Group B streptococcal infection

Infection with group B streptococcus (GBS), also known more colloquially as strep B and group B strep, is infection with bacteria of the genus Streptococcus that fall into group B of the Lancefield classification; thus, Streptococcus agalactiae, the sole species of group B, is the pathogen. Group B streptococcal infection can cause serious illness and sometimes death, especially in newborn infants, the elderly, and patients with compromised immune systems. Group B streptococci are also prominent veterinary pathogens, because they can cause bovine mastitis (inflammation of the udder) in dairy cows. The species name "agalactiae" meaning "no milk", alludes to this.

Streptococcus is a genus of spherical, gram-positive bacteria of the phylum Firmicutes. Streptococcus agalactiae is a gram-positive streptococcus characterized by the presence of Group B Lancefield antigen, and so takes the name Group B Streptococcus. The CAMP test is an important test for identification. GBS (group B Streptococcus species) are screened through this test. It is characterized by the presence of group B Lancefield antigen and by its ability to hydrolyze sodium hippurate. It is also sensitive to bile, and will lyse in its presence.

S. agalactiae's polysaccharide antiphagocytic capsule is its main virulence factor.

Perinatal disease

Group B Streptococcus (GBS) is a part of normal flora of the gut, about (15-20%) in the genital tract and is found in 20â€"40% women. It may be harmful to both mother and the baby itself. Maternal colonisation by this organism may result in neonatal death due to severe neonatal infection. It may also result in maternal death, though only occasionally, by causing upper genital tract infection that progresses to septicemia. Carriage of the organism is asymptomatic.

Newborn GBS disease is separated into early-onset disease, which occurs in the first seven days of lifeâ€"and late-onset disease, which starts between seven and 90 days after birth. Early-onset septicemia is more prone to accompaniment by pneumonia. This is believed due to aspiration of GBS during birth, while late-onset septicemia is more often accompanied by meningitis.

Positive culture

25% of women are colonized with GBS in the vagina or rectum. Since the bacteria can come and go, testing for GBS is recommended by US public health protocols at the 36 week antenatal appointment of every pregnancy. The vagina and rectum are swabbed and cultures grown in enriched culture media. In the UK, cultures are not routinely taken from pregnant women for testing, but rather women are treated according to their risk in labor â€" antibiotics are given to women where GBS has been found incidentally from their urine or vaginal/rectal swabs taken during the pregnancy, women who have previously had a baby infected with GBS disease, women whose membranes are ruptured more than 18 hours and those who have fever in labor. In some countries, including the UK, suboptimal culture methods are used, which result in up to half of women carrying GBS, given a false-negative test result. Treatment of GBS positive women with intravenous penicillin G or Ampicillin at the onset of labor and then again at every four hours reduces early onset infection, but research has shown that treatment at least 2 hours prior to birth may also reduce the risk of neonatal infection. For women known to carry GBS where it is not expected that the intravenous antibiotics can be given for at least four hours before delivery, an intramuscular injection of 4.8 MU (2.9 g) of Penicillin G at about 35 weeks of pregnancy may be useful in addition to intravenous antibiotics given from the onset of labour or membranes rupturing at intervals until delivery to try to eradicate GBS colonisation until after the baby is born.

Where insufficient intravenous antibiotics are given before delivery, the baby may be given antibiotics immediately after birth, although evidence is inconclusive as to whether this is necessary or effective. Some maternity units take a watchful approach for 24â€"48 hours, only giving antibiotics if the baby shows any symptoms of infection, or if there is laboratory evidence on complete blood count or culture of infection. If a woman presents late in her prenatal period then there may be no time to grow cultures prior to labor, or she may present in active labor without documentation of prenatal care. In this situation, some clinicians advocate empirical antibiotic coverage of mother and baby, although most would only advocate antibiotics for the mother if other recognized risk factors were present.

Prevention

Intrapartum antibiotic prophylaxis (IAP) is recommended for:

• Women who delivered a previous infant with GBS disease
• Women with GBS bacteriuria in the current pregnancy
• Women with a GBS-positive screening result in the current pregnancy
• Women with unknown GBS status who deliver at less than 37 weeks’ gestation, have an intrapartum temperature of 38°C (100.4°F) or greater, or have rupture of membranes for 18 hours or longer.

Penicillin is the preferred agent for intrapartum antibiotic prophylaxis, and ampicillin is an acceptable alternative.

Simple anti-septic wipes do not prevent mother-to-child transmission. Up to 90% of early-onset GBS infection would be preventable if intravenous antibiotics were offered in labour to all GBS carriers identified by universal sensitive testing late in pregnancy plus to the mothers of babies in the recognised higher risk situations. Early onset GBS infection is most likely to present with breathing problems and pneumonia; late onset GBS infection is more likely to present with meningitis and septicaemia. Once symptoms are present, the condition can be difficult to treat.

Group B Streptococcus vaccine research

Group B Streptococcus, also known as Streptococcus agalactiae colonize the vaginal and gastrointestinal tracts in healthy women, with carriage rates ranging from 15%-45%. The absence of antibody to group B streptococci in infants is a risk factor for infection. Group B streptococcal infection in elderly people (≥70 y) is strongly linked to congestive heart failure and being bedridden, with urinary tract infection, pneumonia, and soft-tissue infection as the most common manifestations of infection. Neurologic illness is associated with pneumonia in elderly people, due to aspiration of group B streptococci from the upper respiratory tract. Urinary tract infections are a common manifestation of group B streptococcal disease and are observed in both pregnant and nonpregnant adults. Vaccine development was once promising, but shifting serotypes of group B streptococci responsible for clinical disease have limited this approach. The broad use of antibiotics in pregnant women is of concern to public health officials. Many women are allergic to penicillin and penicillin-type antibiotics that are the preferred treatment, and GBS is increasingly resistant to other common antibiotics. A Phase II clinical study that indicates a vaccine to prevent Group B Streptococcus (GBS) infection is possible by 2019.

Diagnosis

Babies at greatest risk of developing GBS disease are those born to women who carry GBS during labour. Testing women during pregnancy for GBS is not currently done in the UK, allegedly because of the costs and logistics involved. Research has shown that testing pregnant women, using the more sensitive ECM tests, and giving antibiotics in labour to those carrying GBS and to high-risk women, was significantly more cost-effective than using a risk-factor approach. One research paper calculated an expected net benefit to the Government of such an approach at around £37 million a year, compared with the current RCOG approach

GBS tests are performed by using a swab test. Swabs are ideally taken from the lower vagina and rectum at 35â€"37 weeks of pregnancy. They can be taken by healthcare professionals, or by the mother, following simple instructions.

Routine screening of pregnant women is performed in many countries, including USA, Canada, Australia, New Zealand, Israel, Belgium, France, Spain, Germany, Italy, Hong Kong, Bulgaria, Czech Republic, Slovenia, Argentina and Kenya. Published evidence has shown universally falling incidences of GBS infection in these countries following introduction of these screening-based preventive measures. A reliable test is not routinely offered within the NHS in the UK, and the number of GBS infections as a result is rising. Sensitive tests for GBS carriage are available privately in the UK and charity, Group B Strep Support, lists those that adhere to the Health Protection Agency's Standard Operating Procedure (BSOP58) for processing these. In the UK, only 1% of maternity units test for the presence of Group B Streptococcus.

Direct plating method

If the swabs are processed directly on to laboratory plates and GBS is grown, then this positive result is very reliable. Special growth plates can be used that indicate the presence of GBS by a colour change. However, this method is very susceptible to giving false negative results when the swabs don't bring up GBS â€" this can be as high as 50% of samples, leaving up to half of the pregnant women who were carrying GBS at the time the swab was taken under the false impression that they are not carrying GBS and their baby is not at risk.

Enriched culture medium

To reduce the number of false negative results, the laboratory can take an extra step to improve the accuracy of the test. This involves growing the samples in an enriched medium to improve the viability of the GBS in the same as opposed to the other naturally occurring bacteria. This usually takes 24â€"48 hours. Following this, the sample is plated as before, to determine whether GBS is present. This enriched culture medium (or ECM) method is the "Gold Standard" of GBS testing and is the best GBS test currently available. It may miss a very small number of women who carry GBS, though it does not give false positives. It is the method described by the Heath Protection Agency's BSOP58, Processing swabs for group B Streptococcal carriage. The ECM test is believed to be offered on a handful of UK NHS hospitals, including the Royal Shrewsbury Hospital, John Radcliffe Hospital, Princess Elizabeth (Guernsey) and Royal Free Hospital. The test is also available privately, for around £32 for a UK-wide postal service. Organisations that offer the test privately and follow the HPA's BSOP58 are listed on the website of charity Group B Strep Support. The ECM test costs more than the direct plating method, due to the extra step involved, and would requirea change both in antenatal care and in what is available from laboratories serving the NHS. However, none of the constituent parts of the ECM tests are difficult to obtain or expensive, and the tests has proven safe over decades of use in other countrines. The implememtation of standardised ECM testing nationally in the UK is a viable option. At present, culture for GBS (using enriched culture medium) at 35â€"37 weeks to define an at-risk group is the most cost-effective strategy currently practicable.

PCR intrapartum testing

No current cultured based tests are both accurate enough and fast enough to recommend for detecting GBS once labour starts. Plating of swab samples requires time for the bacteria to proliferate, meaning it is unsuitable as an intrapartum test. An alternative method is the Polymerase Chain Reaction (or PCR) method. In-labour PCR testing for GBS carriage could in future be sufficiently sensitive to guide offering of antibiotics in labour, but the technique must be improved and simplified to make the method cost effective.

Testing women for GBS colonisation using vaginal or rectal swabs at 35â€"37 weeks of gestation and culturing them in enriched mediaâ€"as practised in many countriesâ€"may not be quite as sensitive as a PCR test in labour would be at predicting whether the pregnant woman is carrying GBS at delivery. It would, however, allow starting antibiotics on admission to the labour ward. The PCR technology must be simplified and sped up to be useful as a point-of care test.

Epidemiology

UK

The following are estimates of the chances that a baby in Britain will be infected with Group B streptococcal infection (GBS) if no preventative measures are taken and no other risk factors are present:

• 1 in 1,000* where the woman is not a known GBS carrier
• 1 in 400 where the woman carries GBS during the pregnancy
• 1 in 300 where the woman carries GBS at delivery
• 1 in 100 where the woman had a previous baby infected with GBS

(*This is a broadly accepted estimate of the number of GBS infections in newborn babies that would occur if no preventative intravenous antibiotics in labour are given and this estimate has been used throughout this document. However, recent UK research has suggested this may be a serious underestimate of the incidence of GBS infection in newborns, which could be as high as 3.6 per 1,000.)

If a woman who carries GBS is given antibiotics during labour the baby’s risk is reduced significantly:

• 1 in 8,000 where the mother carries GBS during pregnancy;
• 1 in 6,000 where the mother carries GBS at delivery; and
• 1 in 2,200 where the mother has previously had a baby infected with GBS.

Guidelines

Royal College of Obstetricians & Gynaecologists

RCOG issued their Green Top Guideline No 36 "Prevention of early onset neonatal Group B streptococcal disease" in November 2003. This document was reviewed in July 2012, but there were no substantial changes made, the most notable being the clarification of procedure when a woman carrying GBS has PROM and the clarification that oral antibiotics are not recommended in labour against GBS infection in the baby. The review also dealt with a common misconception regarding vaginal cleansing, stating that there is no evidence it reduces GBS infection in the baby. The next review is due in 2015. The guidelines is flawed, however, as it uses minimum incidence figures from a surveillance study undertaken in 2000-1 and therefore not only underestimate the true incidence of GBS infection, but also underestimate the risks to babies from GBS infection. GBS infection in babies has increased in England, Wales and Northern Ireland since 2003 (when the guideline was introduced) â€" voluntarily reported cases from the CDR/HPA show 0.48 cases per 1000 live births in 2003, which increased to 0.64 per 1000 in 2009 In 2007, RCOG published the findings of their audit to evaluate practice in UK obstetric units against their recommendations. The audit started out by comparing international guidelines for early onset GBS disease: highlighting the fact that, in contrast to the UK and New Zealand guidelines, most of the other countries surveyed recommended identifying women for intravenous antibiotics in labour by offering sensitive tests to all pregnant women. The audit reviewed hospitals’ protocols against GBS infection in newborn babies â€" of the 161 UK units, which submitted their protocol, four units did not even have a protocol for GBS, of those that did, 35% did not mention the 2003 RCOG guideline, and only a minority of units had protocols that were entirely consistent with the guideline. Further UK research published in 2010 looked at the opportunities for prevention amongst cases of early onset group B Strep infection in babies following introduction of the RCOG Guideline. They found that, in the 48 cases of GBS during 2004 to 2007 (0.52/1000 live births), only 19% of the mothers in whom risk factors were present were given adequate intravenous antibiotics in labour. The researchers stated that, “if all women with risk factors received prophylaxis, 23 cases (48%) may have been prevented.”

National Institute for Clinical Excellence

NICE does not recommend routine testing for GBS, saying, “Pregnant women should not be offered routine antenatal screening for group B streptococcus because evidence of its clinical and cost effectiveness remains uncertain”. However, the evidence of similar screening studies clearly demonstrates the clinical effectiveness of testing pregnant women for GBS and offering intravenous antibiotics in labour to women whose babies are at increased risk. Countries that introduced such programmes have seen in the incidence of GBS infection fall dramatically. These countries include the USA, Australia, New Zealand, Belgium, France, Spain, and Italy. The issue of cost-effectiveness is less clear-cut, though a study published in September 2007 indicated testing low risk women, plus antibiotics being given to high-risk women and those found to carry GBS was more cost-effective than current UK practice. Further research also found screening to be more cost effective than risk factors The guideline was reviewed in March 2008 though no significant changes were made, and in the May 2011 review - no changes at all were made to the section regarding GBS. The next review will be after 2014.

National Screening Committee

The National Screening Committee’s current policy position on group B Strep is that screening should not be offered. This policy was reviewed in November 2008 but no significant changes were made. The policy was reviewed again in 2012, and despite receiving 212 responses, of which 93% advocated screening, the NSC decided to not recommend antenatal screening. This decision was strongly criticised by the charity Group B Strep Support as ignoring both the wishes of the public and the rising incidence rates of group B Strep infection.

In May 2006, the UK National Screening Committee launched their GBS online learning package. This learning package was developed to raise awareness of GBS amongst health care professionals. Developed by the Women’s Health Specialist Library (part of the National Library for Health), the learning package is based upon the current UK guidelines published by the Royal College of Obstetricians & Gynaecologists. It is divided into three sections â€" antenatal, delivery and postnatal. Within each section, there is the option to access an introduction to GBS, different clinical scenarios, a series of quiz questions to test knowledge and a FAQs section.

Other

The United States uses the most effective strategy: all pregnant women are screened for Group B Strep and prophylactic antibiotics are given to all women testing positive and to those who deliver before 37 weeks of pregnancy plus to women with unknown GBS test result and other recognised risk factors. Because of this strategy, the US has seen a major reduction in babies born with early-onset infection of over 80% since preventative strategies were introduced. Countries that routinely screen women for GBS carriage late in pregnancy, and give intrapartum antibiotics to those who test positive include USA, Canada, France, Germany, Italy, Spain, Belgium, Canada, Australia, Czech Republic, Slovenia, Kenya, and Argentina. Published papers report reductions of 70â€"86% in early onset group B Strep infections in France, Spain and Australia whilst, as expected, the rate of late onset GBS infection in babies has remained constant.

Part of the neonatal care in Mexico includes undergoing a screening with culture of a cervicovaginal swab during the third trimester of pregnancy, though chemoprophylaxis based on positive results remains below 50%

In animals

Group B strep has been found in many mammals such as camels, dogs, cats, crocodiles, seals and dolphins.

Cattle

Group B Strep was recognised as a pathogen in cattle before the Second World War. Its significance as human pathogene was not discovered before the 1950s. In cattle it causes mastitis, an infection of the udder. It can either give acute, febrile disease or sub-acute, more chronic disease. Both lead to diminishing milk production (hence its name: agalactiae meaning "no milk"). Outbreaks in herds are common. This is of major significance for the dairy industry and programs to reduce the impact of Group B Strep have been enforced in many countries over at least the last 30â€"40 years.

Fish

Fisheries and wildlife officers from Queensland, Australia, have been investigating the deaths of more than 50 grouper fish, between 2008 and 2010, that have washed up dead on beaches in the north of the state. The fish had been infected with Group B Streptococcus.

References

External links

• Group B Strep Association
• Group B Strep Support, UK charity (Group B Strep Support)
• 2010 Guidelines for the Prevention of Perinatal Group B Streptococcal Disease of the Centers for Disease Control and Prevention (CDC) - (earlier guidelines of 2002: Prevention of Perinatal Group B Streptococcal Disease 16 August 2002 MMWR 2000;49:228â€"232 - summary of main differences between 2002 and 2010 guidelines)
• The Canadian Strep B Foundation
• Meningitis UK
• Group B Strep International