Current epidemiology of meningococcal disease in the African meningitis belt and new WHO outbreak response guidelines after the Meningitis Vaccine Project http://www.meningitis.org/conference2015

1. Current epidemiology
of meningococcal disease
in the African meningitis belt
and new WHO
outbreak response guidelines
Olivier Ronveaux
ronveauxo@who.int

2. Magnitude of the problem:
20 000 cases [7000 - 180000] of meningitis per year across the belt
20 000
40 000
60 000
80 000
100 000
120 000
140 000
160 000
180 000
200 000
1985
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1991
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1999
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2003
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2013
2014
2015
Suspected cases
Start of the MenA conjugate
vaccine roll-out

3. Epidemiological picture has changed
since MenA conjugate vaccine introduction
Incidence of confirmed meningitis by pathogen
before and after the introduction of Men A conjugate
2004 - 2010
2011 - 2013
From countries contributing data to WHO/IST each year between 2004 and 2013
(Benin, Burkina Faso, Chad, DRC, Ghana, Ivory Coast, Mali, Niger, Nigeria, Togo)

4. NmW had become the No1 epidemic threat
Districts reporting NmW outbreaks, 2002 - 2013

5. Examples of seasonal Attack Rates (AR)
of Nm W and Nm X at district level
Nm W
AR / 100,000
Nm X
AR / 100,000
Reference
Niger 2010 135 WHO Unpublished
Burkina Faso 2012 114 WHO Unpublished
The Gambia 2012 142 Hossain et al
Niger 2006 28 Boisier et al
Kenya 2006 16 Mutonga et al
Togo 2007 33 Delrieu et al
Burkina Faso 2010 120 Delrieu et al

6. WHO Guidelines revision, 2014
Rationale: changing epidemiology
• MenA conjugate vaccine roll out, NmA disappearing
• Cases due to other Nm (eg NmW) and Spn continue
• Epidemics of lower magnitude
• Falling overall incidence
4 selected issues for review
• Current thresholds may be too high
• Diagnostic: identifying the causal agent becomes more important
• Single dose treatment may no longer be appropriate
• Prophylaxis of case contacts might be considered

7. Meningitis incidence thresholds:
improving vaccination timeliness
 Alert Threshold
Preparedness
 field investigation
 surveillance strengthening
 serogroup identification
 vaccination microplans
 Epidemic Threshold
Action
 immediate mass vaccination
 case management strengthening
 longitudinal lab surveillance
Weekly surveillance - suspected case attack rates at district level
alert
epidemic

8. Thresholds: 2014 Recommendations (1)
• Main issue: more benefit from shortening the response time
than from lowering the threshold
• 4 week interval:
• 17 cases per event prevented at a threshold 10 cases / 100 000
• 46 cases per event at a threshold of 3/100 000.
• 2 week interval:
• 54 cases per event prevented (threshold at 10)
• Main changes from previous guidelines:
(i) Implement vaccination campaigns as soon as possible, and within 4 weeks of
crossing the epidemic threshold (previously time not specified)
(ii) Use lower thresholds in populations 30,000 – 100,000
Alert threshold: 3 cases / 100,000 / week
(previously 5)
Epidemic threshold: 10 cases / 100,000 / week
(previously 10 if at risk, otherwise 15)

9. Rapid Diagnostic Tests (RDTs)
2014 Recommendations (2)
(i) RDTs (latex agglutination or dipsticks) recommended in outbreaks
(ii) If RDTs positive for a vaccine preventable serogroup, verification by
PCR or culture recommended before vaccine response
(iii) Need
– To promote development of more affordable dipsticks
– To promote development of NmX dipstick
– To do more field evaluations of all tests
Picture courtesy of

10. Antibiotic Treatment during outbreaks
2014 Recommendation (3)
• Main issue: single dose vs 5 day courses of antibiotics
Important % of cases due to Spn and Hib in NmW epidemics (9%)
• Main changes from previous guidelines:
For adults and children >=2 months of age
5 days ceftriaxone recommended (previously single dose)
For suspected bacterial meningitis in children <2 months of age
7 days ceftriaxone recommended (No change)
In large meningitis epidemics confirmed due to Nm,
single dose ceftriaxone can be used
Oily chloramphenicol not recommended anymore

11. Prophylaxis: 2014 Recommendation (4)
• Main issue: uncertain effectiveness of prophylaxis in
meningitis belt
• Main changes from previous guidelines:
(i) Antibiotics recommended as a prophylactic measure for household
contacts of all ages in non-epidemic periods, but not during epidemics
(No change)
(ii) Ciprofloxacin preferred, with ceftriaxone as an alternative
NB, 2015 findings: Case households at higher risk than others during NmC outbreak

12. Meningitis Outbreak Response
WHO guidelines 2014 revision

13. An unexpected re-emergence: NmC
 Epidemics due to serogroup C (NmC) have been rare in the
meningitis belt
 Prior to 2013, the last reported NmC epidemics were reported in the
1970s in Burkina Faso (539 cases) and Northern Nigeria (133 cases).
 Since 2013: observed in one particular area with expanding
tendency

14. 0
500
1,000
1,500
2,000
2,500
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
Cases
Week
Epidemic of serogroup C meningitis
Niger, January – June 2015
• 8,502 suspected meningitis cases
• 1,456 of 4,039 CSF PCR positive.
1087; 79%
196;
14%
101, 7% Nm C
Nm W
S.pn

15. The 2015 NmC epidemic: sharp and high
15
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Cases
Year
Suspected Meningitis Cases by Week, Niger – 2003-2015
Cumulative attack rate Niamey: 474/100 000
Cumulative attack rate Niger: 46/100 000

16. Ouallam district
Major challenges, NmC epidemic, 2015
• Statistics
– Official case counts and CFRs (6-7%) underestimated
• Niger, 2015: probably > 9000 cases
• Nigeria 2015: probably > 5000 cases (official 2845 cases)
• Laboratory capacity
– Nigeria: only 51 samples confirmed
• Outbreak response: vaccine availability
– Delayed response
– Limited to 2-15
year old
– New vaccines brought in, not necessarily adapted to African context
0
20
40
60
80
100
120
< 2 2-4 5-14 15-29 30+ in years
Niger, attack rates by age group
(per 100 000)
0
10
20
30
40
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60
11 12 13 14 15 16 17 18 19 20 21 22 23
campaign

17. Diversity of vaccines used during the response, Niger 2015
Type
(PS: polysaccharide)
Quantity Origin
Tétravalent PS Menomune 28 000 National stock
Trivalent PS Finlay 38 000 ICG
Trivalent PS Finlay 180 000 ICG
Trivalent PS Finlay 82 500 ICG
Tétravalent PS Menomune 200 000 Mali (loan)
Trivalent PS Finlay 160 000 ICG
Menactra conjugate 200 000 ICG
Tetravalent PS Mencevax 500 000 ICG
Total 1 388 500
ICG: International Coordinating Group on Vaccine Provision for Epidemic Meningitis Control

18. Vaccine Supply - a chronic shortage
Vaccine requested to and sent by the ICG, by type of vaccine, 2007-2013

19. • NmC strains have the same molecular profile, Niger and Nigeria
• Antibiotic susceptibility
Molecular features of NmC, 2013-2015
Serogroup PorA FetA ST ST-complex
C 21-15,16 F1-7 10217 UA
PenG Chlor Cipro Rif Sulfa Ceftr Tet
0.032-
0.125
0.5-1 0.006-
0.032
0.006-
0.064
64-128 <0.002 0.25-
0.5

20. W
Relationships of ST-10217 to other
serogroup C African isolates
Genetically unrelated to the epidemic clones
causing disease in Africa in the past decades or
to the rare serogroup C isolates that have
circulated since the 1980s
Courtesy of Dominique Caugant

21. 2016: NmC expansion risk is high
• Unique clone, genetically distinct
from previous disease strains
• Low immunity to C expected
• Increasing numbers
each year 2013 to 2014 to 2015
• Similar epidemic pattern
to NmA epidemics

22. Coincidence or consequence?
Geneva, October 2015, expert group conclusions:
– Likely due to natural evolutionary changes in the bacterial
population
– Probably not due to serogroup replacement
• NmA carriage outside epidemics before the introduction of MenA
conjugate vaccine was usually not detectable or at very low levels,
leaving little opportunity for replacement of the bacterium in its
ecological niche;
• large and rapid fluctuations in serogroup/strain distribution are known
to occur in absence of vaccine intervention;
• the NmC outbreak strain is a completely new clone
• NmC emergence in Nigeria before the campaign
– Likely not associated with the elimination of Nm A epidemics
following introduction of MenA conjugate vaccine

23. Conclusions
• Non A serogroups continue to be a threat in Africa
• Unprecedented NmC epidemic
– Risk of further regional expansion of this new NmC strain
 adequate global supply of C containing vaccine for
epidemic response
 country preparedness to be strengthened, in particular
the laboratory confirmation component
• 2014 guidelines recommendations applicable to NmC
– Prophylaxis to be further explored
• Development of an affordable, multivalent conjugate
meningococcal vaccine to be accelerated
23