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Group B Streptococcus
Group B streptococci are one of the most important infectious causes of neonatal morbidity and mortality. Women vaginally or rectally colonized with Group B streptococci during pregnancy are at increased risk of transmitting the bacteria to their newborn infant during labour and delivery. Pregnancy-associated streptococcal infection can result in maternal sepsis. It also is the leading cause of chorioamniotitis and one of several infections now thought to enhance the risk of preterm rupture of membranes. In the newborn, early onset of the disease is recognized as pneumonia and bacteraemia within the first seven days of life, whereas late onset disease primarily occurs in the form of meningitis between 7 and 90 days of age. Vaginal group B streptococcal colonization has been reported to occur in about 12–27% of women in North Africa, India, the Middle East, Pakistan, Saudi Arabia and the USA. Surprisingly, a WHO collaborative study on serious infections in young infants conducted in four developing countries showed that Group B streptococci were found in only 2 of 167 blood culture isolates and 1 of 40 CSF isolates, whereas Group A streptococci were recovered from 29/167 blood isolates and 3/40 CSF isolates. These data may have been biased by the fact that infants who develop streptococcal sepsis on the day of birth will usually not survive. It might also be that Group B streptococcal-related morbidity in developing counties often manifests itself through miscarriage or preterm delivery, in which case infants may not survive to develop confirmed sepsis.
Invasive group B streptococcus disease has also been frequently reported in adults with diabetes, neurological impairment, breast cancer and cirrhosis. Its manifestations include soft tissue infections, bone and joint infections and pneumonia or, more rarely, endocarditis and meningitis. Adults over 65 years of age are at the highest risk of dying from invasive group B disease.
Early onset of Group B disease in neonates can be prevented by the use of intrapartum chemoprophylaxis, as was done in South Africa. Active immunization of mothers during the third trimester of pregnancy to elicit an antibody response and passively protect the newborns represents an attractive alternative strategy. Streptococcal capsular polysaccharides (PS) have been found to elicit serotype-specific protective immunity, but showed low immunogenicity if not conjugated to a protein carrier. Conjugated PS vaccines have been developed using as a protein carrier either the tetanus toxoid (TT) or a recombinant cholera toxin B subunit (CTB) administered intranasally to increase the mucosal antibody response, or group B streptococcal surface antigens such as the C5a peptidase or the C protein. Most of the resulting formulations have been tested in mice and a few in non-pregnant women. A bivalent Ia and Ib PS-TT conjugate vaccine was well-tolerated in women and elicited a dose-dependent antibody response that correlated with in vitro opsonophagocytosis. A type III PS-TT conjugate vaccine administered to third-trimester pregnant women was well tolerated and induced PS-specific antibodies that were efficiently transported to the infant and could be detected through two months of life. Microscience (USA) and Intercell (UK) are developing vaccines based on novel surface protein candidates.
A major difficulty in developing Group B streptococcal vaccines is the existence of a multiplicity of serotypes with different geographical distributions. A vaccine suitable for Asian or European populations may not be suitable for African populations. Another difficulty, similar to that encountered with Group A streptococcal vaccines, is the implementation of efficacy trials. A Phase III evaluation of candidate vaccines in women before pregnancy will require large sample sizes and take a long time. Administration of the vaccine to pregnant women may be difficult because of fear of risks of birth defects and subsequent liability.