Annals of Disaster Medicine
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Updated
July 18, 2003
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Contents:
Volume 2, Number 1; July, 2003 |
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Applicability of Bioterrorism
Preparedness in SARS:
Focus on Laboratory Examination |
Li-Pin
Chang, MD; Tzong-Luen Wang, MD, PhD; Hang
Chang, MD, PhD |
From the Department of Emergency Medicine ( Chang
LP, Wang TL, Chang H), Shin-Kong Wu Ho-Su Memorial Hospital.
Correspondence to Dr. Hang Chang, Department
of Emergency Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, 95
Wen Chang Road, Taipei, Taiwan. E-mail M001043@ms.skh.org.tw
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Abstract
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To investigate the laboratory preparedness for bioterrorism,
we studied the laboratories in 7 medical centers in Taipei that
were implemented for SARS and compared with the laboratory requirements
by the criteria of bioterrorism preparedness. Of seven medical centers in Taipei,
one was categorized into Level A, four
were categorized into Level C laboratories and two Level B ones.
There were 100% of the laboratories possessing the capacity of bacterial
and viral cultures, 100% microscopic examinations for all specimens,
44% electromicroscopic examinations, 100% serology
such as FA and ELISA, 71% PCR, 71% HPLC, 86% GC, 100% general requirements,
and 100% pathologic examination. Among them, one was categorized
into Level A, five Level C laboratories and one Level B. The availabilities
of laboratory equipments were the same as described. The major pitfall
for all laboratories was the lack of personnel training for common
agents for bioterrorism such as anthrax,
smallpox and rabies. In conclusion, our survey revealed that the
laboratory requirements were similar for both bioterrorism
preparedness and SARS response. The laboratories in the medical
centers could be considered to be designed under the ˇ§dual
useˇ¨ model.
Key words---SARS; Bioterrorism; Laboratory; Hospital Preparedness |
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Introduction
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For bioterrorism,
early diagnosis can be critical to saving lives after a biological
weapon release. Unfortunately, clinical diagnosis is often difficult
because many of these diseases present initially as nonspecific
febrile illness. Therefore, laboratory confirmation is particularly
important with suspected biologic terrorism patients. The clinician
should consider obtaining the samples for study. 1,2
Most laboratories can do the crucial initial evaluation with
light microscopy, primary culture, and serology. Rapid antibody-based
assay detector kits that can provide presumptive identification
also have to be developed. A gene amplification assay such as polymerase
chain reaction (PCR) is also an important part for the laboratory
under such purposes. 3,4
Severe acute respiratory syndrome (SARS) is a disease manifested
by atypical pneumonia and rapid progression to respiratory distress. 5-10
It has been proven to be caused by the coronavirus. 11-13
In the viewpoint of disaster medicine, the preparedness for such
an infectious disease should be similar to that for bioterrorism.
Some diagnostic tools such as PCR, 11-13
indirect fluorescent antibody (FA) or enzyme-linked immunosorbent
assay (ELISA) antibody have been rapidly developing, 13
although there are still many clinical difficulties in diagnosing
the disease in a time-efficient manner. 14,15
The design and structure of the laboratories for SARS deserves to
be investigated.
According to Advanced Health in America,16 the hospitalˇ¦s
patient care role begins with and follows the disaster. However,
there have never been any events of bioterrorism or devastating
infectious diseases such as SARS in recent decades. We therein retrospectively
analyzed the design and structure of the laboratories for SARS in
Taiwan and compared them with the laboratories for bioterrorism.
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Methods |
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Requirements of the laboratory for bioterrorism |
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For comparison, we
collected the information about the requirements of the laboratories
for bioterrorism from related references.11 The general recommendations
for specimens to confirm a specific disease (caused by bioterrorism)
include (1) Nasal and throat swabs or induced respiratory secretions
for culture, FA, or PCR within 24 hours; (2) Serum for toxin assays;
blood for PCR and culture; sputum for FA, PCR, and culture from
24 to 72 hours; and (3) Serum for toxin assays and IgM or IgG agglutination
titers, blood and tissues for culture, and pathologic samples.
The classification of bioterrorism laboratories include:
Level A: These laboratories have a minimum biosafety level of BSL-2.
They may be involved in early detection and will be capable of ruling
out the priority agents of bioterrorism. They may be also capable
of the presumptive identification of some of these organisms but
will refer isolates to a level B reference laboratory.
Level B: These laboratories also have a minimum biosafety level
of BSL-2. They are state public health and large private labs capable
of definitive and rapid identification of organisms referred by
Level A labs. They are also capable of a rapid response to announced
events. These laboratories will rule in and refer organisms. When
appropriate, Level B labs will forward specimens to higher level
labs.
Level C: These laboratories are state public health, federal and
academic labs capable of advanced diagnostic testing. These labs
will have a minimum biosafety level of BSL-3. They also are capable
of testing toxicity as well as evaluating new tests and reagents.
Level D: These laboratories are federal labs like the CDC and the
military which have highly specialized capabilities for isolation
and identification and have maximum containment facilities. They
are capable of dealing with rare organisms such as Ebola and smallpox.
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Requirements of the laboratory for SARS |
According to the
WHO, positive SARS diagnostic test findings depended upon (a) confirmed
PCR for SARS virus (at least 2 different clinical specimens, or
the same clinical specimen collected on 2 or more days during the
course of the illness, or 2 different assays or repeat PCR using
the original clinical sample on each occasion of testing); (b) seroconversion
by ELISA or indirect FA (negative antibody test on acute serum followed
by positive antibody test on convalescent serum, or four-fold or
greater rise in antibody titer between acute and convalescent phase
sera tested in parallel); (c) virus isolation (isolation in cell
culture of coronavirus from any specimen, plus PCR confirmation
using a validated method.
Confirmation of positive PCR required appropriate negative and positive
control in each run, which should yield the expected results, i.e.,
1 negative control for the extraction procedure and 1 water control
for the PCR run, 1 positive control for extraction and PCR run,
and the patient sample spiked with a weak positive control to detect
PCR inhibitory substances (inhibitory control). If a positive PCR
result has been obtained, it should be confirmed by repeating the
PCR using the original sample or having the same sample tested in
a second laboratory. Amplifying a second genome region could further
increase test specificity. It was recommended that reference laboratories
should be identified at national level.
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Table 1. Laboratory requirements for SARS (from
CDC, Taiwan) |
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Data enrollment |
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We reviewed the data of 7 medical centers in Taipei
provided by Department of Health, Taipei City Government. The checklist
of laboratory equipment and guidelines were provided by Taiwan Center
for Disease Control, which was actually modified from the WHO requirements
(Table). |
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Statistical analysis |
The categorical data were inputted
in Microsoft Excel 2000 for descriptive statistics and further qualitative
analysis. The correlation between the laboratory requirements evaluated
by different criteria was made by a linear logistic regression model.
A P<0.05 was considered to be statistically significant. |
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Results |
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Of seven medical centers
in Taipei, one was categorized into Level A, four were categorized
into Level C laboratories and two Level B ones.
According to the checklist derived from the Center for Disease Control,
the presence of the cultures for bacteria and viruses was 100% (7/7),
microscopic examinations for all specimens 100% (7/7), electromicroscopic
examinations 44% (3/7), serology such as FA and ELISA 100% (7/7),
PCR 71% (5/7), HPLC 71% (5/7), GC 86% (6/7), general requirements
100% (7/7), and pathologic examination 100% (7/7).
If checked by the requirements for bioterrorism, one was categorized
into Level A, five Level C laboratories and one Level B. The availabilities
of laboratory equipments were the same, that is, bacterial and virus
cultures (100%), microscopic examinations (100%), electromicroscopic
examinations, serology (100%), PCR (71%), HPLC (71%), GC (86%),
general requirements (100%), and pathologic examination (100%).
The major pitfall for all laboratories was the lack of personnel
training for common agents for bioterrorism such as anthrax, smallpox
and rabies.
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Discussion |
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In the United States,
the Center for Disease Control (CDC), in collaboration with the
Association of Public Health Laboratories and the Federal Bureau
of Investigation (FBI), established the Laboratory Response Network
(LRN) to develop federal, state, and local public health laboratory
capacity to respond to bioterrorism events. 4
This network is a strategic partnership designed to link front-line
clinical microbiology laboratories in hospitals and other institutions
to state and local public health laboratories and supports advanced
capacities of public health, military, veterinary, agricultural,
water and food-testing laboratories at the federal level. This partnership
operates both domestically and internationally. Depending on a laboratory's
ability to handle dangerous pathogens, the laboratory is designated
either as a reference laboratory or a sentinel laboratory. Reference
laboratories are the core, advanced technology laboratories that
can provide confirmatory testing for agents in biosafety levels
3 and 4. This includes the centralized, state-of-the-art national
reference laboratory located at CDC to rapidly and accurately identify
any agent used in a biological terrorism attack (the Rapid Response
and Advanced Technology Laboratory). Reference laboratories have
access to a secure Website which allows for timely reporting and
monitoring. These reference laboratories, which total about 120
laboratories, can access on-line agent protocols, share information,
and order reagents. The estimated 25,000 sentinel laboratories play
an important role in reporting possible outbreaks and ensure that
specimens are sent to the appropriate reference laboratory for confirmation.
According to Advanced Health in America, Mass casualty incidents
that result from infectious causes are different from all other
types of incidents for many reasons, including: (1) the onset of
the incident may remain unknown for several days before symptoms
appear; (2) even when symptoms appear, they may be distributed throughout
the communityˇ¦s health system and not be recognized immediately
by any one provider or practitioner; (3) once identified, the initial
symptoms are likely to mirror those of the flu or the common cold
so that the health system will have to care for both those infected
and the ˇ§worried wellˇ¨; (4) having gone undetected
for several days or a week, some infectious agents may already be
in their ˇ§second waveˇ¨ before the first wave of casualties
is identified; (5) public confidence in government officials and
health care authorities may be undermined by the initial uncertainty
about the cause of and treatment for the outbreak; (6) health care
authorities and hospitals may want to restrict those infected to
a limited number of hospitals but the public may seek care from
a wide range of practitioners and institutions, and (7) health care
workers may be reluctant to place themselves or family members at
increased risk by reporting to work.
In a recent investigation from American Hospital Association16 revealed
that most of the hospitals in the United States were unprepared
for bio-attack. In other words, most of the hospitals had emergency
plans but lacked certain capacities for bioterrorism response. The
percentage of urban hospitals that reported the laboratories specifying
in emergency response plan to contact the specified entities during
an emergency were 58.5% (range 34.0% to 75.7% among different states).
As the reports demonstrated, In order to be adequately prepared
for bioterrorism, hospitals would need to have several basic capabilities,
whether they possess them directly or have access to them through
regional agreements. Plans that describe how hospitals would work
with state and local officials to manage and coordinate an emergency
response would need to be in place and to have been tested in an
exercise, both at the state and local levels and at the regional
level. Regional plans can help address capacity deficiencies by
providing for the sharing, among hospitals and other community and
state agencies and organizations, of resources that, while adequate
for everyday needs, may be in short supply on a local level in an
emergency. In addition, hospitals would need to be able to communicate
easily with all organizations involved in the response as events
unfold and critical information is acquired. Staff would need to
be able to recognize and report to their state or local health department
any illness patterns or diagnostic clues that might indicate an
outbreak of a disease caused by a biological agent likely to be
used by a terrorist. Finally, hospitals would need to have the capacity
and staff necessary to treat large numbers of severely ill patients
and limit the spread of infectious disease. They would need adequate
stores of equipment and supplies, including medications, personal
protective equipment, quarantine and isolation facilities, air handling
and filtration equipment, and laboratory support.
Many of the capabilities required for responding to a large-scale
bioterrorist attack are also required for response to naturally
occurring disease outbreaks. Such a ˇ§dual-useˇ¨ response
infrastructure improves the capacity of local public health agencies
to respond to all hazards. For example, a large-scale outbreak of
SARS would require many of the same capabilities that would be needed
to respond to an intentionally caused epidemic.
Our study revealed that the ˇ§dual-useˇ¨ response infrastructure
also could be applied in Taiwan. The laboratory requirements for
bioterrorism and for SARS were similar. Most of the laboratories
of the medical centers could provide similar supports for the above
two purposes. Although there is still no evidence that the bioterrorism
would occur in Taiwan, the laboratories constructed under such a
ˇ§dual-useˇ¨ infrastructure will be a good way for hospital
preparedness.
In conclusion, our survey revealed that the laboratory requirements
were similar for both bioterrorism preparedness and SARS response.
The laboratories in the medical centers could be considered to be
designed under the ˇ§dual useˇ¨ model.
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