Haemophilus Meningitis Clinical Presentation

Initial manifestations of meningitis, seen in more than half of all cases of Haemophilus influenzae type b (Hib) meningitis, include the following:

• Altered cry

• Lethargy

• Nausea or vomiting

• Fever

• Headache

• Photophobia

• Meningismus

• Irritability

• Anorexia

• Seizures

An altered cry is an important and statistically significant indicator of meningitis or other severe illness, especially in children younger than 2 years; it is noted in as many as 80% of young children with meningitis. Alterations of importance include high-pitched cry, inconsolable crying, weak cry, moaning, or severe reduction or absence of cry. Cry may suggest discomfort or severe distress for which no source outside of the nervous system can be identified.

Lethargy is an early sign in at least half of all cases of bacterial meningitis, versus approximately one third of all viral meningitis cases. Increasing lethargy or the occurrence of convulsive seizures is the usual reason for parents to bring such children to medical attention. These patients should be carefully examined for any evidence of meningismus.

Vomiting is reported as an early manifestation in nearly 50% of Hib meningitis cases. Some data suggest that in individuals with suspected meningitis who have associated vomiting, the lumbar puncture discloses evidence for either bacterial or viral meningitis in 15% of cases. If vomiting occurs, it generally does so within hours to days after the onset of fever.

The presentation of Hib meningitis may be considerably less fulminant than either meningococcal or pneumococcal meningitis, leading to misinterpretation of the initial symptoms or discounting of the significance of the somewhat more leisurely progression of illness. In such subacute cases, fever, irritability, and drowsiness may be the only reported initial signs and symptoms. These subtle manifestations may be mistakenly attributed to a preceding bout of otitis media or other form of upper respiratory illness.

Seizures occur in 23-44% of Hib meningitis cases. They tend to appear during the acute phase, usually within the first 3 days of illness. They are often focal but may secondarily generalize. If this focality is overlooked, seizures due to Hib meningitis may be mistakenly designated as febrile seizures.

Obtaining a history in children younger than 16 months (ie, those at greatest risk for Hib meningitis) may pose particular challenges. The absence of clinical evidence of severe illness cannot be relied upon to exclude the diagnosis of Hib meningitis, particularly in infants and toddlers, whose personal histories cannot readily be obtained. Irritability may be the only presenting sign of Hib meningitis in these young children, and meningismus may be difficult to demonstrate.

Factors suggestive of Hib meningitis

Some elements of the history are helpful in establishing the possibility that a patient with possible meningitis has Hib meningitis. These risk factors are pertinent to children older than 2 months and younger than 5 years.

Time of year is a factor. Presentation between June and November is suggestive of Hib meningitis (in the temperate or sub-Arctic latitudes of the Northern hemisphere).

Vaccination status—both group and individual—is important. With a child who is a member of an unvaccinated population, the likelihood of meningitis being caused by Hib is as high as 95%. A child presenting with meningitis who has not been vaccinated against Hib has a considerably greater chance for Hib diagnosis. Hib remains the most common cause of meningitis in unvaccinated children aged 2 months to 5 years even in a vaccinated population.

Although Hib vaccines have considerably reduced the likelihood that Hib is the cause of meningitis in children in this age group, they have not eliminated Hib meningitis in this naturally susceptible population, especially those children with compromised immune function. Remember that Hib-immunized children may develop Haemophilus meningitis because of unrecognized immunodeficiency or vaccine failure or because they are infected with an untypable or non-B Haemophilus strain.

A history of a presumed viral upper respiratory illness or otitis media preceding the onset with an intervening period of improvement or recovery is fairly characteristic of Hib meningitis. From 60–80% of children who develop Hib meningitis have had otitis media or an upper respiratory illness (presumably viral) immediately before the onset of meningitis; others develop Hib meningitis after a presumably viral gastrointestinal (GI) illness. A meningitic presentation in the wake of epiglottitis may be particularly suggestive of Hib etiology, although this presentation is uncommon.

Conditions that predispose individuals to Hib meningitis include the following:

• Abnormalities of immunoglobulin (Ig) production or function(eg, agammaglobulinemia, IgG2 subclass deficiency)

• Sickle cell disease or other causes of actual or functional splenectomy

• Nephrosis and other forms of chronic renal disease

• Cystic fibrosis and other forms of chronic pulmonary disease

• Malignancy requiring chemotherapy or radiotherapy

• Other diseases requiring the use of immunosuppressive agents

• HIV infection: Cranial defects associated with abnormal communications of the external environment with the subarachnoid space (Go to HIV-1 Associated CNS Conditions – Meningitis for complete information on this topic.)

Although meningitis in a child older than 5 years is much more likely to be due to meningococcus or pneumococcus than to Hib, some cases of Hib meningitis occur in older children and adolescents, particularly those with the above conditions. Hib meningitis does occur in adults, albeit rarely. Predisposing conditions for Hib meningitis infection in adults are the same as those in children and adolescents. It is unclear whether diabetes mellitus or alcoholism, which may also predispose to Hib meningitis in adults, predisposes adolescents to Hib meningitis as well.

The patient’s race should be considered. The risk for Hib is greater in blacks than in whites and greater in Native Americans than in blacks. (See Epidemiology.)

Fulminant meningitis

Occasionally, children present with the report of fulminant deterioration in mental status, with or without seizures, sometimes after cardiopulmonary arrest. In fulminant cases, medical attention is often sought because of medical emergencies such as coma or status epilepticus.

Infants younger than 2 months very seldom develop Hib meningitis, justifying in part the current vaccination schedule for children. In the rare instances when these very young infants do develop Hib meningitis, their manifestations tend to be fulminant, even if no contemporary evidence exists for an epidemic due to a particularly virulent Hib strain.

Presentations in these cases suggest sepsis because the infants tend to be moribund with high fever. Meningismus may or may not be found. Pneumonia with pneumatocele formation, pericarditis, or osteomyelitis may further complicate the diagnosis and management of these severely ill infants.

Findings on general physical examination of children with Hib meningitis are helpful in arriving at the diagnosis, although they may be subtle or equivocal.

General findings

Temperature higher than 38.5°C is found in at least 94% of individuals with meningitis. The temperature tends to be higher in bacterial meningitis than in viral. Studies wherein most cases of childhood meningitis were due to Hib have shown that approximately 80% of children with meningitis have temperatures higher than 38.8°C on presentation, compared with 40% of children with viral meningitis. The fever may exert protective effects, reducing bacterial replication; hence, aggressive treatment of fever may be counterproductive.

The combination of fever with either change in behavior/mental status or new seizures compels consideration of meningitis in children, especially those younger than 1 year.

Occasionally, children with Hib meningitis are hypothermic. These patients tend to be severely ill at presentation, and the hypothermia portends a worse prognosis. In part, the poorer outcome may be due to enhanced bacterial replication at lower temperatures.

The combination of anorexia or vomiting with fever may cause an infant to appear dehydrated (ie, dry oral mucous membranes, diminishment of the usual glabrous appearance of the skin, altered skin texture to finger stroke). These findings are especially important indicators of meningitis in patients without associated diarrhea.

Skin color may be abnormal; the skin may appear pale, cyanotic, ashen, or pasty. These skin-color changes and associated dehydration are statistically significant indicators of meningitis in children younger than 2 years with fever and no clear alternative diagnosis.

In more severe cases, the infant or child may appear cachectic, with loss of skin turgor or capillary refill. Very ill children may have tachycardia and thready pulse in addition to high fever.

Changes in mental status have been shown to be important indicators of enhanced risk for serious infectious illnesses (ie, meningitis, sepsis, pneumonia, urinary tract infection) in children younger than 2 years. Most children with meningitis show changes in mental status, and at least 40% of patients exhibit other neurologic deficits at or shortly after presentation. Special care must be taken to exclude meningitis in such cases because it is has the greatest potential to produce devastating consequences if it is not recognized and treated swiftly.

An altered level of consciousness ranging from drowsiness to stupor or coma is common. This can have an effect on cry. In young children, consciousness may be assessed with reference to their reaction to parent stimulation/smile/holding or their reaction to brightly colored interesting toys, presentation of their bottle, or an approach from the examiner. The eyes may appear glazed over. Marked changes in their reaction, to which parents can attest, are statistically significant indicators of serious infectious disease in children younger than 2 years.

Irritability is common in meningitis and is often associated with loss of interest in surroundings or various forms of visual or auditory stimulation. Photophobia may also be found.

The combination of abnormalities in cry, skin color, hydration, and mental status as measured by response to parental or social stimulation has 88% specificity and 77% sensitivity for the diagnosis of meningitis in small children. If a suggestive history and examination findings are also found, the sensitivity rises to 92%.

Signs suggestive of meningeal pathology

Meningeal signs that may be found in children include nuchal rigidity to passive flexion and the signs of Kernig or Brudzinski. Sometimes the presence of these signs may be difficult to judge in irritable infants. Although resistance to passive neck flexion is found in most cases of childhood meningitis at presentation, Kernig and Brudzinski signs are found in approximately half.

In order to test for Kernig sign, the hip of a recumbent patient is passively flexed to 90 degrees, permitting the knee to be fully flexed. The attempt is then made to passively extend the knee joint. If significant pain or involuntary resistance to the knee extension is encountered, the Kernig sign is present.

Three Brudzinski signs exist: the nape of the neck sign, the identical contralateral hip sign, and the reciprocal contralateral hip sign. All are elicited in the recumbent patient.

The nape of the neck sign is elicited by passive neck flexion, and a positive result is indicated if the hips and knees flex in response. The identical contralateral hip sign is elicited by passive flexion of the hip and knee on one side, and a positive result is indicated if the other leg responds by assuming flexion of the hip and knee. The reciprocal contralateral sign is found if a patient who has manifested an identical contralateral hip sign immediately follows it by a small kick due to sudden partial extension at the knee.

Meningeal signs are found in 77-98% of children older than 12 months presenting with meningitis, in as many as 98% of those aged 12-18 months, and in nearly all of those older than 18 months when properly examined by an experienced individual. Kernig and Brudzinski signs may be difficult to judge in irritable infants.

Meningismus may be universal in fulminant cases or once a child has entered a moderate-to-severe stage of illness. The absence of meningismus does not exclude the diagnosis of meningitis, however, especially in children younger than 8 months. Absence of meningismus at the onset of meningitis is reported in rare instances in children who are older than 2 years. In all such cases of bacterial meningitis, other indicators are present, such as fever, mental status changes, seizures, or elevation of the circulating white blood cell count to greater than 10,000/µL.

Signs of elevated intracranial pressure

Evidence for elevation of intracranial pressure (ICP) must be sought on physical examination, both because it supports the diagnosis of meningitis in febrile infants or children and because it raises important questions about the advisability of performing lumbar puncture.

Signs of increased ICP are especially likely to be found in children with a fulminant history and those who are moribund on presentation. In addition to meningismus and diminished mental status, these patients may have dilated and poorly reactive pupils, as well as loss of lateral eye movements or abnormal convergence of gaze. Reflexes may be increased in the lower extremities, and clonus may be present. The Cushing reflex (hypertension with bradycardia) may be detected. Papilledema may be found.

Unilateral pupillary dilatation, a unilateral field cut, or unilateral loss of lateral eye movement suggests the possibility of a lateralized mass lesion such as empyema or brain abscess and may contraindicate lumbar puncture, at least until a diagnostic scan is obtained.

Generally, papilledema is not found in the early stages of meningitis. Therefore, absence of papilledema cannot exclude the possibility of elevated ICP. Moreover, correct interpretation of funduscopic findings in infants or even young children who present acutely with fever and serious illness exceeds the competence of most physicians.

Detection of papilledema at presentation with mental status changes after a brief course of illness is more suggestive of brain abscess or some other focal process, especially if unilateral papilledema, lateral gaze palsy, or other focal signs are found.

Acute complications of Hib meningitis are as follows:

• Persistent fever

• Recurrence of fever after an afebrile interval (termed secondary fevers)

• Increased ICP

• Prolonged obtundation or coma

• Development of focal neurologic signs

• Development or recurrence of seizures

Repeat blood cultures or lumbar puncture or other testing may be indicated in patients who develop these complications. However, lumbar puncture may sometimes be contraindicated or must be deferred until after brain imaging is performed.

Prolonged primary fevers are found in about 10-15% of all Hib meningitis cases and necessitate reconsideration of the antibiotic regimen. Additional considerations include the exclusion of pneumonia, urinary tract infection, intravenous line sepsis, or the development of subdural effusions or empyema. ^[21] The differential diagnosis should also be revisited; for example, the patient may have a brain abscess rather than meningitis.

Subdural effusions may develop in as many as half of all cases of Hib meningitis, but few are clinically significant. They are the putative cause of approximately 25% of all instances of prolonged primary fevers after initiation of appropriate antibiotic therapy in Hib meningitis. Along with nosocomial infections (eg, intravenous line infections), infected subdural effusions are the most commonly identified causes for secondary fevers.

Prolonged coma or progressive deterioration in function raises the possibility of increased ICP. The presence of bulging fontanelle, papilledema, sunsetting or convergence of the eyes, pupillary dilatation, Cushing reflex, or other brainstem signs of herniation suggests potential elevation of ICP, which may be due to brain edema or hydrocephalus.

Brain edema may develop because of hypoxia, ischemia, hypoglycemia, prolonged seizures, inflammatory vasculitis, or other derangements of brain during the initial or subsequent stages of fulminant Hib meningitis. It may also result from brain infarction or from the development of either communicating or noncommunicating hydrocephalus. Management of brain edema entails careful attention to metabolic parameters and avoidance of excessive hypotonic fluids. On the other hand, sufficient fluids must be provided to maintain cerebral perfusion.

Management of this combination of cytotoxic and vasogenic edema by hyperventilation and administration of mannitol is a complex subject, the review of which falls beyond the scope of this article. Suffice it to say that generalizations accepted several years ago concerning the potential efficacy of hyperventilation to achieve carbon dioxide concentrations in the range of 25-30 mm Hg are no longer widely accepted and that evidence suggests such manipulations may be deleterious. Mannitol, in some instances, may prove useful if used over a short term.

Hydrocephalus of either the communicating or the noncommunicating variety responds to interventions much more reliably than brain edema does. Urgent consultation with a neurosurgeon is indicated for the alleviation of pressure. If communicating hydrocephalus develops in Hib meningitis, it is probably because inflammatory exudate across the vertices impaired the resorptive function of arachnoid granulations. Noncommunicating hydrocephalus usually develops because of exudative blockage of the foramina of Magendie and Luschka.

Focal deficits or seizures can be the result of focal processes that should be identified by computed tomography (CT) of the brain. Brain edema or hydrocephalus may produce focal brainstem signs through compression or herniation. Subdural effusions or empyemas may grow large enough to compress the cortex and produce hemiparesis. Other processes that may be identified include cerebral infarctions, cerebritis, or brain abscess. Generally speaking, magnetic resonance imaging (MRI) is far superior to CT scanning in identifying these processes.