Haemophilus influenzae serotype b conjugate vaccine failure in twelve countries with established national childhood immunization programmes

Abstract

The present study describes the clinical and immunological features of children with Hib vaccine failure, who were identified through national surveillance between 1996 and 2001 in Europe, Israel and Australia. True vaccine failure was defined as invasive Hib disease occurring ≥2 weeks after one dose, given after the first birthday, or ≥1 week after ≥2 doses, given at <1 year of age. Of the 423 cases (representing 0.2 cases per 100,000 child-years at risk) reported, 330 (78%) had received three doses in the first year of life and developed disease at a median age of 28 months. Of the remaining 93, 48 had received two doses in infancy, 34 had received four doses including a booster, and 11 had received a single dose after 12 months of age. These children developed disease at a median age of 12, 33 and 71 months, respectively. In total, 47 out of 258 children (18%) with available information had an underlying medical problem (including prematurity) and 53 out of 161 (33%) had immunoglobulin deficiency. Convalescent Hib antibody concentrations were above the putative protective concentration of 1.0 mg/L in 147/194 (76%) children; low concentrations were associated with both the presence of an underlying medical problem and young age at the time of Hib disease. Almost all children who received an additional vaccine dose developed antibodies at protective concentrations. Thus, Hib vaccine failure is rare, but can occur with any immunization schedule. Children with Hib vaccine failure should have immunoglobulin and convalescent Hib antibody concentrations measured after infection and receive additional vaccination, if required.

Epidemiology of InvasiveHaemophilus influenzaeDisease, Europe, 2007–2014

“…Among children <5 years of age with invasive H. influenzae disease, almost 1 in 5 cases is still caused by Hib, a potentially preventable disease. Breakthrough cases of invasive disease following Hib vaccination have been reported in immunocompromised and healthy children ( 25 , 26 ); however, vaccine failures are rare, and additional vaccine doses have are an effective way to achieve protective antibody levels in such instances ( 25 ). Although Hib vaccination has notably decreased the incidence of invasive Hib disease in all age groups, this reduction has been greatest among young children ( 3 , 10 , 11 , 27 ), and most Hib cases now occur in older adults with concurrent conditions ( 27 , 28 ).…”

Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

“…The incidence of invasive H. influenzae disease may actually have increased in recent years (227,229), but since Hib vaccine failure is rare (236), most invasive infections occur in the extreme ages of life and in patients with predisposing conditions (224,226,229,232).…”

Factors affecting vaccine handling and storage practices among immunization service providers in Ibadan, Oyo State, Nigeria

“…A study conducted in Lagos, showed that ¾ of the vaccines at the local government level were sub-potent with the situation failing to improve over the three-year study period 1 . Studies have also reported that improper vaccine storage leading to the administration of sub-potent vaccines may have been associated with outbreaks of vaccine preventable diseases in Israel 2 and several developing countries 3 . Poor handling and storage, cold chain deficiencies such as inadequate infrastructure, power shortages and poor maintenance are associated with vaccine wastage.…”