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A case exercise: outbreak investigation at a Vermont community hospital.

Fifteen employees became ill with headaches, nausea, and vomiting due to chemical poisoning at a Vermont community hospital on January 3, 1980. An epidemiologic and environmental investigation was conducted to determine the source of the illness. The investigation discovered that the vapors of a chemical called xylene, which had previously been disposed of down a drain, were drawn back through the sewer into specific work areas. These vapors were determined to be the most likely cause of the illnesses. This outbreak investigation was used to create an exercise that has been used in a variety of teaching settings.

Adult↗

Plasmid profile typing can be used to subdivide phage-type 49 of Salmonella typhimurium in outbreak investigations.

Plasmid profile typing has been used to subdivide phage-type 49 of Salmonella typhimurium, the most common phage type in humans in England and Wales since 1985. Twenty profile patterns have been identified in 350 strains examined. Four profile patterns have been identified in 143 isolates from patients infected in 33 epidemiologically unrelated incidents and two patterns have predominated, ST49:62 and ST49:62, 1. These patterns were also common amongst S. typhimurium phage-type 49 isolated from cattle and poultry; however ST49:62 was more common in bovines whereas ST49:62, 1 predominated in poultry. S. typhimurium phage-type 49 with a different profile pattern, ST49:62, 3, was responsible for a large outbreak in London in 1988 which was traced to mayonnaise made from eggs supplied by one producer. Plasmid profile typing can now be regarded as a method of supplementing phage typing in investigating outbreaks caused by this organism.

Animals↗

Comparative and library epidemiological typing systems: outbreak investigations versus surveillance systems.

A number of high-resolution molecular typing systems have been developed in recent years. Their availability raises the new issues of selecting the method (s) best suited for a particular purpose and interpreting and communicating typing results. Most of the currently available methods are comparative only: they allow testing of a sample of isolates for delineation of those closely related from those markedly different in genomic backgrounds. This approach is adequate for outbreak investigation, allowing determination of clonal spread in a microenvironment and identification of the source of infection. Comparative methods with sufficient resolution for most pathogens include restriction fragment-length polymorphism (RFLP), pulsed-field gel electrophoresis (PFGE), and arbitrarily primed and randomly amplified polymorphic DNA-polymerase chain reaction (PCR) analysis. For surveillance systems, monitoring clonal spread and prevalence in populations over extended periods of time requires library typing systems. These must be standardized, must have a high throughput, and must use a uniform nomenclature. Promising or validated methods include serotyping, insertion sequence fingerprinting, ribotyping, PFGE, amplified fragment-length polymorphism (AFLP), infrequent-restriction-site amplification PCR, interrepetitive element PCR typing (rep-PCR) and PCR-RFLP of polymorphic loci. PCR methods generating arrays of size-specific amplicons (AFLP, rep-PCR) can be more reproducibly analyzed by using denaturing polyacrylamide gel or capillary electrophoresis with automated laser detection. Binary probe typing systems appear optimal and should be enhanced further through use of DNA chip technology. In these systems, amplification of polymorphic regions is followed by solid-phase hybridization with a reference panel of sequence-variant specific probes. The resulting binary type results allow determination of reproducible, numeric profiles. However, interpretation and nomenclature of typing results for large-scale surveillance purposes still require a better understanding of population structure and microevolution of most microbial pathogens.

Bacterial Infections↗

Risk groups for clinical complications of norovirus infections: an outbreak investigation.

Norovirus infections have been described as self-limiting diseases of short duration. An investigation of a norovirus outbreak in a university hospital provided evidence for severe clinical features in patients with several underlying diseases. Clinical outcomes of norovirus infection were defined. Risk-factor analysis targeting underlying diseases and medication was performed using multivariate analyses. In five outbreak wards, 84 patients and 60 nurses were infected (an overall attack rate of 32% in patients, and 76% in nurses). The causative agent was the new variant Grimsby virus. Severe clinical features, including acute renal failure, arrhythmia and signs of acute graft organ rejection in renal transplant patients, were observed in seven (8.3%) patients. In multivariate analyses, cardiovascular disease (OR 17.1, 95% CI 2.17-403) and renal transplant (OR 13.0, 95% CI 1.63-281) were risk-factors for a potassium decrease of >20%. Age >65 years (OR 11.6, 95% CI 1.89-224) was a risk-factor for diarrhoea lasting >2 days. Immunosuppression (OR 5.7, 95% CI 1.78-20.1) was a risk-factor for a creatinine increase of >10%. Norovirus infections in patients with underlying conditions such as cardiovascular disease, renal transplant and immunosuppressive therapy may lead to severe consequences typified by decreased potassium levels, increased levels of C-reactive protein and creatine phosphokinase. In the elderly, norovirus infection may lead to an increased duration of diarrhoea. Therefore patients at risk should be hospitalised early and monitored frequently. Strict preventional measures should be implemented as early as possible to minimise the risk of nosocomial outbreaks.

Aged↗

Bacillus cereus and Bacillus thuringiensis isolated in a gastroenteritis outbreak investigation.

During investigation of a gastroenteritis outbreak in a chronic care institution, Norwalk virus was found in stool specimens from two individuals and bacterial isolates presumptively identified as Bacillus cereus were isolated from four individuals (including one with Norwalk virus) and spice. Phage typing confirmed all Bacillus clinical isolates were phage type 2. All clinical isolates were subsequently identified as B. thuringiensis when tested as a result of a related study (L. Leroux, personal communication). Eight of 10 spice isolates were phage type 4. All B. cereus and B. thuringiensis isolates showed cytotoxic effects characteristic of enterotoxin-producing B. cereus. An additional 20 isolates each of B. cereus and B. thuringiensis from other sources were tested for cytotoxicity. With the exception of one B. cereus, all showed characteristic cytotoxic patterns.

Bacillaceae Infections↗

An outbreak of hepatitis B associated with reusable subdermal electroencephalogram electrodes. Hepatitis B Outbreak Investigation Team.

BACKGROUND: In early 1996 an outbreak of hepatitis B was detected among patients who attended an electroencephalogram (EEG) clinic in Toronto operated by a neurologist. In this article we report the results of an investigation conducted to determine the extent and source of the outbreak. METHODS: Notifications were sent to 18 567 patients who had attended any of 6 EEG clinics operated by the neurologist between 1990 and 1996 asking them to see their physician to be tested for hepatitis B virus (HBV) infection; 2957 envelopes were returned. Of the remaining 15 610 patients, results of laboratory tests were available for 10 244 (65.6%). A detailed follow-up of patients with newly acquired hepatitis B and those with chronic infection (carriers) was conducted. Viral DNA sequencing was used to compare strains of available HBV isolates. RESULTS: A total of 75 patients were identified in whom hepatitis B developed between 1991 and 1996; all of them had had at least one EEG performed in which reusable subdermal electrodes had been used. No cases were detected among patients who participated only in sleep studies, for which disk electrodes had been used. The peak rate of HBV infection (18.2 cases per 1000 person-EEGs) occurred in 1995. One technician performed all of the EEGs at the clinics and was found to be positive for hepatitis B e antigen. DNA sequencing confirmed that the virus isolated from the technician was identical to the virus isolated in 4 cases of hepatitis B tested. Infection control procedures were found to be inadequate. INTERPRETATION: The hepatitis B outbreak was a result of a common source of infection, the technologist, and inadequate infection control practices. Reusable subdermal EEG electrodes were the likely vehicles of transmission. Health care workers should follow recommended infection control practices and be vaccinated against hepatitis B.

Cross Infection↗

Evolution of a laboratory based system for investigating outbreaks of infectious intestinal disease.

In 1995 Preston Public Health Laboratory introduced an incident logging system intended to improve the investigation of suspected outbreaks of infectious intestinal disease. A unique incident log (Ilog) number assigned and issued to the reporting individual and other interested parties when the laboratory is informed of a potential outbreak is used to identify all associated specimens submitted to the laboratory and is quoted in all communications about the incident. The results are reviewed formally each month. Between January 1995 and December 1998, 349 potential outbreaks of infectious intestinal disease were investigated, 325 of which were considered to be general outbreaks. Small round structured viruses were identified in 45% of these outbreaks, salmonellas in 8%, and no pathogens in 35%. Data from the national surveillance scheme for general outbreaks of infectious intestinal disease included 104 general outbreaks in 1996 and 1997 for the entire North West region, but our laboratory alone reported 184 general outbreaks during that period. The Ilog system is a simple and effective means for reviewing data from outbreaks, and helps to coordinate their investigation.

Clinical Laboratory Techniques↗

Pseudomonas aeruginosa and Enterobacteriaceae bacteremia after biliary endoscopy: an outbreak investigation using DNA macrorestriction analysis.

PURPOSE: An outbreak of gram-negative bacteremia in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) was investigated to determine the sources of infection and to control transmission. PATIENTS, METHODS, AND RESULTS: The incidence of post-ERCP bacteremia increased from 1.6% (60 of 3,696) procedures to 3.6% (53 of 1,454) procedures (relative risk 2.3, p < 0.0001) after endoscopes were processed in a new automated disinfector. Bacteremia involved nine species of Pseudomonas and Enterobacteriaceae, which were also isolated from processed endoscopes. Seven epidemic strains with highly related genomic macrorestriction profiles each infected 2 or more patients, accounting for 29 (55%) episodes of post-ERCP bacteremia. Strains recovered from endoscopes and from the disinfector were associated with 22 (42%) and 5 (9%) bacteremic episodes respectively. Effective endoscope disinfection was achieved by cleansing and disinfection of a blind channel not processed in the disinfector, additional isopropanol-air flush of all channels, and auto-disinfection of the disinfector. In the following period, the incidence of post-ERCP bacteremia returned to the pre-epidemic rate (1.7%, p = 0.0001). CONCLUSION: Bacterial genome fingerprinting by macrorestriction analysis enabled delineation of a multi-strain outbreak of post-ERCP bacteremia. Cross-contamination, and to a lesser extent, common-source contamination, appeared related to inadequate disinfection of endoscopes processed in an automated disinfector.

Bacteremia↗

A low-cost, community-based measles outbreak investigation with follow-up action.

An outbreak of measles in Kampala, Uganda, in 1990 raised concern about the effectiveness of the measles vaccine that was used. The Uganda EPI programme and the medical office of the Kampala City Council therefore conducted a community-based investigation, with door-to-door interviews in two selected communities. They revealed 68 measles cases ranging in age from 5 months to 12 years; the highest age-specific attack rate (32%) was found in children aged 12 to 23 months. BCG immunization coverage was high (85%), but measles immunization coverage was moderate (48%). One community, served by a mobile clinic, presented a vaccine efficacy of only 55%. Responses by mothers revealed that many had failed to have their children completely immunized because of a lack of information, and not because of difficulties in access to the service. In a follow-up, community leaders initiated monthly checking of immunization cards of both children and mothers. The low vaccine efficacy found in one of the communities resulted in a thorough assessment of the city's cold chain. This community-based approach proved to be cost-effective and practical for identifying the obstacles to effective immunization delivery.

Child↗

Outbreak investigation in a neonatal intensive care unit.

Outbreaks of healthcare-acquired infection can be devastating in neonatal intensive care units. Neonates are especially susceptible hosts because of prematurity of organ systems, low birth weight, and the use of invasive devices. This article outlines methodologies for infection surveillance and recognition of outbreak events. Principles of infection control in the neonatal intensive care unit are reviewed in reference to an outbreak setting, and a multidisciplinary team approach to developing a plan of action to halt the outbreak and find the source is discussed. Epidemiologic methods for determining the geographical extent and timeline of an outbreak, potential reservoirs or a common source of infection are reviewed.

Cross Infection↗

[Measles outbreaks: considerations apropos of the outbreaks investigated in Catalonia (1990-1995)].

OBJECTIVES: To determine the factors associated with outbreak size in Catalonia. METHODS: Outbreaks over the period 1990-95 were investigated. A comparison was run between outbreaks of more than 6 cases with respect to outbreaks of 2-6 cases in function of the following variables: median age of cases, transmission setting and year of presentation. Multiple logistic regression was used to asses the independent effect of each variable, with the adjusted odds ratio (ORa) and their 95% confidence interval (CI) being obtained. RESULTS: In all, 45 outbreaks were studied, with 595 cases of measles 39.5% of outbreaks occurred in the 6-10 age group. Outbreaks of more than 6 cases had a higher likelihood of appearing in a school setting (ORa = 4.3, CI 95% 1.0-17.6); but there were no association with age (ORa = 2.1, CI 95% 0.5-9.2) or occurring prior to 1994 (ORa = 0.9, CI 95% 0.2-3.6). CONCLUSIONS: School setting determines the outbreak size of measles and demands to apply specific preventive strategies.

Adolescent↗

Tularemia outbreak investigation in Kosovo: case control and environmental studies.

A large outbreak of tularemia occurred in Kosovo in the early postwar period, 1999-2000. Epidemiologic and environmental investigations were conducted to identify sources of infection, modes of transmission, and household risk factors. Case and control status was verified by enzyme-linked immunosorbent assay, Western blot, and microagglutination assay. A total of 327 serologically confirmed cases of tularemia pharyngitis and cervical lymphadenitis were identified in 21 of 29 Kosovo municipalities. Matched analysis of 46 case households and 76 control households suggested that infection was transmitted through contaminated food or water and that the source of infection was rodents. Environmental circumstances in war-torn Kosovo led to epizootic rodent tularemia and its spread to resettled rural populations living under circumstances of substandard housing, hygiene, and sanitation.

Adolescent↗

A Streptococcus pyogenes outbreak caused by an unusual serotype of low virulence: the value of typing techniques in outbreak investigations.

OBJECTIVES: To investigate and stop the spread of an outbreak of Streptococcus pyogenes infection in a district general hospital, involving 19 patients and two nurses over a 20-day period. METHODS: All suspected persons were investigated using conventional bacteriological techniques, followed by M, T and exotoxin gene-typing of the isolates in a national reference laboratory. RESULTS: 11 patients and both nurses were associated with the acute surgical ward on one floor of the hospital. They were infected with serotype M 9/T B3264, a strain with apparently low virulence, which has not been previously associated with outbreaks. Two other patients on the same floor each had different types and there were two clusters of another S. pyogenes serotype on other floors, each involving two patients. Two (unrelated) patients yielded other types of S. pyogenes. The patients were not seriously ill but had some delay in wound healing. CONCLUSIONS: The value of typing the isolates of S. pyogenes in this outbreak was in defining which patients were involved. No added value could be ascribed to the exotoxin gene-typing results.

Adult↗

Chromosomal rearrangements in Salmonella enterica serotype typhi affecting molecular typing in outbreak investigations.

Salmonella enterica serotype Typhi strains belonging to eight different outbreaks of typhoid fever that occurred in Spain between 1989 and 1994 were analyzed by ribotyping and pulsed-field gel electrophoresis. For three outbreaks, two different patterns were detected for each outbreak. The partial digestion analysis by the intron-encoded endonuclease I-CeuI of the two different strains from each outbreak provided an excellent tool for examining the organization of the genomes of epidemiologically related strains. S. enterica serotype Typhi seems to be more susceptible than other serotypes to genetic rearrangements produced by homologous recombinations between rrn operons; these rearrangements do not substantially alter the stability or survival of the bacterium. We conclude that genetic rearrangements can occur during the emergence of an outbreak.

Bacterial Typing Techniques↗

Detection and isolation of Salmonella from naturally contaminated alfalfa seeds following an outbreak investigation.

Naturally contaminated alfalfa seeds, epidemiologically linked to foodborne disease outbreaks in Oregon and British Columbia, were tested for the presence of Salmonella. Ten sample units from the suspected lot were sprouted and grown for 4 days. After enrichment of the grown sprouts, an enzyme immunoassay (EIA) and culture method (modified procedure of the Food and Drug Administration Bacteriological Analytical Manual) were used for the detection and isolation of Salmonella. Four of the 10 sample units were positive with the EIA; however, 5 of the 10 sample units were culture positive (four were positive for Salmonella serotype Newport and a fifth was positive for Salmonella serotype Albany and serotype Schwarzengrund). The positive alfalfa seed sample units were further tested after shredding, soaking, and washing before culturing. Results suggest that sprouting and shredding methods may yield greater detection and recovery rates of Salmonella, but more research with a larger sample size is warranted.

British Columbia↗

Genotyping of measles and mumps virus strains using amplification refractory mutation system analysis combined with enzyme immunoassay: a simple method for outbreak investigations.

A simple method, based on a modification of the amplification refractory mutation system (ARMS), for genotyping outbreak strains of measles and mumps viruses and detecting these in a simple enzyme immunoassay (EIA) is described. Fifty-three measles strains circulating at the time of an outbreak in London in 2000 and 26 strains circulating at the time of a mumps outbreak in Accrington, UK, in 1999 were investigated. All strains were genotyped by direct sequencing. ARMS primers were then designed to amplify the outbreak strain. The ARMS-EIA for measles and mumps detected all 36 measles outbreak strains as genotype D6, and all 15 mumps outbreak strains as genotype F, respectively. The sensitivity and specificity of both the measles D6 and Mumps F genotype ARMS EIA was 100% compared with direct sequencing. The results show that ARMS-EIA can be used as a rapid alternative to genotyping by direct sequence analysis in outbreak situations.

Alleles↗

Comparison of pulsed-field gel electrophoresis and amplified fragment length polymorphism techniques for investigating outbreaks of enteritis due to campylobacters.

Campylobacters are the most commonly reported cause of acute bacterial enteritis in the United Kingdom and United States, with poultry, milk, and water implicated as sources or vehicles of infection. The majority of campylobacter infections are sporadic, although outbreaks may occur, and these provide an opportunity to evaluate genotypic fingerprinting techniques. In this study, pulsed-field gel electrophoresis (PFGE) was compared with single-enzyme-amplified fragment length polymorphism (SAFLP). The results for the three separate episodes indicated that SAFLP and PFGE both clustered the strains from the first incident as 100% homologous. The strains from the second and third incidents clustered as distinct from both the first incident and from each other. PFGE is well recognized as a discriminatory fingerprinting technique for campylobacters; however, SAFLP has proven to be equally discriminatory, but far less labor intensive and with the added advantages of less "hands-on" time and inexpensive equipment, it is an excellent alternative to PFGE for investigation of outbreaks.

Bacterial Typing Techniques↗

Use of restriction endonuclease analysis of plasmids and pulsed-field gel electrophoresis to investigate outbreaks of methicillin-resistant Staphylococcus aureus infection.

We used restriction endonuclease analysis of plasmids (REAP) and pulsed-field gel electrophoresis (PFGE) to investigate clusterings of methicillin-resistant Staphylococcus aureus (MRSA) infections in our orthopedic unit, neurosurgery unit, intensive care unit, and burn unit. Fourteen different strain types were identified by REAP and 10 different strain types were identified by PFGE among 25 MRSA isolates collected during these incidents of infection. Though neither technique was clearly superior to the other for typing MRSA isolates, REAP is recommended as a relatively simple and reproducible technique for the preliminary investigation of MRSA infection outbreaks in clinical settings.

Bacterial Typing Techniques↗