Invasive Group A Streptococcal Infection

in Children, Florida,1996-2000

December 7, 2005

Zuber D. Mulla, Ph.D.Division of Epidemiology

UT Health Science Center at HoustonAnd

Dept. of OB/GYNTexas Tech University School of Medicine

El Paso, Texas

Sabiha S. Khadim, M.D.University of Miami School of Medicine

Conflicts of Interest

NONE

Introduction

Group A Streptococcus (GAS) or Streptococcus pyogenes

Very important human pathogen

Impetigo, scarlet fever, puerperal fever, pharyngitis, erysipelas

Introduction

Streptococcal toxic-shock syndrome

Necrotizing fasciitis

Septicemia

Septic arthritis

Descriptive Epidemiology

663,000 new cases

163,000 deaths

Carapetis J et al., Lancet Infectious Diseases, November 2005

Descriptive Epidemiology

>10 million noninvasive infections a year in the U.S.

10,000 cases of invasive GAS disease (U.S. annual incidence = 3.7 per 100,000)

4 times that of meningococcal disease

Biology

Group A streptococci are gram-positive, non-spore forming, facultative anaerobic bacteria

Pairs and chains

Beta-hemolytic: complete lysis of red blood cells surrounding the colony

Biology

M protein, phagocytosis

Spe

Superantigens, T cells, cytokines, shock

Necrotizing fasciitis

Deep-seated infection of subcutaneous tissue

Rapidly progressive

Described in 1924 by Meleney

Risk Factors for Invasive Disease

Chickenpox

Old age

Immunosuppression

Diabetes (peripheral vascular disease soft tissue necrosis)

Risk Factors for Invasive Disease

Chronic pulmonary & heart disease

NSAIDs (?)

Skin lesions

Blacks and Native Americans

Predictors of Hospital Mortality

STSS

Age>65 years

Shock/Hypotension

Limitations

Small N

Single hospital

Southern Medical Journal, August 2003

Zuber D. Mulla, Ph.D.

Paul E. Leaverton, Ph.D.

Steven T. Wiersma, M.D., M.P.H.

Support for clindamycin study

Florida Department of Health

Bureau of Epidemiology, Tallahassee

Study Question

What are the clinical and epidemiologic features of children hospitalized for IGASI in Florida during a four-year period?

Materials and Methods

Source of data

Mid 1996

Surveillance data

Case report form

Surveillance Case Definition

Isolation of GAS from normally sterile site (e.g., blood, cerebrospinal fluid, joint fluid, pleural fluid, or pericardial fluid), and a clinically-compatible presentation.

The definition of a clinically-compatible presentation is as follows: Pneumonia, bacteremia in association with cutaneous infection (e.g., cellulitis, erysipelas, or infection of a surgical or nonsurgical wound), deep soft-tissue infection (e.g., myositis), meningitis, peritonitis, osteomyelitis, septic arthritis, postpartum sepsis, neonatal sepsis, and nonfocal bacteremia.

Surveillance Case Definition

The original study also included cases of necrotizing fasciitis if GAS was isolated from a nonsterile site.

CDC’s ABCs Program

Cases

Hospitalized throughout Florida

Admitted between August 1996 and August 2000

25 children: 0 to 17 years of age

Data Analysis

Line listing

Frequency distributions

Crude pediatric IGASI hospital mortality compared to crude adult IGASI rate using Fisher’s exact test

Results

Figure 1. Reported Incidence of Invasive Group A Streptoccal Infection by Age, Florida, USA, 1997-2000

0

0.3

0.6

0.9

1.2

1.5

1.8

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 >79

Age (years)

Inci

denc

e pe

r 100

,000

Age Number0 to 6 weeks 3

7 weeks to 51 weeks 31 year to 3 years 44 years to 9 years 9

10 years to 14 years 415 years to 17 years 2

TOTAL 25

Age Distribution, 25 cases

Results

Boys: 14 cases (56%)

GAS bacteremia: 18 cases

IVIG

ID Yr Age Sex Race Clinical Presentation Under-lying

Condi-tion

Out-come

1 96 4 w F Asian Primary bacteremia None Lived

2 97 13 y M Black Primary bacteremia NA Lived

3 97 2 m F White Low appetite, secondary bacteremia

None Lived

4 98 2 y M NA Pneumonia, pleural effusion, secondary bacteremia, streptococcal toxic shock syndrome

None Lived

ID Yr Age Sex Race Clinical Presentation Under-lying

Condi-tion

Out-come

5 98 4 y F Black Impetigo, secondary bacteremia

None Lived

6 98 7 y M Black Cellulitis, necrotizing fasciitis

None Lived

7 98 9 y F White Meningitis None Lived

8 98 16 y

F Black Pharyngitis, secondary bacteremia

Cancer NA

9 98 3 y M Black Septic arthritis, cellulitis, secondary bacteremia

None Lived

ID Yr Age Sex Race Clinical Presentation Under-lying

Condi-tion

Out-come

10 99 4 y M White Pneumonia, secondary bacteremia

None Lived

11 99 1 y M White Otitis media, pharyngitis, pneumonia, secondary bacteremia

Asthma Lived

12 99 8 m M Black Meningoencephalitis, cellulitis, secondary bacteremia

Varicella Lived

13 99 4 y F White Necrotizing fasciitis Varicella Lived

ID Yr Age Sex Race Clinical Presentation Under-lying

Condi-tion

Out-come

14 99 6 y M White Pneumonia, pleural effusion

None Lived

15 99 17 y M White Necrotizing fasciitis, gangrene, cellulitis

NA Lived

16 99 12 y F White Myositis, cellulitis, secondary bacteremia

NA Lived

17 99 3 y M White Osteomyelitis, myositis, secondary bacteremia

None Lived

18 99 4 y M White Cellulitis, septic arthritis

None Lived

ID Yr Age Sex Race Clinical Presentation Under-lying

Condi-tion

Out-come

19 99 6 y F White Pharyngitis, secondary bacteremia

None Died

20 99 5 y F White Infection of nonsurgical wound site

Nonsurgical wound

Lived

21 99 3 w M Black Primary bacteremia None Lived

22 99 10 y M White Osteomyelitis, secondary bacteremia

None Lived

ID Yr Age Sex Race Clinical Presentation Under-lying

Condi-tion

Out-come

23 00 4 w M White Upper respiratory tract infection, secondary bacteremia

None NA

24 00 8 m F Black Pneumonia, secondary bacteremia

NA Lived

25 00 14 y

F Black Primary bacteremia Sickle cell disease

Lived

Crude hospital mortality

Children: 4.4% (1/23)

Adult: 19.5% (40/205)

P (Fisher’s exact two-tailed) = 0.09

Conclusions and Strengths

Low case-fatality rate in children, similar to other pediatric IGASI case series

Current series larger than 11 other previous pediatric case series

Strengths

Davies et al. reported on 24 children ranging in age from 0.03 to 17 years who presented to their institution with IGASI.

One of these patients met definition for probable streptococcal toxic shock syndrome.

None of these cases died and 79% had bacteremia.

Strengths

We report 1 case of streptococcal toxic shock syndrome (Case 4).

Overall, 1 of our 23 cases with a known mortality status expired in hospital.

Approximately 72% of our cases had bacteremia.

Strengths

Data on recent varicella infection was available for 21 of our 25 cases.

2 of the 21 patients (9.5%) had a recent history of varicella infection.

Result is similar to one reported by Factor et al. Population-based case-control study of risk factors for pediatric IGASI.

8% (3/38) of their cases had varicella-zoster infection.

Limitations

Retrospective, so no cultures to study the molecular epidemiology

M protein serotyping PFGE PCR for toxin encoding genes

Public Health Implications

1. Varicella vaccination. Florida: 2001 – 2002 school year

2. Add clindamycin to pen regimen to protect against mortality in pts with NF

Interaction between Clindamycin and NF (N=195)

NF Present?

Total N

Adjusted OR (95% CI )

Yes 33 0.11 (0.01-0.89)

No 162 1.01 (0.31-3.33)

The Sanford Guide

2005 (35th edition)

Skin infections, Page 38

IDSA Guidelines 2005