Emergence of a virulent new meningococcal W sequence type 11 in

South America: experience, control measures and impact

Marco Aurélio P. Sáfadi, MD, PhDFCM da Santa Casa de São Paulo

Outline • A brief overview of the current epidemiology

of MD in Brazil, Argentina and Chile.• The emergence of the serogroup W ST-11 cc

(“South American” strain).• Control measures implemented and lessons

learned

Annual number of cases and Incidence of Invasive Meningococcal Disease: Latin America, 2008-2011.

Notified incidence rates/100,000

persons

Safadi M. et al. Epidemiol and Infect, 2012

Not reported<0.3

> 10.3 to 1

0

500

1000

1500

2000

2500

3000

Argentina Brazil Chile Uruguay Mexico Colombia Venezuela

Annual number of cases

0,9

0,4

0,4

1,5

0,33

4

Year

Fonte: A. Lutz/SINAN

%70%

19%

7,5%3%

Meningococcal Disease: Distribution by Serogroup. Brazil, 1990 - 2014

ST-103cc

Brazil started MenC conjugate vaccination of all children <2 years of age in 2010.

• Infant immunisation (3 and 5 months) with booster dose at 12 months.

• Children between 12 and 23 months: 1 dose• No catch up campaign in older age groups

Safadi M, et al. JPIDS. 2014;3:91-93.

Incidence rates before and after routine Men C vaccination. Brazil, 2008-2014

Cases/100,000

Early impact on incidence rates of meningococcal disease observed only in the age groups targeted for vaccination.

Safadi M, et al. JPIDS. 2014;3:91-93.

Prevalence of carriage by serogroup

High carriage rates for serogroup C among adolescents of all age groups

Moraes JC; et al. Ped Infect Dis J, 2015

9.2 8.9

12.9

0

2

4

6

8

10

12

14

11- 13 years 14 - 16 years 17 - 19 years

Prevalence of carriage. N=1,200 adolescents

N=45/487 N=40/450 N=35/271

8

J Infect, 2008Journal of Infection, 2008

North

Southeast

South

WestCenter

Northeast

Case Fatality Rates of MD. Brazil 2001-2014

MCC

MM + MCC

MM

• Unacceptably high CFR for serogroup W cases (26%)

0

10

20

30

40

50

60

70

80

90

100B C Y W135

%

Year

%

49%

47%

3%

1%

Epidemiology of Meningococcal Disease in Argentina.

Servicio Bacteriología Clínica. INEI-ANLIS C.G. Malbrán /SIREVA 2015

Incidence rates of MD, Argentina, 2006-2014

in 2006, there were only four invasive MenW isolates detected in Argentina, increasing to 63 in 2010, 73 in 2011 and 96 isolates in 2012

Age group distribution of MD cases. Argentina.• Only 6% of the MenB cases occurred

in adults older than 30 years of age vs. 21% of the MenW cases.

Debbag R et al . ESPID, 2015

Epidemiology analysis of MD in Argentina. 2012 - 2014

• 848 cases. Incidence rate of 0.7 /100,000 hab.• 43.3% (368) < 2 years, 78.8% < 1 year.• I.R. in infants: 14.7/100.000; 1-4 y: 2.8/100,000. • serogroup W 50% and serogroup B 41%.• Argentina decided to implement ACWY-CRM

vaccine in infants (3,5 and 15 months). Adolescents with 11 years will receive one dose

Rancano C et al. SADI, 2015

Incidence rates and CFR of Meningococcal Disease in Chile. 1990-2012

Increased incidence of MD in 2012 (from 0.4 to 0.8), associated to emergence of serogroup W (3 cases in 2010, 20 in 2012 and 60 in 2012).

http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf

CFR

(%)

Inci

denc

e ra

tes

(per

100

,000

hab

)

2008

%

0

15

30

45

60

75

90

2000 2002 2004 2006

24%

2%

Meningococcal Disease: Distribution by Serogroup. Chile, 1999 - 2014

73%

Serogroup BSerogroup CSerogroup W

Fuente : Instituto de Salud Publica Lab. Referencia Fuente : Instituto de Salud Publica Lab. Referencia Neisseria Neisseria Chile week 42, 2014.Chile week 42, 2014.

2010 20121998 2014

Age group distribution of MD cases. Chile, 2011 - 2014

The proportion of MenW cases in older adults is significantly higher when compared to the MenB cases

Serogroup B casesSerogroup W cases

Boletín ISP, Vol 4, N° 9, September 2014

Case fatality rates of serogroup W MD by age group. Chile, 2010 - 2013

Moreno G. Rev Chilena Infect 2013

Increasing CFR according to age and overall CFR as high as 28% associated to serogroup W (compared to 14% for serogroup B and C cases).

Reactive MenW Immunisation action in Chile

http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf

• An immunisation campaign started in 2012 with the tetravalent conjugate vaccine (Men ACWY), initially targeting children aged 9 months to < 5 years.

• 9 m to < 2 y: 2 doses (MenACWY-DT) and > 2 y: 1 dose (MenACWY-CRM).

• Approximately 1 million children vaccinated (Coverage >95%).

• From 2014: 1 dose (MenACWY-TT) in toddlers at 12 months.

Vaccine effectiveness of MenACWY-D: Case-Control Study in US Adolescents*

Cases (N=157)*Controls (N=180) VE (95% CI)

Vaccinated <1 year 82% (54%-93%)

Vaccinated 1-2 years 80% (52%-92%)

Vaccinated ≥3-6 years 59% (5%-83%)

McNeil J et al. IPNC, 2012

Impact of the Impact of the MenACWY immunisation campaign in Chile, 2012-2014Chile, 2012-2014

Inci

denc

e ra

tes

(cas

es/1

000)

ISP, Chile]

58% reduction

• Reduction of 58% in the incidence rates of MD in children aged 1- 5 years• No impact on incidence rates of other age groups

Age (years)http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf

Pre-vaccine

Post-vaccine

Number of cases of MD. Chile, 2010 - 2014

0

20

40

60

80

100

120

140

160

2010 2011 2012 2013 2014

W

Others

Vaccination

Number of cases of serogroup W MD. Chile, 2010 - 2014

0

20

40

60

80

100

120

2010 2011 2012 2013 2014

W

Vaccination

Incidence rates of Meningococcal Disease in Chile. 2014

http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf

Incidence (2014): 0.8 /100,000 hab. Santiago – 1.1/100,000Number of cases of W in 2014: 99CFR: 19%

Gobierno de Chile / Ministerio de Salud 23

Carriage study – Chile, 2013

N= 4,217 adolescents, 10-19 years

Strains (N)

Prevalence (%)

24

What do you, in UK, have to do with the South-American situation?

Jay Lucidarme et al. Journal of Infection 2015An expanding South American/UK MenW strain was distinct from the ‘Hajj outbreak’ strain.

Mustapha M et al. Ebio Medicine, 2015:These data also demonstrate the co-circulation of W ST-11 strains in South America, UK and other regions that are phylogenetically and antigenically distinct from the Hajj clone

25

Laboratory-confirmed cases of invasive meningococcal disease by capsular group in UK, 2000 – 2014.

Ladhani S et al. CID, 2015

• A quarter of cases occurred in children aged <5 years, and half the cases in adults aged ≥45 years.

• 49% of the cases presenting with septicemia• CFR of 13%

26

UK decision

• In the light of the rapidly increasing W (cc11) disease from 2009/10 to 2014/15, ACWY conjugate vaccine will be used from August 2015 in 14-18 years teenagers and university freshers and is intended to induce herd protection.

27

• A hypervirulent MenW cc11 strain that became endemic in South America is now expanding in UK

• The experience in Chile showed that no early impact was observed in unvaccinated age groups with the reactive ACWY vaccination program including only young children.

• We have to acknowledge that unlike serogroups A, C and Y we do not have available data showing impact of serogroup W conjugate vacines on carriage to predict the magnitude of indirect effects of vaccination programs.

Key Points

28

The South American-UK connection is now elucidated!