Group B Streptococcus is an important cause of maternal and neonatal morbidity and mortality in many parts of the world. The last two decades have seen intensified efforts in the Western hemisphere in the prevention of this devastating infection by identifying and treating pregnant women who carry group B streptococci or who are at highest risk of transmitting the organism to newborns. The intrapartum use of antibiotics in these women has led unequivocally to a decrease in the rate of neonatal group B streptococcal disease. Although studies in India show a predominance of Gram negative bacterial sepsis among infants, contributing to infant mortality, it is possible that the role of group B Streptococcus has been underestimated. This review discusses its epidemiology in India, and summarizes current concepts of microbiology, pathogenesis, clinical management and preventative issues regarding group B streptococcal disease.
Key words Chemoprophylaxis * colonization * group B Streptococcus * neonatal mortality * perinatal transmission * sepsis
Group B Streptococcus (GBS) is a leading cause of neonatal infection in the Western hemisphere. The recognition that maternal colonization with the organism is a key factor in the occurrence of GBSassociated neonatal morbidity and mortality was a milestone in the history of perinatal health1. A nationwide change in health practices helped diminish mortality and morbidity associated with the disease. In India, however, the spectrum of group B streptococcal disease remains a largely underrecognized problem.
Puerperal sepsis has been described for centuries, and ancient Indian texts in 1500 BC have recorded that good hygiene leads to a reduction in perinatal disease2. In 1879 Louis Pasteur identified the streptococcus as the causative organism for puerperal sepsis3. Since the early 1930s when Rebecca Lancefield reported her grouping system for haemolytic streptococci, group A Streptococcus (Streptococcus pyogenes} was widely acknowledged as the major pathogen associated with puerperal sepsis4. GBS was initially thought to be a commensal, until 1937, when Fry reported seven cases of GBSassociated puerperal fever with 3 deaths5.
Epidemiology and transmission
During the 1970s and 1980s, GBS emerged as a significant neonatal and maternal pathogen in the United States (US) and Western Europe with reported mortality rates of 15 to 50 per cent6,7. In the US, 10 to 35 per cent of pregnant women are asymptomatic carriers of GBS in the genital and gastrointestinal tract at the lime of delivery8. The prevalence of GBS colonization during pregnancy is variable; in one study, among women who had positive GBS cultures between 26 and 28 wk gestation, only 65 per cent remained colonized at term, while 8 per cent of those with negative prenatal cultures were positive for GBS at terrn9. Treatment of these colonized mothers succeeded in temporarily eradicating the organism, but most of the women were re-colonized within 6 wk. At birth, 50 to 65 per cent of infants who are born to colonized mothers have positive GBS cultures from mucus membranes and skin (external car canal, throat, umbilicus, anorectal sites)1,10. Approximately 98 per cent of colonized newborns remain healthy, but 1 to 2 per cent develop invasive GBS infection7. The overall incidence of neonatal GBS infection was approximately 2 per 1000 live births in the United States prior to the introduction of intrapartum prophylaxis7.
Epidemiological studies in India have shown lower colonization and infection rates in gcneral11-15. However on closer analysis, taking into consideration use of adequate culture techniques and microbiological media, some of the GBS colonization rates reported from India and other developing countries are similar to those reported in the United States11. In a study done in 507 pregnant Indian women, 12 percent were reported to have GBS isolated from the throat and vagina, and 10 per cent had positive vaginal cultures alone12. Similarly, another study showed the overall carriage rate in pregnant women to be 16 per cent13. Although both these studies used selective broth media, culture sites did not include the anorectum and this might have lowered the yield of positive cultures. Other studies have reported colonization rates of 5 to 6 per cent, but no selective broth media were used in these cases14,15. Colonization rates in infants born to asymptomatic maternal carriers of GBS are 53 to 56 per cent and are consistent with rates reported in other parts of the world13,15. Despite significant GBS colonization rates, reports of invasive neonatal GBS disease in India are infrequent. During a 10-yr study between 1988 and 1997 in Vellore, only 10 cases of neonatal GBS infection were identified, giving an incidence of 0.17 per 1000 live births16. However, this number represents only the cases occurring among deliveries in a tertiary care hospital located in a predominantly rural community. In India where 65 per cent of women give birth at home, the true incidence of invasive GBS disease in the newborn is largely unknown17. In addition, blood cultures from ill neonates are not always done in many rural primary health care centres, which may contribute to the underestimation of the number of GBS cases. Preterm births and stillbirths are also usually not investigated, and thus the total burden of perinatal GBS disease remains unrecognized.
The estimated incidence of neonatal GBS infection in India can be calculated from Indian cpidemiological data reporting maternal and infant GBS colonization rates as 10 and 50 per cent respectively.12,13,15. Since about 2 per cent of colonized neonates develop true infection6, the attack rate of neonatal GBS infection in India may be calculated as approximately 1 per 1000 live births. Bearing in mind the above estimated attack rate and current Indian demographic data (midyear population count in the year 2001 was approximately 1027 million, and birth rate was 26 births per 1000 population pcryear)18, the projected total number of GBS infection in newborn infants in India may be as high as 26,700 cases per year.
GBS serotypes and pathogcnesis
Group B streptococci (also called Streptococcus agalatiae) are Gram positive cocci belonging to Lancefield group B. There are 9 antigenically distinct serotypes based on their capsular polysaccharide structure (types Ia, Ib, II - VIII) identified to date. In the US and Western Europe, types Ia, II, and III accounted for 85 per cent of the isolates from infants19,20. Recent studies in the US have demonstrated that serotypes Ia, IM, and V (in descending frequency) accounted for 78-87 per cent of early-onset (less than seven days after birth) invasive disease in newborn infants and parturient women21,22. Late-onset GBS disease in infants 7-90 days of age is dominated by serotype III, followed by serotypes Ia and V22. Studies from the state of Minnesota from January 1993 through December 1999 reflected the above national trends in the US (Fig.), (Ferrieri P. unpublished data). Studies from India show a variable distribution of serotypes, but the most common isolates belong to types III, II and Ib13-15,23.
The most important risk factor for early-onset GBS infection in the neonate is the presence of the organism in the maternal genitourinary tract at delivery. Ascending bacteria from the maternal genital tract reach the amniotic fluid, usually after rupture of the amniotic membranes1,24. Alternatively, the newborn can come into contact with GBS during passage through the birth canal. When the foetus aspirates contaminated amniotic fluid, group B streptococci reach the lower respiratory tract and damage pulmonary epithelial cells, resulting in pneumonia and respiratory distress usually within the first few hours after birth. Severe GBS sepsis occurs with intravascular invasion of bacteria and failure of the host to eliminate the pathogen25,26. Ascending infection can also occur through intact chorioamniotic membranes, with subsequent events occurring in utero, resulting in stillbirths or death within hours after birth24. The pathogenesis in late-onset disease is less clear. Horizontal transmission plays a major role: close contact with the mother, breast-feeding and nosocomial transmission.
