title: Burden of invasive group B Streptococcus disease and early neurological sequelae in South African infants.
abstract: BACKGROUND
  Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0-6 days of life, EOD) and late-onset (7-89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women.
  
  
  METHODS
  A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were identified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age.
  
  
  RESULTS
  We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24-9.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37; 95%CI: 1.94-386.50) and maternal GBS bacteriuria (aOR: 8.41; 95%CI: 1.44-49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17-10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44-120.95) greater in cases (13.2%) than controls (0.4%).
  
  
  CONCLUSIONS
  The high burden of invasive GBS disease in South Africa, which is also associated with high case fatality rates and significant neurological sequelae among survivors, is partly due to the heightened risk for LOD in infants born to HIV-infected women. An effective trivalent GBS conjugate vaccine targeted at pregnant women could prevent invasive GBS disease in this setting.
authors: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa; Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
authors: Ziyaad
authors: Z
authors: Dangor
authors: Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
authors: Sanjay G
authors: SG
authors: Lala
authors: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
authors: Clare L
authors: CL
authors: Cutland
authors: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
authors: Anthonet
authors: A
authors: Koen
authors: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
authors: Lisa
authors: L
authors: Jose
authors: Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
authors: Firdose
authors: F
authors: Nakwa
authors: Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
authors: Tanusha
authors: T
authors: Ramdin
authors: Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
authors: Joy
authors: J
authors: Fredericks
authors: Department of Clinical Microbiology and Infectious Diseases, National Health Laboratory Service, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
authors: Jeannette
authors: J
authors: Wadula
authors: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa; National Institute for Communicable Diseases: a division of National Health Laboratory Service, Centre for Vaccines and Immunology, Sandringham, Gauteng, South Africa.
authors: Shabir A
authors: SA
authors: Madhi
mesh_terms: D044383:Black People; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000209:etiology*; D008297:Male; D009422:Nervous System Diseases / Q000453:epidemiology / Q000209:etiology*; D011159:Population Surveillance; D011247:Pregnancy; D011446:Prospective Studies; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D013290:Streptococcal Infections / Q000150:complications* / Q000453:epidemiology / Q000276:immunology; D013292:Streptococcus agalactiae / Q000276:immunology / Q000472:pathogenicity*