Current epidemiology of meningococcal disease

in the African meningitis belt and new WHO

outbreak response guidelines

Olivier Ronveauxronveauxo@who.int

Magnitude of the problem: 20 000 cases [7000 - 180000] of meningitis per year across the belt19

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Start of the MenA conjugatevaccine roll-out

Epidemiological picture has changed since MenA conjugate vaccine introduction

Incidence of confirmed meningitis by pathogenbefore 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)

NmW had become the No1 epidemic threat

Districts reporting NmW outbreaks, 2002 - 2013

Examples of seasonal Attack Rates (AR) of Nm W and Nm X at district level

Nm WAR / 100,000

Nm XAR / 100,000

Reference

Niger 2010 135 WHO UnpublishedBurkina Faso 2012 114 WHO UnpublishedThe Gambia 2012 142 Hossain et al

Niger 2006 28 Boisier et alKenya 2006 16 Mutonga et alTogo 2007 33 Delrieu et alBurkina Faso 2010 120 Delrieu et al

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

Meningitis incidence thresholds: improving vaccination timeliness

Alert ThresholdPreparedness

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

alertepidemic

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)

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

Antibiotic Treatment during outbreaks2014 Recommendation (3)

• Main issue: single dose vs 5 day courses of antibioticsImportant % 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

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

Meningitis Outbreak Response WHO guidelines 2014 revision

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

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sEpidemic 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 CNm WS.pn

The 2015 NmC epidemic: sharp and high15

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Suspected Meningitis Cases by Week, Niger – 2003-2015

Cumulative attack rate Niamey: 474/100 000Cumulative attack rate Niger: 46/100 000

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 2-15year old

– New vaccines brought in, not necessarily adapted to African context

< 2 2-4 5-14 15-29 30+0

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Niger, attack rates by age group (per 100 000)

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Diversity of vaccines used during the response, Niger 2015

Type (PS: polysaccharide) Quantity Origin

Tétravalent PS Menomune 28 000 National stockTrivalent PS Finlay 38 000 ICGTrivalent PS Finlay 180 000 ICGTrivalent 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

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

• 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 Tet0.032-0.125

0.5-1 0.006-0.032

0.006-0.064

64-128 <0.002 0.25-0.5

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

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

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

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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