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Quote “These are my principles.  If you don’t like them ‐ I have others”. Groucho Marx

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Page 1: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Quote

• “These are my principles.  If you don’t like them ‐ I have others”.

• Groucho Marx

Page 2: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Analysis of the Auckland 2014 Measles Outbreak Indicates that Adolescents and Young Adults could 

Benefit from Catch up Vaccination.

• Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins 

• In Press NZ Medical Journal

• Auckland Regional Public Health Service, Private Bag 92605, Symonds Street, Auckland 1150, New Zealand

Page 3: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Measles Outbreak Auckland, NZ 2014

• December 2013 to June 2014• Epidemiology• Immunology• Vaccinology

• Aim : To analyse the Measles 2014 outbreak in Auckland to guide future preventive measures

Page 4: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In
Page 5: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

A contagious disease…

Source: http://www.healthline.com/health/r‐nought‐reproduction‐number#Conditions4

Page 6: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Background

• Measles is highly contagious (Ro = 12‐18)• Burden of disease in developing countries• Declined markedly in western countries –after  mass vaccination campaigns with MMR

• 45 years of MMR vaccine ‐measles and its complications still persist

• Australia – (But not NZ) is declared by WHO “measles free”

• Notifiable in NZ since 1996

Page 7: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Imported measles common

Page 8: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

The MMR

• Highly efficacious and safe vaccine• Live vaccine so no boost required • Second dose improves efficacy from 90 to 95%• NZ schedule 15 months and 4 years • Under 1 year – interference circulating maternally derived antibodies

• Modeling shows over 95% coverage required to eliminate disease

• Historical unjustified controversy since 1998 

Page 9: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Methods

• The setting • Auckland (1.4 million)• Essentially Indigenous Measles free

• The Method• All Measles Notifications go to Public Health Services• Each notification is assigned to PH Nurse• Collect clinical information, immunisation history and immune status 

Page 10: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Methods: The diagnosis of Measles

Confirmed Probable Under investigation

Not a case

Laboratory results consistent with measles ORFever ≥ 380Cand a generalised maculopapular rash and: cough or coryza or conjunctivitis or Koplik’s spotsand link to confirmed case

Fever ≥ 380Cand a generalised maculopapular rash and: cough or coryza or conjunctivitis or Koplik’s spots

Note: No link to confirmed case Lab work not needed

All measles notifications with outstanding diagnostic lab results

No clinically compatible illnessORLaboratory results not consistent with measles infectionORDiagnosed vaccine reaction

Page 11: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Methods

• Outbreak coordination• Initiated case management• Contact tracing (Waiting rooms, schools, sport clubs, flights)

• Management of households• Identified high risk contacts of cases• Quarantine, Self isolation, Prophylaxis (Active and Passive Immunisation) as appropriate

Page 12: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Methods

• Laboratory analysis• PCR if symptoms in the first 5 days• Thereafter serology (anti‐measles IgM and IgGdetection)

• Purely qualitative detection  of anti measles IgM and IgG

• Serology was also requested for exposed contacts to establish immune status

• 1 sample from each linked chain of transmission –genotyped (National Measles Lab)

Page 13: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Statistical Analysis

• Vaccine effectiveness (VE) was calculated using the screening method (Gail) 

• Vaccine effectiveness=1‐ odds(vaccinated |case)odds(vaccinated| non‐case)

• Where: – odds(vaccinated | case) is  the odds of being vaccinated against measles, among cases.

– odds(vaccinated | non‐case) is the odds of being vaccinated against measles, in the general population.

Page 14: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Results

• First case visited Sydney• Later Genotyped and linked to a traveller to same international camp in the Philippines

• Total 113 Cases in the Auckland region • 13 of which were imported cases • 9 had travelled to the Philippines• 16/18 local cases linked to known imported cases• 82 (73%) were linked to either sporadic or imported cases

Page 15: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

The number of measles cases overseas and locally acquired in the 2014 Auckland outbreak showing a local peak in March 2014.  There is a temporal seeding of local cases from people 

travelling to New Zealand from overseas

Month (2014)

Cou

nt

0

10

20

30

40

50

Jan Feb Mar Apr May Jun

Overseas

Jan Feb Mar Apr May Jun

Local

Page 16: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Results

• Cases peaked in March 2014• Temporal seeding of local cases from overseas• Majority of cases occurred in adolescents and young adults

• 41/113 (36.3%) in 15‐19 year age group• 27/113 (23.4%) in 10‐14 year age group

Page 17: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

The numbers of confirmed and probable measles cases overseas and locally acquired by age, showing peaks in the under 1 and adolescent age groups.

Cou

nt

0

10

20

30

40

Overseas

0 10 20 30 40

Local

Page 18: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Results

• Among cases 44/113 (38.9%) occurred in the unimmunised

• 36/113 (31.8%) unknown immune status• 16/113 (14%) occurred in infants too young to vaccinate

• 17/113 (15%) had received one or two doses of vaccine

Page 19: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Age appropriately immunised Unimmunised

2014 Surveillance Year Measles Cases by Immunisation StatusConfirmed and Probable Cases only

Unknown / Uncertain

Unimmunised

Too young

First MMR post exposure

Age appropriately immunised (1 dose)

Age appropriately immunised (2 doses)

Extract Date:  1/07/2014

Source: NDCMS Index Case records

Page 20: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Incidence by age & ethnic group

0.0

5.0

10.0

15.0

20.0

25.0

30.0

0 to 4 5 to 14 15 to 24 25 to 44 45 to 64

Incide

nce rate (p

er 100

,000

)

Age category (years)

  European or Other ethnicity

  Maori

  Pacific peoples

Asian

Page 21: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Results

• Of the total cases 26/113 (23%) required hospital treatment

• Secondary cases linked by contact at 1 school (n=37)

• Household contact (n=29)• Social contacts (n=8)• Primary care (n=3)• Hospital (n=5)

Page 22: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Results‐Contacts

• 3113 Contacts were traced by ARPHS• Immune status established by ‐

• Documented 2x MMR vaccination history• Or proven Serology• n= 2,594• Highest non immune gp was under 1 year olds 68/75 ; 90.7%)

• Non immune 20‐29 year olds (60/ 325; 18.5%)• Non immune 15‐19 year olds (28/186; 15.1%)• Non immune 10‐14 year olds (22 /149; 14.8%)

Page 23: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Results – Contacts 

• Contacts underwent serological (IgG) testing• N= 737• Tested negative median age 27.4• Tested equivocal median age 26.6• Tested positive median age 34.0

• Serological immunity lower in people aged 10‐24 years

Page 24: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Proportion of tested exposed contacts who were either serologically immune or equivocal, by age (n=737; 597 positive, 57 equivocal and 83 negative).

0.00

0.25

0.50

0.75

1.00

< 1 1 to 4 5 to 9 10 to 14 15 to 19 20 to 24 25 to 29 30 to 39 40 plus

Age group (years)

pg

yq

Page 25: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Serological testing of contacts

0.00

0.25

0.50

0.75

1.00

< 1 1 to 4 5 to 9 10 to 14 15 to 19 20 to 24 25 to 29 30 to 39 40 plus

Age group (years)

pg

yq

Proportion immune or equivocal

Page 26: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

The contacts

101 247 203 163 240 455 475 465 7790

10

20

30

40

50

60

70

80

90

100

 <1  1 to 4  5 to 9 10 to 14 15 to 19 20 to 29 30 to 39 40 to 49 +50

Prop

ortio

n of Im

mun

e Expo

sed Co

ntacts

Age Group

Proportion of exposed contacts who were assessed as immune

Source: NDCMS Exposed Contacts records

Exposed contacts with assessed immune status showing 95% Confidence Intervals and total number in each group

Extract Date: 1/07/2014

Page 27: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Vaccine Effectiveness Calculation

• 60/113 (53%) Unimmunised• 16 were less than 15 months (too young)• 44 known unimmunised • 36 unknown vaccine status • Prevalance of vaccination 90%• VE if 36 unknown vaccinated = 89%• VE if 36 unknown unvaccinated = 98%• VE Range = 89‐98%

Page 28: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Discussion

• Adolescents are susceptible• So are the under 1 year olds • MOH figures 400,000 in NZ from a population of 4 million (10%) 

• The MMR vaccine is safe and effective 89‐98%• Reasons previous poor uptake due to safety concerns and structural issues with delivery

• Effective cold chain did not start until 2004 in NZ• ?waning immunity low immunity without natural boosting

Page 29: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Limitations of this Analysis

• It is only one part of an outbreak • Countrywide 280 cases

• Relative small numbers affecting power• Lack of Quantitative Serology Analysis

Page 30: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Conclusion

• Rapid expansion of Outbreak likely due to• Unimmunised European adolescents and young adults in a close contact environment ‐ school

• Measles is highly contagious nature of disease

• Outbreaks will likely continue until coverage is improved in at risk groups (up to 30 years)

• Most secondary cases occurred at school and were bought home 

Page 31: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Recommendations

• Early prompt reporting • Check all adolescence have 2x recorded MMR• ?Use of Dose 0 for under 1 year olds• ? A targeted Catch up campaign

Page 32: Friday Gary Reynolds 1.30pm - Immunisation Advisory Centre · • Gary Reynolds, Cassandra Dias, Simon Thornley, Ronald King, Angela Matson, Anne Morrison & Richard Hoskins • In

Acknowledgements

• Richard Hoskins• Simon Thornley • Cassandra Dias• Angela Matson• Anne Morrison• Ronald King• Staff at ARPHS