Group B streptococcal infection, also known as Group B streptococcal disease or just Group B strep infection, is the infectious disease caused by the bacterium Streptococcus agalactiae. Streptococcus agalactiae is the most common human pathogen belonging to group B of the Lancefield classification of streptococci—hence the name of group B streptococcal (GBS). Infection with GBS can cause serious illness and sometimes death, especially in newborns, the elderly, and people with compromised immune systems. The most severe form of group B streptococcal disease is neonatal meningitis in infants, which is frequently lethal and can cause permanent neuro-cognitive impairment. S. agalactiae was recognized as a pathogen in cattle by Edmond Nocard and Mollereau in the late 1880s. It can cause bovine mastitis (inflammation of the udder) in dairy cows. The species name "agalactiae" meaning "no milk", alludes to this. Its significance as a human pathogen was first described in 1938, and in the early 1960s, GBS came to be recognized as a major cause of infections in newborns. In most people, Streptococcus agalactiae is a harmless commensal bacterium that is part of the normal human microbiota colonizing the gastrointestinal and genitourinary tracts. Up to 30% of healthy human adults are asymptomatic carriers of GBS.
Laboratory identification of Group B streptococcus S. agalactiae is a Gram-positive coccus with a tendency to form chains, beta-haemolytic, catalase-negative, and facultative anaerobe (anaerobic organism). GBS grows readily on blood agar plates as microbial colonies surrounded by a narrow zone of β-haemolysis. The presence of the group B antigen of the Lancefield classification (Lancefield grouping) in the cell wall, which can be detected directly in intact bacteria using latex agglutination tests characterizes GBS.
The CAMP test is also another important test for the identification of GBS. The CAMP factor acts synergistically with the staphylococcal β-haemolysin, inducing enhanced haemolysis of sheep or bovine erythrocytes. GBS is also able to hydrolyze hippurate, and this test can also be used to identify GBS.
Hemolytic GBS strains, when cultivated on granada medium after 24- 48 h at 35-37 °C, produce (granadaene) and develop as orange-brick or red colonies that allow their straightforward and unequivocal identification.
Identification of GBS could also be carried out easily using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. and Nucleic acid tests (NAATs).
Additionally, GBS colonies can be tentatively identified after their appearance in chromogenic agar media.Nevertheless, GBS-like colonies that develop in chromogenic media should be confirmed as GBS using additional reliable tests (e.g., latex agglutination or the CAMP test) to avoid potential misidentification.
A summary of the laboratory techniques for GBS identification is depicted in Ref.
GBS Colonization versus GBS infection GBS is usually an asymptomatic and harmless colonizer of the vagina and gastrointestinal human tract in up to 30% of healthy adults, including pregnant women, GBS is found in the gastrointestinal, genitourinary tract, and oropharynx of humans. GBS is also a normal component of the intestinal and vaginal microbiota in some women. In different studies, GBS vaginal colonization rates range from 4 to 36%, with most studies reporting rates over 20%. An estimated maternal GBS colonization rate worldwide is 18%, with large variations among countries (11%–35%).
Vaginal or rectal GBS colonization may be intermittent, transitory, or persistent. These variations in the reported prevalence of asymptomatic (presenting no symptoms of disease) colonization could be related to the different detection methods used and differences in populations studied.
Nevertheless, this opportunistic harmless bacterium can, in some circumstances, cause severe invasive infections (opportunistic infection).
GBS produces more than twenty different virulence factors (pathogenicity factors) that contribute to the GBS pathogenesis and are critical for its ability to cause disease. Among them, the capsular polysaccharide (rich in sialic acid) and the β-hemolysin (a pore-forming toxin) are the most important virulence factors of GBS. By expressing high levels of sialic acids on the bacterial cell surface, GBS can weaken the innate immune system, leading leukocytes to mistake the bacteria for human cells. Today, it is pondered that GBS hemolysin and the GBS red pigment (granadaene) are identical or nearly identical molecules.
It has also been suggested that GBS pigmentation on Granada agar can help to identify pregnant women and newborns at increased risk for developing invasive GBS disease.
GBS and Pregnancy Though GBS colonization is asymptomatic and, in general, does not cause problems, it can sometimes cause serious illness for the mother and the baby during gestation and after delivery. GBS infections in the mother can cause chorioamnionitis (intra-amniotic infection or severe infection of the placental tissues) infrequently, postpartum infections (after birth), and have been related to prematurity and fetal death.
GBS urinary tract infections, more than 100.000 CFU (colony forming units) /mL, may induce labour in pregnant women and cause premature delivery (preterm birth) and miscarriage and require antibiotic treatment. The presence of GBS in the urine in any colony count is a marker of heavy GBS colonization and an indication for Intrapartum Antibiotic Prophylaxis.
GBS and newborns In the Western world, GBS (in the absence of effective prevention measures) is the main cause of bacterial infections in newborns, such as sepsis, pneumonia, and meningitis, which can lead to death or long-term sequelae, after effects.
GBS infections in newborns are separated into two clinical types, early-onset disease (GBS-EOD) and late-onset disease (GBS-LOD). GBS-EOD manifests from 0 to 7 days of life in the newborn, with most of the cases of EOD being apparent within 24 h from birth. GBS-LOD starts between 7 and 90 days after birth.
Roughly 50% of newborns of GBS-colonized mothers are also GBS-colonized, and (without prevention measures) 1-2% of these newborns will develop GBS-EOD.
The most common clinical syndromes of GBS-EOD are sepsis, pneumonia, and (less commonly) meningitis. Pneumonia and sepsis are frequently seen together or sequentially. Neonates with meningitis often present similarly to those with other syndromes before progressing to symptoms of meningitis. Examination of the infant's cerebrospinal fluid is often necessary to rule out meningitis.
A minority of infants with S. agalactiae sepsis have a coinfection, with one or more other bacterial species also contributing to the septic disease. The most common of these organisms is Staphylococcus aureus.
Colonization with GBS during labor is the primary risk factor for the development of GBS-EOD. GBS-EOD is acquired vertically (vertical transmission), through exposure of the fetus or the baby to GBS from the vagina of a colonized woman, either in utero (because of ascending infection) or during birth, after rupture of membranes. Infants can also be infected during passage through the birth canal; however, newborns who acquire GBS through this route can only become colonized, and these colonized infants usually do not develop GBS-EOD.
Though maternal GBS colonization is the key determinant for GBS-EOD, other factors also increase the risk. These factors are: Onset of labor before 37 weeks of gestation (premature birth) Prolonged rupture of membranes (longer duration of membrane rupture) (≥18 h before delivery) GBS bacteriuria during pregnancy Intrapartum (during childbirth) fever (>38 °C, >100.4 °F) Amniotic infections (chorioamnionitis) Young maternal age Maternal HIV infection.
Nevertheless, most babies who develop GBS-EOD are born to colonized mothers without any of these risk factors. Heavy GBS vaginal colonization may be associated with a higher risk for GBS-EOD. Women who had one of these risk factors but who were not GBS colonized during labor are at low risk for GBS-EOD compared to women who were colonized prenatally but had none of the aforementioned risk factors.
The presence of low levels of anticapsular antibodies against GBS in the mother is also of great importance for the development of GBS-EOD. Because of that, a previous sibling with GBS-EOD is also an important risk factor for the development of the infection in subsequent deliveries, probably reflecting the lack of protective antibodies in the mother.
Overall, the case fatality rates from GBS-EOD have declined, from 50% observed in studies from the 1970s to between 2 and 10% in recent years, mainly as a consequence of improvements in therapy and management. Fatal neonatal infections by GBS are more frequent among premature infants.
Today, the mortality associated with GBS EOD in the US is 2.1% among term newborns and 19.2% among preterm newborns.
GBS-LOD affects infants from 7 days to 3 months of age and has a lower case fatality rate (1%-6%) than GBS-EOD. Clinical syndromes of GBS-LOD are bacteremia without a focus (65%), meningitis (25%), cellulitis, osteoarthritis, and pneumonia. Prematurity has been reported to be the main risk factor. Each week of decreasing gestation increases the risk of developing GBS-LOD by a factor of 1.34.
A heightened risk of GBS-LOD is also related in addition to prematurity, with low birth weight, maternal colonization, and multiple-gestation pregnancies.
GBS-LOD can not only be acquired through vertical transmission during delivery; it can also be acquired later from the mother through breast milk, or throat, or from environmental, nosocomial, and community sources. GBS-LOD commonly shows nonspecific signs, and diagnosis should be made by obtaining blood cultures in febrile newborns. S.agalactiae neonatal meningitis does not present with the hallmark sign of adult meningitis, a stiff neck. Instead, it presents with nonspecific symptoms, such as fever, vomiting, and irritability, and can consequently lead to a late diagnosis. Hearing loss and mental impairment can be long-term consequences of GBS meningitis.
Prevention of GBS neonatal infection - Intrapartum Antibiotic Prophylaxis (IAP) Currently, the only reliable way to prevent GBS-EOD is the administration of intrapartum intravenous (IV) antibiotics before delivery, referred to as intrapartum antibiotic prophylaxis (IAP). IAP interrupts vertical transmission of GBS from the mother to the newborn and decreases the incidence of GBS-EOD.
Intravenous penicillin or ampicillin given to GBS-colonized women at the onset of labor and then again every four hours until delivery has been proven to be very effective at preventing vertical transmission of GBS from mother to baby and GBS-EOD. Penicillin G, 5 million units IV initial dose, then 3 million units every 4 hours until delivery, or ampicillin, 2 g IV initial dose, then 1 g IV every 4 hours until delivery. Appropriate IAP in GBS colonized women should start as soon as possible once labour starts or the waters have broken. When the first dose is given at least 4 hours before delivery, the risk of neonatal infection is very small; moreover, when given between 2–4 hours before delivery, the risk is only partially reduced.
Penicillin-allergic women without a history of anaphylaxis (angioedema, respiratory distress, or urticaria) following administration of a penicillin or a cephalosporin (low risk of anaphylaxis) could receive cefazolin (2 g IV initial dose, then 1 g IV every 8 hours until delivery) instead of penicillin or ampicillin. If the woman has a severe allergy to beta-lactams and the GBS isolated is susceptible to clindamycin, then clindamycin is the recommended alternative.