Elsevier

The Lancet

Volume 379, Issue 9815, 11–17 February 2012, Pages 547-556
The Lancet

Articles
Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis

https://doi.org/10.1016/S0140-6736(11)61651-6Get rights and content

Summary

Background

Despite widespread use of intrapartum antibiotic prophylaxis, group B streptococcus remains a leading cause of morbidity and mortality in infants in Europe, the Americas, and Australia. However, estimates of disease burden in many countries outside of these regions is not available. We aimed to examine the current global burden of invasive disease and the serotype distribution of group B streptococcus isolates.

Methods

We searched Medline, Embase, and Wholis databases for studies on invasive early-onset (day 0–6) and late-onset (day 7–89) group B streptococcal disease. Eligible studies were those that described incidence, deaths, or serotypes. We also reviewed reference lists and contacted experts to seek unpublished data and data missed by our search. Random effects meta-analysis was used to pool data.

Findings

74 studies met the inclusion criteria; 56 studies reported incidence, 29 case fatality, and 19 serotype distribution. An additional search for studies that reported serotype distribution from Jan 1, 1980, yielded a total of 38 articles. Only five low-income countries were represented in the review and contributed 5% weight to the meta-analysis. 47 (69%) studies reported use of any intrapartum antibiotic prophylaxis. Substantial heterogeneity existed between studies. Mean incidence of group B streptococcus in infants aged 0–89 days was 0·53 per 1000 livebirths (95% CI 0·44–0·62) and the mean case fatality ratio was 9·6% (95% CI 7·5–11·8). Incidence of early-onset group B streptococcus (0·43 per 1000 livebirths [95% CI 0·37–0·49]) and case fatality (12·1%, [6·2–18·3]) were two-times higher than late-onset disease. Serotype III (48·9%) was the most frequently identified serotype in all regions with available data followed by serotypes Ia (22·9%), Ib (7·0%), II (6·2%), and V (9·1%). Studies that reported use of any intrapartum antibiotic prophylaxis were associated with lower incidence of early-onset group B streptococcus (0·23 per 1000 livebirths [95% CI 0·13–0·59]) than studies in which patients did not use prophylaxis (0·75 per 1000 livebirths [0·58–0·89]).

Interpretation

More high-quality studies are needed to accurately estimate the global burden of group B streptococcus, especially in low-income countries. A conjugate vaccine incorporating five serotypes (Ia, Ib, II, III, V) could prevent most global group B streptococcal disease.

Funding

Child Epidemiology Reference Group (CHERG), WHO.

Introduction

Group B streptococcus (Streptococcus agalactiae) is the most common cause of neonatal sepsis in high-income countries.1, 2 Disease risk is highest during the first 3 months of life and declines substantially thereafter. Early-onset disease (day 0–6) is the result of vertical transmission from a colonised mother during or just before delivery.3 Late-onset disease (day 7–89) can be acquired from the mother or from environmental sources.4, 5 Case fatality from both early-onset and late-onset disease is high, even with antibiotic therapy.2, 3 Group B streptococcus is also an important cause of preterm delivery, antepartum and intrapartum stillbirth, and puerperal sepsis.6, 7

Prevention of early-onset group B streptococcus has become a realistic option, through the use of intrapartum antibiotics given to pregnant women with risk factors or known carriage of the bacteria (intrapartum antibiotic prophylaxis).8, 9, 10 This prophylaxis has been implemented in most high-income countries since the late 1990s, but has been difficult to implement in many low-income countries and middle-income countries.11, 12, 13 Several group B streptococcus vaccines are also at various stages of testing and could allow prevention of both early-onset disease and late-onset disease.6, 14 However, many challenges exist to obtaining accurate estimates of disease burden, especially for low-income and middle-income countries, including difficulties with obtaining specimens and poor laboratory capacity for diagnosis of group B streptococcus.

We aimed to estimate the incidence of group B streptococcal invasive disease and case fatality in infants aged 0–89 days in the era of intrapartum prophylaxis, estimate the incidence of early and late onset invasive disease, and estimate distribution of group B streptococcal serotypes in invasive disease specimens. Secondary objectives were to assess how the incidence of group B streptococcus varies with gross national income (GNI) per head and geographical region.

Section snippets

Definitions and classification

We defined invasive group B streptococcal disease as laboratory isolation of Streptococcus agalactiae from a normally sterile site in an infant aged 0–89 days with any signs of clinical disease (eg, sepsis, pneumonia, or meningitis).

Search strategy and selection criteria

We searched Medline, Embase, and Wholis databases using the search terms (“Streptococcus agalactiae”[Mesh] OR “Streptococcus Group B” OR “Group B Streptococcal”) AND Limits: Humans, Publication date 2000/01/01–2011/09/01. We restricted our search from January 2000,

Results

2709 papers were identified from the Medline and Wholis search from Jan 1, 2000, to Sept 1, 2011, and 423 titles were retained. No additional articles were obtained from the Embase search, 111 titles were obtained from the concurrent WHO Global Burden of Disease neonatal-infection search, and 114 titles were obtained from experts in neonatal care and reference lists. No unpublished data that met our inclusion criteria were identified. 74 papers were retained after the abstracts were reviewed

Discussion

More studies are needed to accurately estimate the global burden of group B streptococcus, especially in low-income countries. We judge our overall estimate of group B streptococcus incidence (0·53 per 1000 livebirths) to be an underestimate of the global incidence. Incidence and case fatality were two-times higher in infants who had group B streptococcal disease in the first week of life (0–6 days) compared with later infancy (7–89 days). The disease is often rapidly fulminating and many cases

References (92)

  • CL Cutland et al.

    Chlorhexidine maternal-vaginal and neonate body wipes in sepsis and vertical transmission of pathogenic bacteria in South Africa: a randomised, controlled trial

    Lancet

    (2009)
  • JS Kim et al.

    Incidence of Haemophilus influenzae type b and other invasive diseases in South Korean children

    Vaccine

    (2004)
  • K Matsubara et al.

    Invasive group B streptococcal infections in a tertiary care hospital between 1998 and 2007 in Japan

    Int J Infect Dis

    (2009)
  • CJ Chang et al.

    Neonatal bacterial meningitis in southern Taiwan

    Pediatr Neurol

    (2003)
  • AK Zaidi et al.

    Hospital-acquired neonatal infections in developing countries

    Lancet

    (2005)
  • BJ Stoll

    The global impact of neonatal infection

    Clin Perinatol

    (1997)
  • KL O'Brien et al.

    Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates

    Lancet

    (2009)
  • CL Trotter et al.

    Optimising the use of conjugate vaccines to prevent disease caused by Haemophilus influenzae type b, Neisseria meningitidis and Streptococcus pneumoniae

    Vaccine

    (2008)
  • BJ Stoll et al.

    Early onset neonatal sepsis: the burden of group B Streptococcal and E coli disease continues

    Pediatrics

    (2011)
  • J Guilbert et al.

    Late and ultra late onset Streptococcus B meningitis: clinical and bacteriological data over 6 years in France

    Acta Paediatr

    (2009)
  • MK Van Dyke et al.

    Evaluation of universal antenatal screening for group B streptococcus

    N Engl J Med

    (2009)
  • Heath PT. An update on vaccination against group B streptococcus. Expert Rev Vaccines 10:...
  • JA Walsh et al.

    Group B streptococcal disease: its importance in the developing world and prospect for prevention with vaccines

    Pediatr Infect Dis J

    (1989)
  • SJ Schrag et al.

    A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates

    N Engl J Med

    (2002)
  • TE Colbourn et al.

    Preventive strategies for group B streptococcal and other bacterial infections in early infancy: cost effectiveness and value of information analyses

    BMJ

    (2007)
  • SJ Schrag et al.

    Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis

    N Engl J Med

    (2000)
  • SA Madhi et al.

    High burden of invasive Streptococcus agalactiae disease in South African infants

    Ann Trop Paediatr

    (2003)
  • E Molyneux et al.

    Acute bacterial meningitis in children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi in 1996–97

    Trop Med Int Health

    (1998)
  • Child Health Epidemiology Reference Group (CHERG)

  • Global Burden of Diseases, Injuries, and Risk Factors Study

  • GNI per capita, Atlas method

  • P Bromberger et al.

    The influence of intrapartum antibiotics on the clinical spectrum of early-onset group B streptococcal infection in term infants

    Pediatrics

    (2000)
  • ACOG Committee Opinion: number 279, December 2002, Prevention of early-onset group B streptococcal disease in newborns

    Obstet Gynecol

    (2002)
  • L Strakova et al.

    Active surveillance of early onset disease due to group B streptococci in newborns

    Indian J Med Res

    (2004)
  • J Andersen et al.

    Clinical features and epidemiology of septicaemia and meningitis in neonates due to Streptococcus agalactiae in Copenhagen County, Denmark: a 10 year survey from 1992 to 2001

    Acta Paediatr

    (2004)
  • K Ekelund et al.

    Invasive group B streptococcal disease in infants: a 19-year nationwide study. Serotype distribution, incidence and recurrent infection

    Epidemiol Infect

    (2004)
  • P Kuhn et al.

    Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics

    Paediatr Perinat Epidemiol

    (2010)
  • K Fluegge et al.

    Incidence and clinical presentation of invasive neonatal group B streptococcal infections in Germany

    Pediatrics

    (2006)
  • A Berardi et al.

    Group B streptococcal infections in a northern region of Italy

    Pediatrics

    (2007)
  • M Trijbels-Smeulders et al.

    Epidemiology of neonatal group B streptococcal disease in the Netherlands before and after introduction of guidelines for prevention

    Arch Dis Child Fetal Neonatal Ed

    (2007)
  • A van den Hoogen et al.

    Long-term trends in the epidemiology of neonatal sepsis and antibiotic susceptibility of causative agents

    Neonatology

    (2009)
  • V Hasseltvedt et al.

    Systemic streptococcal group B disease in Norway-an increasing health problem

    Euro Surveill

    (2001)
  • A Hajdu et al.

    Unexpected increase in case fatality of invasive group B streptococcal infections in infants in Norway, January–July 2006

    Euro Surveill

    (2006)
  • MT Neto

    Group B streptococcal disease in Portuguese infants younger than 90 days

    Arch Dis Child Fetal Neonatal Ed

    (2008)
  • J Lea

    Screening of hemolytical streptococcus of group B in pregnancy and prevention of infection in newborns

    Ceska Gynekologie

    (2004)
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