Meningococcal Disease and Meningococcal Vaccines

Meningitis
Infection causing inflammation of the membranes covering the brain and spinal cord
Medical emergency with significant mortality 
Characteristic pathogens
1. Bacterial meningitis or purulent meningitis
2. Non-bacterial meningitis often referred to as aseptic meningitis
Aseptic Meningitis
All non-bacterial causes of meningitis
Typically less ill appearing than bacterial meningitis
Most common cause is viral
 Viral Meningitis : A relatively common but rarely serious clinical syndrome with multiple viral etiology , characterized by sudden onset  febrile illness with sign of meningeal involvement. 
Infectious agents:
A wide variety of infectious agents exist , many associated with other specific diseases. In epidemic period mumps may be responsible for more than 25% of cases of non immunized etiology.
Occurrence: worldwide , as epidemic and sporadic cases, true incidence unknown.
Seasonal increase in the summer and early autumn are due mainly to arboviruses and enteroviruses, while late winter outbreaks may be due primarily to mumps

CSF findings are pleocytosis( usually mononuclear, occasionally polymorphonuclear in early stages) increased protein, normal sugar and absence of bacteria. A rubella like rash characterizes certain types caused by echoviruses, vesicular and petechial rash may occur. Active illness seldom exceeds 10 days. Recovery may be complete 

Bacterial Meningitis:
Most frequent in children age 2 months to 2 years of age
Higher incidence during winter and spring Neisseria meningitidis, Streptococcus pneumoniae and Hemophilus influenza type b cause more than 75% of all cases of bacterial in most study and 90% of bacterial meningitis in children. Previously Hemophilus influenza type b is the most common cause of bacterial meningitis has been largely eliminated by immunization programs.  

Neisseria meningitidis
Severe acute bacterial infection.
Cause of meningitis, sepsis, and focal infections.
Epidemic disease in sub-Saharan Africa
Current polysaccharide vaccine licensed in 1978
Conjugate vaccine licensed in 2005
Neisseria meningitidis
Aerobic gram-negative bacteria
At least 13 serogroups based on characteristics of the polysaccharide capsule
Most invasive disease caused by  serogroups A, B, C, Y, and W-135
Relative importance of serogroups depends on geographic location and other factors (e.g. age)
Meningococcal Disease
Pathogenesis
Organism colonizes nasopharynx
Nasal carrier in 25% of 18y-25y.
In some persons organism invades bloodstream and causes infection at distant site
Antecedent URI may be a contributing factor
Meningococcal Disease
Clinical Features
Incubation period 3-4 days (range 2-10 days)
Abrupt onset of fever, meningeal symptoms, hypotension, and rash
Fatality rate 9%-12%; up to 40% in meningococcemia
Neisseria meningitidis
Clinical Manifestations*

Meningococcal Meningitis
Most common pathologic presentation
Result of hematogenous dissemination
Clinical findings:
Fever
headache 
stiff neck
petechial/purpuric rash
hypotension
multiorgan failure

Meningococcemia
Meningococcemia is defined as dissemination of meningococci into the bloodstream and is a medical emergency, making early recognition of the disease.
Patients with acute meningococcal infection can present clinically with one of 3 syndromes: meningitis, meningitis with meningococcemia, or meningococcemia without obvious meningitis. Prior to the advent of antibiotics, almost all cases resulted in death or marked morbidity.
 	 
Meningococcal Disease
Laboratory Diagnosis
The gold standard for diagnosis is recovery of meningococci from a sterile site( CSF, OR BLOOD) Bacterial culture
Gram stain
Non-culture methods
    Antigen detection in CSF
    Serology

Epidemiology
Frequency

International
Serogroups A, B, and C account for most cases worldwide. Serogroups A and C predominate in Asia and Africa, and serogroups B and C predominate in Europe, North America, and South America.
For more than a century, serogroup A meningococcal disease has been endemic in the African Meningitis Belt, which extends from Ethiopia in eastern Africa to Senegal in West Africa.

Outbreaks of meningococcal disease occurred during the annual hajj (pilgrimage) in Saudi Arabia in 2000 and 2001 among pilgrims and household contacts Outbreaks have also occurred in Africa, parts of Asia, South America, and the former Soviet republics. Serogroup A is usually implicated in these epidemics. Outbreaks are also occasionally reported in the United States.

Meningococcal disease may be a significant but under-reported problem in developing Asian countries.
Serogroup W-135 has been associated with pilgrims returning from the hajj.
Up to 95% of patients with meningococcal disease have meningococcemia and/or meningitis. Up to 50% have meningococcemia without meningitis. Fulminant meningococcemia occurs in up to 20%.
 Nosocomial transmission to patient care personnel and laboratory staff is rare.

Neisseria meningitidis 
Medical Management
Initial empiric antibiotic treatment after appropriate cultures are obtained
Treatment with penicillin alone recommended after confirmation 
of N.
Occurrence:
In Europe and North America the incidence of the disease is higher during winter and spring.
In Sub-Saharan Africa the disease classically peaks during dry season.
Risk Factors:
1.	 Age: Infants have the highest risk of the disease . Rates decrease after infancy and then increase in adolescence and young adulthood.
           In some countries : male are at higher risk than female
           2. Immune deficiency:
  
2.	Terminal complement pathway deficiency
4.	Asplenia( absence of the spleen).
, functional asplenia  impaired reticuloendothelial function of the spleen, as seen in children with sickle cell anemia.
5.	Genetic risk factors
Exposure factors
6.	Household exposure 
7.	Demographic and socioeconomic factors and crowding                                       
8.	Concurrent upper respiratory tract infection
9.	Active and passive smoking
Meningitis-Differential Diagnosis
•	Brain abscess
•	Encephalitis
•	Epidural abscess
•	Bacterial endocarditis with septic embolism
•	Subarachnoid hemorrhage
•	Tumor

Meningococcal Disease 
Epidemiology
•	Reservoir		   Human
				  
•	Transmission	   Respiratory droplets

•	Temporal pattern   Peaks in late winter–early 				   spring
 
•	Communicability	   Generally limited

Methods of control
Preventive measures:
1. Educate the public on the need to reduce direct contact and exposure to droplet infection.
2. Quadrivalent meningococcal polysaccharide vaccine containing groups (A, C, Y, W-135) ,
 ( bivalent AC) two polysaccharide vaccines are currently available on the market
Administered by subcutaneous injection
10-dose vial contains thimerosal as a preservative
 Vaccine Recommendations
•	(bivalent AC) two polysaccharide vaccines approved for persons 2 years of age and older, do not elicit long term protection particularly in children under 5. Serogroup A polysacharide can induce antibodies in children as young as 3 months ,but C polysacharide is poorly immunogenic  and not effective in children under 2. 
•	Not recommended for routine vaccination of civilians
•	Should be used only for persons at increased risk of N. meningiditis infection who are 56 years of age or older, outbreak control and for prevention of among high risk group.
Meningococcal Vaccine
Recommendations
•	Recommended for persons at increased risk of meningococcal disease:
Microbiologists who are routinely exposed to isolates of N. meningitidis
Military recruits
Persons who travel to and U.S. citizens who reside in countries in which N. meningitidis is hyperendemic or epidemic
terminal complement component deficiency
functional or anatomic asplenia 

Meningococcal Vaccine Recommendations
•	Because these vaccines are often poorly immunogenic  in young children and have limited duration of efficacy they are not generally used in routine child hood examination programs. Re immunization may be considered within 3-5 years     
•	 Outbreak definition:
10.	3 or more confirmed or probable primary cases
11.	Period <3 months
12.	Primary attack rate >10 cases per 100,000 population.

Meningococcal Vaccines
Contraindications and Precautions
•	Severe allergic reaction to vaccine component or following prior dose of vaccine
•	Moderate or severe acute illness

Meningitis- Prevention
•	Chemoprophylaxis for close contacts of index case if Neisseria; treat contacts less than 4 years of age.
•	Vaccinate all children, especially those at risk or those with a splenia
Control of patient, contacts and the immediate environment:
1. Report to local health authority.
2. Isolation : for 24 hours after start chemotreatment.
3. Concurrent disinfection.
Protection of contacts: close surveillance of household day care and other intimate contact for early signs of illness  

Specific treatment: penicillin given paranterally in adequate dose is the drug of choice, ampicilline and chloramphinicol are also effective.