© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
COMMENTARY
Late-onset group B streptococcal disease is a rare
but devastating disease
KL Hon, MB, BS, MD1,2; Karen KY Leung, MB, BS, MRCPCH1; Alexander KC Leung, FRCP(UK), FRCPCH3; KW So, MB, BS, FRCPCH2
1 Department of Paediatrics and Adolescent Medicine, The Hong Kong Children’s Hospital, Hong Kong
2 Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong
3 Department of Pediatrics, The University of Calgary and the Alberta Children's Hospital, Calgary, Alberta, Canada
Corresponding author: Dr KL Hon (ehon@hotmail.com)
Group B streptococcus (GBS) or Streptococcus
agalactiae is an organism colonising the maternal
gastrointestinal and genital tracts which may lead to
significant morbidities and mortalities in infants.1 2 3 4
Universal screening of pregnant mothers for GBS
carriage has been implemented in Hong Kong since
2012 but we continue to encounter late-onset GBS
disease.4 This commentary reviews the epidemiology,
risk factors, mortality, and morbidity of late-onset
GBS especially pertinent to Hong Kong.
A 2017 global study revealed some 21.7 million
pregnant women carry GBS and infections cause
150 000 preventable stillbirths and infant mortality
annually.5 Before 2012, a risk-based screening
strategy was used to select patients for intrapartum
antibiotics prophylaxis and the incidence of early-onset
GBS disease was 0.58 to 1.1 per 1000 live births
in Hong Kong.3 A universal screening swab-based
screening programme was implemented in Hong
Kong after 2012.6 The worldwide incidence of late-onset
GBS disease is 0.26 per 1000 live births, while
the incidence in Hong Kong was 0.38 per 1000 live
births despite intrapartum antibiotics.7 8
Maternal risk factors for early-onset GBS
disease include vaginal GBS colonisation, GBS
bacteriuria, intrapartum maternal fever, and
chorioamnionitis. Overall 18% of women worldwide
and 21.8% of Hong Kong mothers are colonised.5 6
A local study has shown that highly educated and
socially advantaged professional women were
more likely to be carriers, and that there were no
differences in the colonisation rate between Hong
Kong and mainland Chinese citizens.9 The risk of
neonatal GBS septicaemia for infants born to women
diagnosed with vaginal GBS colonisation can be as
high as 25 times compared with women who are
not colonised.4 Vertical transmission of GBS occurs
after rupture of the amniotic membranes or after the
onset of labour. The risk of early-onset GBS disease
is extremely low if the mother is undergoing planned
caesarean section in the absence of labour and with
intact membranes.10 Other risk factors include
prematurity, premature or prolonged rupture of
amniotic membranes, multiple gestation pregnancy, and prior delivery of an infant with GBS disease.3 11
For late-onset GBS disease, in contrast to
early-onset GBS disease, vaginal GBS colonisation is
not a crucial factor. Reported risk factors includes
prematurity, exposures to colonised family members
and medical equipment.4 The use of maternal
intrapartum chemoprophylaxis has been shown to
be ineffective in the prevention of late-onset GBS
disease.12 The probability of recurrence after the first
episode of GBS infection is between 1% and 6%.4
The mortality rate of invasive GBS diseases
ranges from 5% to 37%.3 12 13 14 15 Late-onset GBS disease
are associated with higher morbidity and significant
neurodevelopmental impairments.13 16 As late-onset
GBS disease is not a notifiable disease in
Hong Kong it is difficult to comment on the local
prevalence. Only two case reports had been found
in the literature and both cases were managed in the
intensive care unit. Both cases survived the episode
of GBS disease, however, long-term morbidity was
not mentioned.4 14 17
In the management of an infant with GBS
infection, penicillin G is generally recommended
for the treatment of GBS infection as well as for
intrapartum prophylaxis to prevent early-onset
GBS disease.18 However, tolerance to penicillin in
penicillin-sensitive GBS strains has been reported
and might be a contributing factor of treatment
failure, necessitating very high dosages or change of
antibiotics.18 19
Late-onset GBS disease is not preventable
despite the use of intrapartum antibiotics for
selective high-risk patients.15 Treatment with
rifampin can be tried to eradicate the colonisation
but variable efficacy is variable.20
The timing of the universal GBS screening
programme in Hong Kong, which at present is
recommended to be performed between 35 to
37 weeks’ gestation, might need to be reviewed.6
The latest American College of Obstetricians and
Gynecologists suggested that the optimal window for
antenatal screening is at 36 to 37 weeks’ gestation; as
the correlation between antenatal GBS colonisation
results and colonisation status at the time of delivery decreases significantly when the culture-to-birth
interval is longer than 5 weeks.21 22
Given the lack of an effective solution for
preventing GBS disease, administration of an
effective vaccine in the third trimester of pregnancy
could provide a sensible and cost-effective solution
in all settings. It is estimated a GBS vaccine with 80%
efficacy and 90% coverage could prevent 108 000
fetal and infant deaths.5 The vaccine will protect
neonates from GBS disease through transplacental
transfer of antibodies to the fetus in utero. There are
a few potential vaccines in development, and some
are already undergoing Phase I and II trials; however,
studies are still in progress to assess the optimal
dose, need for adjuvant, immunogenicity in pregnant
women, placental transfer and persistence in babies.5 23
The widespread use of intrapartum antibiotics
has effectively reduced the rate of early-onset GBS
disease, but not the rate of late-onset GBS disease.
Although it is uncommon in Hong Kong, late-onset
GBS disease is a serious condition with significant
consequences, including stillbirths, and high infant
mortality and morbidity. At present, effective ways
to reduce late-onset infection are limited, but with
the development of a safe and effective maternal
vaccination, it is a potentially a preventable infection.
Author contributions
All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the
data, drafting of the manuscript, and critical revision of the
manuscript for important intellectual content. All authors
had full access to the data, contributed to the study, approved
the final version for publication, and take responsibility for its
accuracy and integrity.
Conflicts of interest
As an editor of the journal, KL Hon was not involved in the peer review process. Other authors have disclosed no conflicts of interest.
Funding/support
This commentary received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References
1. Huang S, Liu X, Lao W, et al. Serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolates collected at a Chinese hospital from 2011 to 2013. BMC
Infect Dis 2015;15:312.Crossref
2. Wang P, Ma Z, Tong J, et al. Serotype distribution, antimicrobial resistance, and molecular characterization
of invasive group B Streptococcus isolates recovered from
Chinese neonates. Int J Infect Dis 2015;37:115-8. Crossref
3. Chan SH, Lau SP, Fok TF, Liang ST. Early onset neonatal group B streptococcal infection in Hong Kong. Asia
Oceania J Obstet Gynaecol 1986;12:341-6. Crossref
4. Hon KL, Chan KH, Ko PL, So KW, Leung AK. Late onset Streptococcus agalactiae meningitis following early onset
septicemia: a preventable disease? Case Rep Pediatr
2017;2017:8418105. Crossref
5. Seale AC, Bianchi-Jassir F, Russell NJ, et al. Estimates of
the burden of Group B Streptococcal disease worldwide for pregnant women, stillbirths, and children. Clin Infect Dis
2017;65(Suppl 2):S200-19.
6. Ma TW, Chan V, So CH, et al. Prevention of early onset
group B streptococcal disease by universal antenatal
culture-based screening in all public hospitals in Hong
Kong. J Matern Neonatal Med 2018;31:881-7. Crossref
7. Madrid L, Seale AC, Kohli-Lynch M, et al. Infant Group B
streptococcal disease incidence and serotypes worldwide:
systematic review and meta-analyses. Clin Infect Dis
2017;65(Suppl 2):S160-72. Crossref
8. Rivera L, Sáez-Llorens X, Feris-Iglesias J, et al. Incidence
and serotype distribution of invasive group B streptococcal
disease in young infants: a multi-country observational
study. BMC Pediatr 2015;15:143. Crossref
9. Tsui MH, Ip M, Ng PC, Sahota DS, Leung TN, Lau TK. Change in prevalence of group B Streptococcus maternal
colonisation in Hong Kong. Hong Kong Med J 2009;15:414-9.
10. Prevention of early-onset neonatal group B Streptococcal disease: Green-top Guideline No. 36 [editorial]. BJOG
2017;124:e280-305. Crossref
11. Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention
of perinatal group B streptococcal disease. Revised
guidelines from CDC. MMWR Recomm Rep 2002;51:1-22.
12. Berardi A, Rossi C, Lugli L, et al. Group B streptococcus late-onset disease: 2003-2010. Pediatrics 2013;131:e361-8. Crossref
13. Libster R, Edwards KM, Levent F, et al. Long-term outcomes of group B streptococcal meningitis. Pediatrics
2012;130:e8-15. Crossref
14. Hon KL, Chow TC, Cheung TS, et al. Severe Group A and Group B Streptococcus diseases at a pediatric ICU: are
they still sensitive to the penicillins? Curr Clin Pharmacol
2020;15:125-31. Crossref
15. Jordan HT, Farley MM, Craig A, et al. Revisiting the need for vaccine prevention of late-onset neonatal group
B streptococcal disease: a multistate, population-based
analysis. Pediatr Infect Dis J 2008;27:1057-64. Crossref
16. Bartlett AW, Smith B, George CR, et al. Epidemiology of
late and very late onset Group B Streptococcal disease:
fifteen-year experience from two Australian tertiary
pediatric facilities. Pediatr Infect Dis J 2017;36:20-4. Crossref
17. Chan LT, Law K, Law CW, Lee WH. Late-onset group B streptococcal cellulitis in a premature infant. HK J Paediatr
2010;15:48-51.
18. Heelan JS, Hasenbein ME, McAdam AJ. Resistance of group B streptococcus to selected antibiotics, including
erythromycin and clindamycin. J Clin Microbiol
2004;42:1263-4. Crossref
19. Betriu C, Gomez M, Sanchez A, Cruceyra A, Romero J, Picazo JJ. Antibiotic resistance and penicillin tolerance
in clinical isolates of group B streptococci. Antimicrob
Agents Chemother 1994;38:2183-6. Crossref
20. Thomas SR, Dawoud T, Doss I, Al-Salam Z. Recurrent late-onset group B streptococcus sepsis in a neonate from
breast milk. J Clin Neonatol 2017;6:192-4. Crossref
21. Puopolo KM, Lynfield R, Cummings JJ, Committee on
Fetus and Newborn and Committee on Infectious Diseases.
Management of infants at risk for group B Streptococcal
disease. Pediatrics 2019;144:e20191881. Crossref
22. Hon KL, Fu A, Leung TF, et al. Cardiopulmonary morbidity
of streptococcal infections in a PICU. Clin Respir J
2015;9:45-52. Crossref
23. Heath PT. Status of vaccine research and development of vaccines for GBS. Vaccine 2016;34:2876-9. Crossref