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.

Findings: 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.

Interpretation: 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.

Funding: Gavi, the Vaccine Alliance, Wellcome Trust, European Society for Paediatric Infectious Diseases, and National Institute for Health Research.

Figure 1

Incidence of invasive Haemophilus influenzae type b disease in children younger than 5 years in the Kilifi Health and Demographic Surveillance System, 2000–14 Hib vaccine was introduced in November, 2001. Error bars show 95% CI.

Figure 2

Children with anti-PRP concentrations of >1 μg/mL, by age group and survey year Data for 1998 and 2000 combined (A), 2004–05 (B), 2007 (C), and 2009 (D). The proportion of children aged 4–7 months in (A) is 0%. Error bars show 95% CI. PRP=polyribosylribitol phosphate.

Figure 3

Reverse cumulative proportions of children with anti-PRP concentrations that exceed thresholds, by age group and survey year Data for children aged 4–11 months (A) 1–2 years (B), 3–4 years (C), and 5–12 years (D). Vertical lines indicate thresholds for short-term (0·15 μg/mL) and long-term (1 μg/mL) protection against invasive H influenzae type b disease.