Group-B streptococci: developing a correlate of protection for future vaccine trials
My main research interests are the effect of maternal immunity of infant disease.
Group-B Streptococcal (GBS) disease is a major cause of infant mortality and morbidity globally. In low/middle income settings, the disease burden remains uncertain although in several countries of Southern Africa appears comparable to that of high-income countries (1.4/1000 live births). Colonization rates in pregnant women range from 12-50% and around 50% of their infants will be colonized. Of these, ca. 1% are known to develop GBS disease with 10% mortality and subsequent severe disability in up to 50% in survivors of GBS meningitis. Early-onset disease (EOD) is caused by transmission from a colonized mother to her newborn infant. Late-onset disease (LOD) occurs both from colonization and environmental factors. Protection from neonatal invasive disease is known to be associated with maternal antibody to certain GBS-serotypes. Therefore, maternal immunization to elicit antibody to be transmitted via the placenta and protect newborns represents an attractive disease prevention strategy for both EOD and LOD. However, phase III trials of GBS vaccines, now in clinical development, are hampered by large sample numbers required to prove efficacy. It is widely acknowledged that availability of a surrogate marker would have enormous impact as an alternative endpoint in clinical trials aimed at licensure.
Since there are geographical differences in strain distribution, the global effectiveness of GBS vaccines currently in development is unknown, and GBS-serotype specific recent data from West Africa are lacking to predict potential impact. The effect of maternal GBS carriage on serotype-specific antibody transfer to her infant and subsequent antibody function, and the natural history of decline in antibody in infant blood and breastmilk has not been evaluated but matters for future vaccination strategies.
I am currently developing several studies to answer important questions about serocorrelates of protection, including the standardisation of GBS antibody assays.
Le Doare K., Allen, L., Taylor, S. Kampmann, B., Heath, P., Gorringe, A., Hesseling, A., Jones CE. Anti-Group B streptococcus antibody in infants born to mothers with human immunodeficiency virus (HIV) infection, Vaccine, 2015 29;33 (5) 621-7
Le Doare K, Mackie NE, Kaye S, Bamford A, Walters S, Foster C. Virtual support for paediatric HIV treatment decision making. Arch Dis Child. 2015 Jun;100(6):527-31
Wells R, Le Doare K, Sharland M, Heath P, Ladhani SN; CABIN Network. Targeted empiric antibiotic therapy for children with non-oncological comorbidities and community-onset invasive bacterial infections. J Infect. 2015 Sep;71(3):294-301
Watson G, Jallow B, Le Doare K, Pushparajah K, Anderson ST. Acute rheumatic fever and rheumatic heart disease in resource-limited settings. Arch Dis Child. 2015 Apr;100(4):370-5
Herbert J, Thomas S, Brookes C, Turner C, Turner P, Nosten F, Le Doare K, Hudson M, Heath PT, Gorringe A, Taylor S. Antibody-mediated complement C3b/iC3b binding to group B Streptococcus in paired mother and baby serum samples in a refugee population on the Thailand-Myanmar border. Clin Vaccine Immunol. 2015 Mar;22(3):319-26
Le Doare K, Menson E, Patel D, Lim M, Lyall H, Herberg J. 15 min consultation: Managing neonatal and childhood herpes encephalitis.Arch Dis Child Educ Pract Ed. 2015 Apr;100(2):58-63
Le Doare, K., Barker, C., Irwin, A., Sharland, M. Improving antibiotic prescribing for children in the resource-poor setting, Br J Clin Pharmacol. 2015 Mar;79(3):446-55
Le Doare, K., Kampmann, B. Breast milk and Group B streptococcal infection: vector of transmission or vehicle for protection? Vaccine. 2014 May 30;32(26):3128-32.
Calton EA, Le Doaré K, Appleby G, Chisholm JC, Sharland M, Ladhani SN; CABIN Participants. Invasive bacterial and fungal infections in paediatric patients with cancer: incidence, risk factors, aetiology and outcomes in a UK regional cohort 2009-2011. Pediatr Blood Cancer. 2014 Jul;61(7):1239-45.
Le Doare, K., Bieliki, J., Heath, P., Sharland, M. Systematic review of antibiotic resistance rates among Gram-negative bacteria in children with sepsis in resource-limited countries, J. Paediatr. Infect. Dis., 2014 Jul; 4(1): 11-20
Le Doare K, Nichols AL, Payne H, Wells R, Navidnia S, Appleby G, Calton E, Sharland M, Ladhani SN; the CABIN Network.Very low rates of culture-confirmed invasive bacterial infections in a prospective 3-year population-based surveillance in Southwest London. Arch Dis Child. 2014 Jun;99(6):526-31
Le Doare, K., Hullah, E., Challacombe, S., Menson, E. 15-minute consultation – recurrent mouth ulcers, Arch Dis Child Educ Pract Ed. 2014 Jun;99(3):82-6
Le Doare, K., Heath P. An overview of global Group-B Streptococcal Epidemiology, Vaccine, 31 (4) D7-D12
Le Doare, K., Booker, E, Ladhani, S. Travell-associated salmonella-mbandaka sacroiliac osteomyelitis in a health adolescent, Case Rep Infect Dis. 2013:543147
Le Doare, K., Barber, N., Doerholt, K., Sharland, M. Rifampicin pharmacokinetics in extreme prematurity to treat congenital tuberculosis, BMJ Case rep. 2013, Jan . 25
Le Doare, K., Gannon, H., Handforth, J. Missed Opportunities to Treat, Syphilis in Pregnancy, Sex Transm Infect. 2012 Dec;88(8):594
Le Doare, K, Bland, R, Newell, M-L., Neurodevelopment in children born to HIV infected mothers by infection and treatment status, Pediatrics. 2012 Nov;130(5):e1326-44
Le Doaré K., Ameli-Renani, S., Banerjee, D., Brecker, S., Eastwood, J.B., Acute Renal Failure and Multiple Sites of Ischaemia, what is the unifying diagnosis? NDT Plus 1, 5; (2008) 359-360.
Le Doaré K, Akerman S, Holland PR, Lasalandra MP, Bergerot A, Classey JD, Knight YE, Goadsby PJ. Occipital afferent activation of second order neurons in the trigeminocervical complex in rat. Neurosci Lett. 2006 Jul 31;403(1-2):73-7
Books and Book Chapters:
Le Doare K. Two chapters: Congenital infection, Neonatal Infection and immunity In MRCPCH Master Course in Paediatrics, Wiley-Blackwell. In Press
Le Doare K Four chapters: Varicella Infection, Neonatal Infection, Congenital Infection, Herpes Infection. In Manual of Childhood Infections. Oxford University Press. In Press
Dr. Pia Panneraj, University of California, breastmilk microbiome, 2016
Prof. Andrew Gorringe, Public Health England, 2012
Group B Streptococcus epidemiology, Univeristy of Barcelona, Barcelona, 2016