REFERENCE STUDY

Postpartum Group A Streptococcus

Infection

Presented by : dr. Danu Lestariyanto

Supervisor : dr. M. Adrianes Bachnas, SpOG (K)

OBSTETRY AND GYNECOLOGY DOCTOR SPECIALIST PROGRAM

OBSTETRY AND GYNECOLOGY DEPARTMENT
DR. MOEWARDI CENTRAL HOSPITAL / UNS FACULTY OF MEDICINE
SURAKARTA 2015

INTRODUCTION

Group A Streptococcus (GAS) is an

historically important cause of puerperal
infections and sepsis.

Despite preventive measures (including

antibiotic use and hospital sanitation
efforts) GAS infections are re-emerging
worldwide and remain the most common
cause of severe puerperal infections

INTRODUCTION
The ability of GAS to establish infection in
postpartum patients is influenced by :
1. disrupted mucosal barriers,
2. altered immune status of the mother,
3.
antibiotic administration during labor
and delivery,
4. delayed diagnosis,
5. environmental exposures of the mother,
and
6. specific virulence factors utilized by GAS

OVERVIEW
Postpartum Sepsis
Puerperal infections cause morbidity in 5-10%
of all pregnant women with over 75,000 deaths
/ year .
Several bacterial
postpartum sepsis

pathogens

can

cause

Group B Streptococcus is more prevalent than

GAS, but typically causes less severe maternal
disease
Other causal organisms include staphylococci,
Mycoplasma, Chlamydia, Clostridium sordellii,

OVERVIEW
Postpartum Sepsis
Popularization of hand hygiene and raise the
standards of hospital cleanliness, maternal
postpartum infections decreased drastically

The past two decades have witnessed an

unexplained increase in severe postpartum
GAS infections, resulting in greater numbers
of maternal deaths worldwide
A new urgency to better understand the
host-microbial determinants of disease that
might be targeted for improving preventive
and therapeutic measures.

OVERVIEW
Postpartum Sepsis

GAS
is
a
ubiquitous
human
pathogencellulitis, pharyngitis, necrotizing
soft tissue infections, scarlet fever and
invasive puerperal infections

Puerperal infections present rapidly, within

2 to 48 hours postpartum and can be nonspecific, delaying treatment

G.A.S

GAS is a ubiquitous human pathogen

that causes a wide array of disease
including cellulitis, pharyngitis,
necrotizing soft tissue infections,
scarlet fever and invasive puerperal
infections

G.A.S

Streptococcus pyogenes, also known as

Group A Streptococcus (GAS), causes
mild human infections such as
pharyngitis and impetigo and serious
infections such as necrotizing fasciitis
and streptococcal toxic shock
syndrome. Furthermore, repeated GAS
infections may trigger autoimmune
diseases

EPIDEMIOLOGY

Puerperal sepsis causes at least 75.000

maternal deaths annually, mostly
indeveloping countries and the
morbidity of puerperal infections
affects an estimated 5-10% of pregnant
women
Group A -hemolytic Streptococcus
(GAS, S. Pyogenes), was the major
microbial cause of post partum
infection.

EPIDEMIOLOGY

Severe GAS disease (including acute

rheumatic fever and invasive
infections) is responsible for over
50.000 deaths annually
According to the CDC, approximately
232 cases of postpartum invasive GAS
infection occured in the United States
in 1997, an incidence of 0,06 cases per
1000 live births.

EPIDEMIOLOGY

Epidemics of puerperal sepsis were

responsible for about two-thirds of
maternal mortality in the
eighteenth and nineteenth centuries
Maternal deaths have been
reported from group A
streptococcal infection complicated
by DICs

EPIDEMIOLOGY

The mortality rate for all invasive cases

is about 10% to 15% whereas more
than 50% of streptococcal toxic shock
and 20% of necrotizing fasciitis cases
end in death.
In addition, approximately 2.2% of
persons with invasive disease meet the
case definition for invasive postpartum
GAS, averaging about 220 cases per
year in the United States

PATHOFISIOLOGY
Postpartum Sepsis

Primary symptoms of puerperal infection

include :
myalgias,
fever,
confusion,
euphoria,
dizziness, and
abdominal pain
Once GAS is diagnosed, the infection is
often advanced

PATHOFISIOLOGY
Route of Maternal Infection

GAS (Group A Streptococcus) :

can be found in the normal biota of the
female reproductive tract,
its colonization is considered to be relatively
rare (0.03%)
its presence alone is not sufficient to cause
disease
asymptomatically carried on the skin or in
the throat by 5-30% of the population and
easily spread by person-to-person contact or
aerosolization

PATHOFISIOLOGY
Route of Maternal Infection
The host and microbial factors that influence

colonization
progressing
unresolved,

to

infection

It is apparent that postpartum and pregnant

women are predisposed to bacterial infections
in general
Women can be a source of contamination of
their own reproductive tract

PATHOFISIOLOGY
Route of Maternal Infection
Mothers with a recent history of sore throat
succumb to GAS postpartum sepsis infect

themselves after delivery : contamination of

the perineum or through bacterial travel in the
bloodstream from distal organ sites
Source of GAS exposure in the maternal
environment is through interaction with
children in the house or at work (children
frequent GAS carriers)

PATHOFISIOLOGY
Route of Maternal Infection
Lamagni et al. invasive GAS infections as a

whole are on the rise in the general population

: perhaps contributing to the increase in
maternal exposure in the community
Nosocomial infections are a significant
potential route of maternal infection
High incidence of healthcare-associated GAS
infections (asymptomatic healthcare-worker
carriers, resulting in sporadic postpartum GAS
outbreaks in hospitals )

PATHOFISIOLOGY
Route of Maternal Infection
Cesarean section : the single most important
risk factor for postpartum maternal infection in
a hospital the invasive nature of the surgery

Antibiotic administration during or after

surgery significantly reduces the risk for
postpartum infection but is not 100%
effective at preventing infections from
progressing and rapidly causing maternal death
It is easy to regard uncomplicated pregnancies
with vaginal deliveries as low-risk for sepsis in a
hospital setting, but there has been an increase

PATHOFISIOLOGY
Route of Maternal Infection
The non-specific symptoms at the onset of

GAS sepsis result in healthy women becoming

critically ill and dying within a few hours or
days
Regardless of delivery type, postpartum
patients have a 20-fold increased incidence of
GAS- induced disease compared to nonpregnant women

PATHOFISIOLOGY
Route of Maternal Infection

PATHOFISIOLOGY
Route of Maternal Infection
GAS virulence factors and Streptococcal Toxic
Shock Syndrome (STSS)
GAS is a versatile human pathogen that utilizes
numerous virulence factors to evade immune
recognition or clearance
GAS virulence factors aid in evading phagocytosis
and facilitate in adherence to host cells, leading to
colonization and invasion of the host
GAS has a family of bacterial antigens that are
associated with streptococcal toxic shock syndrome
(STSS) SpeA (Streptococcal pyogenic exotoxin A),
SpeC, and others that bind to the MHC class II

PATHOFISIOLOGY
Route of Maternal Infection
GAS virulence factors and Streptococcal Toxic
Shock Syndrome (STSS)
Familys GAS of Bacterial Antigens

resulting
in
an
excessive
release
of
immunomodulators that activate complement,
coagulation,
and
fibrinolytic
cascades,
resulting in toxic shock and death
STSS has been reported with invasive GAS
soft-tissue infections with a mortality rate of
approximately 30%
Study of 11 European countries showed a

PATHOFISIOLOGY
Route of Maternal Infection
GAS virulence factors and Streptococcal Toxic
Shock Syndrome (STSS)
SpeA is the superantigen most commonly

GAS infections that result in STSS in the US

and
Genome sequence comparisons of GAS
patient isolates reveal new variants of speA
increased severity of these clinical strains in
postpartum infections

PATHOFISIOLOGY
Route of Maternal Infection

Immune recognition of GAS

GAS is recognized by the innate immune
response.
GAS is recognized by an unidentified MyD88dependent receptor (independent of TLR2,
TLR4 and TLR9 activation)
in vitro studies GAS activation of p38
MAPK, NF-B, TNF, IL-6, and type 1 IFN
production [42], indicating host immune
activation.
GAS (an extracellular pathogen), but recent
research GAS survival within multiple host

PATHOFISIOLOGY
Route of Maternal Infection

Immune recognition of GAS

Biopsies from patients with severe GAS tissue
infections contained viable GAS within
macrophages, confirming their intracellular
survival ability.
GAS survival in epithelial cells may contribute
to severe GAS postpartum infections by
providing a location for systemic invasion or
the initiation of STSS

PATHOFISIOLOGY
Postpartum Physiology and Imunology
The gravid female reproductive tract (FRT)
environment is unique in its immunology
The maternal immune system must be tolerant
to the indigenous bacteria in the reproductive
tract, to paternal antigens in sperm and to the
immunologically-distinct fetus
Pregnancy takes place in a physiologically and
immunologically distinct organ with its own
mucosal barrier (uterus and decidua) and
accommodates an allogeneic fetus
Hormonal products (FRT) alter the immune
response, and the fetus challenges the
maternal immune system as its size and

PATHOFISIOLOGY
Postpartum Physiology and Imunology

Prostaglandin (PG)E2, IL-4 and IL-10 are

induced by pregnancy and suppress the
maternal Th1 immune response (reviewed in
[103]) and the systemic down-regulation of the
Th1 response results in immune alterations
that promote maternal susceptibility to
infection
Pregnancy has often been referred to as a
Th2-type immune state, but pregnancy is a
modulated immune state that is not simply
anti-inflammatory, but is continually changing
during fetal development

PATHOFISIOLOGY
Prostaglandin E2

The lipid mediator PGE2 deserves special

mention because it has emerged as an
important modulator of host immunity,
especially during pregnancy and the
postpartum period
PGE2 is an arachidonic acid-derived mediator
that modulates cell behavior via the ligation of
four distinct G protein coupled receptors called
E prostanoid (EP) receptors, which are
numbered EP1-4
Throughout gestation, PGE2 dampens
maternal immune responses against fetal

PATHOFISIOLOGY
Prostaglandin E2

Elevation in PGE2 levels has previously been

shown to play a role in host susceptibility to
infections in many patient populations
including pregnant women
The capacity for PGE2 to regulate hostmicrobial interactions is increasingly evident in
the context of streptococcal infections
Prostaglandin endoperoxide synthase 2 (COX2) is the enzyme that converts arachidonic
acid into prostaglandin endoperoxide H2
(PGH2) before PGH2 is converted into other
prostaglandins.

PATHOFISIOLOGY
FRT Mucus,pH, Indigenous Microbiota

Vaginal colonization by GAS appears to be an

important preceding event in some cases of
puerperal sepsis (following vaginal delivery)
The innate immune mechanisms that prevent
GAS from ascending through the cervical canal
into
the
postpartum
uterus
remain
incompletely understood
Mucus within the FRT protects epithelial cells
from bacterial infections through several
mechanisms.
Mucus can physically trap potential
pathogens and inhibit pathogen survival due

PATHOFISIOLOGY
FRT Mucus,pH, Indigenous Microbiota

The indigenous bacteria in the reproductive

tract also provide pathogen resistance through
several means, including competitive
exclusion of pathogenic microbes and
contributing to the acidic vaginal environment
through lactic acid production.
Lactobacillus spp. are the most common
bacteria present across all ethnic groups and
produce lactic acid in the FRT

PATHOFISIOLOGY
FRT Mucus,pH, Indigenous Microbiota

Membranes collected from healthy women

following at term cesarean sections
demonstrate bacterial DNA in up to 70% of
samples indicating a dynamic host control of
individual bacterial diversity in healthy
pregnancies

CLINICAL FEATURE

GAS pelvic infections may have a

paucity of symptoms or signs related to
the genital tract with non-specific
symptoms or gastrointestinal
manifestations predominating

CLINICAL FEATURE

CLINICAL FEATURE

The signs and symptoms of infection by

GAS, including pyrexia/fever, swelling,
erythema, drainage and pain at the site
of the wound.

This is of special importance, given the

frequency of early discharge after a
normal vaginal birth

CLINICAL FEATURE

DIAGNOSIS

Physical Examination
Although streptococcal toxic shock syndrome from
GAS occurs very rarely in the postpartum period, its
prevalence is on the rise, requiring increased
recognition and surveillance of the disease among all
clinicians caring for women in the puerperium.
As primary practitioners for women in this period,
midwives must maintain aseptic technique, emphasize
proper care and cleaning of vaginal tears, and educate
women about the signs and symptoms of infection,
including swelling, erythema, drainage, and pain at
the site of the wound.

DIAGNOSIS

Laboratory (Blood Culture)

Although serologic grouping by the
Lancefield method is the criterion
standard
for
differentiation
of
pathogenic
streptococcal
species,
group A organisms can be identified
more cost effectively by numerous
latex agglutination, coagglutination, or
enzyme immunoassay procedures

DIAGNOSIS

STREPTOCOCCUS GROUP A IS DEMONSTRATED IN

BLOOD AGAR MEDIA

DIAGNOSIS

Sign and Symptom

Signs of sepsis (eg, fever, tachycardia,
tachypnea,
hypotension)
may
be
present in invasive infections but usual
symptom may occur like fever /
pyrexia, myalgia, anorexia and fatique.
The symptoms usually occur at 20 days
postpartum.

DIAGNOSIS

Streptococcal Toxic Shock Syndrome

Criteria proposed by the Working Group on Severe
Streptococcal Infections for the diagnosis of
streptococcal toxic shock are outlined as follows 6:
Isolation of group AStreptococcus- From a sterile site or
from a nonsterile body site
Clinical signs of severity (2 or more of the following
clinical and laboratory abnormalities are required) Renal impairment, coagulopathy, liver abnormalities,
acute respiratory distress, extensive tissue necrosis
(necrotizing fasciitis), erythematous rash
Definite case - Isolation of group AStreptococcusfrom a
sterile site plus compatible clinical signs
Probable case - Isolation of group AStreptococcusfrom a
nonsterile body site plus compatible clinical signs

THERAPY

Drug of Choice GAS Infection :

Penicillin

Allergi to Penicillin : Erythromycin or

another macrolide

Oral
extended-spectrum
(2nd/3rd
generation) cephpalosporins, although
cefixime may be suboptimal

THERAPY

Treatment with ampicillin / sulbactam,

amoxicillin / clavunamic acid or
clindamycin

In cases of streptococcal toxic shock

syndrome, treatment consists of high
dose of penicillin and clindamycin,
given with intravenous immunoglobulin

PROGNOSIS

Small risk of recurrence in subsequent

pregnancies

Better hand higiene and sanitation and

also good of imun condition is required
to prevent GAS Infection

CONCLUSIONS

45

Pregnancy is a highly immunomodulated state

that permits implantation and development of
the immunologically distinct fetus.

This may result in an immunologically

vulnerable FRT that is more easily infected
after delivery.

The immune changes progress during

pregnancy : complex and remain largely
uncharacterized

Recent research suggests GAS infections

are re-emerging
Postpartum patients are particularly prone
to severe GAS infections that result in
death
The mechanisms behind GAS bacterial
virulence, postpartum susceptibility and
the immune response to FRT infections
remain poorly understood and future work
must be done to address the increase in
maternal mortality from postpartum GAS
infections.
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THANK YOU

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