Roderick C. Jones

Clinical Characteristics and Functional Outcomes of West Nile Fever

Context The frequency of infection with West Nile virus is increasing rapidly in the United States. While the most fatal and closely studied manifestations of the disease are meningitis and encephalitis, little is known about the symptoms and clinical outcomes of West Nile fever. Contribution The authors interviewed 98 people with nonparalytic West Nile fever following recovery. Muscle weakness, fatigue, headache, difficulty concentrating, and fever were common manifestations. Approximately one third of patients required hospitalization. Median time to full recovery was 60 days. Implications Even in the absence of neurologic manifestations, West Nile virus infection is a potentially severe and debilitating illness. The Editors West Nile virus is a mosquito-borne pathogen with a wide geographic distribution in the eastern hemisphere (1). The first documented West Nile virus infections in the United States occurred in 1999 in New York City (2). Since then, the distribution of the virus has expanded rapidly and the number of infections has increased (3-5). In 2002, 4156 cases of West Nile virus disease and 284 deaths were reported throughout the United States (6), compared with 62 cases and 7 deaths in 1999 (2). Illinois had 884 documented cases with 66 deaths in 2002 (7). In 2003, the expansion continued; 9858 cases and 262 deaths were reported nationally (8). Since the initial identification and isolation of West Nile virus in 1937 (9), associated outbreaks have typically been characterized by mild febrile illnesses (10). Starting in the mid-1990s, however, the frequency and severity of outbreaks increased (11). Recent outbreaks in Romania, Russia, and Israel involved hundreds of persons and high rates of severe neurologic disease and fatalities (12-14). Most recent studies on infections caused by West Nile virus have focused on persons with neurologic disease, such as meningitis or encephalitis (10). However, 3 serologic studies of persons in the United States and Romania found that meningitis or encephalitis occurred in only about 1 of 150 infected persons (12, 15, 16). In addition, the serologic study conducted by Mostashari and colleagues (15) during the 1999 New York City outbreak found that most infections are not clinically apparent; only approximately 20% of infected persons developed symptoms that could be attributed to the virus. On the basis of the number of meningitis and encephalitis cases reported in 1999, the authors estimated that 3500 to 13000 West Nile virus infections occurred throughout the greater New York City area that year. West Nile fever is often the term used to describe symptomatic infections without neurologic disease. The typical description is a febrile illness of sudden onset lasting 3 to 6 days and often accompanied by malaise, anorexia, nausea, vomiting, eye pain, headache, myalgias, and rash (17). Clinical characterization of West Nile fever cases, however, is poor (10). Methods Case Finding and Case Definition Human cases of aseptic meningitis and encephalitis are reportable conditions in Illinois. In 2002, the Illinois Department of Public Health tested all cerebrospinal fluid and blood specimens submitted for suspected arboviral infection, regardless of clinical picture. In addition, the Illinois Department of Public Health accepted positive results on laboratory tests for West Nile virus infection from commercial laboratories. Whenever the Illinois Department of Public Health notified a local health authority of a West Nile viruspositive result in a resident of its jurisdiction, the local health authority conducted an epidemiologic investigation of the case. Persons who had positive test results but did not meet the Centers for Disease Control and Prevention definition for meningitis or encephalitis and did not satisfy published criteria for diagnosis of West Nile virusassociated acute flaccid paralysis (18) were considered to have West Nile fever. As part of the West Nile virus outbreak investigation conducted by the Illinois Department of Public Health and the Chicago Department of Public Health, West Nile fever cases were characterized in terms of reported symptoms and illness severity. We classified cases of West Nile virus disease on the basis of the Centers for Disease Control and Prevention case definitions for meningitis and encephalitis due to arboviral disease (19). The laboratory criterion for a confirmed diagnosis of West Nile virus disease was West Nile virus IgM in cerebrospinal fluid or West Nile virus genomic sequences in blood or cerebrospinal fluid. The laboratory criterion for a probable diagnosis of West Nile virus disease was West Nile virus IgM in serum. Cases were then classified on the basis of reported clinical criteria. We excluded patients with meningitis (fever, headache, stiff neck, and pleocytosis) or encephalitis (fever, headache, altered mental status, and pleocytosis). Patients with acute, progressive, asymmetric weakness, with or without the signs and symptoms of meningitis or encephalitis, were excluded because of the possibility of acute flaccid paralysis. The remaining patients were classified as having West Nile fever, defined as West Nile virus IgM or genomic sequences in serum but no symptoms or signs of meningitis, encephalitis, or acute flaccid paralysis. To ensure the exclusion of patients exhibiting more serious neurologic signs, we checked West Nile fever case reports before interviews to confirm that no patients had had lumbar puncture performed or cerebrospinal fluid submitted for laboratory evaluation and that confusion was not listed on the case report as a symptom. We confirmed this information with patients at the time of the interview. In addition, we obtained information from hospital records of selected patients when necessary to verify classification of illness. Data Collection To assess the clinical syndrome and functional outcomes of West Nile fever, we interviewed affected patients by telephone using a standard questionnaire. The questionnaire contained questions about the presence and duration of 18 different symptoms, hospitalization and other medical visits, medications taken or prescribed, the impact of the illness on daily activities, the amount of work or school missed, and underlying medical conditions during the illness (diabetes mellitus, history of cancer of any type, hypertension, heart disease, liver disease, kidney disease, and history of organ transplantation or immunosuppression). We determined duration of illness using self-reported illness information obtained at the time of the interview. Patients who lived in areas under the jurisdiction of participating local health departments and who were able to independently answer questions were eligible for inclusion. Statistical Analysis We used Epi Info (version 6.04b, Centers for Disease Control and Prevention, Atlanta, Georgia) and SAS (version 8.2, SAS Institute, Inc., Cary, North Carolina) to analyze the collected data. Simple proportions and medians were generated to describe the frequencies with which symptoms were reported, symptom duration, and the effects of symptoms on daily activities. We used the t-test to determine the statistical significance of differences in the means of continuous data and the MantelHaenszel chi-square test to determine the statistical significance of differences in proportions. We calculated 95% CIs of proportions using Wald methods. Because some individuals had continuing symptoms at the time of the interview, we examined the relationship between age and duration of illness using proportional hazards modeling; illness durations in persons with continuing symptoms were considered to be censored. We assessed the proportional hazards assumptions by introducing a time-dependent covariatethe interaction between age and timeto test whether there was a systematic increase or decrease in the effect of age across time. We assessed possible confounding due to hospitalization and underlying illness by including terms in the proportional hazards regression model. Results In 2002, 331 West Nile virus infections reported in Illinois residents met the case definition for West Nile fever. Of these, 140 persons (42%) lived in jurisdictions of participating local health departments and were eligible for inclusion in the study. No information was obtained on 191 individuals (58%) who lived in jurisdictions of nonparticipating health departments. Of the 140 persons eligible for inclusion, 29 were not interviewed because of incorrect telephone numbers; 9 could not be reached in at least 3 attempts; 3 were unwilling or unable to participate; and 1, who was 3 years of age, was not evaluated. The remaining 98 patients, who did not report having a lumbar puncture and had no record of submission of cerebrospinal fluid for laboratory testing, were enrolled in the study. Interviews were conducted from 18 December 2002 to 27 April 2003, a median of 168 days (range, 84 to 254 days) after illness onset. Thirty-eight of 98 patients (39%) had ongoing symptoms at the time of the interview. Questionnaire responses were missing for fever duration in 4 patients, for presence of fever in 1 patient, for duration of muscle weakness in 1 patient, and for duration of rash in 2 patients. Patients with missing responses were not included in the calculated proportions. One patient had unclear information about onset of illness, and date of laboratory diagnosis was used in place of illness onset date. In addition, 1 patient had unclear duration information and was excluded from the analysis of illness duration. The respondents were not significantly different in terms of sex and age from nonparticipating Illinois patients with West Nile fever (Table 1). Table 1. Characteristics of Respondents and Nonrespondents Laboratory Confirmation Standard laboratory methods were used to identify evidence of West Nile virus infection in the serum specimens of the 98 enrolled p

Management of outbreaks of methicillin-resistant Staphylococcus aureus infection in the neonatal intensive care unit : A consensus statement

OBJECTIVE In 2002, the Chicago Department of Public Health (CDPH; Chicago, Illinois) convened the Chicago-Area Neonatal MRSA Working Group (CANMWG) to discuss and compare approaches aimed at control of methicillin-resistant Staphylococcus aureus (MRSA) in neonatal intensive care units (NICUs). To better understand these issues on a regional level, the CDPH and the Evanston Department of Health and Human Services (EDHHS; Evanston, Illinois) began an investigation. DESIGN Survey to collect demographic, clinical, microbiologic, and epidemiologic data on individual cases and clusters of MRSA infection; an additional survey collected data on infection control practices. SETTING Level III NICUs at Chicago-area hospitals. PARTICIPANTS Neonates and healthcare workers associated with the level III NICUs. METHODS From June 2001 through September 2002, the participating hospitals reported all clusters of MRSA infection in their respective level III NICUs to the CDPH and the EDHHS. RESULTS Thirteen clusters of MRSA infection were detected in level III NICUs, and 149 MRSA-positive infants were reported. Infection control surveys showed that hospitals took different approaches for controlling MRSA colonization and infection in NICUs. CONCLUSION The CANMWG developed recommendations for the prevention and control of MRSA colonization and infection in the NICU and agreed that recommendations should expand to include future data generated by further studies. Continuing partnerships between hospital infection control personnel and public health professionals will be crucial in honing appropriate guidelines for effective approaches to the management and control of MRSA colonization and infection in NICUs.

Outbreak of Adenovirus Genome Type 7d2 Infection in a Pediatric Chronic-Care Facility and Tertiary-Care Hospital

An outbreak of adenovirus infection that involved residents of a pediatric chronic-care facility, staff of a tertiary-care hospital, and a nosocomial hospital case was studied. In the pediatric facility, 31 (33%) of 93 residents had adenovirus infection, and 8 died. Risk factors for illness were an age of < 7 years (P = .004), presence of a tracheostomy (P = .015), and residence on a particular floor (P < .001). In the tertiary-care hospital, 36 health care workers had adenovirus infection; 26 (72%) had failed to follow strict contact and droplet precautions, and 30 (83%) continued to care for patients while they had symptoms. A 5-month-old patient with underlying lung disease acquired severe adenovirus infection in this hospital. All isolates were adenovirus type 7 (Ad7). DNA restriction analysis revealed the band patterns of all isolates to be identical and characteristic of the genome type d2. Thus, Ad7d2 caused significant morbidity and mortality in persons in the pediatric chronic-care facility and tertiary-care hospital. This is the first published description of Ad7d2 strains in the United States.

Outbreak of Human Adenovirus Type 3 Infection in a Pediatric Long-Term Care Facility—Illinois, 2005

BACKGROUND Human adenovirus type 3 (HAdV-3) causes severe respiratory illness in children, but outbreaks in long-term care facilities have not been frequently reported. We describe an outbreak of HAdV-3 infection in a long-term care facility for children with severe neurologic impairment, where only 3 of 63 residents were ambulatory. METHODS A clinical case of HAdV-3 was defined as fever (temperature, > or = 38.0 degrees C) and either a worsening of respiratory symptoms or conjunctivitis in a resident, with illness onset from June through August 2005. We reviewed medical records; conducted surveillance for fever, conjunctivitis, and respiratory symptoms; and collected nasopharyngeal and conjunctival specimens from symptomatic residents. Specimens were cultured in HAdV-permissive cell lines or were analyzed by HAdV-specific polymerase chain reaction assay. RESULTS Thirty-five (56%) of 63 residents had illnesses that met the case definition; 17 patients (49%) were admitted to intensive care units, and 2 (6%) died. Patients were hospitalized in the intensive care unit for a total of 233 patient-days. Illness onset dates ranged from 1 June through 24 August 2005. Thirty-two patients (91%) had respiratory infection, and 3 (9%) had conjunctivitis. HAdV was identified by culture or PCR in 20 patients. Nine isolates were characterized as HAdV-3 genome type a2. CONCLUSIONS Considering the limited mobility of residents and their reliance on respiratory care, transmission of HAdV-3 infection during this outbreak likely occurred through respiratory care provided by staff. In environments where patients with susceptible underlying conditions reside, HAdV infection should be considered when patients are identified with worsening respiratory disease, and rapid diagnostic tests for HAdV infection should be readily available to help identify and curtail the spread of this pathogen.

Design and implementation of a privacy preserving electronic health record linkage tool in Chicago

OBJECTIVE To design and implement a tool that creates a secure, privacy preserving linkage of electronic health record (EHR) data across multiple sites in a large metropolitan area in the United States (Chicago, IL), for use in clinical research. METHODS The authors developed and distributed a software application that performs standardized data cleaning, preprocessing, and hashing of patient identifiers to remove all protected health information. The application creates seeded hash code combinations of patient identifiers using a Health Insurance Portability and Accountability Act compliant SHA-512 algorithm that minimizes re-identification risk. The authors subsequently linked individual records using a central honest broker with an algorithm that assigns weights to hash combinations in order to generate high specificity matches. RESULTS The software application successfully linked and de-duplicated 7 million records across 6 institutions, resulting in a cohort of 5 million unique records. Using a manually reconciled set of 11 292 patients as a gold standard, the software achieved a sensitivity of 96% and a specificity of 100%, with a majority of the missed matches accounted for by patients with both a missing social security number and last name change. Using 3 disease examples, it is demonstrated that the software can reduce duplication of patient records across sites by as much as 28%. CONCLUSIONS Software that standardizes the assignment of a unique seeded hash identifier merged through an agreed upon third-party honest broker can enable large-scale secure linkage of EHR data for epidemiologic and public health research. The software algorithm can improve future epidemiologic research by providing more comprehensive data given that patients may make use of multiple healthcare systems.

Clostridium difficile outbreak strain BI is highly endemic in Chicago area hospitals.

OBJECTIVE Describe the clinical and molecular epidemiology of incident Clostridium difficile infection (CDI) cases in Chicago area acute healthcare facilities (HCFs). DESIGN AND SETTING Laboratory, clinical, and epidemiologic information was collected for patients with incident CDI who were admitted to acute HCFs in February 2009. Stool cultures and restriction endonuclease analysis typing of the recovered C. difficile isolates was performed. PATIENTS Two hundred sixty-three patients from 25 acute HCFs. RESULTS Acute HCF rates ranged from 2 to 7 patients with CDI per 10,000 patient-days. The crude mortality rate was 8%, with 20 deaths occurring in patients with CDI. Forty-two (16%) patients had complications from CDI, including 4 patients who required partial, subtotal, or total colectomy, 3 of whom died. C. difficile was isolated and typed from 129 of 178 available stool specimens. The BI strain was identified in 79 (61%) isolates. Of patients discharged to long-term care who had their isolate typed, 36 (67%) had BI-associated CDI. CONCLUSIONS Severe disease was common and crude mortality was substantial among patients with CDI in Chicago area acute HCFs in February 2009. The outbreak-associated BI strain was the predominant endemic strain identified, accounting for nearly two-thirds of cases. Focal HCF outbreaks were not reported, despite the presence of the BI strain. Transfer of patients between acute and long-term HCFs may have contributed to the high incidence of BI cases in this investigation.

Methicillin-resistant Staphylococcus aureus infections among healthy full-term newborns

Objective: Methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged in the community, causing disease among healthy people lacking traditional risk factors for MRSA infection. This article describes an outbreak of MRSA among healthy full-term newborns. Design: Cases were identified and corresponding medical information collected. Telephone interviews were conducted with mothers of cases ands surveillance cultures from mothers and newborns were performed. MRSA isolates were genotyped. Setting: Hospital in Chicago, Illinois, USA. Participants: Newborns, their mothers and hospital healthcare workers. Intervention: Nursery infection control practices were enhanced. The MRSA-colonised healthcare workers received intranasal mupirocin. Main outcome: Within 4–23 days of birth, 11 newborns were identified with pustules, vesicles or blisters located on the head, groin, perineum, ears, legs, chin and trunk. All received antimicrobials and recovered without incident. Results: None of 432 peripartum women, one of 399 newborns, and two of 135 healthcare workers were nasal MRSA carriers. Available isolates from six patients, two healthcare workers, and one from an MRSA-colonised newborn were similar by pulsed-field gel electrophoresis. Other than contact with the hospital, no common exposures of MRSA transmission were identified. Conclusions: MRSA strains that initially emerged in the community are now causing disease in healthcare settings. Providers should be aware that MRSA can cause skin infections among healthy newborns. Adherence to standard infection control practices is important to prevent transmission of MRSA in nurseries.

Molecular Epidemiology of Neisseria meningitidis Isolates from an Outbreak of Meningococcal Disease among Men Who Have Sex with Men, Chicago, Illinois, 2003

ABSTRACT We characterized five Neisseria meningitidis serogroup C isolates from a Chicago outbreak of meningococcal disease that occurred in 2003 among a community of men who have sex with men. Isolates from this outbreak were identical to each other but distinct from the clone that caused a similar outbreak in Canada in 2001.

Acute Emergence of Elizabethkingia meningoseptica Infection among Mechanically Ventilated Patients in a Long-Term Acute Care Facility

OBJECTIVE To describe an outbreak of infection associated with an infrequently implicated pathogen, Elizabethkingia meningoseptica, in an increasingly prominent setting for health care of severely ill patients, the long-term acute care hospital. DESIGN Outbreak investigation. SETTING Long-term acute care hospital with 55 patients, most of whom were mechanically ventilated. METHODS We defined a case as E. meningoseptica isolated from any patient specimen source from December 2007 through April 2008, conducted an investigation of case patients, obtained environmental specimens, and performed microbiologic testing. RESULTS Nineteen patients had E. meningoseptica infection, and 8 died. All case patients had been admitted with respiratory failure that required mechanical ventilation. Among the 8 individuals who died, the time from collection of the first specimen positive for E. meningoseptica to death ranged from 6 to 43 days (median, 16 days). Environmental sampling was performed on 106 surfaces; E. meningoseptica was isolated from only one swab. Three related pulsed-field gel electrophoresis patterns were identified in patient isolates; the environmental isolate yielded a fourth, unrelated pattern. CONCLUSION Long-term acute care hospitals with mechanically ventilated patients could serve as an important transmission setting for E. meningoseptica. This multidrug-resistant bacterium could pose additional risk when patients are transferred between long-term acute care hospitals and acute care hospitals.

Emergency Care Physicians' Knowledge, Attitudes, and Practices Related to Surveillance for Foodborne Disease in the United States

During the past decade, the incidence of certain bacterial pathogens that are commonly transmitted through food in the United States has decreased. Concurrently, the emergency department has become an increasingly common setting for health care. Because public health surveillance for bacterial foodborne diseases fundamentally depends on stool cultures, we conducted a survey of physicians who attended an emergency medicine conference to describe knowledge, attitudes, and practices among this provider population. A convenience sample of 162 physicians, representing 34 states, provided responses. Thirty-eight percent reported having ordered a stool culture for the most recent patient with acute diarrheal illness examined in the emergency department, but only 26% of the physicians subsequently received the stool culture results. For only 2 pathogens (Escherichia coli O157:H7 and Salmonella species) did at least one-half of the respondents provide the correct response regarding whether selected diarrheal disease pathogens were reportable in their state. Responses indicated familiarity with the Infectious Diseases Society of Americas practice guidelines regarding stool cultures for patients with severe symptoms and a history of travel, but less so with characteristics of public health importance (i.e., attendance at day care and employment as a restaurant cook). We recommend that educational opportunities be made available to emergency care physicians that highlight the public health significance of acute diarrheal illness and that reinforce guidelines regarding culturing stool specimens, making recommendations to prevent further transmission, and reporting to local health authorities.