Bioresponse challenges

• Effective preparedness could make the difference between a contained outbreak of disease and a potential world pandemic.
• Current levels of intercontinental travel could turn a localised deliberate release of biological weapons into a world pandemic.
• If the causative agent were to remain unknown, governments could be forced to deal with a pandemic using isolation, quarantine and restricting people's movements.

The threat of bioterrorism has heightened in recent years and could increase further in the future due to new genetic manipulation techniques and other developments in the life sciences. However, in the event of a biological attack, effective preparation could make the difference between a contained outbreak and a possible pandemic.

Rapid communication between health workers and monitoring agencies is crucial in any deliberate release of a biological agent. These workers must introduce the appropriate counter-measures quickly, including vaccination, drug distribution and possible quarantine and travel restrictions.

Frontline workers

Doctors, hospital workers and medical academics in the UK may dismiss bioterrorism as merely a theoretical possibility that does not warrant extra resources. However, in such an incident, these workers are responsible for detecting, diagnosing and responding appropriately to biological weapons.

General practitioners, as well as specialists in infectious diseases, are likely to be among the first to detect diseases caused by a covert bioterrorist act. Pharmacists are also likely to see victims with similar symptoms in such an incident. Emergency room staff and laboratory workers are responsible for identifying the cause and treating victims.

Diagnosis poses a challenge, as most infectious diseases caused by biological weapons have early symptoms that resemble those of influenza and could be overlooked by doctors. For example, four anthrax victims in the October 2001 attacks in the US were discharged without being diagnosed correctly.

A person infected with smallpox would not set off sensors in buildings or airports and would be highly infectious during a 17-day incubation period without showing signs of illness. Aerosolised release of pathogens such as anthrax could also be used as a delivery method, although dispersing the pathogens in sufficiently small particles would pose significant challenges to a bioterrorist.

Epidemiology and testing

Any unexpected variations in the incidence of specific syndromes prompts epidemiological investigation and co-operation between doctors and medical authorities. In the UK, unusual disease patterns are reported to public health authorities and the Health Protection Agency, which has replaced the Public Health Laboratory, for epidemiological analysis. The agency is tasked with monitoring infections reported by doctors and the National Health Service's telephone advice service. Its Centre for Emergency Preparedness and Response provides a central source of specialist advice on infectious diseases, guidance on diagnosing unusual illnesses, planning and operational responses to major incidents and clinical management and protection in emergency clinical situations.

Once a deliberate attack has been established as the cause of an outbreak, a criminal investigation is instigated. Doctors must preserve microbial samples and other items for forensic evidence and maintain detailed patient records for the use of investigating authorities. They are required to report cases where bioterrorism is suspected to local police and the Anti-terrorist Branch.

Training and exercises

Training for those who must deal with biological attacks is vital. Medical schools are being urged to incorporate more information and training into their curricula, and health services occasionally conduct special programmes and community drills to prepare healthcare workers for a bioterrorist attack. The Health Protection Agency's training division works with partner organisations to deliver specialist courses for healthcare providers and managers. It also conducts exercises to test emergency preparation in the health service community and improve current emergency health plans. Each exercise involves co-ordinating many organisations on a national, regional and local level.

An example of co-operative training is Exercise White Pegasus, held on 18 October 2004 in southeast England. The exercise simulated a biological contamination incident in a crowded public area. It involved representatives from the National Health Service, the Health Protection Agency, the emergency services, local and regional authorities, transport organisations and specialist health advisers.

Developing vaccines

Many vaccination programmes are based on protecting the armed forces against potential biological agents. However, pre-emptive immunisation of the entire susceptible civilian population is considered impractical and expensive and could have adverse effects. In the case of smallpox bioterrorism, post-attack vaccinations of those who may have been exposed - including healthcare and emergency workers - would be implemented. In the UK, the Health Protection Agency monitors the effectiveness of national disease control programmes and the efficacy, safety and uptake of vaccines in routine use.

A significant advance in disease prevention is offered by DNA vaccines, which if proved effective in trials will overcome the long period that traditional methods require to produce vaccine. Traditional vaccines must be incubated using chicken's eggs, which can take several months. They are also extremely strain specific, meaning the body's immune system only reacts to the particular strain of disease the vaccine has sensitised it to.

Whereas traditional vaccines work by injecting a damaged pathogen to evoke an immune response, DNA vaccine works by taking a single gene from a pathogen and artificially copying and multiplying it, then injecting it into muscle. The product is recognised by the body's immune system as foreign but harmless. Such vaccine can be made in a purer form than that made directly from pathogens. In June, positive pre-clinical trial results were announced for an avian flu DNA vaccine produced by the US National Institutes of Health.

A template for disease response

The World Health Organisation's (WHO) global alert following the outbreak of severe acute respiratory syndrome (SARS) triggered responses from health experts in dozens of countries. SARS could be a rehearsal for a naturally occurring avian flu pandemic, or an epidemic caused by deliberate release.

The SARS outbreak was the first time the WHO co-ordinated so many laboratories against a threat of unknown dimensions. It was also the first example of response activity under the revision of the International Health Regulations, which provide the legal framework for the surveillance and reporting of infectious disease and for the use of measures to prevent their worldwide spread. The US Centers for Disease Control instigated an emergency operations centre to provide round-the-clock co-ordination and response and conducted extensive laboratory testing of clinical specimens from SARS patients to identify the cause of the disease.

As a respiratory illness that is often called 'flu-like' because if its onset symptoms, SARS is difficult to diagnose, like many bioterrorism-related diseases. Its causative agent actually has no relation to the influenza virus. As in a bioterrorist release of an infectious disease, the incubation period and the mode of spread (close person-to-person contact, contact with infectious material or inhalation of droplets spread by coughing and sneezing) are of prime importance for assessing the potential reach of an epidemic. Doctors were asked to look for symptoms in patients who had recently returned from overseas and to notify public health services so the spread of the illness could be monitored.

Pinpointing the origin of a disease, deliberately released or otherwise, is also crucial. In the case of SARS, a Hong Kong physician first pinpointed the territory's Metropole Hotel as the disease's launchpad beyond southern China. In February 2003, a Guangdong doctor staying at the hotel most likely infected 12 people, who then disseminated the virus around the world.

Hong Kong healthcare workers were quick to begin interviewing patients and sending out questionnaires. The WHO conducted a massive co-ordination campaign, distributing data among authorities in all the affected areas. China, however, was blamed for not revealing the true extent of the disease for months after it first appeared in the country in November 2002 and was then spread internationally by air travellers via Hong Kong. Only in late March 2003 did Chinese officials finally present a report on the illness to the WHO. China's attempts to cover up the outbreak may well have contributed to the severity of the epidemic.

Modern communication systems, particularly the internet, can provide epidemiologists with early notification of clusters of unexpected disease. They can then alert civil authorities to take action to prevent its spread. However, as in the case of China and SARS, much depends on how much information governments are prepared to give.

Current levels of intercontinental travel could well turn a localised deliberate release into a world pandemic. During the SARS outbreak, airlines were asked to look for passengers who appeared unwell while checking in. Aircraft were also disinfected in an attempt to stop the spread of SARS. Travel agencies in countries including China and Japan were told to suspend operations.

In cases where the causative agent remains unknown, governments could be forced to resort to containment methods such as isolation, quarantine and restricting people's movement. During the SARS outbreak, Chinese companies employing migrant workers were warned not to allow them to return to their villages. The Chinese authorities quarantined at least 8,000 people in Beijing in an isolation camp for SARS patients. Hong Kong and Singapore shut down schools and quarantined anyone who had come into close contact with patients. Also in Singapore, six public hospitals banned most visitors to control the spread of SARS. Taiwan quarantined for 10 days all people arriving from SARS-affected countries.

Other counter-measures, such as widespread use of surgical masks, are only effective if the masks filter expired air. John Oxford, a virology expert at Queen Mary's College, London, said during the SARS epidemic: "There is not much you can do to avoid this unless you live as a hermit."

Andy Oppenheimer is the editor of Jane's Nuclear, Biological and Chemical Defence