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MENIGITIS

DR.MAGDY A. DARWISH

Overview :

Meningitis is an infection of the meninges, the thin membrane that surrounds the brain and the spinal cord. Several organisms can cause meningitis but Neisseria meningitides is one of the most important because of its potential to cause epidemics. Meningococcal disease was first described in 1805 when an outbreak swept through Geneva, Switzerland. The causative agent, Neisseria meningitides (the meningococcus), was identified in 1887.

Overview :

Twelve subtypes or serogroups of N. meningitides have been identified and four (N. meningitides. A, B, C and W135) are recognized to cause epidemics. The pathogenicity, immunogenicity, and epidemic capabilities differ according to the serogroup. Thus the identification of the serogroup responsible of a sporadic case is crucial for epidemic containment.

Meningitis:

Meningitis or inflammation of the meninges is identified by an abnormal number of white blood cells in cerebrospinal fluid (CSF). Acute meningitis is clinically defined as a syndrome characterized by the onset of meningeal symptoms over the course of hours up to several days. Headache is a prominent early symptom, often followed later by confusion or coma. Chronic meningitis is has an onset measured in weeks to months (but is generally defined when symptoms, signs, and the CSF remain abnormal for at least 4 weeks), Whereas encephalitis is distinguished by the presence of decreased mentation (i.e., confusion or stupor) early in the course of disease and minimal meningeal signs.

Bacterial Meningitis:

The three most common meningeal pathogens: Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae, accounted for more than 80% of cases

In patients 16 years or older the most common causes of community-acquired bacterial meningitis are S. pneumoniae, N. meningitidis, and Listeria monocytogenes.

Most common cause of nosocomial bacterial meningitis in hospitalized patients is gram-negative bacilli.

Bacterial Meningitis:

Patients with deficiencies in the terminal complement components (C5, C6, C7, C8, and perhaps C9), the so-called membrane attack complex, have a markedly increased incidence of neisserial infection, but for unknown reasons their mortality is lower. Anatomical or Functional asplenia e.g. SCD have a markedly increased incidence of neisserial infection

Viral Meningitis:

Enteroviruses Currently the leading recognizable cause of aseptic meningitis syndrome, account for 85 to 95% of all cases in which a pathogen is identified. Infants and young children are the primary victims of enteroviral meningitis.

Mumps Virus In an unimmunized population, mumps is one of the most common causes of aseptic meningitis and encephalitis. Cases of vaccine-associated mumps meningitis have also been reported.

HIV virus Can infect the meninges early and persist in the CNS after initial infection.

Viral Meningitis:

Herpesviruses

Herpesviruses are DNA viruses and include herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesviruses 6, 7, and 8. Overall, herpes simplex viruses account for approximately 0.5 to 3% of all cases of aseptic meningitis. The syndrome of herpes simplex virus aseptic meningitis is most commonly associated with primary genital infection with herpes simplex virus type 2. Acute aseptic meningitis has also been associated with herpes zoster in patients with or without typical skin lesions

Cytomegalovirus and Epstein-Barr virus may cause aseptic meningitis in association with a mononucleosis syndrome, particularly in an immunocompromised host.

How is the disease transmitted?

The bacteria are transmitted from person to person through droplets of nasopharyngeal secretions. Close and prolonged (not casual) contact (e.g. kissing, sneezing and coughing on someone, living in close quarters or dormitories (military recruits, school or college students), sharing eating or drinking utensils, tooth brushing or cigarette etc.) facilitate the spread of the disease. Close personal contact is defined as being an arms length or less from infected person for 15 minutes or more

How is the disease transmitted?

N. meningitides only infects humans; there is no animal reservoir. The bacteria can be carried in the nasopharynx and sometimes, for reasons not fully known, overwhelm the body’s defenses allowing infection to spread through the bloodstream and to the brain. It is estimated that between 5 to 25% of the population carry N.meningitidis at any given time, but of course the carriage rate may be much higher in epidemic situations (50-80%).

Features of the disease:

The average incubation period is 4 days, ranging between 2 and 10 days. The most common symptoms are headaches high fever, stiff neck, confusion, and sensitivity to light (photophobia), and vomiting. Even when the disease is diagnosed early and adequate therapy instituted, 5% to 15% of patients die, typically within 24-48 hours of onset of symptoms. Untreated up to 50-80% of patients die.

Features of the disease:

Bacterial meningitis may result in brain damage, hearing loss, or learning disability in 5 to 15% of survivors. A less common but more severe (often fatal) form of meningococcal disease is meningococcal septicemia which is characterized by a hemorrhagic rash and rapid circulatory collapse.

Neisseria meningitidis rash

Meningococcemia

petechial and ecchymotic hemorrhages over large portions of the body

CLINICAL FEATURES

Initial Symptoms in Patients with Meningitis Headache 90 % Fever 90 % Meningismus 85 % Altered sensorium >80 % Kernig's Brudzinski's sign 50 % Vomiting 35 % Seizure 30 % Focal findings 10-20 % Papilledema <1 %

Diagnosis :

The diagnosis of meningococcal meningitis is suspected by the clinical presentation and confirmed by a lumbar puncture ,CSF examination , culture and sensitivity both CSF and /or bloods. More specialized laboratory tests are needed for the identification of the serogroups

DIAGNOSIS - Cerebrospinal Fluid Examination:

The CSF in cases of acute bacterial meningitis often demonstrates a purulent (cloudy) appearance and contains large numbers of neutrophils (5,000 to 10,000 per cubic millimeter of CSF). In addition, the protein is usually elevated and the sugar decreased. A definitive diagnosis of pyogenic meningitis depends on the demonstration of bacteria with a gram stain and/or subsequent culture.

Pyogenic Meningitis

Neutrophils

Elevated protein

Decreased sugar Positive gram stain

Treatmen t:

Meningococcal disease is potentially fatal and should always be viewed as a medical emergency. Admission to a hospital is necessary. Isolation of the patient is not necessary. Six hours after effective treatment patient is not infectious and carriers out number cases during epidemics. Antimicrobial therapy must be commenced as soon as possible after the lumbar puncture has been carried out. A range of antibiotics may be used for treatment including penicillin, ampicillin, chloramphenicol, and ceftriaxone. Under epidemic conditions in Africa, oily chloramphenicol is the drug of choice in areas with limited health facilities because a single dose of this long-acting formulation has been shown to be effective.

Epidemiology of meningococcal:

Meningococcal meningitis occurs sporadically in small clusters throughout the world with seasonal variations and accounts for a variable proportion of endemic bacterial meningitis. In temperate regions the number of cases increases in winter and spring.

Epidemiology of meningococcal meningitis:

Serogroups B and C together account for a large majority of cases in Europe and the Americas. Major African epidemics are associated with N. meningitides serogroups A and C and serogroup A is usually the cause of meningococcal disease in Asia. There is increasing evidence of serogroup W135 being associated with outbreaks of considerable size. In 2000 and 2001 several hundred pilgrims attending the Hajj in Saudi Arabia were infected with N. meningitides W135. Then in 2002, W135 emerged in Burkina Faso, striking 13,000 people and killing 1,500.

The African Meningitis Belt:

The highest burden of meningococcal disease occurs in sub-Saharan Africa, which is known as the “Meningitis Belt”, an area that stretches from Senegal in the west to Ethiopia in the east, with an estimated total population of 300 million people.

Senegal

The Gambia GuineaBissau Guinea Mali d'Ivoire Cote Burkina Faso Niger Benin Nigeria Cameroon Chad Central African Republic Sudan Uganda Kenya Eritrea Ethiopia

The African Meningitis Belt:

This hyperendemic area is characterized by particular climate and social habits. During the dry season, between December and June,  because of dryness, dust winds and upper respiratory tract infections due to cold nights, the local immunity of the pharynx is diminished increasing the risk of meningitis.  At the same time, the transmission of N. meningitides is favored by overcrowded housing at family level and  large population displacements due to pilgrimages and traditional markets at regional level.  This conjunction of factors explains the large epidemics which occur during this season in the meningitis belt area.

Due to herd immunity (whereby transmission is blocked when a critical percentage of the population had been vaccinated, thus extending protection to the unvaccinated), these epidemics occur in a cyclic mode (8-13 years). N. meningitides A, C and W135 are now the main serogroups involved in the meningococcal meningitis activity in Africa. In major African epidemics, attack rates ranges from 100 to 800 per 100 000 population, but individual communities have reported rates as high as 1000 per 100 000. While in endemic disease the highest attack rates are observed in young children, during epidemics, older children, teenagers and young adults are also affected.

The African Meningitis Belt:

The African Meningitis Belt:

In 1996, Africa experienced the largest recorded outbreak of epidemic meningitis in history, with over 250 000 cases and 25 000 deaths registered. Between that crisis and 2002, 223,000 new cases of meningococcal meningitis were reported to the World Health Organization. The countries most affected countries have been Burkina Faso, Chad, Ethiopia and Niger; in 2002, the outbreaks occurring in Burkina Faso, Ethiopia and Niger accounted for about 65% of the total cases reported in the African continent. Furthermore, the meningitis belt appears to be extending further south. In 2002, the Great Lakes region was affected by outbreaks in villages and refugees camps which caused more than 2,200 cases, including 200 deaths.

Prevention :
Several vaccines are available to prevent the disease.  Polysaccharide vaccines, which have been available for over 30 years, exist against serogroups A, C, Y, and W135 in various combinations.  No vaccine is yet available to offer protection against serogroup B.  Meningococcal vaccines are chemically defined serogroup-specific antigens consisting of purified bacterial capsular polysaccharides, each inducing serogroup-specific immunity.

Prevention :
A monovalent conjugate vaccine against serogroup C, has recently been licensed in developed countries for use in children and adolescents.  This vaccine is immunogenic, particularly for children under 2 years of age whereas polysaccharide vaccines are not.
 

All these vaccines have been proven to be safe and effective with infrequent and mild side effects. Adverse reactions to meningococcal vaccine are consisting principally of localized erythema that lasts 1–2 days. Transient fever may develop in up to 2% of especially children after vaccination.

Prevention :

Studies of vaccination during pregnancy have not documented adverse effects among either women or neonates (1 month of age and younger). Based on data from studies involving the use of meningococcal vaccines and other polysaccharide vaccines administered during pregnancy, altering meningococcal vaccination recommendations during pregnancy is unnecessary.

Vaccination is used in the following circumstances:

Routine vaccination: Routine preventive mass vaccination has been attempted and its effect has been extensively debated. Saudi Arabia, for example, offers routine immunization of its entire population. Sudan and other countries routinely vaccinate school children. Preventive vaccination can be used to protect individuals at risk (e.g. travelers, military, college students and pilgrims). This approach adopted by countries like Egypt, Saudi Arabia ,Sudan by early 90s . Since then these countries didn’t face any unusual occurrence meningitis Protection of close contacts: When a sporadic case occurs, the close contacts need to be protected by a vaccine and chemoprophylaxis with antibiotics to cover the delay between vaccination and protection .

N. meningitidis prophylaxis:
  

Up to 10% of cases have had close contact with another case. Estimated carriage rate is 5-25% at baseline, may be up to 40-90% in closed, confined populations Household cases have 500-800 fold increased risk of disease with secondary attack rate of 4 cases/100,000 Close contacts include household contacts, institutional members living in close quarters or dormitories (military recruits, school or college students) , day care members e.g. nursery care , anyone exposed to oral secretions kissing, and, sharing eating or drinking utensils, tooth brushing or cigarette etc. etc Initiate as soon as possible not more 48 h of exposure.

N. meningitidis prophylaxis:

Rifampin 600mg q 12 h for 2 days. This gives an 80% nasopharyngeal eradication rate. Ceftriaxone 250mg IM x 1 may be effective (125mg IM x 1 <15 y) Ciprofloxacin 500mg PO x 1 may be effective only for adults >18 y not pregnant or lactating CDC does not recommend antimicrobial chemoprophylaxis for returning pilgrims. Mass chemoprophylaxis to control epidemics not recommend by WHO

Vaccination is used in the following circumstances:

Vaccination for epidemic control: In the African Meningitis Belt context, enhanced epidemiological surveillance and prompt case management with oily chloramphenicol are used to control the epidemics. Routine immunization is not possible with the current available vaccines  As the polysaccharide vaccines provide protection for only three to five years and  Cannot be used in children under 2 years of age because they lack the ability to develop antibodies.  Furthermore, even large scale coverage with current vaccines does not provide sufficient “herd immunity”.  Consequently, the current WHO recommendation for outbreak control is to mass vaccinate every district that is in an epidemic phase, as well as those contiguous districts that are in alert phase. It is estimated that a mass immunization campaign, promptly implemented, can avoid 70 % of cases.

Vaccination is used in the following circumstances:

Emergence of W135: Bivalent AC vaccine is commonly used in Africa but the emergence of N. meningitides W135 as an epidemic strain involves revising this control strategy. A tetravalent ACYW135 polysaccharide vaccine exists but its high price and limited availability restricts its use in the African context. In 2003, WHO reached an agreement with a manufacturer to produce an affordable polysaccharide vaccine for Africa which would protect against A, C and W135 strains

Travelers’ health information:

Travelers to areas affected by meningococcal outbreaks are advised to be vaccinated. For pilgrims to the Hajj and Ramadan Omra, Saudi Arabia requires visitors obtain a tetravalent vaccine (against A, C, Y, W135) at least ten days prior to their arrival in the country. (Ref: WHO International Travel and Health. Vaccination requirements and Health Advice).

Meningococcal vaccine:
(is not routinely recommended for most people)

People who should get the vaccine include:  Military recruits  People who might be affected during an outbreak of certain types of meningococcal disease.  Anyone traveling to, or living in, a part of the world where meningococcal disease is common,.  Anatomical or Functional asplenia or terminal complement component deficiency  The vaccine should also be considered for: Some laboratory workers who are routinely exposed to the meningococci.  The vaccine may also be given to  college students who choose to be vaccinated.  College freshmen, especially those who live in dormitories,  Meningococcal vaccine is usually not recommended for  children under two years of age. But under special circumstances it may be given to infants as young as 3months (the vaccine does not work as well in very young)