scholarly journals Estimation of invasive Group B Streptococcus disease risk in young infants from case-control serological studies

2021 ◽  
Author(s):  
Alane Izu ◽  
Gaurav Kwatra ◽  
Shabir A Madhi ◽  
Fabio Rigat
Keyword(s):  
Disease Risk ◽  
Group B Streptococcus ◽  
Case Control ◽  
Antibody Concentration ◽  
Case Control Studies ◽  
Clinical Interpretation ◽  
Young Infants ◽  
Risk Estimates ◽  
Group B ◽  
Non Parametric

Abstract Background: Group B Streptococcus (GBS) infections are a major cause of invasive disease (IGbsD) in young infants and cause miscarriage and stillbirths. Immunization of pregnant women against GBS in addition to intrapartum antibiotic prophylaxis could prevent disease. Establishing accurate serological markers of protection against IGbsD could enable use of efficient clinical trial designs for vaccine development and licensure, without needing to undertake efficacy trials in prohibitively large number of mother-infant dyads. The association of maternal naturally acquired serotype-specific anti-capsular antibodies (IgG) against serotype-specific IGbsD in their infants has been studied in case-control studies. The statistical models used so far to estimate IGbsD risk from these case-control studies assumed that the antibody concentrations measured sharing the same disease status are sampled from the same population, not allowing for differences between mothers colonised by GBS and mothers also potentially infected (e.g urinary tract infection or chorioamnionitis) by GBS during pregnancy. This distinction is relevant as infants born from infected mothers with occult medical illness may be exposed to GBS prior to the mother developing antibodies measured in maternal or infant sera. Methods: Unsupervised mixture model averaging (MMA) is proposed and applied here to accurately estimate infant IGbsD risk from case-control study data in presence or absence of antibody concentration subgroups potentially associated to maternal GBS carriage or infection. MMA estimators are compared to non-parametric disease risk estimators in simulation studies and by analysis of two published GBS case-control studies. Results: MMA provides more accurate relative risk estimates under a broad range of data simulation scenarios and more accurate absolute disease risk estimates when the proportion of IGbsD cases with high antibody levels is not ignorable. MMA estimates of the relative and absolute disease risk curves are more amenable to clinical interpretation compared to non-parametric estimates with no detectable overfitting of the data. Antibody concentration thresholds predictive of protection from infant IGbsD estimated by MMA from maternal and infant sera are consistent with non-parametric estimates. Conclusions: MMA is a flexible and robust method for design, accurate analysis and clinical interpretation of case-control studies estimating relative and absolute IGbsD risk from antibody concentrations measured at or after birth.

scholarly journals OC 8465 THE DEVELOPMENT OF A CONJUGATE VACCINE AGAINST GROUP B STREPTOCOCCUS: AN AFRICAN PERSPECTIVE

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A8.1-A8
Author(s):  
Seanette Wilson ◽  
Patrick Tippoo
Keyword(s):  
South Africa ◽  
Clinical Trial ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Disease Risk ◽  
Group B Streptococcus ◽  
International Health ◽  
Infant Deaths ◽  
Young Infants ◽  
Group B

BackgroundStreptococcus agalactiae, or group B streptococcus (GBS), is a gram-positive streptococcal bacterium that is well-recognised as one of the leading causes of infant death, particularly in the early neonatal period (the first week of life). An estimated one in five pregnant women around the world carries GBS bacteria in their gastrointestinal or genitourinary tracts and vertical transmission from colonised mothers can lead to invasive disease in their offspring. A recent study conservatively estimated that out of 410,000 GBS cases globally every year, there are at least 1 47 000 stillbirths and infant deaths. Despite being home to only 13% of the world’s population, Africa has the highest GBS disease burden, with 54% of estimated cases and 65% of stillbirths and infant deaths.An effective GBS vaccine, given during pregnancy, is a promising strategy to protect against GBS disease. Currently, no licensed vaccine exists to prevent it, but scientific evaluation of feasibility is favourable. The leading vaccine candidates are capsular polysaccharide-protein conjugate vaccines. Evidence suggests maternal immunisation with a safe and effective GBS vaccine may reduce the disease risk in neonates and young infants.The Biovac Institute was established as a private-public partnership and is the only Southern African vaccine manufacturer. Located in Cape Town, South Africa, Biovac’s mission is to become a leading vaccine developer and producer in South Africa to increase capacity in Africa which only has four other vaccine manufacturers.In collaboration with PATH, an international health organisation, and other partners, Biovac is developing a multivalent conjugate vaccine against GBS. The first stage of the project involves the development of biopharmaceutical manufacturing processes and analytical tests, the preparation of clinical trial product, and execution of a first-in-human clinical trial.This presentation will provide an overview of the project, progress to date, and the path to commercialisation.

Risk factors for group B streptococcus early-onset disease: an Italian, area-based, case-control study

2019 ◽  
Vol 33 (14) ◽  
pp. 2480-2486 ◽  
Author(s):  
Alberto Berardi ◽  
Caterina Spada ◽  
Roberta Creti ◽  
Simone Ambretti ◽  
Rossana Chiarabini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Early Onset ◽  
Case Control Study ◽  
Group B Streptococcus ◽  
Case Control ◽  
Group B ◽  
Control Study

scholarly journals Significant association between the endothelial lipase gene 584C/T polymorphism and coronary artery disease risk

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Yue-e Wu ◽  
Lan Ma ◽  
Hao Zhang ◽  
Xin-ran Chen ◽  
Xin-yi Xu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Disease Risk ◽  
Meta Analysis ◽  
Case Control ◽  
Endothelial Lipase ◽  
Case Control Studies ◽  
Lipase Gene ◽  
Comparison Model ◽  
Artery Disease

Abstract Several studies have investigated a potential association between the endothelial lipase gene (LIPG) 584C/T polymorphism and susceptibility to coronary artery disease (CAD), but a uniform conclusion is yet to be reached. To better evaluate the true relationship between the LIPG 584C/T polymorphism and the risk of CAD, a meta-analysis of 14 case–control studies with 9731 subjects was performed. Relevant articles published through August 2020 were searched in the CNKI, PubMed, Embase and Web of Science databases. Thirteen articles, including 14 eligible case–control studies with 4025 cases and 5706 controls, were enrolled in the present meta-analysis. The Newcastle–Ottawa Scale (NOS) scores of the case–control studies ranged from 6 to 8. The pooled results indicated that there is a significant association between the LIPG 584C/T polymorphism and CAD in the homozygote comparison model and the allelic comparison model. Subgroup analyses revealed that the LIPG 584C/T mutation significantly decreased the risk of CAD in the subgroups of African, CAD, hospital-based (HB), and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) populations in some genetic models. No publication bias was found in our meta-analysis, which certifies the robustness of the current meta-analysis. Trial sequential analysis (TSA) also confirmed the stability of our results. The results of our meta-analysis indicate that the LIPG 584C/T polymorphism plays a protective role in the incidence of CAD. More high-quality case–control studies on various ethnicities are needed to confirm our results.

scholarly journals Seroepidemiology of maternally-derived antibody against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda - PROGRESS GBS

2020 ◽  
Vol 4 ◽  
pp. 155
Author(s):  
Mary Kyohere ◽  
Hannah Georgia Davies ◽  
Philippa Musoke ◽  
Annettee Nakimuli ◽  
Valerie Tusubira ◽  
...  
Keyword(s):  
Placental Transfer ◽  
Young Infant ◽  
Group B Streptococcus ◽  
Maternal Blood ◽  
Antibody Concentration ◽  
Large Sample Size ◽  
High Burden ◽  
Resource Limited ◽  
Entry Points ◽  
Group B

Background: Group B Streptococcus (GBS) is a major contributor to the high burden of neonatal and young infant infectious disease in resource- limited settings. As disease protection during the first six months of life is provided via placental transfer of maternal antibodies, a maternal GBS vaccine may provide an effective strategy to reduce infectious death and disability. An efficacy study may be difficult because of the large sample size required and alternative approaches such as serocorrelates of protection based on natural antibody concentration are being considered. Such studies would need to be undertaken in high burden settings such as Uganda. We therefore aim to evaluate the feasibility and acceptability of a GBS sero-epidemiology study in Kampala, Uganda. Methods: This is a prospective cohort and nested case-control study, conducted across two-centres with two entry points. A) consecutive women and their infants at birth, with collection of maternal swab, cord and maternal blood, and follow up by telephone until the infant is 3 months old; B) any infant under 3 months of age, presenting with signs of sepsis to any of the paediatric units, with collection of blood culture, cerebrospinal fluid and nasopharyngeal swabs. Any infants identified as having GBS disease (defined as GBS isolated from a normally sterile site) will be recruited and followed up for two years to assess their neurodevelopment. A nested qualitative study will investigate stakeholder (pregnant women and their families, healthcare workers and community leaders) opinions of sampling for such a study and understanding and potential uptake of vaccines in pregnancy. Discussion: The primary aim is to determine anti-GBS antibody concentration in infants with GBS disease compared to healthy controls. Secondary outcomes include stillbirth and all-cause infection and acceptance of sample methods and vaccination. The findings will inform scalability and sustainability of the programme in Uganda.

scholarly journals Seroepidemiology of maternally-derived antibody against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda - PROGRESS GBS

2020 ◽  
Vol 4 ◽  
pp. 155
Author(s):  
Mary Kyohere ◽  
Hannah Georgia Davies ◽  
Philippa Musoke ◽  
Annettee Nakimuli ◽  
Valerie Tusubira ◽  
...  
Keyword(s):  
Placental Transfer ◽  
Young Infant ◽  
Group B Streptococcus ◽  
Maternal Blood ◽  
Antibody Concentration ◽  
Large Sample Size ◽  
High Burden ◽  
Resource Limited ◽  
Entry Points ◽  
Group B

Background: Group B Streptococcus (GBS) is a major contributor to the high burden of neonatal and young infant infectious disease in resource- limited settings. As disease protection during the first six months of life is provided via placental transfer of maternal antibodies, a maternal GBS vaccine may provide an effective strategy to reduce infectious death and disability. An efficacy study may be difficult because of the large sample size required and alternative approaches such as serocorrelates of protection based on natural antibody concentration are being considered. Such studies would need to be undertaken in high burden settings such as Uganda. We therefore aim to evaluate the feasibility and acceptability of a GBS sero-epidemiology study in Kampala, Uganda. Methods: This is a prospective cohort and nested case-control study, conducted across two-centres with two entry points. A) consecutive women and their infants at birth, with collection of maternal swab, cord and maternal blood, and follow up by telephone until the infant is 3 months old; B) any infant under 3 months of age, presenting with signs of sepsis to any of the paediatric units, with collection of blood culture, cerebrospinal fluid and nasopharyngeal swabs. Any infants identified as having GBS disease (defined as GBS isolated from a normally sterile site) will be recruited and followed up for two years to assess their neurodevelopment. A nested qualitative study will investigate stakeholder (pregnant women and their families, healthcare workers and community leaders) opinions of sampling for such a study and understanding and potential uptake of vaccines in pregnancy. Discussion: The primary aim is to determine anti-GBS antibody concentration in infants with GBS disease compared to healthy controls. Secondary outcomes include stillbirth and all-cause infection and acceptance of sample methods and vaccination. The findings will inform scalability and sustainability of the programme in Uganda.

scholarly journals Enhanced identification of Group B streptococcus in infants with suspected meningitis in Ethiopia

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242628
Author(s):  
Alene Geteneh ◽  
Tesfaye Kassa ◽  
Yared Alemu ◽  
Derbie Alemu ◽  
Mulugeta Kiros ◽  
...  
Keyword(s):  
Detection Rate ◽  
Causes Of Death ◽  
Late Onset ◽  
Group B Streptococcus ◽  
Young Infants ◽  
Specialized Hospital ◽  
Tikur Anbessa Specialized Hospital ◽  
One Year ◽  
Group B ◽  
Culture Negative

Meningitis is one of the top ten causes of death among Ethiopian infants. Group B streptococcus (GBS) has emerged as a leading cause of meningitis in neonates and young infants, resulting in high mortality. Despite this, there is no report on GBS associated meningitis in Ethiopia where infant meningitis is common. Hence, the aim of this study was to determine the proportion of GBS associated meningitis among Ethiopian infants. PCR was prospectively used to detect GBS in culture-negative cerebrospinal fluid (CSF) samples, which were collected from infants suspected for meningitis, at Tikur Anbessa specialized hospital, Ethiopia, over a one-year period. GBS was detected by PCR in 63.9% of culture-negative CSF samples. Out of the 46 GBS positive infants, 10.9% (n = 5) of them died. The late onset of GBS (LOGBS) disease was noted to have a poor outcome with 3 LOGBS out of 5 GBS positive samples collected from patients with the final outcome of death. PCR was advantageous in the identification of GBS in culture-negative CSF samples. GBS was detected in 64% of the CSF samples from infants with meningitis compared with zero-detection rate by culture.

scholarly journals Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2355 ◽  
Author(s):  
Miwako Kobayashi ◽  
Johan Vekemans ◽  
Carol J. Baker ◽  
Adam J. Ratner ◽  
Kirsty Le Doare ◽  
...  
Keyword(s):  
At Risk ◽  
Disease Burden ◽  
Vaccine Development ◽  
Young Infant ◽  
Group B Streptococcus ◽  
Current Status ◽  
Middle Income ◽  
Young Infants ◽  
Group B ◽  
Low And Middle Income

Globally, group BStreptococcus(GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation.This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations.

Determinants of Neonatal Readmission in Healthy Term Infants: Results from a Nested Case–Control Study

2020 ◽  
Author(s):  
Angelita M. Hensman ◽  
Debra A. Erickson-Owens ◽  
Mary C. Sullivan ◽  
Brian J. Quilliam
Keyword(s):  
Case Control Study ◽  
Conditional Logistic Regression ◽  
Group B Streptococcus ◽  
Case Control ◽  
Term Infants ◽  
True Incidence ◽  
Large Level ◽  
Group B ◽  
Nested Case Control ◽  
Control Study

Abstract Objective The aim of this study was to estimate the incidence and identify the factors associated with neonatal readmission among healthy term infants. Study Design A nested case–control study with matching was conducted at a large level III perinatal hospital with approximately 8,700 deliveries each year. Each case infant (n = 130) was matched to two control infants (n = 260) on the case infant's date of birth (±7 days) and the mother's maternal age (<20 years, 20–29, 30–39, and >39 years). All infants were selected from a cohort of eligible term, healthy, in-state infants admitted to the newborn unit postdelivery from January 1, 2016 to May 8, 2017. Data were analyzed using hierarchical conditional logistic regression. Results The incidence of neonatal readmission was 2.2%, and all readmissions occurred within 8.6 days of birth. Earlier gestational age (37 weeks; odds ratio [OR]: 4.11, 95% confidence interval [CI]: 1.79–9.45; 38 weeks OR: 1.29, CI 0.60–2.75; [ref] 39 weeks), jaundice on day two of life (OR: 2.45; CI: 1.40–4.30), maternal group B streptococcus chemoprophylaxis (OR: 2.55; CI: 1.23–5.28 [Ref N/A]) were associated with readmission. Delivery by cesarean section (OR: 0.31, CI: 0.12–0.79) and each milliliter of formula [first three days] (OR: 0.96; CI: 0.993–0.999) were protective. Conclusion Neonatal readmission in healthy term infants may potentially be reduced with identification of modifiable determinants of readmission prior to discharge. Policies to capture the true incidence of neonatal readmissions should include admissions to hospitals other than the birth hospital.

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