Naval Respiratory Disease Laboratory
DoD Center for Deployment Health Research
Naval Health Research Center
GAS Surveillance at U.S. Military Basic
Training Camps
1998-2006
CDR Kevin L. Russell, MC, USN
Mr. Tony Hawksworth
LCDR Dennis Faix
CDR Margaret Ryan
Presentation to the Defense Health Board
5 December, 2006
Little Creek NAB, Norfolk, VA
Outline
• History of Group A Streptococcus in Military Populations
• Relevant Instructions
• Current Chemoprophylaxis Regimens at Recruit Training Centers
• Service-Specific Implemented Surveillance Initiatives
• GAS Surveillance Initiatives by the Naval Health Research Center Respiratory
Disease Laboratory
– Antibiotic resistance patterns—geographic and temporal distribution
– Strain identification—geographic and temporal distribution
– Associations between strain, antibiotic resistance, and site
• Recent GAS Outbreaks
• Recent Fatalities with Presumed GAS Etiology
• Conclusions
History
• Long recognized as an important pathogen contributing to morbidity within Armed
Forces
– WWII: 1,600 recognized cases of streptococcal illness for every 108 cases of malaria1
• Elegant transmission studies conducted in the 1940s
– Demonstrated predominance of person-to-person transmission1,2
– Nasal carriage individuals more infectious than pharyngeal carriage individuals3
– Carriage common; contributions of sick call exposures to transmission1
• Antibiotic era ensued
– Sulfonamides, then penicillins were tested4
– Near complete control of illness, dramatic reduction in sequelae, and reduced carrier state (pens) demonstrated4
• HOWEVER, treatment regimens still often proved ineffective because:
– Spread from asymptomatic individuals or carriers
– Avoidance of medical care; not presenting for treatment
• Mass chemoprophylaxis became widespread at Recruit Training Centers by the 1950s.
1Coburn AFY, Donald C. The Epidemiology of Hemolytic Streptococcus During World War II in the United States. Baltimore, MD: Waverly Press Inc; 1949. 2Wannamaker LW. The epidemiology of streptococcal infections. In: McCarty M, ed. Streptococcal Infections. New York, NY: Columbia University Press; 1954. 3Hambuger M Jr, Lemon HM. The problem of the dangerous carrier of hemolytic streptococci. III. The chemotherapeutic control of nasal carriers. JAMA. 1946;130:836. 4Various: Denny FW, Wannamaker LW, Seal JR, Bernstein SH and others. 1951-1954.
• Thomas and colleagues recommended streptococcal surveillance programs continue1
– data generated should “influence prophylaxis decisions”
– 1.2 M units of benzathine penicillin G IM regimen adopted
• Subsequent Decades demonstrated:
– Mass prophylaxis was effective in decreasing infections and sequelae
– When mass efforts stop, recurrences often occur
– Individuals allergic to penicillin should receive alternate chemoprophylaxis2
– History repeating itself
• NTC San Diego; mass prophylaxis until 1980, discontinued; 1986-1987, 10 cases of ARF, 3 cases carditis, 6 cases GAS
pneumonia3
• Army: low incidence of ARF, discontinued mass prophylaxis in 1970s; 1980s, GAS-related illnesses identified: ARF, carditis,
carriage >70%4
• Gunzenhauser demonstrated that with institution of BPG prophylaxis, ARDs fell 64%...not all explainable by GAS.
Suggesting effective against pathogens other than GAS4
– IMPORTANT PARAGIGM SHIFT: BPG indicated to decrease rates of GAS pharyngitis, despite rarity of sequelae
1Thomas RJ, Conwill DE, et al. Peniciillin prophylaxis for streptococcal infections in the United States Navy and Marine Corps recruit camps, 1951-1985. Rev Infect Dis. 1988;10(1):125-130. 2Gray GC et al. Hyperendemic Streptococcus pyogenes infection despite prophylaxis with penicillin G benzathine. N Engl J Med. 1991;325(2):92-97. 3Wallace et al. The return of acute rheumatic fever in young adults. JAMA. 1989;262(18):2557-2561. 4Gunzenhauser JD et al. Broad and persistent effects of benzathine penicillin G in the prevention of febrile, acute respiratory disease. J Infect Dis. 1992;166(2):365-373.
History
– History repeating itself (CONT)
• Despite year-round and 2X per training prophylaxis, 2002 outbreak of 127 GAS pneumonias in Marine recruits in San Diego1
– 30% reported as “Pen allergic”; less than 20% compliance with Erythromycin alternate chemoprophylaxis
– Illnesses began at around day 20-21 post BPG injection
• Erythromycin demonstrated effective in 2X daily dose of 250 mg2
• Azithromycin is also highly efficacious with potentially better compliance3
1Crum NF, Russell KL, Kaplan EL et al. Pneumonia outbreak associated with group A streptococcus species at a military traiing facility. Clin Infect Dis. 2005;40(4):511-518.
2Fujikawa J et al. Oral erythromycin prophylaxis against Streptococcus pyogenes infection in penicillin-allergic military recruits: A randomized clinical trial. J Infect Dis. 1992;166(1):162-165.\ 3Gray GC et al. Weekly oral azithromycin as prophylaxis for agents causing acute respiratory disease. Clin Infect Dis. 1998;26(1):103-110.
History
Streptococcal Pharyngitis Rates in Navy Recruits
(cases/1000 recruits/week)
0
2
4
6
8
10
Oc
t-9
5
Ja
n-9
6
Ap
r-9
6
Ju
l-9
6
Oc
t-9
6
Ja
n-9
7
Ap
r-9
7
Ju
l-9
7
Oc
t-9
7
Ja
n-9
8
Ap
r-9
8
Ju
l-9
8
Oc
t-9
8
Ja
n-9
9
Ap
r-9
9
Use of Bicillin for incoming recruits
Use of Bicillin for late-training recruits
Relevant Correspondences and Instructions
1. AFEB Memorandum of 19 Sept 1983
Selective Streptococcal monitoring programs should be continued in the Navy and Marine Corps recruit facilities
Tailored chemoprophylaxis
Two areas should be studied:
Desirability of a second dose of bicillin four weeks after the first
Occurrence of streptococcal skin infections, particularly in the summer, as justification for bicillin prophylaxis
2. Army regulation 40-562/BUMEDINST 6230.15/Air Force Instruction 48-
110(I)/CG COMDTINST M6230.4F: “Immunizations and
Chemoprophylaxis”. Date: 20 Jan 1995, currently updated version at press.
“it may be required to administer penicillin prophylactically to the entire group to terminate disease transmission”
“Consider penicillin G benzathine (IM, also known as Bicillin LA)”
“Customized approach. ….each Service will develop policies for surveillance and prophylaxis of streptococcal
disease at training centers.”
3. BUMED Instruction 6220.8 (dated 3/16/91); Under BUMED review for revision
– Current guidance: Culture everyone with sore throat
• Sites find this burdensome, and rarely comply
– Action point for decisions on antibiotic prophylaxis based on surveillance at 10 cases per 1,000 recruits per week.
– Suggested Revisions:
• Treat Navy and Marines differently, as “Marine Corps and Navy recruit training is significantly different”
– Marines, calculate GABHS incidence rates by company, and administer only to those that meet criteria
– At RTC, record rates for 2 groups: all recruits, and after the 4th week “second half recruits”
• Follow a “validated clinical prediction scoring system” for culture and treatment, including following morphology—4
criteria
– Fever >100.4
– Absence of cough
– Tender anterior cervical lymphadenopathy
– Tonsillar swelling or exudates
• Graded 1-4 pts.
– 0-1 pts: tested and treated at investigator discretion
– 2-3 pts: Rapid test recommended; also culture for monitoring of culture morphology
– 4 pts: Cultured and empirically treated
Relevant Correspondences and Instructions
GAS Prophylaxis Strategies at Recruit Training Sites
PCN Supply
Mode
Abx Given
PCN Allergic
Mode
Primary abx Targeted Prophylaxis per Surveillance Data
PCN Allergic National Shortage
Mode
Primary abx Targeted Prophylaxis per Surveillance Data
PCN Allergic
Mode Automatic Accesion Dose
Primary abx Automatic Second Dose
PCN Allergic Surveillance
Mode
Primary abx
PCN Allergic
Mode Bicillin
Primary abx Bicillin or Azithromycin
PCN Allergic Oral PCN
Azithromycin
Mode Erythromycin
Primary abx Levaquin
PCN Allergic None
Mode
Primary abx
PCN Allergic
Mode
Primary abx
PCN Allergic
Fort Benning
Fort Jackson
Fort Knox
Fort Leonard Wood
Fort Sill
NSTC Great Lakes
Lackland AFB
MCRD Parris Island
MCRD San Diego
1998 1999 2000
Prophylaxis Mode
Bicillin Supply
Prophylaxis Drug
2005 20062001 2002 2003 2004
NSTC Great Lakes
Data retrieved from NHCGL Weekly Recruit & Student Health Surveillance Report – Nov 10 2006
NSTC Great Lakes Data
Strep Pharyngitis per 1,000 Recruits
0
5
10
15
20
25
30
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51
Calendar Weeks
CY 2005 CY 2006 CY 2004
Ft Jackson Ft Benning
Data retrieved from USACHPPM Acute Respiratory Disease Surveillance System Weekly Summary Report – Nov 2006
Army Data
Ft Leonard Wood Ft Knox
Ft Sill
Data retrieved from USACHPPM Acute Respiratory Disease Surveillance System Weekly Summary Report – Nov 2006
Army Data (cont.)
NHRC GAS Surveillance at U.S. Military Basic Training
Camps
• NHRC instituted surveillance for GAS in 1998
• A systematic sample of GAS-positive clinical isolates are collected from
laboratories at 9 military training sites
• Over 2,000 isolates collected to date
– Antibiotic sensitivity testing is performed on all isolates
– emm gene typing is performed on a subset of isolates
– Implementation of Advanced Diagnostic Methodology helping with throughput
• NHRC also offers support for outbreak response and fatal case investigations
NHRC Respiratory Disease Surveillance Sites
NMC San Diego
Wilford Hall
Great Lakes
Portsmouth
Bethesda
Madigan Army MC
Ft Jackson MCRD Parris Island
Ft Sill
WRAIR Ft Knox
Ft Leonard Wood
MCRD San Diego
S. pyogenes
Viral pathogens
RSV
BUDS
Ft Bragg
Ft Benning
Cape
May
S. pneumoniae
Pneumo vaccine
Pertussis
NHRC GAS Surveillance at U.S. Military Basic Training
Camps
• Barrozo CP, Russell KL, Smith TC, Hawksworth AW, Ryan MA, Gray GC. National
Department of Defense surv3eillance data for antibiotic resistance and emm gene types of
clinical group A streptococcal isolates from eight basic training military sites. J Clin
Microbiol. 2003 Oct;41(10):4808-11.
– 1998-2001: analysis of 692 isolates:
• 44/692 (6.4%) resistant to erythromycin; 34/692 (4.9%) resistant to tetracycline
• Macrolide resistance was associated with geographic site—Lackland AFB
• Erythromycin resistance strongly associated with emm75 isolates (p < 0.0001)
0
50
100
150
200
250
MCRD P
I
NSTC
Gre
at Lak
es
MCRD S
D
Ft. Sill
Lackla
nd AFB
Ft. Ja
ckso
n
Ft. Knox
Ft. Ben
ning
Ft. W
ood
1998
1999
2000
2001
2002
2003
2004
2005
2006
GAS Isolates Received From Each Training Site
1998-2006 (n = 2077)
0%
20%
40%
60%
80%
100%
Perc
en
t o
f Is
ola
tes
Penic
illin
Eryth
rom
ycin
Clin
damyci
n
Tetra
cycl
ine
Levoflo
xaci
n
Vanco
myc
in
Sensitive
Intermediate
Resistant
Antibiotic Resistance Patterns of Clinical
Streptococcus pyogenes Isolates from Military Trainees
n=2077 isolates collected between Feb 1998 and Nov 2006
Pe
rce
nt
of
Iso
late
s
241/2077
(11.6%)
Antibiotic Resistance Patterns of Clinical
Streptococcus pyogenes Isolates Over Time
0%
20%
40%
60%
80%
100%
1998
1999
2000
2001
2002
2003
2004
2005
2006
1998
1999
2000
2001
2002
2003
2004
2005
2006
1998
1999
2000
2001
2002
2003
2004
2005
2006
Sensitive
Intermediate
Resistant
Pe
rce
nt
of
Iso
late
s
Erythromycin Clindamycin Tetracycline
n=2077 isolates collected between Feb 1998 and Nov 2006
143 84 177 371 416 494 115 169 107
Erythromycin Resistance Patterns of Streptococcus
pyogenes Isolates by Recruit Camp Location
0%
20%
40%
60%
80%
100%
Gre
at L
ake
s
MC
RD
-SD
MC
RD
-PI
Ft.
Jac
kso
n
Ft.
Knox
Ft.
L. W
ood
Ft.
Sill
Lackl
and
Ft.
Ben
nin
g
Perc
en
t o
f Is
ola
tes
Sensitive
Intermediate
Resistant
Recruit Camp
n=2077 isolates collected between Feb 1998 and Nov 2006
n = 316 n = 32 n = 655 n = 4 n = 23 n = 463 n = 354 n = 159 n =71
Emm Type Distribution of GAS Isolates Received by Site
1998-2005
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Ft. Ben
ning
Ft. Ja
ckso
n
Ft. Kno
x
Ft. Le
n Wood
Ft. Sill
Gre
at Lake
s
Lack
land
MCRD P
I
MCRD S
D
Other
75
6
5
44/61
3
29
2
12
1
n = 20 n = 4 n = 22 n = 120 n = 103 n = 284 n = 115 n = 394 n = 18
GAS Isolates MCRD-PI
GAS Isolates MCRD-PI with Antibiotic Sensitivities
GAS Isolates LAFB
GAS Isolates LAFB with Antibiotic Sensitivities
GAS Isolates FLW
GAS Isolates FLW with Antibiotic Sensitivities
Erythromycin Resistance of Streptococcus pyogenes
by emm-gene Type
0%
20%
40%
60%
80%
100%
Pe
rce
nt o
f Iso
late
s
1 2 3 5 6 12 29 44/61 75 Other
Sensitive
Intermediate
Resistant
emm-Gene Types
n=1080 emm-gene typed isolates collected between 2/98 and 12/05
n = 67 n = 56 n = 249 n = 66 n = 118 n = 41 n = 125 n = 81 n = 91 n = 186
Recent GAS Outbreaks
MCRD Parris Island: November 2006 • Five recruits with retropharyngeal abscesses
• Reported + GAS in two of these cases – One GAS isolate obtained by NHRC, emm Type 118
Fort Leonard Wood: October 2006 • Short on Bicillin since Summer 2005. No alternative chemoprophylaxis was given until this outbreak.
• Earliest invasive GAS (iGAS) case reported to the Reportable Medical Events System (RMES) on 12 Aug 2006.
• During the week of 2-9 Oct, 12 additional GAS+ cases were reported – Bicillin given
• Starting 28 Oct: All incoming recruits are given oral Pen VK
• 04 Nov: Began giving Bicillin to all current trainees on post
• Testing at NHRC revealed emm Type 5 as most common type. Types 18, 77, and 101 also seen
Fort Knox: August 2006 • Sentinel event: 16 Aug 06, recruit admitted to Ireland Army Hospital (IRACH) for peritonsillar abscess
• Entire unit of index case cultured for GAS: 34% were found to be carriers of GAS
• Two additional GAS+ patients from different units as index case hospitalized during the week of 21 Aug
• Summary of intervention: targeted prophylaxis (Bicillin or Zithromax)
• Testing at NHRC revealed emm Type 5 as most common type. Type 4 also seen
Fort Jackson: • November 2005
• Testing at NHRC revealed emm Type 5 as most common type
Fort Leonard Wood: • October 2005 – February 2006
• Testing at NHRC revealed emm Type 5 as most common type
MCRD Parris Island: • September - November 2005
• Testing at NHRC revealed emm Type 5 as most common type
Recent GAS Outbreaks (Cont)
MCRD-SD, 2002
127 pneumonias, 44% with evidence of GAS
Crum NF, Russell KL, Kaplan EL, Wallace MR, Wu J, Ashtari P, Morris DJ, Hale BR. Pneumonia outbreak associated with Group A streptococcus at a military training facility.
CID 2005;40:511-518.
Recent GAS Fatal Cases
Camp Pendleton, CA: • October 2006
• 1 death
• Testing at NHRC found S. pyogenes emm Type 77
Texas: • March 2006
• 2 deaths
• Testing at NHRC found S. pyogenes emm Type 5 in both cases
Advanced Diagnostics
• Currently certified T-5000 in our new “Advanced Diagnostics
Laboratory”, providing high-throughput diagnostic support
for:
– Respiratory Panel
– Adenovirus
– Influenza (publication pending)
– **Streptococcus pyogenes (PNAS, 2005 May 31;102(22):8012-7)
Conclusions
• Recent increase in GAS morbidity among trainees – at least partly due to shortage of bicillin and subsequent lack of prophylaxis
• Overall Macrolide (erythromycin) resistance of 11.6% (240/2077)
• High macrolide resistance seen in emm Type 75 – decreasing prevalence of emm 75 in recent years
• No temporal or geographical trends in resistance
• Increasing prevalence of emm Type 5 associated with outbreaks, 2005-2006 – associated with most recent outbreaks
– remains largely sensitive to antibiotics
• NHRC passive surveillance of clinical GAS among trainees provides valuable data
QUESTIONS?
COMMENTS?
SUGGESTIONS?
NHRC San Diego,
California
Naval Health Research Center Web Site http://www.nhrc.navy.mil/
Navy Node for the DoD Global Emerging Infections Surveillance and Response Systems
(GEIS)
Back-Pocket Slides
Proportion of GAS Isolates Received
From Each Training Site, 1998-2006 (n = 2077)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1998 1999 2000 2001 2002 2003 2004 2005 2006
Ft. Wood
Ft. Benning
Ft. Knox
Ft. Jackson
Lackland AFB
Ft. Sill
MCRD SD
MCRD PI
NSTC Great Lakes
n = 143 n = 84 n = 177 n = 371 n = 416 n = 494 n = 115 n = 169 n = 107
emm 3
22%
emm 6
11%
emm 44/61
8%
emm 75
8%
emm 1
6%
emm 2
5%
emm 5
6%
emm 12
4%
Other
18%
emm 29
12%
Distribution of emm types among isolates collected from 1998-2005 (n = 1080)
Emm Type Distribution of GAS Isolates Received by Year
1998-2005
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1998 1999 2000 2001 2002 2003 2004 2005
Other
75
6
5
44/61
3
29
2
12
1
n = 143 n = 81 n = 176 n = 362 n = 125 n = 115 n = 26 n = 52
