1. MENINGOCOCCAL MENINGITIS
Dr LAWRENCE AKUNGA
MEDICAL ADVISOR SANOFI PASTEUR /

2. MENINGOCOCCAL MENINGITIS
References: – accessed 01/July/2018
- accessed on 01/July/2018

3. Causative Agent: Neisseria meningitidis
Meningococci are bacteria surrounded by a polysaccharide capsule6
The polysaccharide structure determines the pathogen’s serogroup (SG)6
Six (A, B, C, Y, X, and W*) of 12 known SGs account for the majority of meningococcal infections worldwide7,8
Neisseria
meningitidis
Main Points
Neisseria meningitidis causes invasive meningococcal disease.6,7
This pathogen is a gram-negative, aerobic, diplococcal bacterium, encapsulated by a polysaccharide structure.6
Six of the 12 know serogroups of N. meningitidis (A, B, C, Y, X, and W) cause the majority of epidemics worldwide.7,8
Background
N. meningitidis only infects humans.6 The bacteria are transmitted from person-to-person via aerosolized respiratory droplets or throat secretions.8
Ten percent to 20% of the population carries N. meningitidis in their throat at any given time.8
References
6. Pollard AJ. Meningococcal infections. In: Longo DL, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012; chapter 143.
7. Harrison LH. The epidemiology of meningococcal disease in the United States. Clin Infect Dis. 2010;50(Suppl 2);S37-S44.
8. WHO. Meningococcal meningitis. Accessed January 3, 2014.
Polysaccharide capsule6,9
*W-135 has been replaced with W per new nomenclature.11 6Pollard AJ. In: Harrison's Principles of Internal Medicine. 18th ed. 2012;chapter 143; 7Harrison LH. Clin Infect Dis. 2010;50(Suppl 2);S37. 8http:// 9Image adapted from Criss AK. Nat Rev Microbiology. 2012;10(3):178; 11Harrison OB. Emerg Infect Dis. 2013;19(4):566.

4. From carriage to invasive disease
Bacteria attach and multiply on mucosal cells of the nasopharynx1,2
In <1% of colonized persons, the organism penetrates mucosal cells and enters the bloodstream1
In 50% of bacteremic persons, the meningococcal organism crosses the blood-brain barrier into cerebrospinal fluid1
References: 1. van Deuren M, et al. Clin Microbiol Rev. 2000;13(1): CDC. Meningococcal disease. In: Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). Atkinson W, Wolfe S, Hamborsky J, McIntyre L, eds. 11th ed. Washington, DC, Public Health Foundation, 2009:

5. Meta-analysis of 89 Studies in 28 Countries16
Worldwide carriage rates are low during infancy and peak at 19 years of age16
Young adults are the most common source of transmission to the community17
Up to 10% of adolescents and adults are asymptomatic transient carriers18
Meta-analysis of 89 Studies in 28 Countries16
Prevalence (%)
Age 20 40 60 80
100
Fitted data
Range of 95% CI
Main Point
N. meningitidis carriage rates vary with age. The highest rate of carriage occurs in adolescents aged 15 to 19 years.16 Adolescents and young adults are the most common source of transmission in the community.17,18
Background
Rates of meningococcal disease vary geographically and tend to be higher in developing countries.19
Carriage rates are greatest in childhood, peak during adolescence, and wane during adulthood.16
While this pattern of bacterial colonization mirrors that of overt, invasive meningococcal disease, it must be emphasized that bacterial carriage does not correlate well with clinical disease. Further, unlike invasive meningococcal disease, carriage rates do not generally vary by season.20
Literature searches aimed at identifying papers reporting carriage of N. meningitidis in defined age groups in European countries or countries with a similar epidemiological pattern resulted in a total of 110 papers. Carriage prevalence as a function of age was modeled using mixed-effects logistic regression.16
Carriage prevalence increased from 4.5% in infants to a peak of 23.7% in 19 year olds, decreasing in adulthood to 13.1% in 30 year-olds and 7.8% in 50 year olds.
References
16. Christensen H, May M, Bowen L, Hickman M, Trotter CL. Meningococcal carriage by age: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(12):
17. Pelton SI. Prevention of invasive meningococcal disease in the United States. Pediatr Infect Dis J. 2009;28(4):
18. CDC. Meningococcal disease. In: Atkinson W, Hamborsky J, Stanton A, Wolfe C, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. (The pink book.) 12th ed. Washington DC: Public Health Foundation; 2012:
19. Khatami A, Pollard AJ. The epidemiology of meningococcal disease and the impact of vaccines. Expert Rev Vaccines. 2010;9(3):
20. Trotter CL, Greenswood BM. Meningococcal carriage in the African meningitis belt. Lancet Infect Dis. 2007;7(12):
16Christensen H. Lancet Infect Dis. 2010;10(12):853; 17Pelton SI. Pediatr Infect Dis J. 2009;28(4):329; 18CDC. In: Epidemiology and Prevention of Vaccine-Preventable Diseases. (The Pink Book.) 12th ed

6. Invasive meningococcal disease (IMD) is difficult to diagnose and might be rapidly lethal
Definitive diagnosis is challenging due to the aspecific “flu-like” early symptoms1
Rapid progression, with death in as little as 24 hours1,2
4–8 Hours1,2
Nonspecific
12–15 Hours1,2
Characteristic
15–~24 Hours1,2
Late
Fever, irritability, nausea or vomiting, drowsiness, poor appetite, sore throat, coryza, general aches
Hemorrhagic rash, neck stiffness, photophobia
Confusion or delirium, seizure, unconsciousness; possible death
Main Points
The early symptoms of invasive meningococcal disease appear flu-like in nature (eg, irritability, fever, loss of appetite) and tend to be nonspecific, which confounds definitive diagnoses.1
Characteristic, or tell-tale, symptoms manifest approximately 12 hours after initial presentation. However, this often leaves insufficient time for proper treatment, as death can occur as rapidly as within 24 to 48 hours of disease onset.1,2
Background
This schematic depicts a typical time course for meningococcal meningococcemia and meningitis and is based on a study of 448 children ≤16 years of age with invasive meningococcal disease.1
Most presented with nonspecific symptoms in the first 4 to 8 hours, but many were near death within 24 hours.
Hospitalization occurred a median of 19 hours after symptom onset, ranging from 13 hours in children <1 year of age to 22 hours in those 15 to 16 years of age.
More classic symptoms such as hemorrhagic rash and meningismus did not emerge until later (13 to 22 hours). In this report, 23% (103/448) of cases were fatal.
References
Thompson MJ, Ninis N, Perera R, et al. Clinical recognition of meningococcal disease in children and adolescents. Lancet. 2006;367(9508):
Branco RG, Amoretti CF, Tasker RC. Meningococcal disease and meningitis. J Pediatr (Rio J). 2007; 83(2 suppl):S46-S53.
Hospital admission at median of ~19 hours1
1Thompson MJ, et al. Lancet. 2006;367:397; 2Branco RG, et al. J Pediatr (Rio J). 2007;83(2 suppl):S46.

7. Morbi-Mortality related to Meningococcal disease
Rare and mostly sporadic disease
Affects all ages
Associated with significant morbidity and high fatality rates3
Main Points
Bacterial meningitis is a devastating disease that causes substantial mortality and morbidity.3
Causative bacteria are responsible for “worldwide epidemic meningitis and rapidly progressing fatal shock.”3
The incidence of meningococcal disease can vary from very rare to over 1,000 cases per 100,000 population every year.3
Case fatality rates range from 7% in high income to as high as 50% in resource-poor countries.4
The sporadic nature of meningococcal disease emphasizes the need for an effective disease prevention strategy using vaccines.5
References
3. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet. 2007;369(9580):
4. Van de Beek D. Progress and challenges in bacterial meningitis. Lancet. 2012;380(9854):
5. Keyserling H, Papa T, Koranyi K, et al. Safety, immunogenicity, and immune memory of a novel meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine (MCV-4) in healthy adolescents. Arch Pediatr Adolesc Med. 2005;159(10):
3Stephens DS, et al. Lancet. 2007;369(9580):2196.
92Photo reprinted with permission from Schoeller T, Schmutzhard E. N Engl J Med. 2001;344(18):1372. Copyright © 2001 Massachusetts Medical Society. All rights reserved.

8. Crowding6,13,14 (students, military, Hajj, oil refineries)
At-Risk Populations
Impaired immune system6,12/ lack of antibodies6
Exposure through close contact with infected person or the live bacteria6
Infants, children6,12
Travelers to endemic areas13
Caregivers13
Crowding6,13,14 (students, military, Hajj, oil refineries)
Immunocompromised12
6Pollard AJ. In: Harrison's Principles of Internal Medicine. 18th ed. 2012;chapter 143; 12Bilukha O. Pediatr Infect Dis J. 2007;26(5):371; 13MacNeil J. In: Manual for the Surveillance of Vaccine‐Preventable Diseases. 5th ed. 2012; 14Liphaus BL. Enferm Infecc Microbiol Clin. 2013;31(2):88.
CIRC.14/05/FGMS/814 – Approved 12 May 2014 10

9. Incidence rates of Invasive Meningococcal Disease Important variations across populations
[1] World Health Organization. Control of Epidemic Meningococcal Disease. WHO Practical Guidelines. WHO/EMC/BAC/ nd ed. Geneva, Switzerland, World Health Organization, Available at: Accessed April 12, [2] WHO. Wkly Epidemiol Rec 2003;78:294-6; [3] Wilder-Smith A, et al. Clin Infect Dis 2003;36:679-83; [4] Harrison LH, et al. JAMA 2001;286:694-9; [5] CDC. MMWR Recomm Rep 2000;49(RR-7):11-20; [6] Neal KR, et al. Epidemiol Infect 1999;122:351-7; [7] Brundage, JF, et al. Clin Infect Dis 2002;35: ; [8] Spiegel A, et al. Santé 1996;6:383-8; [9] CDC. MMWR Morbid Mortal Wkly Rep 2004;51(53):1-84; [10] Squires SG, et al. Can Commun Dis Rep 2004; 30:17-28; [11] European Union Invasive Bacterial Infection Surveillance network. Invasive Neisseria meningitidis in Europe Dec Available at Accessed April 12, 2005.

10. Meningitis belt Meningitis belt : 26 countries Epidemic season :
cases / habitants
November to June
Before 2010 :
Serogroup A : Large marjority of epidemics
View Larger Meningitis belt – Photo Courtesy of CDC
test

11. Meningitis Vaccine Project
Menafrivac introduction : 2010
The MenAfriVac vaccine is being rolled out across the 26 nations of Africa’s meningitis belt over the course of seven years.
Illustration: PATH/David Simpson.
test

12. INTRODUCTION OF VACCINATION AGAINST NEISSERIA MENINGITIDIS A INTO AFRICAN MENINGITIS BELT
Meningococcal A vaccine introduced into countries in African meningitis belt in phases.
We’re currently in the last phase of implementation and and countries like Kenya are to introduce the vaccine
Private sector vaccination with conjugate quadrivalent meningococcal vaccines already available in these countries
African meningitis belt has a substantial number of muslims who go for Hajj pilgrimage, where vaccination with a quadrivalent meningococcal vaccine is a requirement before entry into the country, due to high risk of transmission during the pilgrimage
References
– accessed 21 June 2018

13. Background The emergence of new serogroups MenAfriVac
M.M. Mustapha et al. Vaccine 34 (2016) 1515–1523
test

14. Neisseria meningitis serogroup C outbreak
Major meningococcal epidemics in sub-Saharan Africa over the past 40 years1
1 Mohammed I, Iliyasu G, & al. Pathogens and global health. 2017;111(1):1-6.
test

15. Serogroup Replacement
N.meningitidis serogoup distribution in Africa
African Meningitis Belt n=1 783
African Meningitis Belt n=3 211
DATE
1WHO Regional Office Africa. MDSC Meningitis Weekly Bull.2009;Week 27-31; 2NICD. Communicable Diseases Surveillance Bulletin. 2009;7(1)
2WHO/AFRO Inter country Support Tam for WestAfrica. Meningitis Weekly bulletin for the whole (weeks 1-52) , except for Nigeria (weeks 1-26)
test

16. Background: New NmC outbreak
Historical of this new outbreak
2013
2014
2015
Northwest Nigeria: new strain emerged
452 suspected case
Expanded rapidly: all regions
2845 suspected cases
Northwest Nigeria: other state
796 suspected case
Entered Niger: zz8502 suspected cases
test

17. Immunization can help prevent widespread meningococcal Infection
N. meningitidis responsible for epidemic and endemic disease41
Geographic and temporal variability41,19
Outbreak and spontaneous resolution41,34
Much disease is vaccine preventable5,42
Invasive meningococcal disease42
Rapid onset, with death possible within 24 hours of clinical presentation42
High mortality rates observed among those <5 years of age15
Main Points
N. meningitidis is responsible for epidemic and endemic disease that is both variable and devastating. The underlying epidemiology of invasive meningococcal disease varies from country to country—even those that share borders—and over time, with temporal shifts observed in the relative proportion of each serogroup contributing to disease burden.41,19
Vaccines against meningococcal disease have been around for more than 30 years and are the best source of prevention.5,42
Invasive meningococcal disease is devastating, with an ability to precipitate death in as little as 24 hours after clinical presentation and with debilitating sequelae, including limb loss.42 Sadly, the highest mortality rates are observed among those <5 years of age.15
References
Keyserling H, Papa T, Koranyi K, et al. Safety, immunogenicity, and immune memory of a novel meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine (MCV-4) in healthy adolescents. Arch Pediatr Adolesc Med. 2005;159(10):
Poland GA. Prevention of meningococcal disease: current use of polysaccharide and conjugate vaccines. Clin Infect Dis. 2010;50(Suppl 2):S45-S53.
19. Khatami A, Pollard AJ. The epidemiology of meningococcal disease and the impact of vaccines. Expert Rev Vaccines. 2010;9(3):
41. Apicella MA. Neisseria meningitidis. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2010:
42. Anonychuk A, Woo G, Vyse A, Demarteau N, Tricco AC. The cost and public health burden of invasive meningococcal disease outbreaks: a systematic review. PharmacoEconomics. 2013;31(7):
5Keyserling H. Arch Pediatr Adolesc Med. 2005;159(10):907; 15Poland GA. Clin Infect Dis. 2010;50(Suppl 2):S45-S53; 19Khatami A. Expert Rev Vaccines. 2010;9(3):285; 34Traoré Y. Clin Infect Dis. 2006;43(7):817; 41Apicella MA. In: Principles and Practice of Infectious Diseases. 2010: ; 42Anonychuk A. PharmacoEconomics. 2013;31(7):563.
CIRC.14/05/FGMS/814 – Approved 12 May 2014

18. Outbreaks and response
Vaccine stockpile 1
Managed by: International Coordinating Group
Emergency vaccine stockepile
Financial support:
Reactive mass vaccination campaigns remain an important pillar of meningitis outbreak response. are managed by the International Coordinating Group on Vaccine Provision for Epidemic Meningitis Control (ICG), with financial support from GAVI, the Vaccine Alliance.
In 2017, national authorities organized mass vaccination campaigns in response to the epidemics in Cameroon, Niger, Nigeria and Togo, with support from partners including the United States Centers for Disease Control and Prevention, Médecins Sans Frontières, the National Red Cross Societies, UNICEF and WHO. The ICG released 7200 doses of ACYW polysaccharide (PS) vaccine to Cameroon; doses of ACYW PS vaccine, doses of AC PS vaccine and doses of C conjugate vaccine to Nigeria; doses of AC PS, and doses of ACYW PS vaccine to Niger; and doses of ACW PS vaccine to Togo.
The expert group recommended that WHO and the ministries of health of countries in the meningitis belt should advocate with GAVI to increase the vaccine stockpile to meet a target of 5 million; develop a 5-year procurement strategy; reduce the cost of conjugate vaccines; and expedite trials of polyvalent conjugate vaccines (20). According to the latest data, the 2018 international emergency stockpile has just 2.5 million doses of the C containing vaccine (3). An additional 10 million doses are required to complement the stockpile for (3) The International Coordinating Group for vaccine provision (ICG) estimated the needs of the international stockpile at 5 million doses of serogroup C and W containing vaccines, preferably conjugate vaccines, for the 2018 epidemic season.
1 WHO. Epidemic meningitis control in countries of the African meninigitis belt Weekly epidemiological record. 2018;No 14, 2018, 93:
test

21. Reference: http://www. who
Reference: - accessed 15/06/2018

22. HEALTHCARE WORKERS
Reference: - accessed 15/06/2018

24. THANK YOU
FOR ANY SAFETY INFORMATION OR REPORTING OF ANY ADVERSE EVENTS KINDLY TO: