Critical immunity thresholds for measles elimination

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1 Critical immunity thresholds for measles elimination Sebastian Funk Centre for the Mathematical Modelling of Infectious Diseases London School of Hygiene & Tropical Medicine 19 October, 2017!"vöå"!(}å!öZ&! u'öz"u'ü!'o! u},"oo]vp!of! ]v("!ü}µê!,]ê"'ê"ê

2 Outline 1.Background Immunity targets for measles Age-specific contact patterns 2.Results Immunity profiles and elimination Comparison to serological profiles 3.Conclusions and recommendations

3 1. Background

4 Background - When the number of secondary infections generated by each infective person is less than 1, transmission will stop. - To achieve this for measles, the population immune needs to be 93-95%, the herd immunity threshold. - This is based on two assumptions: 1. homogeneous mixing among individuals 2. stationary, uniform immunity (through vaccination)

5 Basic Reproduction number R Measles R = Herd-immunity threshold: Vaccinate at least so many that R = 1 Measles: 93-95% (randomly mixing population) Limitations: Population immunity reflects vaccination and case history Mixing (person-to-person contact) is age-dependent

6 Measles immunity profile (e.g., UK) Cases + vaccination Seroprevalence 100% Cases per year 600, , ,000 Cases MCV1 MCV Vaccine coverage [%] Proportion seropositive 95% 90% 85% 80% % Age group Andrews, 2008 Question: Which levels of immunity are required for elimination?

7 Vaccination vs immunity targets Vaccination target Vaccinate (e.g. 95%) in each birth cohort. Immunity target Aim for age-specific levels of immunity, including past birth cohorts.

8 Target immunity levels for measles WHO European Region 100% Immunity 95% 90% 85% 80% Age Ramsay, 1997 Question: Are these appropriate? If yes, in which settings?

9 Age-specific differences in contacts Mossong et al., 2008

10 100% + Immunity 95% 90% 85% 80% Age Calculate R from mixing pattern and given immunity levels

11 Contact data used in this study

12 2. Results

13 Results: homogeneous vs age-specific mixing Elimination Outbreaks possible Germany Italy Poland United Kingdom Netherlands Finland Uganda Viet Nam Taiwan Germany Italy Poland United Kingdom Netherlands Finland Uganda Viet Nam Taiwan R homogeneous age specific only takes into account differences in demography takes into account observed age-specific contact patterns Plot shows effective reproduction number R if countries had immunity levels according to current target levels.

14 Results: scenarios Immunity added Immunity removed Immunity 100% 95% 90% 85% 80% Finland Germany Italy Netherlands Poland Taiwan Uganda United Kingdom Viet Nam A B C D E F R Plot shows effective reproduction number R if countries had immunity levels as shown at the top.

15 Finding gaps in immunity: serology Serology 100% 90% 80% 70% 60% Belgium Cyprus Czech Republic Hungary Proportion imune 100% 90% 80% 70% 60% 100% 90% 80% 70% 60% Ireland Israel Latvia Lithuania Luxembourg Malta Romania Slovakia 100% 90% 80% 70% 60% Slovenia Spain Sweden United Kingdom [0,5) [5,10) [10,15) [15,20) [20,25) [25,30) [0,5) [5,10) [10,15) [15,20) [20,25) [25,30) Age group [0,5) [5,10) [10,15) [15,20) [20,25) [25,30) [0,5) [5,10) [10,15) [15,20) [20,25) [25,30) Andrews et al. (2008)

16 Results: homogeneous vs age-specific mixing Estimated reproduction numbers (R) from serological studies conducted around 2000 vs cases incidence in the 10 years following.

17 Annual measles incidence (per million, log scale) all 5 9 year olds % 80% 90% 100% 70% 80% 90% 100% Proportion immune to measles Belgium Bulgaria Cyprus Ireland Israel Latvia Romania Spain United Kingdom other Serological data from the around 2000 vs cases incidence in the 10 years following.

18 3. Conclusions and recommendations

19 Lessons from the United States Measles eliminated in Pre-elimination outbreaks in vaccinated school-aged populations (>90% uptake) => high vaccination levels needed to prevent outbreaks in schools. - Lower coverage at 2 nd birthday may be sufficient to prevent outbreaks IF population immunity is high among school-age children (except if there are high contact rates among preschool children, e.g, childcare)

20 Conclusions - Old immunity targets are not sufficient for measles elimination. - For elimination in all scenarios, need higher immunity levels in 5-9 year olds compared to previous targets. - Besides, it is important to maintain high levels of immunity in older age groups. - Serological studies can help identify gaps in in immunity in key age groups.

21 Limitations - National targets don t take into account heterogeneity and clustering of susceptibles. - Targets don t take into account waning immunity. - Results depend on reported contact rates. - Range of for R0 may not apply to all settings

22 Programmatic implications - Achievements towards elimination usually expressed via coverage levels, but they only tell part of the story - School-entry checks could be a method to identify and correct missing immunity in 5 year olds - Serological studies could be needed to identify immunity gaps in older age groups

23 Measles and Rubella SAGE WG proposed recommendations (1) 1. Achieving at least 95% immunity across all age groups, geographical regions and population subgroups through coverage of at least 95% of each birth cohort with 2 doses of MCV remains the primary goal for measles elimination. 2. To achieve this, countries ideally should assess age-group specific immunity levels to identify age-groups with levels of immunity below predefined thresholds to be targeted for vaccination.

24 Measles and Rubella SAGE WG proposed recommendations (2) 3. Neglecting immunity gaps in children older than five years of age, adolescents and adults could make it more difficult and costly to achieve measles elimination. 4. Immunity gaps in school-aged children are important and could increase the disease burden and mortality among infants younger than 1 year of age as school-aged children are likely sources of measles virus infection within families (as siblings in school or in the future as parents). Therefore, the MR SAGE WG recommends that: Countries conducting follow-up MCV vaccination campaigns should target school-age children 5-9 years of age whenever MCV coverage among this epidemiologically important age group is assessed to be significantly lower than 95%. Countries should put into place school entry checks for vaccination as they are an important tool to help identify and address immunity gaps in schoolage children.

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