epidemiology, etiology, clinical feature, treatment, and prevention

1. Meningococcal Meningitis
Dr. Rakesh Kumar
Pediatrician and Neonatologist
Sunrise Newborn and Child Hospital

2. Discussed under following headings
• Introduction
• Epidemiology – world, India & Bihar
• Clinical manifestation
• Diagnosis
• Treatment
• Prevention

3. Introduction
• First described in 1805 after an epidemic of
meningitis in Geneva.
• It was not until 1882 this pathogen N.
Meningitides was recovered from CSF.
• N. Meningitides is gram negative diplococcus.
• Meningococcus sub divided into serogroup
based on distinct capsular polysaccharides.
• Humans are the only natural reservoir.

4. Contd…
• N. menigitidis is leading cause of meningitis in
both children and young adults.
• Overall mortality rate of 10%.
• 2nd most common cause of community
acquired adult bacterial meningitis in USA
• C/F are quite varied ranging from transient
fever and bacteremia to fulminant disease
with death ensuing within hours.

5. Contd…
• Acute systemic Meningococcal disease manifest
by 3 syndrome
-meningitis alone
-meningitis with meningococcemia
-meningococcemia alone
• Morbidity and mortality has changed very little
since 1950.
• Long term sequelae can be severe even in
successfully managed cases.

6. Epidemiology
• Meningococcal disease is found worldwide,
with the highest incidence of disease found in
the ‘meningitis belt’ of sub-Saharan Africa. In
this region, major epidemics occur every 5 to
12 years with attack rates reaching 1,000
cases per 100,000 population. Other regions
of the world experience lower overall rates of
disease and occasional outbreaks, with annual
attack rates of around 0.3 to 3 per 100,000
population.

7. Epidemiology
• Epidemics occur at irregular interval often
every 7-10 yr. in “meningitis belt” of sub
Saharan Africa.
-The case rate is 1 in 1000 population and 1 in
100 in children less than 2 year of age.
• It is endemic in USA incidence is 0.5 to
1.5/lakh population and 10 times higher in
children less than 2 year of age.
-predominant serogroup B, C & Y

9. Risk factor for epidemics
• The reason for epidemic spread is not known.
• Spread is more likely by aerosol route.
• High attack rates are in part due to poverty,
crowding, poor sanitation & malnutrition.
• Herd immunity & specific virulence strains is
implicated in rapid spread e.g. clonal analysis
from pilgrims from Mecca.
• Nasopharyngeal carriage is major associated
environmental and host factor associated with
endemicity of this disease.

10. Epidemiology India
• As per review of Sinclair et al N. Meningitidis
is 3rd most common cause of meningitis in
children less than 5year of age. (prevalance of
meningitis is 1.5-3.0% of all hospital
admission)
• N. meningitides is responsible for an
estimated 1.9% of all cases regardless of age.
• Epidemic in India- New Delhi(2005-2009),
Meghalaya (2008-2009) and Tripura(2009)

11. Contd…
• The epidemic period coincide with dry season
of November – March
• Existence of endemic disease is recognized
with highest attack rates in infants aged 3-12
months.
• India is low endemic zone as per WHO
• High carriage rate found in close contacts
justifies chemoprophylaxis
• PGI Chandigarh - tertiary care- serotype A & C

12. Year Location Suspected cases Deaths
1966-67 Delhi 616 129
1985-88 Delhi 6133 799
1985-88 Maharashtra 1573
1985-87 Surat 197 34
2005-09 Delhi 1725 -
2008 Meghalaya ~2000 ~ 200
2009 Tripura ~ 200 ~ 50
D. Sinclair et al. Tropical Medicine and International Health 2010;15(12):1421-35; V Manchanda et al. Indian J Med Microbiol 2006;24(1): 7-19; CD Alert.
Prevalence & Distribution of Neisseria meningitidis
isolates during epidemic periods

13. Meningococcal Meningitis
(2006-2014) 9 years state wise data
National Health Profile , India 2006-2015, Central Bureau of Health Intelligence. Available at http://cbhidghs.nic.in
• >45,000 cases reported in India
• West Bengal (East) & Andhra Pradesh (South)
together accounts for 55% of all cases
*states/UT with >100 cases in atleast one year from 2006 to 2014
*Bihar, Jharkhand, Assam & Chandigarh: Incomplete data
Epidemic
2005-
2008 Epidemic
2008 Epidemic
2009
13943
6391
4435
3681
2597

14. As Per IDSP report 2016, SHS Bihar

15. Clinical Features
• Typical initial presentation is sudden onset of
fever, nausea, vomiting, headache, decreased
ability to concentrate and myalgia in
otherwise health patient.
• Myalgia is an imp differential, pain is quite
intense.
• Non suppurative pharyngitis can be a
preceding symptoms.

16. • High index of suspicion is required particularly
in non epidemic setting.
• Worrisome signs- leg pain, cold hand and feet,
abnormal skin color
• Low BP with elevated pulse rate
• Intensive search for petechiae and ecchymosis
• Provocative test for meningeal irritability
Kernigs and Brudzinski.

17. • Shock, DIC and purpura fulminans.
• Immune complex associated complications-
arthritis, pleurisy, vasculitis & pericarditis
• Chronic meningococcemia acute arthritis-
dermatitis syndrome is increasing
• Pneumonia and pharyngitis
• Urethritis and ascending infections
• occult bacteremia

18. Diagnosis
• Gold standard is isolation of N. Meningitidis
from sterile body fluids eg- blood or csf
• Culture permits antibiotic susceptibility testing
• Blood culture(50-60% positive) as against CSF
(80-90% positive)
• Gram stain and latex agglutination even in
partially treated meningitis.
• Skin biopsy – gram stain and culture increase
sensitivity from 36 to 56%

19. • Antibiotics should not be delayed waiting for
LP
• CSF- glucose below 45, protein above
500mg/dL, cells above 1000
• Latex agglutination- five capsular types A, B, C,
Y and W-135. sensitivity for B is low and false
negative results can occur
• Multiplex PCR is available

20. Treatment
• Once suspected not more than 30 minutes
should elapse for appropriate antibiotics
• Third generation cephalosporin Cefotaxime or
Ceftriaxone as empiric therapy in non
epidemic setting
• As per WHO 1995 oily chloramphenicol or
ceftriaxone in epidemic setting.
• Penicillin G- 3lakh units/kg with max dose of
24 lakh units.

21. • Chloramphenicol in 100mg/kg max 4gm/day in
penicillin allergic patient
• Duration of Therapy – 7 days
• Supportive care- treatment of shock with
aggressive fluid therapy & inotropes.
• Glucocorticoids- suspected pneumococcal adult
meningitis and children with H. influenza type b.
• Protein C concentrate- purpura fulminans and
sepsis

22. • DIC – the primary treatment is directed at
underlying infection.

23. Prevention
• Antimicrobial chemoprophylaxis following
identification of an index case
• use of droplet precautions
• vaccination prior to exposure
• avoidance of risk factors

24. Droplet Precaution
• Droplet precautions should be continued for
24 hours after institution of effective
antibiotics in patients with suspected or
confirmed Neisseria meningitidis infection

25. Antimicrobial chemoprophylaxis
• The reported attack rate for close contacts of
patients with sporadic meningococcal disease
is approximately 1 in 250 persons exposed
(0.4 percent)
• Chemoprophylaxis is indicated in close
contacts of patients with meningococcal
infection, and should be given as early as
possible following the exposure.

26. Timing of chemoprophylaxis
• antimicrobial chemoprophylaxis should be
administered as early as possible (ideally <24
hours after identification of the index patient).
Conversely, chemoprophylaxis administered
>14 days after exposure to the index case is
probably of limited or no value, and is
therefore not recommended by the United
States Centers for Disease Control and
Prevention (CDC)

27. Regimens for antimicrobial prophylaxis

28. Nasopharyngeal Carriage
• There are no recommendations for eradicating
nasopharyngeal carriage in the community
outside of an outbreak or a patient with
invasive meningococcal disease.

29. Meningococcal Vaccine
• Two types of are vaccines available in India-
-MPSV (quadrivalent and bivalent)
-MCV (quadrivalent and monovalent)

30. Meningococcal Polysaccharide vaccine(MPSV)
• Either bivalent (A+C) or quadrivalent (A,C,Y,W-
135) containing 50µg of each of individual
polysaccharides.
• Indicated for individual older than 2 years.
• Antibody response is serogroup specific and
independent.
• Protective Ab level achieved within 14 days of
vaccination

31. Contd…
• Serogroup A & C has clinical efficacy rate of 85%
among children age > 5yr and above.
• Ab level significantly decrease after 3 yr of 1st
dose but in healthy adults it is detectable up to
10 yr
• Repeated dose are known to cause hypo
responsiveness
• Quadrivalent- Mencevac (Gsk), Quadrimening
(Biomed)
• Bivalent- MPV A+C (gsk), BiMeningo (Biomed)

32. Meningococcal Conjugate Vaccine(MCVs)
• Two typed of MCVs is available in India
• Menactra by Sanofi is quadrivalent (A,C,Y,W-
135) conjugate vaccine using diphtheria toxin
as carrier protein lecensed in US in 2005.
• Lincensed in India in 2012 for use in person
age 2 to 55 years

33. Contd…
• This contain 4µg of each of A, C, Y, W-135
conjugated to 48µg of diptheria toxoid
• A single dose of 0.5mL is recommended
• Recent estimate of effectiveness is 80-85%
within 3-4 yr of vaccination.
• There is higher level of evidence of protection
in children between age of 1yr-5 yr compared
to age> 5yr.

34. Contd…
• S/E – pain and swelling
• In GBS know case it is avoided
• CDC ACIP recommend 1 month gap between
PCV 13 and MenACWY-D.

35. Monovalent A conjugate vaccine
• Men AfriVac by SII using tetanus toxoid as carrier
protein.
• It contain 10µg of group A polysaccharide
conjugated to 10-33µg tetanus toxoid with alum
as adjuvant and thiomersal as preservative
• Licensed in India since 2009 and pre qualified by
WHO in 2010
• Administered as single IM of 0.5ml to individual
1-29 yr of age.

36. Contd..
• Induces Ab level which are significantly higher
and more persistent then corresponding
Polysaccharide vaccine
• It has a very good safety profile.

37. Vaccines against serogroup B
• Serogroup B polysaccharide capsule has
chemical identity with glycosylated protein
antigens in the human fetus so it is not
immunogenic in humans.
• One vaccine that is developed for adolescent
immunization was licensed in the United
States in 2014 and contains two variants of
factor H-binding protein; it appears highly
immunogenic in the target population.
Recommendations for its use are awaited.

38. Contd…
• Several countries (including Cuba, Norway,
and New Zealand) successfully controlled
serogroup B epidemics by immunizing with
tailor-made outer membrane vesicle
vaccines(sub capsular protein antigen)
prepared from blebs of outer membrane
harvested from the respective epidemic
strains. Limitation is that it is strain specific

39. ACIP Recommendation

40. • Countries with intermediate or high (2-10 or >10 cases/ 100000 population/year) endemic rates
of IMD or with frequent epidemics introduce appropriate large scale vaccination programmes
• Countries where disease occurs less frequently (<2 cases/ 100 000 population/year), vaccination is
recommended for defined risk groups:
o Children and young adults residing in closed communities, e.g. boarding schools or
military camps.
o Laboratory workers at risk of exposure to meningococci
o Travellers to high endemic areas
o All individuals suffering from immunodeficiency including asplenia, terminal
complement deficiencies, or advanced HIV infection
WHO recommendations 2011 :
meningococcal vaccination
WHO position paper November 2011-11-28