title: Spread of yellow fever virus outbreak in Angola and the Democratic Republic of the Congo 2015-16: a modelling study.
abstract: Since late 2015, an epidemic of yellow fever has caused more than 7334 suspected cases in Angola and the Democratic Republic of the Congo, including 393 deaths. We sought to understand the spatial spread of this outbreak to optimise the use of the limited available vaccine stock.
  
  
  
  We jointly analysed datasets describing the epidemic of yellow fever, vector suitability, human demography, and mobility in central Africa to understand and predict the spread of yellow fever virus. We used a standard logistic model to infer the district-specific yellow fever virus infection risk during the course of the epidemic in the region.
  
  
  
  The early spread of yellow fever virus was characterised by fast exponential growth (doubling time of 5-7 days) and fast spatial expansion (49 districts reported cases after only 3 months) from Luanda, the capital of Angola. Early invasion was positively correlated with high population density (Pearson's r 0·52, 95% CI 0·34-0·66). The further away locations were from Luanda, the later the date of invasion (Pearson's r 0·60, 95% CI 0·52-0·66). In a Cox model, we noted that districts with higher population densities also had higher risks of sustained transmission (the hazard ratio for cases ceasing was 0·74, 95% CI 0·13-0·92 per log-unit increase in the population size of a district). A model that captured human mobility and vector suitability successfully discriminated districts with high risk of invasion from others with a lower risk (area under the curve 0·94, 95% CI 0·92-0·97). If at the start of the epidemic, sufficient vaccines had been available to target 50 out of 313 districts in the area, our model would have correctly identified 27 (84%) of the 32 districts that were eventually affected.
  
  
  
  Our findings show the contributions of ecological and demographic factors to the ongoing spread of the yellow fever outbreak and provide estimates of the areas that could be prioritised for vaccination, although other constraints such as vaccine supply and delivery need to be accounted for before such insights can be translated into policy.
  
  
  
  Wellcome Trust.
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK. Electronic address: moritz.kraemer@zoo.ox.ac.uk.
authors.forename: Moritz U G
authors.initials: MUG
authors.lastname: Kraemer
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Nuno R
authors.initials: NR
authors.lastname: Faria
authors.affiliation: Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Reiner
authors.affiliation: Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Oxford, UK; School of BioSciences, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Nick
authors.initials: N
authors.lastname: Golding
authors.affiliation: Mathematical Modelling of Infectious Diseases and Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, France; Centre National de la Recherche Scientifique, URA 3012, Paris, France.
authors.forename: Birgit
authors.initials: B
authors.lastname: Nikolay
authors.affiliation: Health Programme, European Commission, International Cooperation and Development, Delegation en RDC, Kinshasa, Democratic Republic of the Congo.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Stasse
authors.affiliation: Centers for Disease Control and Prevention, San Juan, PR, USA; Center for Communicable Disease Dynamics, Harvard T H Chan School of Public Health, MA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Johansson
authors.affiliation: Mathematical Modelling of Infectious Diseases and Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, France; Centre National de la Recherche Scientifique, URA 3012, Paris, France; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Henrik
authors.initials: H
authors.lastname: Salje
authors.affiliation: Arbovirus and Viral Hemorrhagic Fever Unit, Institut Pasteur da Dakar, Dakar, Senegal.
authors.forename: Ousmane
authors.initials: O
authors.lastname: Faye
authors.affiliation: Environmental Research Group Oxford, Department of Zoology, Oxford, UK.
authors.forename: G R William
authors.initials: GRW
authors.lastname: Wint
authors.affiliation: Robert Koch Institut, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Niedrig
authors.affiliation: Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Oxford, UK.
authors.forename: Freya M
authors.initials: FM
authors.lastname: Shearer
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Hill
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Robin N
authors.initials: RN
authors.lastname: Thompson
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Donal
authors.initials: D
authors.lastname: Bisanzio
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Portugal; Centro de Investigacao Interdisciplinar Egas Moniz, Instituto Superior de Ciencias da Saude Egas Moniz, Caparica, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Taveira
authors.affiliation: Computational Social Science, ETH Zurich, Zurich, Switzerland.
authors.forename: Heinrich H
authors.initials: HH
authors.lastname: Nax
authors.affiliation: Computational Social Science, ETH Zurich, Zurich, Switzerland.
authors.forename: Bary S R
authors.initials: BSR
authors.lastname: Pradelski
authors.affiliation: Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.
authors.forename: Elaine O
authors.initials: EO
authors.lastname: Nsoesie
authors.affiliation: School of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Murphy
authors.affiliation: Divisions of General Internal Medicine and Infectious Diseases, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: Isaac I
authors.initials: II
authors.lastname: Bogoch
authors.affiliation: Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada.
authors.forename: Kamran
authors.initials: K
authors.lastname: Khan
authors.affiliation: Harvard University Medical School Boston, MA, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Brownstein
authors.affiliation: WorldPop, Department of Geography and Environment, University of Southampton, Southampton, UK; Flowminder Foundation, Stockholm, Sweden.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tatem
authors.affiliation: School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Tulio
authors.initials: T
authors.lastname: de Oliveira
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK; Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; Sanaria Institute for Global Health and Tropical Medicine, Rockville, MD, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Smith
authors.affiliation: Arbovirus and Viral Hemorrhagic Fever Unit, Institut Pasteur da Dakar, Dakar, Senegal.
authors.forename: Amadou A
authors.initials: AA
authors.lastname: Sall
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Pybus
authors.affiliation: Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Oxford, UK.
authors.forename: Simon I
authors.initials: SI
authors.lastname: Hay
authors.affiliation: Mathematical Modelling of Infectious Diseases and Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, France; Centre National de la Recherche Scientifique, URA 3012, Paris, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Cauchemez
mesh_terms: D000330:Aedes / Q000821:virology; D000810:Angola; D000818:Animals; D015023:Democratic Republic of the Congo; D004196:Disease Outbreaks / Q000517:prevention & control*; D006801:Humans; D007115:Immunization Schedule; D015233:Models, Statistical; D012424:Rural Population / Q000706:statistics & numerical data; D014195:Travel; D014505:Urban Population / Q000706:statistics & numerical data; D014611:Vaccination; D015004:Yellow Fever / Q000453:epidemiology* / Q000401:mortality / Q000635:transmission; D015005:Yellow fever virus / Q000302:isolation & purification*