1. Meningococcal Meningitis
Dr Saleh H. Al Rowaily
Pediatric Consultant
General Director Assistant for Curative Services
ARAR-Northern Border Region -November 2015

2. Meningococcal Meningitis
Meningitis is the inflammation of the membranes surrounding the brain & spinal cord, including the dura, arachinoid & pia matter

3. Meningococcal Meningitis
Meningococcal meningitis is a bacterial form of meningitis, a serious infection of the thin lining that surrounds the brain and spinal cord
The most important pathogen for meningitis is Neisseria meningitides
because of its potential to cause epidemics

4. Problem Statement Occurs worldwide in both endemic and epidemic forms.
It is estimated to be responsible for over 500,000 cases and about 135,000 deaths annually
‘African meningitis belt’, stretches across sub – Saharan Africa from Senegal in the west, to Ethiopia in the east.
During epidemics this region has a disease incidence rate of >1,000 cases per 10,000 population.
The largest recorded outbreak occurred in Africa in 1996
Major epidemics reported from Asia over the past 35 years. China, Vietnam, Mongolia, and Nepal
The highest level of meningococcal disease occurs in the
‘African meningitis belt’, which stretches across sub - Saharan
Africa from Senegal in the west, to Ethiopia in the east. During
epidemics this region has a disease incidence rate of >1,000
cases per 10,000 population. The largest recorded outbreak of
meningococcal disease in history occurred in Africa in 1996
where 250,000 cases including 25,000 deaths were reported to
the WHO. Major epidemics of menincococcal meningitis have
been reported from Asia over the past 35 years. China, Vietnam,
Mongolia, Bhutan, and Nepal have all reported large outbreaks
with Serogroup B being implicated most often.

5. Problem Statement
Isolated in 1887, N. meningitides is an exclusive human pathogen
Natural habitat and reservoir - The mucosal surfaces of the human nasopharynx
In most cases colonization of the human nasopharynx is asymptomatic.
However, blood stream invasion can lead to meningitis and septicaemia with serious consequences.
Even with adequate chemotherapy, meningococcal meningitis has a fatality rate of about 10% and about 15% of the survivors have residual Central Nervous System (CNS) damage

6. Agent: Neisseria meningitides
Bean shaped gram negative, aerobic diplococci.
At least 13 serogroups have been
described :
A, B, C, D, E, H, I, K, L, W - 135, X, Y and Z.
Almost all meningococcal infections are caused by five serogroups A, B, C, 29 E or W – 135
Worldwide serogroups A, B and C account for most cases of meningococcal disease
The predominant serogroups in Asia and Africa are A & C
Recent outbreaks among Haj pilgrims have been attributed to serogroup W – 135
The capsular polysaccharide provides the basis for their classification into serogroups.
They differ in their agglutination reactions to sera directed against polysaccharide antigens.
Pathogenic meningococci are enveloped by a polysaccharide capsule.

7. Host and Environment
Maternal antibodies offer protection against invasive disease till the age of six months.
Susceptibility peaks at age months and decreases again after colonization of closely related nonpathogenic bacteria.
Subsequent colonization with Neisseria Meningitides induces antibodies to the infecting strain, thus reinforcing natural immunity.
Invasive disease occurs if no protective bactericidal antibodies are mounted against the infecting strain.
Those infected with the Human Immunodeficiency Virus are probably also at increased risk for sporadic meningococcal disease

8. Host and Environment Highest incidence – 6 months to 2 yrs
Rarely reported over 50 years of age.
No gender predilection, though males account for slightly more than half the reported cases.
Increased Risk with smoking (both active and passive), antecedent upper respiratory tract infection, underlying chronic illnesses are all associated with increased risk of meningococcal disease.
Low socioeconomic status - poor housing, overcrowding, and inadequate ventilation consistently associated with higher risk for meningococcal disease
The risk of invasive disease is higher in the first few days after exposure to a new strain.

9. Transmission & Communicability
The main modes of transmission are direct contact and respiratory droplets.
Close contact like living in close quarters (like military dormitories) and sharing of utensils enhance the risk of transmission
The average incubation period is days with a range of 2 to 10 days.
This is also the period of communicability.
The bacteria are rapidly eliminated from the nasopharynx after starting antibiotics, usually within 24 hours.

10. Reservoir Humans are the only reservoir.
Both cases and carriers serve as the source of infection.
5 - 10% adults are asymptomatic nasopharyngeal carriers during inter - epidemic periods.
This figure can, however, rise to % in closed populations like military recruits in camps

11. Pathogenic Strain
Susceptible Host
Colonized on naso - oropharyngeal mucosa
Overcome host defense & attach to the microvillous surface
of nonciliated columnar mucosal cells of the nasopharynx,
mucosal penetration followed by invasion of blood stream and
finally, invasion of meninges
meningococcemia leading to systemic disease, usually precedes meningitis by 24 to 48 hours
Meningococcemia leads to diffuse vascular injury with circulatory collapse and disseminated intravascular coagulation.

12. Clinical Features
Acute onset (within several hrs to 2 days) of intense headache, high fever, nausea, vomiting, photophobia, and stiff neck, altered mental state
Less commonly reported symptoms include stupor or coma, which carries a poorer prognosis.
A more severe form of disease is meningococcal septicaemia, characterized by a haemorrhagic rash which usually indicates disease progression and rapid circulatory collapse

13. Clinical Features
The symptoms of meningitis vary and depend on the age of the child and cause of the infection. Common symptoms are:
Flu-like symptoms
fever
lethargy
Altered consciousness
irritability
headache
photophobia
stiff neck
Brudzinski sign
Kernig sign
skin rashes
seizures

14. Clinical Features

15. Clinical Features
Other symptoms of meningitis in Neonates/infants can include:
Apnea
jaundice
neck rigidity
Abnormal temperature (hypo/hyperthermia)
poor feeding /weak sucking
a high-pitched cry
bulging fontanelles
Poor reflexes

16. Clinical features
In infants and young children there is a slower onset of signs and symptoms with nonspecific symptoms and neck stiffness may be absent.
Irritability and projectile vomiting may be the presenting features.
Seizures occur in 40% of children with meningitis.
The Waterhouse - Friderichsen syndrome may develop in % of children with meningococcal infection, characterized by large petechial haemorrhages in the skin & mucous membranes, fever, septic shock
Even when the disease is diagnosed early and adequate therapy instituted, 5% to 10% of patients die, typically within hours of onset of symptoms.
Bacterial meningitis may result in brain damage, hearing loss or learning disability in 10 to 20% of survivors

17. Clinical features
The Waterhouse - Friderichsen syndrome may develop in % of children with meningococcal infection, characterized by large petechial haemorrhages in the skin & mucous membranes, fever, septic shock
Death from Waterhouse-Friderichsen

18. Diagnosis Investigations CBC Blood culture Gram staining
LP- D/r, C/s (color, leukocyte count, differential, glucose, protein)
Electrolytes
PCR
Coagulation profile
liver and kidney function
Chest X-ray
CT/ MRI
Blood gases
EEG
ECG

19. Diagnosis LP

20. Diagnosis
Suspected by the clinical presentation and a L.P. showing a purulent spinal fluid
CSF - increased pressure (>180 mm water), WBC counts between10 and 10,000 cells/μL, (predominantly neutrophils), decreased glucose concentration (<45 mg/dL) and increased protein concentration (>45 mg/dL)

21. Diagnosis Bacteriological diagnosis by Gram staining of CSF,
Direct antigen detection using latex agglutination, or
Culture- only CSF samples are generally positive.
Kits to detect polysaccharide antigen in CSF are rapid and specific and can provide a serogroup - specific diagnosis, but false negatives!

22. Management
Since its potentially fatal, should always be viewed as a medical emergency
Early recognition of the disease, prompt initial parenteral antibiotic therapy and close monitoring with frequent repeated prognostic evaluations
Several antibiotics can be used for treatment including penicillin, ampicillin, chloramphenicol and ceftriaxone
Isolation of the patient is not necessary

23. A single intramuscular dose of an oily suspension of chloramphenicol has been shown to be as effective as a five - day course of crystalline penicillin in the treatment of meningococcal meningitis.
During epidemics, this may offer a practical alternative to penicillin or ceftriaxone which require multiple injections.
Antibiotic
Adult Dose
Pediatric Dose
Penicillin
4 million units IV X 4 a day
250,000 Units/Kg/day I.V. in devided doses
Ceftriaxone
4 gram IV per day divided into two doses
50 mg/Kg IV divided into two doses (not to exceed 4 g/d).

24. Prevention and Control
Chemoprophylaxis : as soon as possible (ideally within 24 hours), limited or no benefit if given more than 14 days after the onset of disease
Adults -
Ciprofloxacin single oral dose of 500 mg,
Rifampicin 600 mg 12 hourly for two days,
or ceftriaxone 250 mg IM single dose
Rifampicin should be avoided during pregnancy.
Children - rifampicin 10 mg/Kg 12 hourly for two days (5mg/Kg for infants) or injection ceftriaxone 125 mg IM single dose.

25. Prevention & Control
Chemoprophylaxis is not recommended during epidemics because of multiple and prolonged sources of exposure
Logistic problems and high cost
Secondary cases comprise less than 2% of all meningococcal disease
Immunization using safe and effective vaccines is the only rational approach to the control of meningococcal disease.

26. Prevention & Control
Immunization using safe and effective vaccines is the only rational approach to the control of meningococcal disease.

27. Meningococcal Vaccines
Of the five common serotypes responsible for more than 90% of meningococcal disease, vaccines are available for group
A, C, Y and W
At present two types of meningococcal vaccines are licensed;
meningococcal polysaccharide vaccines (bivalent and quadrivalent) and
meningococcal conjugated polysaccharide vaccine.

28. Polysaccharide Vaccines purified, heat - stable, lyophilized capsular polysachrides
Bilvalent- against serogroups A and C,
Quadrivalent against serogroups A, C, Y and W
Single dose - of the reconstituted vaccine contains 50 μg of each of the individual polysaccharides.
The dose for primary vaccination for both adults and children older than two years
is a single ml subcutaneous injection.
The antibody responses
to each of the four polysaccharides in the quadrivalent vaccine
are serogroup - specific and independent.

29. Polysaccharide Vaccines purified, heat - stable, lyophilized capsular polysachrides
Protective levels of antibody are usually achieved within days
The serogroup A and C vaccines have good immunogenicity, with clinical efficacy rates of 85% to 100% among children five years of age or older and adults.
Serogroup Y and W polysaccharides are safe and immunogenic in older children and adults.
Vaccination has been highly effective in the control of community outbreaks and epidemics in military centers.
Carrier status is unaffected by vaccination
Extremely safe, major drawback is the absence of activity against group B meningococci
These unconjugated polysaccharide vaccines confer protection in complement deficient persons also.
Vaccination does not reduce the transfer of bacteria to non - vaccinated persons and carrier status is unaffected.

30. Conjugated polysaccharide vaccine
A quadrivalent A, C, Y and W conjugate vaccine has been licensed since January 2005.
Contains 4 μg each of A, C, Y and W polysaccharide conjugated to 48 μg of diphtheria toxoid.
Induce a T - cell - dependent response, resulting in an improved immune response in infants, priming immunologic memory and leading to a booster response to subsequent doses.
These vaccines provide long - lasting immunity
Nasopharnygeal carriage rates may also be decreased, reducing bacterial transmission.
Induce herd immunity through protection from nasopharyngeal carriage.
The conjugated polysaccharide vaccine is contraindicated in patients with a known hypersensitivity to any component of the vaccine, including diphtheria toxoid and in patients with a history of a severe reaction to any other vaccine containing similar components

31. Recommendations for use of meningococcal vaccine
Routine vaccination is recommended for certain high - risk groups, including persons who have terminal complement component deficiencies and those who have anatomic or functional asplenia.
Travelers above 18 months of age going to an area experiencing an epidemic or to areas with a high rate of endemic disease.
Revaccination may be indicated for persons at high risk for infection particularly for children who were first vaccinated when they were less than four years of age; such children should be considered for revaccination after years if they remain at high risk.
Routine childhood vaccination with the meningococcal
polysaccharide vaccine is not recommended because of its
relative ineffectiveness in young children below two years
of age. Large scale coverage with current vaccines does not
provide sufficient “herd immunity”. Consequently, WHO does
not currently recommend meningococcal polysaccharide vaccine
as part or routine infant immunization. Routine vaccination
with the vaccine is recommended for certain high - risk groups,
including persons who have terminal complement component
deficiencies and those who have anatomic or functional
asplenia. Laboratory personnel and healthcare workers who are
exposed routinely to Neisseria meningitidis in solutions that
may be aerosolized should also be considered for vaccination.
Vaccination with a single dose of polysaccharide vaccine is
recommended for travellers above 18 months of age going to
an area experiencing an epidemic of meningococcal disease or
to areas with a high rate of endemic meningococcal disease.
Since the epidemic of meningococcal disease that occurred in
1987 during the Hajj in Mecca, proof of vaccination against
meningococcus has been required for the pilgrims to the Hajj
or Umra, at their entry in Saudi Arabia. More information
concerning geographic areas for which vaccination is
recommended can be obtained from internet (http : //www. cdc.
gov/travel/).
Revaccination may be indicated for persons at high risk for
Laboratory personnel and healthcare workers who are exposed routinely to Neisseria meningitidis in solutions that may be aerosolized should also be considered for vaccination.

32. THANKS

33. REFERENCES