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Pathogenesis and aetiology History and examination Investigations Management Case studies

The author

Background

Meningitis in children
which may also occur in conjunction with inflammation of the meninges (meningo-encephalitis) or spinal cord (encephalomyelitis). Bacterial meningitis is a medical emergency that requires prompt assessment and treatment. The possibility of encountering a child with meningitis is a source of great anxiety for both parents and doctors. To add to this anxiety, children with meningitis may present in a non-specific manner, and distinguishing a child with meningitis from those with other less serious infections can be very difficult. However, the consequences of overlooking a treatable and potentially lethal condition may be devastating. Up to 58% of children with meningitis have received prior antibiotics, which can modify the clinical presentation and make reaching the
contd page 31

DR MIKE STARR, paediatrician, infectious diseases physician, consultant in emergency medicine, and director of paediatric physician training, Royal Childrens Hospital, Parkville, Victoria.

Clarification
The How to Treat article, Cervical Cancer Screening (July 28th), stated that only women who have been treated for a high-grade lesion within the past two years would be eligible for a Medicare benefit for HPV testing. However, women who are already undergoing annual cytological review for the follow-up of a previously treated HSIL are also eligible.

MENINGITIS is inflammation of the meninges that surround the brain and spinal cord. During meningitis, inflammatory cells spill into the cerebrospinal fluid (CSF) from the meninges and increase the cell count. Encephalitis refers to inflammation affecting the brain parenchyma,

Home improvement
OMR104 CVATE

Studies suggest that self-measured blood pressure levels correlate more closely than in-clinic readings with target-organ damage. Furthermore, the National Heart Foundation believes that patient self-measured blood pressure levels can help give you a more complete, accurate picture of the patients blood pressure, and help

you make more informed therapeutic decisions helping to reduce the risk of cardiovascular events. So when it comes to improving cardiovascular health, it appears theres no place like home.

http://www.heartfoundation.com.au/downloads/SelfMeasurement_BP_HP.pdf

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29

from page 29

correct diagnosis more difficult. It is therefore important to consider the possibility of meningitis in any sick infant or child, particularly if they are already taking antibiotics.

Epidemiology
The annual incidence of bacterial meningitis is 30-50 cases per 100,000 children aged under five years. Rates are highest in infants, Indigenous populations, and during late winter and spring. Viral meningitis is more common in older children and occurs more often in summer and autumn.

Pathogenesis
Meningitis usually follows invasion of the bloodstream by organisms that have colonised mucosal surfaces. In the neonatal period, pathogens are mainly acquired by contact with, and aspiration of, intestinal and genital tract secretions from the mother during birth. Neonates can also be exposed to multiple nosocomial pathogens in neonatal units. In infants and children, meningitis usually develops when encapsulated bacteria that have colonised the nasopharynx are disseminated in the blood. Although viral infections of the upper respiratory tract commonly precede meningitis, invasion is a rare occurrence, given the frequency of viral respiratory infections in children. Factors that may increase this chance include exposure to some bacteria that have virulence factors that promote penetration of the respiratory epithelium, compromise of host defences, (eg, reduced ciliary function or reduced mucosal IgA) and certain environmental factors (particularly exposure to cigarette smoke). Organisms may then penetrate vulnerable sites of the blood-brain barrier (eg, the choroid plexus and cerebral capillaries) and reach the subarachnoid space. Inflammatory mediators, produced in response to the presence of bacteria, are believed to enhance the permeability of the blood-brain barrier and facilitate bacterial invasion of the CSF. Meningitis can also develop by direct extension of infection from a paranasal sinus or from the middle ear through the mastoid to the meninges. Severe head trauma with skull fracture, CSF rhinorrhoea, or both, can lead to meningitis, which is usually caused by Streptococcus pneumoniae. Bacteria can be directly inoculated into the CSF by congenital dural defects (dermal sinus or meningomyelocele), neurosurgical procedures (such as CSF diversion shunts), penetrat-

Pneumococcal meningitis.

Serotypes responsible for invasive pneumococcal disease in children aged <5 year, Australia, 2003
Communicable Diseases Intelligence 2004; 28:455-64. Cumulative percentage
250

Number of isolates

200
69.3 75.7

79.9 62.5 49.2

84%

150 100
34.6

50 0 14 6B 19F 18C 4 23F 9V Nonvaccine

90 80 70 60 50 40 30 20 10 0

Serotype

Penicillin-resistant S pneumoniae, bloodstream isolates

Communicable Diseases Intelligence 2003; 27 Suppl:S61-S66.

80 70

Mean inhibitory concentration > 1mg/L* Mean inhibitory concentration 0.125-1mg/L*

60 50 40 30 20 10 0 Australia 1998-2001 (324)

Japan (15)

Taiwan (0)

China (1)

Hong Kong (21)

Philippines Singapore (7) (17)

South Africa (20)

Country (number of isolates)

*Susceptible 0.06mg/L; intermediate susceptibility 0.1-1mg/L; resistant 2mg/L.

ing wounds or extension from a suppurative parameningeal focus.

the result of a localised or systemic insult, but is most commonly caused by viruses or fungi.
Bacteria

Aetiology
Meningitis is usually broadly classified as bacterial or aseptic. Bacterial meningitis is still a major cause of death and disability in children. Aseptic meningitis may be The bacterial causes of meningitis vary with the age of the child. In infants less than 23 months old, organisms acquired from the

maternal genital tract predominate: group B streptococci, Escherichia coli and Listeria monocytogenes. In older children and adults the most common causes are Neisseria meningitidis (meningococci) and S pneumoniae (pneumococci). Other causes, including Staphylococcus species and Gram-negative bacilli, are occasionally seen in immunocompromised patients or after trauma or neurosurgery. Haemophilus influenzae type b (Hib) rarely causes meningitis now because of widespread immunisation. Mycobacterium tuberculosis meningitis is rare, other than in children who have spent prolonged periods in regions of high prevalence (eg, South-East Asia, the Pacific and Africa, India, China, Indonesia and Vietnam). Meningococci are divided into serogroups on the basis of antigenic differences in their capsular polysaccharides (A, B, C, D, X, Y, Z, W-135 and 29-E). Groups B, C, Y and W135 are the predominant serogroups associated with invasive disease in developed countries, whereas the group A strain accounts for epidemic disease in many other countries, especially subSaharan Africa. In Australia, the most common N meningitidis serogroup causing invasive disease in children under 15 is serogroup B (77%), followed by serogroup C (19%). The predominance of serogroup B declines in children aged 15-19 (serogroup B 54%; serogroup C 40%). Although more than 90 serotypes of pneumococci have been identified on the basis of their capsular polysaccharides, only a few are commonly associated with invasive disease and meningitis. The most common pneumococcal serotypes causing invasive disease (14, 6B, 18C, 19F, 4, 23F and 9V) are contained in the sevenvalent conjugate pneumococcal vaccine, which is now a component of the immunisation schedule in Australia. In the US, where use of conjugate pneumococcal vaccine has been routine since 2000, rates of invasive disease have fallen in both vaccinated children and unvaccinated elderly people because of improved herd immunity. It is too early to judge the impact of universal meningococcal and pneumococcal vaccination in Australia. However, the pneumococcal serotypes contained in the conjugate vaccine include a high proportion of those that are resistant to penicillin and, in Victoria at least, it appears that rates of penicillin-resistant pneumococcal meningitis are decreasing.

Most cases of bacterial meningitis arise sporadically; only meningococcal infections can occur in epidemic form. Meningococci are transmitted from person to person by nasopharyngeal secretions from a patient or carrier, and transmission requires close contact. Major epidemics have occurred in South America, Finland, Mongolia and subSaharan Africa, and outbreaks have been noted in students living in dormitories. Age is a major determinant of susceptibility to meningococcal disease. The age-specific incidence of meningococcal disease is highest in young children, although maternal antibodies usually protect infants in the first few months of life. Teenagers and the elderly also have increased risk. Other risk factors include crowding, low socioeconomic status, exposure to tobacco smoke and certain immune defects (eg, complement deficiency).
Viruses

Enteroviruses, including coxsackie and echoviruses, cause 8595% of cases of viral meningitis. Herpes simplex viruses 1 (HSV-1) and 2 (HSV-2) and other herpes viruses (human herpes viruses 6, 7 and 8, varicellazoster virus, cytomegalovirus and Epstein-Barr virus) tend to cause meningo-encephalitis. However, HSV-1 and HSV-2 are possibly the most important causes to consider, as meningo-encephalitis caused by these viruses is associated with high morbidity and mortality, which may be reduced with early treatment. Enterovirus 71 (EV 71) emerged as a significant nervous system pathogen in Asia after outbreaks in Sarawak (1997), Taiwan (1998) and more recently in Perth (1999). EV 71 is related to the coxsackie A16 virus and both can cause hand, foot and mouth disease in young children. In the 1998 outbreak in Taiwan, 78 patients died and another 405 had severe complications, including brainstem encephalitis, poliomyelitis-like paralysis, myocarditis and pulmonary oedema. In Hong Kong, 427 patients were admitted to hospital with hand, foot and mouth disease in 1998, four of whom were identified with meningo-encephalitis secondary to EV 71.
Fungi

Penicillin resistance (%)

Cryptococcus neoformans is the most common fungal cause of meningitis but occurs almost exclusively in immunocompromised patients.

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How to treat meningitis in children History and examination

OBTAINING a careful history about prodromal symptoms, tempo of the illness and accompanying symptoms may provide clues to the aetiology of a childs meningitis. Important points to consider include: Maternal obstetric history were swabs taken for group B streptococci? Was the labour prolonged or complicated in some other way? Were intrapartum antibiotics given? Perinatal complications was the baby unwell at birth or shortly afterwards? Immunisation status. Infectious contacts. Recent use of antibiotics. sign in this age group. The clinical presentation of meningitis is often non-specific in infants and young children. Manifestations may merely include fever, irritability, lethargy and poor feeding. If the fontanelle is still open, it may bulge in an infant with meningitis, but this may occur as a result of any cause of raised intracranial pressure. The fontanelle must be palpated with the infant sitting upright quietly; if the infant is lying prone and/or crying when examined, the fontanelle may falsely appear to bulge. Photophobia is difficult to ascertain in young children, and other signs of meningeal irritation may be absent or difficult to elicit. In adults with meningitis, Kernigs sign (inability to extend the knee when the leg is flexed at the hip), Brudzinski sign (bending the head forward produces flexion movements of the legs) and nuchal rigidity have been shown to have low positive and negative predictive value; in children these signs are often not present at all. threshold for referral to an emergency department for a lumbar puncture should be lowered. This is one of the reasons why antibiotics should be avoided in children unless there is clear evidence of a bacterial infection.
Rash

Meningococcal sepsis with extensive purpuric lesions of the arm.

Partially treated meningitis

Clinical findings
The classic clinical features of meningitis include: Headache. Vomiting. Neck stiffness. Photophobia. Altered conscious state. However, young children may not (or may not be able to) complain of headache or photophobia, and neck stiffness is not a reliable

Children who have recently been treated with oral antibiotics may present in an even more insidious fashion with subtle clinical findings. It is not uncommon in clinical practice to be faced with a child who is already receiving an oral penicillin or cephalosporin for otitis media or an RTI, and who presents with fever and irritability. Although these symptoms may be attributable to the underlying infection, it is often impossible to reliably exclude meningitis on clinical grounds. In this situation the

Rash may occur with any bacterial meningitis but is less common with pneumococcal infection. Although petechiae or purpura are suggestive of meningococcal sepsis, they occur more often in children with viral meningitis (eg, enteroviral meningitis). Meningococcal infection may also present with other rashes, including blanching maculopapular spots, but up to half of cases may present with no rash. Unfortunately, the type of rash does not predict the severity of the disease, although a rapidly evolving petechial or purpuric rash is a sign of very poor prognosis. It is impossible to reliably differentiate between bacterial and viral meningitis on clinical grounds. However, features that are more suggestive of (entero)viral meningitis include:

Presentation in summer or autumn, particularly in clusters. Gradual onset of non-specific constitutional symptoms including diarrhoea, cough and myalgia. Low-grade fever. It is very difficult to predict which of the innumerable children seen in general practice with probable viral RTIs will be the one with meningitis. However, it is essential to do so, because a short period between onset of disease and admission has been shown to improve outcome. Looking for features that suggest that the child has more than just an RTI is very important. These may include: Drowsiness on history or examination. Decreased activity. Pallor on history or examination. Breathing difficulty or chest wall recession. Temperature >38C or <36.4C. Feeding less than 50% of the normal amount for the infant. More than five vomits in the previous 24 hours. Fewer than four wet nappies in the previous 24 hours.

Investigations
DEFINITIVE diagnosis of meningitis relies on biochemical analysis, microscopy and culture of the CSF. Children with suspected meningitis should have a lumbar puncture performed, unless there is a contraindication. The only absolute contraindication is raised intracranial pressure. It may be difficult to determine whether intracranial pressure is raised, but the following signs may be indicative: Coma (absent or non-purposeful response to painful stimulus). Abnormal pupillary responses. Abnormal posturing. Focal neurological signs or seizures. Recent (within 30 minutes), prolonged (>30 minutes) or tonic seizures. Papilloedema although this is an unreliable and late sign. Lumbar puncture may need to be delayed if there is cardiovascular compromise or shock, respiratory compromise, coagulopathy or thrombocytopenia. The following are not contraindications to performing a lumbar puncture: Drowsiness or irritability. Vomiting. Bulging fontanelle in the absence of other signs of raised intracranial pressure. Seizures, per se. Suspected meningococcal disease. Cerebral CT should not be used to decide if it is safe to proceed with lumbar puncture in patients suspected of having meningitis, and

Serotypes of pneumococcal isolates with reduced susceptibility to penicillin in children aged <5 years, Australia, 2003 (n=71)
Communicable Diseases Intelligence 2004; 28:45564. Serotype No of isolates 19F 19 9V 16 14 16 6B 8 23F 1 19A 6 6A 4 33F 1 Total 71

(Mauve = serotypes in vaccine)

Table 1: Typical CSF profiles in normal children and those with meningitis
White cell count Neutrophils (10 cells/L) Normal (age >1 month) Normal term neonate Bacterial meningitis Viral meningitis 0 0
6

Biochemistry Protein (g/L) <0.4 <1.0 0.4-1.0 Glucose (CSF:blood ratio) 0.6 (or 2.5mmol/L) 0.6 (or 2.1mmol/L) Usually normal

Lymphocytes (10 cells/L)

5 10
6

Meningococcal sepsis with extensive purpuric lesions of the hand.

should certainly not delay ongoing management: raised intracranial pressure cannot be excluded with CT. In a prospective study of children with bacterial meningitis, CT findings obtained during the acute stages of meningitis failed to reveal any significant abnormalities that were not suspected on neuro1 logical examination. Moreover, cerebral herniation can occur with a normal CT. CT scans should be reserved for children with focal neurological signs, focal seizures or signs of raised intracranial pressure.

Examination of the CSF

Normal CSF is clear and contains few cells (and no neu6 trophils). As few as 200 10

cells/L will cause CSF to appear turbid. The CSF profile may help differentiate between bacterial and viral meningitis, but findings vary. The white blood cell differential may be misleading early in the course of meningitis: more than 10% of patients with bacterial infection will have an initial lymphocytic predominance, while the pattern in patients with viral meningitis may initially be dominated by neutrophils. Culture is the gold standard for determining the causative organism in meningitis. However, PCR is much faster and more sensitive in some circumstances (see later). Table 1 indicates the typical CSF profiles in normal

children and those with meningitis. However, results should always be interpreted in the context of the clinical picture. For example, in early bacterial meningitis the CSF cell count may be normal, while in enteroviral meningitis there is typically an early neutrophil predominance that may remain for more than 24 hours. Organisms are seen on CSF Gram stain in 6080% of cases of meningitis, provided that prior antibiotics have not been given. The sensitivity is highest in patients with pneumococcal meningitis. Prior antibiotics may preclude culture of the causative organism, but the biochemistry and white cell count remain abnormal for several days after treatment has begun. A traumatic tap occurs in 15-20% of lumbar punctures in children. Several formulae have been devised for interpreting CSF contaminated with blood, but the safest practice if meningitis is suspected is to disregard the red cell count and begin treatment for meningitis. If the clinical course is not as expected, another diagnosis such as cerebral haemorrhage should be suspected. A repeat lumbar puncture showing a persistently high red cell count would be suggestive and require further investigation with cerebral CT. Seizures do not cause an increased CSF cell count in the absence of meningitis. Bacterial or viral DNA can be detected in blood and/or CSF using PCR analysis. Sensitivity and

specificity are high, particularly for N meningitidis, HSV and enterovirus. PCR for N meningitidis is particularly useful in patients with a clinical picture consistent with meningococcal meningitis but who have already received antibiotics. Latex agglutination allows rapid detection of bacterial antigens in CSF and urine but lacks sensitivity and specificity, other than for Hib, and is therefore rarely used.

Other investigations
Other investigations include: Culture of blood, throat swab or swab of skin lesions may yield a causative organism if lumbar puncture cannot be performed (or will be delayed until after antibiotics are given). Knowledge of the causative organism and its antibiotic susceptibility may alter the choice and duration of antibiotics. Gram stain on blood smear may be positive. Blood glucose should be measured at the same time as CSF glucose (see DEFG page 33). Baseline serum sodium should be measured. Hyponatraemia occurs in about one-third of children with meningitis and may be due to increased antidiuretic hormone secretion, increased urine sodium losses, or excessive electrolyte-free water intake or administration. FBC and acute-phase reactants (eg, C-reactive protein) may provide supportive information. Enterovirus may be isolated from throat swab or stool.

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| Australian Doctor | 15 September 2006

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Management
Initial management
ABC

CHECK airway, breathing and circulation and manage appropriately. Children with clinical signs of shock or hypovolaemia should be given 0.9% (normal) saline at 20mL/kg.
DEFG (dont ever forget glucose)

This is particularly true for a child who is fitting with (or without) fever. The child may have meningitis, but fitting may also be secondary to hypoglycaemia associated with serious illness and reduced glucose intake. Check the blood sugar level and treat if low.
Antibiotics

Typical raised purpuric lesion of meningococcal disease.

After initial fluid resuscitation, the emphasis is on starting parenteral antibiotics promptly (see table page 34). Delay in antibiotic therapy has been associated with adverse clinical outcome in adults with bacterial meningitis. Age <2 months. Benzylpenicillin plus cefotaxime is the treatment of choice. Because of the morbidity associated with neonatal Gram-negative meningitis, and the high rates of recrudescence, many neonatologists also add gentamicin. Age >2 months. Use cefotaxime alone. Note that vancomycin is added in many centres for suspected pneumococcal meningitis; however, rates of resistance to penicillin and cephalosporin among pneumococci appear to be decreasing in Australia since the introduction of conjugate pneumococcal vaccine into the routine schedule, and this may not be necessary. Infant with severe meningococcal sepsis in the ICU. Duration of antibiotic treatment. The duration of antibiotic therapy depends on the organism isolated. For S pneumoniae and H influenzae, 10-14 days treatment is generally recommended, while for N meningitidis a seven-day course is generally recommended. Even shorter courses have been successfully used in New Zealand. In L monocytogenes and group B streptococcal meningitis, antibiotics should be given for 14-21 days. For Gram-negative bacilli a minimum of three weeks is needed.
Steroids

Child with suspected meningitis awaiting lumbar puncture, with topical anaesthetic applied to the lumbar region.

Neurological damage in patients with meningitis is caused by intense inflammation secondary to activation of inflammatory pathways by the bacteria or bacterial products.

After entry into the CSF, the bacteria replicate rapidly and liberate active cell-wall or membrane-associated components. Antibiotics that act on cell walls (eg, cephalosporins and penicillins) cause rapid lysis of bacteria, which can initially cause enhanced release of these active bacterial products into the CSF. If steroids are given before antibiotics, this process may be diminished, but routine administration of steroids as adjunctive therapy has been controversial. The evidence that steroids protect against neurological (particularly audiological) complications of childhood meningitis is strongest in cases of Hib meningitis, if dexamethasone is given before the first dose of antibiotics, and when a third-generation cephalosporin such as ceftriaxone is used.

A recent large European trial in adults with meningitis showed a reduction in mortality and severe morbidity with pneumococcal meningitis when subjects were treated with adjunctive steroids either with, or 1520 minutes before, the first dose of antibiotic, then every 2 six hours for four days. A recent Cochrane metaanalysis including adult and paediatric trials concluded that adjuvant steroids are beneficial for children with 3 bacterial meningitis. However, evidence from animal studies shows that dexamethasone reduces penetration of vancomycin into infected CSF. Thus there is concern that use of dexamethasone with vancomycin could compromise the efficacy of vancomycin in thirdgeneration cephalosporinresistant strains. Fortunately, most cases of pneumococcal meningitis are still caused by strains that are susceptible to penicillin and third-generation cephalosporins. Accordingly, children older than four weeks who are being treated for possible meningitis (but who have not yet received parenteral antibiotics, or who have received their first dose less than one hour previously) should be given IV dexamethasone 0.15mg/kg six-hourly. Steroids should preferably be given 15-30 minutes before antibiotics, although antibiotic administration should not be delayed for more than 30 minutes. If a GP sees a child with suspected meningitis in the surgery or on a home visit, the decision about whether to administer antibiotics will depend on the distance from the nearest emergency department. If there is any doubt about how quickly the child will be investigated and treated, IM or IV antibiotics should be given immediately. If a thirdgeneration cephalosporin is available, this would be the preferred choice, although early administration of penicillin has been shown to reduce mortality. The only absolute contraindication is known severe penicillin anaphylaxis. When a history of brief rashes or illness (not requiring treatment) after administration of penicillin is reported, the benefit from administration of penicillin will outweigh any side effects and administration should be continued. The administration of steroids can be delayed in this instance.

important in treating meningitis. Over- or under-hydration is associated with adverse outcomes. Many children with meningitis have increased antidiuretic hormone secretion, and some will have dehydration due to vomiting, poor fluid intake or septic shock. Initial fluid resuscitation to treat shock should be given as required with isotonic saline. Thereafter, isotonic fluids should be given to maintain systemic blood pressure (and thereby cerebral blood flow). The optimal ongoing fluid requirement for children with meningitis is not clearly established. Previous guidelines have suggested the importance of fluid restriction but more recent studies have questioned this approach. Assessment of the clinical signs of hydration, including weight, measurement of serum sodium, documentation of urine output and clinical assessment of the neurological state should be monitored closely, and the total fluid intake adjusted accordingly. Although it may be necessary to restrict fluids if the serum sodium concentration is <130mmol/L or if there are signs of fluid overload, fluid restriction does not generally improve outcome and has even been associated with worse neurological outcomes. Treatment of viral meningitis is generally symptomatic, but meningitis caused by HSV and other herpes group viruses is usually treated with high-dose aciclovir. In immunocompromised children, IV immunoglobulin may also be considered.
Notification

incidence of bacterial meningitis.

Chemoprophylaxis

Contacts of patients with meningococcal meningitis may require chemoprophylaxis to prevent secondary spread. Those who should receive chemoprophylaxis include: The index case if treated only with penicillin (does not eradicate carriage). All intimate, household or day-care contacts who have been exposed to the index case within 10 days of onset of symptoms. Any person who had mouth-to-mouth resuscitation or direct airway secretion contact with the index case. One of the following antibiotics should be prescribed for chemoprophylaxis: Rifampicin 10mg/kg (5mg/kg in babies less than one month old) orally 12hourly (maximum 600mg) for two days, or Ceftriaxone 125mg (children 12 years old) or 250mg (>12 years) IM as a single dose, or Ciprofloxacin 500mg orally as a single dose. Rifampicin and ciprofloxacin should not be used in pregnant women.

Complications
Bacterial meningitis is associated with an overall 4.5% mortality rate; this may be as low as 2% in infants and children and as high as 2030% in neonates. Mortality is generally higher for pneumococcal meningitis. Morbidity, including intellectual, cognitive and auditory impairments, occurs in 10-20% of survivors. The risk for sequelae is greatest in those who experience acute neurological complications at the time of their illness. Use of antibiotics has had a profound effect on the clinical course and prognosis of meningitis.

All cases of presumed or confirmed N meningitidis (or Hib) disease should be urgently notified to the appropriate health authority which varies from state to state. Invasive S pneumoniae infections must also be notified, although only written notification within five days of diagnosis is required.

Pitfalls
Partially treated meningitis

Prevention
Immunisation

Ongoing management
Fluids

Careful management of fluid and electrolyte balance is

With the introduction of effective conjugated vaccines against Hib, the incidence of bacterial meningitis caused by this pathogen has declined by more than 99% in countries such as Australia that have adopted universal immunisation. Conjugate serogroup C meningococcal vaccine and conjugate seven-valent pneumococcal vaccine are now also part of the routine schedule for all children and should further reduce the

As mentioned previously, the child who has recently been treated with oral antibiotics may present in a more insidious fashion, resulting in subtle clinical findings. The threshold for a CSF examination may need to be varied accordingly, particularly in the younger child or if the possibility of partially treated meningitis exists.
Apparent improvement with paracetamol

Clinical improvement with reduction of fever may occur in children with serious bacterial infection. However, this is less likely in children with bacterial meningitis.

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How to treat meningitis in children Authors case studies

Clinical signs of meningitis in a fully vaccinated infant
A 13-MONTH-old previously well infant presented to a peripheral hospital with a 24-hour history of fever and lethargy. His immunisations were up to date for his age (he had previously had three doses of Hib-containing vaccine, three doses of conjugate pneumococcal vaccine and one dose of conjugate meningococcal vaccine). He was initially admitted for observation but remained drowsy and had two generalised tonic-clonic convulsions the next day. Ceftriaxone and aciclovir were started and he was transferred to the Royal Childrens Hospital. At hospital he was noted to have clinical signs consistent with meningitis. He was haemodynamically stable and there were no signs of raised intracranial pressure. A lumbar puncture was performed and initial CSF analysis revealed: 6 Neutrophils 220 10 cells/L. 6 Lymphocytes 30 10 cells/L. Protein 3g/L. Glucose 2.1mmol/L (serum glucose 4.6mmol/L). Gram stain: no bacteria seen. Antibiotic activity detected.
Management

Drugs used in meningitis

Drug name Aciclovir Brand name Aciclovir, Acihexal, Acyclo-V, Lovir, Zovirax, Zyclir Dosage < 3 months of age: 20mg/kg/dose 8-hourly 2 3 months-12 years: 500mg/m /dose 8-hourly >12 years: 10mg/kg/dose 8-hourly

Management Duration of treatment 3 weeks

Benzylpenicillin

Benpen

50mg/kg/dose (max 3g), IV 4-hourly

7 days for meningococci, 10 days for pneumococci 7 days for meningococci, 10 days for pneumococci Single dose

Cefotaxime

Cefotaxime

50mg/kg (max 2g) IV 6-hourly

Ceftriaxone

Ceftriaxone, Rocephin

100mg/kg (max 2g) IV daily For prophylaxis: 125mg (<12 years) 250mg (>12 years) IM 500mg orally

Ciprofloxacin

C-Flox, Ciprol, Ciproxin, Ciprofloxacin, Profloxin, Proquin Dexamethasone Gentamicin, Septopal

Single dose

Dexamethasone Gentamicin

0.15mg/kg IV 6-hourly Up to 10 years: 7.5mg/kg/dose (max 240mg) IV or IM 24-hourly Over 10 years: 6mg/kg/dose (max 360mg) IV or IM 24 hourly

4 days Adjunctive treatment of Gram-negative meningitis for first 48 hours

This girl sounds as if she has had a simple febrile convulsion secondary to otitis media. If meningitis is not suspected, she does not require any investigations, but a period of observation until she is less drowsy would be sensible. Otitis media does not necessarily require antibiotic treatment. It would be reasonable to give her paracetamol and review her the next day, with instructions to the parents to contact you if she worsens. The parents will need to be educated about febrile convulsions and appropriate management of a potential subsequent convulsion.

Viral meningitis
A 14-year-old girl reports abdominal pain, diarrhoea and headache for three days. Her headache has worsened today and she has developed a painful neck and vomited once. On examination she has a temperature of 37.8C but does not look too unwell. She has neck stiffness and photophobia and a generalised macular rash. She is neurologically normal.
Management

Rifampicin Vancomycin

Rifadin, Rimycin Vancocin, Vancomycin

10mg/kg orally 12-hourly (max 600mg) 15mg/kg (max 500mg) IV 6-hourly

2 days 10 days (for resistant pneumococci)

Practice points

Bacterial meningitis can be rapidly progressive and result in substantial morbidity and mortality. A high index of suspicion of the possibility of meningitis must be maintained in any sick infant or child. Symptoms and signs are frequently non-specific, particularly with younger age, and in children who have already begun treatment with antibiotics. Antibiotic treatment must not be delayed. Steroids may improve outcome if given before the first dose of antibiotic. Careful management of fluid and electrolyte balance is critical. Conjugate meningococcal and pneumococcal vaccines may affect the epidemiology of meningitis in children. Viral meningitis cannot be reliably differentiated on clinical grounds from bacterial meningitis.

It was felt that the cause of the infants meningitis was more likely to be meningococcal than pneumococcal. His three doses of conjugate pneumococcal vaccine should have protected him against the most likely serotypes to cause meningitis, and conjugate meningococcal vaccine should protect him against serogroup C disease, but serogroup B was a more likely cause in this age group. The third-generation cephalosporin was continued and aciclovir and vancomycin added (just in case this was a case of resistant pneumococcal meningitis). The infants presumed meningococcal infection was notified to the Department of Human Services and the family was given rifampicin prophylaxis. As the CSF culture was antibiotic affected, CSF was sent for meningococcal PCR. Pneumococcal PCR (a new test not routinely offered and mainly used in research centres) was also performed. The meningococcal PCR was negative but pneumococcal PCR was positive. This case illustrates several principles: Always treat empirically with antibiotics that will cover the most common causes of meningitis. Although prior antibiotics may sterilise the CSF (so that Gram stain and cul-

This girl probably has enteroviral meningitis. She needs a lumbar puncture to confirm the diagnosis, and a stool sample may be helpful. If the CSF demonstrates pleocytosis, it should be sent for viral culture and enteroviral PCR. Treatment is supportive. She should be told that the headache of viral meningitis may persist for many days. Toddler with early purpuric rash typical of meningococcal infection. ture are negative), meningitis can be confirmed, as pleocytosis (presence of more cells than normal) persists for at least several days. Newer molecular tests may yield the aetiology. Although the infant had been given three doses of conjugate pneumococcal vaccine, there are more than 90 serotypes altogether, and several types can cause invasive disease. Despite routine immunisation with conjugate pneumococcal and meningococcal vaccines, it is important to consider these organisms as potential causes of serious bacterial infection in children. he has felt hot, been off his food and spent the morning lying on the couch. On examination he has an aural temperature of 40C. He looks flushed and miserable but not too sick. He is lying quietly in his mothers arms and is well hydrated. He has red tympanic membranes and pharyngitis but does not have neck stiffness. There are no other clinical findings.
Management

References
with the child if there is any deterioration. It would be preferable to avoid antibiotics unless there is an obvious bacterial focus. If there is any doubt, it would be sensible to send the child to an emergency department (paediatric if possible) for assessment.
1. Cabral D, et al. Prospective study of computed tomography in acute bacterial meningitis. Journal of Pediatrics 1987; 111:201-05. 2. De Gans J, van de Beek D. European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. New England Journal of Medicine 2002; 347:1549-56. 3. van de Beek D, et al. Corticosteroids in acute bacterial meningitis. Cochrane Database of Systematic Reviews 2003; CD004405.

A febrile convulsion in an infant with otitis media

A three-year-old girl is brought in by her mother after a two-minute generalised tonic-clonic convulsion that occurred 15 minutes ago at home. She had woken with a slightly runny nose but was otherwise well and had been playing happily all morning. On examination she was slightly drowsy but oriented and interactive, with a temperature of 38.5C. She had a unilateral red bulging tympanic membrane but no neck stiffness or other neurological abnormalities.

The child who probably only has a viral URTI

A child aged two and a half is brought in to see you by his mother. He has been unwell for three days with coryza and cough and today

It is more difficult to know how to deal with this child than the previous one. He probably has a viral URTI, but his presentation would not be inconsistent with meningitis. The most appropriate management will depend on how sick you feel the child is. If he is not particularly unwell, it would be reasonable to review him later in the day, with clear instructions for the parent to return

Online resources

Royal Childrens Hospital Melbourne. Meningitis guideline: www.rch.org.au/ clinicalguide/cpg.cfm? doc_id=5179 Meningitis Research Foundation: www.meningitis.org

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How to treat meningitis in children GPs contribution

Case study
JASON is a five-month-old child I saw late one evening. His mum was concerned, as he was unwell with a cold and he was her first child. Jason was a little pale, with a respiratory rate of 28 breaths/minute and aural temperature 37.1C. His chest was clear, he had mildly hyperaemic tympanic membranes and his pharynx was normal. His abdomen was soft and both testes had descended. As I could not find a specific cause for his low-grade temperature, I kept him in the surgery while I saw my last two patients. Mum attempted to breastfeed him. He seemed to feed a little and looked better, so I let them go home, warning Mum to ring me if she had any concerns. My diagnosis was a non-specific viral illness. The next morning Jason was brought back to the surgery at 8am. He had been restless through the night unusual for him. His temperature had risen to 37.3C and he seemed a little irritable. He refused to feed through the night. Again when I examined him there was no neck stiffwithout access to immediate lumbar puncture, would it have been preferable to treat Jason with cefotaxime IM injections and dexamethasone IM injections simultaneously? If so, what are the doses? I think it would be very reasonable to treat a five-monthold like this with IM or IV antibiotics in the situation you describe. Ceftriaxone 100mg/kg would be the best choice, although cefotaxime 50mg/kg or penicillin 50mg/kg would be good alternatives. It would be fine to give dexamethasone 0.15mg/kg although I would definitely not delay the antibiotics. What is the role of an urgent CT scan in this case? There is no role for a CT in this situation. CT scans should be reserved for children with focal neurological signs, focal seizures or signs of raised intracranial pressure. meningococcal disease. Myalgia and arthralgia may also be seen with meningococcal disease (and viral meningitis) and might be misinterpreted as bone pain. If there are no definite symptoms and signs of meningitis (headache, vomiting, neck stiffness, photophobia) and if there is no definite source of infection, would you advise lumbar puncture for all children aged under two years with irritability? Alternatively, for children in the grey zone, what are your criteria for lumbar puncture? It is mainly younger infants in the grey zone, as you put it, that really need a lumbar puncture to exclude meningitis. Febrile or sick babies under one month of age must have a lumbar puncture (as well as culture of blood and urine). From 1-3 months of age I would err on the side of caution, although it may be reasonable to do other tests first and await the results of these before proceeding to lumbar puncture. After three months of age the decision about doing a lumbar puncture would depend on how sick the child was.

DR ASHLEY BERRY
Lugarno, NSW

ness or photophobia. In view of his irritability and because there was no definite source of infection, I referred him to accident and emergency. There he immediately underwent lumbar puncture and was found to have viral meningitis, with raised CSF lymphocytes and protein, and reduced glucose level. He was observed in hospital for two days, improved and was subsequently discharged. I saw him six days after his initial presentation and he was back to his normal self.

Meningitis is not common although its quite possible that a small number of children we presume to have nonspecific viral illnesses may have viral meningitis. Given Jason had already had his first two immunisations, how likely was this to be bacterial rather than viral? The first two lots of immunisations provide some protection (not complete) against Hib and seven pneumococcal serotypes (as well as hepatitis B, DTP and polio). And of course, viral infections are much more common than bacterial infections. All in all, this was more likely to be a viral illness. If I was in an isolated town

General questions for the author

Ive heard that severe bone pain may be an indicator of meningitis in older children. Is this your experience? Ankle pain is certainly often seen in adolescents with

Questions for the author

As a GP of 25 years, this was my first case of meningitis. How common is this in a general practice setting?

How To Treat Quiz

Meningitis in children 15 September 2006
1. Which TWO statements about meningitis are correct? a) Distinguishing a child with meningitis from one with a less serious infection is usually easy b) Children with meningitis have often received prior antibiotics c) Rates of bacterial meningitis are highest in infants, Indigenous populations and during late winter and spring d) Meningitis related to skull fracture is usually caused by Neisseria meningitidis 2. Crystal attends with her three-week-old son, Kyle. He has been feeding poorly for one day. Which THREE questions about Crystals labour may be significant in Kyles illness? a) Were swabs taken for group B streptococci? b) Did Crystal have an epidural? c) Were intrapartum antibiotics given? d) Was the labour prolonged or complicated? 3. Which TWO signs are you most likely to find in Kyles examination if he has meningitis? a) Neck stiffness b) Fever c) Positive Kernig sign d) Irritability

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c) Marks grandmother, who last cared for Mark three weeks ago d) Marks mother 9. What role do steroids play in the treatment of meningitis (choose TWO)? a) Adjunctive steroids benefit adults with bacterial meningitis, but not children b) If steroids are given, antibiotic administration should not be delayed for more than 30 minutes c) Steroids can be used in children who have received oral antibiotics as long as the first dose was given less than one hour earlier d) Steroids have no role in suspected, but unproven, meningitis 10. Which ONE statement about the epidemiology of meningitis is correct? a) Group A meningococcus is the serotype most likely to cause meningitis in Australia b) The predominance of infection with serogroup B meningococcus declines in children aged 15-19 years c) Most cases of bacterial meningitis occur in epidemics d) Meningococci are transmitted by the faecal-oral route

a) Marks presentation in winter b) Petechial rash c) Low-grade fever d) Systolic murmur

4. Which TWO actions are most important to take if you suspect meningitis and Kyle has not had any prior antibiotics? a) Start antibiotics b) Refer for urgent lumbar puncture c) Order brain CT d) Order a white cell count to exclude infection 5. Paul attends with his three-year-old son, Mark. He has been lethargic and irritable for two days and has had diarrhoea once. Which ONE factor in Marks history is LEAST important in establishing the diagnosis? a) Infectious contacts b) Hearing loss c) Recent use of antibiotics d) Immunisation status 6. After examination you are concerned that Mark may have viral meningitis. Which TWO factors or findings would support, but not prove, your diagnosis?

7. You send Mark to hospital. Soon after arrival he deteriorates and has a seizure. After stabilisation an urgent lumbar puncture shows neutrophils and red cells. Which ONE conclusion can you reach? a) Marks meningitis must be bacterial b) The presence of red cells in the CSF should not delay starting treatment for suspected meningitis c) Seizures, not meningitis, may have caused Marks raised neutrophil level d) Hypoglycaemia could not be the cause of his seizure 8. Mark is proven to have meningococcal meningitis. His mother is six months pregnant. Treatment of which of Marks contacts would be appropriate (choose TWO)? a) Any day-care contacts, if they have been exposed to Mark within 10 days of symptom onset b) All staff in the emergency department where Mark was admitted

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HOW TO TREAT Editor: Dr Lynn Buglar

Co-ordinator: Julian McAllan Quiz: Dr Lynn Buglar

The mark required to obtain points is 80%. Please note that some questions have more than one correct answer. Your CPD activity will be updated on your RACGP records every January, April, July and October.

NEXT WEEK Significant changes have occurred in the delivery of palliative care, due to recognition of a wider role for GPs, and a shift from management of largely acute care to largely chronic disease. The next How To Treat presents an update on palliative care in the home. The author is Dr Geoffrey Mitchell, principal research fellow, discipline of general practice, University of Queensland.

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