Stephen M. Ostroff

Public Health Assessment of Potential Biological Terrorism Agents

As part of a Congressional initiative begun in 1999 to upgrade national public health capabilities for response to acts of biological terrorism, the Centers for Disease Control and Prevention (CDC) was designated the lead agency for overall public health planning. A Bioterrorism Preparedness and Response Office has been formed to help target several areas for initial preparedness activities, including planning, improved surveillance and epidemiologic capabilities, rapid laboratory diagnostics, enhanced communications, and medical therapeutics stockpiling (1). To focus these preparedness efforts, however, the biological agents towards which the efforts should be targeted had to first be formally identified and placed in priority order. Many biological agents can cause illness in humans, but not all are capable of affecting public health and medical infrastructures on a large scale. The military has formally assessed multiple agents for their strategic usefulness on the battlefield (2). In addition, the Working Group on Civilian Biodefense, using an expert panel consensus-based process, has identified several biological agents as potential high-impact agents against civilian populations (3–7). To guide national public health bioterrorism preparedness and response efforts, a method was sought for assessing potential biological threat agents that would provide a reviewable, reproducible means for standardized evaluations of these threats. In June 1999, a meeting of national experts was convened to 1) review potential general criteria for selecting the biological agents that pose the greatest threats to civilians and 2) review lists of previously identified biological threat agents and apply these criteria to identify which should be evaluated further and prioritized for public health preparedness efforts. This report outlines the overall selection and prioritization process used to determine the biological agents for public health preparedness activities. Identifying these priority agents will help facilitate coordinated planning efforts among federal agencies, state and local emergency response and public health agencies, and the medical community.

Illnesses Associated with Escherichia coli 0157:H7 Infections: A Broad Clinical Spectrum

STUDY OBJECTIVE To describe the spectrum of illnesses associated with Escherichia coli O157:H7 infections. DESIGN Described an outbreak that showed the broad spectrum of these infections. Reviewed the clinical findings in the other eight major outbreaks reported between 1982 and 1986. Also reviewed reports of sporadic cases. SETTING Outbreaks in communities, nursing homes, a day care center, and a kindergarten. CASES Persons identified in outbreaks of E. coli O157:H7 infections. RESULTS Escherichia coli O157:H7 infection causes bloody diarrhea (hemorrhagic colitis), nonbloody diarrhea, the hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Infection can be asymptomatic, can involve extraintestinal sites, and can be fatal. Bloody diarrhea is the commonest symptom. Most patients have severe abdominal cramps; fever is documented in less than half. Findings from fecal leukocyte examinations often suggest a noninfectious cause. Results of radiologic and colonoscopic examinations can be consistent with a diagnosis of inflammatory bowel disease or ischemic colitis. Patients at the extremes of age are at increased risk for E. coli O157:H7-associated diarrhea, the hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and death. Antimicrobial agents have not been shown to modify the illness, but there are few data on individual agents. CONCLUSION Infection with E. coli O157:H7 should be considered in all patients with bloody diarrhea, the hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura because the infection can masquerade as gastrointestinal bleeding of noninfectious cause, the antecedent diarrhea may be resolved and forgotten by the time the hemolytic uremic syndrome or thrombotic thrombocytopenic purpura is diagnosed, and the detection of E. coli O157:H7 requires specific stool culture techniques.

Sources of sporadic Yersinia enterocolitica infections in Norway: a prospective case-control study.

Yersinia enterocolitica is a recognized cause of gastroenteritis in northern Europe. During October 1988-January 1990, a prospective case-control study was performed to address risk factors associated with sporadic Y. enterocolitica infections in southeastern Norway. Sixty-seven case-patients (mean age 23.4 years, range 8 months-88 years) and 132 age-, sex- and geographically-matched controls were enrolled in the study. Multivariate analysis of the data showed that persons with Y. enterocolitica infection reported having eaten significantly more pork items (3.79 v. 2.30 meals, P = 0.02) and sausage (2.84 v. 2.20 meals, P = 0.03) in the 2 weeks before illness onset than their matched controls; only one patient had eaten raw pork. Patients were also more likely than controls to report a preference for eating meat prepared raw or rare (47 v. 27%, P = 0.01), and to report drinking untreated water (39 v. 25%, P = 0.01) in the 2 weeks before illness onset. Each of these factors was independently associated with disease, suggesting a link between yersiniosis and consumption of undercooked pork and sausage products and untreated water. Efforts should be directed towards developing techniques to reduce Y. enterocolitica contamination of pork and educating consumers about (1) proper handling and preparation of pork items and (2) the hazards of drinking untreated water.

Incidence and Clinical Implications of Isolation of Mycobacterium kansasii: Results of a 5-Year, Population-Based Study

Mycobacterium kansasii, a nontuberculous mycobacterium, causes pulmonary disease that is indistinguishable from M. tuberculosis infection in immunocompetent persons. Before the AIDS epidemic, M. kansasii was a relatively infrequent pathogen [1]: In 1980, the incidence of M. kansasii infection was estimated to be 0.52 cases per 100 000 persons [2]. However, recent case series suggest increased isolation of M. kansasii from HIV-positive patients [3, 4] and increasing rates of M. kansasii infection in HIV-negative patients [5]. National surveillance between 1981 and 1987 detected 138 cases of disseminated M. kansasii infection per 100 000 persons with AIDS [6]; this incidence is more than 200-fold higher than the incidence in the general population. In both the HIV-positive and HIV-negative populations, the highest rates of M. kansasii infection were detected in an inverted-T geographic distribution that covered the southern and central United States [2, 6]. This endemic distribution suggests an environmental reservoir; however, M. kansasii has not been recovered from soil [7, 8], has only rarely been detected in natural bodies of water [9, 10], and has infrequently been cultured from potable water supplies [8, 11-14]. Mycobacterium kansasii has traditionally been considered the most virulent of the nontuberculous mycobacteria [15]; 75% to 97% of HIV-negative persons fulfill criteria for infection [1, 16]. Co-infection with HIV seems to alter the spectrum of clinical disease. Cavitary lung disease, which is diagnostic of pulmonary infection in HIV-negative patients [16-18], is documented in less than 50% of HIV-positive patients [19, 20]. Concomitant pathogens are identified in 30% to 46% of HIV-positive patients [21, 22], further obscuring the relative contribution of M. kansasii as a cause of pulmonary disease. Disparate reports documenting the frequency of colonization in the HIV population have led to confusion about the clinical significance and need for treatment of M. kansasii infection [4, 19, 23, 24]. Despite the changing epidemiology of M. kansasii infections, no updated population-based evaluation has been done in the AIDS era. Limitations of existing studies include hospital-based case ascertainment, which biases toward more seriously ill patients, and exclusion of HIV-negative patients. These limitations mask changing disease patterns in the population as a whole. Monitoring disseminated disease as part of AIDS surveillance may significantly underestimate the overall incidence of M. kansasii infection because pulmonary disease accounts for more than 65% of infections [4, 19]. Our study used population-based laboratory surveillance to find all cultures that were positive for M. kansasii in three counties in northern California. By including both HIV-positive and HIV-negative patients, we could assess the role of impaired immunity in the clinical presentation, significance of a positive respiratory culture, and risk for infection. Methods Surveillance Strategy and Case Mapping Active laboratory-based surveillance and auditing of all 43 hospital and clinic laboratories and 4 health departments in Alameda County, Contra Costa County, and San Francisco County between 1 January 1992 and 31 December 1996 were used to identify persons with positive cultures for M. kansasii. The organism was isolated by using standard methods [25]. Between 1992 and 1993, a designated laboratory employee at each facility prospectively notified surveillance staff of each positive culture. Monthly summaries of laboratory isolates were reviewed to ensure complete ascertainment of cases. We accrued cases identified between 1994 and 1996 by retrospectively reviewing laboratory records using a combination of computerized database searches and manual audits of mycobacteriology laboratory records. To abstract clinical, demographic, and microbiological data, we reviewed charts by using a standardized definition to establish the presence of pulmonary infection [26]. A diagnosis of HIV or AIDS was established by using the 1993 Centers for Disease Control and Prevention case definition [27]. Patients with negative serologic test results in the 6 months before M. kansasii culture were classified as HIV negative; those who were not tested or were seronegative more than 6 months before the index culture were classified as HIV unknown. Serostatus was validated by cross-referencing patients with the California Office of AIDS database of patients who had a confirmed AIDS diagnosis. California Department of Finance data [28] that projected the annual population of each county were used as rate denominators for the general population. The California Office of AIDS provided midyear estimates of the number of living persons with AIDS and HIV [29, 30]. Cumulative incidence rates were calculated for each year of the study by dividing the number of adult patients older than 20 years of age by the annual estimated adult population. Atlas GIS software (Strategic Mapping, Inc., Santa Clara, California) was used to assign patients living in San Francisco County to residential census tracts. Demographic and socioeconomic data were obtained by linkage with the 1990 U.S. Census report through the Summary Tape File 3 database. The geographic analysis was restricted to San Francisco County. Statistical Analysis Data were entered into an EPI-Info 6.04 database (Centers for Disease Control and Prevention, Atlanta, Georgia) and analyzed by using Stata 4.0 statistical software (Stata Corp., College Station, Texas). Dichotomous variables were assessed by using chi-square tests or the Fisher exact test. Continuous variables were compared by using the Student t-test or the two-sample Wilcoxon rank-sum test for nonparametric data. Poisson exact CIs were calculated for rates. All tests were two-sided; a P value of 0.05 or less was considered statistically significant. Results Mycobacterium kansasii was isolated from 283 patients. Thirteen patients were excluded because they lived outside the surveillance area (n = 7) or because their place of residence was unknown (n = 6). One hundred eighty-seven patients (69.3%) were HIV-positive, 33 (12.2%) were HIV-negative, and 50 (18.5%) had an unknown HIV status. The HIV-negative and HIV-unknown patients had homogeneous demographic characteristics (data not shown) and were combined to form a presumed HIV-negative group. Cross-reference of these patients with the California State AIDS Registry identified one (1.2%) potential case of misclassification: a patient with unknown HIV status at the time of M. kansasii isolation who subsequently received an AIDS diagnosis. Demographic and Socioeconomic Characteristics Patients who were HIV positive and those who were HIV negative differed significantly with respect to several characteristics (Table 1). The median age of HIV-negative patients was 22 years greater than that of HIV-positive patients, although the single infected child was an HIV-negative 2-year-old boy. Patients who were HIV positive were more likely to be male and African American and to have reported use of injection drugs. Homelessness (defined as no housing or housing in shelters) or marginal housing (defined as temporary residence in a low-rent hotel) in the year before M. kansasii culture was significantly more common among HIV-positive patients. Table 1. Baseline Characteristics of HIV-Positive and Presumed HIV-Negative Patients with Mycobacterium kansasii Cultured from Clinical Specimens* Incidence and Geographic Analysis The mean annual incidence of M. kansasii infection between 1992 and 1996 (based on the 269 adult patients) was 2.4 cases per 100 000 persons (95% CI, 2.1 to 2.7 cases per 100 000); the rate of infection was higher among male patients (5.1 cases per 100 000 [CI, 4.5 to 5.9 cases per 100 000]) and African Americans (8.1 per 100 000 [CI, 6.5 to 10.0 cases per 100 000]). Mean incidence varied markedly by HIV status: The rate per 100 000 persons was 0.75 in the general population (CI, 0.6 to 0.9 cases per 100 000), 115.1 in HIV-positive persons (CI, 99.2 to 132.9 cases per 100 000), and 646.5 in persons with AIDS (CI, 553.5 to 750.7 cases per 100 000). Among persons with AIDS, the rate of isolation of M. kansasii was disproportionately elevated for African Americans (1533 cases per 100 000 [CI, 1197 to 1933 cases per 100 000]) and women (1450 cases per 100 000 [CI, 873 to 2265 cases per 100 000]). African-American women with AIDS had the highest isolation rate of M. kansasii (2137 cases per 100 000 [CI, 1196 to 3524 cases per 100 000]). The geographic analysis was restricted to San Francisco County, which contributed 78% of HIV-positive patients and 46% of HIV-negative patients even though it had the smallest population of the three surveillance counties. Fifteen residents of San Francisco County were excluded from the geographic analysis because of homelessness (n = 14) or incomplete address (n = 1). Patients with M. kansasii infection resided in 72 (47.4%) of the 152 county census tracts, and 38 (53%) of these tracts had more than one case (Figure 1). Ten census tracts had an isolation rate of more than 1 case per 1000 residents (range, 1.08 to 7.35 cases per 1000 residents). These high-density tracts, which contained 5.6% of the San Francisco County population, accounted for 34.5% of mapped M. kansasii cases in the county. Figure 1. Map of San Francisco, California, showing geographic distribution of patients with Mycobacterium kansasii infection by HIV status and median household income of census tract. Median income differed between the 72 census tracts that contained patients with M. kansasii infection and the 80 census tracts that did not (

Human Salmonella Infections Linked to Contaminated Dry Dog and Cat Food, 2006–2008

32 317 compared with

Enzyme-linked immunosorbent assays for detecting antibodies to Shiga-like toxin I, Shiga-like toxin II, andEscherichia coli O157:H7 lipopolysaccharide in human serum

38 048; P = 0.001). Median incomes were

Outbreak of influenza A (H3N2) variant virus infection among attendees of an agricultural fair, Pennsylvania, USA, 2011.

24 112 for tracts with more than 1 case per 1000 residents and

EMERGING INFECTIOUS DISEASES AND TRAVEL MEDICINE

32 514 for low-density case-containing tracts (P = 0.03). Median income of the census tracts was similar for HIV-positive and HIV-ne

Clinical Features of Sporadic Campylobacter Infections in Norway

OBJECTIVE: Human Salmonella infections associated with dry pet food have not been previously reported. We investigated such an outbreak of Salmonella Schwarzengrund and primarily affecting young children. PATIENTS AND METHODS: Two multistate case-control studies were conducted to determine the source and mode of infections among case-patients with the outbreak strain. Study 1 evaluated household exposures to animals and pet foods, and study 2 examined risk factors for transmission among infant case-patients. Environmental investigations were conducted. RESULTS: Seventy-nine case-patients in 21 states were identified; 48% were children aged 2 years or younger. Case-households were significantly more likely than control households to report dog contact (matched odds ratio [mOR]: 3.6) and to have recently purchased manufacturer X brands of dry pet food (mOR: 6.9). Illness among infant case-patients was significantly associated with feeding pets in the kitchen (OR: 4.4). The outbreak strain was isolated from opened bags of dry dog food produced at plant X, fecal specimens from dogs that ate manufacturer X dry dog food, and an environmental sample and unopened bags of dog and cat foods from plant X. More than 23 000 tons of pet foods were recalled. After additional outbreak-linked illnesses were identified during 2008, the company recalled 105 brands of dry pet food and permanently closed plant X. CONCLUSIONS: Dry dog and cat foods manufactured at plant X were linked to human illness for a 3-year period. This outbreak highlights the importance of proper handling and storage of pet foods in the home to prevent human illness, especially among young children.

Measles outbreak associated with an international youth sporting event in the United States, 2007.

Shiga-like toxin-producingEscherichia coli O157:H7 are important causes of bloody diarrhea and hemolytic uremic syndrome. To facilitate the epidemiologic study of these organisms, we developed enzyme-linked immunosorbent assays (ELISAs) for antibodies to Shiga-like toxin I (SLT I), Shiga-like toxin II (SLT II), andE. coli O157 lipopolysaccharide (LPS). We tested serum samples from 83 patients in two outbreaks ofE. coli O157:H7 diarrhea and from 66 well persons. Forty-three patients (52%) had at least one serum sample positive for anti-O157 LPS antibodies; among 26 culture-confirmed patients, 24 (92%) had at least one positive serum sample. Two (3%) of 66 control sera had positive anti-O157 LPS titers. ELISA results for SLT I and II were compared with those of HeLa cell cytotoxicity neutralization assays on both patient and control sera. Neutralization assays detected anti-SLT I antibodies in at least one serum sample from each of 17 (20%) patients and 7 (10.6%) controls, while 16 (19%) patients and 7 controls had positive titers by anti-SLT I ELISA. Although all serum samples, including control sera, showed nonspecific neutralization of SLT II, no antibody titers to SLT II were detected by either neutralization or ELISA. These results indicate that ELISAs for SLT I and SLT II antibodies are comparable to HeLa cell cytotoxicity neutralization assays. Both the ELISAs and neutralization assays are insensitive in detecting infected patients. However, the ELISA for antibodies toE. coli O157 LPS is both sensitive and specific, and may be more useful than assays for antitoxic antibodies in detecting persons withE. coli O157:H7 infection.