Application of a Risk Analysis Tool to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Outbreak in Saudi Arabia.

The Grunow-Finke assessment tool (GFT) is an accepted scoring system for determining likelihood of an outbreak being unnatural in origin. Considering its high specificity but low sensitivity, a modified Grunow-Finke tool (mGFT) has been developed with improved sensitivity. The mGFT has been validated against some past disease outbreaks, but it has not been applied to ongoing outbreaks. This study is aimed to score the outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia using both the original GFT and mGFT. The publicly available data on human cases of MERS-CoV infections reported in Saudi Arabia (2012-2018) were sourced from the FluTrackers, World Health Organization, Saudi Ministry of Health, and published literature associated with MERS outbreaks investigations. The risk assessment of MERS-CoV in Saudi Arabia was analyzed using the original GFT and mGFT criteria, algorithms, and thresholds. The scoring points for each criterion were determined by three researchers to minimize the subjectivity. The results showed 40 points of total possible 54 points using the original GFT (likelihood: 74%), and 40 points of a total possible 60 points (likelihood: 67%) using the mGFT, both tools indicating a high likelihood that human MERS-CoV in Saudi Arabia is unnatural in origin. The findings simply flag unusual patterns in this outbreak, but do not prove unnatural etiology. Proof of bioattacks can only be obtained by law enforcement and intelligence agencies. This study demonstrated the value and flexibility of the mGFT in assessing and predicting the risk for an ongoing outbreak with simple criteria.

An Evaluation of Situation Reports and Incident Notices: The DBPR/ESRB Experience.

OBJECTIVE: The main objective of this study is to review information within the situation reports (SITREPs) and incident notices (INs) prepared by the Division of Bioterrorism Preparedness and Response/Epidemiology Surveillance and Response Branch, (DBPR/ESRB), Centers for Disease Control and Prevention (CDC). The secondary objective is to evaluate accuracy and completeness of the information provided in these documents. METHODS: The authors reviewed all SITREPs/INs prepared by DBPR/ESRB from January 2007 to June 2009. Data were abstracted for variables related to the type of incidents, the type of CDC assistance requested, the geographic origin of the calls, and the organization reporting the event or requesting CDC assistance or both. In addition, variables were also created to assess the accuracy and completeness of reports for quality improvement analysis. RESULTS: The DBPR/ESRB prepared 77 SITREPs and 22 INs. Most of them were related to unknown white powders/suspicious packages or BioWatch Actionable Reports (78%). Most calls (79%), requesting CDC assistance or not, were domestic. Almost all calls requesting CDC assistance were for clinical and/or laboratory consultation and/or request for analysis of samples. Most of the calls requesting CDC assistance came from city, county, state, or federal government agencies and military organizations (82%). However, 14 of the analyzed documents (14.4%) were misclassified, that is, a SITREP was written when it should have been an IN or vice versa. The authors also noted the absence of some relevant information among some of the documents, for example, date/time of update. CONCLUSIONS: All of the issues/incidents reported in this article to which DBPR/ESRB responded were cause for legitimate concern. However, significant improvement can be made in the preparation of these reports by CDC staff to ensure efficient and effective response from CDC and its partners. Finally, local entities may wish to develop a similar documentation and reporting process to help manage significant incidents.

[Evaluation of the Number of Varicella Patients Estimated by Prescription Surveillance].

OBJECT: It is important to know the precise number of varicella patients infected for evaluation of routine immunization and anti-bioterrorism attack using smallpox. Prescription Surveillance (PS) has been providing the estimated number of varicella patients up to the present. However, the estimated number of varicella patients cannot be validated because to date there has been no other comparable precise method of estimation. Recently, all electronic medical claims nationwide (NDB) have been disclosed. In this paper, we compare the number of varicella patients estimated by PS with NDB data, and adjust the number estimated with PS, if necessary. METHOD: For both NDB and PS, we used the monthly data from April, 2010 to March, 2013. The estimation of the number of varicella patients from the PS data was adjusted by the proportion of estimated number based on PS to the one based on NDB in the entire study period. Moreover, we adjusted it month by month, if the former method may not be enough to compensate for the discrepancy between the two datasets. RESULTS: The average discrepancy between NDB and PS was 48.00% in three years. By the adjustment using NDB in the three years, the discrepancy was improved to 11.49%. However, seasonal patterns of overestimation or underestimation were found. Conversely, by the adjustment using NDB month by month, the discrepancy was greatly reduced to 4.33%. Moreover, the seasonal patterns of overestimation or underestimation disappeared. CONCLUSION: The number of patients based on NDB would appear the most precise number, however, there may be a delay of about one year before it becomes available. On the other hand, PS data are updated every day and provide us with the up-to-date situation. This paper found that combining the timeliness of the PS data and preciseness of the NDB data will provide substantial benefit for public health.

[Lessons learnt from the German smallpox outbreaks after World War II]. / Pockenausbrüche nach dem zweiten Weltkrieg in Deutschland.

BACKGROUND: Even though smallpox was declared eradicated by WHO in 1980, it cannot be ruled out that the etiological variola virus could be used as a biological weapon. Undestroyed viruses from biowarfare programmes, virus strains left undetected in a freezer or dangerous recombinant poxvirus constructs could cause dangerous outbreaks in a relatively unprotected population. OBJECTIVES: Despite an abundance of studies performed during the eradication of smallpox, epidemiological data for preparedness planning and outbreak control in modern, industrialized countries are scarce. MATERIAL AND METHODS: Full-text hand search for the period from 1945 to 1975 in the main German public health journals. RESULTS: After World War II 12 smallpox outbreaks occurred in Germany. They were studied with the focus on the period of contagiousness, the protective effect of vaccination, booster-effect of revaccination and the place of infection. A total of 95 individuals contracted smallpox, including 10 fatalities. Despite having been previously vaccinated, 81 vaccinated persons came down with smallpox, yet 91% of them developed only mild symptoms. These patients presented a high risk for spreading the infection to contact persons due to misinterpretation of symptoms and the continuing social contacts. Basically, the risk of transmission in the first 2 to 3 days after onset of symptoms was low, thus facilitating antiepidemic measures. The importance of hospital preparedness is emphasized by the fact that most infections occurred in hospitals. CONCLUSION: The data analyzed provide valuable information for today's outbreak response planning and counter bioterrorism preparedness.

Syndromic surveillance: STL for modeling, visualizing, and monitoring disease counts.

BACKGROUND: Public health surveillance is the monitoring of data to detect and quantify unusual health events. Monitoring pre-diagnostic data, such as emergency department (ED) patient chief complaints, enables rapid detection of disease outbreaks. There are many sources of variation in such data; statistical methods need to accurately model them as a basis for timely and accurate disease outbreak methods. METHODS: Our new methods for modeling daily chief complaint counts are based on a seasonal-trend decomposition procedure based on loess (STL) and were developed using data from the 76 EDs of the Indiana surveillance program from 2004 to 2008. Square root counts are decomposed into inter-annual, yearly-seasonal, day-of-the-week, and random-error components. Using this decomposition method, we develop a new synoptic-scale (days to weeks) outbreak detection method and carry out a simulation study to compare detection performance to four well-known methods for nine outbreak scenarios. RESULT: The components of the STL decomposition reveal insights into the variability of the Indiana ED data. Day-of-the-week components tend to peak Sunday or Monday, fall steadily to a minimum Thursday or Friday, and then rise to the peak. Yearly-seasonal components show seasonal influenza, some with bimodal peaks.Some inter-annual components increase slightly due to increasing patient populations. A new outbreak detection method based on the decomposition modeling performs well with 90 days or more of data. Control limits were set empirically so that all methods had a specificity of 97%. STL had the largest sensitivity in all nine outbreak scenarios. The STL method also exhibited a well-behaved false positive rate when run on the data with no outbreaks injected. CONCLUSION: The STL decomposition method for chief complaint counts leads to a rapid and accurate detection method for disease outbreaks, and requires only 90 days of historical data to be put into operation. The visualization tools that accompany the decomposition and outbreak methods provide much insight into patterns in the data, which is useful for surveillance operations.

Smallpox, risks of terrorist attacks, and the Nash equilibrium: an introduction to game theory and an examination of the smallpox vaccination program.

INTRODUCTION: The smallpox vaccination emergency preparedness program has been unsuccessful in enrolling sufficient numbers of healthcare workers. OBJECTIVE: The objective of this study was to use game theory to analyze a pre-event vaccination versus post-event vaccination program using the example of a terrorist considering an attack with smallpox or a hoax. METHODS: A three-person game (normal and extensive form), and an in-person game are played for pre-event and post-event vaccinations of healthcare workers facing the possibility of a smallpox attack or hoax. RESULTS: Full pre-event vaccinations of all targeted healthcare workers are not necessary to deter a terrorist attack. In addition, coordinating vaccinations among healthcare workers, individual healthcare worker risk aversion, and the degree to which terrorists make the last move based on specific information on the status of pre-event vaccination all greatly impact strategy selection for both sides. A Nash Equilibrium of pre- and post-event vaccination strategies among a large number of healthcare professionals will tend to eliminate the advantage (of the terrorists) of a smallpox attack over a hoax, but may not eliminate some probability of a smallpox attack. CONCLUSIONS: Emergency preparedness would benefit from game theory analysis of the costs and payoffs of specific terrorism/counter-terrorism strategies.

Anthrax Exposure, Belief in Exposure, and Postanthrax Symptoms Among Survivors of a Bioterrorist Attack on Capitol Hill.

BACKGROUND: Following chemical, biological, radiological, and nuclear disasters, medically unexplained symptoms have been observed among unexposed persons. OBJECTIVES: This study examined belief in exposure in relation to postdisaster symptoms in a volunteer sample of 137 congressional workers after the 2001 anthrax attacks on Capitol Hill. METHODS: Postdisaster symptoms, belief in exposure, and actual exposure status were obtained through structured diagnostic interviews and self-reported presence in offices officially designated as exposed through environmental sampling. Multivariate models were tested for associations of number of postdisaster symptoms with exposure and belief in exposure, controlling for sex and use of antibiotics. RESULTS: The sample was divided into 3 main subgroups: exposed, 41%; unexposed but believed they were exposed, 17%; and unexposed and did not believe that they were exposed, 42%. Nearly two-thirds (64%) of the volunteers reported experiencing symptoms after the anthrax attacks. Belief in anthrax exposure was significantly associated with the number of ear/nose/throat, musculoskeletal, and all physical symptoms. No significant associations were found between anthrax exposure and the number of postdisaster symptoms. CONCLUSIONS: Given the high incidence of these symptoms, these data suggest that even in the absence of physical injury or illness, there may be surges in health care utilization. (Disaster Med Public Health Preparedness. 2019;13:555-560).

Birth defects among infants born to women who received anthrax vaccine in pregnancy.

In response to bioterrorism threats, anthrax vaccine has been used by the US military and considered for civilian use. Concerns exist about the potential for adverse reproductive health effects among vaccine recipients. This retrospective cohort evaluated birth defects, in relation to maternal anthrax vaccination, among all infants born to US military service women between 1998 and 2004. Department of Defense databases defined maternal vaccination and infant diagnoses; multivariable regression models described potential associations between anthrax vaccination and birth defects in liveborn infants. Among 115,169 infants born to military women during this period, 37,140 were born to women ever vaccinated against anthrax, and 3,465 were born to women vaccinated in the first trimester of pregnancy. Birth defects were slightly more common in first trimester-exposed infants (odds ratio = 1.18, 95% confidence interval: 0.997, 1.41) when compared with infants of women vaccinated outside of the first trimester, but this association was statistically significant only when alternative referent groups were used. Although the small observed association may be unlikely to represent a causal relation between vaccination in early pregnancy and birth defects, this information should be considered when making decisions about administering anthrax vaccine to pregnant women.

Extracting key information from historical data to quantify the transmission dynamics of smallpox.

BACKGROUND: Quantification of the transmission dynamics of smallpox is crucial for optimizing intervention strategies in the event of a bioterrorist attack. This article reviews basic methods and findings in mathematical and statistical studies of smallpox which estimate key transmission parameters from historical data. MAIN FINDINGS: First, critically important aspects in extracting key information from historical data are briefly summarized. We mention different sources of heterogeneity and potential pitfalls in utilizing historical records. Second, we discuss how smallpox spreads in the absence of interventions and how the optimal timing of quarantine and isolation measures can be determined. Case studies demonstrate the following. (1) The upper confidence limit of the 99th percentile of the incubation period is 22.2 days, suggesting that quarantine should last 23 days. (2) The highest frequency (61.8%) of secondary transmissions occurs 3-5 days after onset of fever so that infected individuals should be isolated before the appearance of rash. (3) The U-shaped age-specific case fatality implies a vulnerability of infants and elderly among non-immune individuals. Estimates of the transmission potential are subsequently reviewed, followed by an assessment of vaccination effects and of the expected effectiveness of interventions. CONCLUSION: Current debates on bio-terrorism preparedness indicate that public health decision making must account for the complex interplay and balance between vaccination strategies and other public health measures (e.g. case isolation and contact tracing) taking into account the frequency of adverse events to vaccination. In this review, we summarize what has already been clarified and point out needs to analyze previous smallpox outbreaks systematically.

Misrepresentation of health risks by mass media.

BACKGROUND: Mass media are a leading source of health information for general public. We wished to examine the relationship between the intensity of media coverage for selected health topics and their actual risk to public health. METHODS: Mass media reports in the United States on emerging and chronic health hazards (severe acute respiratory syndrome (SARS), bioterrorism, West Nile Fever, AIDS, smoking and physical inactivity) were counted for the year 2003, using LexisNexis database. The number of media reports for each health risk was correlated with the corresponding death rate as reported by the Centers for Disease Control and Prevention. RESULTS: The number of media reports inversely correlated with the actual number of deaths for the health risks evaluated. SARS and bioterrorism killed less than a dozen people in 2003, but together generated over 100 000 media reports, far more than those covering smoking and physical inactivity, which killed nearly a million Americans. CONCLUSIONS: Emerging health hazards are over-reported in mass media by comparison to common threats to public health. Since premature mortality in industrialized societies is most often due to well-known risks such as smoking and physical inactivity, their under-representation on public agendas may cause suboptimal prioritization of public health resources.

Distributed data processing for public health surveillance.

BACKGROUND: Many systems for routine public health surveillance rely on centralized collection of potentially identifiable, individual, identifiable personal health information (PHI) records. Although individual, identifiable patient records are essential for conditions for which there is mandated reporting, such as tuberculosis or sexually transmitted diseases, they are not routinely required for effective syndromic surveillance. Public concern about the routine collection of large quantities of PHI to support non-traditional public health functions may make alternative surveillance methods that do not rely on centralized identifiable PHI databases increasingly desirable. METHODS: The National Bioterrorism Syndromic Surveillance Demonstration Program (NDP) is an example of one alternative model. All PHI in this system is initially processed within the secured infrastructure of the health care provider that collects and holds the data, using uniform software distributed and supported by the NDP. Only highly aggregated count data is transferred to the datacenter for statistical processing and display. RESULTS: Detailed, patient level information is readily available to the health care provider to elucidate signals observed in the aggregated data, or for ad hoc queries. We briefly describe the benefits and disadvantages associated with this distributed processing model for routine automated syndromic surveillance. CONCLUSION: For well-defined surveillance requirements, the model can be successfully deployed with very low risk of inadvertent disclosure of PHI--a feature that may make participation in surveillance systems more feasible for organizations and more appealing to the individuals whose PHI they hold. It is possible to design and implement distributed systems to support non-routine public health needs if required.

Using Ontario's "Telehealth" health telephone helpline as an early-warning system: a study protocol.

BACKGROUND: The science of syndromic surveillance is still very much in its infancy. While a number of syndromic surveillance systems are being evaluated in the US, very few have had success thus far in predicting an infectious disease event. Furthermore, to date, the majority of syndromic surveillance systems have been based primarily in emergency department settings, with varying levels of enhancement from other data sources. While research has been done on the value of telephone helplines on health care use and patient satisfaction, very few projects have looked at using a telephone helpline as a source of data for syndromic surveillance, and none have been attempted in Canada. The notable exception to this statement has been in the UK where research using the national NHS Direct system as a syndromic surveillance tool has been conducted. METHODS/DESIGN: The purpose of our proposed study is to evaluate the effectiveness of Ontario's telephone nursing helpline system as a real-time syndromic surveillance system, and how its implementation, if successful, would have an impact on outbreak event detection in Ontario. Using data collected retrospectively, all "reasons for call" and assigned algorithms will be linked to a syndrome category. Using different analytic methods, normal thresholds for the different syndromes will be ascertained. This will allow for the evaluation of the system's sensitivity, specificity and positive predictive value. The next step will include the prospective monitoring of syndromic activity, both temporally and spatially. DISCUSSION: As this is a study protocol, there are currently no results to report. However, this study has been granted ethical approval, and is now being implemented. It is our hope that this syndromic surveillance system will display high sensitivity and specificity in detecting true outbreaks within Ontario, before they are detected by conventional surveillance systems. Future results will be published in peer-reviewed journals so as to contribute to the growing body of evidence on syndromic surveillance, while also providing an non US-centric perspective.

To be vaccinated or not? A survey of Turkish emergency physicians regarding smallpox.

We investigated Turkish emergency physicians' opinions about the threat of smallpox, smallpox vaccination, and the treatment of patients with suspected smallpox, and sought to identify factors that affect willingness to receive smallpox vaccination. Anonymous surveys were sent by mail to university-affiliated Emergency Departments in Turkey. Ten of the 21 university-based Emergency Medicine programs participated in the study, and 125 physicians (48% of all emergency physicians in Turkey) completed the survey. The probability of a bioterror attack using smallpox within Turkish borders was viewed as none or minimal by 43.2% of participants. Only 22.4% of the participants stated that they would agree to be vaccinated. The only factor that affected the rate of participants' willingness to receive smallpox vaccination was the occurrence of a smallpox case within Turkish borders. Decisions about the treatment of patients with suspected smallpox are strongly influenced by whether or not the physician has been vaccinated against smallpox. At the time of the survey, even during the weeks leading up to and during the war in Iraq, Turkish emergency physicians' perceived risk of a bioterror attack using the smallpox virus was low. A significant number of Turkish emergency physicians were unwilling to participate in a hypothetical vaccination program. This study shows that the occurrence of a smallpox case within Turkish borders would significantly increase the willingness of emergency physicians to receive the smallpox vaccine. Decisions about treatment of patients with suspected smallpox are strongly influenced by whether or not the physician has been vaccinated against smallpox.

[Risk of smallpox, vaccination, bioterrorism]. / Risque de variole, vaccination et bioterrorisme.

The use of the smallpox virus as a biological weapon is very old. Confronted with a high probability of a current bioterrorist menace, counteracting strategies have been developed. One of the principle aims relies on the vaccination of teams dedicated to the management of persons infected and the stocking of vaccine for the whole population of a country. Following worldwide eradication of the disease, preventive vaccination was topped in 1978 in France for the primo-vaccination, and in 1984 for repeat vaccinations. The various strains used in the first generation vaccinations are weakened living vaccine, the natural host and origin of which is unknown. Second and third generations vaccines are under study; the principle objective is to obtain efficacy with a minimum of side effects. There are two types of adverse events, generally observed with the first generation vaccines: the first, extremely rare, can be life-threatening; the others, more frequent (10 to 15% of patients) are benign. In emergency situations, in the presence of smallpox, there should be no absolute contraindications to vaccination. In the bioterrorist context, massive vaccination campaigns of the population are unadvisable (because of the considerable risk of death and severe adverse events) in the absence of any real permit, in each case, definition of the vaccinal strategy to be adopted.

[Viral encephalitis virus, a new bioterrorist menace]. / Les virus des encéphalites virales, une nouvelle menace bioterroriste.

Often responsible for little known infections, today viral encephalitis viruses appear as a new bioterrorist menace, because of their easy production and their great pathogenic potential. Spraying is the best way to permit the rapid diffusion of certain encephalitis viruses. Diagnosis of viral encephalitis, predominating in tropical surroundings, is difficult. In the majority of cases, symptoms differ little from those of common flu. With supplementary examinations, the biological abnormalities are usually non-specific. There are no characteristic images on scans or MRI. Identification of the virus in the nasopharynx, blood or cerebrospinal fluid, in serology, PCR or RT-PCR permits confirmation of the virus. Treatment is essentially symptomatic and relies on appropriate reanimation measures. Ribavirin can be indicated in some cases such as the Rift Valley fever, but is formally contraindicated in West Nile encephalitis. The aim of terrorist groups who would use this type of weapon is more to provoke panic and disorganisation than to kill as many people as possible.

[Haemorrhagic fever viruses, possible bioterrorist use]. / Fièvres hémorragiques virales, possibilité d'utilisation bioterroriste.

The majority of haemorrhagic fever viruses are responsible for various clinical manifestations, the mutual characteristics of which are fever and haemorrhage in 5 to 70% of cases. All degrees of severity can be observed, ranging from isolated fever to multi-organ failure and death. These viruses belong to one of the following families: filoviridae, arenaviridae, bunyaviridae, and flaviviridae. They must be considered as dangerous biological weapons that could potentially be used. Most of the viruses responsible for haemorrhagic fever can be transmitted to humans through the air in spray form, except the dengue virus and the agents of haemorrhagic fever from the Congo Crimea and the haemorrhagic fever with renal syndrome that are difficult to handle in cell culture. In the event of a bioterrorist act, the management of persons infected or suspected of being so will be made by the referent departments of infectious diseases, defined by the French Biotox plan. Management includes isolation, confirmation or invalidation of the diagnosis and rapid initiation of treatment with ribavirin. Ribavirin is recommended for the treatment and prophylaxis of arenavirus and bunyavirus infections; it is not effective for the other families of virus. Except for yellow fever, there is no vaccination for the other forms of viral haemorrhagic fever.