eMedicine Specialties > Neurology > Neurological Infections

Haemophilus Meningitis: Follow-up

Author: Robert Rust Jr, MD, Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, University of Virginia School; Clinical and Residency Training, Child Neurology, University of Virginia Hospital and Clinics
Coauthor(s): Robert Cavaliere, MD, Assistant Professor of Neurology, Neurosurgery and Medicine, Ohio State University College of Medicine
Contributor Information and Disclosures

Updated: Sep 28, 2006

Follow-up

Further Inpatient Care

• Follow-up care of individuals diagnosed with Hib meningitis entails careful attention to metabolic parameters, close attention to timely replacement and management of intravenous lines to prevent secondary infections, and management of pulmonary and cardiovascular function as is necessary in light of the severity of illness.
• Head circumference, fontanelle pressure, funduscopy, and other measures of secondary increases in intracranial volume due to postmeningitic hydrocephalus or the development of extra-axial collections (eg, abscess, empyema, subdural hemorrhage, noninfectious subdural collections) should be monitored as indicated in individual cases. Repeat scans of the intracranial contents should be ordered as needed when unexpected deteriorations of function occur that might be explained by structural processes.
• Physical and occupational therapy evaluations and therapy should be initiated as soon as is judged feasible in cases where neurologic abnormalities persist after initial treatment. Hearing testing should be performed at the conclusion of treatment, and posthospitalization interventions for such deficits as are found should be arranged.

Further Outpatient Care

• Outpatient care is indicated for the management of deficits resulting from Hib meningitis, including static encephalopathy, seizures, behavioral changes, or epilepsy.

Inpatient & Outpatient Medications

• No specific medications are generically indicated. Patients may in some instances require anticonvulsants, analgesics, and medications to promote sleep or to attenuate behavioral, attention, or learning problems that develop in the wake of Hib encephalitis. The type and duration of these treatments depends upon the specific circumstances of the individual case.

Deterrence/Prevention

• Immunoprophylaxis
  • The virulence of Hib is related to its polysaccharide capsule. Antibodies directed against the capsule have been shown to confer protection against Hib infection. An inverse relationship exists between the serum level of antibodies and invasive infections.
  • With this knowledge, the development of a vaccine that would induce such antibodies was pursued.
  • The first vaccines were produced from the polysaccharide capsule material and were licensed for routine use in children older than 2 years in 1985. However, this vaccine proved ineffective for children younger than 18 months (who are those most likely to develop Hib meningitis) and had only moderate effectiveness in older children (Peltola, 1984).
  • Subsequently, new vaccines were developed that conjugated a carrier protein to the PRP molecule. These were first licensed in the United States in 1987 but were not approved for use in children as young as 2 months until 1990.
  • Currently 4 vaccines, all conjugated, are approved for use within the Unites States. All of these agents have demonstrated a considerable degree of immunogenicity, even in very young children.
  • The failure rate of Hib conjugate vaccines is exceedingly low. Such failures are related, in slightly less than half of all cases, to defined underlying immunological deficiency or other pertinent risk factors. Immunoglobulin deficiency and asplenia are the most commonly encountered impediments to effective vaccination (Krueger, 2004).
  • IgG3-deficient individuals, who may be infection-prone due to low capacity to generate protective antibody levels have been shown to respond well to immunization with the conjugate ACT-HIB vaccine, achieving sufficient levels of antibodies to provide protection against both Hib infections and tetanus (Hahn-Zoric, 2004).
• Vaccination
• Several studies have demonstrated a significant reduction in the rate of carriage of the organism. Carriage of the organism increases the risk of infection in the colonized individual. Reduction in rates of carriage also reduces the exposure to other children who may be at risk.
• The achievement of reduced nasopharyngeal carriage in older children, who received conjugated vaccines prior to their approval for use in infants, may account for the fact that many studies showed a decline in incidence of Hib meningitis in infants who were not as yet eligible for vaccination.
• Clinical efficacy
  • Several studies in the United States and abroad have demonstrated a significant reduction in the incidence of invasive infection soon after the introduction of the vaccine. Within the United States, the incidence of invasive Hib diseases has fallen from 85% to 90%. These results have been reproducible in both regional and multistate studies and are not accounted for by interannual variations. The population that received the greatest benefit is that consisting of infants younger than 14 months, a group with the highest incidence of Hib meningitis.
  • Canada, which has had an immunization program since 1992, has discerned a shift in population prevalence for Hib meningitis, with cases occurring more frequently in infants younger than 6 months. Two thirds of cases occur in individuals with no or incomplete vaccination (due to age, parental refusal, or other delaying circumstances). However, some cases occur in individuals who have completed the primary series of immunizations. It has also been demonstrated that the conjugate vaccine efficacy is not affected by coadministration of other typical age-indicated vaccinations. Higher case-fatality rates are observed in the postimmunization epoch in Canada and in older individuals, and two thirds of these cases occur in males (Schiefele, 2005).
  • Studies in the Netherlands have detected a disturbing trend toward an increase in the rate of invasive Hib disease in children younger than 5 years. The increased annual incidence is from 0.66 cases per 100,000 in 1998 to 2.96 cases per 100,000 in 2001. The investigators are concerned that this increase is due to the change from the use of whole-cell pertussis vaccine to the conjugate DTaP-Hib vaccine. This newer vaccine has been associated with the achievement of lower levels of anti-Hib antibodies, although in the Netherlands that effect has not been observed (Peltola, 2005).
  • Unfortunately, even vaccination producing "adequate" Hib antibody levels may in rare instances not prevent the development of severe Hib infection, as has been observed recently in a case of fatal Hib septic purpura fulminans (Krueger, 2004).
• Lack of effect on mortality
  • Despite effective reduction in the incidence of disease, the case-fatality rate has remained about the same in the United States in the era of effective vaccination as it was prior to the availability of an effective vaccine. However, fewer deaths related to Hib meningitis in vaccinated populations have occurred annually since the number of cases has been so greatly reduced.
  • On the other hand, in developing nations, the effect of vaccination on case-fatality and case-morbidity rates may be expected to be much higher since these outcome measures are so much worse in nations where diagnosis and treatment may be delayed due to the inadequacies of transportation and medical infrastructure. Moreover, in developing nations the rates of antibiotic resistance (which elevated morbidity and mortality) is high and steadily increasing. In Pakistan, where 35% of childhood meningitis is Hib, occurring mostly in the first year of life, the rates of Hib resistance to antibiotics is approximately 33% for ampicillin, 22% for chloramphenicol, and 49% for cotrimoxazole (Saha, 2005).
  • The increasing role that nontypeable strains of H influenzae, for which no effective immunization is available, has been noted. So has recognition of such typeable strains as Hif (serotype f), suggesting that the place of Hib as the overwhelmingly most common cause of invasive disease due to H influenzae may be taken to some degree by other capsular types. It is troubling that there has been recognition of what may be clonal expansion of several strains of Haemophilus that are the same in the United States and Denmark (Bruun, 2004).
• Adverse reactions: Side effects of the vaccine are difficult to assess because Hib vaccination is administered concurrently with other vaccinations. The most commonly reported reactions are local erythema and induration and irritability. Fever has also been reported. No serious adverse reactions have as yet been clearly linked to the currently employed Hib vaccines.
  
• The current controversies and difficulties concerning establishment of immunization programs in developing nations has been discussed in the section above concerning international incidence of Hib meningitis. In 2005, the Global Alliance for Vaccines and Immunization (GAVI) created the Hib Initiative, aiming to spend $37 million, over a 4-year period, for the funding of immunization programs in countries where immunization is inadequate.
  • The importance of such programs, irrespective of the controversies concerning regional annual incidence of Hib meningitis, is the fact that, in many targeted countries, Hib meningitis has much higher rates of morbidity and mortality than in wealthier nations with superior infrastructure such as roads and hospitals. Thus, in rural Papua, New Guinea, as many as 63% of children surviving meningitis (excluding a rather high rate of children lost to follow up) manifested major neurological sequelae. The high rates of morbidity and mortality have been ascribed in part to the high rates of resistance to chloramphenicol and the unavailability of third-generation cephalosporins. However, the introduction of greater supplies of third-generation cephalosporins cannot be expected to significantly lower these rates since nations such as Papua, New Guinea, are unavoidably plagued by delayed presentation of sick children to centers capable of administering appropriate antibiotic treatment.
  • Those who are one the front lines of this healthcare problem have pleaded to wealthier nations for assistance in sponsoring vaccination and encouraging vaccine manufacturers to lower the costs of vaccines (Wandi, 2005).

Complications

• Some complications of Hib meningitis are transient; others lead to chronic or even permanent problems. Complications and permanent deficits are more likely to arise in individuals who have delays in diagnosis and treatment and who are treated with less effective antibiotics, such as those for which there is Hib resistance. The general categories are as follows:
  • Seizures and epilepsy
  • Hearing loss
  • Other cranial nerve deficits
  • Ataxia
  • Hemiparesis
  • Subdural effusions
• Seizures that occur on presentation and during the earliest acute phase of Hib meningitis do so because of transient focal derangements in cortex or because of metabolic disturbances such as hyponatremia or hypoglycemia. Treatment may require the administration of anticonvulsants, the choice of which involves consideration of type of seizures, age of patient, and route of administration of drugs.
• Occasionally, children with meningitis manifest subtle change in mental status in the wake of prolonged generalized seizures. Signs of such a process include poor responsiveness and the presence of widespread irregularly repetitive minipolymyoclonic jerks or twitches. EEG assessment may be necessary.
• During the acute phase of presentation, care must be taken to diagnose and appropriately treat seizures prior to sedating or paralyzing patients for such procedures as brain imaging. Failure to do so may permit seizures to persist unrecognized for intervals of 40 minutes or more, which may have a very deleterious effect on outcome.
• Initial administration of anticonvulsants may precede discernment of the cause of seizure in cases where seizures are prolonged or in cases where they may increase intracranial pressure or metabolic demand. In such instances, children are generally treated with intravenously administered benzodiazepines, phenytoin, or phenobarbital. The decision to continue providing maintenance during the course of hospitalization depends on the cause and severity of seizures as well as the likelihood of recurrence.
• Hemiconvulsive seizures at presentation with low-grade fever may necessitate the exclusion of Hashimoto encephalopathy. Focal or hemiconvulsive seizures in children may suggest such alternative diagnoses as herpes I, LaCrosse, Japanese B, or other forms of encephalitis, depending on time of year, region of the world, and historical exposures.
• Transient brief focal seizures occurring within the acute setting do not raise the risk of epilepsy. Five to 10% of patients continue to manifest seizures after discharge from the hospital. Those who tend to be the sickest patients are those who are found to have persistent focal signs such as hemiparesis and those who show persistence of abnormalities of mental status, feeding, and movement at discharge. Provision of appropriately selected anticonvulsants with consideration of seizure type and age of patient is necessary in such cases.
• Generally, patients to whom such outpatient medications are administered may respond well and have no recurrence for the ensuing year, or to the contrary, they may continue to have seizures despite the first appropriately chosen drug. The former category tends to do well and may have medications discontinued at the end of a year of treatment with small risk for recurrence. The second group tends to exhibit intractable epilepsy, and their seizures remain difficult to control despite multiple anticonvulsants.
• The presence of a persistent neurologic deficit other then sensorineural hearing loss is a risk factor for late manifestation of seizures (ie, seizures appearing for the first time in the late stages of hospitalization or after a period of weeks to years after discharge). In one study, all patients with a persistent deficit other than sensorineural hearing loss went on to have recurrent seizures after Hib meningitis. Structural lesions are often discerned on brain imaging.
• Occasionally, persistent seizures manifest in children who have had Hib meningitis but who recover fully and without any evidence on examination of focal neurologic deficits. These uncommon cases are usually found to have structural brain abnormalities on brain imaging. In some of these cases, if seizures are intractable, as well as in cases where persistent deficits are mild or moderate, epilepsy surgery can be considered at an appropriately remote time from acute hospitalization.
• Hearing impairment is a common complication of meningitis. It is among the most common sequelae of Hib meningitis, occurring in about 20% of cases, although reports indicate a range of 10-30%. Hearing loss is sensorineural and may be unilateral or bilateral with deficits ranging from mild hearing loss to deafness in the involved ear. Persistent hearing deficits may be associated with learning disabilities and language delay.
• The actual mechanisms of damage to the hearing system are not fully understood. The absence of all waveforms on BAER suggests a peripheral process. One explanation of injury is that, during the acute phase of illness, the eighth cranial nerve becomes encased by inflammatory exudate within its sleeve in the subarachnoid space. Another possible mechanism is bacterial invasion of the spiral ganglia or cochlear perilymph via the internal auditory canal or cochlear aqueduct, resulting either in direct damage or in damage secondary to toxins or inflammatory products. Evidence for either of these mechanisms has been found in pathological studies.
• Although sensorineural hearing loss is the most common finding, occasional patients with postmeningitic deafness are found to have conductive hearing loss. This type of deficit may result from the otitis media that fairly commonly precedes the development of Hib meningitis. Unlike sensorineural hearing loss, conductive hearing deficits resolve without permanent impairment.
• Cranial neuropathies other then the eighth cranial nerve may occur. The involvement of cranial nerves other than the eighth is found in approximately 6% of children who have had Hib meningitis. Nerves most commonly involved are the facial, abducens, and oculomotor, but any of the nerves may be involved. The mechanisms for these forms of injury include the inflammatory investment of the nerve within the nerve sheath near the brainstem (ie, due to the basilar meningitic inflammatory process), or they may be injured by compression due to elevation in intracranial pressure.
• Ataxia is among the less common manifestations of Hib meningitis. It is typically sensory/vestibular in origin. Although it occurs less often than hearing deficits, the presumed mechanism of disease is similar to that of sensorineural hearing loss, namely inflammatory investment of the vestibular division of the eighth cranial nerve. It is generally a self-limited process, although it is predictive of more permanent hearing loss.
• Hemiparesis is found in approximately 6% of children recovering from Hib meningitis. In some instances, it is due to cerebral strokes that occur because of vasculitic inflammation of the brain. In other instances, it is the result of large subdural effusions that are commonly observed in meningitis.
• Subdural effusions are common in Hib meningitis and are usually the result of inflammatory effects on vessels and the BBB, permitting leakage of sterile fluid into the subdural space. These collections are generally benign and do not cause symptoms and should in general be left alone. Eventually they resorb spontaneously. However, on occasion they can create local mass effect with involvement of local tissue. They may even result in elevated intracranial pressure, herniation, or focal signs such as hemiparesis. On occasion they may become infected. Such a process should be suspected in the setting of a persistent fever despite adequate antibiotic coverage.
• Epilepsy, which may be difficult to control despite multiple antiepileptic medications, is present in less then 10% of survivors. The first seizure after the acute phase usually occurs within the first 2 years, although it may occur much later. Seizures are generally focal or have a focal onset. A complication other than sensorineural hearing loss during the acute phase is associated with an increased risk of epilepsy. Most patients with epilepsy had seizures during the acute phase. However, seizures during the acute phase do not independently predict the occurrence of late seizures.
• Despite adequate treatment of children with Hib meningitis, approximately 20-40% are left with persistent sequelae. Some studies report that deficits are present in more than 50% of survivors.

Prognosis

• The mortality rate for Hib meningitis is 15-20% and is higher in very young infants (ie, <2 mo), individuals who have immunodeficiencies, and children who present with fulminant meningitis. Delays in diagnosis and treatment increase rates of mortality.
• Severely handicapping neurologic sequelae are found in 10% of cases, some significant neurologic problem is found in 20-40% of cases, and 15-25% manifest mild neurologic impairments. Approximately 45% of children who have had Hib meningitis recover without sequelae.
• Cognitive and behavioral disturbances are found in as many as 40% of children who have had Hib meningitis.
  • Many studies have been undertaken to evaluate the association of cognitive impairment and meningitis. When compared to siblings closest in age, children who have had meningitis have lower average full-scale IQ. The magnitude of difference is greater then one standard deviation in 30% of cases. In one such study, 28% of patients were found to have significant handicaps, including 11% with mental retardation.
  • In addition, a wide range of neurologic and learning disabilities is found in a large percentage of survivors who are successfully treated with antibiotics and subsequently considered to be normal by parents, teachers, and peers.
  • However, more recent studies have not demonstrated large differences in intellectual outcomes. No difference was detected in the IQ between index cases and nearest-age siblings. Differences that were significant were mild and of questionable clinical significance.
• Other long-term problems that are experienced by children who have had Hib meningitis include epilepsy, hemiparesis, and hearing loss. These problems are considered in Complications.

Patient Education

• For excellent patient education resources, visit eMedicine's Children's Health Center, Brain and Nervous System Center, Blood and Lymphatic System Center. Also, see eMedicine's patient education articles Meningitis in Children, Spinal Tap, Brain Infection, Sepsis (Blood Infection), Epiglottitis, and Cellulitis.

Miscellaneous

Medicolegal Pitfalls

• Potential medicolegal vulnerability may arise in the following situations:
  • Failure to administer Hib vaccine
  • The occurrence of a possible reaction to the administration of Hib vaccine
  • Failure to recognize and treat Hib meningitis in a timely fashion with appropriate antimicrobials
  • Failure to recognize and treat in a timely and appropriate fashion increased intracranial pressure complicating Hib meningitis
  • Failure to recognize and provide in an appropriate and timely fashion treatment for other complications of Hib meningitis, such as seizures, status epilepticus, hyponatremia due to SIADH or cerebral salt wasting, subdural effusions, or empyemas
  • Overtreatment or inappropriate treatment of any of these complications

• Search for CME/CE on This Topic »

• Brain and Nervous System Center
• Meningitis in Children Overview
• Meningitis in Children Symptoms
• Spinal Tap Introduction
• Sepsis Overview
• Cellulitis Overview
• Blood and Lymphatic System Center
• Meningitis in Children Causes
• Meningitis in Children Treatment
• Brain Infection Overview
• Epiglottitis Overview