The document discusses the necessity and implications of the meningococcal vaccine in India, highlighting the disease's high case fatality rates and the challenges in diagnosis and treatment. It provides statistical data on the incidence of meningococcal disease, the serotypes involved, and the recommendations for vaccination. Additionally, it outlines the evolution of vaccination strategies and the importance of early diagnosis to improve outcomes for patients.

1. Meningitis
Vaccine
Is it Needed in India?
Dr. Gaurav Gupta

2. Conflict of interest
• Received grants from various vaccine manufacturers
including
o Sanofi Pasteur
o Pfizer
o GSK
o Abbott
o MSD etc.

3. Overview
• Is meningococcal vaccine REALLY needed in India?

4. Overview
• What makes IMD unique?
• Do we have reliable Indian data about IMD?
• Does the vaccine work?
• When should we use vaccine? What guidelines are
available?

5. Meningococcal disease &
prevention

6. • Caused by Neisseria meningitides (Gram –ve
diplococci)1
• Strictly human pathogen
• Around 10 % asymptomatic nasal carriage rate
• Six (A, B, C, Y, X, and W) of 12 known SGs account for
the majority (around 90 %) of epidemics worldwide1,2.
Meningococcal disease
1. Pollard. In: Harrison's Principles of Internal Medicine. 18th ed.
2012;chapter 143
2. WHO. http://www.who.int/mediacentre/factsheets/fs141/en/

7. Meningococcal disease

9.  Highest disease
incidence in epidemics1
•10 to >1000 per
100,000 persons1
•800,000 cases in 20-
year period1
•Marked seasonality2
 Most commonly caused
by serogroup A;
 10% – 50% case fatality
rates1
Most regions endemic for
meningococcal disease
includes countries where
Yellow-fever vaccination
certificate is required for
travelers
Libya
Tunisia
Algeria
Morocco
Western Sahara
Guinea Bissau
Mauritania
Egypt
Chad
Niger
Eritrea
Sudan
Central African
Republic
Nigeria
Mali
Senegal
Liberia
Togo
Cameroon
Ethiopia
Somalia
DjiboutiGambia
Sierra Leone
Guinea
Ivory
Coast
Benin
DR of Congo
Uganda
Gabon
Kenya
Burkina
Ghana Equatorial
Guinea
Congo
Rwanda
Tanzania
Mozambique
Angola
Zambia
Burundi
Malawi
MadagascarBotswana
Zimbabwe
Namibia
South Africa
Lesotho
Swaziland
Endemic Region
1 Control of epidemic meningococcal disease: WHO practical guidelines. 2nd ed (WHO/EMC/BAC/98.3).
http://www.who.int/csr/resources/publications/meningitis/whoemcbac983.pdf
2 Meningitis Vaccine Project. http://www.meningvax.org/illo-meningbelt-cycle.htm
3 Report of a WHO Consultation (WHO/CDS/CSR/GAR/2002.1). http://whqlibdoc.who.int/hq/2002/WHO_CDS_CSR_GAR_2002.1.pdf:
Sub-Saharan Africa

10. Why is Meningococcal Disease
Unique?
• High CFR
• Short Incubation Period
• Limitations of diagnostic tools

11. Top 5 diseases with highest CFR
1. Rabies
2. JE
3. AES
4. Meningococcal Meningitis
5. Neonatal Tetanus

12. Diseases with High Case Fatality Rates in India1,
2014 (Provisional)
4th Highest CFR
(Disease with CFR
>1)
1. National Health Profile data, India 2015
2. D. Sinclair et al. Tropical Medicine and International Health 2010;15(12):1421-35
3. V Manchanda et al. Indian J Med Microbiol 2006;24(1): 7-19

13. Case Series from 10 Children’s Hospitals
Sequelae
distribution
among
survivors
n = 146
Mortality
n = 159
Percent of
patients
1.4
2.1
2.8
6.2
9.6
9.6
4.8
21.2
8.0
0 5 10 15 20 25
Amputation
Hemiplegia
Ataxia
Seizures
Skin Necrosis
Hearing Loss
≤11 Years (n=126)
≥11 Years (n=33)
Overall
Kaplan SL, et al. Pediatrics. 2006;118:e979
Percent of patients
13|
Meningococcal Disease: Death and Disability

14. Critical need for diagnosis as early as possible
• The younger, the faster disease progression:
• Median time between onset of symptoms and hospital admission:
≤22 hours1
• aged 15 to 16 years  22 hours1
• aged 5 to 14 years  20 hours1
• aged 1 to 4 years 14 hours1
• younger than 1 year  13 hours1
1Thompson et al. Lancet. 2006; 367(9508)
Narrow Time-Window Between Progression
from Initial Symptoms to Death

15. • Meningococcal meningitis clinically indistinguishable from meningitis due to
other bacteria. Non-blanching petechial rash is present in only a few cases. 1.
• 110 cases of IMD in Meghalaya Jan 08 –June 09 during an outbreak 2
• In the same study, meningococcal meningitis was seen in 61.8% of cases,
meningococcemia in 20 %. 18.2% had both.
1. Nelson text book of Pediatrics. 19th Ed. 2. Hazarika RD et al, Indian J Pediatr 2012 doi:10.1007/s12098-012-0855-0
100
56.4 53.6
23.6
9.1 6.4
0
50
100
Fever Headache Vomiting Rashes Seizures Deaths
Clinicalprofileof 110 cases of IMD
%
Diagnostic Limitations

16. Detection rates of Hib, Pneumococcus & IMD by
Culture, Latex agglutination and PCR
~80%
reduction
1.7X
8.3X
0.8X
4.6X
1.6X
6X
Mehmet Ceyhan et al. A Prospective Study of Etiology of Childhood Acute Bacterial Meningitis, Turkey. Emerging Infectious Diseases Vol. 14,
No. 7, July 2008
(For all 3 organism)

17. Indian burden of IMD

18. • Endemic Disease – Low background incidence, more common in
dry regions of North India.
• Epidemics – 20 year cycles previously, now increasing frequency
• Disease occurs in dry season  monsoon low  recurs next year
• Serogroup A majorly responsible for endemic and epidemics
• Some reports of B, C & W serotypes
• Surveillance:
• Notifiable disease under Integrated Disease Surveillance Programme (IDSP)
• Part of IAP ‘ID Surv’ program under acute bacterial meningitis
1. D. Sinclair et al. Tropical Medicine and International Health 2010;15(12):1421-35 2. Manchanda V et al. Indian J Med
Microbiol 2006;24(1): 7-19 3. Aggarwal M. Indian Pediatrics 2013;50: 601-3
Epidemiology in India

19. National Health Profile, 2006-2015
Cases and Deaths due to Meningococcal Meningitis in
India

21. • Pyogenic meningitis - 3.3% of
acute admissions
• N meningitidis Isolation : 1.9 %
(0.6-23.4%)
• Variable sample size (n=30-385)
and involved children < 12 years
of age.
• No organism identified in a large
proportion of patients (often with
significant mortality).
TAMIL NADU
• Achar & Rao (1953): 12.2%
• Ahmed et al (1964): 2%
• Deivanayagam (1993): 1%
DELHI
• Paul (1963): 6.3%
• Bhaumik (1998): 20%
• Jain et al (2000): 18.8%
UTTAR PRADESH
• Srivastava et al (1968): 3%
• Kalra and Dayal (1977): 5.1%
GUJARAT
• Gandhi (1969): 16.7%
• Javadekar et al. (1997): 8%
• Deivanayagam (1993): 1%
ANDHRA PRADESH
• Achar & Rao (1953): 12.2%
• Ahmed et al (1964): 2%
• Deivanayagam (1993): 1%
MADHYA PRADESH
• Tamaskar and Bhandari (1976): 14.3%
CHANDIGARH
• Ayyagari et al. (1980): 0.6%
• Singhi et al. (2002b): 4.3%
• Singhi et al. (2004): 1.1%
ORISSA
• Suvarna Devi et al (1982): 4.3%
MAHARASHTRA
• Pal and Sant (1982): 23.4%
• Chinchankar et al. (2002): 1.9%
KERALA
• Vincent et al. (1987): 15.7%
KARNATAKA
• Shivaprakash et al (2004): 1%
• Mani et al. (2007): 1%
• Shameem et al. (2008): 7.6%
D. Sinclair et al. Epidemiology of meningococcal disease in India. Tropical Medicine and International Health. 2010
The proportion of Neisseria meningitidis isolates in case series
of endemic bacterial meningitis
Prevalence & Distribution of Neisseria
meningitidis isolates during ENDEMIC periods

22. 21 22
8
14
44
23
0
10
20
30
40
50
No organism identified
in
720 / 852 cases
Numberofcultureconfirmedcases
Bacterial Meningitis in hospitalized patients
An IJP Survey in 6 Indian tertiary care hospitals
S.K. Kabra et al. Bacterial Meningitis in India : An IJP Survey. Indian J Pediatr 1991; 58 : 505-511

23. 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 EPIDEMICS

24. Meningococcal Conjugate
Vaccines (MCV)

25. A Not all vaccines are licensed for use in every country
1Novartis Vaccines. Menjugate® [PI]. 2013; 2Pfizer. Meningitec® [PI]. 2011; 3GSK. NeisVac-C® [Product Monograph]. 2015; 4GSK Australia Menitorix® [PI]. 2014;
5Serum Institute of India. MenAfriVac® [PI] 6Sanofi Pasteur.Menactra [PI]. 2014; 7Novartis Vaccines.Menveo [PI]. 2013; 8GSK UK. Nimenrix® [Product Monograph].
2015; 9Sanofi Pasteur. Meningo A+C® [Public assessment report]. 2013; 10GSK Australia. Mencevax® [PI]. 2014; 11Sanofi Pasteur.Menomune® [PI]. 2013;
12GSK. MenHibrix® [PI]. 2013.
Conjugate Vaccines
Carrier
Protein1-8,12
Menjugate MenC CRM197
Meningite
c
MenC CRM197
NeisVac-C MenC TT
Menitorix MenC-Hib TT
MenAfriV
ac
MenA TT
Menactra
MenACY
W
DT
Menveo
MenACY
W
CRM197
Nimenrix
MenACY
W
TT
MenHibri
x
MenCY-
Hib
TT
Polysaccharide Vaccines9-11
Meningo A+C MenAC
Mencevax MenACWY
Menomune MenACWY
Quadrimeningo MenACWY
Bimeningo MenAC
Worldwide Available Meningococcal
Polysaccharide and Conjugate Vaccines

26. Property
Polysaccha
ride
Conjugate
Effective in infants No Yes
Immune memory No Yes
Prolonged duration of protection No Yes
Booster effect No Yes
Reduction of carriage No Yes
Contributes to herd effect No Yes
Hyporesponsiveness with repeated
dosing
Yes No
1Khatami & Pollard. Expert Rev Vaccines. 2010;9(3); 2Granoff. In: Vaccines. 6th ed. 2013: chapter 21.
Comparison of Polysaccharide and Conjugate
Vaccines

27. 1Erlich & Congeni. Hum Vaccin Immunother. 2012;8(8)
While some diseases, such as hep B, do not require high circulating antibodies because of their slow
pathogenesis , innate immunity and high levels of protective circulating antibodies are the primary
immune defenses against rapidly progressing diseases such as IMD.
Day 1 Day 2 Day 3 Day 4 Day 5 Day 6
Bacterium Enters Body
Meningococcus incubation 3-4 days
(average)
Meningococcal Disease Onset
Innate Immunity and Circulating Antibodies
Primary source of protection
Immune Memory
Reactivation may take > 5 days
Maintaining Protective Levels of Circulating Antibodies by
Vaccination is Necessary for Clinical Protection Against
IMD

28. Phase III Indian trial with MenACWY-DT
% ≥ 4-fold rise in GMT measured by SBA-B
Sangeeta Yadav et al. Indian Pediatrics June 2014, Volume 51, Issue 6, pp 451-456

29. RL Castelblanco et al. The Lancet Infectious Diseases Volume 14, Issue 9, September 2014, Pages 813–819
Meningitis trends for different bacteria in US, 1997 to
2010
*P values calculated on the basis of the comparison betwee
& 2010

30. Hospitalizations(n)
Bivalent
(A/C)
Monovalent (group C)
Year
Quadrivalent
(A/C/Y/W-135)
1Adapted from Defraites. MSMR. 2000;6; 2Broderick. Emerg Infect Dis. 2012;18(9)
IncidenceRate(per100,000person-years)
Bars indicate hospitalization frequencies; line indicates rates
35
30
25
20
15
10
5
0
Vaccinating US Military Recruits Since 1971 Has Reduced
the Incidence of Meningococcal Disease by >90%1,2

31. • 69% overall effectiveness at 6 years post vaccination in
adolescents 13 to 17 years of age (95% CI=50%–81%)1
Time Since
Vaccination
Estimate of Vaccine
Effectiveness 95% CI
<1 year 82% 54%–93%
1 to <2 years 80% 52%–92%
2 to <3 years 71% 34%–87%
3 to <6 years 59% 5%–83%
Preliminary adolescent case control data (157 cases; 180 controls—August 2012) show vaccine effectiveness wanes
over time1
1Cohn. MMWR Recomm Rep. 2013;62(RR2)
Vaccine Remains Effective in Adolescents up to 6
Years Postimmunization in US

32. • The Kaiser Permanente study - 2005-2006 among >30,000 members
o Conclusion: “We did not identify any serious, clinically meaningful safety
concerns”
• The Harvard study involved 12.5 million adolescents who received 1.4 million
doses from 2005-2008
o Conclusion: MenACYW-DT vaccine “was not associated with increased
GBS risk”
• The Vaccine Safety Datalink study - additional 0.9 million doses among
adolescents and confirmed and extended the preceding results, providing
further assurance regarding the safety of MenACYW-DT vaccine.
1Zhang. ID Week 2012, Abstract #378, San Diego, October 18, 2012; 2Valentgas. Pharmacoepidemiol Drug Saf. 2012;21(12)
3Yih. Pharmacoepidemiol Drug Saf. 2012;21(12);
MenACYW-DT : Post-Licensure Safety Experience

33. MENAFRIVAC

34. 1Daugla. Lancet. 2014;393(99-11)
Incidence of Reported Cases of Meningitis in Chad, 2009–2012
WeeklyIncidenceper100,000
Population
0
Year
1
2
3
4
5
6
7
8
9
2009 2010 2011 2012
Vaccinated
Non-vaccinated*
Vaccination
with PsA-TT
*Non-vaccinated: incidence of reported cases of meningitis in districts of epidemic alert in Chad that did not receive the vaccine
Introduction of Men A Conjugate Vaccine (PsA–TT) in Chad
Has Strongly Reduced Disease Incidence and Carriage

35. Interesting Facts about
MCV
• PCV13 & MenACWY-D
• MenACWY-D and GBS
• MenACWY-D and Pregnancy

36. Recommendations

37. ACIP Recommendations
1. MMWR, March 22, 2013, Vol 62, #RR02
2. MMWR, June 20, 2014 / 63(24);527-530
• Routine vaccination of adolescents aged 11-18 years
oOne dose at age 11-12 years, with a booster dose at age
16 years.
oMenACWY may be administered up to age 21 years as
Single dose catch-up vaccination for those who have not
received a dose after their 16th birthday
• Routine vaccination not recommended for children aged 2
months-10 years

38. ACIP Recommendations
1. MMWR, March 22, 2013, Vol 62, #RR02
2. MMWR, June 20, 2014 / 63(24);527-530
• Routine vaccination of persons aged ≥2 months at increased
risk for meningococcal disease, including:
o complement component deficiency.
o anatomical or functional asplenia
o healthy infants in communities with a outbreak
o ≥9 months old who travel to hyperendemic or epidemic
countries
• Special populations

39. 1Pollard. In: Harrison's Principles of Internal Medicine. 18th ed. 2012;chapter 143; 2Bilukha. Pediatr Infect Dis J. 2007;26(5); 3MacNeil. In: Manual for the Surveillance of
Vaccine-Preventable Diseases. 5th ed. 2012; 4Liphaus. Enferm Infecc Microbiol Clin. 2013;31(2)
Impaired immune system1,2/
lack of antibodies1
Exposure through close contact with
infected person or the live bacteria
Travelers to endemic areas3
Immunocompromised2
Infants, children1,2 Caregivers3
Personnel working with
N. meningitidis2,3
Crowding1,3,4
(students, military, Hajj,
oil refineries)
At-Risk Populations

40. Current IAP
recommendations
• Current epidemiology does not justify routine use
• High risk recommendation
• Conjugate preferred over polysaccharide

41. IAP recommendations
cont.• Epidemics – Conjugate preferred, Monovalent vaccine
maybe used
• High risk recommendation
o Immune compromised - 2 doses 8 weeks apart
o HCW, lab personnel , contacts – Single dose of MCV4, booster as
appropriate
• International travel
o Study - < 21 years – 1 dose within last 5 years
o Hajj – Quadrivalent vaccine within last 3 years
o Africa – MCV4 preferred, within last 5 years.

42. Global MCV uptake in mass immunization program
USA
Canada
Chile
Brazil African
Meningitis
Belt
12/26 countries
Benin
Ghana
Chad
Ethiopi
a
Gambia
Mali
Cuba
Australia
New
Zealand
Burkina
Faso
Cameroo
n
Niger
Nigeria
Senegal
Norway
France
Italy
Poland
Germany
Spain
Austria
Belgium
Cyprus
Greece
Ireland
Holland
Liechtenste
in
Luxembour
g
Czech
Republic
Portugal
England
Saudi Arabia
UAE
1. Halil Özdemir et al. J Pediatr Inf 2014; 8: 178-86
2. Kate O'Brien presented in SAGE 22 Oct 2014
38

43. Take Home Message
• IMD is a serious problem
• It exists in India in endemic & epidemic form – limited
data
• MCV is safe & effective & preferred vaccine
• Judicious use of Meningococcal vaccines can help
protect high risk individuals

44. Altman DG et al. BMJ
1995;311:485