Freya M Shearer

The global distribution of the arbovirus vectors Aedes aegypti and Ae. albopictus

Dengue and chikungunya are increasing global public health concerns due to their rapid geographical spread and increasing disease burden. Knowledge of the contemporary distribution of their shared vectors, Aedes aegypti and Aedes albopictus remains incomplete and is complicated by an ongoing range expansion fuelled by increased global trade and travel. Mapping the global distribution of these vectors and the geographical determinants of their ranges is essential for public health planning. Here we compile the largest contemporary database for both species and pair it with relevant environmental variables predicting their global distribution. We show Aedes distributions to be the widest ever recorded; now extensive in all continents, including North America and Europe. These maps will help define the spatial limits of current autochthonous transmission of dengue and chikungunya viruses. It is only with this kind of rigorous entomological baseline that we can hope to project future health impacts of these viruses. DOI: http://dx.doi.org/10.7554/eLife.08347.001

Mapping global environmental suitability for Zika virus

Zika virus was discovered in Uganda in 1947 and is transmitted by Aedes mosquitoes, which also act as vectors for dengue and chikungunya viruses throughout much of the tropical world. In 2007, an outbreak in the Federated States of Micronesia sparked public health concern. In 2013, the virus began to spread across other parts of Oceania and in 2015, a large outbreak in Latin America began in Brazil. Possible associations with microcephaly and Guillain-Barré syndrome observed in this outbreak have raised concerns about continued global spread of Zika virus, prompting its declaration as a Public Health Emergency of International Concern by the World Health Organization. We conducted species distribution modelling to map environmental suitability for Zika. We show a large portion of tropical and sub-tropical regions globally have suitable environmental conditions with over 2.17 billion people inhabiting these areas. DOI: http://dx.doi.org/10.7554/eLife.15272.001

The global compendium of Aedes aegypti and Ae. albopictus occurrence.

Aedes aegypti and Ae. albopictus are the main vectors transmitting dengue and chikungunya viruses. Despite being pathogens of global public health importance, knowledge of their vectors’ global distribution remains patchy and sparse. A global geographic database of known occurrences of Ae. aegypti and Ae. albopictus between 1960 and 2014 was compiled. Herein we present the database, which comprises occurrence data linked to point or polygon locations, derived from peer-reviewed literature and unpublished studies including national entomological surveys and expert networks. We describe all data collection processes, as well as geo-positioning methods, database management and quality-control procedures. This is the first comprehensive global database of Ae. aegypti and Ae. albopictus occurrence, consisting of 19,930 and 22,137 geo-positioned occurrence records respectively. Both datasets can be used for a variety of mapping and spatial analyses of the vectors and, by inference, the diseases they transmit.

Spread of yellow fever virus outbreak in Angola and the Democratic Republic of the Congo 2015–16: a modelling study

Summary Background 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. Methods 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. Findings 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 (Pearsons r 0·52, 95% CI 0·34–0·66). The further away locations were from Luanda, the later the date of invasion (Pearsons 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. Interpretation 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. Funding Wellcome Trust.

Global yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis

Summary Background Substantial outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. The aims of this study were to estimate global yellow fever vaccination coverage from 1970 through to 2016 at high spatial resolution and to calculate the number of individuals still requiring vaccination to reach population coverage thresholds for outbreak prevention. Methods For this adjusted retrospective analysis, we compiled data from a range of sources (eg, WHO reports and health-service-provider registeries) reporting on yellow fever vaccination activities between May 1, 1939, and Oct 29, 2016. To account for uncertainty in how vaccine campaigns were targeted, we calculated three population coverage values to encompass alternative scenarios. We combined these data with demographic information and tracked vaccination coverage through time to estimate the proportion of the population who had ever received a yellow fever vaccine for each second level administrative division across countries at risk of yellow fever virus transmission from 1970 to 2016. Findings Overall, substantial increases in vaccine coverage have occurred since 1970, but notable gaps still exist in contemporary coverage within yellow fever risk zones. We estimate that between 393·7 million and 472·9 million people still require vaccination in areas at risk of yellow fever virus transmission to achieve the 80% population coverage threshold recommended by WHO; this represents between 43% and 52% of the population within yellow fever risk zones, compared with between 66% and 76% of the population who would have required vaccination in 1970. Interpretation Our results highlight important gaps in yellow fever vaccination coverage, can contribute to improved quantification of outbreak risk, and help to guide planning of future vaccination efforts and emergency stockpiling. Funding The Rhodes Trust, Bill & Melinda Gates Foundation, the Wellcome Trust, the National Library of Medicine of the National Institutes of Health, the European Unions Horizon 2020 research and innovation programme.

Geographical distributions of African malaria vector sibling species and evidence for insecticide resistance.

BackgroundMany of the mosquito species responsible for malaria transmission belong to a sibling complex; a taxonomic group of morphologically identical, closely related species. Sibling species often differ in several important factors that have the potential to impact malaria control, including their geographical distribution, resistance to insecticides, biting and resting locations, and host preference. The aim of this study was to define the geographical distributions of dominant malaria vector sibling species in Africa so these distributions can be coupled with data on key factors such as insecticide resistance to aid more focussed, species-selective vector control.ResultsWithin the Anopheles gambiae species complex and the Anopheles funestus subgroup, predicted geographical distributions for Anopheles coluzzii, An. gambiae (as now defined) and An. funestus (distinct from the subgroup) have been produced for the first time. Improved predicted geographical distributions for Anopheles arabiensis, Anopheles melas and Anopheles merus have been generated based on records that were confirmed using molecular identification methods and a model that addresses issues of sampling bias and past changes to the environment. The data available for insecticide resistance has been evaluated and differences between sibling species are apparent although further analysis is required to elucidate trends in resistance.ConclusionsSibling species display important variability in their geographical distributions and the most important malaria vector sibling species in Africa have been mapped here for the first time. This will allow geographical occurrence data to be coupled with species-specific data on important factors for vector control including insecticide resistance. Species-specific data on insecticide resistance is available for the most important malaria vectors in Africa, namely An. arabiensis, An. coluzzii, An. gambiae and An. funestus. Future work to combine these data with the geographical distributions mapped here will allow more focussed and resource-efficient vector control and provide information to greatly improve and inform existing malaria transmission models.

Estimating Geographical Variation in the Risk of Zoonotic Plasmodium knowlesi Infection in Countries Eliminating Malaria

Background Infection by the simian malaria parasite, Plasmodium knowlesi, can lead to severe and fatal disease in humans, and is the most common cause of malaria in parts of Malaysia. Despite being a serious public health concern, the geographical distribution of P. knowlesi malaria risk is poorly understood because the parasite is often misidentified as one of the human malarias. Human cases have been confirmed in at least nine Southeast Asian countries, many of which are making progress towards eliminating the human malarias. Understanding the geographical distribution of P. knowlesi is important for identifying areas where malaria transmission will continue after the human malarias have been eliminated. Methodology/Principal Findings A total of 439 records of P. knowlesi infections in humans, macaque reservoir and vector species were collated. To predict spatial variation in disease risk, a model was fitted using records from countries where the infection data coverage is high. Predictions were then made throughout Southeast Asia, including regions where infection data are sparse. The resulting map predicts areas of high risk for P. knowlesi infection in a number of countries that are forecast to be malaria-free by 2025 (Malaysia, Cambodia, Thailand and Vietnam) as well as countries projected to be eliminating malaria (Myanmar, Laos, Indonesia and the Philippines). Conclusions/Significance We have produced the first map of P. knowlesi malaria risk, at a fine-scale resolution, to identify priority areas for surveillance based on regions with sparse data and high estimated risk. Our map provides an initial evidence base to better understand the spatial distribution of this disease and its potential wider contribution to malaria incidence. Considering malaria elimination goals, areas for prioritised surveillance are identified.

Existing and potential infection risk zones of yellow fever worldwide: a modelling analysis

Summary Background Yellow fever cases are under-reported and the exact distribution of the disease is unknown. An effective vaccine is available but more information is needed about which populations within risk zones should be targeted to implement interventions. Substantial outbreaks of yellow fever in Angola, Democratic Republic of the Congo, and Brazil, coupled with the global expansion of the range of its main urban vector, Aedes aegypti, suggest that yellow fever has the propensity to spread further internationally. The aim of this study was to estimate the diseases contemporary distribution and potential for spread into new areas to help inform optimal control and prevention strategies. Methods We assembled 1155 geographical records of yellow fever virus infection in people from 1970 to 2016. We used a Poisson point process boosted regression tree model that explicitly incorporated environmental and biological explanatory covariates, vaccination coverage, and spatial variability in disease reporting rates to predict the relative risk of apparent yellow fever virus infection at a 5 × 5 km resolution across all risk zones (47 countries across the Americas and Africa). We also used the fitted model to predict the receptivity of areas outside at-risk zones to the introduction or reintroduction of yellow fever transmission. By use of previously published estimates of annual national case numbers, we used the model to map subnational variation in incidence of yellow fever across at-risk countries and to estimate the number of cases averted by vaccination worldwide. Findings Substantial international and subnational spatial variation exists in relative risk and incidence of yellow fever as well as varied success of vaccination in reducing incidence in several high-risk regions, including Brazil, Cameroon, and Togo. Areas with the highest predicted average annual case numbers include large parts of Nigeria, the Democratic Republic of the Congo, and South Sudan, where vaccination coverage in 2016 was estimated to be substantially less than the recommended threshold to prevent outbreaks. Overall, we estimated that vaccination coverage levels achieved by 2016 avert between 94 336 and 118 500 cases of yellow fever annually within risk zones, on the basis of conservative and optimistic vaccination scenarios. The areas outside at-risk regions with predicted high receptivity to yellow fever transmission (eg, parts of Malaysia, Indonesia, and Thailand) were less extensive than the distribution of the main urban vector, A aegypti, with low receptivity to yellow fever transmission in southern China, where A aegypti is known to occur. Interpretation Our results provide the evidence base for targeting vaccination campaigns within risk zones, as well as emphasising their high effectiveness. Our study highlights areas where public health authorities should be most vigilant for potential spread or importation events. Funding Bill & Melinda Gates Foundation.

Updates to the zoonotic niche map of Ebola virus disease in Africa

As the outbreak of Ebola virus disease (EVD) in West Africa is now contained, attention is turning from control to future outbreak prediction and prevention. Building on a previously published zoonotic niche map (Pigott et al., 2014), this study incorporates new human and animal occurrence data and expands upon the way in which potential bat EVD reservoir species are incorporated. This update demonstrates the potential for incorporating and updating data used to generate the predicted suitability map. A new data portal for sharing such maps is discussed. This output represents the most up-to-date estimate of the extent of EVD zoonotic risk in Africa. These maps can assist in strengthening surveillance and response capacity to contain viral haemorrhagic fevers. DOI: http://dx.doi.org/10.7554/eLife.16412.001

Local, national, and regional viral haemorrhagic fever pandemic potential in Africa: a multistage analysis

Summary Background Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean–Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease. Methods In this multistage analysis, we quantified three stages underlying the potential of widespread viral haemorrhagic fever epidemics. Environmental suitability maps were used to define stage 1, index-case potential, which assesses populations at risk of infection due to spillover from zoonotic hosts or vectors, identifying where index cases could present. Stage 2, outbreak potential, iterates upon an existing framework, the Index for Risk Management, to measure potential for secondary spread in people within specific communities. For stage 3, epidemic potential, we combined local and international scale connectivity assessments with stage 2 to evaluate possible spread of local outbreaks nationally, regionally, and internationally. Findings We found epidemic potential to vary within Africa, with regions where viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa) and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both ranking highly. Tracking transitions between stages showed how an index case can escalate into a widespread epidemic in the absence of intervention (eg, Nigeria and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly susceptible to any outbreak at subnational levels. Interpretation Our analysis provides a unified assessment of potential epidemic trajectories, with the aim of allowing national and international agencies to pre-emptively evaluate needs and target resources. Within each country, our framework identifies at-risk subnational locations in which to improve surveillance, diagnostic capabilities, and health systems in parallel with the design of policies for optimal responses at each stage. In conjunction with pandemic preparedness activities, assessments such as ours can identify regions where needs and provisions do not align, and thus should be targeted for future strengthening and support. Funding Paul G Allen Family Foundation, Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development.