A Tale of Two
Cities and the Trojan Horse: Lessons in Biological Defence
by CPT (DR) (NS) Donald Poon
and CPT (DR) Khaw Seong Lin
History is replete with ancient civilisations
decimated to virtual extinction by the introduction of novel
pathogens to a uniformly vulnerable people. Unlike any projectile
or explosive, infectious disease, like wildfire, is self-perpetuating
until successful containment or exhaustion of substrate.
The conquest and colonisation of the New
World for example, was aided in no small part by the largely
inadvertent but advantageous exposure of the indigenous
population to new diseases that accompanied the Europeans
settlers, to which they were completely defenceless. In
fact, there were occasions when this was exploited as a
deliberate tactic. The American whites are documented to
have offered blankets used by smallpox sufferers as peace
offerings to obstinate local Indian tribes.1 Biological
warfare (BW) is thus certainly not a recent invention.
International awareness of the chillingly
destructive potential of biological agents has in the last
decade been heightened for three reasons.
Firstly, BW and BT (biological threat)
tap into the same visceral fear of emergent lethal pathogens
already deeply etched in the public psyche by the bloody
footprints of the human immunodeficiency virus (HIV),
the architect of the most recent global pandemic.
Adding fuel to the fire has been the massive
and wide-ranging nature of several recent outbreaks. For
example, the 1994 salmonellosis2 outbreak traced
to contaminated ice cream, affected over 250,000 Americans,
while mass water contamination caused over 400,000 cases
of cryptosporidiosis in Milwaukee. Meanwhile, the
world has also witnessed urban epidemics of the pneumonic
plague in Surat, India, Ebola haemorrhagic fever
in Central Africa, avian influenza (H5N1)3 in Hong Kong,
Hendra virus 4 in Australia, Nipah virus in Malaysia and
Singapore, and the West Nile virus in New York City.
The second key factor has been the public
confirmation during this decade of the existence of state-sponsored
advanced biological weapons development programs. Firstly,
post-Gulf War United Nations Special Commission (UNSCOM)
investigations in Iraq have corroborated Iraqi claims of
possessing at least 25 SCUD/Al-Hussein missiles, each armed
with a warhead carrying 145 litres of a wide variety of
biological agents including botulinum toxin, anthrax
spores or clostridium perfringens spores5.
More recently has been the disclosure
of the true scale of biological weapons research in the
former Soviet Union, including the admission of an accidental
release in 1979 of anthrax spores from a Soviet military
research facility in Sverdlovsk6 , which resulted in 66
deaths. With the disintegration of the Soviet Union, the
security of both the technology and products of the program
has become a matter of some concern.
Most nations have the capability to develop
and manufacture biological weapons in facilities which are
inexpensive and inconspicuous, under the guise of legitimate
commercial or research purposes. Some 18 nations are believed
to have done so, including several which the US State Department
lists as supporting terrorism. In addition, there are more
than 1,500 biological culture libraries worldwide as well
as numerous research institutions which maintain sample
cultures of various BW agents7 . These constitute a broad
and easily accessible reservoir of knowledge and material,
which is effectively impossible to police.
Thirdly, the revelation that the Japanese
cult Aum Shinrikyo8 had made repeated but failed
attempts on at least 10 occasions to disperse BW agents
in aerosol form, prior to their notorious 1995 sarin nerve
gas attack on the Tokyo subway, shocked the world into accepting
the reality of the emerging threat of BT. BT is however
not new. In 1984, the Rajneeshee cult used salmonella
typhimurium bacteria to contaminate restaurant salad
bars in Oregon, causing 751 cases of non-fatal food poisoning.
Fortunately, such incidents are rare, with only 66 criminal
events and 55 terrorist events9 involving biological agents
recorded between 1960 and 1999, although most (mainly hoaxes)
have occurred in recent years.
There is clearly the need for an effective
national biological defence system, to provide a mechanism
for the early detection and containment of both naturally
occuring and artificially spawned disease outbreaks. Two
recent outbreaks offer useful lessons and insights into
the critical prerequisites for such a system.
A Novel Virus in Malaysia
An epidemic of viral encephalitis
affecting mostly pig farm workers in the state of Perak,
Malaysia, was first reported in late 1998. Early suspicions
focused on Japanese encephalitis (JE), a locally
endemic, mosquito-borne virus known to cause periodic outbreaks
of such illness. Pigs are the natural reservoir for JE,
and the disease thus tends to occur in pig farming areas.
At about the same time, a cluster of sudden
severe illness and deaths among domestic pigs was noted
in Ulu Piah Tambun and Ampang near Ipoh town; Sikamat Nipah,
Sawah and Bukit Pelanduk in Negri Sembilan, and Sepang and
Sungei Buloh in Selangor. Because of the similarity in timing
and location, the pig disease was attributed to the same
virus by public health authorities.10
Measures routinely used to control Japanese
encephalitis, such as mosquito fogging, were stepped
up, but failed to contain either the human or pig epidemics.
The number of cases continued to mount, as did the number
of areas affected.
From October to May 1999, 265 cases of
viral encephalitis with 105 deaths were recorded,
and eventually, more than 50 farms in Perak, Malacca, Penang,
Selangor and Johor were identified to have been infected.
The virus was able to propagate to the
extent that seven Singaporean abattoir workers developed
the disease, after contact with infected pigs from Malaysia.
The lack of success of control efforts,
and increasing inconsistencies in the epidemiology of the
outbreak led to a search for an alternative causative agent.
International assistance was sought from the Centres for
Disease Control and Prevention (CDC) as well as laboratories
This led to the discovery of a new virus,
belonging to the paramyxoviridae family, which had
never been encountered. It was named 'Nipah', after the
village Sungei Nipah in Negri Sembilan, which was home to
the first human identified to have been infected with the
virus. The virus was subsequently confirmed to be the same
agent responsible for the human and pig disease.
With the discovery of the etiological
agent of the outbreak, an immediate 'stamping out' policy
was instituted to cull all pigs in the outbreak areas. A
total of 901,228 pigs from 896 farms were destroyed in the
infected areas from 28 February to 26 April 1999. The culling
programme was stopped when a new test was made available
to identify infected farms in a national pig testing and
surveillance programme. 172,750 pigs from 50 positive farms
were further culled under this surveillance programme. The
epidemic was successfully controlled by May 1999.
West Nile Encephalitis
in New York
In late August 1999, the CDC was called
in by the New York City Health Department to assist in investigating
a cluster of viral encephalitis cases.11 Tests were performed
on blood and spinal fluid taken from the patients, for antibodies
to six insect borne viruses commonly seen in the US. They
returned positive results for St Louis encephalitis,
a mosquito borne viral disease usually found in south-eastern
US. Immediately, a mosquito eradication campaign was launched
to halt further transmission of the virus.
Since late July 1999, officials at the
Bronx Zoo had been receiving calls regarding birds dying
suddenly in the Bronx and Queens. Within four days of the
St Louis encephalitis outbreak being declared, several
exotic birds at the zoo perished. Pathological examination
of the birds revealed severe brain and heart damage of an
The head of the Department of Pathology
at the zoo suspected a link between the bird deaths and
the human encephalitis outbreak. There was however,
one significant inconsistency - the St Louis encephalitis
virus is not lethal to birds.
To elucidate the cause of the bird fatalities,
samples from the dead birds were sent to the National Veterinary
Services Lab which is a part of the US Department of Agriculture.
They were however, unable to identify the causative agent.
Samples were also sent to the CDC. Unable to contact anyone
at the agency, she contacted a friend at the US Army Medical
Research and Material Command, which usually does not handle
civilian requests, for assistance. He agreed to analyse
some samples, which was sent on 21 September.
Meanwhile, the CDC had also begun to make
the association and requested for more samples the same
On 23 September, both agencies came to
the conclusion that West Nile virus was the agent
killing the birds in New York City. There was also a strong
suspicion that it was the same virus killing humans. On
24 September, a laboratory in California, which had received
brain tissue samples taken from people who had died from
the outbreak, confirmed that they had been infected with
the West Nile virus.
The West Nile virus had never previously
been seen in the Western hemisphere as it is usually found
in Africa and Asia, with occasional outbreaks in Europe.
The virus is closely related to the St Louis encephalitis
virus. Both are flaviviruses, sharing a similar clinical
spectrum, mode of transmission (mosquitoes) and reservoir
(birds). This close relationship accounts for the early
false positive tests for St Louis encephalitis. Also,
the flawed initial diagnosis did not have any actual detrimental
effect, as the control measures employed were entirely appropriate.
Lest We Forget
The two outbreaks share many uncanny parallels,
illustrating clearly the shortcomings of the present biological
threat surveillance and management systems, and present
opportune lessons which demand closer scrutiny and application.
A tabulated summary comparing them is as follows:
The Trojan Horse - Two
Cases of Mistaken Identity
In both outbreaks, the aetiological agents
were not immediately recognised. The outbreak in Malaysia
was initially and erroneously thought to be caused by the
JE virus, while the causative agent in the New York outbreak
was first mis-diagnosed as the St Louis encephalitis
The adage "common things occur commonly"
is a useful guiding principle for efficient targeting of
investigative efforts, but it also lays a trap for the unwary
||Nipah Virus Outbreak (October 1998 - May
||West Nile Virus Outbreak (August 1999
- October 1999)
||Paramyxovirus family - newly emerged
virus never before isolated, structurally similar to
||Flavivirus family - not known to
exist in New York or the Western Hemisphere before outbreak.
||Direct contact with infected pig's excreta
||Vector borne - bite of infective mosquito
belonging to Culex spp. univittatus, pipiens,
||Malaysia and Singapore
||New York City
|Duration of Outbreak
|No of Casualties
|No of Deaths
|| 105 (40%)
|| 7 (13%)
Twice, unknown pathogens sparked mysterious
clusters of disease, and twice, health authorities were
quick to attribute blame to known local pathogens. While
this is usually a sound epidemiological practice, it becomes
a pitfall if investigators then rest on their laurels, as
they did here. They failed to question their initial conclusions
until much later, even in the light of increasing inconsistencies.
An example of the latter was the unusual casualty age distribution
during the Nipah virus outbreak. Victims were overwhelmingly
working age adults. This is epidemiologically inconsistent
with JE, which tends to affect those at the extremes of
age - the young and elderly.
There is the need for an open-minded and
lateral approach to disease outbreaks, that appreciates
the implications of increasing urbanisation and global traffic,
and consequently, the effective breakdown of natural geographic
barriers. Diagnostic kits targeting the usual bacteria and
viruses will no longer suffice as micro-organisms skip from
continent to continent, from animal to human, and from the
jungle, into our cities. And of course, non-indigenous diseases
may be artificially introduced in the BT and BW context.
Moreover, interpreting tests for exposure
to viruses, which usually involve isolation of antibodies
produced in the course of the body's defence, is often complicated
by cross-reactivity - closely related but distinct viruses
may induce the production of similar antibodies. Therefore,
exposure to the West Nile virus may result in a positive
St Louis encephalitis antibody test.
The obvious means of maximising the speed
and accuracy with which outbreak-causing pathogens are identified,
is to maintain diagnostic capabilities for the widest possible
variety of biological agents. Investigations into the West
Nile outbreak were hampered by the limited capabilities
of the National Veterinary Services Lab, which was first
lab to receive the bird samples. There are only about 50
candidate micro-organisms12 suitable for use in BW and BT.
Once BW or BT is suspected, every possible test, as guided
by clinical presentation, should be applied to all animals
and human beings deemed to have succumbed to the attack.
It is an expensive proposition to stockpile
a wide range of diagnostic equipment with only narrow applicability.
Because of resource constraints, only a very limited number
of centres will be able to maintain such capabilities. It
is essential that the doors to these centres be kept open.
The diagnostic technology must be made as accessible as
possible to all who are in a position to sound the alarm
It is an unfortunate fact of life however,
that many of these personnel are not able to recognise situations
in which such resources should be called into play. Most
physicians in industrialised countries have never seen cases
of many exotic diseases such as anthrax, and the last case
of naturally acquired small pox worldwide13 was seen in
October 1977. Adequate specific training is critical if
our frontline personnel are to effectively operate as the
first echelon of defence. Learning to maintain an open mind
and awareness of the myriad manifestations of BW and BT
must be reinforced. It would be ideal to have at least one
BW/BT trained physician in all emergency and outpatient
A particularly unsavoury aspect of BW/
BT is that they may not be immediately manifest, unlike
conventional or chemical attacks, because of the incubation
period inherent in all diseases. This facilitates the geographic
dissemination of the disease.
At the forefront of a truly sensitive and
responsive biological defence therefore, must be a vigilant
and broad network of sentinels, providing data for consolidation
and assimilation by a centralised body. Such pooling of
information means not only a more accurate situation appraisal,
but also facilitates more simplified and direct links with
those responsible for effecting a response.
The 10 Commandments
Just as crucial as collecting adequate
data is its appropriate interpretation. The following 10
epidemiological clues14 do not constitute proof of intentional
use of biological agents but they can assist greatly in
determining if further investigation is warranted. A biological
threat must not be urgently ruled out if any of the 10 conditions
Applying these principles to our two case
studies, it is evident that conditions (i), (iii), (v) and
(vi) were present in the two outbreaks. Condition (viii)
was relevant in the New York outbreak as there were reports
of Iraq experimenting with the West Nile virus for
BW/BT purposes.15 Even though a deliberate source of the
outbreak was categorically ruled out, a good biological
defence system triggered by this association could possibly
have achieved a more rapid identification of causative agent.
Of Birds and Pigs
The BW/BT frontline is not limited to
human disease surveillance. Few pathogens infect humans
exclusively. The great majority are far from finicky about
their victims, and latent carriage in a variety of animals
provides a lasting reservoir of infection. Human disease
in fact, often represents the mere tip of the iceberg, in
terms of the disease burden of a given locality.
In the course of investigating the two
outbreaks, important clues provided by disease patterns
in local animals were completely overlooked by public health
professionals initially. The fact that pigs are only the
amplifying hosts for the Japanese encephalitis virus,
and do not die from infection was astutely pointed out by
certain veterinarians and microbiologists16 . The observation
to the contrary during the Nipah outbreak should
have been the first vital clue that it was due to some other
History repeated itself in New York. Once
again, the significance of the dying birds was not immediately
appreciated by human disease specialists. It took an attentive
veterinary pathologist to spot the anomaly. Furthermore,
her observation that emus in the Bronx zoo were thriving
enabled her to eliminate another candidate pathogen - the
equine encephalitis virus, which is usually lethal
to that species.
The need to include professionals from
all walks in a holistic biological defence system cannot
be overemphasised. As illustrated in the two outbreaks,
it is not only the medical care provider who is in the position
to make crucial observations. Key information can come from
the microbiologist seeing unusual strains of organisms,
the zoo keeper noticing strange deaths in animals, pharmacists
distributing more antibiotics than usual, or even funeral
directors with increased business.
Once again, the common denominator must
be an easily accessible and well known central surveillance
agency tasked to capture such input, analyse the information
and aggressively track the leads.
Most of the discussion so far has centred
on an impromptu information supply rather than a proactive
one. While a reactive detection system may on occasion be
able to provide early warning of a health threat, proactive
surveillance on strategic fronts is the key to pre-emptive
intervention. Disease in animals presents one hitherto untapped
area which potentially offers a wealth of invaluable data.
Dead Birds Do Tell Tales
In the month prior to the recognition
of the New York City viral encephalitis outbreak, municipal
health departments had received well over 1,000 reports
of birds dying suddenly around the region. Investigations
after the outbreak confirmed that a significant proportion
of these had resulted from exposure to the West Nile
Likewise, reports of pigs dying in Malaysia
were received months before the virus spread to humans.
And that these pigs were not the only animals being infected
at this time is demonstrated by the results of a sero-survey
done after the outbreak, which found that wild fruit bats,
dogs and even pigs from farms outside the epidemic areas17
had already been exposed to the Nipah virus.
These findings point to the possible ubiquity
of both viruses in the animal reservoir prior to the human
outbreaks. Had this been detected earlier, they may well
have been preventable.
As many biological agents may be amplified
in zoonotic hosts, routine sentinel surveillance of disease
in both native and imported animal species is clearly valuable.
In fact, much useful intelligence may be clandestinely garnered
about the health threats of a particular area by testing
animals commercially imported from there.
Animal disease surveillance will also
guard against wilful introduction of biological agents through
livestock. Biological agents need not always be delivered
by the dramatic release of millions of spores in an air
drop as popularly imagined. A single bird carrying a genetically
engineered agent may be enough to infect the local population
of birds establishing endemicity in the ornithic reservoir
before spilling over to the human population.
Maintaining sentinel flocks of birds or
herds of other animals for the purpose of revealing the
entry of foreign pathogens, or estimating local disease
burden, is analogous to the centuries old practice of using
canaries to detect poisonous gases in the coal mines, or
even, in the military context, using special papers to detect
toxic chemical agents.
Peeping into the Trojan
Horse - Is It Worth It?
To summarise the discussion so far, the
key components of any responsive bio-defence system, as
demonstrated by the two outbreaks, are as follows:
i) Comprehensive diagnostic capabilities.
ii) Continuing BW/BT emergency/primary
iii) Established and accessible communication
links between relevant agencies.
iv) Centralised collection and analysis
of peripheral input.
v) Randomised and selective zoonotic disease
The overall effectiveness of such a system
is of course contingent upon the availability of appropriate
intervention. This means that stockpiles of costly vaccines,
therapeutic drugs and prophylactic drugs, and post-attack
damage control plans must already be in existence. How much
is such a system worth? Is it economically viable?
Using the insurance model is one way to
estimate the benefits of investment in a bio-defence system18
. An actuarially fair annual premium is calculated on the
basis of savings from averted health care costs, as well
as the value of economically productive activities which
would have been lost due to the morbidity and mortality
resulting from any outbreak. The latter includes not only
the human and livestock cost resulting from the disease
itself, but also from control measures. After the Nipah
outbreak, the standing pig population in Malaysia was reduced
from 2.4 million to 1.32 million and the number of farms
was reduced from 1885 to 829
In the context of bio-defence, a significant
consideration which influences its cost effectiveness is
the speed with which post-detection intervention can be
delivered. Using these principles, an elaborate biological
defence system may or may not be justifiable depending on
the cost and risk assessment done by individual nations.
It must be emphasised that a bio-defence
system will address not only the threat of low intensity
sabotage or rogue weapons of mass destruction, but also
the equally serious danger of emerging infectious diseases
such as the Nipah and West Nile viruses. Thus
may benefits be reaped even in the absence of biological
In the 1500s, 95 percent of the Aztec
Indian population perished within a matter of months as
a result of having zero immunity to smallpox, which was
unintentionally introduced by the Spanish Conquistadores19
. It happened in an age without motor highways, railroads
or supersonic air travel, when physical boundaries were
still formidable. With these amenities in the present age,
will this tragedy be repeated on a global scale?
1. Hopkins, Donald,
Princes and Peasants: Smallpox in History, Chicago,
University of Chicago Press, 1983.
2. Documented in Journal
of American Medical Association, JAMA by Torok TJ et al
- A Large Community Outbreak of Salmonellosis Caused
by Intentional Contamination of Restaurant Salad Bars,
JAMA 1997; 278:389-95.
3. Detailed information
on these outbreaks may be found in the Weekly Mortality
and Morbidity Reports of Centers for Disease Control
and Prevention, Atlanta, Georgia, USA.
4. Philby AW et al, An
Apparently New Virus (family Paramyxoviridae) Infectious
For Pigs, Humans, and Fruit Bats, Emerging Infectious
5. Carus S. Bioterrorism
and Biocrimes: The Illicit Use of Biological Agents in the
20th Century, Washington: Center for Counterproliferation
Research, National Defense University; 1998, Page 230.
6. Meselson M et al.
The Sversdlovsk Anthrax Outbreak of 1979, Science 1994;266:1202-8..81
7. US Department of State.
1996 Patterns of Global Terrorism Report. Available from
8. WuDunn S, Miller J,
Broad WJ. How Japan Germ Terror Alerted World. New
York Times 1998 May 26;Sect A:1 (col 1), A:10 (col 1-5).
9. Jonathan B. Tucker,
Director of the Chemical and Biological Weapons Nonproliferation
Project, Center for Nonproliferation Studies, Monterey Institute
of International Studies.
10. A succinct summary
of the Nipah outbreak is found in Centers for Disease Control
and Prevention, Mortality and Morbidity Weekly Reports 1999;48:265-269.
11. The West Nile
Virus episode was closely covered in the New York Times
National from 29/9/1999 - 11/10/1999. We are indebted to
the Military Adviser Office, Singapore Mission to the UN
for sending the relevant articles to HQMC on a regular basis.
12. As listed in Departments
of the Army, Navy, and Airforce NATO Handbook on the
Medical Aspects of NBC Defensive Operations. Washington,
13. World Health Organisation
Group of Consultants. Health Aspects of Chemical and
Biological Weapons Geneva, The Organisation;1990.
14. Noah DL et al. Biological
Warfare Training: Infectious Disease Outbreak Differentiation
Criteria Military Medicine 1998;163:198-201.
15. Jennifer Steinhauer
and Judith Miller in an article in the New York Times dated
10 October 1999 first drew attention to the fact that the
West Nile virus was allegedly experimented on by
Saddam Hussein as a potential biological weapon. CIA later
concluded that the West Nile outbreak is not related
16. This view was widely
held by several virologists, including the late Professor
Chan YC (former Head of Microbiology Department in National
University of Singapore), in his capacity as regional moderator
for Asia in the highly respected Internet website renowned
for expeditious reports of infectious disease outbreaks
in the world -Program for Monitoring Emerging Diseases (ProMED).
ProMED covered the Nipah outbreak very closely and
critically. Their role in providing accurate and prompt
information during the Nipah outbreak was acknowledged
in the international medical journal, Lancet.
17. Field et al. Nipah
Virus - The Search for a Natural Reservoir. A working
paper for WHO Meeting on Zoonotic Paramyxoviruses, Kuala
Lumpur, Malaysia, 19-21st July1999.
18. Arnold F. Kaufmann,
former US Public Health Officer, who developed an insurance
analogy economic model to provide justification for the
investment of US Federal funds in a bio-defence system for
USA. The US President has since proposed $230 million in
his Fiscal Year 2000 budget to prepare for biological terrorism
19. Henry Dobyns' work
'Their Number Became Thinned' (Knoxville: University
of Tennessee Press, 1983) marshals evidence for the view
that European-introduced diseases killed 95 percent of all
R and Bellamy RF (eds), Textbook of Military Medicine:
Medical Aspects of Chemical and Biological Warfare,
Office of the Surgeon General, Department of the Army, Washington,
2. Committee on R&D
Needs for Improving Civilian Medical Response to Chemical
and Biological Terrorism Incidents, Institute of Medicine,
National Academy of Sciences. Chemical and Biological
Terrorism. Research and Development to Improve Civilian
Medical Response, Washington, National Academy Press;
3. Morse, Stephen, ed.,
Emerging Viruses, New York, Oxford University Press,
4. Ewald, Paul, Evolution
of Infectious Diseases, New York, Oxford University
5. Special Issue
on Biological Terrorism and Warfare, Emerging Infectious
Diseases Journal published by the US National Centre for
Infectious Diseases, Vol 5, No. 4.
CPT (DR) (NS) Donald Poon (left) holds
an MBBS from NUS. CPT (DR) Khaw Seong Lin (right) is a staff
officer with HQ Medical Corps and holds an MBBS (Hons) from
the University of Adelaide.