A simulation model for assessing aberration detection methods used in public health surveillance for systems with limited baselines.

Public health officials continue to develop and implement new types of ongoing surveillance systems in an attempt to detect aberrations in surveillance data as early as possible. In public health surveillance, aberrations are traditionally defined as an observed value being greater than an expected historical value for that same time period. To account for seasonality, traditional aberration detection methods use three or more years of baseline data across the same time period to calculate the expected historical value. Due to the recent implementation of short-term bioterrorism surveillance systems, many of the new surveillance systems have limited historical data from which to calculate an expected baseline value. Three limited baseline aberration detection methods, C1-MILD, C2-MEDIUM, and C3-ULTRA, were developed based on a one-sided positive CUSUM (cumulative sum) calculation, a commonly used quality control method used in the manufacturing industry. To evaluate the strengths and weakness of these methods, data were simulated to represent syndromic data collected through the recently developed hospital-based enhanced syndromic surveillance systems. The three methods were applied to the simulated data and estimates of sensitivity, specificity, and false-positive rates for the three methods were obtained. For the six syndromes, sensitivity for the C1-MILD, C2-MEDIUM, and C3-ULTRA models averaged 48.2, 51.3, and 53.7 per cent, respectively. Similarly, the specificities averaged 97.7, 97.8, and 96.1 per cent, respectively. The average false-positive rates for the three models were 31.8, 29.2, and 41.5 per cent, respectively. The results highlight the value and importance of developing and testing new aberration detection methods for public health surveillance data with limited baseline information.

Multiple risk factors and population attributable risk for ischemic heart disease mortality in the United States, 1971-1992.

The objective of this study was to assess the associations and population attributable risks (PAR) of risk factor combinations and ischemic heart disease (IHD) mortality in the United States. We used logistic regression models to assess the association of risk factors with IHD in the First National Health and Nutrition Examination Survey (1971-1974) and Epidemiologic Follow-up Study (1982-1992) among white and black men and women. We examined eight modifiable risk factors: hypertension, elevated serum cholesterol, diabetes, overweight, current smoking, physical inactivity, depression, and nonuse of replacement hormones. Risk factors associated with IHD mortality were the same among white and black men (i.e., age, education, smoking, diabetes, hypertension, and serum cholesterol). Age, education, smoking, diabetes, and hypertension were the risk factors among white and black women. Physical inactivity, nonuse of replacement hormones, serum cholesterol, and overweight were the additional risk factors among white women. Adjusted for demographic risk factors, overall PARs for study risk factors were 41.2% for white men, 60.5% for white women (with five risk factors only), 49.2% for black men, and 71.2% for black women. Much IHD mortality attributable to individual risk factors is caused by those factors in combination with other risk factors; relatively little mortality is attributable to each risk factor in isolation. Analysis that does not examine risk factor combinations may greatly overestimate PARs associated with individual risk factors.

Factors influencing a communitywide campaign to administer hepatitis A vaccine to men who have sex with men.

OBJECTIVES: A hepatitis A outbreak among men who have sex with men (MSM) led to a publicly funded vaccination campaign. We evaluated the MSM community's response. METHODS: A cohort of MSM from 5 community sites was surveyed. RESULTS: Thirty-four (19%) of 178 potential vaccine candidates received the vaccine during the campaign. We found a linear relation between the number of exposures to campaign information and the likelihood of vaccination (P < .001). Vaccination was independently associated with awareness of the outbreak and the vaccine, having had sexual relations with men for 12 years or longer, having recently consulted a physician, and routinely reading a local gay newspaper. CONCLUSIONS: The difficult task of vaccinating MSM can be aided by repetitive promotional messages, especially via the gay media.

Multiple modes of hepatitis A virus transmission among methamphetamine users.

Methamphetamine users are at increased risk of hepatitis A, but modes of transmission are unclear. The authors conducted a case-control study among methamphetamine users during an outbreak in Iowa in 1997. Twenty-eight reported, laboratory-confirmed, hepatitis A cases did not differ from 18 susceptible controls with respect to age, sex, or number of doses used. When compared with controls in multivariate analysis, case-patients were more likely to have injected methamphetamine (odds ratio (OR) = 5.5, 95% confidence interval (CI): 1.1, 27), to have used methamphetamine with another case-patient (OR = 6.2, 95% CI: 0.95, 41), and to have used brown methamphetamine (OR = 5.5, 95% CI: 0.51, 59). Receptive needle sharing was reported by 10 of the 20 case-patients who injected. Methamphetamine use with another case-patient was also associated with hepatitis A in an analysis restricted to noninjectors (OR = 17, 95% CI: 1.0, 630). During this outbreak, hepatitis A may have been transmitted from person to person among methamphetamine users through the fecal-oral and the percutaneous routes. Methamphetamine users should be vaccinated against hepatitis A and should be given immune globulin if they used methamphetamine with a case-patient in the last 2 weeks. Persons who intend to continue using methamphetamine should be advised about safer practices.

A prolonged outbreak of Pseudomonas aeruginosa in a neonatal intensive care unit: did staff fingernails play a role in disease transmission?

OBJECTIVES: To describe an outbreak of Pseudomonas aeruginosa bloodstream infection (BSI) and endotracheal tube (ETT) colonization in a neonatal intensive care unit (NICU), determine risk factors for infection, and make preventive recommendations. DESIGN: A 15-month cohort study followed by a case-control study with an environmental survey and molecular typing of available isolates using pulsed-field gel electrophoresis. SETTING AND PATIENTS: Neonates in the NICU of a university-affiliated children's hospital. INTERVENTIONS: Improved hand washing and restriction of use of long or artificial fingernails. RESULTS: Of 439 neonates admitted during the study period, 46 (10.5%) acquired P aeruginosa; 16 (35%) of those died. Fifteen (75%) of 20 patients for whom isolates were genotyped had genotype A, and 3 (15%) had genotype B. Of 104 healthcare workers (HCWs) from whom hand cultures were obtained, P aeruginosa was isolated from three nurses. Cultures from nurses A-1 and A-2 grew genotype A, and cultures from nurse B grew genotype B. Nurse A-1 had long natural fingernails, nurse B had long artificial fingernails, and nurse A-2 had short natural fingernails. On multivariate logistic regression analysis, exposure to nurse A-1 and exposure to nurse B were each independently associated with acquiring a BSI or ETT colonization with P aeruginosa, but other variables, including exposure to nurse A-2, were not. CONCLUSION: Epidemiological evidence demonstrated an association between acquiring P aeruginosa and exposure to two nurses. Genetic and environmental evidence supported that association and suggested, but did not prove, a possible role for long or artificial fingernails in the colonization of HCWs' hands with P aeruginosa. Requiring short natural fingernails in NICUs is a reasonable policy that might reduce the incidence of hospital-acquired infections.

Cryptococcosis: population-based multistate active surveillance and risk factors in human immunodeficiency virus-infected persons. Cryptococcal Active Surveillance Group.

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.

Using laboratory-based surveillance data for prevention: an algorithm for detecting Salmonella outbreaks.

By applying cumulative sums (CUSUM), a quality control method commonly used in manufacturing, we constructed a process for detecting unusual clusters among reported laboratory isolates of disease-causing organisms. We developed a computer algorithm based on minimal adjustments to the CUSUM method, which cumulates sums of the differences between frequencies of isolates and their expected means; we used the algorithm to identify outbreaks of Salmonella Enteritidis isolates reported in 1993. By comparing these detected outbreaks with known reported outbreaks, we estimated the sensitivity, specificity, and false-positive rate of the method. Sensitivity by state in which the outbreak was reported was 0%(0/1) to 100%. Specificity was 64% to 100%, and the false-positive rate was 0 to 1.

Etiology of bloody diarrhea in Bolivian children: implications for empiric therapy. Bolivian Dysentery Study Group.

In Bolivia, few data are available to guide empiric therapy for bloody diarrhea. A study was conducted between December 1994 and April 1995 to identify organisms causing bloody diarrhea in Bolivian children. Rectal swabs from children <5 years old with bloody diarrhea were examined for Salmonella, Shigella, and Campylobacter organisms; fecal specimens were examined for Entamoeba histolytica. A bacterial pathogen was identified in specimens from 55 patients (41%). Shigella organisms were found in 39 specimens (29%); 37 isolates (95%) were resistant to ampicillin, 35 (90%) to trimethoprim-sulfamethoxazole, and 24 (62%) to chloramphenicol, but all were susceptible to nalidixic acid. Only 1 of 133 stool specimens contained E. histolytica trophozoites. Multidrug-resistant Shigella species are a frequent cause of bloody diarrhea in Bolivian children; E. histolytica is uncommon. Clinical predictors described in this study may help identify patients most likely to have Shigella infection. Laboratory surveillance is essential to monitor antimicrobial resistance and guide empiric treatment.

A coccidioidomycosis outbreak following the Northridge, Calif, earthquake.

OBJECTIVE: To describe a coccidioidomycosis outbreak in Ventura County following the January 1994 earthquake, centered in Northridge, Calif, and to identify factors that increased the risk for acquiring acute coccidioidomycosis infection. DESIGN: Epidemic investigation, population-based skin test survey, and case-control study. SETTING: Ventura County, California. RESULTS: In Ventura County, between January 24 and March 15, 1994, 203 outbreak-associated coccidioidomycosis cases, including 3 fatalities, were identified (attack rate [AR], 30 cases per 100,000 population). The majority of cases (56%) and the highest AR (114 per 100,000 population) occurred in the town of Simi Valley, a community located at the base of a mountain range that experienced numerous landslides associated with the earthquake. Disease onset for cases peaked 2 weeks after the earthquake. The AR was 2.8 times greater for persons 40 years of age and older than for younger persons (relative risk, 2.8; 95% confidence interval [CI], 2.1-3.7; P<.001). Environmental data indicated that large dust clouds, generated by landslides following the earthquake and strong aftershocks in the Santa Susana Mountains north of Simi Valley, were dispersed into nearby valleys by northeast winds. Simi Valley case-control study data indicated that physically being in a dust cloud (odds ratio, 3.0; 95% CI, 1.6-5.4; P<.001) and time spent in a dust cloud (P<.001) significantly increased the risk for being diagnosed with acute coccidioidomycosis. CONCLUSIONS: Both the location and timing of cases strongly suggest that the coccidioidomycosis outbreak in Ventura County was caused when arthrospores were spread in dust clouds generated by the earthquake. This is the first report of a coccidioidomycosis outbreak following an earthquake. Public and physician awareness, especially in endemic areas following similar dust cloud-generating events, may result in prevention and early recognition of acute coccidioidomycosis.

Molecular subtype distribution of Cryptococcus neoformans in four areas of the United States. Cryptococcal Disease Active Surveillance Group.

To improve understanding of the epidemiology of cryptococcal disease, we analyzed the multilocus genotype distribution of 358 Cryptococcus neoformans isolates obtained from 251 patients through active surveillance in four U.S. geographic areas from 1992 through 1994. Isolates of the predominant enzyme electrophoretic type (ET), ET-1, were recovered in significantly greater proportion from Atlanta, Ga., Houston, Tex., and all major metropolitan areas of Alabama than from San Francisco, Calif. ET-2 and ET-7 complex (serotype AD) isolates were recovered predominantly from San Francisco. ET-3 was recovered less frequently from San Francisco than from the three other locations. These findings may reflect geographic differences in exposure to environmental strains or the identification of previously unrecognized C. neoformans clusters. Analysis by random amplified polymorphic DNA-PCR subtyping further divided 67 ET-1 isolates into 19 additional subtypes, none of which could be associated with a particular geographic region. Multiple isolates from the same patient always revealed the same multilocus enzyme electrophoresis and random amplified polymorphic DNA subtypes. No differences in subtype distribution were found when isolates from AIDS patients were compared with those from persons without or with another underlying disease, although one C. noeformans var. gattii isolate was obtained from an AIDS patient. When body site distribution was analyzed, ET-4 was disproportionately recovered from skin or surface body sites. Evidence for linkage disequilibrium in this fungal population suggests that virulent C. neoformans possesses a clonal population structure. Continued application of molecular subtyping methods will be useful in tracking the source, transmission, and relative virulence of different C. neoformans strains.

Comparison of multilocus enzyme electrophoresis and random amplified polymorphic DNA analysis for molecular subtyping of Cryptococcus neoformans. The Cryplococcal Disease Active Surveillance Group.

We evaluated multilocus enzyme electrophoresis (MEE) and random amplified polymorphic DNA (RAPD) for their usefulness in subtyping 344 Cryptococcus neoformans clinical isolates obtained from four U.S. metropolitan areas in 1992 to 1994. MEE and RAPD with five primers both discriminated between the two varieties of C. neofromans. MEE divided C. neoformans var. neoformans isolates into 15 enzyme electrophoretic subtypes (ETs) arranged in three complexes. The predominant ET 1 complex contained 10 ETs, with isolates from 70% of patients in 1 ET. RAPD with five primers further sorted this predominant ET into 19 subtypes, with 60% of isolates sorting into three RAPD types. The ET 8 MEE complex, containing three ETs, could not be divided further by RAPD. The ET 7 complex (two ETs) included isolates from all serotype AD patients. Although both MEE and RAPD identified isolates of C. neoformans var. gattii, neither distinguished between serotypes B and C. These results showed that the two C. neoformans varieties could be identified by MEE or RAPD profile as well as by biochemical methods. RAPD improved the discriminatory power of MEE for isolates within the ET 1 complex but with other ETs offered little additional sensitivity over MEE and was less sensitive than MEE with isolates of C. neoformans var. gattii. This information will be useful in identifying particular environmental sources of disease-causing exposures, in seeking clusters of cases, and in determining whether an infecting strain changes over time.

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.

Clinical and laboratory comparison of botulism from toxin types A, B, and E in the United States, 1975-1988.

Cases of adult botulism (n = 309) were studied to identify clinical differences between toxin types and to evaluate the sensitivity of diagnostic laboratory testing. Patients with illness from type E toxin had the shortest incubation periods. Sporadic case-patients were more severely ill: 85% required intubation compared with only 42% in multiperson outbreaks. Of patients with type A botulism, 67% required intubation compared with 52% with type B and 39% with type E. Toxin testing was positive for 40%-44% of serum and stool specimens obtained within 3 days of toxin ingestion and for 15%-23% of specimens obtained thereafter, while 37% of stool specimens obtained > 3 days after toxin ingestion were positive by culture. Patients with type A botulism have more severe illness. In general, specimens obtained early are more likely to be positive by toxin assay, and stool cultures are more sensitive than toxin detection for specimens obtained later in the illness.

Pathogenic potential of filoviruses: role of geographic origin of primate host and virus strain.

African filoviruses have caused outbreaks of fulminating hemorrhagic fever among humans. In 1989, related filoviruses were isolated from cynomolgus monkeys imported into the United States from the Philippines. The pathogenic potential of these new filoviruses was compared in 16 Asian monkeys (Macaca fascicularis-cynomolgus) and 16 African monkeys (Cercopithecus aethiops-African green) using African filoviruses from Zaire (Ebola virus) and Sudan or Asian filoviruses (Reston and Pennsylvania). African filovirus infections resulted in earlier death (P = .005), had a shorter duration of disease and median incubation period (3-4 vs. 7 days), and had earlier peak viremia (5-7 vs. 7-9 days). African green monkeys showed significantly higher survival than cynomolgus monkeys (P less than .01), and some were asymptomatic as have been humans accidentally infected with Asian filovirus. Rechallenge experiments showed that protection in survivors of filovirus infections against fatal challenge with Ebola (Zaire) virus is unpredictable. The minimal clinical disease observed in humans infected with the Reston strain is consistent with host- and virus-dependent pathogenicity.