The global burden of yellow fever.

Yellow fever (YF) is a viral, vector-borne, haemorrhagic fever endemic in tropical regions of Africa and South America. The vaccine for YF is considered safe and effective, but intervention strategies need to be optimised; one of the tools for this is mathematical modelling. We refine and expand an existing modelling framework for Africa to account for transmission in South America. We fit to YF occurrence and serology data. We then estimate the subnational forces of infection for the entire endemic region. Finally, using demographic and vaccination data, we examine the impact of vaccination activities. We estimate that there were 109,000 (95% credible interval [CrI] [67,000-173,000]) severe infections and 51,000 (95% CrI [31,000-82,000]) deaths due to YF in Africa and South America in 2018. We find that mass vaccination activities in Africa reduced deaths by 47% (95% CrI [10%-77%]). This methodology allows us to evaluate the effectiveness of vaccination and illustrates the need for continued vigilance and surveillance of YF.

The effect of climate change on yellow fever disease burden in Africa.

Yellow Fever (YF) is an arbovirus endemic in tropical regions of South America and Africa and it is estimated to cause 78,000 deaths a year in Africa alone. Climate change may have substantial effects on the transmission of YF and we present the first analysis of the potential impact on disease burden. We extend an existing model of YF transmission to account for rainfall and a temperature suitability index and project transmission intensity across the African endemic region in the context of four climate change scenarios. We use these transmission projections to assess the change in burden in 2050 and 2070. We find disease burden changes heterogeneously across the region. In the least severe scenario, we find a 93.0%[95%CI(92.7, 93.2%)] chance that annual deaths will increase in 2050. This change in epidemiology will complicate future control efforts. Thus, we may need to consider the effect of changing climatic variables on future intervention strategies.

Eliminating yellow fever epidemics in Africa: Vaccine demand forecast and impact modelling.

BACKGROUND: To counter the increasing global risk of Yellow fever (YF), the World Health Organisation initiated the Eliminate Yellow fever Epidemics (EYE) strategy. Estimating YF burden, as well as vaccine impact, while accounting for the features of urban YF transmission such as indirect benefits of vaccination, is key to informing this strategy. METHODS AND FINDINGS: We developed two model variants to estimate YF burden in sub-Saharan Africa, assuming all infections stem from either the sylvatic or the urban cycle of the disease. Both relied on an ecological niche model fitted to the local presence of any YF reported event in 34 African countries. We calibrated under-reporting using independent estimates of transmission intensity provided by 12 serological surveys performed in 11 countries. We calculated local numbers of YF infections, deaths and disability-adjusted life years (DALYs) lost based on estimated transmission intensity while accounting for time-varying vaccination coverage. We estimated vaccine demand and impact of future preventive mass vaccination campaigns (PMVCs) according to various vaccination scenarios. Vaccination activities conducted in Africa between 2005 and 2017 were estimated to prevent from 3.3 (95% CI 1.2-7.7) to 6.1 (95% CI 2.4-13.2) millions of deaths over the lifetime of vaccinees, representing extreme scenarios of none or maximal herd effects, respectively. By prioritizing provinces based on the risk of urban YF transmission in future PMVCs, an average of 37.7 million annual doses for PMVCs over eight years would avert an estimated 9,900,000 (95% CI 7,000,000-13,400,000) infections and 480,000 (180,000-1,140,000) deaths over the lifetime of vaccinees, corresponding to 1.7 (0.7-4.1) deaths averted per 1,000 vaccine doses. CONCLUSIONS: By estimating YF burden and vaccine impact over a range of spatial and temporal scales, while accounting for the specificity of urban transmission, our model can be used to inform the current EYE strategy.

Quantifying model evidence for yellow fever transmission routes in Africa.

Yellow fever is a vector-borne disease endemic in tropical regions of Africa, where 90% of the global burden occurs, and Latin America. It is notoriously under-reported with uncertainty arising from a complex transmission cycle including a sylvatic reservoir and non-specific symptom set. Resulting estimates of burden, particularly in Africa, are highly uncertain. We examine two established models of yellow fever transmission within a Bayesian model averaging framework in order to assess the relative evidence for each model's assumptions and to highlight possible data gaps. Our models assume contrasting scenarios of the yellow fever transmission cycle in Africa. The first takes the force of infection in each province to be static across the observation period; this is synonymous with a constant infection pressure from the sylvatic reservoir. The second model assumes the majority of transmission results from the urban cycle; in this case, the force of infection is dynamic and defined through a fixed value of R0 in each province. Both models are coupled to a generalised linear model of yellow fever occurrence which uses environmental covariates to allow us to estimate transmission intensity in areas where data is sparse. We compare these contrasting descriptions of transmission through a Bayesian framework and trans-dimensional Markov chain Monte Carlo sampling in order to assess each model's evidence given the range of uncertainty in parameter values. The resulting estimates allow us to produce Bayesian model averaged predictions of yellow fever burden across the African endemic region. We find strong support for the static force of infection model which suggests a higher proportion of yellow fever transmission occurs as a result of infection from an external source such as the sylvatic reservoir. However, the model comparison highlights key data gaps in serological surveys across the African endemic region. As such, conclusions concerning the most prevalent transmission routes for yellow fever will be limited by the sparsity of data which is particularly evident in the areas with highest predicted transmission intensity. Our model and estimation approach provides a robust framework for model comparison and predicting yellow fever burden in Africa. However, key data gaps increase uncertainty surrounding estimates of model parameters and evidence. As more mathematical models are developed to address new research questions, it is increasingly important to compare them with established modelling approaches to highlight uncertainty in structures and data.

POLICI: A web application for visualising and extracting yellow fever vaccination coverage in Africa.

Recent yellow fever (YF) outbreaks have highlighted the increasing global risk of urban spread of the disease. In context of recurrent vaccine shortages, preventive vaccination activities require accurate estimates of existing population-level immunity. We present POLICI (POpulation-Level Immunization Coverage - Imperial), an interactive online tool for visualising and extracting YF vaccination coverage estimates in Africa. We calculated single year age-disaggregated sub-national population-level vaccination coverage for 1950-2050 across the African endemic zone by collating vaccination information and inputting it into a demographic model. This was then implemented on an open interactive web platform. POLICI interactively displays age-disaggregated, population-level vaccination coverages at the first subnational administrative level, through numerous downloadable and customisable visualisations. POLICI is available at https://polici.shinyapps.io/yellow_fever_africa/. POLICI offers an accessible platform for relevant stakeholders in global health to access and explore vaccination coverages. These estimates have already been used to inform the WHO strategy to Eliminate Yellow fever Epidemics (EYE).

Epidemiology of Chikungunya in the Americas.

Chikungunya virus (CHIKV) emerged in the Americas in late 2013 to cause substantial acute and chronic morbidity. About 1.1 million cases of chikungunya were reported within a year, including severe cases and deaths. The burden of chikungunya is unclear owing to inadequate disease surveillance and underdiagnosis. Virus evolution, globalization, and climate change may further CHIKV spread. No approved vaccine or antiviral therapeutics exist. Early detection and appropriate management could reduce the burden of severe atypical and chronic arthritic disease. Improved surveillance and risk assessment are needed to mitigate the impact of chikungunya.

Risk Assessment and Meningococcal A Conjugate Vaccine Introduction in Africa: The District Prioritization Tool.

BACKGROUND: A group A meningococcal (MenA) conjugate vaccine has progressively been introduced in the African meningitis belt since 2010. A country-wide risk assessment tool, the District Prioritization Tool (DPT), was developed to help national stakeholders combine existing data and local expertise to define priority geographical areas where mass vaccination campaigns should be conducted. METHODS: DPT uses an Excel-supported offline tool that was made available to the countries proposed for immunization campaigns. It used quantitative-qualitative methods, relying predominantly on evidence-based risk scores complemented by expert opinion. RESULTS: DPT was used by most of the countries that introduced the group A conjugate vaccine. Surveillance data enabled the computation of severity scores for meningitis at the district level (magnitude, intensity, and frequency). District data were scaled regionally to facilitate phasing decisions. DPT also assessed the country's potential to conduct efficient preventive immunization campaigns while paying close attention to the scope of the geographic extension of the campaigns. The tool generated meningitis district profiles that estimated the number of vaccine doses needed. In each assessment, local meningitis experts contributed their knowledge of local risk factors for meningitis epidemics to refine the final prioritization decisions. CONCLUSIONS: DPT proved to be a useful and flexible tool that codified information and streamlined discussion among stakeholders while facilitating vaccine distribution decisions after 2011. DPT methodology may be tailored to prioritize vaccine interventions for other diseases.

Serogroup W Meningitis Outbreak at the Subdistrict Level, Burkina Faso, 2012.

In 2012, Neisseria meningitidis serogroup W caused a widespread meningitis epidemic in Burkina Faso. We describe the dynamic of the epidemic at the subdistrict level. Disease detection at this scale allows for a timelier response, which is critical in the new epidemiologic landscape created in Africa by the N. meningitidis A conjugate vaccine.

Response thresholds for epidemic meningitis in sub-Saharan Africa following the introduction of MenAfriVac®.

BACKGROUND: Since 2010, countries in the African meningitis belt have been introducing a new serogroup A meningococcal conjugate vaccine (MenAfriVac(®)) through mass campaigns. With the subsequent decline in meningitis due to Neisseria meningitidis serogroup A (NmA) and relative increase in meningitis due to other serogroups, mainly N. meningitidis serogroup W (NmW), the World Health Organisation (WHO) initiated a review of the incidence thresholds that guide response to meningitis epidemics in the African meningitis belt. METHODS: Meningitis surveillance data from African meningitis belt countries from 2002 to 2013 were used to construct a single NmW dataset. The performance of different weekly attack rates, used as thresholds to initiate vaccination response, on preventing further cases was estimated. The cumulative seasonal attack rate used to define an epidemic was also varied. RESULTS: Considerable variation in effect at different thresholds was observed. In predicting epidemics defined as a seasonal cumulative incidence of 100/10(5) population, an epidemic threshold of 10 cases/10(5) population/week performed well. Based on this same epidemic threshold, with a 6 week interval between crossing the epidemic threshold and population protection from a meningococcal vaccination campaign, an estimated 17 cases per event would be prevented by vaccination. Lowering the threshold increased the number of cases per event potentially prevented, as did shortening the response interval. If the interval was shortened to 4 weeks at the threshold of 10/10(5), the number of cases prevented would increase to 54 per event. CONCLUSIONS: Accelerating time to vaccination could prevent more cases per event than lowering the threshold. Once the meningitis epidemic threshold is crossed, it is of critical importance that vaccination campaigns, where appropriate, are initiated rapidly.