Group B streptococcal disease in newborns: a global perspective on prevention

Biomed

& Pharmacother

0 Elsevier.

(1995)

49,

19-25

Paris

Dossier “Infectious

diseases”

Group

B streptococcal disease in newborns: a global perspective on prevention A Schuchat

Childhood

and

Respiratory

Diseases

Branch, Prevention,

National Mailstop

Center C-09,

for Infectious Diseases, Atlanta, GA 30333, USA

Centers

for

Disease

Control

and

Summary - Group B Sfreprococcus (GBS) is an important cause of neonatal sepsis in many areas. Although incidence data are available for a minority of countries, the magnitude of illness due to this bacterium appears to vary substantially. Disease may vary due to the prevalence of asymptomatic GBS colonization, the virulence of circulating strains, the frequency of predisposing conditions such as low birth weight, or differences in obstetric practices. Approaches to prevention of neonatal GBS disease include administering antibiotics to high risk mothers intrapartum, use of intrapartum vaginal disinfectants, development of CBS vaccines, and nonspecific approaches. Determinants of prevention policies in a given area depend on the incidence of disease, the structure of health care delivery, cost-effectiveness, and cultural attitudes. Much GBS disease among newborns is now preventable, yet data on incidence are needed to guide selection of appropriate approaches to disease prevention. group

B Streptococcus

I prevention

! epidemiology

INTRODUCTION

CLINICAL

Since the 197Os, Streptococcus agafactiae, or group B Streptococcus (GBS), has been a common cause of neonatal sepsis in many areas [2]. The global burden of disease due to GBS is not known, but the importance of this pathogen appears to vary throughout the world [ 1, 31. Recently, controversy regarding approaches to prevention of neonatal GBS disease has drawn renewed attention to this disease [4-71. Regional differences in neonatal morbidity, childbirth practices, and even the structure of health care systems may account for the diversity of strategies advocated for control of GBS disease. This article will review the epidemiology and prevention of neonatal GBS disease from a global perspective.

“Now that the hopes of effective B streptococaal disease is more

prevention important

BACKGROUND

In newborns, two distinct syndromes of invasive GBS infection occur. Early onset disease is characterized by presentation of the illness within the first week of life, although most of these infections are evident soon after birth. Late onset disease occurs in infants one week to three months of age. The most common clinical forms of GBS disease in newborns are sepsis and pneumonia, but meningitis, cellulitis, and other focal infections also occur. Mortality due to GBS disease has decreased from 50% in some series from the 1970’s to less than 10% in large population-based studies in the 1990’s [8, 91. Neurologic sequelae, particularly among infants with meningitis, can be severe but are of undetermined frequency.

are being realised, the need for a knowledge than ever to all countries.” R.T. Mayon-White,

of the true incidence 1985 (11

of neonatal

group

20

A Schuchat

COLONIZATION GBS colonizes the gastrointestinal and genitourinary tracts of humans. Asymptomatic carriage is frequent, and has been detected in 5 to 35% of subjects in various studies [2]. A pregnant women who is colonized with GBS may transmit the organism to her fetus through ascending spread from the genital tract, or the newborn may acquire the organism during passage through the birth canal. Up to 80% of infants born to colonized mothers become colonized with GBS at skin or mucous membrane sites; however, early onset GBS disease occurs in only l-2% of infants born to colonized women [2]. Substantial variation in the prevalence of GBS carriage among pregnant women has been reported. Some of these differences are probably artifactual, a result of variable culture methodology. GBS is most likely to be isolated when specimens are collected from both vagina and rectum [IO121 and when selective broth medium, containing nalidixic acid and either colistin or gentamicin, is used for culture of the organism [ 13, 141. Nonetheless, studies performed with similar methods demonstrate that GBS carriage can vary among pregnant women in different populations (table I). A large multicenter study of GBS colonization in the United States, in which 7,742 pregnant women were evaluated with identical methods, found the prevalence of GBS carriage varied nearly three-fold between study sites, from 9% for women in San Antonio, Texas to 26% among women studied in New York City. The incidence of invasive GBS disease does not correlate precisely with colonization rates. Fac-

Table

I. Colonization

with Number

India Canada Greece Spain Netherlands Sweden Nigeria Ivory Coast United States Gambia Britain Jordan

group

B Streprococcus

of women

325 237 200 1,050 762 786 388 150 1,742

136 I .457 500

among Culture

pregnant sires

rectum,

RISK

urine

FACTORS

FOR

NEONATAL

DISEASE

Intrauterine infection is most likely to occur in deliveries complicated by prolonged membrane rupture or prematurity. Women with GBS colonization who develop clinical chorioamnionitis are more likely than others to deliver infants with early onset GBS disease. In an elegant series of studies, Boyer and Gotoff followed a cohort of pregnant women who had prenatal cultures collected for GBS colonization, and estimated the incidence of early onset disease according to presence or absence of maternal colonization and intrapartum complications (prematurity, intraparturn fever, or prolonged membrane rupture) [lo, 20-221. Incidence was highest in infants born to women with prenatal GBS carriage who also had an intrapartum complication (41/10’ births); early onset GBS disease occurred at lower rates in the other groups: colonized without intrapartum complications = 5/10’ births; noncolonized with intrapartum complications = 0.9/103 births; noncolonized without intrapartum complications = 0.3/103 births [23]. Others have shown that early onset disease incidence varies according to birth weight [18] and the heaviness of genital colonization 1241.

women Culture

Vagina, endocervix Vagina, rectum Vagina Vagina, rectum Vagina, cervix, rectum Urethra, cervix Vagina Vagina, cervix, vulva Vagina, cervix Vagina, rectum Vagina. rectum Vagina,

tors other than the prevalence of carriage, such as the virulence of circulating strains [ 1.5-171. frequency of predisposing conditions such as low birth weight [ 181, or differences in obstetric practices [ 191 may be more important influences on GBS incidence in a community.

in different

countries

medium

Selective broth Selective broth Selective broth Not stated Selective broth Selective broth Selective broth Not specified Selective broth Selective broth Selective broth and selective agar Selective broth

Colonized

67c II% 12% 12% 14% 16% 18% 19% 19% 22%

Reference

28%

I6 46 47 17 48 49 50 51 52 I5 42

30%

53

GBS disease

INCIDENCE Because the diagnosis of GBS disease requires isolation of the bacterium, diagnostic practices can influence recognition of cases. Since facilities with microbiologic capability are not widely available in developing countries, the incidence of GBS disease is unknown for many areas. Increasing use of blood cultures in industrialized countries could theoretically have contributed to enhanced detection of GBS cases [l]. Most incidence estimates for neonatal GBS disease originated from hospital-based studies (table II). However, in a single community, referral patterns can skew the risk profile of women delivering at a hospital and thus have major impact on disease rates. Small numbers of deliveries in many hospitals limit the reliability of incidence calculations, since a few cases can lead to substantial fluctuation in estimated rates. The most robust estimates of incidence are therefore based on large numbers of births distributed among a heterogeneous population. True regional differences in incidence of neonatal GBS disease do exist. Population-based surveillance in five geographic areas in the United States, with greater than 250,000 births, identified large geographic differences in the incidence of early onset disease [9]. More striking than geographic variation were differences in race-specific rates in all areas (incidence of early onset disease among Blacks: 2.9/103 births; incidence among Whites: 1.3/10’ births). Although some of the ra-

Table

II. Incidence

COUntiT

Denmark Britain Netherlands Mexico Australia New Zealand Scotland Jamaica Sweden United States Cameroon South Africa * Denominator

of neonatal

group

Setting

Population-based Population-based Hospital Hospital Hospital Hospital Hospital Hospital Hospital Population-based Hospital Hospital not stated;

estimated

B steptococcal

Dates

1978-83 1978-79 1977-82 1986.88 1981.88 1983-90 1972-77 1982-85 1975-76 1990 1985-89 1986-89

disease

Number births

of

-333,000” 226.899 100,000 20,054 57,112 - 37,000’ 20.040 7,820 32,143 180,000 7,428 14,327

based on number

21

in newborns

cial gap in early onset disease can be attributed to a higher prevalence of prematurity and low birth weight among Black infants, other factors, such as access to medical care, might play a role. In nearly all populations studied, early onset disease occurs more commonly than late onset disease (table II). Late onset cases usually account for less than one-third of neonatal GBS disease. In the report by Faxelius ef al, only 5% of neonatal GBS cases were late onset; the authors speculated that hospital hygienic practices led to their very low rate of late onset infection [25]. A report from Cameroon was remarkable for the predominance of late onset cases: the authors suggested that very early discharge from maternity hospitals may have delayed detection of illness in many infants, until persistent infection led to the late onset syndrome [26]. The variation in ratios of early to late onset disease observed is consistent with different pathogenetic mechanisms for the two syndromes; obstetric factors and maternal genital colonization influence early onset infection, while nonmaternal sources appear to account for acquisition of GBS in many late onset cases [27]. APPROACHES

TO PREVENTION

Regional differences in childbirth practices and population characteristics may contribute to global variation in the incidence of neonatal GBS disease. The priority given to GBS disease pre-

in different

countries

Early onset disease (caws per IO’ births)

Late onset disease (cases per IO’ births)

Ratio Earl? onset to l&tonset cases

0.08 0.05 0.09 0.05 NA 0.11 0.04 0.40 0.06 0.32 6.20 0.56

2.1.1 4.8:l 4.0: 1 12.0: 1 NA 7.3:1 16.0: I 2.5: 1 20.0: I 4.4: I .31:1 3.8:l

0.16 0.24 0.36 0.60 0.75 0.78 0.80 1.OO 1.20 1.40 I .90 2.09

of cases and incidence

cited;

NA:

Not

available.

Rqference

54 55 56 57 32 58 59 60 25 8 26.61 62

22

A Schuchat

vention will correspond to the perceived magnitude of the problem in a locality as well as its rank among other health problems. Thus it is not surprising that numerous approaches to prevention of perinatal infections in general, and GBS infections in particular, have emerged.

cient quantities to protect the fetus in ufero and newborns during the first months of life. Investigators have purified the major capsular polysaccharide antigens and conjugated them to carrier proteins, and data from animal protection studies are encouraging [38-411.

Antibiotic

Nonspecific

prophylaxis

Investigators initially documented that oral antibiotic therapy during pregnancy did not eliminate maternal carriage or reduce intrapartum GBS transmission [28, 291. Intramuscular antibiotics administered to infants at birth appeared promising in one trial [30], but had no impact on illness or death among low birthweight infants in another trial [31]. Intrapartum antibiotics are clearly effective at eliminating neonatal colonization and preventing perinatal infection, but investigators have proposed a variety of strategies for selection of women who warrant prophylaxis. Selection criteria may include prenatal GBS colonization [32], heavy maternal colonization [24], prenatal colonization and intrapartum complications [22], and intrapartum complications without determination of GBS colonization status [4, 61. Vaginal

disinfectants

A different method of interrupting vertical transmission of GBS has been studied in Scandinavia, where vaginal disinfectants were used nonselectively in women presenting in labor with the goal of reducing the bacterial inoculum to which the infant is exposed [33, 341. In a trial conducted in Sweden, use of chlorhexidine vaginal douches decreased admission to the neonatal special care unit, but the study was of insufficient size to estimate efficacy of this approach in the prevention of early onset GBS disease [34]. Norwegian investigators reported preliminary data on chlorhexidine obstetric cream used during intrapartum vaginal examinations [35]. Immunization Type-specific anticapsular antibody protects against GBS disease and investigators are therefore pursuing development of GBS vaccines [36, 371. Vaccination of pregnant women could theoretically prevent perinatal disease, if vaccineinduced antibody crosses the placenta in suffi-

approaches

Nonspecific approaches to GBS prevention are directed at preventing the obstetric complications that increase risk of GBS disease - such as prematurity and obstructed labor. These are most appropriate in areas where GBS incidence is low relative to other perinatal complications. However, substantial progress is still needed in identifying effective approaches to the prevention of prematurity. DETERMINANTS

OF PREVENTION POLICIES

Attempting to identify determinants of GBS prevention policies may presuppose that approaches to prevention arise from conscious decision-making. All too often in industrialized countries, prevention has been neglected while tremendous efforts are aimed at enhancing therapeutic options. In the developing world, disease-specific prevention programs are often less appropriate than integrated approaches to health concerns, such as the broad focus afforded by safe motherhood programs. Where approaches to prevention of GBS disease have been considered explicitly, a few factors appear to have a major influence on what approach is selected. The incidence of recognized disease is a primary consideration in whether focusing resources on a GBS prevention program is indicated [42]. However, even where neonatal GBS disease incidence is relatively high (> 2 per 1,000 births), surveillance in large populations is needed to accurately identify the magnitude of the problem. The structure of health care delivery also influences the selection of a prevention strategy. Since most early onset disease occurs within a few hours of birth, in a health care system where home births predominate and access to health care facilities is limited, medical attention may not be available in time to treat infants, let alone in time to identify high risk mothers for preventive mea-

GBS

dtsease

sures. In systems where women and children are cared for by different specialists, prevention of perinatal GBS disease may also be problematic. GBS disease may be considered a major problem for pediatricians because it is common among ill newborns, but prevention programs need to be implemented by obstetricians, for whom GBS may be viewed as a rare complication among pregnant patients. Additional factors influencing prevention policies are economic [43-451. For example, the decision to give intrapartum chemoprophylaxis to all prenatal carriers [32] instead of treating only those carriers who develop labor complications [22] is in part an economic decision. Medical liability can also play a role, as the decision to limit antibiotic use to one high risk group over another may appear difficult to explain to those low risk women whose infants develop GBS disease. Medico-legal judgments may consider the failure to prevent a bad outcome (ie, GBS disease) differently from causing a bad outcome (ie, anaphylaxis to penicillin) in an attempt to prevent disease. Cultural attitudes are also important, and may account for researchers in Scandinavia taking the lead in vaginal antisepsis studies while investigators in the United States have focused on vaccine development as well as studies of systemic antimicrobials. Some communities may prefer evaluating a prevention strategy which poses essentially no risk to asymptomatic women (ie, topical disinfectant) while others favor a strategy which may have higher efficacy in disease prevention (ie, intravenous antimicrobials) even though adverse effects (ie, anaphylaxis and potentially emergence of antimicrobial resistant infections) are more likely to occur. Attitudes among clinicians and researchers have traditionally guided the research agenda for GBS disease. However, recent efforts initiated outside the medical community have focused on promoting GBS disease prevention. Based on the activism of a community-based parents’ group, certain state legislatures in the United States have considered the issue of mandatory patient education regarding options for GBS disease prevention. Media attention to the topic in Canada eventually prompted medical professionals there to prepare a national prevention policy, jointly endorsed by obstetric and pediatric professional organizations [7].

23

in newborns

CONCLUSION A growing body of evidence suggests that group B Streptococcus is an important cause of perinatal morbidity in many countries. Substantial information is now available regarding effective means of preventing perinatal cases, yet numerous factors contribute to selecting among prevention programs, In the future, effective GBS vaccines may offer highly efficacious means of disease prevention. Yet decisions for the use of vaccines as well as prevention modalities that are already available will be based in part on how important a problem GBS disease is considered in a particular area. Even in areas where GBS accounts for a major proportion of preventable perinatal illness, the magnitude of the problem may not be recognized. Surveillance for neonatal GBS disease thus becomes critical for identifying the need for disease prevention and monitoring the impact of prevention programs.

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GBS

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in newborns

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56

57

58 59

60

61

62

25