Variation of invasive neonatal GBS disease across the regions
Authors: Musa Mohammed Ali, Daniel Asrat
Journal: The Lancet Global Health (2022)

Group B streptococcus (GBS) emerged in the 1960s as the leading cause of neonatal disease in the USA,1Schuchat A Epidemiology of group B streptococcal disease in the United States: shifting paradigms.Clin Microbiol Rev. 1998; 11: 497-513Crossref PubMed Google Scholar and yet the reason for its emergence is unknown. Possible reasons are past underdiagnosis or a change in the population structure of GBS.2Da Cunha V Davies MR Douarre PE et al.Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline.Nat Commun. 2014; 54544 Crossref PubMed Scopus (145) Google Scholar Intrapartum antibiotic prophylaxis (IAP) was recommended as the prevention strategy for early-onset invasive GBS (EOGBS),3Verani JR Spina NL Lynfield R et al.Early-onset group B streptococcal disease in the United States: potential for further reduction.Obstet Gynecol. 2014; 123: 828-837Crossref PubMed Scopus (41) Google Scholar and was adopted by various high-income countries. As a result, a substantial decline in the incidence of neonatal disease was observed.3Verani JR Spina NL Lynfield R et al.Early-onset group B streptococcal disease in the United States: potential for further reduction.Obstet Gynecol. 2014; 123: 828-837Crossref PubMed Scopus (41) Google Scholar, 4Garland SM Cottrill E Markowski L et al.Antimicrobial resistance in group B Streptococcus: the Australian experience.J Med Microbiol. 2011; 60: 230-235Crossref PubMed Scopus (37) Google ScholarDespite high rates of maternal GBS colonisation, which is a prerequisite for early-onset GBS disease, in low-income countries5Russell NJ Seale AC O'Driscoll M et al.Maternal colonization with group B Streptococcus and serotype distribution worldwide: systematic review and meta-analyses.Clin Infect Dis. 2017; 65: S100-S111Crossref PubMed Scopus (208) Google Scholar data on the causes of EOGBS are few,6Seale AC Mwaniki M Newton CR Berkley JA Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa.Lancet Infect Dis. 2009; 9: 428-438Summary Full Text Full Text PDF PubMed Scopus (101) Google Scholar and of the data available, they rarely report GBS as one of the causes.7Weldu Y Naizgi M Hadgu A et al.Neonatal epticemia at intensive care unit, Ayder Comprehensive Specialized Hospital, Tigray, north Ethiopia: bacteriological profile, drug susceptibility pattern, and associated factors.PLoS ONE. 2020; 15e0235391 Crossref PubMed Scopus (6) Google Scholar, 8Jatsho J Nishizawa Y Pelzom D Sharma R Clinical and bacteriological profile of neonatal sepsis: a prospective hospital-based study.Int J Pediatr. 2020; 20201835945 Crossref PubMed Scopus (11) Google Scholar This result could be for various reasons, including the absence of appropriate laboratory facilities to isolate GBS and detect the presence of antibodies acquired from mother. A high incidence of invasive neonatal GBS disease has been shown in a primary study in South Africa9Dangor Z Lala SG Cutland CL et al.Burden of invasive group B Streptococcus disease and early neurological sequelae in South African infants.PLoS One. 2015; 10e0123014 Crossref PubMed Scopus (58) Google Scholar and in a proxy estimate study in sub-Saharan African countries.10Seale AC Blencowe H Manu AA et al.Estimates of possible severe bacterial infection in neonates in sub-Saharan Africa, south Asia, and Latin America for 2012: a systematic review and meta-analysis.Lancet Infect Dis. 2014; 14: 731-741Summary Full Text Full Text PDF PubMed Scopus (175) Google Scholar The incidence of invasive neonatal GBS disease might not be high in all countries in sub-Saharan African countries and primary data are not available from all regions in sub-Saharan Africa. Within any region heterogeneity is expected; however, the extent to which it affects the estimate is unclear. But the role of laboratory facilities in detecting the organism, detecting immunity acquired from mother, and identifying any other factors that affect EOGBS, needs to be established before further studies are done.In The Lancet Global Health, Bronner Gonçalves and colleagues11Gonçalves BP Procter SR Paul P et al.Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.Lancet Glob Health. 2022; (published online April 28.)https://doi.org/10.1016/S2214-109X(22)00093-6PubMed Google Scholar use data from novel studies and apply a new statistical approach to estimate, for 183 countries, the regional and global burden of GBS infection in pregnancy and infancy for 2020. They find that, although the highest burden of invasive GBS disease was in sub-Saharan Africa, cases still occurred in high-income countries, indicating the limitations of IAP. The limitations mentioned include an inability to prevent GBS-associated stillbirth, excess preterm births associated with maternal GBS, and late-onset invasive GBS disease. There are also cases of EOGBS caused by GBS in countries implementing IAP. The study by Gonçalves and colleagues11Gonçalves BP Procter SR Paul P et al.Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.Lancet Glob Health. 2022; (published online April 28.)https://doi.org/10.1016/S2214-109X(22)00093-6PubMed Google Scholar suggests the implementation of multicentre cohort studies that involve following-up pregnant women throughout gestation to establish GBS-associated outcomes. In some countries, without sufficient evidence, it is difficult to convince health-care providers and policy makers that GBS is the main cause of infection in EOGBS, especially when GBS is not recovered from blood cultures. As a result, the recommendation from the authors is not ambitious; instead, it is something that should be addressed as soon as possible, especially in countries where GBS is not being isolated from the blood of newborn babies suspected of EOGBS.Gonçalves and colleagues11Gonçalves BP Procter SR Paul P et al.Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.Lancet Glob Health. 2022; (published online April 28.)https://doi.org/10.1016/S2214-109X(22)00093-6PubMed Google Scholar also indicated the importance of estimating the risk of EOGBS in newborn babies born to mothers colonised with GBS for global burden of disease estimation compared with routine surveillance data, which might miss cases. Surveillance is not feasible in all countries, particularly in areas where there are few resources and it is difficult to establish a laboratory. The inherent limitation of estimating risk in newborn babies is that all neonates born to mothers who are colonised might not develop invasive disease, either because of passive immunity or the types of GBS that colonised the mother. It is important to establish the advantages and disadvantages of both methods. In low-income countries where there are blood culture facilities, reports of GBS in neonatal infection are uncommon. Surveillance might not change these findings unless a better diagnostic method with a high sensitivity is in place. To complement the current estimates of GBS infection in low-income countries including sub-Saharan Africa, a study with better diagnostic methods in some low-income countries is required.Gonçalves and colleagues11Gonçalves BP Procter SR Paul P et al.Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.Lancet Glob Health. 2022; (published online April 28.)https://doi.org/10.1016/S2214-109X(22)00093-6PubMed Google Scholar also estimate the burden of neurodevelopmental impairment (NDI) after invasive GBS disease, GBS-associated stillbirths, and excess preterm birth, which were missed in previous reviews. These estimates will strengthen the importance of the GBS vaccine, because it will not only prevent early-onset and late-onset GBS disease but also NDI, stillbirths, and excess preterm births associated with GBS. It is equally important to interpret the aforementioned estimates with caution, particularly in regions where there are few data on invasive GBS disease.Overall, the global GBS estimates reported by the study have a substantial role in establishing the number of GBS-related unwanted outcomes that could be averted by existing prevention strategies and new vaccines. The study mentions that there is a knowledge gap regarding the effect of NDI on children's school performance; future studies might explore how GBS-associated NDI affects children's educational performance. Group B streptococcus (GBS) emerged in the 1960s as the leading cause of neonatal disease in the USA,1Schuchat A Epidemiology of group B streptococcal disease in the United States: shifting paradigms.Clin Microbiol Rev. 1998; 11: 497-513Crossref PubMed Google Scholar and yet the reason for its emergence is unknown. Possible reasons are past underdiagnosis or a change in the population structure of GBS.2Da Cunha V Davies MR Douarre PE et al.Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline.Nat Commun. 2014; 54544 Crossref PubMed Scopus (145) Google Scholar Intrapartum antibiotic prophylaxis (IAP) was recommended as the prevention strategy for early-onset invasive GBS (EOGBS),3Verani JR Spina NL Lynfield R et al.Early-onset group B streptococcal disease in the United States: potential for further reduction.Obstet Gynecol. 2014; 123: 828-837Crossref PubMed Scopus (41) Google Scholar and was adopted by various high-income countries. As a result, a substantial decline in the incidence of neonatal disease was observed.3Verani JR Spina NL Lynfield R et al.Early-onset group B streptococcal disease in the United States: potential for further reduction.Obstet Gynecol. 2014; 123: 828-837Crossref PubMed Scopus (41) Google Scholar, 4Garland SM Cottrill E Markowski L et al.Antimicrobial resistance in group B Streptococcus: the Australian experience.J Med Microbiol. 2011; 60: 230-235Crossref PubMed Scopus (37) Google Scholar Despite high rates of maternal GBS colonisation, which is a prerequisite for early-onset GBS disease, in low-income countries5Russell NJ Seale AC O'Driscoll M et al.Maternal colonization with group B Streptococcus and serotype distribution worldwide: systematic review and meta-analyses.Clin Infect Dis. 2017; 65: S100-S111Crossref PubMed Scopus (208) Google Scholar data on the causes of EOGBS are few,6Seale AC Mwaniki M Newton CR Berkley JA Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa.Lancet Infect Dis. 2009; 9: 428-438Summary Full Text Full Text PDF PubMed Scopus (101) Google Scholar and of the data available, they rarely report GBS as one of the causes.7Weldu Y Naizgi M Hadgu A et al.Neonatal epticemia at intensive care unit, Ayder Comprehensive Specialized Hospital, Tigray, north Ethiopia: bacteriological profile, drug susceptibility pattern, and associated factors.PLoS ONE. 2020; 15e0235391 Crossref PubMed Scopus (6) Google Scholar, 8Jatsho J Nishizawa Y Pelzom D Sharma R Clinical and bacteriological profile of neonatal sepsis: a prospective hospital-based study.Int J Pediatr. 2020; 20201835945 Crossref PubMed Scopus (11) Google Scholar This result could be for various reasons, including the absence of appropriate laboratory facilities to isolate GBS and detect the presence of antibodies acquired from mother. A high incidence of invasive neonatal GBS disease has been shown in a primary study in South Africa9Dangor Z Lala SG Cutland CL et al.Burden of invasive group B Streptococcus disease and early neurological sequelae in South African infants.PLoS One. 2015; 10e0123014 Crossref PubMed Scopus (58) Google Scholar and in a proxy estimate study in sub-Saharan African countries.10Seale AC Blencowe H Manu AA et al.Estimates of possible severe bacterial infection in neonates in sub-Saharan Africa, south Asia, and Latin America for 2012: a systematic review and meta-analysis.Lancet Infect Dis. 2014; 14: 731-741Summary Full Text Full Text PDF PubMed Scopus (175) Google Scholar The incidence of invasive neonatal GBS disease might not be high in all countries in sub-Saharan African countries and primary data are not available from all regions in sub-Saharan Africa. Within any region heterogeneity is expected; however, the extent to which it affects the estimate is unclear. But the role of laboratory facilities in detecting the organism, detecting immunity acquired from mother, and identifying any other factors that affect EOGBS, needs to be established before further studies are done. In The Lancet Global Health, Bronner Gonçalves and colleagues11Gonçalves BP Procter SR Paul P et al.Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.Lancet Glob Health. 2022; (published online April 28.)https://doi.org/10.1016/S2214-109X(22)00093-6PubMed Google Scholar use data from novel studies and apply a new statistical approach to estimate, for 183 countries, the regional and global burden of GBS infection in pregnancy and infancy for 2020. They find that, although the highest burden of invasive GBS disease was in sub-Saharan Africa, cases still occurred in high-income countries, indicating the limitations of IAP. The limitations mentioned include an inability to prevent GBS-associated stillbirth, excess preterm births associated with maternal GBS, and late-onset invasive GBS disease. There are also cases of EOGBS caused by GBS in countries implementing IAP. The study by Gonçalves and colleagues11Gonçalves BP Procter SR Paul P et al.Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.Lancet Glob Health. 2022; (published online April 28.)https://doi.org/10.1016/S2214-109X(22)00093-6PubMed Google Scholar suggests the implementation of multicentre cohort studies that involve following-up pregnant women throughout gestation to establish GBS-associated outcomes. In some countries, without sufficient evidence, it is difficult to convince health-care providers and policy makers that GBS is the main cause of infection in EOGBS, especially when GBS is not recovered from blood cultures. As a result, the recommendation from the authors is not ambitious; instead, it is something that should be addressed as soon as possible, especially in countries where GBS is not being isolated from the blood of newborn babies suspected of EOGBS. Gonçalves and colleagues11Gonçalves BP Procter SR Paul P et al.Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.Lancet Glob Health. 2022; (published online April 28.)https://doi.org/10.1016/S2214-109X(22)00093-6PubMed Google Scholar also indicated the importance of estimating the risk of EOGBS in newborn babies born to mothers colonised with GBS for global burden of disease estimation compared with routine surveillance data, which might miss cases. Surveillance is not feasible in all countries, particularly in areas where there are few resources and it is difficult to establish a laboratory. The inherent limitation of estimating risk in newborn babies is that all neonates born to mothers who are colonised might not develop invasive disease, either because of passive immunity or the types of GBS that colonised the mother. It is important to establish the advantages and disadvantages of both methods. In low-income countries where there are blood culture facilities, reports of GBS in neonatal infection are uncommon. Surveillance might not change these findings unless a better diagnostic method with a high sensitivity is in place. To complement the current estimates of GBS infection in low-income countries including sub-Saharan Africa, a study with better diagnostic methods in some low-income countries is required. Gonçalves and colleagues11Gonçalves BP Procter SR Paul P et al.Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.Lancet Glob Health. 2022; (published online April 28.)https://doi.org/10.1016/S2214-109X(22)00093-6PubMed Google Scholar also estimate the burden of neurodevelopmental impairment (NDI) after invasive GBS disease, GBS-associated stillbirths, and excess preterm birth, which were missed in previous reviews. These estimates will strengthen the importance of the GBS vaccine, because it will not only prevent early-onset and late-onset GBS disease but also NDI, stillbirths, and excess preterm births associated with GBS. It is equally important to interpret the aforementioned estimates with caution, particularly in regions where there are few data on invasive GBS disease. Overall, the global GBS estimates reported by the study have a substantial role in establishing the number of GBS-related unwanted outcomes that could be averted by existing prevention strategies and new vaccines. The study mentions that there is a knowledge gap regarding the effect of NDI on children's school performance; future studies might explore how GBS-associated NDI affects children's educational performance. We declare no competing interests Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burdenOur analysis provides a comprehensive assessment of the pregnancy-related GBS burden. The Bayesian approach enabled coherent propagation of uncertainty, which is considerable, notably regarding GBS-associated preterm births. Our findings on both the acute and long-term consequences of iGBS have public health implications for understanding the value of investment in maternal GBS immunisation and other preventive strategies. 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