Bacterial meningitis in children

Bacterial Meningitis in Children: An Overview

Bacterial meningitis represents a significant cause of morbidity and mortality in children worldwide. Meningitis is defined as inflammation of the protective membranes, known as meninges, that surround the brain and spinal cord (Chavez-Bueno et al., 2005). The most common types of bacteria that cause bacterial meningitis in children aged 3 months and older are S. pneumoniae and N. meningitdis, and are responsible for 80% of cases in the United States (Brouwer et al., 2010). Symptoms of bacterial meningitis in children vary between infants and older children: infants typically present with fever, poor feeding, irritability, lethargy, and vomiting, while older children generally present with more clinically characteristic meningeal irritability, vomiting, photophobia, headache, and neck stiffness (Brouwer et al., 2010). Risk factors associated with bacterial meningitis in children include penetrating head injuries, neurosurgical procedures, or incidence of cerebrospinal fluid leaks (Chavez-Bueno et al., 2005). Once the bacteria are present in the bloodstream, the blood-brain barrier is penetrated and the pathogens enter the subarachnoid space, which results in an intense inflammatory response.

Establishing a definitive diagnosis of bacterial meningitis requires a lumbar puncture and subsequent cerebrospinal fluid analysis (Chavez-Bueno et al., 2005). Various antibiotic regimens are available for treatment and recent studies have inquired into the use of corticosteroids in children to reduce hearing loss complications associated with bacterial meningitis (Mongelluzzo et al., 2008). Parents must be educated on the potential risk factors associated with meningitis, as well as such potential outcomes such as hearing loss and learning disability. Lack of treatment and vaccination availability indicate disadvantaged children who do not have access to necessary treatment; mortality levels are 5% in developed nations, while mortality in the developing world is approximately 30% (Best, & Hughes, 2008). Bacterial meningitis poses a critical health threat to children, and it is imperative that parents understand the symptoms of the infection and seek prompt treatment in order to increase a child's likelihood of survival.

Paper Overview

This paper will evaluate current literature to present a medical and educational overview of bacterial meningitis in the youth population. It will discuss such topics as the global presence of bacterial meningitis, symptoms, basic pathophysiology, diagnostic measures, treatment options, relevant education concerning the illness, consider underserved populations and controversial implications.

Prevalence

Bacterial meningitis occurs when a bacterial pathogen infects the dural layers of the central nervous system and results in severe inflammation (Best, & Hughes, 2008). The inflammation of the meninges is a serious condition that claims many lives, and is responsible for high incidence of disability and affects long-term health. The prevalence of bacterial meningitis is greatest in developing nations; every year, bacterial meningitis epidemics impact more than 400 million people in Africa alone (WHO, 2011). Over a 15-year period, from 1996-2011, approximately 800,000 cases were reported in the "African meningitis belt" that extends from Senegal to Ethiopia. In the United States, the prevalence of bacterial meningitis can average 3 cases per 100,000 population, while incidence rates can average 101 cases per 100,000 in Niger (Brouwer et al., 2010). Studies from Brazil, Israel, Canada, Northwest and Southern Europe show similar trends to those studied in the U.S. (Brouwer et al., 2010). Studies conducted by the Centers for Disease Control indicate males are more likely than females to contract bacterial meningitis: 3.3 versus 2.6 cases per 100,000 (Brouwer et al., 2010). The incidence disparity between developing and developed nations illustrates the effectiveness of conjugate vaccines, and how its availability in developed nations has altered the epidemiology of bacterial meningitis.

Signs and Symptoms

Symptomatic manifestations of bacterial meningitis depend on the age of the child. Infants present with more nonspecific signs than older children, such as fever, vomiting, lethargy, irritability, and poor feeding (Brouwer et al., 2010). Older children have greater probability of presenting with common signs of meningeal irritability, such as headache, photophobia, and neck stiffness (Brouwer et al., 2010); however, the common symptoms of neck stiffness and mental status change are less apparent in children than in adults (Chavez-Bueno et al., 2005). Fever is one of the most common presenting symptoms for patients with bacterial meningitis, but is less frequent in infants 1-12 months of age (Best, & Hughes, 2008). Although fever is a common complaint for patients, it is not the defining symptom of bacterial meningitis. Seizure is a greater indicator of bacterial meningitis in children outside of the febrile convulsion age range of 6 months to 6 years (Best, & Hughes, 2008).

Indicators of altered consciousness, ranging from confusion to coma, have also been studied as signs of bacterial meningitis in children. The degree of this symptom varies by the age of the child, as older children are more likely to present with coma than infants (Best, & Hughes, 2008). Other manifestations are considered signs of bacterial meningitis only when compared in relation to other symptoms, including respiratory tract infections, headache, and gastrointestinal abnormalities (Best, & Hughes, 2008). Some studies also indicate rash as a sign in a limited number of childhood cases; other studies report lack of symptoms in patients, in which case lumbar puncture was the only means for diagnosis of bacterial meningitis (Best, & Hughes, 2008).

Bacteria Strains

The two most common types of bacteria responsible for community-acquired bacterial meningitis in children aged 3 months and older are S. pneumoniae and N. meningitdis (Brouwer et al., 2010). One French study surveying the incidence of meningitis in children from 2001 to 2003 found the majority of fatalities caused by S. pneumoniae occurred in infants aged 2-12 months, and N. meningitdis was the most frequent pathogen among children aged greater than 12 months (Bingen et al., 2005). The third most common of cause of bacterial meningitis is Haemophilus influenzae type b (Hib); however, its incidence has dramatically decreased in areas of the world where Hib conjugate vaccines are administered (Chavez-Bueno et al., 2005). The remaining causative bacteria are group B. streptococcus, group A streptococci, Escherichia coli, nontypeable H. influenzae, and L. monocytogenes (Brouwer et al., 2010).

Anatomy and Pathophysiology

The bacteria responsible for meningitis often reside within an individual's mouth or throat and become harmful when the bacteria reach the central nervous system. Bacteria reach the central nervous system by hematogenous spread or by direct extension from a neighboring site (Chavez-Bueno et al., 2005). In infants and children, many of the causative bacteria colonize in the upper respiratory tract. Direct introduction of bacteria into the central nervous system can be caused by trauma, skull defects with cerebrospinal fluid leaks, or birth defects that affect dermal sinuses (Chavez-Bueno et al., 2005). The bacteria cause a significant threat to the central nervous system due to the poor ability of the cerebrospinal fluid to respond to bacterial infection. Inadequate presence of immunoglobulins and other immune molecules limits the innate elimination of bacteria from the cerebrospinal fluid (Yogev et al., 2005). Surface bacterial proteins that have been identified in facilitating the bacterial crossing of the blood-brain barrier are: E. coli proteins IbeA, IbeB, ompA; S. pneumonia protein CpbA; and N. meningitidis proteins Opc, Opa, and PilC (Chavez-Bueno et al., 2005). The presence of the bacteria in the subarachnoid space elicits an inflammatory response, and inflammation continues after bacteria are destroyed by antibiotic treatment and host responses. The production of inflammatory mediators such as tumor necrosis factor-?, interleukin (IL)-1, IL-6, IL-8, IL-10, macrophage induced proteins 1 and 2, in addition to other mediators, are initiated as bacteria products react with astrocytes, ependymal, glial, and endothelial cells in the central nervous system (Chavez-Bueno et al., 2005). As a result, there is granulocyte influx, cytokine release, and the blood-brain barrier permeability is altered, which causes the release of proteolytic products and toxic oxygen radicals (Chavez-Bueno et al., 2005). This process results in cerebral swelling and intracranial pressure. The edema and pressure lead to neuron damage, apoptosis, and loss of brain function.

Diagnostic Procedures

Diagnosing bacterial meningitis requires a lumbar puncture and subsequent cerebrospinal fluid analysis (Chavez-Bueno et al., 2005). Analyzing the cerebrospinal fluid culture is considered the fundamental and mandatory procedure to obtain a definitive diagnosis. The culture undergoes Gram staining, latex agglutination testing (Brouwer et al., 2010), white blood cell count and differential, glucose and protein concentration testing (Chavez-Bueno et al., 2005). Centrifugation of the cerebrospinal fluid and polymerase chain reactions may also be needed for more accurate diagnosis; these techniques might aid in diagnosing patients with negative cerebrospinal fluid cultures after antibiotic treatment (Brouwer et al., 2010).

The signature cerebrospinal fluid findings in patients with bacterial meningitis are: polymorphonuclear pleocytosis, hypoglycorrhachia, and increased cerebrospinal fluid protein levels (Brouwer et al., 2010). One study created a prediction model that indicated individual predictors of bacterial meningitis. The model consists of: glucose concentrations less than 0.34g/liter; a ratio of cerebrospinal fluid glucose to blood glucose of less than 0.23; protein concentration of more than 2.2g/liter, or a white blood cell count of more than 2,000 cells per mm3; neutrophil count greater than or equal to 100; and concentration of cerebrospinal fluid protein greater that 0.5g/liter (Brouwer et al., 2010).

Developmental diagnostic techniques that are still being researched and refined include sTREM-1 testing, blood culture testing, and skin biopsy testing. Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) were found to be a biomarker in cerebrospinal fluid during the presence of bacterial meningitis; however, it is not yet recommended for clinical practice (Brouwer et al., 2010). Blood cultures and skin biopsy have been used to detect causative pathogens in patients when cerebrospinal fluid cultures are negative or unavailable, but these tests are not definitive enough to be used as the standard diagnostic method (Brouwer et al., 2010). Improvements to blood culture and skin biopsy testing could result in a quicker, more cost effective diagnostic technique that is also safer for the patient.

Treatment Modalities

There are a variety of antibiotic regimens and therapies used for children with bacterial meningitis. Selecting the necessary antibiotic for treatment requires the assessment of its activity against the causative pathogen, its ability to penetrate the cerebrospinal fluid, and to determine the minimum antibiotic concentration for effective results (Chavez-Bueno et al., 2005). The compromised nature of the blood-brain barrier caused by meningitis also increases the permeability of most antibiotics, and must be considered when evaluating treatment dosage. Empirical therapy treatments are selected for children based on the most probable causative pathogen for the patient's age and the susceptibility patterns in the patient's geographical location (Yogev et al., 2005). Once the bacterial pathogen is known, or assumed, treatment providers will base the antibacterial regimen based on penicillin resistance and ?-Lactam allergy. The antibacterial treatments of choice for N. meningitidis are ceftriaxone or cefotaxime; Hib is cefotaxime or ceftriaxone; S. pneumoniae is cefotaxime or ceftriaxone plus vancomycin (Yogev et al., 2005). Peniciliin G. Or ampicillin is also considered standard therapies for susceptible (non-resistant) strains of N. meningitidis and S. pneumoniae (Chavez-Bueno et al., 2005). Antibiotic pretreatment of bacterial meningitis (treatment prior to lumbar puncture) is also employed in a significant number of childhood cases of bacterial meningitis, and is known to affect cerebrospinal fluid glucose and protein levels (Nigrovic et al., 2008).

One of the damaging effects of the inflammatory processes associated with bacterial meningitis causes permanent neurological sequelae, and most commonly, hearing loss (Yogev et al., 2005). Corticosteroid treatment, namely dexamethasone, is used (either before or with antibiotic treatment) to reduce hearing loss in children (Mongelluzzo et al., 2008). There are concerns with corticosteroid treatment due to the potential decrease in cerebrospinal fluid penetration of antibiotics; as well as side effects, such as gastrointestinal bleeding and prevention of secondary fever which indicates antimicrobial failure (Mongelluzzo et al., 2008). Anticonvulsant medications such as benzodiazepines and phenobarbital are recommended to prevent and control seizures (Chavez-Bueno et al., 2005).

Non-pharmacological strategies used to reduce the intracranial pressure caused by inflammation include the avoidances of vigorous procedures such as intubation, 30? head elevation, and short-term hyperventilation (Chavez-Bueno et al., 2005). Complications from treatment and bacterial meningitis include seizures, subdural effusions, brain abscesses, persistent fever, and fatality (Chavez-Bueno et al., 2005). The cost of treatment is relatively small due to lack of surgical intervention needed for bacterial meningitis. The majority of costs relevant to the patient concern the cost of vaccinations, antibiotics, and costs associated with hospital care. Costs of referral treatments must also be considered. From a research and development perspective, the greatest cost is vaccine development; the cost of which drives vaccination policies (Ceyhan et al., 2008).

Education

Educating parents on the signs and risk factors for bacterial meningitis is critical in order for children to receive appropriate medical care as quickly as possible. Although symptoms such as fever and vomiting are not obvious signs of meningitis, educating parents on the risk of penetrating head injuries, and any immunosuppressive states (such as HIV infection), greatly increase the likelihood of acquiring bacterial meningitis (Chavez-Bueno et al., 2005). Children who undergo cochlear implants are also at a high risk of acquiring bacterial meningitis; the rate of which is 30 times greater than children in the general U.S. population (Biernath et al., 2006). Once a child is recovering from bacterial meningitis, parents and the patient must also be educated on potential lifestyle changes. Etiology, patient age, concentration of bacteria, and cerebrospinal fluid findings at the time of diagnosis can all impact the outcome of bacterial meningitis (Chavez-Bueno et al., 2005). The most common outcome in children is hearing loss, in which some measure of hearing loss occurs in 25% to 35% of patients; there is also risk of neuromotor, speech, and learning disabilities in children, in which approximately 10% of children will develop (Chavez-Bueno et al., 2005).

Follow-up and Referral

Hearing loss, learning disabilities, speech difficulties, behavioral problems, and neuromotor impairment are all known consequences of bacterial meningitis in childhood (Chavez-Bueno et al., 2005). To address these outcomes, patients may be referred to neurologists for further testing. A patient experiencing these outcomes may also be referred to speech therapists, psychologists, and utilize additional assisted learning programs to accommodate lasting effects of meningitis.

Underserved Populations and Ethical Considerations