title: Effect of Haemophilus influenzae type b vaccination without a booster dose on invasive H influenzae type b disease, nasopharyngeal carriage, and population immunity in Kilifi, Kenya: a 15-year regional surveillance study.
abstract: BACKGROUND
  Haemophilus influenzae type b (Hib) conjugate vaccine, delivered as a three-dose series without a booster, was introduced into the childhood vaccination programme in Kenya in 2001. The duration of protection and need for a booster dose are unknown. We aimed to assess vaccine effectiveness, the impact of the vaccine on nasopharyngeal carriage, and population immunity after introduction of conjugate Hib vaccine in infancy without a booster dose in Kenya.
  
  
  METHODS
  This study took place in the Kilifi Health and Demographic Surveillance System (KHDSS), an area of Kenya that has been monitored for vital events and migration every 4 months since 2000. We analysed sterile site cultures for H influenzae type b from children (aged ≤12 years) admitted to the Kilifi County Hospital (KCH) from Jan 1, 2000, through to Dec 31, 2014. We determined the prevalence of nasopharyngeal carriage by undertaking cross-sectional surveys in random samples of KHDSS residents (of all ages) once every year from 2009 to 2012, and measured Hib antibody concentrations in five cross-sectional samples of children (aged ≤12 years) within the KHDSS (in 1998, 2000, 2004-05, 2007, and 2009). We calculated incidence rate ratios between the prevaccine era (2000-01) and the routine-use era (2004-14) and defined vaccine effectiveness as 1 minus the incidence rate ratio, expressed as a percentage.
  
  
  RESULTS
  40,482 children younger than 13 years resident in KHDSS were admitted to KCH between 2000 and 2014, 38,206 (94%) of whom had their blood cultured. The incidence of invasive H influenzae type b disease in children younger than 5 years declined from 62·6 (95% CI 46·0-83·3) per 100,000 in 2000-01 to 4·5 (2·5-7·5) per 100,000 in 2004-14, giving a vaccine effectiveness of 93% (95% CI 87-96). In the final 5 years of observation (2010-14), only one case of invasive H influenzae type b disease was detected in a child younger than 5 years. Nasopharyngeal H influenzae type b carriage was detected in one (0·2%) of 623 children younger than 5 years between 2009 and 2012. In the 2009 serosurvey, 92 (79%; 95% CI 70-86) of 117 children aged 4-35 months had long-term protective antibody concentrations.
  
  
  CONCLUSIONS
  In this region of Kenya, use of a three-dose primary series of Hib vaccine without a booster dose has resulted in a significant and sustained reduction in invasive H influenzae type b disease. The prevalence of nasopharyngeal carriage is low and the profile of Hib antibodies suggests that protection wanes only after the age at greatest risk of disease. Although continued surveillance is important to determine whether effective control persists, these findings suggest that a booster dose is not currently required in Kenya.
  
  
  BACKGROUND
  Gavi, the Vaccine Alliance, Wellcome Trust, European Society for Paediatric Infectious Diseases, and National Institute for Health Research.
authors: Department of Epidemiology and Demography, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: lhammitt@jhu.edu.
authors: Laura L
authors: LL
authors: Hammitt
authors: Department of Epidemiology and Demography, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors: Rosie J
authors: RJ
authors: Crane
authors: Department of Epidemiology and Demography, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya.
authors: Angela
authors: A
authors: Karani
authors: Department of Epidemiology and Demography, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya.
authors: Alex
authors: A
authors: Mutuku
authors: Department of Epidemiology and Demography, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
authors: Susan C
authors: SC
authors: Morpeth
authors: Institute of Child Health, University College London, London, UK.
authors: Polly
authors: P
authors: Burbidge
authors: Institute of Child Health, University College London, London, UK.
authors: David
authors: D
authors: Goldblatt
authors: Kenya Ministry of Public Health and Sanitation, Kilifi, Kenya.
authors: Tatu
authors: T
authors: Kamau
authors: Kenya Ministry of Public Health and Sanitation, Kilifi, Kenya.
authors: Shahnaaz
authors: S
authors: Sharif
authors: Department of Epidemiology and Demography, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya.
authors: Neema
authors: N
authors: Mturi
authors: Department of Epidemiology and Demography, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
authors: J Anthony G
authors: JA
authors: Scott
mesh_terms: D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006192:Haemophilus Infections / Q000453:epidemiology / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage*; D019741:Haemophilus influenzae type b / Q000276:immunology*; D006801:Humans; D017589:Immunization Programs / Q000379:methods*; D007115:Immunization Schedule; D015994:Incidence; D007223:Infant; D007630:Kenya / Q000453:epidemiology; D008297:Male; D009305:Nasopharynx / Q000382:microbiology*; D015995:Prevalence; D018074:Vaccines, Conjugate / Q000008:administration & dosage
chemical_list: D018073:Haemophilus Vaccines; D018074:Vaccines, Conjugate