Which host factors are conducive to invasiveness in the pathophysiology of Haemophilus influenzae type b (Hib) meningitis?

Updated: Jul 09, 2018
  • Author: Prateek Lohia, MD, MHA; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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Answer

Hib meningitis is quite rare in the first 2 months of life, accounting for 0-0.3% of all meningitis cases in this age group. Children of this age group are likely protected from infection by passively transferred maternal antibodies. Levels of these antibodies are considerably diminished by 2 months of life and they are often completely gone by 4 months of life. This period of protection appears to be prolonged in breastfed infants, likely because of continued passive transfer of antibodies.

After the loss of passively transferred antibodies, children do not develop adequate immune-mediated bactericidal capacity for Hib until several additional years of life have passed. This is the period of highest risk for Hib meningitis.

In immunocompetent children, the capacity to mount resistance to invasive Hib disease rises rapidly after age 3 years and, once acquired, tends to be permanent. Most older children and adults who develop Hib meningitis have underlying medical conditions that interfere with immune function.

The development of resistance to Hib infection appears to be due to gradual acquisition of antibodies directed at capsular determinants of Hib and possibly to other aspects of immune system maturation. More than 90% of 2- to 12-month-old infants have very low titers of antibodies to the alpha–polyribosyl-ribitol-phosphate (PRP) capsular constituent of Hib, compared with resistant adults. These antibodies likely play a role, with complement, in opsonization and bactericidal effects that may prevent colonization, invasion, or persistence in circulation of Hib.

Exposure to Hib and colonization with it is the only possible cause of a rise in specific antibody titers. Possibly, pertinent antibodies develop as the result of exposure to other genera of encapsulated bacteria that express cross-reactive epitopes in their capsules. Among the most important of the likely causes of such cross-reactive protection are enteric bacteria.

Persistent Hib-related PRP antigenemia due to failure of these containment and killing activities may in turn delay the development of a type-specific antibody response to Hib. Infants and young children who develop Hib meningitis take as long as 3 months to mount a type-specific response to the causative Hib strain.

To varying degrees, the development of these protective immune responses is delayed and less robust in children who have immune system compromise, such as those with agammaglobulinemia, immunoglobulin G (IgG2) subclass deficiency, or various degrees of asplenia due to sickle cell anemia or other causes, as well as those with cancer, HIV infection, chronic pulmonary or renal disease, or immunosuppression due to organ transplant or other causes. Hib meningitis is more common in such infants.

Young children with these immunocompromising conditions may continue to be vulnerable to Hib meningitis longer than children who experience the normal course of immune development that renders Hib meningitis unlikely in children older than 5 years. Some diseases that otherwise interfere with normal immune function, such as cerebrospinal fluid (CSF) fistulae or other abnormalities of BBB function, may also predispose to Hib meningitis.


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