Risk of invasive Haemophilus influenzae type b (Hib) disease in adults with secondary immunodeficiency in the post-Hib vaccine era

Abstract

Prior to the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, invasive Hib disease affected almost exclusively children. According to some recent studies, in the postvaccine era, adults, the elderly, and immunocompromised persons can be affected more often than children. As the production of type-specific anti-capsular polysaccharide antibodies is the major defense mechanism against Hib, individuals with defects in humoral immune responses have high susceptibility to infections caused by Hib. We hypothesized that nonvaccinated adults with chronic conditions causing immunosuppression may lack protective antibody to Hib. We assessed serum anti-Hib IgG levels and bactericidal activity in 59 patients with chronic renal failure, 30 patients with type 2 diabetes mellitus, 28 patients with chronic obstructive pulmonary disease (COPD), and 20 patients with multiple myeloma compared to 32 healthy controls of similar age. Considering antibody at >0.15 μg/ml as the protective correlate in unvaccinated individuals, we detected subprotective Hib antibody levels in 29% of chronic renal failure, 20% of diabetes, 14% of COPD, and 55% of myeloma patients compared to 3% of healthy controls. Additionally, 70% of myeloma and 58% of chronic renal failure patients did not have detectable serum bactericidal activity against Hib. Among individuals with severe diseases causing secondary immunodeficiency, patients with multiple myeloma and chronic renal failure are at an increased risk of invasive Hib disease. Considering that Hib continues to circulate in the population, this study provides a rationale for the immunization of some adult patients with secondary immunodeficiency with the pediatric Hib vaccine to achieve protective immunity.

Fig 1

(a) Distribution of individual anti-PRP IgG antibody levels in patients with secondary immunodeficiency and healthy controls (geometrical mean concentrations are indicated for each group). The dashed line indicates the correlate of protection (0.15 μg/ml). (b) Antibody-mediated bactericidal activity in patients and controls. The dashed line indicates the lower limit of detection. CRF, chronic renal failure; DM, diabetes mellitus; MM, multiple myeloma. *, P = 0.029 for CRF and P = 0.048 for MM compared to controls. The numbers of individual samples with antibody levels or SBA scores below the lower limit of detection are indicated on each graph.

Fig 2

Correlation of anti-PRP IgG antibody levels with age among ≥60-year-old individuals. (a) Healthy controls. (b) All patient cohorts.

Fig 3

Correlation of anti-PRP IgG antibody levels with serum bactericidal assay geometric mean titers. (a) Healthy controls. (b) All patient cohorts.