Imperial College London

Dr Kirsty Le Doare

Faculty of MedicineDepartment of Infectious Disease

Honorary Clinical Senior Lecturer
 
 
 
//

Contact

 

k.mehring-le-doare

 
 
//

Location

 

Medical SchoolSt Mary's Campus

//

Summary

 

Publications

Publication Type
Year
to

62 results found

Blakeway H, Prasad S, Kalafat E, Heath PT, Ladhani SN, Le Doare K, Magee LA, Obrien P, Rezvani A, Dadelszen PV, Khalil Aet al., 2021, COVID-19 Vaccination During Pregnancy: Coverage and Safety, American Journal of Obstetrics and Gynecology, ISSN: 0002-9378

Journal article

Kyohere M, Davies HG, Musoke P, Nakimuli A, Tusubira V, Tasimwa HB, Nsimire JS, Heath P, Cose S, Baker C, Le Doare K, Sekikubo Met al., 2020, Seroepidemiology of maternally-derived antibody against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda - PROGRESS GBS, Gates Open Research, Vol: 4, Pages: 155-155

<ns4:p><ns4:bold>Background</ns4:bold>: Group B <ns4:italic>Streptococcus</ns4:italic> (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.</ns4:p><ns4:p> <ns4:bold>Methods</ns4:bold>: 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.</ns4:p><ns4:p> <ns4:bold>Discussion</ns4:bold>: The primary aim is to determine anti-GBS antibody concentration in infants with GBS disease compared to healthy contr

Journal article

Emms H, Lee R, Thomas A, Doerholt K, Le Doare Ket al., 2020, Return of vivax malaria in Cyprus, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 105, Pages: 102-103, ISSN: 0003-9888

Journal article

Kyohere M, Davies HG, Musoke P, Nakimuli A, Tusubira V, Tasimwa HB, Nsimire JS, Heath P, Cose S, Baker C, Le Doare K, Sekikubo Met al., 2020, Seroepidemiology of maternally-derived antibody against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda - PROGRESS GBS., Gates Open Res, Vol: 4

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.

Journal article

Vekemans J, Moorthy V, Friede M, Alderson MR, Sobanjo-Ter Meulen A, Baker CJ, Heath PT, Madhi SA, Mehring-Le Doare K, Saha SK, Schrag S, Kaslow DCet al., 2019, Maternal immunization against Group B streptococcus: World Health Organization research and development technological roadmap and preferred product characteristics, VACCINE, Vol: 37, Pages: 7391-7393, ISSN: 0264-410X

Journal article

Le Doare K, Heath PT, Plumb J, Owen NA, Brocklehurst P, Chappell LCet al., 2019, Uncertainties in Screening and Prevention of Group B Streptococcus Disease, CLINICAL INFECTIOUS DISEASES, Vol: 69, Pages: 720-725, ISSN: 1058-4838

Journal article

Le Doare K, Kampmann B, Vekemans J, Heath PT, Goldblatt D, Nahm MH, Baker C, Edwards MS, Kwatra G, Andrews N, Madhi SA, ter Meulen AS, Anderson AS, Corsaro B, Fischer P, Gorringe Aet al., 2019, Serocorrelates of protection against infant group B streptococcus disease, LANCET INFECTIOUS DISEASES, Vol: 19, Pages: E162-E171, ISSN: 1473-3099

Journal article

Zhong Z, Haltalli M, Holder B, Rice T, Donaldson B, O'Driscoll M, Le-Doare K, Kampmann B, Tregoning JSet al., 2019, The impact of timing of maternal influenza immunisation on infant antibody levels at birth., Clinical and Experimental Immunology, Vol: 195, Pages: 139-152, ISSN: 1365-2249

Pregnant women and infants are at an increased risk of severe disease after influenza infection. Maternal immunisation is a potent tool to protect both of these at-risk groups. Whilst the primary aim of maternal influenza vaccination is to protect the mother, a secondary benefit is the transfer of protective antibodies to the infant. A recent study using the tetanus, diphtheria and acellular pertussis (Tdap) vaccine indicated that children born to mothers immunised in the second trimester of pregnancy had the highest antibody titres compared to children immunised in the third trimester. The aim of the current study was to investigate how timing of maternal influenza immunisation impacts infant antibody levels at birth. Antibody titres were assessed in maternal and cord blood samples by both IgG-binding ELISA and haemagglutination inhibition assay (HAI). Antibody titres to the H1N1 component were significantly higher in infants born to mothers vaccinated in either the second or third trimesters than infants born to unvaccinated mothers. HAI levels in the infant were significantly lower when maternal immunisation was performed less than four weeks before birth. These studies confirm that immunisation during pregnancy increases the antibody titre in infants. Importantly antibody levels in cord blood were significantly higher when mother was vaccinated in either trimester two or three, though titres were significantly lower if the mother was immunised less than 4 weeks before birth. Based on this data, seasonal influenza vaccination should continue to be given in pregnancy as soon as it becomes available.

Journal article

Saso A, Blyuss O, Munblit D, Faal A, Moore S, Le Doare Ket al., 2019, Breast milk cytokines and early growth in Gambian infants, Frontiers in Pediatrics, Vol: 6, ISSN: 2296-2360

Background: Breast milk provides nutrition for infants but also delivers other bioactive factors that have key protective and developmental benefits. In particular, cytokines are thought to play a role in immunomodulation, although little is known about their impact on health outcomes in early life.Objective: The purpose of this pilot study was to evaluate the relationship between cytokines in breast milk and infant growth outcomes in a low-income setting.Methods: 100 mother-infant pairs were followed up to 2–3 months postpartum as part of a prospective longitudinal cohort study in urban Gambia, West Africa. The concentrations of 9 pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNFα), IGF-1 and TGFβ2 were measured in colostrum within 12 h of birth and in breast milk at the final visit, scheduled between day 60 and 89 postpartum. Infant weight was recorded and converted to weight-for-age Z-scores (WAZ) at the same time points. Growth outcomes were defined in our study as (a) change in WAZ between birth and final visit (b) WAZ at final visit. Linear regression analysis was used to determine the ability of colostrum and breast milk cytokine concentrations to predict growth outcomes up to 2–3 months postpartum.Results: Gambian infants demonstrated growth faltering across the first 2–3 months postpartum. There was no significant relationship between cytokines in colostrum and subsequent change in WAZ between birth and the final visit, in either unadjusted or adjusted models. However, cytokines in mature breast milk, TNFα, IFNγ, IL1β, IL2, IL4, and IL6, were weak negative predictors of WAZ scores at the final visit, in unadjusted models (p < 0.05). When adjusted for maternal anemia (as a proxy for maternal nutrition), TNFα and IL6 remained significant predictors (p < 0.05).Conclusions: Variations in breast milk cytokine levels do not play a substantial role in the growth

Journal article

, 2018, 74th Congress of the Italian Society of Pediatrics: Rome, Italy. 12-16 June 2018 Abstracts, ITALIAN JOURNAL OF PEDIATRICS, Vol: 44, ISSN: 1720-8424

Journal article

Ayechu-Muruzabal V, van Stigt AH, Mank M, Willemsen LEM, Stahl B, Garssen J, van't Land Bet al., 2018, Diversity of Human Milk Oligosaccharides and Effects on Early Life Immune Development, FRONTIERS IN PEDIATRICS, Vol: 6, ISSN: 2296-2360

Journal article

Le Doare K, Holder B, Bassett A, Pannaraj Pet al., 2018, Mother’s milk: A purposeful contribution to the development of the infant microbiota and immunity, Frontiers in Immunology, Vol: 9, ISSN: 1664-3224

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant’s developing mucosal immune system. It is believed that bacteria from the mother’s intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell–cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development.

Journal article

Jones CE, Calvert A, Mehring-Le Doare K, 2018, Vaccination in pregnancy – recent developments, Pediatric Infectious Disease Journal, Vol: 37, Pages: 191-193, ISSN: 0891-3668

Journal article

Le Doare K, O'Driscoll M, Turner K, Seedat F, Russell NJ, Seale AC, Heath PT, Lawn JE, Baker CJ, Bartlett L, Cutland C, Gravett MG, Ip M, Madhi SA, Rubens CE, Saha SK, Schrag S, Sobanjo-ter Meulen A, Vekemans J, Kampmann Bet al., 2017, Intrapartum Antibiotic Chemoprophylaxis Policies for the Prevention of Group B Streptococcal Disease Worldwide: Systematic Review, Clinical Infectious Diseases, Vol: 65, Pages: S143-S151, ISSN: 1058-4838

BackgroundIntrapartum antibiotic chemoprophylaxis (IAP) prevents most early-onset group B streptococcal (GBS) disease. However, there is no description of how IAP is used around the world. This article is the sixth in a series estimating the burden of GBS disease. Here we aimed to review GBS screening policies and IAP implementation worldwide.MethodsWe identified data through (1) systematic literature reviews (PubMed/Medline, Embase, Literature in the Health Sciences in Latin America and the Caribbean [LILACS], World Health Organization library database [WHOLIS], and Scopus) and unpublished data from professional societies and (2) an online survey and searches of policies from medical societies and professionals. We included data on whether an IAP policy was in use, and if so whether it was based on microbiological or clinical risk factors and how these were applied, as well as the estimated coverage (percentage of women receiving IAP where indicated).ResultsWe received policy information from 95 of 195 (49%) countries. Of these, 60 of 95 (63%) had an IAP policy; 35 of 60 (58%) used microbiological screening, 25 of 60 (42%) used clinical risk factors. Two of 15 (13%) low-income, 4 of 16 (25%) lower-middle–income, 14 of 20 (70%) upper-middle–income, and 40 of 44 (91%) high-income countries had any IAP policy. The remaining 35 of 95 (37%) had no national policy (25/33 from low-income and lower-middle–income countries). Coverage varied considerably; for microbiological screening, median coverage was 80% (range, 20%–95%); for clinical risk factor–based screening, coverage was 29% (range, 10%–50%). Although there were differences in the microbiological screening methods employed, the individual clinical risk factors used were similar.ConclusionsThere is considerable heterogeneity in IAP screening policies and coverage worldwide. Alternative global strategies, such as maternal vaccination, are needed to enhance the scope of global preve

Journal article

Seale AC, Blencowe H, Bianchi-Jassir F, Embleton N, Bassat Q, Ordi J, Menendez C, Cutland C, Briner C, Berkley JA, Lawn JE, Baker CJ, Bartlett L, Gravett MG, Heath PT, Ip M, Le Doare K, Rubens CE, Saha SK, Schrag S, Sobanjo-ter Meulen A, Vekemans J, Madhi SAet al., 2017, Stillbirth With Group B Streptococcus Disease Worldwide: Systematic Review and Meta-analyses, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: S125-S132, ISSN: 1058-4838

Journal article

Seale AC, Bianchi-Jassir F, Russell NJ, Kohli-Lynch M, Tann CJ, Hall J, Madrid L, Blencowe H, Cousens S, Baker CJ, Bartlett L, Cutland C, Gravett MG, Heath PT, Ip M, Le Doare K, Madhi SA, Rubens CE, Saha SK, Schrag SJ, Sobanjo-ter Meulen A, Vekemans J, Lawn JEet al., 2017, Estimates of the Burden of Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: S200-S219, ISSN: 1058-4838

Journal article

Lawn JE, Bianchi-Jassir F, Russell NJ, Kohli-Lynch M, Tann CJ, Hall J, Madrid L, Baker CJ, Bartlett L, Cutland C, Gravett MG, Heath PT, Ip M, Le Doare K, Madhi SA, Rubens CE, Saha SK, Schrag S, Sobanjo-ter Meulen A, Vekemans J, Seale ACet al., 2017, Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: S89-S99, ISSN: 1058-4838

Journal article

Bianchi-Jassir F, Seale AC, Kohli-Lynch M, Lawn JE, Baker CJ, Bartlett L, Cutland C, Gravett MG, Heath PT, Ip M, Le Doare K, Madhi SA, Saha SK, Schrag S, Sobanjo-ter Meulen A, Vekemans J, Rubens CEet al., 2017, Preterm Birth Associated With Group B Streptococcus Maternal Colonization Worldwide: Systematic Review and Meta- analyses, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: S133-S142, ISSN: 1058-4838

Journal article

Hall J, Adams NH, Bartlett L, Seale AC, Lamagni T, Bianchi-Jassir F, Lawn JE, Baker CJ, Cutland C, Heath PT, Ip M, Le Doare K, Madhi SA, Rubens CE, Saha SK, Schrag S, Sobanjo-ter Meulen A, Vekemans J, Gravett MGet al., 2017, Maternal Disease With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: S112-S124, ISSN: 1058-4838

Journal article

Madrid L, Seale AC, Kohli-Lynch M, Edmond KM, Lawn JE, Heath PT, Madhi SA, Baker CJ, Bartlett L, Cutland C, Gravett MG, Ip M, Le Doare K, Rubens CE, Saha SK, Sobanjo-ter Meulen A, Vekemans J, Schrag Set al., 2017, Infant Group B Streptococcal Disease Incidence and Serotypes Worldwide: Systematic Review and Meta-analyses, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: S160-S172, ISSN: 1058-4838

Journal article

Russell NJ, Seale AC, O'Sullivan C, Le Doare K, Heath PT, Lawn JE, Bartlett L, Cutland C, Gravett M, Ip M, Madhi SA, Rubens CE, Saha SK, Schrag S, Sobanjo-ter Meulen A, Vekemans J, Baker CJet al., 2017, Risk of Early-Onset Neonatal Group B Streptococcal Disease With Maternal Colonization Worldwide: Systematic Review and Meta-analyses, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: S152-S159, ISSN: 1058-4838

Journal article

Kohli-Lynch M, Russell NJ, Seale AC, Dangor Z, Tann CJ, Baker CJ, Bartlett L, Cutland C, Gravett MG, Heath PT, Ip M, Le Doare K, Madhi SA, Rubens CE, Saha SK, Schrag S, Sobanjo-ter Meulen A, Vekemans J, O'Sullivan C, Nakwa F, Ben Hamouda H, Soua H, Giorgakoudi K, Ladhani S, Lamagni T, Rattue H, Trotter C, Lawn JEet al., 2017, Neurodevelopmental Impairment in Children After Group B Streptococcal Disease Worldwide: Systematic Review and Meta-analyses, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: S190-S199, ISSN: 1058-4838

Journal article

Tann CJ, Martinello KA, Sadoo S, Lawn JE, Seale AC, Vega-Poblete A, Russell NJ, Baker CJ, Bartlett L, Cutland C, Gravett MG, Ip M, Le Doare K, Madhi SA, Rubens CE, Saha SK, Schrag S, Sobanjo-ter Meulen A, Vekemans J, Heath PT, GBS Neonatal Encephalopathy Investigator Groupet al., 2017, Neonatal Encephalopathy With Group B Streptococcal Disease Worldwide: Systematic Review, Investigator Group Datasets, and Meta-analysis, Clinical Infectious Diseases, Vol: 65, Pages: S173-S189, ISSN: 1058-4838

BackgroundNeonatal encephalopathy (NE) is a leading cause of child mortality and longer-term impairment. Infection can sensitize the newborn brain to injury; however, the role of group B streptococcal (GBS) disease has not been reviewed. This paper is the ninth in an 11-article series estimating the burden of GBS disease; here we aim to assess the proportion of GBS in NE cases.MethodsWe conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups reporting GBS-associated NE. Meta-analyses estimated the proportion of GBS disease in NE and mortality risk. UK population-level data estimated the incidence of GBS-associated NE.ResultsFour published and 25 unpublished datasets were identified from 13 countries (N = 10436). The proportion of NE associated with GBS was 0.58% (95% confidence interval [CI], 0.18%–.98%). Mortality was significantly increased in GBS-associated NE vs NE alone (risk ratio, 2.07 [95% CI, 1.47–2.91]). This equates to a UK incidence of GBS-associated NE of 0.019 per 1000 live births.ConclusionsThe consistent increased proportion of GBS disease in NE and significant increased risk of mortality provides evidence that GBS infection contributes to NE. Increased information regarding this and other organisms is important to inform interventions, especially in low- and middle-resource contexts.

Journal article

Russell NJ, Seale AC, O'Driscoll M, O'Sullivan C, Bianchi-Jassir F, Gonzalez-Guarin J, Lawn JE, Baker CJ, Bartlett L, Cutland C, Gravett MG, Heath PT, Le Doare K, Madhi SA, Rubens CE, Schrag S, Sobanjo-ter Meulen A, Vekemans J, Saha SK, Ip Met al., 2017, Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: S100-S111, ISSN: 1058-4838

BackgroundMaternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide.MethodsWe conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels.ResultsThe dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%–19%), with regional variation (11%–35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%–15%]) and Eastern Asia (11% [95% CI, 10%–12%]). Bacterial serotypes I–V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%–28%), but is less frequent in some South American and Asian countries. Serotypes VI–IX are more common in Asia.ConclusionsGBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype da

Journal article

Mehring-Le Doare KEK, Bellis K, Faal A, Birt J, Munblit D, Humphries H, Taylor S, Warburton F, Heath PT, Gorringe A, Kampmann Bet al., 2017, SIgA, TGF-ß1, IL-10 and TNFa in colostrum are associated with infant Group B Streptococcus colonisation, Frontiers in Immunology, Vol: 8, ISSN: 1664-3224

Background: Group B Streptococcus is a major cause of mortality and morbidity in infants and is associated with transmission from a colonised mother at birth and via infected breastmilk. Although maternal/infant colonisation with Group B Streptococcus (GBS) is common, the majority of infants exposed to GBS remain unaffected. The association between breastmilk immune factors and infant colonisation and disease prevention has not been elucidated. Objectives: We have investigated the association between SIgA and cytokines in breastmilk and infant GBS colonisation and clearance. Methods: Mother/infant GBS colonisation was determined in a prospective cohort of 750 Gambian mother/infant pairs followed to day 90 of life. Anti-GBS secretory IgA bound to the surface of whole bacteria was assessed by flow cytometry and a panel of 12 cytokines quantified by mesoscale discovery in colostrum, breastmilk and serum.Results: Compared with infants receiving low anti-GBS SIgA in colostrum, infants receiving high anti-GBS SIgA were at decreased risk of GBS colonisation for serotypes III and V. Infants colonised at day 6 were twice as likely to receive colostrum with high TGF- β1, TNFα, IL10 and IL-6 compared to uncolonised infants. Infants receiving high colostral TGF- β1, TNFα and IL-6 had two-fold enhanced GBS clearance between birth and day 90. Conclusion: Our results suggest that the infant GBS colonisation risk diminishes with increasing anti-GBS SIgA antibody in breastmilk and that key maternally-derived cytokines might contribute to protection against infant colonisation. These findings might be leveraged to develop interventions including maternal vaccination that may reduce infant GBS colonisation.

Journal article

Idoko OT, Mboizi RB, Okoye M, Laudat F, Ceesay B, Liang JZ, Le Dren-Narayanin N, Jansen KU, Gurtman A, Center KJ, Scott DA, Kampmann B, Roca Aet al., 2017, Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) formulated with 2-phenoxyethanol in multidose vials given with routine vaccination in healthy infants: An open-label randomized controlled trial, Vaccine, Vol: 35, Pages: 3256-3263, ISSN: 0264-410X

BackgroundThis open-label randomized controlled trial in infants compared safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated with the preservative 2-phenoxyethanol (2-PE) in a multidose vial (MDV) to the current PCV13 without 2-PE in a single-dose syringe (SDS).MethodsGambian infants were randomized 1:1 to receive PCV13 as either MDV or SDS at ages 2, 3, and 4 months. Serotype-specific antipneumococcal antibody responses and opsonophagocytic activity ([OPA]; subset) were measured at age 5 months. Noninferiority was declared if the lower bound of the 97.5% CI for the difference (MDV-SDS) in proportions of subjects achieving IgG concentrations ≥0.35 μg/mL (primary endpoint) was greater than −10%. IgG geometric mean concentrations (GMCs) were noninferior if the lower limit of the two-sided 97.5% CI of the geometric mean ratio (MDV vs SDS) was greater than 0.5. Reactogenicity and other adverse events were collected.Results500 participants were randomized and vaccinated; 489 (MDV: n = 245; SDS: n = 244) completed the trial. Noninferiority of MDV was demonstrated for all serotypes as measured by percentage of subjects achieving antibody responses above ≥0.35 μg/mL. IgG GMCs (coprimary endpoint) also demonstrated noninferiority of MDV; OPA results supported these findings. Safety and tolerability were comparable between groups.ConclusionsPCV13 in MDV was safe and immunogenic when administered according to the routine schedule to infants. MDV was noninferior to SDS for all 13 pneumococcal serotypes. Comparable immunogenicity and safety profiles of PCV13 MDV and SDS suggest PCV13 MDV can help optimize vaccination in resource-limited settings. ClinicalTrials.gov NCT01964716 https://clinicaltrials.gov/ct2/show/NCT01964716.

Journal article

Mehring-Le Doare KEK, 2017, Association between functional antibody against Group B Streptococcus and maternal and infant colonization in a Gambian cohort, Vaccine, Vol: 35, Pages: 2970-2978, ISSN: 1873-2518

BackgroundVertical transmission of Group B Streptococcus (GBS) is a prerequisite for early-onset disease and a consequence of maternal GBS colonization. Disease protection is associated with maternally-derived anti-GBS antibody. Using a novel antibody-mediated C3b/iC3b deposition flow cytometry assay which correlates with opsonic killing we developed a model to assess the impact of maternally-derived functional anti-GBS antibody on infant GBS colonization from birth to day 60–89 of life.MethodsRectovaginal swabs and cord blood (birth) and infant nasopharyngeal/rectal swabs (birth, day 6 and day 60–89) were obtained from 750 mother/infant pairs. Antibody-mediated C3b/iC3b deposition with cord and infant sera was measured by flow cytometry.ResultsWe established that as maternally-derived anti-GBS functional antibody increases, infant colonization decreases at birth and up to three months of life, the critical time window for the development of GBS disease. Further, we observed a serotype (ST)-dependent threshold above which no infant was colonized at birth. Functional antibody above the upper 95th confidence interval for the geometric mean concentration was associated with absence of infant GBS colonization at birth for STII (p < 0.001), STIII (p = 0.01) and STV (p < 0.001). Increased functional antibody was also associated with clearance of GBS between birth and day 60–89.ConclusionsHigher concentrations of maternally-derived antibody-mediated complement deposition are associated with a decreased risk of GBS colonization in infants up to day 60–89 of life. Our findings are of relevance to establish thresholds for protection following vaccination of pregnant women with future GBS vaccines.

Journal article

Heath PT, Culley FJ, Jones CE, Kampmann B, Le Doare K, Nunes MC, Sadarangani M, Chaudhry Z, Baker CJ, Openshaw PJMet al., 2017, Group B streptococcus and respiratory syncytial virus immunisation during pregnancy: a landscape analysis, Lancet Infectious Diseases, Vol: 17, Pages: e223-e234, ISSN: 1473-3099

Group B streptococcus and respiratory syncytial virus are leading causes of infant morbidity and mortality worldwide. No licensed vaccines are available for either disease, but vaccines for both are under development. Severe respiratory syncytial virus disease can be prevented by passively administered antibody. The presence of maternal IgG antibody specific to respiratory syncytial virus is associated with reduced prevalence and severity of respiratory syncytial virus disease in the first few weeks of life, whereas maternal serotype-specific anticapsular antibody is associated with protection against both early-onset and late-onset group B streptococcus disease. Therefore, vaccination in pregnancy might protect infants against both diseases. This report describes what is known about immune protection against group B streptococcus and respiratory syncytial virus, identifies knowledge gaps regarding the immunobiology of both diseases, and aims to prioritise research directions in maternal immunisation.

Journal article

Boodhun N, 2016, BMC Pediatrics reviewer acknowledgement 2015, BMC Pediatrics, Vol: 16

Journal article

Kobayashi M, Vekemans J, Baker CJ, Ratner AJ, Le Doare K, Schrag SJet al., 2016, Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries, F1000 Research, Vol: 5, ISSN: 2046-1402

Globally, group B Streptococcus (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.

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00799246&limit=30&person=true