Paul J. Carson

Long-Term Clinical and Neuropsychological Outcomes of West Nile Virus Infection

BACKGROUND Since its introduction in 1999, West Nile virus has rapidly become the most common arboviral infection in North America. Little is known about the long-term clinical sequelae of West Nile virus infection. METHODS A total of 49 patients with laboratory-confirmed West Nile virus infection were identified through state-based surveillance. Stratification for disease severity was based on hospitalization during the infection episode. Assessment occurred a mean of 13 months after diagnosis. Medical records were reviewed, and a complete neurologic examination was performed. Standardized surveys for quality of life, functional ability, fatigue, and depression were performed for all subjects. An extensive battery of neuropsychological tests was performed to assess cognitive function. RESULTS Self-reported fatigue, memory problems, extremity weakness, word-finding difficulty, and headache were common complaints. Standardized survey data confirmed an overall sense of poor physical health, fatigue, depression, and moderate-to-severe disability in 24 (49%), 24 (49%), 12 (24%), and 4 (8%) patients, respectively. New tremor was seen or reported for 10 (20%) of the patients. Neuropsychological testing showed abnormalities of motor skills, attention, and executive functions. Univariate analysis of multiple risk factors did not identify any predictors of adverse outcomes. CONCLUSIONS Multiple somatic complaints, tremor, and abnormalities in motor skills and executive functions are common long-term problems among patients who have had West Nile virus infection. Patients with milder illness are just as likely as patients with more-severe illness to experience adverse outcomes.

Clinical and economic outcomes of a prospective antimicrobial stewardship program

PURPOSE A pre-post analysis of an antimicrobial stewardship program (ASP) involving the use of data-mining software to prospectively identify cases for ASP intervention was conducted. METHODS The investigators evaluated clinical outcomes and cost metrics before and after implementation of the ASP, which entailed daily physician review of summary reports on all adult inpatients receiving antimicrobial therapy. The primary outcome measures were annual antimicrobial expenditures and rates of infections due to common nosocomial pathogens; secondary outcome measures included patient survival and length of stay (LOS) in cases involving the indicator diagnoses of pneumonia and abdominal sepsis. RESULTS Antimicrobial expenditures, which had increased by an average of 14.4% annually in the years preceding ASP implementation, decreased by 9.75% in the first year of the program and remained relatively stable in subsequent years, with overall cumulative cost savings estimated at

Neuroinvasive Disease and West Nile Virus Infection, North Dakota, USA, 1999–2008

1.7 million. Rates of nosocomial infections involving Clostridium difficile, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci all decreased after ASP implementation. A pre-post comparison of survival and LOS in patients with pneumonia (n = 2186) or abdominal sepsis (n = 225) showed no significant differences in those outcomes in either patient group, possibly due to the hospitals initiation of other, concurrent infection-control programs during the study period. CONCLUSION A prospective collaborative ASP employed automated reports to efficiently identify key data for ASP review. After ASP implementation, antimicrobial expenditures and rates of nosocomial infections caused by resistant pathogens dropped without significant changes in patient survival, LOS, and readmissions for the two studied illness categories.

Plasma Cell Pleocytosis in Cerebrospinal Fluid in Patients with West Nile Virus Encephalitis

To determine risk for West Nile virus (WNV) neuroinvasive disease in North Dakota, we tested plasma samples from blood donors for WNV IgG and compared infection rates with reported WNV neuroinvasive disease incidence. We estimate that 1 in 244 WNV infections leads to neuroinvasive disease; risk is substantially increased among men and older persons.

Identification of Clinical Risk Factors for Nosocomial Pneumococcal Bacteremia

We describe 4 patients with West Nile virus encephalitis who all displayed previously unreported plasma cell pleocytosis of the cerebrospinal fluid (CSF). Three patients recovered but had varying degrees of mild neurologic disability on discharge from the hospital, and 1 patient died. The finding of significant numbers of plasma cells in CSF may serve as a useful early diagnostic clue for West Nile virus encephalitis.

Characteristics of Antibody Responses in West Nile Virus-Seropositive Blood Donors

Clinical risks for nosocomial pneumococcal bacteremia (NPB) have been analyzed previously in case series, a study design inadequate for this purpose. Therefore, we performed a case-control study of NPB, pairing each of 37 cases identified retrospectively at the Minneapolis Veterans Affairs Medical Center from the period of 1984-1994 with four or five hospitalized controls. Comorbidities identified at the time of admission that were significantly associated with NPB on univariate and multivariate analysis included respiratory or hematologic malignancy, anemia, chronic obstructive pulmonary disease, and coronary artery disease. All characteristic symptoms and signs of pneumococcal infection were significantly more common in cases than in controls. NPB was strongly associated with death within 7 days of the index blood culture date, and the mortality rate among cases was 40.5%, compared with 1.2% among nonbacteremic controls (P < .00001). We conclude that NPB is a highly lethal infection that is associated with distinct but identifiable clinical risks, symptoms, and signs.

Catholic Social Teaching and the Duty to Vaccinate

ABSTRACT West Nile virus (WNV) is now endemic in the United States. Protection against infection is thought to be conferred in part by humoral immunity. An understanding of the durability and specificity of the humoral response is not well established. We studied the magnitude and specificity of antibody responses in 370 WNV-seropositive blood donors. We also recalled 18 donors who were infected in 2005 to compare their antibody responses at 6 months following infection versus at 5 years postinfection. There were no significant differences in IgG antibody levels based on age, sex, or recent infection (as evidenced by IgM positivity). Specific antibody responses by viral plaque reduction neutralization testing (PRNT) were seen in 51/54 subjects evaluated. All donors who were seropositive in 2005 remained seropositive at 5 years and maintained neutralizing antibodies. IgG levels at 5 years postinfection showed fairly minimal decreases compared with the paired levels at 6 months postinfection (mean of paired differences,−0.54 signal-to-cutoff ratio (S/CO) units [95% confidence interval {CI}, −0.86 to −0.21 S/CO units]) and only minimal decreases in PRNT titers. WNV induces a significant antibody response that remains present even 5 years after infection.

Plasma Cell Cerebrospinal Fluid Pleocytosis Does Not Predict West Nile Virus Infection

Since the last century, vaccination has been one of the most important tools we possess for the prevention and elimination of disease. Yet the tremendous gains from vaccination are now threatened by a growing hesitance to vaccinate based on a variety of concerns or objections. Geographic clustering of some families who choose not to vaccinate has led to a number of well-publicized outbreaks of vaccine-preventable diseases. Of note is that some of these outbreaks are centered within some Christian religious groups that increasingly avoid vaccination due to moral concerns, fears about safety, or doubts about the necessity of vaccines. We argue from the perspective of Catholic social teaching on why there is a moral duty to vaccinate.

Estimated cumulative incidence of West Nile virus infection in US adults, 1999–2010

Purpose. Diagnosis of WNV (WNV) relies upon serologic testing which may take several days after the onset of clinical symptoms to turn positive. Anecdotal reports suggest the presence of plasma cells or plasmacytoid lymphocytes in the cerebrospinal fluid (CSF) may be an early indicator of WNV infection. Methods. The CSFs of 89 patients (12 with WNV, 12 with other viral illness {OVI}, and 65 with nonviral illness{NVI}) were compared for the presence of either plasma cells or plasmacytoid lymphocytes. Results. Plasma cells were rarely seen in any of the patients. Plasmacytoid lymphocytes were more commonly seen in WNV (58%) and OVI (50%) than NVI (11%). The differences were significant for WNV versus NVI, but not WNV versus OVI (P < 0.001 and P = 0.58, resp.). Conclusions. A CSF pleocytosis with plasma cells or plasmacytoid lymphocytes was neither sensitive nor specific for the diagnosis of WNV infection.