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The Journal of TRAUMA威 Injury, Infection, and Critical Care
Epidemiology of Infections Associated With Combat-Related
Injuries in Iraq and Afghanistan
Clinton K. Murray, MD
Enhanced medical training of front
line medical personnel, personal protective equipment, and the presence of far
forward surgical assets have improved the
survival of casualties in the current wars
in Iraq and Afghanistan. As such, casualties
are at higher risk of infectious complications of their injuries including sepsis,
which was a noted killer of casualties in
previous wars. During the current conflicts, military personnel who develop
combat-related injuries are at substantial
risk of developing infections with multidrug resistant bacteria. Herein, we describe the bacteriology of combat-related
injuries in Operation Iraqi Freedom and
Operation Enduring Freedom that develop infections with particular attention
to injuries of the extremities, central
nervous system, abdomen and thorax,
head and neck, and burns. In addition,
the likely sources of combat-related injuries with multidrug resistant bacteria infections are explored.
Key Words: Iraq, Afghanistan, Infection, Combat.
J Trauma. 2008;64:S232–S238.
B
y September 30, 2006, approximately 1.4 million military
personnel had been deployed to Iraq and Afghanistan in
support of Operation Iraqi Freedom (OIF) and Operation
Enduring Freedom (OEF) (http://www1.va.gov/opa/fact/docs/
amwars.pdf, accessed June 14, 2007). In total, 29,531 were
wounded in action, of which 13,514 did not return to duty
(http://www.defenselink.mil/news/casualty.pdf, accessed September 21, 2007). The number of casualties died of wounds has
gradually declined from 8% in World War I, to 4.5% in World
War II, 2.5% in Korea, 3.6% in Vietnam, 2.1% in Desert storm,
and 6.4% in Somalia.1 The total number of died of wounds has
not yet been determined for OIF/OEF. Deployment of forward
surgical assets, rapid evacuation to medical care, enhanced training and expertise of combat medics and corpsmen, and improved body armor has culminated in a greater number of
casualties surviving initial injuries.
Extremity injuries account for the majority of wounds
(⬃65%), followed by head and neck (⬃15%), thorax
(⬃10%), and abdomen (⬃7%). This has remained stable
throughout the last century of warfare and during
OIF/OEF.2– 6 Historically, burns complicate 5% to 10% of
combat casualties; this has been true in OIF/OEF.7,8 Although there are differences between combat theaters and
over time as individual theaters mature, wounding is most
frequently caused by explosive devices.4,9,10 Gunshots,
Submitted for publication November 29, 2007.
Accepted for publication November 29, 2007.
Copyright © 2008 by Lippincott Williams & Wilkins
From the Brooke Army Medical Center, Fort Sam Houston, Texas.
The views expressed herein are those of the author and do not reflect
the official policy or position of the Department of the Army, Department of
Defense, or the US Government. This work was prepared as part of their
official duties and, as such, there is no copyright to be transferred.
Address for reprints: Clinton K. Murray, MD, MAJ, MC, USA, Infectious
Disease Service (MCHE-MDI), Brooke Army Medical Center, 3851 Roger Brooke
Drive, Fort Sam Houston, TX 78234; email: [email protected].
DOI: 10.1097/TA.0b013e318163c3f5
S232
grenades (including rocket-propelled), and mortars are
also responsible for a number of injuries. Patients typically
suffer multiple injuries, involving, on average, 1.6 different body parts.4 Explosive devices typically result in a
greater number of injury sites and greater severity of
injuries.
Despite our extensive knowledge of wounding patterns, we
have not adequately characterized the trends of infectious complications and associated outcomes of personnel injured in OIF/
OEF. During the Vietnam War, sepsis was the third leading
cause of death for combat casualties in theater.11 Among the
casualties of the Vietnam War, 2% to 4% developed wound
infections during hospitalization in that country. Data regarding
infections that developed after transportation out of theater are
more difficult to describe.12 Factors influencing the development of wound infections in a combat theater include wound
type and severity, the presence of embedded foreign material or
fragments (such as soldier’s clothing, dirt, and debris), evacuation time from point of injury to medical care, initiation of
antimicrobial agents, adequacy of initial wound debridement,
immediate wound care, definitive surgical care, rehabilitative
care, prior antimicrobial pressure, and the presence of nosocomial pathogens, (especially multidrug resistant pathogens) at
treatment facilities. The appropriate management of injury and
subsequent infection should be influenced by the mechanism
and type of injury, whether caused by low- or high-velocity
weaponry, mines, mortars, or explosive devices. Some systems,
such as mines and other explosive devices, can increase the risk
of infection caused by contamination of wounds from ground
material or other matter placed in the devices (e.g. animal carcasses, discarded dirty syringes, or fecal material). Although it
has been argued that the heat generated from firing high-velocity
weapons sterilizes bullets, this has proven not to be true.13
Overall, the management of combat casualties and finding methods to prevent infections is challenging to healthcare providers
throughout the military medical system.
March Supplement 2008
Infections of Combat Casualties-OIF/OEF Epidemiology
Levels of Medical Care
Medical care capability increases as a casualty is transported from point of injury to level (formerly echelon) I
through level III and outside the combat zone to level IV and
V (Table 1). Level I provides care as close as possible to the
time of injury, and consists of immediate stabilization and
evacuation to an initial aid station. Level II offers short-term
holding capacity and initial resuscition.3 This level of care is
currently subdivided into IIa and IIb, reflecting the absence or
presence of acute, life-saving surgical care. The Army can
augment a level II facility with a Forward Surgical Team
(FST).14 The Navy supports the Marines with Forward Resuscitative Surgical Systems to improve care at forward Surgical Shock Trauma Platoons.15 The Air Force has Mobile
Field Surgical Teams (MFST) to provide level II surgical
care. Level III, such as the Army’s Combat Support Hospital
(CSH), the Air Force Theater Hospital (AFTH), and Navy’s
hospital ship that provided care during the early stages of
OIF, supply complete resuscitative and hospital care. Assets
at this level of care include a myriad of surgical specialties
and support and are equivalent to a well-staffed community
hospital.16 Care provided at level IV during the current conflict is delivered at the Landstuhl Regional Medical Center,
Germany, rendering more definitive surgical care outside the
combat zone.6 Level V care is the most definitive rehabilitative and tertiary level of care and is provided in military and
Veterans Affairs medical centers located in the United States.
Medical care within the combat theater is provided to
both US and non-US personnel, including coalition forces,
host nation personnel, and detainees.17 The AFTH at Balad
Air Base, Iraq, had 10,953 total hospital admissions between
September 2004 and August 2006.18 Of these admissions,
4,323 were not US or coalition patients. Typically, US and
coalition forces are evacuated out of country in as little as 48
to 72 hours from time of injury in Iraq. Usually, evacuation
time to the patient’s final US facility is around 7 days. This
contrasts sharply to evacuation times in many previous US
conflicts.18,19 Non-US personnel receive therapy at level III
facilities until they are stable for transfer to a local healthcare
facility or until care is completed, which take weeks.20,21
sualties in these US facilities included multidrug resistant
P. aeruginosa and Klebsiella pneumoniae. Infections with
multidrug resistant bacteria were also reported on the
USNS Comfort at the beginning of OIF, mostly among
non-US personnel.25 A total of 211 trauma patients were
managed from March to May 2003 of which 56 were
infected. Of these infected patients, 85% were Iraqi, with
an average of 4.2 days elapsing from injury to presenting
to the Comfort. Sites of infection were wounds in 84% of
cases and blood in 36%. The most common pathogens
recovered were ABC (33%), Escherichia coli (14%), and
P. aeruginosa (14%). Assessments of bacteria from blood,
urine, wound and other sites during 2003 and 2004 at a
CSH in Iraq revealed a preponderance of gram-positive
bacteria among US patients.26 In contrast, non-US patients
mostly had gram-negative bacteria, including P. aeruginosa, K. pneumoniae, E. coli, and ABC, largely multidrug
resistant in nature.
One of the most disconcerting facts about the bacteria
complicating combat casualties is their increasing antimicrobial resistance.27,28 Between 2002 and 2005, in ABC, P.
aeruginosa, and K. pneumoniae there was increased resistance to nearly all antibiotics tested at one treatment
facility.28 This has resulted in a steady decline in the number
of available antimicrobial agents. In ABC isolates collected
between 2003 and 2005 in a US military treatment facility,
the difference in broad spectrum antimicrobial resistance between personnel injured in OIF/OEF and nondeployed patients was statistically significant, with higher resistance in
those isolates from OIF/OEF injuries.27 Over time, resistance
increased against all antimicrobial agents tested; however,
only imipenem resistance was statistically significant at the
end of the study period in comparison to the beginning (56%
vs. 87% susceptible). In isolates recovered from deployed
personnel, only colistin and minocycline agents were effective more than 75% of the time. Minocycline is not currently
available in the United States in an intravenous form, limiting
its application in the severely ill. Colistin is associated with
toxicity and ABC can develop resistance during treatment
with this agent.
Infectious Complications of Combat Trauma
Wound Bacteriology
Staphylococcus aureus and aerobic gram-negative bacteria such as Pseudomonas aeruginosa have traditionally
complicated battlefield injuries.11,22,23 Near the early stages
of OIF/OEF, there was a notable increase in casualties
developing infections with resistant bacteria (multidrug
resistant organisms such as Acinetobacter baumannii calcoaceticus complex (ABC).24 At one US military treatment facility, the incidence of blood-stream infection with
ABC in 2005 was 0.3 cases per 1,000 admissions in contrast to 2002, when the incidence was 0.087 cases per
1,000 admissions (personal communication, Kim Moran).
Other notable gram-negative bacteria infecting combat caVolume 64 • Number 3
Extremity Injuries
Extremity injuries have been seen in the greatest number
of casualties from OIF/OEF, but small single hospital reviews
suggest that a large percentage of these wounds are complicated by infections. Data obtained from Brooke Army Medical Center reveal that between January and June of 2006, 223
OIF/OEF persons were evaluated at Brooke Army Medical
Center with 66 (30%) evaluated for orthopedic-related
trauma, of which 26 (40%) received courses of antibiotics for
various bacteria, including ABC (13), Klebsiella spp. (9), P.
aeruginosa (6), Enterobacter spp. (5), and methicillin resistant S. aureus (MRSA) (6). Antibiotics included expensive
and potentially toxic medications such as colistin, imipenemS233
S234
Level II
Level III
Level IV
Level V
Point of care: self-aid, Army: treatment platoon within a medical company Army: combat support hospital (CSH) Army: field hospitals Care within the United
buddy aid, combat
(IIa) that can be augmented with a Forward
and general
States
lifesaver, combat
Surgical Team (FST) (IIb)
hospitals have
medic, corpsman
been replaced by
CSH
Army: battalion aid
Air Force: Mobile Field Surgical Team (MFST) (IIb) Air Force: EMEDS⫹25; Air Force
Outside combat
station (BAS)
that can be augmented with Expeditionary
Theater Hospital
zone facility:
Medical Support (EMEDS) or Small Portable
Landstuhl,
Expeditionary Aeromedical Rapid Response
Germany
(SPEARR) team
Marines: Shock
Marines: Surgical Company with Forward
Navy: hospital ships
Trauma Platoon
Resuscitative Surgical System (FRSS) (IIb)
(STP)
Point of care:
Increased medical capacity with limited inpatient
Highest level of medical care within a Definitive medical
Ultimate treatment
immediate first aid
bed space
combat zone
and surgical care
capability
on the scene;
along with
including early
convalescent care
tourniquet
outside of the
Battalion aid station:
Basic primary care with life saving surgical support Resuscitation, initial surgery,
combat zone
triage, treatment,
Army must augment the medical company for
postoperative care, return to duty
evacuation
surgical support
or evacuation
No holding capacity
Holding capacity (72 hours)
Inpatient beds with holding capacity Permanent or
Includes Department of
(CSH, 250–300 beds; Fleet hospital, semipermanent
Defense hospitals
500 beds; Hospital ship, 1,000
hospital
and Department of
beds; EMEDS⫹25, 25 beds)
Veterans Affairs
Blood support (type-O or whole blood donation)
Surgical subspecialists
hospitals
X-ray capability
Typically modular
Dental
Intensive care units
Basic laboratory
Operating rooms
Basic pharmacy
Blood bank
Laboratory support
X-ray/CT scan
Physical therapy
Pharmacy
Large footprint- CSH ⬃30 acres
* Formerly termed echelons.
Unique
features
Purpose
Facility
Level I
Table 1 Levels* of Medical Care Provided by the US Military
The Journal of TRAUMA威 Injury, Infection, and Critical Care
March Supplement 2008
Infections of Combat Casualties-OIF/OEF Epidemiology
cilastatin, and vancomycin for extended periods of time.
Another study evaluated 62 open tibial fractures in combat
casualties injured between 2003 and 2006. This study identified 40 patients with type III fractures, in whom 35 had data
available for analysis.29 Twenty-seven of the 35 patients had
at least one organism present in initial deep wound cultures at
admission. The most frequently identified pathogens were
ABC, Enterobacter spp, and P. aeruginosa. Thirteen of the
35 patients had healing times longer than 9 months, which
appeared to be associated with infections. None of the gramnegative bacteria identified in the initial wounds were recovered again at the time of repeat operation; however, all
patients had at least one staphylococcal organism and three
had P. aeruginosa at that time. Five of 35 patients ultimately
required limb amputation, with infectious complications cited
as the reason in four. Interestingly, another study early in the
conflict (2001–2003) out of Afghanistan assessed 52 casualties with orthopedic injuries revealed only a 3.8% infection
rate.30 One patient was infected with Pseudomonas and a
second was infected with Acinetobacter and MRSA. In an
unpublished study that assessed osteomyelitis among combat
casualties from OIF/OEF from 2003 to 2006, 110 patients
with 139 hospitalizations were identified (personal communication, CKM). Ninety-nine of these patients had lower
extremity, 44 had upper extremity, and two had axial injuries.
The pathogens initially noted in the wounds were ABC
(71%), K. pneumoniae (24%), P. aeruginosa (26%), methicillin susceptible S. aureus (MSSA) (15%), and MRSA
(10%). After adequate surgical and antimicrobial therapy,
those with recurrent or relapses had a clear transition from
predominantly gram-negative bacteria to gram-positive bacterial infections. ABC, K. pneumoniae, and P. aeruginosa
each represented 5% of these latter infections, whereas
MSSA produced 22% and MRSA 28%.
Although ABC has received substantial emphasis as a
key pathogen complicating combat casualty care, associated
outcomes reveal low virulence. In an assessment of 232
active duty soldiers (151 were OIF/OEF) admitted with injuries to one military treatment facility between March 2003
and May 2004, ABC was recovered in 48 of 84 soldiers
cultured, of which 30 were clinical infections, including 23
with osteomyelitis or wound infections or both. In this group,
all patients cleared their infection even if they received inadequate antimicrobial therapy.31
Unfortunately, because of the scarcity of data regarding
care and associated infectious complications of non-US personnel treated in Iraq or Afghanistan, it is difficult to determine the extent of infection in that population. Among
non-US personnel treated between September 2004 and August 2006 at the AFTH in Iraq, there were 134 extremity
injuries with vascular damage. In that report, there were five
wound infections among 192 major vascular injuries.18 Another study assessed 88 injuries to non-US personnel treated
at the AFTH that included 59 with upper or lower extremity
wounds treated with standard surgical techniques, antibiotics,
Volume 64 • Number 3
and wound VAC.20 There were no reported infectious complications of these extremity injuries, although follow-up was
limited.
Central Nervous System (CNS) Injuries
Numerous casualties have had CNS penetrating trauma
during OIF/OEF.32 Although there have been no systematic
evaluations of the infectious complications of these wounds,
there are two case reports of multidrug resistant bacteria CNS
infections.33,34 Both describe ABC infections that cleared
with appropriate management including the use of broad
spectrum antimicrobial agents.
Head and Neck Injuries
Rates of infectious complications for US head and neck
casualties has not been described. Among Iraqi patients
treated at an Iraqi facility between September 2003 and August 2004 there were 100 patients with multiple and comminuted mandibular fractures.35 Fifty-three injuries were caused
by missiles and 54 patients had comminuted fractures. Three
of the patients with comminuted and one with multiple fractures developed infection, for an overall infection rate of 4%.
The specific bacteria infecting the wounds were not reported.
Of the infected injuries, three were from missiles and one
from a motor vehicle crash.
Thoracic and Abdominal Cavity Injuries
An assessment of casualties treated on the USNS Comfort during the early stages of OIF revealed on multivariate
analysis that abdominal injuries had an odds ration of 2.7 for
developing an infection whereas extremity injuries had a 2.4
odds ratio.25 The bacteria complicating these injuries were
multidrug resistant and included ABC and P. aeruginosa.
Thoracic injury was not associated with infection on univariate or multivariate analysis. There were 175 (5.1%) colon
and rectal injuries among 3,442 patients treated between
September 2003 and December 2004 at a CSH in Iraq.36
Sepsis developed in 27 patients (16%) and had significant
impact upon mortality. Specific bacterial pathogens were not
reported in that report.
Burn Infections
Burn patients have comprised approximately 5% of US
military casualties in OIF/OEF.7,8 Since the onset of these
conflicts, there have been numerous burn casualties infected
with multidrug resistant bacteria. A retrospective study of all
patients admitted to the US Army Institute of Surgical Research burn center from January 2003 to May 2006 was
undertaken to evaluated the impact of bacteremia in that
population.37 One hundred twenty-nine of 1,258 patients admitted to the burn center became bacteremic during their
hospitalization. Fifty-one of 414 OIF/OEF burn patients had
episodes of bacteremia. Ninety-two of the 129 burn patients
had bacteremia with P. aeruginosa, K. pneumoniae, S. aureus, and ABC. Bacteremia with K. pneumoniae was indeS235
The Journal of TRAUMA威 Injury, Infection, and Critical Care
pendently associated with a statistically significant increase
in mortality and prolonged ventilator use when controlled for
age and total body surface area burned. This was not true for
the other pathogens. Infectious outcomes for OIF/OEF burn
injuries did not differ from the outcomes of non-military burn
patients.
The incidence of ABC infection increased from 2.3% in
2001 to 11.9% in 2005 at the US Army Institute of Surgical
Research.38 A retrospective study examined the clinical impact of ABC.38 Among the 802 patients included in this
study, 59 patients were infected between January 2003 and
November 2005, with an additional 52 patients found to be
colonized with ABC during that time period. Bacteremia was
the most common type of infection (31 of 59 infections). In
general, patients with ABC infection had more severe burns,
more comorbidities, and longer lengths of stay than those
patients with colonization or no ABC recovered. ABC infection was associated with 22% mortality in contrast to 7.7% in
those without infection; however, on multivariant analysis
there was no mortality attributable to ABC. Most of the ABC
isolates had broad spectrum antimicrobial resistance; however, there was no statistical difference in mortality between
those treated with effective antimicrobial agents (24.5%) versus those who were not (10%) ( p ⫽ 0.432).
Epidemiologic Source of MDRO Infections
Traditionally, gram-positive bacteria and anaerobes predominate in wounds at the time of injury, and are replaced by
gram-negative bacteria after 5 to 7 days, followed by Streptococci and Staphylococci after 2 to 3 weeks.39 – 41 Resistant
bacteria complicated wounds of combat casualties after the
use of prophylactic or preemptive antibiotics given at the time
of injury in previous wars.23,42– 44 Proposed sources of these
multidrug resistant bacteria include preexisting colonization
of the patient at the time of injury, inoculation into the
wounds at the time of the injury from environmental contamination, and nosocomial transmission during the care of patients within the military healthcare system.
It is known that a person’s skin is colonized with approximately 180 different types of bacteria at any one time.45
Typically, 25% of persons are colonized with S. aureus, and
3% with MRSA. This is true within our military population,
and it has been recognized that colonization can lead to
infections.46 S. aureus, including MRSA, are associated with
colonization at the time of injury and may be introduced into
the wound directly from skin colonization.47 MRSA is also a
known nosocomial pathogen.
Several studies have investigated whether ABC colonizes the skin of casualties before injury. An assessment of
healthy soldiers with no prior deployment history visiting a
troop medical clinic in the United States revealed soldiers
were occasionally colonized with ABC, but these isolates
were not genetically or phenotypically related to the bacteria
recovered from combat casualties of OIF/OEF.48 In addition,
cultures of noninjured military personnel in Iraq or upon
S236
arrival to Germany after leaving Iraq without prior exposure
to theater healthcare facilities have not recovered ABC.49,50
Therefore, it is unlikely that casualties are colonized with
ABC before injury.
One study attempted to evaluate if bacteria from environmental contamination were inoculated into the wounds at
the time of injury.47 Forty-nine casualties with 61 wounds
were screened at the CSH in Baghdad for wound contamination at the time of injury. Most bacteria recovered were
gram-positive (93%). There were only three gram-negative
bacteria detected; none were multidrug resistant and this
group did not include P. aeruginosa or ABC. Although inconclusive based on the small size of the study mentioned, it
is unlikely that patients have their wounds inoculated with
environmental material such as dirt or debris containing multidrug resistant gram-negative bacteria at the time of injury.
Another possibility for cause of resistant gram-negative
bacteria infecting combat casualties is nosocomial transmission. At the onset of OIF/OEF, ABC, and other multidrug
resistant bacteria were increasingly being described worldwide as nosocomial pathogens. ABC has been reported to
infect injuries of noncombat trauma victims.51,52 In addition,
ABC was noted to be a nosocomial pathogen in countries
surrounding Iraq, including Turkey, Saudi Arabia, and
Kuwait.53,54 In Jerusalem, recovery of ABC went from 6% of
nosocomial bacteremia cases in 1999 to 17% in 2002, representing the most common pathogen producing bacteremia in
one hospital.55 An analysis of the bacteria recovered from a
CSH in Baghdad during 2003 and 2004 revealed that non-US
personnel had more multidrug resistant gram-negative bacteria than US personnel.26 This is notable, as non-US patients
spend prolonged periods of time within the CSH, possibly
serving as a reservoir of these bacteria for nosocomial transmission, especially in the combat zone where implementation
of infection control procedures can often be challenging.
Scott et al. performed a key study that supports the role
of nosocomial transmission contributing to infections of combat casualties with multidrug resistant bacteria.50 That study
screened dirt obtained in Iraq and environmental samples
from treatment areas within CSHs in Iraq for the presence of
ABC. It also attempted to link any environmental samples
with ABC isolates recovered from patients cared for in Iraq,
on the USNS Comfort, at Landstuhl, or WRAMC or both. All
field hospitals screened had ABC recovered from treatment
areas. By molecular typing, there were 66 different ABC
strains noted among 170 clinical isolates and 25 different
strains among 34 environmental samples. Although one could
not point to one CSH or one particular strain as the cause of
the outbreak, there were five cluster groups that matched
environmental field hospital isolates to patient isolates. The
largest cluster included 45 isolates from 43 patients at four
different US military hospitals that matched an isolate recovered from an operating room at a CSH. That cluster included
non-US patients and US patients with no deployment history
that were OIF and non-OIF inpatients with no deployment
March Supplement 2008
Infections of Combat Casualties-OIF/OEF Epidemiology
history in military hospitals in the US. These isolates were
related to isolates from the United Kingdom.56 In addition,
ABC strains were similar to some of the isolates previously
found infecting patients in Europe.57 Isolates have also been
recovered from hospitals taking care of Canadian soldiers
injured in Afghanistan and evacuated to Canadian hospitals.58
Although ABC does not appear to cause great harm in
healthy military personnel, when transferred too older or immunosuppressed ill inpatients, this bacteria can cause death.59 In the
US military burn unit, despite aggressive infection control measures, 50 patients (6% of all admissions during the study period)
acquired ABC colonization or infection during their hospital
stay, suggesting nosocomial spread.38
At this time it is not clear what is leading to the increasing antimicrobial resistance in bacteria recovered from our
military treatment facilities. One of the major concerns is that
greater use of broad spectrum antibiotics to empirically treat
wounds of combat casualties in the combat zone or along the
evacuation chain is resulting in selection of more resistant
pathogens. In addition, the use of broader spectrum agents
used to treat multidrug resistant infections of non-US personnel within our hospitals in Iraq is likely driving increasing
resistance of bacteria in this reservoir of patients for potential
nosocomial transmission.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
CONCLUSIONS
As the care of combat casualties continues to improve,
allowing enhanced survival after initial injuries, infectious complications will remain a major cause of short- and long-term
morbidity. At this time, casualties are undergoing therapy for
wounds that are often colonized or infected with multidrug
resistant bacteria such as ABC, P. aeruginosa, K. pneumoniae,
and S. aureus. The role of nosocomial transmission and the over
use of broad spectrum antibiotics resulting in more resistant
pathogens should not be ignored. Continuing to improve our
understanding of wounding patterns, infectious complications,
and modes of transmission will improve care for casualties.
17.
18.
19.
20.
21.
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March Supplement 2008