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CHAPTER 1

INTRODUCTION

Bioterrorism - An Overview

Bioterrorism is terrorism by intentional release or dissemination of biological

agents (bacteria, viruses or toxins) these may be in a naturally occurring or in human
1
modified form. In biological warfare there is a silent release of catastrophic

biological agents, resulting in unrest in population due to large scale sufferings from

diseases and disabilities and this may lead to collapse of administration and

governance. 2

A bioterrorism attack is the deliberate release of viruses, bacteria or other

germs (agents) used to cause illness or death in people, animals or plants 3. These

agents are typically found in nature but it is possible that they could be changed to

increase their ability to cause disease. They are normally resistant to current

medicines and can increase their ability to be spread into the environment. Biological

agents can be spread through the air, water or in food. Terrorists may use biological

agents because they can extremely difficult to detect and do not cause illness for

several hours to several days. Some bioterrorism agents, like the smallpox virus, can

spread from person to person and some, like anthrax, cannot.4

1
A.L. Bhatia and S.K Kulshrestha, Bioterrorism and Biological Warfare, Pointer Publisher, Jaipur,
2009, pp. 70.
2
Sudhir Syal, Bioterrorism: time to wake up,Vol. 95, No.12, Jaypee,Current Science, 2008, p.1665.
3
A.L. Bhatia , Bioterrorism and Biological Warfare, pp. 70.
4
Ibid.

1

Therefore, bioterrorism is the use or threatened use of biologic agents against a

person, group, or larger population to create fear or illnesses for purposes of

intimidation, gaining an advantage, interruption of normal activities, or ideologic

objectives. The resultant reaction is dependent upon the actual event and the

population involved and can vary from a minimal effect to disruption of ongoing

activities and emotional reaction, illness, or death. Bioterrorism is distinct from

biologic warfare. Although there may be similarities in agents considered for use in

the desired effect or the method of dispersion, the anticipated results are different.5

Once a largely hypothetical threat became a harsh reality in the fall of 2001

when letters containing a fine powder of dried anthrax spores were sent through the

United States mail, infecting twenty two people and killing five. Despite the fact that

the attacks involved only about ten grams of powdered anthrax, the ripple effects

temporarily disrupted all three branches of the federal government, closed down

congressional offices and mail processing stations and the incidence had frightened
6
millions of Americans. Recent evidence suggests that the threat of bioterrorism is

real and growing. Documents and computer hard drives seized during the March 1,

2003 had captured of Khalid Shaik Mohammed a key operational planner for Al

Qaeda, revealed that the organisation had recruited a Pakistani microbiologist and

aqquired materials to manufacture botulinum toxin and developed a workable plan for

anthrax production. 7

5
Philip S. Brachman, Bioterrorism: An Update with a Focus on Anthrax, American Journal of
Epidemiology, Volume 155, No.11, 1 June 2002.
6
Jonathan B.Tucker, Biosecurity: Limiting Terrorist Access to Deadly Pathogens,
www.usip.org/files/resources/pwks52.pdf, p. 11, access on 17 March at 2308H.
7
Ibid.

2

The Malaysia’s experience of natural phenomenon bioterrorism by the

outbreak of viral encephalitis invoked scenes of widespread panic for many months

before the virus was identified to be Nipah Virus a recently emerging deadly

paramyxovirus. This outbreak could have been a scenario of bioterrorism because it

produced fear, disease disabilities death, social disruption and severe economic loss to

this country. 8

Global Incident of Bioterrorism

Biological weapons represent a unique “environmental hazards. The

pathogens involved are natural in the sense that they are risks that naturally occur in

our environment. However, they are unnatural in the way in which they are inflicted
9
upon society. The two of the earliest uses of biological weapons reported occurred

in the 6th century B.C, when the Assyrians poisioned enemy wells with rye ergot and

Solon used the purgative herb hellebore during the siege of Krissa. In 1346, plague

broke out in the Tartar army during its siege of Kaffa in the Crimea. The attackers

hurled the corpses of those who died over the city walls. Some of the infected people

who left Kaffa may have started the Balck Death pandemic that spread throughout
10
Europe, killing one third of the population. The first idenfied attack of bioterrorism

in the United States was in 1984, when followers of Bagwan Shree Rajneesh, Indian

terrorist group contaminated salad bars in Oregon. This incident resulted the cases of
11
Salmonella infection from 10 restaurants sickened 751 people with no fatalities.
8
Sai Kit Lim, Nipah Virus a potential agent of Bioterrorism, Antiviral Research Vol 57, 2003, p. 113-
119.
9
Eric K .Noji, Bioterrorism: a new global environmental health threat, Global Change & Human
Helath, Volume 2 No. 1, Kluwer Academic Publishers, 2001, p.2.
10
Ibid.
11
Micheal B. Phillips, Bioterrorism: A brief History, Focus on Bioterrorism 2005,
www.DCMSonline.org access on 19 March 2011 at 2008H.

3

After the Gulf War, Iraq was discovered to have a large biological weapons program.

In 1995, Iraq confirmed that it had produced, filled and deployed bombs, rockets and

aircraft spray tanks containing Bacillus Anthracis and botulinum toxin and its work

force and technologic infrastructure are still wholly intact.

Another attack by terrorist that took place in Japan by the Japanese terrorist

group Aum Shinrikyo. The Cult members released sarin, a neurotoxin in the Tokyo

subway system in March 1995 resulted in thousands of injured civilians with eight

deaths had highlightened the potential impact of dissemination of a small amount of
12
bioweapon in public areas. The recent global threat of Bioterrorism happened in

2001 when the letters containing a fine powder of dried anthrax spores were sent

through the U.S. mail, infecting twenty two people and killing five.13

Overview of Anthrax Outbreak

For centuries, anthrax has caused disease in animals and serious illness in
14
humans. The disease most commonly occurs in herbivoures which are infected by

ingesting spores from the soil. Large anthrax epizootics in herbivores have been

reported during a 1945 outbreak in Iran, 1 million sheep dead. 15

In human, 3 types of anthrax infection occur which is inhalation, cutaneous

and gastrointestinal. Naturally occurring inhalational anthrax is now a rare cause of

human disease. Only 18 cases were reported in the United States from 1900 to 1978
12
D.A. Henderson, Bioterrorism as a Public Health Threat, Emerging Infectious Disease, Vol. 4, No.3,
John Hopkins Univesity, Baltimore July-September 1998, p.488.
13
Jonathan B.Tucker, Biosecurity: Limiting Terrorist Access to Deadly Pathogens,
www.usip.org/files/resources/pwks52.pdf, p. 11, access on 17 March at 2308H.
14
Thomas V.I et all, Anthrax as a Biological Weapon Medical and Public Health Management, JAMA,
Vol. 281, N0.18, May 12 1999, p.1736.
15
Ibid 1736.

4

with the majority occurring in special risk group, including goat hair mill or goatskin

workers. However, the anthrax inhalation caused by biological weapon gives big

number of outbreaks. The accidental aerosolized release of anthrax spores from

military microbiology facility in Sverdlovsk in the former Soviet Union in 1979

resulted in at least 79 cases of anthrax infection and 68 deaths demonstrated the lethal

potential of anthrax aerosols.16 Residents living downwind from this compound

developed high fever and difficulty breathing and large number died, estimated to be

200 to 1,000. 17 In September 2001, four letters sent through United States mail were

found to contain anthrax with cause 22 people were infected and five of them died.

The anthrax showed that bioterrorism has potential to cause not only dead and

disability but also huge social and economic disruption at international levels.

Cutaneous anthrax is the most common naturally occurring form, with an

estimated 2000 cases reported annually. In the United States, 224 cases of cutaneous
18
anthrax were reported between 1944-1994. The largest report epidemic occured in

Zimbabwe between 1979 and 1985 when more than 10,000 human cases of anthrax

were reported, all of them cutaneous. Gastrointestinal anthrax is uncommonly

reported. In 1982, the gastrointestinal outbreaks have been reported with 24 cases of

oral pharyngeal anthrax in rural northern Thailand following the consumption of

contaminated buffalo meat. 19

Problem Statement
16
Giorgos Stamkos, Bioterrorism: The New Invisible Threat, www.e-telescope.gr/en/international
-isssues/79-bioterrorism access on 21 March 2011 at 1208H.
17
Helath, Volume 2 No. 1, Kluwer Academic Publishers, 2001, p.2.
18
Thomas V.I et all, Anthrax as a Biological Weapon Medical and Public Health Management, JAMA,
Vol. 281, N0.18, May 12 1999, p.1736.
19
Ibid 1737.

5

Anthrax is a potential biological threat because the spores are resistant to

destruction and can easily spread by release in the air. It is also most likely to be

encountered because it is easy to produce in large quantities, highly lethal, relatively

easy to develop as a weapon, easily spread over a large area and easily stored and
20
dangerous for a long time. Anthrax is an especially favoured biological weapon.

Research on anthrax as a biological weapon began more than 80 years ago. A few

kilograms of the organism can kill as many people as a Hiroshima sized nuclear

weapon. 21

The anthrax attacks of 2001 in United States heightened concern about the
22
feasibility of large scale aerosol bioweapons attacks by terrorist groups. The

deliberate dissemination of potentially lethal anthrax spores in letters sent through the
23
U.S Postal Service caused a total of 22 persons infected and five people died. This

Anthrax attack caused a huge public health and medical alarming because it caused

health threat by massive disruption of postal services in many countries around the

world and huge economic, public health and security consequences.

Another historical fatal incidence happened involved the inhalation anthrax

occurred after the accidental release of aerosolized anthrax spores in 1979 at a military

biology facility in Sverdlovsk, Russia involving 79 cases of inhalation anthrax which

68 were fatal. According to the study done worldwide, inhalation Anthrax is the most

serious and breathing in airborne spores may lead to inhalation anthrax. Inhalation

20
Md Radzi Johari, Anthrax-Biological Threat in the 21st Century, Malaysian Journal of Medical
Sciences, Vol. 9, No. 1, Jan 2002, pp. 1-2.
21
Alasdair Geddes, Infection in the twenty first century: predictions and postulates, Journal of
Antimicrobial Chemotherapy, Vol. 46, pp. 873.
22
Thomas V.I et all, Anthrax as a Biological Weapon, 2002 Updated Recommendations for
Management, JAMA, Vol. 287, No.17 (Reprinted), May 1 2002, pp. 2237.
23
2009, pp. 162.

6

24
anthrax has a fatality rate that is 80% or higher. A 1979 analysis by World Health

Organization concluded that the release of aerolized anthrax upwind to a population of

5,000,000 could lead to an estimated 250,000 casualities of whom as many as 100,000

could be expected to die.

Some nations continued offensive bioweapons development programs despite

ratification of the Biological Weapons Convention (BWC). In 1995, Iraq

acknowledged producing and weaponizing Basilus anthracis to the United Nations

Special Commission. The former Soviet Union is also known to have had a large

Basilus anthracis production program as part of its offensive bioweapons program. A

recent analysis reports that there is clear evidence of or widespread assertions from

nongovernmental sources alleging the existence of offensive biological weapons

programs in at least 13 countries. 25

By looking the global incidence of Bioterrorism and the threat of anthrax as

biological weapon used by terrorists, Malaysia should develope the strategy to prevent

and response in times of crisis especially when facing this emergence threat or the

outbreak emerging infectious diseases. Steps taken by Malaysian Ministry of Health

to joint venture with Emergent BioSolutions firm to built 52,000 square feet of

vaccine “development and manufacturing infrastructure” in on a 62 acre site in an

industrial park outside Kuala Lumpur is one of the strategies to build defences against

germ attacks.

Furthermore, Malaysia already has three Biosafety Level 3 Labs which are

managing for disease causing organisms that cause death in human, such as anthrax,
24
Md Radzi Johari, Anthrax-Biological Threat in the 21st Century, Malaysian Journal of Medical
Sciences, Vol. 9, No. 1, Jan 2002, pp. 1.
25
Thomas V.I et all, Anthrax as a Biological Weapon, 2002 Updated Recommendations for
Management, JAMA, Vol. 287, No.17 (Reprinted), May 1 2002, pp. 2237.

7

plague and SARS. This study also wants to see the public health response to

bioterrorism with the collaboration between Malaysian Ministry of Health (MOH),

Malaysian Armed Forces (MAF) and Private Sector in term of strategic plan of

preparedness in protecting Malaysia’s national security.

The past experience such as the outbreak of viral encephalitis then identified to

be Nipah Virus a recently emerging deadly paramyxovirus had become the Malaysia’s

agenda in strengthening bioterrorism management and prevention. By taking example

of the anthrax attack in United States in 2001, the program should be stressed on the

instruction and prevention strategy of bioterrorism and or outbreak disease such as

anthrax to Malaysia’s national security.

Research Importance

This study reflects to the global incidence of Bioterrorism worldwide

especially the anthrax attack in United States in 2001 to pursuing the Malaysia’s

strategies prevention of the unexpected emergence anthrax threat to Malaysia’s

national security. This studies also taking into account the magnitude of problem

from the recent pandemic such as SARS and H1N1. By developing the strategy of

prevention will increase the awareness of the relevant government and MAF to

strengthening the biosecurity level and crisis management in response to the possible

emergence athrax attack.

Literature Review

8

The Journal titled Anthrax as a Biological Weapon, 2002 Updated
26
Recommendations for Management by Thomas V. Inglesby et al. was focus on the

study of consensus-based recommendations for medical and public health

professionals following a Bacillus anthracis attack against a civilian’s population.

From this research, the working group had identified a limited of organisms that in

worst case scenarios could cause disease and deaths in sufficient numbers to gravely

impact a city or region. Bacilus anthracis, the bacterium that causes anthrax is one

othe most serious cases.

This study more on the 2001 anthrax attack in United States and do

comparison with the previous incidences such as experiences with inhalational anthrax

in Sverdlovsk, Russia in 1979 by unintentional release of Basilus anthracis

sporesfrom Soviet bioweapons and Aum Shinrikyo, the cult responsible for 1995

release of sarin gas in a Tokyo subway station, dispersed aerosols of an anthrax and

butolism throughout Tokyo for at least 8 times.

The research recommendations include diagnosis of anthrax infection,

indications for vaccination, recommendations for antibiotic and vaccine use in the

setting of an aerosolized Basillus anthracis, postexposure prophylaxis to prevent

inhalational anthrax following the release of a Basilus anthracis aerosol as a

biological weapon, decontamination of environment and additional research by

26
Thomas V. Inglesby, Tara O’Toole, Donald A. Henderson, et al. Anthrax as a Biological Weapon,
2002 Updated Recommendations for Management, JAMA, Vol.287, No.17(Reprinted) May 1 2002, pp.
2236-2251

9

develop a recombinant anthrax vaccine and rapid diagnostic assays to identify early

anthrax infection.

Specific recommendation and steps to be taken in an epidemic by the working

group will permit the comparison to Malaysian response plan. This study will

recommend a focused response plan and selective vaccination program for the

Malaysian Healthcare Provider such as Ministry of Health, Malaysian Armed Forces

Health Services (MAFHS) and Public Health Provider.

27
The other Journal titled Anthrax-Biological Threat in the 21 Century by Md

Radzi Johari mentioned about the anthrax is a potential biological terrorism threat as

biological agents. As biological agents it most likely to be encountered because it is

easy to produce in large quantities, highly lethal, relatively easy to develop as a

weapon, easily spread over a large area and easily stored and dangerous for a long

time. The mortality rate for anthrax varies, depending on exposure and are

approximately 20% for cutanous anthrax without antibiotics and 25-75% for

gastrointestinal anthrax, inhalation anthrax has fatality rate that is 80% or higher.

The only known effective prevention treatment is the anthrax vaccine,

although anti-toxins have long been considered an essential ‘adjunctive’ therapy.

Researcher also suggests that the biomedical scientists should consider biological

weapon as a serious ‘emerging new pathogens’ to controlled and prevented for the

good huminity. New revolution in biology could be misused in offensive biological

27
Md Radzi Johari, Anthrax-Biological Threat in the 21 Century, Malaysian Journal of Medical
Sciences, Vol. 9, No. 1, January 2002, pp.1-2.

10

programs directed against human beings and their staple crops or livestock which

prohibited in the 1975 Biological and Toxin Weapons Convention (BTWC).

28
Among the latest book is Bioterrorism and Biological Warfare by A.L.

Bhatia and S.K. Kulshrestha. This book tells us about the two massive threat,

Bioterrorism and Biological Warfare as the greatest challenges faced by the 21 st

century. Bioterrorism is the use of lethal biological agents which wage a war against a

civilian population. The threat of bioterrorism, long ignored and denied has

heightened over the past few years. The two agents that used by most terrorist and

bring catasthrophic to human life are smallpox and anthrax. The author had

highlighted the magnitude of the problems and the gravity of the scenarios associated

with this release of these organisms by vividly potrayed by two epidemics of smallpox

in Europe during the 1970s and by accidental release of aerosolized anthrax from a

Russian bioweapons facility in 1979.

The most recent anthrax epidemic mentioned in this book is the anthrax attack

(also known as Amerithrax by FBI case name) occurred in U.S in 2001. Letters

containing anthrax spores were mailed to several news media offices and two

Democratic U.S Senators, killing five people and infecting 17 others. The primary

threat from Biological Warefare agents today is from terrorists, civilians in densely

populated regions would like be the targets. Therefore, civilian medical personnel

need to be aware of how a Biological Warfare attack would present to minimize its

effects. There are various ways by which bioterrorism can be prevented and be shared

28
2009.

11

with Malaysia’s National Response Team and MAFHS such as Intellengence to

prevent biowar, open sources by sharing information between country, border

security, Foriegn disease eradication, global surveillance, vaccine stockpiles, rapid

response options and crisis simulation developed and public education and awareness

campaign.

29
The journal entitled Bioterrorism: a ‘new’ global environment health threat

by Eric K. Noji, looking the issues of biological weapon proliferation by the countrys

such as former Soviet Union and Iraq although these countrys had signed the

Convention on Prohibition of the Development, Production and Stockpiling of

Bacteriological and Toxin Weapons and on Their Destruction, called the Biological

Weapons Convention. The violation of this Covention had brought massive disaster

such as an incident in Sverdlovsk in former Soviet Union by accidental release of

anthrax in aerosol form from Soviet Military microbiology facility. Estimated 200 to

1000 civillian around this compound developed high fever, difficulty breathing and

large number died.

The same situation happened in Iraq where the aftermath of Gulf War, the

Iraqi announced to United Nations Special Commission that they had conducted

research into offensive use of Bacillus anthracis, Clostridium perfingens and

botulinum toxins. The smallpox virus eradicated in late 1970’s primarily through the

enormous efforts of the U.S Centers for Disease Control and Prevention (CDC) in

Atlanta and WHO and now stored in only two laboratories at CDC Atlanta and the

29
Helath, Volume 2 No. 1, Kluwer Academic Publishers, 2001.

12

Institute for Viral Precautions in Moscow, Russia. The worry is the “bargained” away

by desperate Russians Scientists in seeking money.

Research Objectives

The general objective of this research paper is to study the bioterrorism with

the related agent of anthrax and the application of prevention strategy from selected

agencies to be Malaysia’s prevention strategy. The specific objectives of this study

are as follows:

a. The objective is to study the Bioterrorism related anthrax, the clinical

features and pathogenesis of anthrax.

b. To identify the prevention strategy in training and strategic plan of

preparedness for possible bioterrorism anthrax attack in Malaysia. This study

will take into consideration of prevention strategy from the previous country

with anthrax attack such as United States.

c. To study the public health awareness and identify the bio defence

capabilities in Malaysia.

d. Finally, the study is to influence the relevant agencies to undertake

corrective measures through this study by government commitment and

international collaboration.

Research Hypotheses

13

Bioterrorism - Anthrax attack as the possible emergence threat to the

Malaysia’s National Security and Malaysia will counter the threat by implying the

national strategy to prevent if it occurs.

Research Methodology

The research is based on qualitative and descriptive analysis and data will be

sought from the printed academics journals and books. Information also accessed

from the online material such as online medical and health journal straight from

internet Google, Google scholar and Yahoo. This study also looking into the

Malaysian Armed Forces (MAF) - Publikasi Perkhidmatan Bersama 15 (PPB 15) or

MAF Nuclear, Biological and Chemical Defence Mannual to develop the prevention

strategy of bioterrorism anthrax. Collecting data on characteristics of the Bacillus

anthrax, mode of infection and symptoms, pathogenicity and treatment of anthrax in

order to provide information for the response plan in the outbreak and prevention

strategy.

During this study, researcher makes full use of the library such as Malaysian

Armed Forces Staff College Library, Ministry of Defence Library, University Malaya

Library and National Library. All data collected based on the past study from journal,

electronic journal, books, e - book and etc. The use of website is based on the

consideration that it provides sufficient materials which are accessible, reliable,

essential and current to complete this research.

14

Limitations of Study

The limitation of this research is primarily because of time constraint. The

study will not be able to cover the bioterrorism fully with the restriction of time frame

and the limited of the documents on Malaysian biological warfare. The Malaysia’s

experience for Bioterrorism is so slim and not many study done on Bioterrorism in

Malaysia. For this study, most of the references taken from United States and several

other country as a main guide to complete the bioterrorism caused by anthrax attack.

Chapter Outline

The research paper will be divided into five chapters in constructive manners

from basic understanding of bioterrorism and anthrax as a biological agent used in

terrorism. The threat of bioterrorism to Malaysia’s national security. The clinical

features and characteristic of anthrax until the discussion and analysing prevention

strategy and the application as preparedness plan for bioterrorism in Malaysia.

The detail chapters are as follows:

Chapter 1 - Introduction

This chapter will consists of the background, problem statement, objectives and the

significance of the study as well as literature review and research methodology. This

15

chapter will guide the layout of the framework of the research and will be the basis for

the outlines of research.

Chapter 2 - Bioterrorism Related Anthrax

This chapter will define anthrax as Biological Weapons and Bioterrorism, the current

threat of anthrax to human population, the possible emergence threat to Malaysia’s

national security and the management bioterrorism from Malaysian perspective.

Chapter 3 - The Clinical Presentation and Manifestation of Anthrax Infection

This chapter will outline and explain the background, clinical characteristic, clinical

and epidemiologic features, mode of infection and symptoms, vaccination of anthrax

infection, treatment and prevention of anthrax infection; and decontamination of site

in anthrax infection.

Chapter 4 - Analysis of Prevention Strategy from Anthrax Infection

This chapter will discuss the prevention strategy in term of training and education to

the first reponser team and strategic plan for bioterrorism preparedness and response.

This prevention strategy will be adopted from the previous country with experience in

bioterrorism anthrax such as United States.

Chapter 5 - Conclusion

This chapter will conclude on the bioterrorism as the possible emergence threat to

Malaysia’s national security in the case of anthrax as biological threat and the

16

prevention strategy. End of this is the conclusion will mentioned the best national

prevention strategy on bioterrorism anthrax.

CHAPTER 2

BIOTERRORISM RELATED ANTHRAX

17

Background of Biological Warfare and Bioterrorism

During the 16th century B.C, the Assyrians poisoned enemy wells with Ergot, a

fungus that would make enemy delusional and Solon of Athens used the poisonous

herb Veratrum to poison water supply of Phocaea during his siege of the city. During

the 4th century B.C Scythian archers used arrows with tips covered with animal faeces

to cause wounds to become infected. In 2004 B.C, Hanibal of Carthage had clay pots

filled vith venomous snakes and instructed his soldiers to throw the pots on to the

decks of Pergamene ships. 30

In 1346 the bodies of Mongol warriors of the Golden Horde who died of

plague were thrown over the walls of besieged Crimean city of Kaffa (now

Theodosia). It has been speculated that this operation may have been responsible for

the advent of the Black Death in Europe. 31

Another attempted use of biological warfare occurred between 1754 and 1767

when the British infiltered small pox infested blankets to unsuspecting American

Indians during the French and Indian war. Small pox decimated the Indians, but it is

unclear if the contaminated blankets or endemic disease brought by the Europeans

caused these epidemics. In 1932, the Japanese began a series of horrific experiments

on human beings at outside Harbin Manchuria China. At least 11 Chinese cities were

30
A.L Bhatia, S.K. Kulshrestha, Bioterrorism and Biological Warfare, Pointer Publisher, Jaipur, 2009,
pp. 363.
31
Ibid.

18

attacked with agents of anthrax, cholera, shigellosis, salmonellas and plague and at

least 10,000 died during their gruesome experiments. 32

The United States started an offensive biological warfare program at Camp

Detrick (today Fort Detrick) in Frederick, Maryland in 1943. By 1969, the U.S had

weaponized the agents causing tularaemia, butolism, anthrax and botulinum toxin.

These were soon destroyed after President Nixon unilaterally ended the U.S offensive

biological warfare program that year. In 1972, U.S signed the Biological Weapons

Convention (BWC) stating that it would ban their production of their biological
33
program.

Despite this convention, the development of Biological weapons has

continued. In late April 1979, an incident in Sverdlovsk (now Yekaterinburg), a city

of 1.2 million people in the former Soviet Union appeared to be an accidental release

of anthrax in aerosol form from Soviet Military Compound 19, a microbiology

facility. Residents downwind from this compound developed high fever and difficulty

breathing and large number died, the final toll was estimated to be 200 to 1000. 34

By 1991, the Iraqis had weaponized anthrax, botulinum toxin and aflatoxin

and fortunately these were not used during Desert Storm Operation. The United

Nations destroyed the final remains of the Iraqi offensive programs in 1996. Between

1990 and 1995, the well financed Japanesed apocalyptic cult Aum Shinrikyo launched

a repeated series of attacks on civilian using both biology and chemical weapons.

32
A.L Bhatia, S.K. Kulshrestha, Bioterrorism and Biological Warfare, Pointer Publisher, Jaipur, 2009,
pp. 363.
33
Ibid.
34
Eric K.Noji, Bioterrorism: a ‘new’ global environmental health threat, Global Change &Human
Health, Volume 2, No. 1, Kluwer Academic Publishers, 2001, pp. 2.

19

The release strain nerve gas in Japanese subway, was found to possess rudimentary
35
biological weapons including anthrax, botulism and Q fever. On September 18,

2001, Basillus anthracis spores were sent to several locations via the US postal

Service. Twenty two confirmed or suspect cases of anthrax infection with 5 were died
36
from this incident. This anthrax attack giving us the situation that the disasters still

exist although many countries had signed the BWC.

Anthrax Bacterium as Biological Weapons and Bioterrorism

Anthrax (Scientific name Bacillus anthracis) was the first microorganism
37
identified as the cause of a specific disease by Dr. Robert Koch in 1876. The word

anthrax is the Greek word for anthracite in reference to the black skin lesions victims

develop in a cutaneous skin infection. Anthrax cannot spread directly from human to

human but spores can be transported by human clothing, shoes and if a person dies of

anthrax their body can be a very dangerous source of anthrax spores. 38

It is a potential biological terrorism threat because it easy to produce in large

quantities, highly lethal, relatively easy to develop as a weapon, easily spread over a

large area and easily stored and dangerous for a long time. The fatality rate in
39
halation for anthrax is 80% or higher. All of this suggests why Bacillus anthracis

35
Ibid, pp.364.
36
Thomas V.Inglesby, Anthrax as a Bilogical Weapon 2002, Updated Recommendations for
Management, JAMA, Vol 287, No. 17 (Reprinted), May 1 2002, pp. 2236.
37
Md Radzi Johari, Anthrax - Biological Threat in The 21st Century, Malaysian Journal of Medical
Sciences, Vol. 9, No. 1, Januari 2002, pp. 1-2.
38
A.L Bhatia & S.K Kulshrestha, Bioterrorism and Biological Warfare, Pointer Publisher,Jaipur, 2009,
pp. 83.
39
Ibid.

20

40
became the agent of choice for most biological warfare programs. There are 89

known strains of anthrax; the most widely recognized being the virulent Ames strain

used in the 2001 anthrax attacks in the United States. The Ames strain is extremely

dangerous, though not quite as virulent as the Vollum strain which was successfully

developed as biological weapon during the Second World War. 41

Anthrax, smallpox, plague, botulism, tularaemia and viral haemorrhagic

fevers are categorised ‘Category A’ biological agents by the Centers for Disease

Control and Prevention (CDC). These are biological agents with both a high potential

for adverse public health impact and that also have a serious potential for large scale
42
dissemination. Aerosol exposure to anthrax spores could cause symptoms as soon

as 2 days after exposure. However, illness could also develop as late as 6-8 weeks
43
after exposure. Once symptoms begin, death follows 1-3 days later for most people.

The aerosol could would be colourless, odourless and invisible following its release.

Given the small size of the spores, people indoors would receive the same amount of

exposure as on the street. There are currently no atmospheric warning systems to

detect an aerosol cloud of anthrax spores. The first sign of a bioterrorist attack would

most likely be patients presenting with symptoms of inhalation anthrax. 44

40
Steven M. Block, The Growing Threat of Biological Weapons, American Scientist, Vol. 89, January-
February 2001, pp. 2.
41
pp. 84.
42
pp. 37.
43
Sciences, Vol. 9, No. 1, Januari 2002, pp. 1-2.
44
Ibid.

21

The analysis performed by the Office of Technology Assessment of the U.S

Congress, estimated that 130,000 to 3 million deaths could occur following the release

of 100 kilograms of aerosolized anthrax over Washington D.C, making such an attack
45
as lethal as a hydrogen bomb. The Centre for Disease Control and Prevention

estimated that such a bioterrorist attack would carry an economic burden of $ 26.2

billion per 100,000 people exposed to the spores. 46

Biological weapon using the anthrax with the first recorded during the World

War I where the introduction of anthrax as weapon against livestock and

transportation animals. A clandestine biological research laboratory was set up in

Baltimore by the German government in 1915. A number of suspected uses of

anthrax by the German government during the World War I were alleged, but not well

documented. Japan, Great Britain and United States all proceeded with research into

the use of Bacillus anthrax weapon in World War II. The former Soviet Union also

developed a biological research programme during the Cold War. The accidental

release of anthrax from a secret bio weapons research facility in Sverdlovsk, Union of

Soviet Socialist Republics resulted in the death of 66 from 77 Russian military and

many others civilian in downwind from this compound. 47

Research on anthrax as a biological weapon began more than 80 years ago.

Most national offensive bio weapons programs were terminated following widespread

ratification or signing of the Biological Weapons Convention (BWC) in the early

45
Ibid.
46
Sciences, Vol. 9, No. 1, Januari 2002, pp. 2.
47
Anthrax as a Weapon of Terrorism and Difficulties Presented in Response to its Use,
www.defencejournal.com/dec98/anthrax.htm access on 12 March 2001 at 2016H.

22

1970’s. 48 However, some nations continued offensive bio weapons develop programs

despite ratification of the BWC. In 1995, Iraq acknowledged producing and

weaponizing Bacillus anthracis to the United Nation Special Commission. The

former Soviet Union is also known to have a large Bacillus anthracis production

program as part of its offensive bioweapons program. A recent analysis reports that

there is clear evidence of or widespread assertions from nongovernmental sources

alleging the existence of offensive biological weapons programs in at least 13
49
countries.

The Current Threat of Anthrax to Human Population

Biological agents may appeal to the new terrorist groups because they affect

people indiscriminately and unnoticed, thereby sowing panic. A pattern is emerging

that terrorists who perpetrate mass and indiscriminate attacks do not claim
50
responsibility. The Bioterrorist attack on October 2001 in the United States by

deliberate dissemination of potentially lethal anthrax spores in letters sent through the

United States Postal Service is the recent use of anthrax as biological weapon to the

realities of life in the 21st century. This anthrax attack caused massive disruption of

postal services in many countries around the world and huge economic, public health
51
and security consequences. In addition to biological agents as weapons of war,

there is also increasing concern over the possibility of terrorist use of biological agents

48
Thomas V.Inglesby, Anthrax as a Bilogical Weapon 2002, Updated Recommendations for
Management, JAMA, Vol 287, No. 17 (Reprinted), May 1 2002, pp. 2237.
49
Ibid.
50
Bruce Hoffman, “Why Terrorists Don’t Claim Credit,” Terrorism and Political Violence, Vol. 9, No.
1, 1999, pp. 1-6.
51
Ibid.

23

52
to threaten civilian populations. Although a relatively new weapon in the hands of

modern potential bioterrorists, the threat of death from the inhalation of anthrax has

been part of human history since antiquity. The deliberate use of biological weapon

has significant potential for not only damaging the human health but also causing

mass panic and public hysteria. 53

An attack using biological weapons may be more sinister than an attack using

conventional, chemical or nuclear weapons, where effects are more immediate and

obvious. By the time the first casualty is recognized, the agent may have already been

ingested, in haled or absorbed by many others and more casualties may be inevitable

despite medical countermeasures. 54 In a minute the particles can silently pass through

the air supply systems of ships, vehicles, command head quarters and even hospitals.

Biological weapon such as anthrax is considered as unique in their ability to

inflict large numbers of casualties over a wide area with minimal logistical

requirements and by means that can be virtually untraceable. In 1970, the World

Health Organisation estimated that if 50 kg of anthrax spores were dispersed upwind

of a population centre of 500,000 people in optimal conditions can effected almost

half of the population of that area would be either disabled or killed in such attack. 55

52
Health, Volume 2, No. 1, Kluwer Academic Publishers, 2001, pp. 3.
53
Ibid.
54
Edward M.Eitzen, Use of Biological Weapons, U.S. Army Medical Research Institute of Infectious
Diseases, Fort Detric, Frederic, Maryland, www.dead-planet .net/med-cbw/Ch20.pdf , pp. 442-443.
Access on 28 March 2011.
55
Ibid,., pp. 443.

24

Anthrax was considered by United States Army Medical Research Institutes of

Infectious Disease (USAMRIID) as the most likely bioterrorist agent and was the first
56
lethal bioterrorist agent used in United States. It is particularly suitable because it
57
can cause widespread illness and death an eventually cripple a city or region.

Inhalational or pulmonary anthrax results most commonly from inhalation of anthrax

spore containing dust and is highly fatal with nearly 100% mortality. A lethal dose of

anthrax is reported to result from inhalation of about 10,000 - 20,000 of spores.

Patients with anthrax inhalational cases characterized by fever, dyspnoea, stridor,

hypoxia and hypotension leading to death within 24 hours. This disease can rarely be

treated, even if caught in early stages of infection. 58

The statement above was supported by the evident from the incident in

Sverdlovsk in 1979 caused by inhalational of anthrax aerosol caused 66 patient died in

the Soviet Military Compound and estimated 200 - 1000 residents died of high fever

and difficulty breathing. The recent incidence was the inhalational of anthrax spores in

United States in 2001, caused 5 people died.

The Emergence Threat to Malaysia’s National Security
56
R Gregory Evans et al, The Threat of Bioterrorism in the U.S, A report Current Healthcare Issues
Bioterrorism, Business Briefing : Global Healthcare Issues, pp. 29.
57
Stefan Riedel, Anthrax: a continuing concern in the era of bioterrorism, BUMC PROCEEDINGS
No. 18, 2005, pp. 234.
58
D.A. Henderson, Bioterrorism as a Public Health Threat, Emerging Infectious Diseases, Vol. 4, No.
3, July – September 1998, pp. 491.

25

The emergence threats of disease outbreak to the security of Malaysia can be

resulted from the deliberate use of pathogens as biological weapons, the accidental

release from research laboratories (such as the accidental release of anthrax from a

military testing facility in Sverdlosk in the former Soviet Union in 1979) or the

naturally occurring outbreaks of particular infectious disease caused by traveller

disease or brought migrating animal, birds or insect from other country to Malaysia.

For example, the migrating of the water fowls is a significant source of this
59
Avian Influenza virus carried in their intestinal tract and shedding it in their faeces.

This is one of the good reasons of the cause of the outbreak of Avian Influenza in

Malaysia for sometimes ago. The disease outbreak as a result of bioterrorism and

pandemic affects international security, regional stability and military readiness in the

nation. The exposure to naturally occurring or resulted from the deliberate use of

pathogens as biological weapons by the bioterrorist poses a global risk to Malaysia’s

national security.

As public health histories record, infectious diseases outbreak whether causes

naturally occurring or intentionally release by terrorist have had a devastating impact

on the quality of life of individuals in most nations. In fact, infectious diseases

morbidity and mortality far exceed war related death and disability in human history.

Given the nature of pathogenic microbes, Malaysia has to cooperate to mitigate the

threat to individuals in their territories from the biological threats. The long history of

59
Christopher Lee, Alert, Enhanced Surveillance and Management of Avian Influenza in Human, 6 Feb
2004, pp. 1-2.

26

international cooperation on infectious diseases control then becomes relevant as a

foreign policy but also a security issue.

The emergence of the biological threats to Malaysia will effected many

aspects such as the human security, economic and global trade security, social security

and delivery of health security. All of these aspects will become the agenda that will

threaten of individual, communities, tourist, traders and governments.

a. Human Security Threat.

In many countries in the world, the pandemic and the endemic of the infectious

diseases caused the bad impact to the public health or the human security. The

outbreak of the disease such as pandemic Influenza, SARS, H1N1, smallpox and

plague could pose threats to large populations because of the potential for person to

person transmission, enabling spread to other cities and states and become a

nationwide emergency.

In the situation of bioterrorism, the disaster caused by from the intentional

release of virulent biological agents would be very different from other natural or

technological disasters, conventional military strikes or even attacks with other

weapons of mass destruction (e.g., nuclear, chemical, or explosive). For example,

when people are exposed to a pathogen such as plague or smallpox they may not be

aware of their exposure and they may not feel sick for some time, although they would

be contagious. The incubation period may range several hours to a few weeks and

27

consequently an attack would not become obvious for a similar period. By the time,

modern transportation could have widely dispersed the pathogen and greatly expanded

the population of victims. 60

In Malaysian medical preparedness, the initial responders to a biological

disaster will most likely include county and city health officers, hospital staff, and

members of the outpatient medical community and wide range of response personnel

in the public health system, military health services and also including the traditional

first responders such as police, fire brigade, rescue team and ambulance services.

A bioterrorist attack has occurred and could occur again at any time, under any
61
circumstances and a magnitude far greater than we have thus far witnessed. The

use of microorganisms as agents of bio weapons is considered inevitable for several

reasons, including ease of production and dispersion, delayed onset, ability to cause

high rates of morbidity and mortality and difficulty in diagnosis. Unfortunately, in

most cases, few physician and doctors in Malaysia have ever seen a case caused by

biological weapons such as anthrax, smallpox or plague and diagnosis of an epidemic

is certain to be delayed. Laboratory capabilities for diagnosis and measuring

antibiotic sensitivity of organisms are similarly limited and caused further delays. The

weakness of the medical response and preparedness would become a fear to the
62
communities and big challenges to the human security. Malaysia should take the

60
Health, Volume 2, No. 1, Kluwer Academic Publishers, 2001, pp. 3- 4.
61
Stacy L. Knobler, Adel A.F, Biological Threats and Terrorism, Accessing the Science and Response
Capabilities, Workshop Summary, National Academy of Science, pp. 2. Available at
http://www.nap.edu/catalog/10290.html. Access on 30 March 2011.
62
Zalini Yunus, Combating and Reducing The Risk of Biological Threats, The Journal of Defence and
Security, Vol.1, No. 1, Science & Technology Research Institute for Defence, MINDEF, 2010, pp. 3.

28

great efforts in establish a national outbreak preparedness plan to meet any

eventualities as a result of infectious diseases outbreaks, including bioterrorist attacks.

b. Economy and Global Trade Security Threat.

The infectious diseases outbreak or the terrorism biological attack could pose

bad impact to the Malaysia’s economic and global trade. Through the Malaysian

experience of diseases outbreak had affected the industry of tourism. In the year

2003, Malaysia too appears most susceptible to damages wrought by Systemic Acute

Respiratory Syndrome (SARS) because this health disaster had given the bad impact

to tourisms which plays important role in Malaysia’s economy. The tourism sector

accounts for 8 percent of real gross domestic product (GDP) and 17 percent of real

private consumption and is the country’s second largest foreign exchange earner. 63

Most of the tourists come to Malaysia are from China, Hong Kong, Singapore,

Thailand, Indonesia, Japan, Taiwan and Vietnam accounted for 80 per cent of total

inbound tourists arrivals to Malaysia. According to the Culture, Arts and Tourism

Ministry, tourist arrivals from China, Hong Kong and Taiwan have fallen some 80 per

cent following the outbreaks of SARS. An economist expects tourist arrivals to

decline by 14 per cent to 11.5 million visitors this year. This means that the local

economy stands to lose an income of some RM 3.4 billion, which is equivalent to 0.8
64
per cent of real GDP.

63
Darshini M. Nathan, SARS impact on industries, The Star (BizNews), Saturday, 19 April 2003.
Available at netinc.net.my/health/s/011.htm. Access on 6 April 2011.
64
Ibid.

29

The other sector that facing the bad impact of the SARS is the Malaysian

Airlines System Bhd (MAS). The outbreak of the deadly virus has sent airlines

scrambling to cancel flights to those countries most affected by the disease. Because

of SARS, MAS has thus far cancelled a total of 716 flights to Asian destinations such

as China, Hong Kong, Taiwan, Thailand, Indonesia and Singapore. Slower

international tourist arrivals are expected to impact negatively on Malaysia Airports

Holdings Bhd’s international volume. According to the Transport Ministry, the Kuala

Lumpur International Airport has already seen a 28 per cent drop in its passenger

traffic over the six weeks of outbreak as travellers cancel their trips due to deadly

virus. The government’s move temporarily restricted the issuance of visas to tourists
65
from China and Hong Kong.

In the scenario of bioterrorism, whether real or perceived, can have a

tremendous negative impact on society. By taking the example of the small scale

2001 anthrax attacks in the United States resulted in a cost of over $200 million to

decontaminate anthrax infected facilities. A study by the Centre for Disease Control

(CDC) in Atlanta estimates that the economic impact of a bioterrorist attack could

range from estimated $ 477.7 million per 100,000 persons exposed in the scenario of

brucellosis attack and to $ 26.2 billion per 100,000 persons exposed in the scenario of

anthrax attack. 66

65
Ibid.
66
Arnold F. Kaufmann, Martin I. Meltzer and George P.Schmid, The Economic Impact of Bioterrorist
Attack: Are Prevention and Postattack Intervention Program Justifiable? Emerging Infecrtious
Diseases, Vol. 3, No. 2, CDC, Atlanta, April-June 1997. pp. 91- 92. Available at
http://www.cdc.gov/ncidod/EID/vol3no2 / kaufman.htm. Access on 6 April 2011.

30

c. Social Security Threat.

The exposure to the naturally occurring or the release of virulent biological

agents by terrorists which highly transmissible infectious diseases poses a global risk

to the certain institution, industries or social organisation. For certain industries which

involved the society gathering and communication such as retail, wholesale, consumer

packaged goods, aviation, hospitality, gaming, sports, media and entertainment may

indirectly suffer severe economic losses due to a decrease in public gatherings, travel

and tourism. Industrial companies may experience reduced attendance due to

infection, fear of infection or absenteeism of workers caring for their families.

Broader economic problems caused by reduced workforces may then initiate
67
economic downturn and further unemployment.

In Malaysian experience, the education sector had to reel from the effects

wrought by the deadly pneumonia type virus in the outbreak of Pandemic Influenza,

SARS and H1N1. During the outbreak, many school in Malaysia had to close for

public in order to control for the further spread caused many school program had to be

cancelled and give the bad impact to Malaysian education. The temporary freeze on

students from SARS affected countries, had given the bad economic impact to the

University and private colleges with student intakes from China. In 2003, foreign

students comprise 17 percent of total student population of 14,300 where 800 consist
68
of Chinese students that already studying at Inti’s campuses.

67
The Economic and Social Impact of Emerging Infectious Diseases: Mitigation Through Detection,
Research and Response. Available at www.healthcare.philips.com/main/shared/assets/documents/...
Access on 6 April 2011, pp. 13.
68
Darshini M. Nathan, SARS impact on industries, The Star (BizNews), Saturday, 19 April 2003.
Available at netinc.net.my/health/s/011.htm. Access on 6 April 2011.

31

d. Delivery of Health Care Security Threat.

The concern continues to mount that a pandemic, bioterrorism or serious

epidemic like SARS will have an enormous and potentially incapacitating impact on

the health care industry. Health care providers are considering and planning for how

to deal with unprecedented numbers of patients in emergency rooms and hospitals,

while coping with severe supply constraints. Quality of health care might further be

compromised as employees on the front line of infectious exposure must deal with

large numbers of patients and uninfected people seeking medical reassurance. These

same workers must also bear the mental burden of the risk they may pose in spreading

the disease to their families. Furthermore, if fears of contamination drive health care

professionals, staff and elective patients away from health care facilities, for profit

ones in particular which rely on patient flow and professional delivery of services on a
69
daily basis may find themselves unable to maintain operations.

Management of Bioterrorim from Malaysian Perspective

The Malaysia’s plan for bioterrorism envisages the setting up of rapid response

teams at district, state and national levels. The rapid response experience and

assembled by matching expertise and incident needs in order to provide rapid response

69
The Economic and Social Impact of Emerging Infectious Diseases: Mitigation Through Detection,
Research and Response. Available at www.healthcare.philips.com/main/shared/assets/documents/...
Access on 6 April 2011, pp. 13.

32

to manage such outbreak effectively. Clear lines of authority and communications

have to be established in such an event. A crucial element of the outbreak

preparedness plan is with regard to surveillance and early detection of outbreak. A

bioterrorism attack is often an insidious and unnoticed event. The classical

bioterrorist weapons like anthrax, plague and smallpox are infections that are no

longer happen in Malaysia. So, it is crucial to build up the Malaysia’s plan for

bioterrorism preparedness to include that health care workers be trained to recognized

such diseases, especially those in the front line such as casualty doctors, outpatient

doctors and general practitioners.

The investigation and management of these outbreaks and bioterrorism

activities also require much planning, coordination of activities and resource

allocation. Public health practitioners are required to investigate and control these

outbreaks and they need to understand the nature of bioterrorism and how to prevent

the spread of disease if an attack occurs. Laboratories have to be prepared to handle

the specimens and make the necessary identifications. Some of the agents involved

are highly pathogenic and would require special high containment facilities for their

processing. For this purpose, Malaysia had established a Bio safety Level 3 facility at

the Institute for Medical Research and the other one at the National Public Health

Laboratory in Sungai Buloh. 70

Clinical facilities must also be prepared for bioterrorist attacks. Hospitals need

to have adequate decontamination and isolation facilities for patients and appropriate

personal protective equipment for health care workers. Infection control measures

70
Anthrax War - the Malaysian Connection. Available at www.propublica.org/.../antrax-war-the-
malaysian-connection. Access on 12 March 2011.

33

have to be put in place and all health care workers have to be appropriately trained.

Sufficient supplies of critical items like essential antibiotics, vaccines, disinfectants

and personal protective equipments must be stockpiled and distributed in a timely and

efficient manner in times of crises.

In this regard, Ministry of Health (MOH) is planning to set up an Institute of

Natural Products Research and Vaccinology with the assistance of the Ministry of

Science, Technology and the Environment (MOSTE) as part of the Bio valley

initiative. It is clear that managing bioterrorist attacks is no easy task and a lot of

thought and planning is required to achieve the necessary level of preparedness.

Training of personnel is crucial and the need to draw up such a training programme

must be put into the plan of bioterrorism preparedness. The need also in upgrading

our infrastructure in the public health sector, laboratories as well as hospitals.

CHAPTER 3

CLINICAL PRESENTATION AND MANIFESTATION

OF ANTHRAX INFECTION

Background

34

Anthrax infection was described in ancient literature and religious writings
71
that struck Egypt around 1500 B.C as anthrax epidemics. The disease is also very

well described in texts of antiquity and it has been suggested that the famous Plague
72
of Athens in 430 - 427 B.C was an epidemic of inhalational anthrax. Periodically,

over the following millennia, there were outbreaks of anthrax worldwide. For

example, there was a substantial outbreak in Germany in the 14th century. During the

17th century, there were large outbreaks in Russia and one in Europe that killed more

than 60,000 head of cattle.

Although the disease anthrax dates back thousands of years, it was recognized

until the 1800s by several scientists who make blood testing from animals that had
73
died of anthrax. However, the researcher at that time generally agreed that anthrax

was an infectious disease, but they did not agree on the cause of diseases and

continued to debate the cause of anthrax. The disease continued to kill large

numbers of animals and peoples. In 1864, more than 72,000 horses died of anthrax in

Russia. Between 1867 and 1870, 528 men as well as 56,000 horses, head cattle and

sheep died in Novgorod, Russia.74

Finally, in 1876, Robert Koch, a German physician discovered that the cause

of the disease was from the blood of infected animals and very infectious. Koch also

discovered that Bacillus anthracis develop protective spores that enabled them to
71
I.W. Fong and Kenneth Alibek, Bioterrorism and Infectious Agents A New Dilemma for the 21st
Century, Springer Science, United States, 2005, pp.1
72
Stefan Riedel, Anthrax: a continuing concern in the era of bioterrorism, BUMC Proceedings,
Vol.18,No. 3, July 2005, pp. 234.
73
Century, pp. 2.
74
Century, pp. 2.

35

withstand unfavorable conditions to reemerge later when condition improved. In

1881, French scientist, Louis Pasteur who developed a vaccine of anthrax had

contributed to the decline of thousands of dead animals and thousands of people dying

each year in Europe, Asia and North America through vaccination program of animals

and anthrax eradication program. This had also contributed the number of cases of
75
industry related infections in human decreased dramatically.

China has also been affected by persistent anthrax outbreak. In 1989, 509

people were infected during the outbreak in Tibet caused 162 died. The Chinese

government had made significant attempts to reduce the incidence of outbreak. The

latest of anthrax outbreaks was the bioterrorist attack involving the use of anthrax

occurred in United States in 2001 caused in total 22 people were infected with 5

died.76

Clinical Characteristics of the Anthrax Bacterium

Anthrax is an acute disease in humans and animals that is caused by the
77
bacterium Bacillus anthracis and is highly lethal in some forms. Bacillus anthracis

is a gram-positive, non motile, facultative anaerobic, spore forming, rode shape

bacterium. Each bacterium is the rectangular shape of the individual cell, in the chain

form gives rise to boxcar like. It is about 1 to 1.5 micron in width and 4-10 micron in

75
Ibid., pp. 3.
76
Ibid., pp. 7.
77
A.L Bhatia and S.K. Kulshrestha, Bioterrorism and Biological Warfare, Pointer Publisher, Jaipur,
2009, pp. 83.

36

78
length. Since sporulation requires the presence of free oxygen and organisms shed

by the dying or dead animal will sporulate on contact with air. Anthrax spores are

highly resistant to heat, ultraviolet and ionizing radiation, pressure and chemical

agents. They are able to survive in the soil for long periods of time even up to

decades or perhaps longer. In suitable environment (e.g., various tissues or organs),

spores start vegetating and multiplying. However, the Bacillus anthracis are poor

survivors and it is unlikely that germination, propagation with further resporulation
79
will occur outside the host in natural conditions.

There are 89 known strains of anthrax, the most widely recognized being the

virulent, Ames strain used in the 2001 anthrax attacks in the United States. The Ames

strain is extremely dangerous, though not quite as virulent as the Vollum strain

(isolated in 1935 from a cow in Oxfordshire, United Kingdom) was successfully
80
developed as biological weapon during the Second World War. Anthrax is

classified as a Category A agents with recognized bioterrorism potential priority by
81
the Centers for Disease Control and Prevention (CDC). Even though anthrax is not

contagious disease, there are certain characteristics of the pathogen that make it

ideally suited for development into a biological weapon. The first characteristic is

that anthrax is relatively easy to produce. Anthrax also has a long shelf life and is

stable in the environment. It spores have a very high survival rate and can be used in

an explosive device. Anthrax has a high mortality rate approaching 100% in the case

78
Ibid., pp. 84.
Ibid., pp. 60.
79
Century, pp.8.
80
2009, pp. 84.
81
2009, pp. 60.

37

of untreated inhalational anthrax. Even with treatment, the mortality rate is still high
82
because there is no effective treatment for advanced forms of inhalational anthrax.

Clinical and Epidemiologic Features.

Human anthrax is a disease acquired following contact with infected animals.
83
Anthrax is not contagious; the illness cannot be transmitted from person to person.

The key to anthrax infection is that there must be contact with spores, either through

natural or intentional circumstances. The disease is initiated by the entry of spores

into the host body. This can occur via a minor abrasion, by eating contaminated meat

or inhaling airborne spores. There are three recognized types of human infection,

determined by where spores germinate, inhalational, cutaneous and gastrointestional.

Each form can progress to fatal systemic anthrax. 84

Inhalational anthrax, which is the most likely form to be seen in bioterrorism

event. The mortality is high ranging from 45% in the 2001 anthrax attacks cases in

United States to 89 % in the 20th century of cases. Cutaneous disease is the most

common form of natural disease comprising 95% of all cases. Mortality is less than

1% in treated cases but up to 20% in cases that are left untreated. Gastrointestinal

82
Century, pp.4.
83
Md Radzi Johari, Anthrax – Biological Threat in The 21st Century, Malaysian Journal of Medical
84
Century, pp.10.

38

disease is rare, comprising less than 5% of all cases worldwide and has never been

reported in the United States. Mortality numbers is estimated to at least 50%. 85

The clinical features of inhalational anthrax have been fairly well described in

the past and have been further validated by the 2001 outbreak. The incubation period

of inhalational anthrax according to current literature may last from 1 to 9 days and

the average incubation period for the patients infected in the United States in 2001
86
was for 4 - 6 days. Symptoms and physical findings are nonspecific in the

beginning of infection. The occasional longer incubation periods are thought to be

related to delayed spore germination which in animal studies occurred up to 98 days
87
after exposure.

After the incubation period, a non specific flulike illness ensues, characterized

by fever, myalgia, headache, a nonproductive cough and mild chest discomfort. A

brief intervening period of improvement sometimes follows 1 to 3 days of these

prodormal symptoms, but rapid deterioration follows; this second phase marked by

high fever, dyspnea, stridor, cyanosis and shock. In many cases, chest wall edema

and hemorharrhagic meningitis (present in up to 50% of cases) may be seen late in the

course of disease. Chest radiographs may show pleural effusions and a widened

mediastinum, although true pneumonitis is not typically present. Death is universal in

85
Biological Terrorism Primary Care Preparedness, Anthrax September 2003.
www.bioterrorism.sku.edu/....ahec_bio/scripts/Anthrax.pdf accessed on 17Apr 2011 at 2244H.
86
Century, pp. 14.
87
Biological Terrorism Primary Care Preparedness, Anthrax September 2003.
www.bioterrorism.sku.edu/....ahec_bio/scripts/Anthrax.pdf accessed on 17Apr 2011 at 2244H.

39

untreated cases and may occur in as many as 95% of treated cases if therapy is begun

more than 48 hours after the onset of symptoms. 88

Mode of Infection and Symptoms

Anthrax is not contagious; the illness cannot be transmitted from person to
89
person. The usual pathway of anthrax exposure for humans through the

occupational exposure to infected animals or their products such as skin, wool and

meat. Workers who are exposed to dead animals and animal products are the highest

risk, especially in countries where anthrax is more common. Anthrax does not

usually spread from an infected human to a non infected human. However, if the

disease is fatal the person’s body and its mass of anthrax bacilli becomes a potential

source of infection to others. Anthrax can enter the human body through the intestine

(ingestion), lungs (inhalation), or skin (cutaneous) and causes distinct clinical

symptoms based on its side of entry. 90

Inhalational or pulmonary anthrax results most commonly from inhalation of

spore containing dust where animal hair or hides are being handled. It is

characterized by fever, dyspnoea, stridor, hypoxia and hypotension leading to death

within 24 hours. This disease can rarely be treated, even if detected in early stages of

infection. Inhalational anthrax is highly fatal, with nearly 100% mortality. A lethal
88
Theodore J. Cieslak and Edward M. Eitzen, Clinical and Epidemiologic Principles of Anthrax,
Emerging Infectious Diseases, Vol. 5, No. 4, Jul-Aug 1999, pp. 553.
89
Md Radzi Johari, Anthrax – Biological Threat in The 21st Century, Malaysian Journal of Medical
90
2009, pp. 252.

40

dose of anthrax is reported to result from inhalational of about 10,000 – 20,000
91
spores.

Cutaneous anthrax is usually acquired through injured skin or mucous

membranes. A minor scratch or abrasion, usually on an exposed area of the face or

neck or arms, is inoculated by spores from the soil or a contaminated animals or

carcass. The spores germinate, vegetative cells multiply, and a characteristic

gelatinous edema develops at the side. This develops into a papule within 12 - 36

hours after infection. The papule changes rapidly to a vesicle, then a pustule

(malignant pustule), and finally into a necrotic ulcer from which infection may

disseminate, giving rise to septicemia. Lymphatic swellings also occur within seven

days. In severe cases, where the blood stream is eventually invaded the disease is

frequently fatal. 92

Gastrointestinal anthrax is analogous to cutaneous anthrax but occurs on the

intestinal mucosa. The bacteria spread from the mucosa lesion to the lymphatic

system. Intestinal anthrax results from the ingestion of poorly cooked meat from

infected animals. Gastro-intestinal anthrax is characterized by serious gastrointestinal

difficulty, vomiting of blood, severe diarrhea, acute inflammation of intestinal tract

and loss of appetite. It can be treated but usually results in fatality rate of 25% to
93
60% depending upon how soon treatment commences.

91
2009, pp.253.
92
Ibid., 252.
93
Ibid., 253.

41

Vaccination of Anthrax Infection

Anthrax and other biological agents which categorized in categories A by

Centre of Control Disease (CDC) are posed the greatest risk for causing large

numbers of casualties in the event of an effective release by a terrorist group, are at

the top of the list of threat agents. Vaccination has been the single most cost effective

public health intervention. The U.S armed forces have recognized the military value

of vaccines against biological threats and have a long standing research and

development program for a series of vaccines to protect service members from hostile
94
use of a biological agent.

Providing the exposed population with antibiotics followed by vaccination

could be lifesaving for exposed persons who would otherwise become ill with

untreatable inhalation anthrax in the subsequent few weeks. Prophylactic antibiotics

alone will prevent disease in persons exposed to antibiotic susceptible organisms, but

incorporating vaccination into the treatment regime can greatly reduce the length of

treatment with antibiotics. Without vaccination, antibiotics must be continued for 60

days; if effective vaccination can be provided this can be reduced to 30 days.

Stockpiling a vaccine capable of inducing protective immunity with two doses could
95
be extremely valuable in reducing the impact of a terrorist release of anthrax.

Anthrax depends on two toxins (lethal factor and edema factor) for virulence.

A protein called protective factor is an essential component of both toxins. The

94
Philip K. Russell, Vaccines in Civilian Defense Against Bioterrorism, Emerging Infectious Diseases,
Vol. 5, No.4, July-August 1999, pp. 531
95
Philip K. Russell, Vaccines in Civilian Defense Against Bioterrorism, Emerging Infectious Diseases,
Vol. 5, No.4, July-August 1999, pp. 532.

42

protective factor content is the basis for the effectiveness of the current vaccine. A

vaccine based on purified protective factor made by recombinant technology has been

protective in animals. Use of a modern adjuvant with purified recombinant protective

factor should make it possible to have a very effective two - dose vaccine. 96

The current anthrax vaccine, produced from one non-virulent strain of the

anthrax bacterium is manufactured by BioPort Corporation, subsidiary of Emergence
97
Bio Solutions. This is the U.S Food and Drug Administration licensed vaccine

derived from the supernatant fluid of an attenuated, none capsulated Bacillus

anthracis strain (Sterne) is available and has been used in hundreds of thousands of

military troops and at risk civilians. The trade name is Bio Thrax, although it is

commonly called “Anthrax Vaccine Adsorbed” (AVA). The vaccination series, as

currently licensed, consists of six doses (0, 2 and 4 weeks and 6, 12 and 18 months)

followed by annual boosters. AVA is administered subcutaneously as a 0.5-mL

dose.98

Recently, there is not enough data from exposure of humans to determine

protective efficacy of the vaccine against anthrax aerosol challenge in bioterrorism

cases, but studies in rhesus monkeys indicate the vaccine is effective, even when as

few as two doses administered. Although, there is no reason to believe that the new

vaccine will be more protective, it will be more easily produced in available

production facilities and may be slightly less reactogenic and possibly lest costly if

large lots are needed. The U.S Institute of Medicine recently published a report that
96
Ibid., 533.
97
2009, pp. 89.
98
Century, pp. 24.

43

concluded that Anthrax Vaccine Adsorbed (AVA) is effective against inhalational

anthrax and may help prevent onset of disease post exposure if given with appropriate

antibiotics. 99

Treatment and Prevention of Anthrax Infection

Direct person to person spread of anthrax is extremely unlikely; but a patient’s

clothing and body may be contaminated with anthrax spores. Effective

decontamination of people can be accomplished by a thorough wash down with anti-

microbe effective soap and water. Waste water should be treated with bleach or other

anti-microbial agent. Effective decontamination of particles can be accomplished by

boiling contaminated particles in water for 30 minutes or longer and using common

disinfectants. Chlorine is effective in destroying spores and vegetative cells on
100
surfaces.

After decontamination, there is no need to immunize, treat or isolate contacts

of person’s ill with anthrax unless they were also exposed to the same source of

infection. Early antibiotic treatment of anthrax is essential to delay seriously lessens

chances for survival. Antibiotic prophylaxis for inhalational anthrax appears to be

most effective before respiratory symptoms develop, but it is difficult in naturally

occurring cases to begin therapy early because the nonspecific prodrome is virtually
101
impossible to distinguish from flu or other less serious diseases. The Centers for
99
Century, pp. 25.
100
2009, pp. 87.
101
Steven M.Gordon, The threat of bioterrorism : A reason to learn more about anthrax and smallpox,
Cleveland Clinic Journal of Medicine, Vol. 66, No.10, Nov/Dec 1999, pp. 595.

44

Disease Control and Prevention (CDC) recommends post exposure prophylaxis with

ciprofloxacin or another fluoroquinolone twice daily, with doxycycline the second

agent of choice.102 CDC also recommended that cutaneous anthrax associated with a

bioterrorism attack should be treated with ciprofloxacin or doxycycline as the first
103
line therapy. Cutaneous anthrax with signs of systemic involvement, extensive

edema or lesions on the head and neck require intravenous therapy and a multidrug

approach is recommended.

Although natural anthrax is very susceptible to penicillin, military experts

decided in 1991 that Iraq and Russia both had technology to develop penicillin -

resistant strains. Antibiotics would have to be taken for at least 8 weeks after

exposure, because the spores can lie dormant in the hilar lymph nodes for up to 6
104
weeks before germinating. Alternately, antibiotics could be given for 4 weeks

while the first 3 doses of vaccine are administered. In either case, these procedures

would clearly strain local supplies of antibiotics as well as vaccine in the event of a

large scale exposure. In possible cases of inhalational anthrax exposure to

unvaccinated personnel early antibiotic prophylaxis treatment is crucial to prevent

possible death. If death occurs from anthrax the body should be isolated to prevent

possible spread of anthrax germs. Burial does not kill anthrax spores. Cremating
105
victims is the preferred way of handling body disposal.

102
Ibid.
103
Century, pp. 25.
104
Steven M.Gordon, The threat of bioterrorism : A reason to learn more about anthrax and smallpox,
Cleveland Clinic Journal of Medicine, Vol. 66, No. 10, Cleveland, Nov/Dec 1999 pp. 595.
105
A.L. Bhatia and S.K. Kulshrestha, Bioterrorism and Biological Warfare, Pointer Publisher, Jaipur,
2009, pp. 87.

45

Decontamination of Site in Anthrax Infection

In the incidence of anthrax outbreak or intentionally anthrax released in

bioterrorism event, the decontamination of site contaminated with anthrax spores is

more crucial. Anthrax spores can survive for long periods of time in the environment

after release. Methods for cleaning anthrax-contaminated sites commonly use

oxidizing agents such as peroxides, ethylene oxide, Sandia Foam, chlorine dioxide

(used in Hart Senate office building in anthrax attack in 2001, in USA) and liquid
106
bleach products containing sodium hypochlorite. These agents slowly destroy

bacterial spores. Chlorine dioxide has emerged as the preferred biocide against

anthrax contaminated sites, having been employed in the treatment of numerous

government building over the past decade.

The process can be speed with trace amounts of a non-toxic catalyst composed

of iron and tetro-amido macro cyclic ligands are combined with sodium carbonate and

bicarbonate and converted into spray. The spray formula is applied to an infested area

and is followed by another spray containing tertiary-butyl hydro peroxide. Using the

catalyst method, a complete destruction of all anthrax spores takes 30 minutes. A

standard catalyst-free spray destroys fewer than half the spores in the same amount of

time.

106
Ibid., pp. 89.

46

CHAPTER 4

ANALYSIS OF PREVENTION STRATEGY

FROM ANTHRAX INFECTION

Even though the threats of bioterrorism are minimal in Malaysia, the risk does

exist. One way or another, national security is vulnerable and can be threatened by

47

the easy availability of biological agents to terrorists and disgruntled individuals who

have no qualms about using them. The problem of many country in facing of

bioterrorism is the time and place of such attacks is difficult to predict. As known that

biological agents have been used for biological warfare and terrorism and their

potential for future use is a major concern. Therefore, Malaysia must be prepared to

respond appropriately to face the unpredictable attack from bioterrorist.

In Malaysia, we are still facing the nation’s bio defense science and response

capabilities is still lagging, with the striking insufficiency of vaccines and

therapeutics, and local public health departments struggling with limited resources.

The Malaysian experience of the natural phenomenon of the bioterrorism is the

outbreak of the Nipah virus, emerging deadly paramyxovirus which invoked scenes of

widespread panic because it produced fear, disease, disabilities, death, social

disruption and severe economic loss to the country. The pandemic of the Influenza

H1N1 and SARS that affect this country a few years ago could be the bench mark of

the nation’s to strategist the level of preparedness towards combating the actual

bioterrorism threat in the future.

There are various strategy of prevention that was produced by various agencies

around the world in order to prepare the nation’s preparedness and response towards

the bioterrorism anthrax threat. This paper will seek to examine the program of

preparedness, response and training aspect in the subsequent sections in order to

provide the best strategy of prevention to the bioterrorism anthrax threat.

STRATEGY OF PREVENTION

48

United States Experience and Response to Anthrax Incidents of 2001

In October 2001, an employee of American Media Inc. (AMI) in Florida was

diagnosed with inhalational anthrax, the first case in the United States in over two

decades. By the end of November 2001, 21 more people had contracted the disease

and 5 people including the original victim had died as a result. Although the FBI

confirmed the existence of only four letters containing anthrax spores, the

Environmental Protection Agency (EPA), United States had confirmed that over 60

sites about one third of which were United States postal facilities had been

contaminated with anthrax spores. 107

The cases of inhalational anthrax in Florida, the first epidemic center

(epicenter) were thought to have resulted from proximity to opened letters containing

anthrax spores. The initial cases of anthrax detected in New York, the second

epicenter, were all cutaneous and were also thought to have been associated with

opened anthrax letters. The cases detected initially in New Jersey, the third epicenter

were cutaneous and were in postal workers who presumably had not been exposed to

opened anthrax letters. The incident on Capitol Hill, the fourth epicenter began with

the opening of a letter containing anthrax spores and resulting exposure. The

discovery of inhalational anthrax in a postal worker in the Washington, D.C., the fifth

epicenter and Connecticut the sixth epicenter revealed that even individuals who had

been exposed only to sealed anthrax letters could contract the inhalational form of the

107
Bioterrorism: Public Health Response to Anthrax Incidents of 2001, Report to the Honorable Bill
First, Majority Leader, U.S. Senate, Oct 2003, pp. 9.

49

108
disease. The incidents of the anthrax attack in United States had national

implications although were limited to six epicenters on the East Coast of U.S. This is

because mail processed at contaminated postal facilities could be cross-contaminated

and end up anywhere in the country.

The U.S. local and state public health officials had identified strengths in their

responses to the anthrax incidents of 2001 as well as areas for improvement. The

planning efforts had helped to promote a rapid and coordinated response that would be

needed across both public and private entities involved in the response to the anthrax

incidents. The response of the public health officials also benefited from previous

experiences, whether gained through exercising their plans or by responding to

emergency of various kinds. One of the key successes in the plan was the effective

communication among response agencies but the responder team still had difficulty

reaching clinicians to provide them with needed guidance.109

The Centers of Disease Control and Prevention (CDC) had served as the focal

point for communicating critical information during the response to the anthrax

incidents and experienced difficulty in managing the voluminous amount of

information coming into the agency and in communicating with public health

officials, media and public. The anthrax incidents also highlighted both shortcomings

in the clinical tools available for responding to anthrax such as vaccines and drugs and

a lack of training for clinicians on how to recognize and response to anthrax. 110

108
First, Majority Leader, U.S. Senate, Oct 2003, pp. 9.
109
Ibid., pp. 4-5.
110
First, Majority Leader, U.S. Senate, Oct 2003, pp. 4-5.

50

CDC also identified areas for improvement and taken steps to implement those

improvements. These include restructuring the Office of the Director, building and

staffing an emergency operations center, enhancing the agency’s communication

infrastructure and developing and maintaining databases of information on and

expertise in biological agents considered most likely to be used in a terrorist attack.

CDC has also been working with other federal agencies as well as private

organizations to support the development of better clinical tools, including new

vaccines and treatments for anthrax and increased training for medical care

professionals. 111

Training for Preparedness and Response

The ability to screen and identify potential biological agents related threats in

bioterrorism have tremendous effect in terms of reduced likelihood of biological harm

to the society. In order to be effective the first responders must be trained and skillful

to identify the potential biological agents that pose fear and devastating to the society.

Training and application are essential to the success of the bioterrorism preparedness,

deterrence and response plan. Each constituency group including law enforcement,

emergency services, hospital personnel, primary care providers, decontamination team

members and medical distribution teams must have ample training and the necessary

equipment for training, practice exercises and simulations. The goal is to enable these

professionals to perform quickly, effectively and efficiently their important roles when

111
Ibid.

51

112
called upon in time of community catastrophe. In preparing the training

procedure, local civilian medical systems both out of hospital and hospital, comprise a

critical human infrastructure that will be integral in providing the early response

necessary for minimizing the devastation of a Weapon Mass Destruction (WMD)

incident.

Training and application also are concerned with using emergency equipment

and feeling trust and respect for this equipment. Each response group must be

thoroughly familiar with the equipment that it will utilize during an actual terrorism

incident. Once plans are developed at the community level and key groups are

identified with specific tasks to perform, training should be conducted with a

systematic approach. Existing structures such as the emergency management system,

law enforcement and the like should be integrated into the plan and they should

participate in training, practice and simulation exercises with newly formed groups

such as decontamination teams. Existing equipment and procedures for responding to

a terrorist incident should be inventoried and reviewed. 113

Simulation and practice exercises are critical for finding flaws or areas of

weakness in combating bioterrorism plan. Practice exercises should be coordinated

with all local agencies. The general population should be kept informed as should

state and federal agencies. During the simulation or practice exercises, all

communication systems and the leadership command structure should be evaluated for

effectiveness. Backup systems, methods and the performance of individuals identified

112
James A. Johnson, Gerald R. Ledlow and Mark A. Cwiek, Community Preparedness and Response
to Terrorism, Vol. 1 The Terrorist Threat and Community Response, Westport Connecticut, London,
2005, pp. 134-139.
113
Ibid., 136.

52

for each role to access equipment failures, needs and training deficiencies should be

also evaluated. 114

Determining and providing the proper equipment for the various community

level groups, and matching equipment and people in teams together to train for
115
competence are vital for terrorism. It is imperative that community based teams

practice with their equipment and become proficient using the appropriate equipment.

When the individual teams become proficient with their tasks, multidisciplinary teams

(EMS, decontamination, firefighting, law enforcement and etc) should work together

in simulation exercises. Federal and state authorities and agencies should be notified

of simulation exercises and invited to participate, since a bioterrorist incidence will

require a total local state and federal effort to reduce damage and to aid the

community’s recovery.

Strategic Plan for Bioterrorism Preparedness and Response - Centres For

Diseases Control and Prevention (CDC’s), Atlanta USA

The CDC was designated by the Department of Health and Human Services,

United States to prepare the United States Public Health system to respond to a

bioterrorism event. CDC’s strategic plan is based on the following five focus areas,

114
James A. Johnson, Gerald R. Ledlow and Mark A. Cwiek, Community Preparedness and Response
to Terrorism, Vol. 1 The Terrorist Threat and Community Response, Westport Connecticut, London,
2005, pp. 134-139.
Ibid., 137.
115
Ibid.

53

with each area integrating training and research concerntrated on (1) preparedness and

prevention; (2) detection and surveillance; (3) diagnosis and characterization of

biological and chemical agents; (4) response; and (5) communication. 116

Under the focus area of preparedness and prevention, CDC’s emphasized on

the detection, diagnosis and mitigation of illness and injury caused by biological and

chemical terrorism is a complex process that involves numerous partners and

activities. Meeting this challenge will require special emergency preparedness in all

cities and states. For this strategies’s effort, CDC will provide public health

guidelines, support and technical assistance to local and state public health agencies as

they develop coordinated preparedness plans and response protocols. Furthermore,

CDC also will provide self asssessment tools for terrorism preparedness, including

performance standards, attack simulations and other exercises. In addition, CDC will

encourage and support applied research to develop innovative tools and strategies to
117
prevent or mitigate illness and injury caused by biological and chemical terrorism.

The second focused area of detection and surveillance will focus on early

detection as an essential for ensuring a prompt response to a biological or chemical

attack including the provision of prophylactic medicines, chemical antidotes or

vaccines. For this effort CDC will integrate surveillance for illness and injury

resulting from biological and chemical terrorism into the United States disease

surveillance systems, while developing new mechanisms for detecting, evaluating and

116
Ali S.Khan, Alexandra M. Levitt, Biological and Chemical Terrorism : Strategic Plan for
Preparedness and Response. Recommendations of the CDC Strategic Planning Workshop, Morbidity
and Mortality Weekly Report, Vol.49, No.RR-4, April 2000. pp. 8. Available at
www.cdc.gov/mmwr/PDF/RR/RR4904.pdf Accessed on 27/4/2011.
117
Ibid., pp. 9

54

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