Group B streptococcal infection

Infection with Group B Streptococcus (GBS), also known as 'Streptococcus agalactiae' and more colloquially as Strep B and group B Strep, 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 and genital tract and is found in 20–40% women. It may be harmful to both mother and the baby itself. Infection of this organism may result in neonatal death due to severe neonatal infection. It may also result in maternal death although this is only occasionally by causing upper genital tract infection which progresses to septicemia. Carriage of the organism is asymptomatic. Newborn GBS disease is separated into early-onset disease occurring on living days 0–7 and late-onset disease which starts on days 7–90. Early-onset septicemia is more prone to be accompanied by pneumonia, this is thought to be due to aspiration of GBS during birth, while late-onset septicimia 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 – 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 when swabbed, and being 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.

The most effective preventative measure is intravenous antibiotic prophylaxis during labour, which minimises the risk of the baby acquiring the infection as he/she passes through the vagina during delivery. The difficulty is in knowing which women should be treated with antibiotics, and which should not – it is not desirable to treat women who are not at risk, as any antibiotic treatment can have side effects. Current UK guidelines use risk factors for determining which women should be treated. Several risk factors, such as previously having had a GBS infected baby, maternal fever during pregnancy and prolonged rupture of membranes, mean that the risk of GBS infection in the baby is substantially higher. However, a significant number of at-risk women will be missed by using risk factors alone

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 24–48 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 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.

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 to be 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 35–37 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 counties, including USA, Canada, Australia, Belgium, France, Spain, Germany, Italy, 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 preventative 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 which 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 cn 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 – 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 24–48 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, although it will not give a false positive result. 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 which offer the test privately and which 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 been proved to be 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 35–37 weeks to define an at-risk group is the most cost-effective strategy currently practicable.

PCR intrapartum testing
No tests are currently available which are both accurate enough and fast enough to recommend their use for detecting GBS once labour has started. 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 needs to be improved and made simpler in order for the method to become a cost effective option.

Testing women for GBS colonisation using vaginal and/or rectal swabs taken at 35–37 weeks of gestation and culturing them in enriched media – as practised in many countries – may not be quite as sensitive as a PCR test in labour would be at predicting whether the pregnant woman will be carrying GBS at delivery, but it would allow antibiotics to be started on admission to the labour ward. The PCR technology needs to be simplified and speeded up to be useful as a point-of care test.

UK
The following are estimates of the chances a baby in Britain will become infected with GBS if no preventative measures are taken and no other risk factors are present:
 * 1 in 1,000* where the woman is not known to be a carrier of GBS;
 * 1 in 400 where the woman is carrying GBS during the pregnancy;
 * 1 in 300 where the woman is carrying GBS at delivery; and
 * 1 in 100 where the woman has 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.

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 is currently under review, and updated guidelines are due later in 2011. However, the guidelines use 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) – 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 – 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’S Guidelines CG6 “Antenatal Care – Routine care for health pregnant women”, October 2003 recommend that “pregnant women should be offered evidence based information and support to enable them to make informed decisions regarding their care … addressing women’s choices should be recognised as being integral to the decision making process.” The guidelines also recommend antenatal appointments for all pregnant women at 36 weeks’ gestation – which would be ideal for sensitive testing for GBS colonisation. However, NICE does not recommend such testing, saying, “evidence of its clinical effectiveness 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 which have introduced such programmes have seen in their incidence of GBS infection fall dramatically, including the USA, Australia, New Zealand, Belgium, France, Spain and Italy. Cost effectiveness issue is less clear-cut though a study published in September 2007 indicated testing low risk women, plus antibiotics given to high-risk women and those found to carry GBS was more cost-effective than current practice. Further research has also found screening to be more cost effective than risk factors

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. It is due to be considered again in 2012 or earlier if significant new peer-reviewed evidence emerges. 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 – 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 which routinely screen women for GBS carriage late in pregnancy and offer intrapartum antibiotics to those where GBS is found include USA, Canada, France, Germany, Italy, Spain, Belgium, Canada, Australia, Czech Republic, Slovenia, Kenya and Argentina. Published papers report reductions of 70–86% 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 or dolphins.

Cattle
Group B Strep was recognised as a pathogene 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 programms to reduce the impact of Group B Strep have been enforced in many countries over at least the last 30–40 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.