was to determine the etiology and risk factors for acute histoplasmosis in two outbreaks in Illinois among laborers at a landfill in 2001 and at a bridge reconstruction site in 2003. Design: We performed environmental investigations during both outbreaks and also performed an analytic cohort study among bridge workers. Participants: Workers at the landfill during May 2001 and those at the bridge site during August 2003 participated in the study. At the landfill, workers moved topsoil from an area that previously housed a barn; at the bridge, workers observed bat guano on bridge beams. Evaluations/Measurements: We defined a case by positive immunodiffusion serology, a ≥ 4-fold titer rise in complement fixation between acute and convalescent sera, or positive urinary Histoplasma capsulatum (HC) antigen. Relative risks (RR) for disease among bridge workers were calculated using bivariate analysis. Results: Eight of 11 landfill workers (73%) and 6 of 12 bridge workers (50%) were laboratory-confirmed histoplasmosis cases. Three bridge workers had positive urinary HC antigen. At the bridge, seeing or having contact with bats [RR = 7.0; 95% confidence interval (CI), 1.1–43.0], jack-hammering (RR = 4.0; 95% CI, 1.2–13.3), and waste disposal (RR = 4.0; 95% CI, 1.2–13.3) were the most significant job-related risk factors for acquiring histoplasmosis. Conclusions: Workers performing activities that aerosolized topsoil and dust were at increased risk for acquiring histoplasmosis. Relevance to Professional and Clinical Practice: Employees should wear personal protective equipment and use dust-suppression techniques when working in areas potentially contaminated with bird or bat droppings. Urinary HC antigen testing was important in rapidly identifying disease in the 2003 outbreak.

Characterization of CD4⁺ T-cell immune activation and interleukin 10 levels among HIV, hepatitis C virus, and HIV/HCV-coinfected patients.

Background:HIV/hepatitis C virus (HCV)–coinfected patients have accelerated liver disease compared with HCV monoinfection. In HIV-positive patients with viral suppression, data comparing inflammatory cytokines and immune activation between HIV/HCV coinfection with chronic hepatitis C (CHC) to HIV/HCV-seropositive patients with cleared HCV are limited. Methods:Fifty-nine age- and sex-matched patients were stratified: (1) HIV monoinfection (n = 15); (2) HCV monoinfection with CHC (n = 15); (3) HIV/HCV coinfection with CHC (n = 14); and (4) HIV/HCV seropositive with cleared HCV (n = 15). All HIV-positive patients had undetectable HIV viremia, and median CD4 was 420 cells per microliter. Liver fibrosis was assessed in each subject using transient elastography. Cells were collected for CD4 and CD8 immune activation (CD38/HLA-DR) markers via flow cytometry and plasma for luminex–multiplex cytokine assays. Results:CD38+HLA-DR+ expression on CD4+ T cells was significantly increased in HIV/HCV coinfection with CHC (7%) versus HCV monoinfection (4%) (P = 0.012). CD4+ total HLA-DR+ expression was significantly increased in HIV/HCV coinfection with CHC (43%) versus HIV monoinfection (31%) (P = 0.010) and HIV/HCV seropositive with cleared HCV (38%) (P = 0.046). Total CD4+CD38+ and CD4+CD38+HLA-DR− expression was significantly higher in HIV monoinfection (23% and 18%) than HCV moninfection (13%, P = 0.002% and 9%, P = 0.001, respectively). Interleukin 10 levels were significantly lower in HIV monoinfection versus HIV/HCV coinfection with CHC (P = 0.0002). In multivariate analysis, severe fibrosis was associated with lower expression of CD4+CD38+HLA-DR+ and CD4+ total CD38+ than mild-moderate fibrosis (P = 0.03 and 0.03, respectively). Conclusions:CD4 immune activation with HLA-DR+ expression in HIV/HCV coinfection with well-controlled HIV may arise from chronic HCV viremia. Conversely, CD4+CD38+ expression may be driven by underlying HIV infection. CD4 immune activation was unexpectedly found to be associated with decreased liver fibrosis.

Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution

BackgroundIn the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL.MethodsDuring December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases.ResultsFive cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045).ConclusionsAn unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.

Rash as a Prognostic Factor in West Nile Virus Disease

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A matched cross-sectional study of the association between circulating tissue factor activity, immune activation and advanced liver fibrosis in hepatitis C infection

BackgroundTissue factor (TF) is a protein that mediates the initiation of the coagulation cascade. TF expression is increased in patients with poorly-controlled HIV, and may be associated with increased immune activation that leads to cardiovascular morbidity. The role of TF in immune activation in liver disease in hepatitis C virus (HCV)-monoinfection and HIV/HCV-coinfection has not been explored.MethodsFifty-nine patients were stratified: A) HIV-monoinfection (N = 15), B) HCV-monoinfection with chronic hepatitis C (CHC) (N = 15), C) HIV/HCV-coinfection with CHC (N = 14), and D) HIV/HCV-seropositive with cleared-HCV (N = 15). All HIV+ patients had undetectable HIV viremia. Whole blood was collected for CD4/CD8 immune activation markers by flow cytometry and plasma was assayed for microparticle TF (MPTF) activity. Subjects underwent transient elastography (TE) to stage liver fibrosis. Undetectable versus detectable MPTF was compared across strata using Fishers Exact test.ResultsMPTF activity was more frequently detected among patients with HCV-monoinfection (40%), compared to HIV-monoinfection and HIV/HCV-seropositive with cleared HCV (7%) and HIV/HCV-coinfection with CHC (14%) (p = 0.02). Mean TE-derived liver stiffness score in kPa was higher in patients with detectable MPTF (12.4 ± 8.5) than those with undetectable MPTF (6.4 ± 3.0) (p = 0.01). Mean CD4 + HLADR+ and CD4 + CD38-HLADR+ expression were higher in those with detectable MPTF (44 ± 9.8% and 38 ± 8.7%, respectively) than those with undetectable MPTF (36 ± 11% and 31 ± 10.4% respectively) (p = 0.05 and 0.04 respectively).ConclusionsHCV-monoinfection and HIV/HCV-coinfection with CHC were associated with MPTF activity. MPTF activity is also associated with advanced liver fibrosis and with CD4 + HLADR+ immune activation.

Myocarditis Outbreak among Adults, Illinois, 2003

An outbreak of myocarditis occurred among adults in Illinois in 2003. Diagnostic testing of myocardial tissues from 3 patients and comprehensive tests for enterovirus and adenovirus of other specimens from patients were inconclusive. Appropriate specimen collection from patients with idiopathic cardiomyopathy and further enhancement of diagnostic techniques are needed.

Pertussis knowledge gaps among physicians

Effective prevention and treatment of pertussis may be more likely to occur if physicians are knowledgeable about this highly communicable infectious disease. Multiple studies have documented under-diagnosis of pertussis in adolescents and adults, but very little data is available regarding physici an knowledge of pertussis. The Advisory Committee on Immunization Practices has recommended booster vaccination for all adolescents and adults through 64 years of age against pertussis since 2006. Despite the recommendations, vaccination coverage with the Tdap (tetanus toxoid, reduced dose diphtheria, acel lular pertussis) vaccine among adolescents 13-17 years was 40.8% compared with 72.2% for Td vaccine in 2008. This survey of physicians from McHenry and Kane counties in Illinois administered from July 2002 to February 2003 and from July 2003 to February 2004 respectively, demonstrated significant gaps in pertussis knowledge and that physicians reported a minority of suspected pertussis cases to the health department. Review of board preparation materials available during this same period of time-demonstrated gaps in pertussis coverage. Baseline and follow-up data quantifying physician knowledge may help target education and determine associations with pertussis vaccination and reporting.