17
Feb 2011
Glanders=
(B.
Mallei ) Antibiotic Post-Exposure Prophylaxis
(PEP) af=
ter a
Deliberate Release: Guidelines in
Glanders
is a rare infection of humans caused by the gram-negative bacteria
Burkholderia
mallei that is included on the US CDC Category B biothreat agents.
In
the
microbiologist
at the U.S. Army Medical Research Institute for Infectious Diseases
(USAMRIID)
in
al. NEJM 2001 (July 26); 345: 256-58. See also the accompanying editorial by Drs.
Ali
Khan and David Ashford pages 287-89 titled: “Ready or Not: Preparedne=
ss
for
Bioterrorism”).
B. Mallei is a zoonotic infection e.g., horses and related equids; however,=
in
the
345:
287). Thus, even one human or animal infection with glanders in the
detection
by an environmental sensor, would be cause for an immediate investigation
and appropriately measured response.
Animal
outbreaks of glanders continue to occur in other parts of the world, for
example
in
horses (UAE 2004, Bahrain 2010) and in lions (Tehran Zoo reported January 1=
7,
2011
in a Washington Post online/Associated Press article by Nasser Karimi, and =
in
the
Istanbul
Zoo published in the German-language literature in February, 1986).
If
glanders were used as an agent of bioterrorism or biowarfare then it would
likely
be
as an inhaled form that could cause a high mortality rate due to respirator=
y
failure. One of the immediate clinical questions would be what antibiotics could be<= o:p>
used
for post-exposure prophylaxis (PEP) to prevent symptomatic disease? The
heading
“Challenges” to “Develop post-exposure antibiotic prophyl=
axis
strategies for
bioterrorism preparedness”.
A
2008 multinational group of co-authors, including from the US CDC (Dr. Ther=
esa
Smith)
and USAMRIID (Dr. David DeShazer), published guidance on “Management =
of
Accidental
laboratory Exposure to Burkholderia pseudomallei and B. mallei” (Peac=
ock
SJ et al. Emerg Infect Dis 2008 (July) ; 14 (7) online.<=
/span> These authors state explicitly,
however,
that: “The guidance does not address actions required after a
bioterrorist
event. (see Introduction section on page 2 of 8). Earlier gui=
dance
from USAMRIID was
published
by Rusnak JM et al. “Management Guidelines for Laboratory Exposure to=
Agents
of Bioterrorism” in the Journal of Occup Environ Med (JOEM) 2004
(August); 46:
791-800
also focused on laboratory exposures (for which “doxycycline or
ciprofloxacin”
for
10 days was recommended for B. mallei PEP (see Table 4, page 795).
In
contrast, guidelines for antibiotic post-exposure prophylaxis after a
“deliberate”
or
“bioterrorism-related” glanders (B. mallei) event have been
published in
in
2008 (by the
Commission
(
(BICHAT)
as quoted below:
The
2008
version 3.3 HPA Centre for Infections. Title: Guidelines for action in the
event
of a deliberate release”. See the UK HPA website (last accessed 17 Feb 2011):
www.hpa.org.uk/Topics/InfectiousDiseases/InfectionAZ/GlandersDR/Gu=
idance/
Section
2.4 (on page 9 of 20 in this pdf) provides the following verbatim
guidelines
under the title “Prophylaxis of persons exposed to glanders/
melioidosis”:
“Although
there is no evidence of a protective efficacy of post-exposure antibiotic
prophylaxis
in preventing human melioidosis or glanders, on the basis of animal
experiments
the following 7 day regimen is currently recommended for those
known
to have been exposed to heavy contamination:
Doxycycline
100mg twice daily
or
Co-trimoxazole
960mg oral twice daily (for children under 12 years of age
sulfamethoxazole
40mg/kg and trimethoprim 8mg/kg oral daily)
Other
exposed persons should be monitored and asked to self-record temperature tw=
ice
daily
for 21 days and to report immediately for medical attention in the event of
febrile
illness (temperature > 38 degrees C) or development of
cough.
On
the following page of these UK HPA guidelines (page 10 of 20) antibiotic
prophylaxis
of
frontline workers is addressed as follows: Section 2.6, titled
“Protection of frontline
workers”,
defines frontline workers as including “all emergency staff involved =
in
management at the scene of a release, and staff involved=
in
the care of patients.”
Section
2.6.2 titled “Antibiotic Prophylaxis” provides the following
verbatim guidelines:
“Frontline
workers entering the exposed zone and others in the exposed area should
be
offered antibiotic prophylaxis (see 2.4).
Although
person-to-person transmission is rare and there is little evidence of autop=
sy
transmission
(glanders only), antibiotic prophylaxis may be considered for workers
involved
in decontamination of exposed workers or management of patients, or
mortuary staff who handle the deceased.
prophylaxis
should be taken on an individual basis according to duration and degree
of
potential exposure, and taking into account the availability and side effec=
ts
of
prophylactic treatments.
In
addition frontline workers involved at the scene of release and healthcare
workers
and
mortuary staff involved in the management of cases should be advised that if
they
develop
febrile disease they should always mention their exposure on seeking medica=
l
attention
(see 2.4.2).”
(Note:
This above-referenced Section 2.4.2 is titled: “Monitoring of exposed
persons”.
It
reads as follows: “Anyone who is known to have been exposed to a
deliberate release
of
either organisms may be at lifelong risk and sho=
uld be
advised always to bring this to
the
attention of any doctor they consult subsequently for a febrile
illness.”).
In
2004 the Task Force on Biological and Chemical Agents Threats (BICHAT),
Public
Health Directorate, European Commission,
in
Eurosurveillance ( www.eurosurveillance.org) volume 9 issue 12; pages 1-6
titled:
“BICHAT Guidelines for the Clinical Management of Glanders and
Melioidosis
and Bioterrorism-Related Glanders and Melioidosis”=
. They stated: “Post-exposure
prophylaxis
with trimethoprim-sulfamethoxazole (co-trimoxazole) is recommended in
case
of a biological attack, although this is based on experimental data: but the
utility of
post-exposure
prophylaxis in humans is still discussed.” (No dosage or duration of =
co-
trimoxazole
was stated for PEP by the authors).
A
multi-organizational committee in the
a
consensus on post-exposure prophylaxis (PEP) for glanders (Burkholderia mal=
lei)
following a deliberate release (bioterrorism or biowarfa=
re). Such a committee should
include,
but not be limited to, representatives from HHS (CDC, FDA, NIH, PHECME),
DHS
(S& T, others), DoD (USAMRIID, USUHS, others), Infectious Disease Socie=
ty
of
America
(IDSA) State and City Health Departments (e.g., NYC DHMH, others), and
other subject matter experts and involved stakeholders.<=
/span>
Daniel
R. Lucey MD, MPH
EROne
Institute, Department of Emergency Medicine,
Adjunct
Professor of Microbiology and Immunology
DRL23@Georgetown.edu