In 2002, revised guidelines for the prevention of perinatal invasive GBS disease were issued by CDC, the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP)47,48
. These guidelines recommend universal screening of pregnant women for rectovaginal GBS colonization at 35–37 weeks gestation. In the United States, the case-fatality ratios are now much lower than in the 1970's (over 50%) and the 1980's (15–25%) 45,49
. The prevalence of early onset GBS disease declined from 2.0 per 1,000 live births in 1990 to 0.6 per 1000 by 2001–2002 and 0.3 per 1,000 in 2004 (REF. 50
). In the United Kingdom and Ireland during 1996–2004, late-onset disease incidence varied little, averaging 0.35 per 1,000 live births, with annual rates ranging from 0.29 to 0.39 per 1,000 live births and 0.7 cases per 1,000 live births51
. In the United States mortality rates were reported to be between 4 and 6% (REF. 52
) and ~10% in the United Kingdom51
. It has been suggested that the rate of neonatal disease is considerably underestimated because the requirement for positive cultures from blood or cerebrospinal fluid under-represents the true burden of disease53
An infection of the female genital tract following childbirth, abortion or miscarriage.
The passage of a disease-causing agent vertically from mother directly to baby during the perinatal period — the period immediately before and after birth. Transmission can also occur across the placenta or through breast milk.
A serious infection of the placental tissues.
During the 1990's there was a decline in the incidence of neonatal GBS disease in the United States, probably as a result of the introduction of surveillance programmes and intrapartum antibiotic prophylaxis45,54,55
. The widespread use of antibiotic prophylaxis to lower the incidence of GBS disease can be problematic, because this measure has been accompanied by an increase in the incidence of early onset sepsis caused by Escherichia coli56
. Stoll et al.
compared the distribution of microorganisms causing early onset sepsis in very-low-birth-weight neonates in the period from 1991 to 1993 with that in the period from 1998 to 2000 — before and after the intrapartum use of antibiotics became widespread. Their analysis revealed that between the two periods, the incidence of early onset GBS sepsis dropped by 4.2 episodes per 1000 live births, but that the incidence of E. coli
sepsis increased by a similar amount — 3.6 episodes per 1000 live births — with little net reduction in the overall incidence of early onset sepsis. These findings relate the increase in early onset E. coli
sepsis to the antibiotics used to prevent GBS sepsis. A conclusion from this study was that immunization with a GBS vaccine has the potential to prevent GBS sepsis without engendering antibiotic resistance. In addition, the use of a vaccine also has the potential to overcome two associated problems in which antibiotic therapy has made little impact: the occurrence of preterm delivery and serious illness following neonatal sepsis56,57
The apparent lower incidence of significant clinical disease due to GBS in less-developed countries is puzzling. It is possible that the role of GBS has been underestimated because of inadequate culture techniques and microbiological methods58,59
. In addition, the low rates of invasive GBS disease reported in developing countries (for example, in India or Gambia) could be due to the combination of several factors, including the prevalence of less virulent strains, higher levels of transplacentally acquired protective antibody in serum or unrecognized/undetermined causes of early neonatal or premature deaths and stillbirths24
. In addition, another important point to note is that in developing countries a large proportion of deliveries occur in rural settings outside health centres, which increase the probability that infants who develop sepsis due to GBS infection at birth will not survive. These fatalities would result in an inaccurate measure of the incidence of early onset cases. Since exposure to the organism seems to be similar in pregnant women in developing and developed countries58
, the failure to recognize GBS as an important cause of neonatal sepsis in developing countries could also reflect either insufficient surveillance or true population differences. It is not known whether human genetic factors have a role in susceptibility to GBS disease. It is of interest to note, however, that in 1999 the incidence of neonatal GBS bacteraemia in India was 0.17 per 1,000 live births60
, whereas a rate of 2.6 per 1,000 live births was reported in 1991 among babies born to native Indians living in South Africa61
. Although these studies were done almost a decade apart, and were not designed to address the impact of genetics on susceptibility to disease, they do offer some insight into the role of healthcare services and environmental influences on disease rates.
The increased incidence of GBS disease among non-pregnant and elderly adults is discussed in detail elsewhere1,62
. Invasive GBS disease in the non-pregnant, adult population has been documented in several countries, including the United States, France, Taiwan and Spain with incidence rates ranging from 4.4 to 23 cases per 100,000 adults. The higher rates of incidence occur in patients that are 60 years of age or older. Primary bacteraemia is the most common form of invasive disease, followed by skin and soft-tissue infection, pneumonia and urinary-tract infections. Risk factors for adult GBS disease include diabetes mellitus, cardiovascular disease, liver disease and cancer, and infections can be community- or nosocomially acquired. In a population-based survey, the incidence of invasive GBS disease among nursing home residents aged 65 years or older was 72.3 per 100,000 compared with 17.5 per 100,000 in age-matched non-nursing home residents4
. GBS serotypes Ia, III, and V predominate in these patients with similar colonization rates (21.7%) to that of younger patients63
. These epidemiological findings, which increase the target population for an efficacious vaccine, have undoubted implications for GBS vaccine development and implementation.