Implications of epidemic pneumococcal meningitis in meningitis belt countries https://www.meningitis.org/mrf-conference-2017

1. Implications of epidemic pneumococcal
meningitis in meningitis belt countries
James Stuart
University of Bristol
London School of Hygiene and Tropical Medicine
World Health Organization
MRF Conference, London
November 2017

2. Bacteriological profile of confirmed meningitis cases
in the African belt 2003-2017
Predominance
of non NmA
after 2010
(Introduction
of MenA)
In 2017:
NmC (35%)
Spn (27%)
NmX (13%)
increasing
NmW (10%)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
(Week
30)
NmA NmB NmW NmC NmX NmY Other Nm S.pneumoniae Hib Other Pathogens
WHO Intercountry Support Team, West Africa

3. Epidemic of pneumococccal meningitis
Ghana 2016

4. Epicurve as of February 15, 2016:
All cause meningitis
1 Dec 15
1 Jan 16
15 Jan
15
23 Jan 15
2 Feb 2016
9 Feb 16
Ghana Health Services

5. Meningitis caseload by district,
Ghana 1 Dec 2015 - 2 Mar 2016
Ghana Health Services
Upper West
NmW
Brong Ahafo
Spn

6. Comparing two districts (popn 100,000)
Wenchi, Brong Ahafo, (23/24 confirmed Spn)
Jirapa, Upper West (18/24 confirmed NmW)
0
5
10
15
20
25
30
51 52 53 1 2 3 4 5 6 7 8 9 10 11
Wenchi
Spn
Jirapa
NmW
Alert threshold
Epidemic threshold
Ghana Health Services

7. Pathogens by age
Ghana Dec 2015 - Feb 2016
Ghana Health Services

8. Brong Ahafo
• 104 Spn/135 confirmed meningitis cases
• Largest outbreak of pneumococcal meningitis to date (886 suspected
cases)
• 80% Spn serotype 1
• 59% Spn cases aged 5-29 years
• Case fatality among all Spn cases 24%
• Six districts with weekly attack rates >10/100,000
• PCV-13 into infant immunisation programme in 2012, coverage 84% in
2013 to 95% in 2015.
Kwambana-Adams BA, BMC Infect Dis, 2016

9. Epidemiology of pneumococcal meningitis in the
meningitis belt
• Many similarities to meningococcal meningitis
– incidence in dry season 10x wet season
– majority of cases in older children and adults
• Previous outbreaks: Burkina Faso 2009 &2011, Chad 2009, Ghana 2010
• Outbreaks of pneumococcal meningitis confined to this region of Africa cf
outbreaks in other countries that are smaller scale and predominantly pneumonia &
bacteraemia
• High burden outside epidemics
– >25% of confirmed meningitis cases in the belt are Spn,
– 53% (1528 Spn/2858 confirmed) in Burkina Faso 2011-13 (45% serotype 1)
– high case fatality ratio of Spn meningitis (20% - 60%)
– severe sequelae

10. Issues raised by Brong Ahafo outbreak
• Large Spn outbreak outside traditional meningitis belt
• NmW and Spn predominant in different parts of the country
• Delays in laboratory confirmation (lack of RDTs, insufficient reference lab
capacity)
• Lack of guidance for Spn outbreaks (definition, case treatment,
chemoprophylaxis)
• Mass vaccination in NmW outbreaks. Why not pneumococcal vaccine in
Spn outbreaks?
• Infant vaccination schedule 3+0. Could 2+1 regime lead to herd protecton
and reduce risk of outbreaks?

11. Rapid diagnosis
• Challenging to identify Spn outbreaks especially if mixed with Nm
• Rapid diagnostic test mainly used in meningitis belt is latex agglutination
test (Pastorex): high cost, limited heat stability, not serotype specific
• Immunochromatographic tests (ICT) preferable: easy to use, heat stable
– Binax, good performance on CSF, Spn only, expensive
Implications
– Improved RDTs needed
– New ICT on trial (WHO)

12. Antibiotic treatment
• WHO recommends 5 days (7 days in children <2/12) treatment of
suspected bacterial meningitis with ceftriaxone during outbreaks of
meningococcal meningitis
• Duration for children based on GRADE review (low quality evidence)
• Longer courses (10-14 days) normally recommended for Spn meningitis
Implications
• New recommendation for suspected cases of bacterial meningitis in
pneumococcal outbreaks or for confirmed Spn cases
– Extend ceftriaxone treatment up to 14 days if clinical condition not
improving
Chemoprophylaxis to household members not recommended given lack of
data on risk or benefit

13. Reactive Vaccination
No guidance for use of PS or PCV vaccines in mass campaigns for
pneumococcal meningitis outbreaks
Implications
• Need for guidance
but
– mass campaigns inefficient, often late in outbreak but recommended
for outbreaks of meningococcal meningitis
– duration of pneumococcal outbreaks, thresholds set for action, age
groups affected would all affect numbers of preventable cases &
deaths
– logistic challenges: vaccine cost, availability, stockpile

14. As reactive vaccination inefficient, how about
preventive vaccination?
• PCV 10 and PCV 13 introduced or being introduced into infant schedule across
meningitis belt as 3+0 schedules (no booster). Alternative schedule 2+1 (with
booster). Both vaccines include serotype 1
• Direct protection: Low attack rates in Ghana in vaccinated age groups
• No suggestion of indirect protection in older age groups in this outbreak nor in
one study from The Gambia using 3+0
Do 2+1 schedules offer higher chance of persistent carriage reduction and herd
protection (South Africa)?
• Current SAGE view: no evidence to recommend one schedule over the other
• Meningitis belt countries at high risk of pneumococcal meningitis in older age
groups, so herd protection important.
Should meningitis belt countries switch to 2+1 schedule?
Should older age groups be immunised in mass campaigns for direct protection?

15. Epidemic pneumococcal meningitis in the belt:
Implications
• Need for
– Heat stable RDTs including Spn in addition to NmW, NmC, NmX, NmY.
– Extension of antibiotic treatment in Spn epidemics
– More evidence on duration of antibiotic treatment for cases
• Reactive vaccination imperfect, but pneumococcal meningitis high risk of
death and disability. Can we deny use of an effective vaccine for outbreak
control when PCV already in country?
• Preventive vaccination should have high priority. Even without conclusive
evidence, will moving to infant schedule with a booster at around 12
months be more likely to offer herd protection at same cost?
• How about mass preventive campaigns with PCV10/13 or a monovalent
conjugate serotype 1 vaccine?

16. Acknowledgements
• Ghana Health Services: Franklin Asiedu-Bekoe
• WHO Country Office, Ghana: Charles Okot
• WHO : Olivier Ronveaux, Katya Fernandez
• University of Cambridge: Laura Cooper, Caroline Trotter