Emerging Infections of International Public Health Importance





Module 2:
Current Challenges in Infectious Diseases
LECTURE 3 Readings


Col. Patrick Kelley, MD, DrPH

  1. Be able to describe key clinical and epidemiological characteristics of classical agents of biological warfare
  2. Be able to explain epidemiologic characteristics that may distinguish a naturally occurring outbreak and one due to bioterrorism
  3. Be able to explain the concept of syndromic surveillance and the technical and administrative challenges associated with implementing some approaches

Note:  All photos are believed to have originated from public domain and/or US government sources. We regret any incorrect or missing attribution and will promptly rectify the situation if so informed


Definition of Bioterrorism
   Bioterrorism is the intentional use (or alleged use) of viruses, bacteria, fungi, or toxins derived from living organisms to produce death or disease in humans, animals and plants.

Characteristics of bioterror or biowarfare weapons include:

  • Low cost: can be as little as $1 per square kilometer of a biologic agent
  • Ease of production and easy concealment: utilize common fermentation technology which can have dual purposes such as production of antibiotics, vaccines and even food
  • Effective delivery system: aerosolization of particles 1-5 microns will settle in lower respiratory tract and is poorly detectable by our senses. Larger particles will settle on environmental surfaces.


[Figure:  Hypothetical Dissemination by Airplane of 50kg of Agent]

This table shows the hypothetical potential dissemination of a biologic agent along a 2 kilometer line and the number who would be dead or incapacitated from such an attack.


Specific Biowarfare Agents


Anthrax is traditionally associated with 3 clinical syndromes: cutaneous, gastrointestinal, and inhalational.

[Figure:  Anthrax Bacteria]

This is the gram stain of the anthrax bacteria with its characteristic morphology.

Cutaneous anthrax is normally associated with specific occupations such as wool sorters, farmers, hide makers etc. It usually causes a black eschar and the organism can be isolated from the wound.

[Figure:  Cutaneous Anthrax]

Gastrointestinal anthrax is usually the result of ingesting raw or inadequately cooked contaminated meat. It causes an acute gastroenteritis with vomiting and bloody diarrhea. The mortality rate can be very high 50-100% even with aggressive treatment.

Inhalational anthrax is the clinical presentation we are most concerned about for biowarfare. The incubation period is 1-6 days. The initial symptoms are non-specific flu-like illness including malaise, low grade fever, and non-productive cough. It can ultimately progress rapidly to a hemorrhagic mediastinitis and shock with abrupt difficulty breathing, tachycardia, and rapid progression to death.

[Figure:  Chest X-ray of Inhalational Anthrax]

This X-ray shows some classic features including the widened mediastinum, enlarged lymph nodes, and hemorrhage in the lung.

Treatment of anthrax is with rapid initiation of appropriate antibacterial either ciprofloxacin or doxycycline and supportive care. This usually needs to be instituted early because there is less efficacy the more symptomatic the person.

Immunization is available for anthrax but is usually given to those at higher risk such as occupational exposure and the military. The vaccine has 90% seropositive after 3 doses but requires 6 initial injections and then yearly boosters.

Post-exposure prophylaxis is recommended by using ciprofloxacin or doxycycline plus vaccination. Antibiotic treatment was the approach taken after the anthrax cases on the East coast.



Plague is another favorite of biowarfare and was actually used in this fashion in the middle ages where the armies would fling persons who had died presumably from plague over the city walls of their enemies. Yersinia pestis, the plague bacteria, is a bipolar bacillus that on gram stain looks like a safety pin stain.

[Figure:  Plague Bacillus in Gram Stain]

Plague is endemic in many parts of the United States and the world. It has a cutaneous manifestation (bubonic plague) and can progress to pneumonic state.

The pneumonic stage can be primary or secondary. It presents as fever with lymphadenopathy, cough with bloody sputum. In the absence of immediate treatment it is usually 100% fatal. It is highly contagious by aerosol in the right environmental conditions. Plague is transmitted by the flea vector and the usual hosts are rats, squirrels, coyotes, and feral cats. The fleas can infect both animals and humans. Humans can then transmit to each other in the pneumonic stage. Treatment is usually doxycycline which is the same as for post-exposure prophylaxis.



The organism getting the most attention recently is the smallpox virus. Smallpox was eradicated as a human disease in the late 1970ís. It was one of the greatest public health achievements of the 20th century. There were only 2 places in the world where the smallpox virus was officially kept in storage, the Soviet Union and the United States. The Soviet Union rather than destroying the stores actually grew the smallpox to be used as a biologic warfare agent. There has been concern that other countries may have kept clandestine stores.

The incubation period of smallpox is approximately 12 days and initially presents as a flu-like illness of fever, chills, headache, backache, vomiting and malaise which then leads to the classic smallpox rash. The disease is not communicable during the incubation period. The rash typically appears on the face and trunk all at the same time thereby distinguishing itself from chicken pox.

[Figure:  Smallpox Rash]

Smallpox can be prevented by use of the vaccination but these programs ended in the 1970ís when the virus was presumably eradicated. The United States has decided to embark on increasing the vaccine stores available for smallpox vaccination and has developed a plan to reinstitute vaccination. This has met with some controversy as the vaccine reaction can be quite severe especially in the immunecompromised.

[Figure:  Vaccine Reaction]

There are also ethical and public health concerns globally. If resource poor countries decide it is important to reinstitute smallpox vaccination then this will further limit resources going into their current disease epidemics.



Botulism is a toxin mediated disease caused by the toxin of the bacteria Clostridium botulinum. It is usually seen as a food-borne illness by improperly prepared or canned foods. It can also be seen in wounds and in infants. The incubation period is usually 24-36 hours or longer. The clinical presentation in a case of food borne or wound botulism is one of neuromuscular flaccid paralysis in a symmetric descending fashion. Cranial nerves causing double vision, droopy eyelids, difficulty speaking or swallowing and then progressive weakness of extremities and respiratory failure. Treatment includes supportive care and use of botulinum antitoxin given as soon as possible after symptoms begin.


Epidemiologic Clues to a Biologic Attack

  • Large unexplained epidemic with similar acutely ill patients
  • More severe cases than usually seen with higher mortality and refractory to usual treatment
  • Multiple diseases in the same patient
  • Unusual geographic, seasonal, or patient distribution
  • Suspicious transmission pattern
  • Unusual genetic or molecular patterns
  • Multiple simultaneous epidemics
  • Unusual clinical presentation
  • Unexplained animal deaths
  • Prior intelligence of an attack, claims by an aggressor, or direct evidence


An example of an intentional attack was the outbreak of Salmonella infection in patrons to a specific restaurant in the Dalles, Oregon. A local cult wanted to prevent people from voting in the local election. Even though there were over 700 people ill it took over one year to make the connection. This was only accomplished by someone in the cult coming to the police. Subsequent epidemiology and laboratory studies confirmed this connection.


Surveillance for Bioterrorism

The ongoing, systematic collection, analysis and interpretation of health date is essential to the planning , implementation and evaluation of public health practice closely integrated with the timely dissemination of these date to those who need to know. This is the classic definition of public health surveillance.

What are some of the approaches for timely biowarfare surveillance?

  • Syndromic surveillance based on the Emergency Medical system (911 calls)
  • Syndromic surveillance based on outpatient clinics, emergency rooms, and nurses hotlines
  • Tracking of laboratory requests such as excess number of stool exams
  • Monitoring of over the counter pharmaceutical sales such as anti-diarrheals
  • Surveillance of ICU diagnosis trends
  • Unexplained death certificates


[Figure:  Detection of Flu-like Illness]

Example of real-time detection of flu-like illness in New York City with selected EMS calls. You can see the usual peaks for respiratory complaints which match the increase in influenza cases during the year.

I wanted to show you two surveillance initiatives: one is a lower technology approach and the other is a more high tech automated approach.


Early Warning Outbreak Recognition System (EWORS)

This is a system operating in Southeast Asia to do surveillance for many diseases. Sentinel sites are set up for syndromic (symptomatic) information to be relayed electronically to a central point. For the case of Indonesia this is Jakarta

[Figure:  Organization of Current Network in Indonesia]

Initial data is entered into a standardized EWORS form by the nurse. The date which includes age, demographics, gender, symptoms etc. are then entered into an access program on a computer system and are downloaded daily in a central location. These data can then be analyzed and plotted on graphs to look at trends.

[Figure:  EWORS Trend by Age for Fever and Hemorrhage]

[Figure:  Cases of Fever by Gender]

Geographic information systems (GIS) can also be utilized to look for clustering of cases in an area.

[Figure:  GIS Display of Fever and Hemorrhage]

This system has worked well in a resource poor area because there are personnel who will take the time to enter the information necessary to make this system function.


Electronic Surveillance System for Early Notification of Community based Epidemics (ESSENCE)

This is an alternative approach to EWORS and would be more acceptable in the United States. We needed to establish a methodology to do 3 things: early detection of clinical patterns, rapid epidemiology-based targeting limited resources, and risk communication to reduce the spread of panic and unrest.

The initial focus was on a collection of clinics and emergency rooms in the Washington area.

[Figure:  Distribution of Hospitals and Clinics Near Washington]

The diagnoses from the clinics and emergency rooms were broken down into broad syndrome categories: Respiratory, Gastointestinal, Neurologic, Dermatologic, Fever/Malaise/Sepsis, and Coma/Sudden Death. This information is entered into the standard information system and the data is downloaded to a central area.

The following slides show some of the preliminary data retrieved by the ESSENCE surveillance.

[Figure:  Lower Respiratory Diagnosis]

[Figure:  Syndrome Counts for National Capital Area]

One of the ways to detect aberrations is through an autoregressive methodology which takes historic data and models the historic data and compares it with the current trend based on current data. The following slides show this method. The ** on this slide represents symptoms which fall outside of the usual trend.

[Figure:  Autoregressive Data Modeling]

This system can also use GIS mapping to se if there is clustering of cases within a specific zip code.

[Figure:  GIS Mapping of Respiratory Syndrome]

Some of the challenges to these systems are to be able to handle massive amounts of data and generate thousands of graphs daily. One way is to divide up the world into 12 tiered regions. Red indicates an alarm, yellow is a warning and green is within expected boundaries. The graphs generated by specific disease will then also carry color coding for the alarms.

[Figure:  ESSENCE Global Alarm]

In summary, bioterrorism and biowarfare is a real concern today. Public health surveillance and prompt recognition of clinical manifestations of potential biowarfare diseases is important to handle these situations urgently. Using electronic surveillance by syndromes or symptoms is a timely, efficient way to look at disease trends at a given time and act accordingly.



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