# Presentation: 588343

-  **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 Houston**
**And**
**Dept. of OB/GYN**
**Texas 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

**Notes:**
Public health significance:  Mention high case-fatality rates of NF and STSS

## 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

## Slide 9

## 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

## Slide 26

## Age Distribution, 25 cases

| Age | Number |
| --- | --- |
| 0 to 6 weeks | 3 |
| 7 weeks to 51 weeks | 3 |
| 1 year to 3 years | 4 |
| 4 years to 9 years | 9 |
| 10 years to 14 years | 4 |
| 15 years to 17 years | 2 |
| TOTAL | 25 |

**Age Distribution, 25 cases**

## Results

- Boys:  14 cases (56%)
- GAS bacteremia:  18 cases
- IVIG

## Slide 29

| 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 |

## Slide 30

| 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 |

## Slide 31

| 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 |

## Slide 32

| 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 |

## Slide 33

| 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 |

## Slide 34

| 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)

## The Sanford Guide

- 2005 (35th edition)
- Skin infections, Page 38

**IDSA Guidelines 2005**

## Slide 44