Lori Hutwagner

An Outbreak of Escherichia coli O157:H7 Infections Associated with Leaf Lettuce Consumption

In July 1995, 40 Montana residents were identified with laboratory-confirmed Escherichia coli O157:H7 infection; 52 residents had bloody diarrhea without laboratory confirmation. The median age of those with laboratory-confirmed cases was 42 years (range, 4- 86); 58% were female. Thirteen patients were hospitalized, and 1 developed hemolytic-uremic syndrome. A case-control study showed that 19 (70%) of 27 patients but only 8 (17%) of 46 controls reported eating purchased (not home-grown) leaf lettuce before illness (matched odds ratio, 25.3; 95% confidence interval, 3.9-1065.6). Pulsed-field gel electrophoresis identified a common strain among 22 of 23 isolates tested. Implicated lettuce was traced to two sources: a local Montana farm and six farms in Washington State that shipped under the same label. This outbreak highlights the increasing importance of fresh produce as a vehicle in foodborne illness. Sanitary growing and handling procedures are necessary to prevent these infections.

Implementing Syndromic Surveillance: A Practical Guide Informed by the Early Experience

Syndromic surveillance refers to methods relying on detection of individual and population health indicators that are discernible before confirmed diagnoses are made. In particular, prior to the laboratory confirmation of an infectious disease, ill persons may exhibit behavioral patterns, symptoms, signs, or laboratory findings that can be tracked through a variety of data sources. Syndromic surveillance systems are being developed locally, regionally, and nationally. The efforts have been largely directed at facilitating the early detection of a covert bioterrorist attack, but the technology may also be useful for general public health, clinical medicine, quality improvement, patient safety, and research. This report, authored by developers and methodologists involved in the design and deployment of the first wave of syndromic surveillance systems, is intended to serve as a guide for informaticians, public health managers, and practitioners who are currently planning deployment of such systems in their regions.

Reptiles, Amphibians, and Human Salmonella Infection: A Population-Based, Case-Control Study

To estimate the burden of reptile- and amphibian-associated Salmonella infections, we conducted 2 case-control studies of human salmonellosis occurring during 1996-1997. The studies took place at 5 Foodborne Diseases Active Surveillance Network (FoodNet) surveillance areas: all of Minnesota and Oregon and selected counties in California, Connecticut, and Georgia. The first study included 463 patients with serogroup B or D Salmonella infection and 7618 population-based controls. The second study involved 38 patients with non-serogroup B or D Salmonella infection and 1429 controls from California only. Patients and controls were interviewed about contact with reptiles and amphibians. Reptile and amphibian contact was associated both with infection with serogroup B or D Salmonella (multivariable odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2; P<.009) and with infection with non-serogroup B or D Salmonella (OR, 4.2; CI, 1.8-9.7; P<.001). The population attributable fraction for reptile or amphibian contact was 6% for all sporadic Salmonella infections and 11% among persons <21 years old. These data suggest that reptile and amphibian exposure is associated with approximately 74,000 Salmonella infections annually in the United States.

Escherichia coli O157: H7 Diarrhea in the United States: Clinical and Epidemiologic Features

Escherichia coli O157:H7 was first recognized as a human pathogen in 1982 [1], and it is increasingly recognized as an important cause of sporadic and outbreak-associated bloody diarrhea [2]. Strains of E. coli O157:H7 are characterized by their ability to produce moderate or large amounts of two types of Shiga toxin. These toxins are important factors in the pathogenesis of postdiarrheal hemolytic uremic syndrome, and E. coli O157:H7 infection is the major cause of this syndrome in children in the United States and Canada [3-6]. Outbreaks of E. coli O157:H7 have involved communities [7-9] and such institutions as nursing homes [10, 11], schools [12], and day care facilities [13, 14]. Routine stool cultures do not identify E. coli O157:H7. Unlike 80% of E. coli serotypes, however, E. coli O157:H7 does not rapidly ferment D-sorbitol and therefore appears colorless on sorbitol-MacConkey agar culture plates read at 24 hours [15, 16]. These sorbitol-negative colonies can then be screened for agglutination in O157 antiserum. Relatively little information is available about the frequency of isolation of E. coli O157:H7 from ill persons in the United States; most U.S. laboratories do not routinely culture for this organism [17]. In single-center studies in the United States in which all stool specimens were cultured for this organism, isolation rates ranged from 0.08% to 0.5% [18-20]. Recent information suggests that E. coli O157:H7 has been isolated from patients in most states [21], but the frequency of this isolation compared with that of other enteric pathogens in different geographic areas during similar time periods has not been described. The reported clinical signs and symptoms of E. coli O157:H7 infection include bloody or nonbloody diarrhea, abdominal cramps, and lack of reported fever [22, 23]. However, this information was derived from relatively few persons in outbreak settings, and few studies have examined the clinical presentation of illness due to E. coli O157:H7 infection compared with the clinical presentation of illness due to other bacterial enteric pathogens. We therefore sought to determine 1) the frequency of isolation of E. coli O157:H7 and 2) the clinical and epidemiologic features of infections with E. coli O157:H7 compared with those of Campylobacter, Salmonella, and Shigella species at 10 hospitals located throughout the United States. Using standard microbiological methods, we assessed the ways in which time of year, geographic location, and the demographic and clinical features of patients affected the likelihood of isolation of these enteric pathogens. Methods Study Sample Our study was announced and participation was requested in a newsletter that was sent to hospitals in the National Nosocomial Infections Surveillance system [24]. Five hospitals in this system and five other hospitals were chosen on the basis of geographic location, willingness to participate, receipt of specimens in a primary care setting, and the expectation that an adequate number of outpatient stool cultures would be done each year. All four census divisions of the United States were represented. Nine hospitals served general patient populations that included all age groups, and one served a primarily pediatric population. All served both inpatients and outpatients. The average annual number of stool specimens screened by each hospital ranged from 400 to 4000 (median, 1300). Four of the hospitals were university hospitals, and six were community hospitals. At each hospital, all of the specimens studied were fecal samples from inpatients and outpatients of all ages that were submitted to the clinical microbiology laboratory for routine pathogen identification. The study was conducted from October 1990 through October 1992. Collection and Handling of Specimens All sites agreed to use the following methods for the collection and handling of specimens. Swabs were transported in Cary-Blair transport medium, Amies transport medium, or Stuart transport medium and were streaked immediately onto plating media or were kept at 4 C for no more than 24 hours. If whole stool specimens were not examined within 1 hour of receipt by the laboratory, a swab of the stool was placed in transport medium, refrigerated, and examined within 24 hours. Specimens were visually inspected for gross blood, and the presence of occult blood was determined by using the hemoccult test. The presence of fecal leukocytes was determined by placing a bit of stool in a drop of methylene blue on a slide or by doing a Gram stain and examining the specimen using the high-power microscope objective. Specimens were graded as having 0, 1 to 4, 5 to 9, or 10 or more leukocytes per high-power field. Standard methods were used to isolate and identify Campylobacter, Salmonella, and Shigella species. Other assays, such as those for Clostridium difficile or rotavirus, were not part of the protocol and were done according to the routines of the individual site laboratories and the physicians ordering the tests. Isolation of Escherichia coli O157:H7 Before the study began, each laboratory received control strains of E. coli O157:H7 and instructions about the isolation and identification of this organism. To identify E. coli O157:H7, fecal specimens were plated onto sorbitol-MacConkey agar and the plates were incubated at 37 C for 24 hours. Three sorbitol-negative colonies were tested for agglutination with O157 latex reagents (Pro-Lab, Inc., Round Rock, Texas). The O157-positive colonies were sent to the Centers for Disease Control and Prevention for biochemical identification and serotyping [25]. Isolates confirmed as E. coli O157:H7 or O157:NM (nonmotile) were tested for production of Shiga toxin 1 and 2 (formerly called Shiga-like toxins I and II [26]) and for the presence of Shiga toxin genes by hybridization with oligonucleotide probes [27]. Isolates were tested by using the disk diffusion technique [28] for susceptibility to a standard panel of antimicrobial agents [28]. Data Collection For each fecal specimen received, data were entered on a standard line list; only the first specimen from each patient was included. The information collected for each specimen included date obtained, date plated, source (whole stool or swab), presence of visible or occult blood, presence and quantity of fecal leukocytes, and presence of pathogens. After permission was obtained from the relevant health care provider, a clinical data form was completed through retrospective chart review for all patients from whom Campylobacter, Salmonella, or Shigella species or E. coli O157:H7 were isolated and from every 25th patient from whom no pathogen was isolated. Information obtained included age, sex, date of the onset of illness, inpatient or outpatient status, symptoms (including presence and date of onset of diarrhea, bloody stools, abdominal pain, vomiting, and fever in the previous 2 weeks), abdominal tenderness, largest number of bowel movements in a 24-hour period, maximum body temperature on the day of culture (as measured by a health practitioner), peripheral blood leukocyte count, and whether the patient was admitted to the hospital. If a patient had a body temperature of at least 37.8 C, he or she was considered to have fever. Data Analysis Salmonella, Shigella, and Campylobacter species and E. coli O157:H7 were considered to be major bacterial enteric pathogens. Isolates that were identified as O157:H7 or O157:NM and that produced Shiga toxin were considered to be strains of E. coli O157:H7. An isolation proportion for a pathogen was defined as the proportion of all fecal specimens that yielded that pathogen. To estimate the age-specific isolation proportion of pathogens from stool specimens, we divided the number of persons in each age group for whom a specific pathogen was isolated by the sum of all persons (both culture-positive and culture-negative) in that age group. We estimated the total number of culture-negative persons in each age group by extrapolating the age group distribution frequency from the sample of culture-negative persons for whom age was known to all culture-negative persons. For the analysis of clinical features associated with infection, patients whose stool cultures yielded more than one bacterial pathogen were excluded. Differences in proportions were analyzed using a chi-square test or the Fisher exact test. For normally distributed data, differences in means were compared using the Student t-test; for nonparametric data, differences in medians were compared using the Wilcoxon two-sample test. Logistic regression analysis was done using generalized estimating equations to assess factors independently associated with E. coli O157:H7 infection while controlling for study site. For all statistical tests, a two-tailed P value less than 0.05 was considered significant. Results Isolation of Pathogens During the study period, fecal specimens from 30 463 persons were examined. A source was specified for 29 355 of these specimens; 63% were from whole stools and 37% were from swabs. Overall, 1708 of the specimens (5.6%) yielded at least one of the four major bacterial enteric pathogens; for 27 902 specimens (91.6%), no pathogen was isolated. Eleven patients had dual infections: Six had Shigella species and Campylobacter species infections, 3 had Salmonella species and Campylobacter species infections, and 2 had Shigella species and Salmonella species infections. The highest isolation proportions from fecal specimens for E. coli O157:H7 were seen in hospitals in Maine and Wisconsin; the lowest proportion was seen in Virginia (Table 1). Of the four bacterial pathogens, E. coli O157:H7 was the second most frequently isolated in Maine, the third most frequently isolated (ahead of Shigella species) in Washington and Wisconsin, and the third most frequently isolated (tied with Shigella species) in Michigan. In the hospitals in northern states (Maine, Michigan, New

Cryptococcosis: Population-Based Multistate Active Surveillance and Risk Factors in Human Immunodeficiency Virus—Infected Persons

To determine the incidence of cryptococcosis and its risk factors among human immunodeficiency virus (HIV)-infected persons, population-based active surveillance was conducted in four US areas (population, 12.5 million) during 1992-1994, and a case-control study was done. Of 1083 cases, 931 (86%) occurred in HIV-infected persons. The annual incidence of cryptococcosis per 1000 among persons living with AIDS ranged from 17 (San Francisco, 1994) to 66 (Atlanta, 1992) and decreased significantly in these cities during 1992-1994. Among non-HIV-infected persons, the annual incidence of cryptococcosis ranged from 0.2 to 0.9/100,000. Multivariate analysis of the case-control study (158 cases and 423 controls) revealed smoking and outdoor occupations to be significantly associated with an increased risk of cryptococcosis; receiving fluconazole within 3 months before enrollment was associated with a decreased risk for cryptococcosis. Further studies are needed to better describe persons with AIDS currently developing cryptococcosis in the era of highly active antiretroviral therapy.

The bioterrorism preparedness and response Early Aberration Reporting System (EARS).

Data from public health surveillance systems can provide meaningful measures of population risks for disease, disability, and death. Analysis and evaluation of these surveillance data help public health practitioners react to important health events in a timely manner both locally and nationally. Aberration detection methods allow the rapid assessment of changes in frequencies and rates of different health outcomes and the characterization of unusual trends or clusters.The Early Aberration Reporting System (EARS) of the Centers for Disease Control and Prevention allows the analysis of public health surveillance data using available aberration detection methods. The primary purpose of EARS is to provide national, state, and local health departments with several alternative, aberration detection methods. EARS helps assist local and state health officials to focus limited resources on appropriate activities during epidemiological investigations of important public health events. Finally, EARS allows end users to select validated aberration detection methods and modify sensitivity and specificity thresholds to values considered to be of public health importance by local and state health departments.

A Massive Epidemic of Multidrug-Resistant Typhoid Fever in Tajikistan Associated with Consumption of Municipal Water

From 1 January through 30 June 1997, 8901 cases of typhoid fever and 95 associated deaths were reported in Dushanbe, Tajikistan. Of 29 Salmonella serotype Typhi isolates tested, 27 (93%) were resistant to ampicillin, chloramphenicol, nalidixic acid, streptomycin, sulfisoxazole, tetracycline, and trimethoprim-sulfamethoxazole. In a case-control study of 45 patients and 123 controls, Salmonella Typhi infection was associated with drinking unboiled water (matched odds ratio, 7; 95% confidence interval, 3-24; P<.001). Of tap water samples, 97% showed fecal coliform contamination (mean level, 175 cfu/100 mL). Samples taken from water treatment plants revealed that fecal coliform contamination occurred both before and after treatment. Lack of chlorination, equipment failure, and back-siphonage in the water distribution system led to contamination of drinking water. After chlorination and coagulation were begun at the treatment plants and a water conservation campaign was initiated to improve water pressure, the incidence of typhoid fever declined dramatically.

Effective Vaccine for Lassa Fever

ABSTRACT Lassa fever has been estimated to cause 5,000 deaths annually in West Africa. Recently, war in the zone where Lassa fever is hyperendemic has severely impeded control and treatment. Vaccination is the most viable control measure. There is no correlation between antibody levels and outcome in human patients, and inactivated vaccines produce high titers of antibodies to all viral proteins but do not prevent virus replication and death in nonhuman primates. Accordingly, we vaccinated 44 macaques with vaccinia virus-expressed Lassa virus structural proteins separately and in combination, with the object of inducing a predominantly TH1-type immune response. Following Lassa virus challenge, all unvaccinated animals died (0% survival). Nine of 10 animals vaccinated with all proteins survived (90% survival). Although no animals that received full-length glycoprotein alone had a high titer of antibody, 17 of 19 survived challenge (88%). In contrast, all animals vaccinated with nucleoprotein developed high titers of antibody but 12 of 15 died (20% survival). All animals vaccinated with single glycoproteins, G1 or G2, died, but all those that received both single glycoproteins (G1 plus G2) at separate sites survived, showing that both glycoproteins are independently important in protection. Neither group had demonstrable antibody levels prior to challenge. We demonstrate that in primates, immune responses to epitopes on both glycoproteins are required to protect against lethal challenge with Lassa virus without having untoward side effects and that this protection is likely to be primarily cell mediated. We show that an effective, safe vaccine against Lassa virus can and should be made and that its evaluation for human populations is a matter of humanitarian priority.

Prospective Study of Histoplasmosis in Patients Infected with Human Immunodeficiency Virus: Incidence, Risk Factors, and Pathophysiology

Histoplasmosis is a common opportunistic infection in patients with human immunodeficiency virus (HIV) infection who reside in areas where Histoplasma capsulatum is endemic. We undertook a prospective study of a cohort of 304 HIV-Infected patients in Kansas City from October 1990 through March 1993 to define the incidence-specific risk factors, and pathophysiology of histoplasmosis. The annual incidence of histoplasmosis was 4.7%; 74% of the patients with histoplasmosis were symptomatic (all of whom had disseminated disease). A history of exposure to chicken coops, a positive baseline serology for complement-fixing antibodies to Histoplasma mycelium antigen, and a baseline CD4+ lymphocyte count of < 150/microL were associated with an increased risk for histoplasmosis. Histoplasmin reactivity and the presence of pulmonary calcifications were not useful markers for patients at high risk. Symptomatic infection occurred in 9.9% of patients with evidence of prior exposure to H. capsulatum, in 4.0% of patients without documented prior exposure, and in 3.0% of patients who were anergic; these findings suggest that the pathophysiology of histoplasmosis in patients with AIDS involves reactivation of latent infection in some cases and dissemination of exogenously acquired infection in other cases.

An outbreak of salmonellosis among children attending a reptile exhibit at a zoo

OBJECTIVE In January 1996, an outbreak of diarrhea caused by Salmonella Enteritidis occurred in children attending a Komodo dragon exhibit at a metropolitan zoo. We sought to determine the extent of the outbreak and mode of transmission. STUDY DESIGN A case-control study was conducted. Controls were randomly selected from zoo membership lists and matched to patients by age group and date of exhibit visit. RESULTS Of 65 patients identified, 39 had confirmed and 26 had suspected cases. The median age was 7 years (range, 3 months to 48 years); 55% were enrolled in the case-control study. No patients and two (4%) controls reported touching a dragon; however, 83% of patients but only 52% of controls touched the wooden barrier that surrounded the dragon pen (odds ratio = 4.0, 95% CI 1.2 to 13.9). Washing hands at the zoo after visiting the dragons was highly protective (OR = 0.14, 95% CI 0.03 to 0.7). Cultures from the patients, one dragon, and the exhibit barriers yielded Salmonella Enteritidis, phage type 8. On the basis of an attack rate of 4.3% among exhibit attendees under 13 years old on whom data were collected, we estimate that 315 additional cases of salmonellosis occurred among visitors in this age group. CONCLUSION This large outbreak demonstrates the importance of environmental contamination in the transmission of Salmonella from reptiles, and the protective value of hand washing. Recommendations regarding reptile exhibits and reptilian pets should emphasize this indirect route.