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

摘要

Background Haemophilus infl uenzae type b (Hib) conjugate vaccine, delivered as a three-dose series without a booster,udwas introduced into the childhood vaccination programme in Kenya in 2001. The duration of protection and need foruda booster dose are unknown. We aimed to assess vaccine eff ectiveness, the impact of the vaccine on nasopharyngealudcarriage, and population immunity after introduction of conjugate Hib vaccine in infancy without a booster doseudin Kenya.udMethods This study took place in the Kilifi Health and Demographic Surveillance System (KHDSS), an area of Kenyaudthat has been monitored for vital events and migration every 4 months since 2000. We analysed sterile site culturesudfor H infl uenzae type b from children (aged ≤12 years) admitted to the Kilifi County Hospital (KCH) from Jan 1, 2000,udthrough to Dec 31, 2014. We determined the prevalence of nasopharyngeal carriage by undertaking cross-sectionaludsurveys in random samples of KHDSS residents (of all ages) once every year from 2009 to 2012, and measured Hibudantibody concentrations in fi ve cross-sectional samples of children (aged ≤12 years) within the KHDSS (in 1998, 2000,ud2004–05, 2007, and 2009). We calculated incidence rate ratios between the prevaccine era (2000–01) and the routineuseudera (2004–14) and defi ned vaccine eff ectiveness as 1 minus the incidence rate ratio, expressed as a percentage.udFindings 40 482 children younger than 13 years resident in KHDSS were admitted to KCH between 2000 and 2014,ud38 206 (94%) of whom had their blood cultured. The incidence of invasive H infl uenzae type b disease in childrenudyounger 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 inud2004–14, giving a vaccine eff ectiveness of 93% (95% CI 87–96). In the fi nal 5 years of observation (2010–14), only oneudcase of invasive H infl uenzae type b disease was detected in a child younger than 5 years. Nasopharyngeal H infl uenzaeudtype b carriage was detected in one (0·2%) of 623 children younger than 5 years between 2009 and 2012. In the 2009udserosurvey, 92 (79%; 95% CI 70–86) of 117 children aged 4–35 months had long-term protective antibodyudconcentrations.udInterpretation In this region of Kenya, use of a three-dose primary series of Hib vaccine without a booster dose hasudresulted in a signifi cant and sustained reduction in invasive H infl uenzae type b disease. The prevalence ofudnasopharyngeal carriage is low and the profi le of Hib antibodies suggests that protection wanes only after the age atudgreatest risk of disease. Although continued surveillance is important to determine whether eff ective control persists,udthese fi ndings suggest that a booster dose is not currently required in Kenya.