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Rumors of disease in the global village: outbreak verification.

Emerging infectious diseases and the growth of information technology have produced new demands and possibilities for disease surveillance and response. Increasing numbers of outbreak reports must be assessed rapidly so that control efforts can be initiated and unsubstantiated reports can be identified to protect countries from unnecessary economic damage. The World Health Organization has set up a process for timely outbreak verification to convert large amounts of data into accurate information for suitable action. We describe the context and processes of outbreak verification and information dissemination.

Communicable Disease Control↗

Lessons from the West Nile viral encephalitis outbreak in New York City, 1999: implications for bioterrorism preparedness.

The involvement and expertise of infectious disease physicians, microbiologists, and public health practitioners are essential to the early detection and management of epidemics--both those that are naturally occurring, such as the 1999 outbreak of West Nile virus (WN virus) in New York City, and those that might follow covert acts of bioterrorism. The experience with the WN virus outbreak offers practical lessons in outbreak detection, laboratory diagnosis, investigation, and response that might usefully influence planning for future infectious disease outbreaks. Many of the strategies used to detect and respond to the WN virus outbreak resemble those that would be required to confront other serious infectious disease threats, such as pandemic influenza or bioterrorism. We provide an overview of the critical elements needed to manage a large-scale, fast-moving infectious disease outbreak, and we suggest ways that the existing public health capacity might be strengthened to ensure an effective response to both natural and intentional disease outbreaks.

Animals↗

Smallpox containment updated: considerations for the 21st century.

The emergence and re-emergence of infectious diseases since the eradication of smallpox has had a direct impact on preparedness for a deliberately-caused smallpox outbreak, should one occur. The emergence of HIV has placed restrictions on the safe and effective use of smallpox vaccines and made the need for vaccinia immune globulin important for outbreak control. At the same time, the threat of international spread of emerging and re-emerging infections has prompted global investments in surveillance and response mechanisms such as the Global Outbreak Alert and Response Network (GOARN), a mechanism that would enhance the world's collaboration in smallpox containment as it did during the recent outbreak of SARS. Though global preparedness for a deliberately-caused smallpox outbreak has increased with the creation of GOARN, it does not replace the need for increased national public health investment to expand surge capacity for the management of patients and their contacts and to strengthen emergency communication networks to ensure effective response.

Bioterrorism↗

An emergency medical services transfer authorization center in response to the Toronto severe acute respiratory syndrome outbreak.

OBJECTIVE: To describe the rapid development and implementation of an innovative emergency medical services (EMS) command, control, and tracking system to mitigate the risk of iatrogenic spread of severe acute respiratory syndrome (SARS) among health care facilities, health care workers, and patients in Ontario, Canada, as a result of interfacility patient transfers. METHODS: A working group of stakeholders in health care and transport medicine developed and implemented a medically based command, control, and tracking center for all interfacility (including acute and long-term care) patient transfers in Ontario, Canada. Development and implementation took place in three distinct but overlapping phases: needs assessment, design and implementation, and expansion and ongoing operations. RESULTS: The needs assessment, design, and implementation were completed in less than 48 hours using existing EMS infrastructure and personnel. The center was successfully handling more than 500 requests for interfacility patient transfer per day within 36 hours of operation and more than 1,100 requests per day within two weeks. Expansion into a new physical space enables 40 staff to process up to 1,500 requests per day. There was no reported spread of SARS resulting from interfacility patient transfers since the center began operation on April 1, 2003, and anecdotal evidence demonstrates it identified up to 13 new SARS cases. The center continues to operate as a part of Ontario's commitment as a result of diligence in transport medicine and infection control, even though no new cases of SARS were reported since June 12, 2003. Further study is needed to determine its overall efficacy at risk mitigation. CONCLUSIONS: Rapid establishment of an EMS-based command, control, and tracking center is possible in the setting of a public health emergency. In addition to risk mitigation, this type of center could provide syndromic surveillance in real time and provide the earliest indication of a potential threat to public health in acute and long-term care facilities.

Communicable Disease Control↗

Diversity of plasmids in Achromobacter xylosoxidans isolates responsible for a seemingly common-source nosocomial outbreak.

Achromobacter xylosoxidans, an uncommon yet highly resistant opportunistic pathogen, was isolated from nine hospitalized patients during an 8-month period. It had been isolated from only seven patients with either nonfatal infection or colonization from 1981 to 1984. From June 1985 to January 1986, A. xylosoxidans was isolated 18 times from seven different sites (sputum, 7 times; urine, 4 times; blood, 3 times; and lung, pleural fluid, wound tissue, and tracheal aspirate, 1 time each). Four patients died, including the three with bacteremia. All but two patients had nosocomial infections and either were on the same ward or were cared for by the same staff members. Eleven A. xylosoxidans strains yielded eight distinct plasmids (8, 21, 23, 26, 38, 50, 51, and 64 megadaltons). Whole-cell peptide patterns of 10 of these strains were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Isolates from the same patient contained the same plasmids and had identical peptide patterns but differed from other strains in both parameters. Plasmids were absent from the two community-acquired isolates. Although nosocomial strains showed similar antibiotic resistance patterns (only moxalactam and ticarcillin-clavulanic acid were uniformly active) and cross-contamination was strongly suggested epidemiologically, results of plasmid and peptide analyses did not support the possibility of a single-strain outbreak.

Adult↗

The genetic portrait of an outbreak strain.

Unique events in the genome of Mycobacterium tuberculosis, including deletions and IS6110 insertions, have been proposed to be responsible for the virulence phenotype of outbreak strains. Based on this premise, we determined ten IS6110 insertion sites in the genome of the M. tuberculosis CH strain, which was responsible for a large outbreak in Leicestershire, England. Together with previous data on genomic deletions, it was found that 16 genes were mutated either by IS6110 insertions or deletions. The likely impact of these genomic events on the phenotype of the CH strain is discussed.

Disease Outbreaks↗

A phylogenetic study of South African Newcastle disease virus strains isolated between 1990 and 2002 suggests epidemiological origins in the Far East.

Genetic comparisons were made of the fusion protein sequences of 155 Newcastle disease virus isolates collected in South Africa between 1990 and 2002. Their evolutionary relationships and origins are described. All of the lentogenic field isolates were shown to be derived from commercial vaccines. No true South African lentogenic wild type strain was identified. Furthermore, it was shown that almost all mesogenic isolates had avirulent F(0) cleavage site sequences. Three major epizootics occurred in South Africa during the period of this study. The first outbreak (1990/1991) was caused by viruses endemic to South Africa since the 1960's (genotype VIII) but were occasionally also isolated in 2000. Genotype VIIb viruses, implicated in the severe outbreaks during 1993/1994, persisted until 1999. Genotype VIId viruses, responsible for the most recent outbreak in 1999/2000, had their origins in the Far East like those of the two previous outbreaks.

Amino Acid Sequence↗

Frequency of adverse events after vaccination with different vaccinia strains.

BACKGROUND: Large quantities of smallpox vaccine have been stockpiled to protect entire nations against a possible reintroduction of smallpox. Planning for an appropriate use of these stockpiled vaccines in response to a smallpox outbreak requires a rational assessment of the risks of vaccination-related adverse events, compared to the risk of contracting an infection. Although considerable effort has been made to understand the dynamics of smallpox transmission in modern societies, little attention has been paid to estimating the frequency of adverse events due to smallpox vaccination. Studies exploring the consequences of smallpox vaccination strategies have commonly used a frequency of approximately one death per million vaccinations, which is based on a study of vaccination with the New York City Board of Health (NYCBH) strain of vaccinia virus. However, a multitude of historical studies of smallpox vaccination with other vaccinia strains suggest that there are strain-related differences in the frequency of adverse events after vaccination. Because many countries have stockpiled vaccine based on the Lister strain of vaccinia virus, a quantitative evaluation of the adverse effects of such vaccines is essential for emergency response planning. We conducted a systematic review and statistical analysis of historical data concerning vaccination against smallpox with different strains of vaccinia virus. METHODS AND FINDINGS: We analyzed historical vaccination data extracted from the literature. We extracted data on the frequency of postvaccinal encephalitis and death with respect to vaccinia strain and age of vaccinees. Using a hierarchical Bayesian approach for meta-analysis, we estimated the expected frequencies of postvaccinal encephalitis and death with respect to age at vaccination for smallpox vaccines based on the NYCBH and Lister vaccinia strains. We found large heterogeneity between findings from different studies and a time-period effect that showed decreasing incidences of adverse events over several decades. To estimate death rates, we then restricted our analysis to more-recent studies. We estimated that vaccination with the NYCBH strain leads to an average of 1.4 deaths per million vaccinations (95% credible interval, 0-6) and that vaccination with Lister vaccine leads to an average of 8.4 deaths per million vaccinations (95% credible interval, 0-31). We combined age-dependent estimates of the frequency of death after vaccination and revaccination with demographic data to obtain estimates of the expected number of deaths in present societies due to vaccination with the NYCBH and Lister vaccinia strains. CONCLUSIONS: Previous analyses of smallpox vaccination policies, which rely on the commonly assumed value of one death per million vaccinations, may give serious underestimates of the number of deaths resulting from vaccination. Moreover, because there are large, strain-dependent differences in the frequency of adverse events due to smallpox vaccination, it is difficult to extrapolate from predictions for the NYCBH-derived vaccines (stockpiled in countries such as the US) to predictions for the Lister-derived vaccines (stockpiled in countries such as Germany). In planning for an effective response to a possible smallpox outbreak, public-health decision makers should reconsider their strategies of when to opt for ring vaccination and when to opt for mass vaccination.

Age Distribution↗

Coping responses of emergency physicians and nurses to the 2003 severe acute respiratory syndrome outbreak.

OBJECTIVES: During the 2003 severe acute respiratory syndrome (SARS) outbreak, health care workers (HCWs) experienced unusual stressors. The study hospital introduced psychosocial interventions to help HCWs. This study aimed to examine the coping strategies adopted by the emergency department (ED) HCWs who cared for the SARS patients. METHODS: In November 2003, a self-administered questionnaire of physicians and nurses was conducted in the hospital ED that is the national SARS screening center in Singapore. Data collected included demographics and responses to these instruments: 1) the Coping Orientation to Problems Experienced (COPE) to assess coping strategies, 2) the Impact of Event Scale (IES) to measure psychological reactions, and 3) the General Health Questionnaire 28 (GHQ 28) to measure psychiatric morbidity. RESULTS: Thirty-eight of 41 (92.7%) physicians and 58 of 83 (69.9%) nurses responded. The respondents reported a preference for problem-focused and emotion-focused coping measures. The physicians chose humor as a coping response significantly more frequently (p < 0.001) than nurses, scoring 9.61/16 (95% CI = 8.52 to 10.69), compared with the nurses' score of 7.05/16 (95% CI = 6.28 to 7.83). The Filipino HCWs turned to religion as a coping response significantly more frequently (p < 0.001) than the non-Filipino HCWs, scoring 14.38/16 (95% CI = 13.33 to 15.42), compared with 9.93/16 (95% CI = 9.00 to 10.87) for the non-Filipinos. Psychiatric morbidity was 17.7% on the IES and 18.8% on the GHQ 28, with the trend for physicians to report lower psychiatric morbidity. CONCLUSIONS: With a supportive hospital environment, ED HCWs chose adaptive coping in response to the outbreak and reported low psychiatric morbidity. Physicians chose humor and Filipinos chose turning to religion as their preferred responses. Psychosocial interventions to help HCWs need to take these preferences into account.

Adaptation, Psychological↗

Evaluation of serotyping, biotyping, plasmid banding pattern analysis, and HEp-2 vacuolation factor assay in the epidemiological investigation of Bacillus cereus emetic-syndrome food poisoning.

To assess the value of the plasmid banding patterns, the vacuolation factor (VF) assay, biotyping, and serological typing as epidemiological markers for strains of Bacillus cereus causing emetic-syndrome illness, 43 isolates from five outbreaks and an additional 76 strains isolated in food-poisoning outbreaks caused by other enteric pathogens were examined by these techniques, and the results were compared. Thirty-eight (88%) of the 43 outbreak strains produced vacuolation responses in HEp-2 cells and were all starch-hydrolysis negative. The other 76 strains associated with outbreaks caused by other food-poisoning bacteria gave all negative VF production results except four strains, and 56 (74%) of these strains produced positive reactions in starch hydrolysis tests. Starch hydrolysis emerged as a convenient screen for VF production, because no starch hydrolysis-positive strains produced VF. With the exception of one isolate, all 38 VF-positive isolates from emtic-syndrome outbreaks were serotype H.1. Isolates from four of the five outbreaks revealed identical plasmid banding patterns in each outbreak, whereas only three of eight serotype H.1 strains from the fifth outbreak exhibited indistinguishable plasmid banding patterns. These results suggest that the plasmid banding pattern analysis may be of value in discriminating between isolates of the same serotype, and establishing if an outbreak arises from a common food source. In conclusion, the vacuolation factor assay combined with the plasmid banding patterns proved to be a valuable tool for the epidemiological investigation of emetic-syndrome outbreaks caused by B. cereus. Moreover, these methods are particularly useful for laboratories that do not have ready access to serotyping facilities.

Bacillus cereus↗

Containing a haemorrhagic fever epidemic: the Ebola experience in Uganda (October 2000-January 2001).

INTRODUCTION: The Ebola virus, belonging to the family of filoviruses, was first recognized in 1976 when it caused concurrent outbreaks in Yambuku in the Democratic Republic of Congo (DRC), and in the town of Nzara in Sudan. Both countries share borders with Uganda. A total of 425 cases and 224 deaths attributed to Ebola haemorrhagic fever (EHF) were recorded in Uganda in 2000/01. Although there was delayed detection at the community level, prompt and efficient outbreak investigation led to the confirmation of the causative agent on 14 October 2000 by the National Institute of Virology in South Africa, and the subsequent institution of control interventions. CONTROL INTERVENTIONS: Public health interventions to contain the epidemic aimed at minimizing transmission in the health care setting and in the community, reducing the case fatality rate due to the epidemic, strengthening co-ordination for the response and building capacity for on-going surveillance and control. Co-ordination of the control interventions was organized through the Interministerial Committee, National Ebola Task Force, District Ebola Task Forces, and the Technical Committees at national and district levels. The World Health Organization (WHO) under the Global Outbreak Alert and Response Network co-ordinated the international response. The post-outbreak control interventions addressed weaknesses prior to outbreak detection and aimed at improving preparations for future outbreak detection and response. Challenges to control efforts included inadequate and poor quality protective materials, deaths of health workers, numerous rumors and the rejection of convalescent cases by members of the community. CONCLUSIONS: This was recognized as the largest reported outbreak of EHF in the world. Control interventions were very successful in containing the epidemic. The community structures used to contain the epidemic have continued to perform well after containment of the outbreak, and have proved useful in the identification of other outbreaks. This was also the first outbreak response co-ordinated by the WHO under the Global Outbreak Alert and Response Network, a voluntary organization recently created to co-ordinate technical and financial resources to developing countries during outbreaks.

Communicable Disease Control↗

Population genetic and evolutionary approaches to analysis of Neisseria meningitidis isolates belonging to the ET-5 complex.

Periodically, new disease-associated variants of the human pathogen Neisseria meningitidis arise. These meningococci diversify during spread, and related isolates recovered from different parts of the world have different genetic and antigenic characteristics. An example is the ET-5 complex, members of which were isolated globally from the mid-1970s onwards. Isolates from a hyperendemic outbreak of meningococcal disease in Worcester, England, during the late 1980s were characterized by multilocus sequence typing and sequence determination of antigen genes. These data established that the Worcester outbreak was caused by ET-5 complex meningococci which were not closely related to the ET-5 complex bacteria responsible for a hyperendemic outbreak in the nearby town of Stroud during the years preceding the Worcester outbreak. A comparison with other ET-5 complex meningococci established that there were at least three distinct globally distributed subpopulations within the ET-5 complex, characterized by particular housekeeping and antigen gene alleles. The Worcester isolates belonged to one of these subpopulations, the Stroud isolates belonged to another, and at least one representative of the third subpopulation identified in this work was isolated elsewhere in the United Kingdom. The sequence data demonstrated that ET-5 variants have arisen by multiple complex pathways involving the recombination of antigen and housekeeping genes and de novo mutation of antigen genes. The data further suggest that either the ET-5 complex has been in existence for many years, evolving and spreading relatively slowly until its disease-causing potential was recognized, or it has evolved and spread rapidly since its first identification in the 1970s, with each of the subpopulations attaining a distribution spanning several continents.

Amino Acid Sequence↗

The genetic basis of resistance to Ostertagia circumcincta in lambs.

The relationship between Ostertagia (Teladorsagia) circumcincta and sheep is one of the best understood host-parasite relationships in any species. The key components of resistance have been quantified, the extent of genetic control has been established for lambs, and methods now exist to breed lambs which will be both more resistant to worms and more productive than unselected lambs. A major gene for resistance has been identified within or around the major histocompatibility complex, and this gene appears to be the strongest yet identified for resistance to any parasite species. The most important mechanisms of resistance are local IgA responses which regulate worm fecundity and immediate hypersensitivity responses which regulate worm burdens. IgA responses develop before effective immediate hypersensitivity responses. Good simulation models now exist to predict, for example, outbreaks of disease and the response of sheep to selection. The challenge now is to use our improved understanding of the population biology to develop even better simulation models and to produce expert systems based on these models which can be used by veterinarians and others to determine optimal procedures for individual farms to control disease and reduce sub-clinical economic losses.

Animals↗

Progress toward measles elimination--region of the Americas, 2002-2003.

In 1994, countries in the Region of the Americas adopted the goal of eliminating endemic measles transmission in the Western hemisphere by 2000. Since 1994, rapid progress has been made. The number of measles cases has declined >99%, from approximately 250,000 in 1990 to 105 confirmed cases reported in six countries in 2003. During 2003, only Mexico and the United States reported outbreaks. The three chains of transmission in Mexico and two U.S. outbreaks were import-related; a third U.S. outbreak was of unknown source. Since November 2002, no transmission of the D6 and D9 genotypes has been reported; these genotypes were responsible for several large outbreaks in the region during 1997-2002. This report summarizes the epidemiology of measles in the Americas during 2002-2003 and highlights progress toward measles elimination, including the lowest ever number of reported measles cases in the region. Because the region is under constant threat of measles importation from regions where the disease is endemic, countries must maintain high population immunity to measles and sensitive surveillance to ensure the timely detection of imported cases and allow for rapid implementation of control measures.

Americas↗

Responding to a community outbreak of syphilis by targeting sex partner meeting location: an example of a risk-space intervention.

BACKGROUND: Effective syphilis control and elimination require community effort and innovative case-finding techniques, especially to identify infected persons from core transmission groups. GOAL: To summarize the implementation and outcomes of a community-oriented response to a localized outbreak of syphilis directed at sex partner meeting places. STUDY DESIGN: Syphilis surveillance and rapid response data from a 7-month period were analyzed for risk behaviors, sex partner meeting locations, field investigation outcomes, and social and sexual network connections. RESULTS: Four (6%) of the sixty-nine persons tested were confirmed syphilis reactors, of whom three were new cases. A sexual and needle-sharing network of 15 persons was identified that included two of the new syphilis cases. These two had not been found through standard field investigation. CONCLUSIONS: Targeting interventions to sex partner meeting places may effectively complement traditional syphilis control tools and find previously unidentified syphilis cases in high-morbidity areas.

Adult↗

Immune response to Giardia lamblia in a water-borne outbreak of giardiasis in Sweden.

In one of the largest outbreaks of waterborne giardiasis reported from Europe, more than 3000 persons were exposed to contaminated water and over 1400 cases of giardiasis were diagnosed by microscopy. The outbreak resulted from an overflow of sewage water into the drinking water system of a Swedish ski resort. The period of contamination was about 1 week. Sweden is a non-endemic area for Giardia lamblia infection and, for most individuals affected, this was their first contact with the parasite. Few other enteropathogens were isolated from the patients involved. Therefore, an immune response to Giardia was unlikely to be biased by other concomitant infections. Serum samples from 352 exposed persons were collected and analysed for specific IgG and IgA antibodies to G. lamblia by indirect immunofluorescence and the results were related to the microscopic examination of faeces and the occurrence of diarrhoea. As controls, sera from 428 healthy persons were analysed at the same time by identical methods. IgG or IgA antibodies, or both, were found in 68% of patients whose diagnosis was made by microscopy, and in 22% of exposed by microscopically Giardia-negative persons, but in only 10% of healthy controls. The findings show that patients reported as negative for parasites might be infected. The time between infection and blood sampling influenced the result of the antibody test. The results suggest that stool examination should be the primary means of diagnosis of G. lamblia infection and that serological analysis performed at least 3 weeks after infection could contribute to diagnosis in a non-endemic region, when giardiasis is suspected but the parasite has not been detected.

Adolescent↗