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BackgroundYellow fever (YF) is a viral haemorrhagic fever endemic in tropical regions of Africa and South America. Current intervention policies, namely the Eliminate Yellow fever Epidemics (EYE) strategy are actioned through vaccination. However, the stockpiles and production mean that vaccination can be in short supply. As such, intervention strategies need to be optimised; one of the tools for doing this is mathematical modelling.MethodsWe fit a generalised linear model of YF reports to occurrence data available from 1987 to 2019 in Africa and South America and available serology survey data to estimate the force of infection across the continents. Then, using demographic and vaccination data, we examine the impact of interventions.FindingsWe estimate that in 2018 there were approximately 51,000 (95%CrI [31,000 - 82,000]) deaths due to YF in Africa and South America. When we examine the impact of mass vaccination campaigns in Africa, these amount to approximately 10,000 (95%CrI [6,000 - 17,000]) deaths averted in 2018 due to mass vaccination activities in Africa; this corresponds to a 47% reduction (95%CrI [10% - 77%]).InterpretationWe find that the majority, 92% (95%CrI [89% - 95%]), of global burden occurs in Africa and that mass vaccination activities have significantly reduced the current deaths per year due to YF. This methodology allows us to evaluate the effectiveness of vaccination campaigns past, present and future and illustrates the need for continued vigilance and surveillance of YF.FundingBMGF and MRC

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., Author summary As large-scale vaccination campaigns are begun or continued with the aim to eliminate yellow fever (YF) epidemics in several countries, estimating disease burden and vaccine impact is timely. We developed two model variants to estimate YF burden in sub-Saharan Africa, each either representing the sylvatic or urban cycle of the disease. Both relied on an ecological niche model fitted to known records of YF in 34 African countries and calibrated using serological survey data. Local numbers of YF infections and deaths were derived while accounting for time-varying vaccination coverage. We estimated vaccine demand and the impact of future preventive mass vaccination campaigns according to various vaccination scenarios. By providing burden and vaccine impact estimates over a range of spatial and temporal scales, and accounting for the specificity of urban transmission, our model can be used to inform the current international strategy to counter the increasing global risk of yellow fever.

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.

Predominantly caused by Neisseria meningitidis group A (NmA), recurrent epidemics of meningococcal meningitis have placed a heavy toll on countries of the African “meningitis belt” [1–7]. Until recently, the combination of early detection, case management, and reactive immunization using polysaccharide vaccines were the sole approaches available to control these epidemics. Logistically intensive, this strategy did not alleviate the burden of meningitis in the long term [8–11]. A group A meningococcal polysaccharide–tetanus toxoid conjugate vaccine (PsA–TT) was developed to eliminate NmA epidemics in the most affected countries. PsA-TT is safe and induces a strong and persistent immunity against NmA, preventing carriage and inducing herd protection [12]. PsA-TT has been progressively introduced in the meningitis belt since 2010 through mass immunization campaigns, following the approval of a World Health Organization (WHO)/United Nations Children's Fund (UNICEF) investment case to the Gavi Alliance [10, 13]. By 2016, it is expected that >450 million people in 26 countries at risk for meningitis epidemics in sub-Saharan Africa will be preventively protected against NmA. Countries were grouped according to meningitis risk across the belt, the global vaccine supply (50–70 million doses), and the funds available to support mass immunization campaigns [10, 13]. Burkina Faso, Mali, and Niger were identified as hyperendemic countries and country-wide campaigns in these 3 countries were completed by the end of 2011 [13, 14]. For the other meningitis belt countries, inter- and intracountry risk assessments were required to identify areas of high priority for vaccination. The District Prioritization Tool (DPT) for NmA immunization was developed to standardize meningitis risk assessment, to define vaccine demand forecasts from 2011 onward, to reinforce in-country advocacy for preventive campaigns, and to support country planning and funding applications. DPT was a decision-making tool that optimized the use of the available country data while ensuring that expert opinion and local knowledge were included into the final decision-making process. Special efforts were made to integrate countries’ ability to mount immunization campaigns [15, 16]. This article describes the tool and presents analytic examples in diverse settings.

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.

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).

Introduction Recent yellow fever (YF) outbreaks in Africa, such as 2016 in Angola, or 2017 in Nigeria, have demonstrated the ongoing threat of large-scale urban YF outbreaks. Moreover, outbreaks of other mosquito-borne diseases (Zika, chikungunya) have increased awareness of the potential for rapid, international spread of arboviruses. Swift outbreak response, for YF primarily in the form of vaccination, is therefore essential to prevent local and international spread. However, limited global stockpiles means that the prioritization of geographic areas for pre-emptive vaccination campaigns is required (i.e. vaccination campaigns targeting areas that are at risk of disease introduction and spread but as yet unaffected). Conducting a rapid prioritization assessment based on the risk of disease spread is thus highly valuable to inform decisions on vaccination activities in a context of emergency. Objective To develop a method for rapid risk assessment of YF spread to prioritize sub-national administrative units (hereafter called province) for pre-emptive campaigns. Specific requirements for this method are: –speed of implementation in the context of emergency response; –transparent methodology to allow discussions with and feedback from decision-makers. Method We developed a heuristic method to quantify the risk of YF spread by integrating multiple data streams: population sizes, estimates of existing vaccine-induced population-level immunity, recent incidence of yellow fever cases in the province and travel flows between provinces. The resulting risk score primarily reflects the expected absolute number of yellow cases in the respective province, accounting for local cases and the risk of case importation. Based on their risk score, provinces are ranked according to priority for vaccination and target population sizes are estimated. This baseline, quick-to-compute, risk assessment can be refined by integrating additional elements. For example, the presence and population size of large urban centres at the province level may be relevant to characterize the risk of urban outbreaks, and of international spread in the case of highly connected urban centres. Similarly, independent estimates of the local transmission potential of the disease produced by a mathematical model can be combined into this risk metric. Results This heuristic method has been used in collaboration with the World Health Organization in the context of urgent response to yellow fever outbreaks that affected Angola and the Democratic Republic of Congo (DRC) in 2016 and Nigeria in 2017. Results were provided in a form that allowed decision-makers to easily and interactively adjust the relative weights of different factors and visualize the effect on the results. Moreover, the transparency of the method allowed decision-makers to provide feedback and to request the integration of additional elements considered as relevant for outbreak control (for instance: trans-border movements in Angola-DRC). This risk assessment contributed to inform decision for mass vaccination campaigns conducted in the DRC in 2017 and for campaigns (still under consideration) in Nigeria in 2018. Conclusion By integrating different, mostly publicly available, data streams, we developed a risk assessment method that can be quickly implemented in the context of yellow fever outbreak response. The transparency and flexibility of the method enhanced interactions with decision-makers to refine estimates.

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.