Spatial patterns on the edge of stability: measles in the Sahel

Great success in measles eradication Distribution of that success has not been equitable Susceptible Infected Immune Poster child for non- linear dynamics and spatial epidemiology

Niger Niamey Culturally and environmentally diverse Highest reported birthrate in the world (51 per 1000) Low vaccine coverage in Niger and surrounding countries Relatively high case fatality

Measles Dynamics in Niger measles All Niger Measles epidemic begin in the dry season Aggregate measures can obscure local complexity measles

Timing is consistent with the national pattern High variability in outbreaks size Frequent local extinction Local Dynamics: Niamey

Estimating Seasonal Transmission Seasonal TSIR Model Susceptible Infected Immune Recovery rate Births Observational Model Observed Cases P obs Fit state space model state using Bayesian MCMC methods

Estimated Seasonality Strong seasonality in Niamey Related to the rainy season - Rural-urban migration due to agriculture? 3-fold greater seasonality than pre-vaccine London

Seasonality Generates Complex Epidemic Dynamics Strength of seasonality Birth rate per 1000 LondonNiamey Stronger seasonality leads to more episodic dynamics at all birthrates Potential for deterministic chaos (!)

Deep Troughs Make Stochastic Extinction Likely Strength of seasonality Birth rate per 1000 LondonNiamey Stronger seasonality leads to more episodic dynamics at all birthrates Potential for deterministic chaos Stochastic extinction is likely when there are few cases

Dynamics set the stage for spatial dynamics Strong seasonality and high birth rates give rise to locally instable dynamics and erratic outbreaks that can vary in size over orders of magnitude public health strategies need to be local and reactive.

outbreak in Niamey Large outbreak (>11,000 cases) following 2 years of few cases. In response a collaborative effort between MOH, WHO, and MSF was mobilized to vaccinate

Timing is Everything Spatially implicit model showed that campaign was unlikely to have had a great impact on the course of the epidemic

Within Niamey Model > 9000 case records 26 health districts

Within Niamey Model > 9000 case records 26 health districts

Within Niamey Model Spatially explicit model of epidemic spread in Niamey d ij = distance between location i and j Susceptibles Infecteds transmission rate

Simulating the fitted model replicates the aggregate dynamics Seasonal transmission is necessary to replicate timing and extinction of outbreaks Weak spatial coupling is required to slow spread through entire city Within Niamey Model rainfall  data simulation

Predict timescale for vaccination response Prioritize spatial surveillance Within Niamey Model rainfall  = Epidemic size | index case

Regional Dynamics Given that measles tends to go extinct locally, even in the largest cities, regional persistence must rely on metapopulation dynamics. Nita Bharti

5 years Weekly reporting County scale health centers Spatial and temporal variation in incidence

5 years Weekly reporting County scale health centers Spatial and temporal variation in incidence

Measles Persistence Measles persistence scales with population size Nowhere is measles endemic Even above the classic CCS Population size Measles cases

Regional Pattern Population size Measles cases

Spatial Metapopulation Model Measles cases

Predicts Regional Pattern Spatial model captures regional trend in persistence Effect of spatial arrangement

Guilt by association Predict that “well connected” locations have frequent immigrants Districts with many neighbors have short periods of measles extinction

Guilt by association Districts with more frequent reintroductions than expected are along the southern road network Trans-national immigration

A Natural Experiment Pulsed vaccination (Unicef, The Measles Initiative) –December 2004 > 80% coverage –January 2008 > 90% coverage We can assume most 2005 and 2008 cases are reintroductions –52 weeks from 2005 –8 weeks from 2008

Isolating Reintroductions 2005 (1 yr)2008 (8 wks) 2005 & 2008 Locations with > average cases per capita

Measles in Chad

Measles in Nigeria Measles killed more than 500 children between January and mid-March in Nigeria (WHO 2005) Measles Outbreak Hits Northern Nigerian State, over 3,000 cases reported (VOA news March 2008)

A regional perspective Suggests that understanding measles persistence (and conversely eradication), requires broadening the regional perspective beyond national borders.

Goals at Multiple Scales Short term goals of reducing measles morbidity and mortality require local response and planning Long-term goals of measles eradication require large-scale coordination that reflects dynamics rather than national boundaries

Acknowledgements Ministry of Health Niger Ali Djibo Rebecca Grais, Phillippe Guerin Nita Bharti, Ottar Bjornstad, Bryan Grenfell Andrew Conlan