register interest

Catherine Moyes BSc PhD

Research Area: Global Health

Catherine heads up three projects within the field of spatial epidemiology. The first, funded by the Bill & Melinda Gates Foundation, is developing novel techniques to combine the group's spatial models with ‘big data' in order to continually update spatial predictions of disease distribution for a wide range of diseases. The aim of this work is to reduce the time it takes to construct and release a global disease risk map from three years to three weeks. The resulting maps are available from the Atlas of Baseline Risk Assessment for Infectious Diseases (ABRAID).

Catherine also leads two malaria research projects as part of the Malaria Atlas Project. The first is investigating the relationship between the zoonotic reservoir of Plasmodium knowlesi parasites and changing land use in SE Asia in order to understand variation in disease risk to humans. Data on P. knowlesi is limited so this project involves modelling the spatial distributions of the monkey species that host this parasite and the mosquito species that transmit it, in addition to mapping parasite infections themselves.

The second malaria project will define spatial variation in insecticide resistance in the mosquitoes that transmit malaria, so that relationships with potential causal factors can be investigated. The Wellcome Trust awarded funds for this work in 2015 and the project will start later this year. Catherine has an interest in tools for malaria vector control planning and represents the group on the Vector-Borne Disease Network (VecNet) management committee.

Name Department Institution Country
Peter Gething Big Data Institute Oxford University, Henry Wellcome Building of Genomic Medicine United Kingdom
Professor David Smith University of Oxford United Kingdom
Paul Newton Tropical Medicine Oxford University, Vientiane Laos
Dr Michael Coleman Liverpool School of Tropical Medicine United Kingdom
Professor Janet Hemingway Liverpool School of Tropical Medicine United Kingdom
Kevin Baird Tropical Medicine Oxford University, Jakarta Indonesia
Hendriks CMJ, Gibson HS, Trett A, Python A, Weiss DJ, Vrieling A, Coleman M, Gething PW, Hancock PA, Moyes CL. 2019. Mapping Geospatial Processes Affecting the Environmental Fate of Agricultural Pesticides in Africa. Int J Environ Res Public Health, 16 (19), pp. 3523-3523. | Show Abstract | Read more

The application of agricultural pesticides in Africa can have negative effects on human health and the environment. The aim of this study was to identify African environments that are vulnerable to the accumulation of pesticides by mapping geospatial processes affecting pesticide fate. The study modelled processes associated with the environmental fate of agricultural pesticides using publicly available geospatial datasets. Key geospatial processes affecting the environmental fate of agricultural pesticides were selected after a review of pesticide fate models and maps for leaching, surface runoff, sedimentation, soil storage and filtering capacity, and volatilization were created. The potential and limitations of these maps are discussed. We then compiled a database of studies that measured pesticide residues in Africa. The database contains 10,076 observations, but only a limited number of observations remained when a standard dataset for one compound was extracted for validation. Despite the need for more in-situ data on pesticide residues and application, this study provides a first spatial overview of key processes affecting pesticide fate that can be used to identify areas potentially vulnerable to pesticide accumulation.

Bender A, Python A, Lindsay SW, Golding N, Moyes CL. Modelling geospatial distributions of the triatomine vectors of Trypanosoma cruzi in Latin America | Show Abstract | Read more

<jats:title>Abstract</jats:title><jats:p>Approximately 150 triatomine species are known to be infected with the Chagas parasite, <jats:italic>Trypanosoma cruzi</jats:italic>, but they differ in the risk they pose to human populations. The largest risk comes from species that have a domestic life cycle and these species have been targeted by indoor residual spraying campaigns, which have been successful in many locations. It is now important to consider residual transmission that may be linked to persistent populations of dominant vectors, or to secondary or minor vectors. The aim of this project was to define the geographical distributions of the community of triatomine species in Latin America. Presence-only data with over 12, 000 observations of triatomine vectors were extracted from a public database and target-group background data were generated to account for sampling bias in the presence data. Geostatistical regression was then applied to estimate species distributions and fine-scale distribution maps were generated for thirty triatomine vector species. The results for <jats:italic>Panstrongylus geniculatus, P. megistus, Triatoma barberi, T. brasiliensis</jats:italic>, and <jats:italic>T. pseudomaculata</jats:italic> are presented in detail and the model validation results for each of the 30 species are presented in full. The predictive maps for all species are made publicly available so that they can be used to assess the communities of vectors present within different regions of the endemic zone. The maps are presented alongside key indicators for the capacity of each species to transmit <jats:italic>T. cruzi</jats:italic> to humans. These indicators include infection prevalence, evidence for human blood meals, and colonisation or invasion of homes. A summary of these indicators shows that the majority of the 30 species mapped by this study have the potential to transmit <jats:italic>T. cruzi</jats:italic> to humans.</jats:p><jats:sec><jats:title>Author summary</jats:title><jats:p>The Pan American Health Organisation’s Strategy and Plan of Action for Chagas Disease Prevention, Control and Care highlights the importance of eliminating those triatomine vector species that colonise homes, and has had great success in many locations. Since indoor residual spraying campaigns have targeted these species, their importance relative to other vectors has diminished and their geographical distributions may also have changed. It is now vital to consider the full community of vector species, including previously dominant vectors as well as secondary or minor vector species, in order to target residual transmission to humans. Our aim was to define the geographical distributions of the most commonly reported triatomine species in Latin America. We extracted reports of triatomine vector species observed at specific locations from a public database and we used a geostatistical model to generate fine-scale predictive maps for thirty triatomine vector species. We present these maps alongside a summary of key indicators related to the capacity of each species to transmit the Chagas parasite to humans. We show that most of the 30 species that we have mapped pose a potential threat to human populations.</jats:p></jats:sec>

Moyes CL, Wiebe A, Gleave K, Trett A, Hancock PA, Padonou GG, Chouaïbou MS, Sovi A, Abuelmaali SA, Ochomo E et al. 2019. Analysis-ready datasets for insecticide resistance phenotype and genotype frequency in African malaria vectors. Sci Data, 6 (1), pp. 121. | Show Abstract | Read more

The impact of insecticide resistance in malaria vectors is poorly understood and quantified. Here a series of geospatial datasets for insecticide resistance in malaria vectors are provided, so that trends in resistance in time and space can be quantified, and the impact of resistance found in wild populations on malaria transmission in Africa can be assessed. Specifically, data have been collated and geopositioned for the prevalence of insecticide resistance, as measured by standard bioassays, in representative samples of individual species or species complexes. Data are provided for the Anopheles gambiae species complex, the Anopheles funestus subgroup, and for nine individual vector species. Data are also given for common genetic markers of resistance to support analyses of whether these markers can improve the ability to monitor resistance in low resource settings. Allele frequencies for known resistance-associated markers in the Voltage-gated sodium channel (Vgsc) are provided. In total, eight analysis-ready, standardised, geopositioned datasets encompassing over 20,000 African mosquito collections between 1957 and 2017 are released.

Corbel V, Durot C, Achee NL, Chandre F, Coulibaly MB, David J-P, Devine GJ, Dusfour I, Fonseca DM, Griego J et al. 2019. Second WIN International Conference on "Integrated approaches and innovative tools for combating insecticide resistance in vectors of arboviruses", October 2018, Singapore. Parasit Vectors, 12 (1), pp. 331. | Show Abstract | Read more

The past 40 years have seen a dramatic emergence of epidemic arboviral diseases transmitted primarily by mosquitoes. The frequency and magnitude of the epidemics, especially those transmitted by urban Aedes species, have progressively increased over time, accelerating in the past 10 years. To reduce the burden and threat of vector-borne diseases, the World Health Organization (WHO) has recently adopted the Global Vector Control Response (GVCR) in order to support countries in implementing effective sustainable vector control. The evidence-base to support vector control is however limited for arboviral diseases which make prioritization difficult. Knowledge gaps in the distribution, mechanisms and impact of insecticide resistance on vector control impedes the implementation of locally tailored Aedes control measures. This report summarizes the main outputs of the second international conference of the Worldwide Insecticide resistance Network (WIN) on "Integrated approaches and innovative tools for combating insecticide resistance in arbovirus vectors" held in Singapore, 1-3 October 2018. The aims of the conference were to review progress and achievements made in insecticide resistance surveillance worldwide, and to discuss the potential of integrated vector management and innovative technologies for efficiently controlling arboviral diseases. The conference brought together 150 participants from 26 countries.

Pfeffer DA, Lucas TCD, May D, Harris J, Rozier J, Twohig KA, Dalrymple U, Guerra CA, Moyes CL, Thorn M et al. 2018. malariaAtlas: an R interface to global malariometric data hosted by the Malaria Atlas Project. Malar J, 17 (1), pp. 352. | Show Abstract | Read more

BACKGROUND: The Malaria Atlas Project (MAP) has worked to assemble and maintain a global open-access database of spatial malariometric data for over a decade. This data spans various formats and topics, including: geo-located surveys of malaria parasite rate; global administrative boundary shapefiles; and global and regional rasters representing the distribution of malaria and associated illnesses, blood disorders, and intervention coverage. MAP has recently released malariaAtlas, an R package providing a direct interface to MAP's routinely-updated malariometric databases and research outputs. METHODS AND RESULTS: The current paper reviews the functionality available in malariaAtlas and highlights its utility for spatial epidemiological analysis of malaria. malariaAtlas enables users to freely download, visualise and analyse global malariometric data within R. Currently available data types include: malaria parasite rate and vector occurrence point data; subnational administrative boundary shapefiles; and a large suite of rasters covering a diverse range of metrics related to malaria research. malariaAtlas is here used in two mock analyses to illustrate how this data may be incorporated into a standard R workflow for spatial analysis. CONCLUSIONS: malariaAtlas is the first open-access R-interface to malariometric data, providing a new and reproducible means of accessing such data within a freely available and commonly used statistical software environment. In this way, the malariaAtlas package aims to contribute to the environment of data-sharing within the malaria research community.

Ndila CM, Uyoga S, Macharia AW, Nyutu G, Peshu N, Ojal J, Shebe M, Awuondo KO, Mturi N, Tsofa B et al. 2018. Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study. Lancet Haematol, 5 (8), pp. e333-e345. | Show Abstract | Read more

BACKGROUND: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms-many related to the structure or function of red blood cells-and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. METHODS: We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. FINDINGS: Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11-0·20; p=2·61 × 10-58), blood group O (0·74, 0·66-0·82; p=6·26 × 10-8), and -α3·7-thalassaemia (0·83, 0·76-0·90; p=2·06 × 10-6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63-0·92; p=0·001) and FREM3 (0·64, 0·53-0·79; p=3·18 × 10-14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49-0·68; p=3·22 × 10-11), as was homozygosity (0·26, 0·11-0·62; p=0·002). INTERPRETATION: Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. FUNDING: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative.

Killeen GF, Chaki PP, Reed TE, Moyes CL, Govella NJ. Entomological Surveillance as a Cornerstone of Malaria Elimination: A Critical Appraisal | Read more

Hancock PA, Wiebe A, Gleave KA, Bhatt S, Cameron E, Trett A, Weetman D, Smith DL, Hemingway J, Coleman M et al. 2018. Associated patterns of insecticide resistance in field populations of malaria vectors across Africa. Proc Natl Acad Sci U S A, 115 (23), pp. 5938-5943. | Show Abstract | Read more

The development of insecticide resistance in African malaria vectors threatens the continued efficacy of important vector control methods that rely on a limited set of insecticides. To understand the operational significance of resistance we require quantitative information about levels of resistance in field populations to the suite of vector control insecticides. Estimation of resistance is complicated by the sparsity of observations in field populations, variation in resistance over time and space at local and regional scales, and cross-resistance between different insecticide types. Using observations of the prevalence of resistance in mosquito species from the Anopheles gambiae complex sampled from 1,183 locations throughout Africa, we applied Bayesian geostatistical models to quantify patterns of covariation in resistance phenotypes across different insecticides. For resistance to the three pyrethroids tested, deltamethrin, permethrin, and λ-cyhalothrin, we found consistent forms of covariation across sub-Saharan Africa and covariation between resistance to these pyrethroids and resistance to DDT. We found no evidence of resistance interactions between carbamate and organophosphate insecticides or between these insecticides and those from other classes. For pyrethroids and DDT we found significant associations between predicted mean resistance and the observed frequency of kdr mutations in the Vgsc gene in field mosquito samples, with DDT showing the strongest association. These results improve our capacity to understand and predict resistance patterns throughout Africa and can guide the development of monitoring strategies.

Weetman D, Kamgang B, Badolo A, Moyes CL, Shearer FM, Coulibaly M, Pinto J, Lambrechts L, McCall PJ. 2018. Aedes Mosquitoes and Aedes-Borne Arboviruses in Africa: Current and Future Threats. Int J Environ Res Public Health, 15 (2), pp. 220-220. | Show Abstract | Read more

The Zika crisis drew attention to the long-overlooked problem of arboviruses transmitted by Aedes mosquitoes in Africa. Yellow fever, dengue, chikungunya and Zika are poorly controlled in Africa and often go unrecognized. However, to combat these diseases, both in Africa and worldwide, it is crucial that this situation changes. Here, we review available data on the distribution of each disease in Africa, their Aedes vectors, transmission potential, and challenges and opportunities for Aedes control. Data on disease and vector ranges are sparse, and consequently maps of risk are uncertain. Issues such as genetic and ecological diversity, and opportunities for integration with malaria control, are primarily African; others such as ever-increasing urbanization, insecticide resistance and lack of evidence for most control-interventions reflect problems throughout the tropics. We identify key knowledge gaps and future research areas, and in particular, highlight the need to improve knowledge of the distributions of disease and major vectors, insecticide resistance, and to develop specific plans and capacity for arboviral disease surveillance, prevention and outbreak responses.

Shearer FM, Longbottom J, Browne AJ, Pigott DM, Brady OJ, Kraemer MUG, Marinho F, Yactayo S, de Araújo VEM, da Nóbrega AA et al. 2018. Existing and potential infection risk zones of yellow fever worldwide: a modelling analysis. Lancet Glob Health, 6 (3), pp. e270-e278. | Show Abstract | Read more

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 disease's 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.

Pigott DM, Deshpande A, Letourneau I, Morozoff C, Reiner RC, Kraemer MUG, Brent SE, Bogoch II, Khan K, Biehl MH et al. 2017. Local, national, and regional viral haemorrhagic fever pandemic potential in Africa: a multistage analysis. Lancet, 390 (10113), pp. 2662-2672. | Show Abstract | Read more

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.

Golding N, Burstein R, Longbottom J, Browne AJ, Fullman N, Osgood-Zimmerman A, Earl L, Bhatt S, Cameron E, Casey DC et al. 2017. Mapping under-5 and neonatal mortality in Africa, 2000-15: a baseline analysis for the Sustainable Development Goals. Lancet, 390 (10108), pp. 2171-2182. | Show Abstract | Read more

BACKGROUND: During the Millennium Development Goal (MDG) era, many countries in Africa achieved marked reductions in under-5 and neonatal mortality. Yet the pace of progress toward these goals substantially varied at the national level, demonstrating an essential need for tracking even more local trends in child mortality. With the adoption of the Sustainable Development Goals (SDGs) in 2015, which established ambitious targets for improving child survival by 2030, optimal intervention planning and targeting will require understanding of trends and rates of progress at a higher spatial resolution. In this study, we aimed to generate high-resolution estimates of under-5 and neonatal all-cause mortality across 46 countries in Africa. METHODS: We assembled 235 geographically resolved household survey and census data sources on child deaths to produce estimates of under-5 and neonatal mortality at a resolution of 5 × 5 km grid cells across 46 African countries for 2000, 2005, 2010, and 2015. We used a Bayesian geostatistical analytical framework to generate these estimates, and implemented predictive validity tests. In addition to reporting 5 × 5 km estimates, we also aggregated results obtained from these estimates into three different levels-national, and subnational administrative levels 1 and 2-to provide the full range of geospatial resolution that local, national, and global decision makers might require. FINDINGS: Amid improving child survival in Africa, there was substantial heterogeneity in absolute levels of under-5 and neonatal mortality in 2015, as well as the annualised rates of decline achieved from 2000 to 2015. Subnational areas in countries such as Botswana, Rwanda, and Ethiopia recorded some of the largest decreases in child mortality rates since 2000, positioning them well to achieve SDG targets by 2030 or earlier. Yet these places were the exception for Africa, since many areas, particularly in central and western Africa, must reduce under-5 mortality rates by at least 8·8% per year, between 2015 and 2030, to achieve the SDG 3.2 target for under-5 mortality by 2030. INTERPRETATION: In the absence of unprecedented political commitment, financial support, and medical advances, the viability of SDG 3.2 achievement in Africa is precarious at best. By producing under-5 and neonatal mortality rates at multiple levels of geospatial resolution over time, this study provides key information for decision makers to target interventions at populations in the greatest need. In an era when precision public health increasingly has the potential to transform the design, implementation, and impact of health programmes, our 5 × 5 km estimates of child mortality in Africa provide a baseline against which local, national, and global stakeholders can map the pathways for ending preventable child deaths by 2030. FUNDING: Bill & Melinda Gates Foundation.

Shearer FM, Moyes CL, Pigott DM, Brady OJ, Marinho F, Deshpande A, Longbottom J, Browne AJ, Kraemer MUG, O'Reilly KM et al. 2017. Global yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis. Lancet Infect Dis, 17 (11), pp. 1209-1217. | Show Abstract | Read more

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 Union's Horizon 2020 research and innovation programme.

Moyes CL, Vontas J, Martins AJ, Ng LC, Koou SY, Dusfour I, Raghavendra K, Pinto J, Corbel V, David J-P, Weetman D. 2017. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans. PLoS Negl Trop Dis, 11 (7), pp. e0005625. | Show Abstract | Read more

Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

Corbel V, Fonseca DM, Weetman D, Pinto J, Achee NL, Chandre F, Coulibaly MB, Dusfour I, Grieco J, Juntarajumnong W et al. 2017. International workshop on insecticide resistance in vectors of arboviruses, December 2016, Rio de Janeiro, Brazil. Parasit Vectors, 10 (1), pp. 278. | Show Abstract | Read more

Vector-borne diseases transmitted by insect vectors such as mosquitoes occur in over 100 countries and affect almost half of the world's population. Dengue is currently the most prevalent arboviral disease but chikungunya, Zika and yellow fever show increasing prevalence and severity. Vector control, mainly by the use of insecticides, play a key role in disease prevention but the use of the same chemicals for more than 40 years, together with the dissemination of mosquitoes by trade and environmental changes, resulted in the global spread of insecticide resistance. In this context, innovative tools and strategies for vector control, including the management of resistance, are urgently needed. This report summarizes the main outputs of the first international workshop on Insecticide resistance in vectors of arboviruses held in Rio de Janeiro, Brazil, 5-8 December 2016. The primary aims of this workshop were to identify strategies for the development and implementation of standardized insecticide resistance management, also to allow comparisons across nations and across time, and to define research priorities for control of vectors of arboviruses. The workshop brought together 163 participants from 28 nationalities and was accessible, live, through the web (> 70,000 web-accesses over 3 days).

Killeen GF, Kiware SS, Okumu FO, Sinka ME, Moyes CL, Massey NC, Gething PW, Marshall JM, Chaccour CJ, Tusting LS. 2017. Going beyond personal protection against mosquito bites to eliminate malaria transmission: population suppression of malaria vectors that exploit both human and animal blood. BMJ Glob Health, 2 (2), pp. e000198. | Show Abstract | Read more

Protecting individuals and households against mosquito bites with long-lasting insecticidal nets (LLINs) or indoor residual spraying (IRS) can suppress entire populations of unusually efficient malaria vector species that predominantly feed indoors on humans. Mosquitoes which usually feed on animals are less reliant on human blood, so they are far less vulnerable to population suppression effects of such human-targeted insecticidal measures. Fortunately, the dozens of mosquito species which primarily feed on animals are also relatively inefficient vectors of malaria, so personal protection against mosquito bites may be sufficient to eliminate transmission. However, a handful of mosquito species are particularly problematic vectors of residual malaria transmission, because they feed readily on both humans and animals. These unusual vectors feed often enough on humans to be potent malaria vectors, but also often enough on animals to evade population control with LLINs, IRS or any other insecticidal personal protection measure targeted only to humans. Anopheles arabiensis and A. coluzzii in Africa, A. darlingi in South America and A. farauti in Oceania, as well as A. culicifacies species E, A. fluviatilis species S, A. lesteri and A. minimus in Asia, all feed readily on either humans or animals and collectively mediate residual malaria transmission across most of the tropics. Eliminating malaria transmission by vectors exhibiting such dual host preferences will require aggressive mosquito population abatement, rather than just personal protection of humans. Population suppression of even these particularly troublesome vectors is achievable with a variety of existing vector control technologies that remain underdeveloped or underexploited.

Browne AJ, Guerra CA, Alves RV, da Costa VM, Wilson AL, Pigott DM, Hay SI, Lindsay SW, Golding N, Moyes CL. 2017. The contemporary distribution of Trypanosoma cruzi infection in humans, alternative hosts and vectors. Sci Data, 4 (1), pp. 170050. | Show Abstract | Read more

Chagas is a potentially fatal chronic disease affecting large numbers of people across the Americas and exported throughout the world through human population movement. It is caused by the Trypanosoma cruzi parasite, which is transmitted by triatomine vectors to humans and a wide range of alternative host species. The database described here was compiled to allow the risk of vectorial transmission to humans to be mapped using geospatial models. The database collates all available records, published since 2003, for prevalence and occurrence of infection in humans, vectors and alternative hosts, and links each record to a defined time and location. A total of 16,802 records of infection have been extracted from the published literature and unpublished sources. The resulting database can be used to improve our understanding of the geographic variation in vector infection prevalence and to estimate the risk of vectorial transmission of T. cruzi to humans.

Longbottom J, Browne AJ, Pigott DM, Sinka ME, Golding N, Hay SI, Moyes CL, Shearer FM. 2017. Mapping the spatial distribution of the Japanese encephalitis vector, Culex tritaeniorhynchus Giles, 1901 (Diptera: Culicidae) within areas of Japanese encephalitis risk. Parasit Vectors, 10 (1), pp. 148. | Show Abstract | Read more

BACKGROUND: Japanese encephalitis (JE) is one of the most significant aetiological agents of viral encephalitis in Asia. This medically important arbovirus is primarily spread from vertebrate hosts to humans by the mosquito vector Culex tritaeniorhynchus. Knowledge of the contemporary distribution of this vector species is lacking, and efforts to define areas of disease risk greatly depend on a thorough understanding of the variation in this mosquito's geographical distribution. RESULTS: We assembled a contemporary database of Cx. tritaeniorhynchus presence records within Japanese encephalitis risk areas from formal literature and other relevant resources, resulting in 1,045 geo-referenced, spatially and temporally unique presence records spanning from 1928 to 2014 (71.9% of records obtained between 2001 and 2014). These presence data were combined with a background dataset capturing sample bias in our presence dataset, along with environmental and socio-economic covariates, to inform a boosted regression tree model predicting environmental suitability for Cx. tritaeniorhynchus at each 5 × 5 km gridded cell within areas of JE risk. The resulting fine-scale map highlights areas of high environmental suitability for this species across India, Nepal and China that coincide with areas of high JE incidence, emphasising the role of this vector in disease transmission and the utility of the map generated. CONCLUSIONS: Our map contributes towards efforts determining the spatial heterogeneity in Cx. tritaeniorhynchus distribution within the limits of JE transmission. Specifically, this map can be used to inform vector control programs and can be used to identify key areas where the prevention of Cx. tritaeniorhynchus establishment should be a priority.

Wiebe A, Longbottom J, Gleave K, Shearer FM, Sinka ME, Massey NC, Cameron E, Bhatt S, Gething PW, Hemingway J et al. 2017. Geographical distributions of African malaria vector sibling species and evidence for insecticide resistance. Malar J, 16 (1), pp. 85. | Show Abstract | Read more

BACKGROUND: Many 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. RESULTS: Within 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. CONCLUSIONS: Sibling 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.

Corbel V, Achee NL, Chandre F, Coulibaly MB, Dusfour I, Fonseca DM, Grieco J, Juntarajumnong W, Lenhart A, Martins AJ et al. 2016. Tracking Insecticide Resistance in Mosquito Vectors of Arboviruses: The Worldwide Insecticide resistance Network (WIN). PLoS Negl Trop Dis, 10 (12), pp. e0005054. | Read more

Shearer FM, Huang Z, Weiss DJ, Wiebe A, Gibson HS, Battle KE, Pigott DM, Brady OJ, Putaporntip C, Jongwutiwes S et al. 2016. Estimating Geographical Variation in the Risk of Zoonotic Plasmodium knowlesi Infection in Countries Eliminating Malaria. PLoS Negl Trop Dis, 10 (8), pp. e0004915. | Show Abstract | Read more

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.

Pigott DM, Millear AI, Earl L, Morozoff C, Han BA, Shearer FM, Weiss DJ, Brady OJ, Kraemer MU, Moyes CL et al. 2016. Updates to the zoonotic niche map of Ebola virus disease in Africa. Elife, 5 (2016JULY), | Show Abstract | Read more

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.

Nsoesie EO, Kraemer MU, Golding N, Pigott DM, Brady OJ, Moyes CL, Johansson MA, Gething PW, Velayudhan R, Khan K et al. 2016. Global distribution and environmental suitability for chikungunya virus, 1952 to 2015. Euro Surveill, 21 (20), pp. 7-18. | Show Abstract | Read more

Chikungunya fever is an acute febrile illness caused by the chikungunya virus (CHIKV), which is transmitted to humans by Aedes mosquitoes. Although chikungunya fever is rarely fatal, patients can experience debilitating symptoms that last from months to years. Here we comprehensively assess the global distribution of chikungunya and produce high-resolution maps, using an established modelling framework that combines a comprehensive occurrence database with bespoke environmental correlates, including up-to-date Aedes distribution maps. This enables estimation of the current total population-at-risk of CHIKV transmission and identification of areas where the virus may spread to in the future. We identified 94 countries with good evidence for current CHIKV presence and a set of countries in the New and Old World with potential for future CHIKV establishment, demonstrated by high environmental suitability for transmission and in some cases previous sporadic reports. Aedes aegypti presence was identified as one of the major contributing factors to CHIKV transmission but significant geographical heterogeneity exists. We estimated 1.3 billion people are living in areas at-risk of CHIKV transmission. These maps provide a baseline for identifying areas where prevention and control efforts should be prioritised and can be used to guide estimation of the global burden of CHIKV.

Moyes CL, Shearer FM, Huang Z, Wiebe A, Gibson HS, Nijman V, Mohd-Azlan J, Brodie JF, Malaivijitnond S, Linkie M et al. 2016. Predicting the geographical distributions of the macaque hosts and mosquito vectors of Plasmodium knowlesi malaria in forested and non-forested areas. Parasit Vectors, 9 (1), pp. 242. | Show Abstract | Read more

BACKGROUND: Plasmodium knowlesi is a zoonotic pathogen, transmitted among macaques and to humans by anopheline mosquitoes. Information on P. knowlesi malaria is lacking in most regions so the first step to understand the geographical distribution of disease risk is to define the distributions of the reservoir and vector species. METHODS: We used macaque and mosquito species presence data, background data that captured sampling bias in the presence data, a boosted regression tree model and environmental datasets, including annual data for land classes, to predict the distributions of each vector and host species. We then compared the predicted distribution of each species with cover of each land class. RESULTS: Fine-scale distribution maps were generated for three macaque host species (Macaca fascicularis, M. nemestrina and M. leonina) and two mosquito vector complexes (the Dirus Complex and the Leucosphyrus Complex). The Leucosphyrus Complex was predicted to occur in areas with disturbed, but not intact, forest cover (> 60% tree cover) whereas the Dirus Complex was predicted to occur in areas with 10-100% tree cover as well as vegetation mosaics and cropland. Of the macaque species, M. nemestrina was mainly predicted to occur in forested areas whereas M. fascicularis was predicted to occur in vegetation mosaics, cropland, wetland and urban areas in addition to forested areas. CONCLUSIONS: The predicted M. fascicularis distribution encompassed a wide range of habitats where humans are found. This is of most significance in the northern part of its range where members of the Dirus Complex are the main P. knowlesi vectors because these mosquitoes were also predicted to occur in a wider range of habitats. Our results support the hypothesis that conversion of intact forest into disturbed forest (for example plantations or timber concessions), or the creation of vegetation mosaics, will increase the probability that members of the Leucosphyrus Complex occur at these locations, as well as bringing humans into these areas. An explicit analysis of disease risk itself using infection data is required to explore this further. The species distributions generated here can now be included in future analyses of P. knowlesi infection risk.

Sinka ME, Golding N, Massey NC, Wiebe A, Huang Z, Hay SI, Moyes CL. 2016. Modelling the relative abundance of the primary African vectors of malaria before and after the implementation of indoor, insecticide-based vector control. Malar J, 15 (1), pp. 142. | Show Abstract | Read more

BACKGROUND: Malaria remains a heavy burden across sub-Saharan Africa where transmission is maintained by some of the world's most efficient vectors. Indoor insecticide-based control measures have significantly reduced transmission, yet elimination remains a distant target. Knowing the relative abundance of the primary vector species can provide transmission models with much needed information to guide targeted control measures. Moreover, understanding how existing interventions are impacting on these relative abundances highlights where alternative control (e.g., larval source management) is needed. METHODS: Using the habitat suitability probabilities generated by predictive species distribution models combined with data collated from the literature, a multinomial generalized additive model was applied to produce relative abundance estimates for Anopheles arabiensis, Anopheles funestus and Anopheles gambiae/Anopheles coluzzii. Using pre- and post-intervention abundance data, estimates of the effect of indoor insecticide-based interventions on these relative abundances were made and are illustrated in post-intervention maps. RESULTS: Conditional effect plots and relative abundance maps illustrate the individual species' predicted habitat suitability and how they interact when in sympatry. Anopheles arabiensis and An. funestus show an affinity in habitat preference at the expense of An. gambiae/An. coluzzii, whereas increasing habitat suitability for An. gambiae/An. coluzzii is conversely less suitable for An. arabiensis but has little effect on An. funestus. Indoor insecticide-based interventions had a negative impact on the relative abundance of An. funestus, and a lesser effect on An. arabiensis. Indoor residual spraying had the greatest impact on the relative abundance of An. funestus, and a lesser effect on An. gambiae/An. coluzzii. Insecticide-treated bed nets reduced the relative abundance of both species equally. These results do not indicate changes in the absolute abundance of these species, which may be reduced for all species overall. CONCLUSIONS: The maps presented here highlight the interactions between the primary vector species in sub-Saharan Africa and demonstrate that An. funestus is more susceptible to certain indoor-based insecticide interventions than An. gambiae/An. coluzzii, which in turn, is more susceptible than An. arabiensis. This may provide An. arabiensis with a competitive advantage where it is found in sympatry with other more endophilic vectors, and potentially increase the need for outdoor-based vector interventions to deal with any residual transmission barring the way to malaria elimination.

Massey NC, Garrod G, Wiebe A, Henry AJ, Huang Z, Moyes CL, Sinka ME. 2016. A global bionomic database for the dominant vectors of human malaria. Sci Data, 3 (1), pp. 160014. | Show Abstract | Read more

Anopheles mosquitoes were first recognised as the transmitters of human malaria in the late 19th Century and have been subject to a huge amount of research ever since. Yet there is still much that is unknown regarding the ecology, behaviour (collectively 'bionomics') and sometimes even the identity of many of the world's most prominent disease vectors, much less the within-species variation in their bionomics. Whilst malaria elimination remains an ambitious goal, it is becoming increasingly clear that knowledge of vector behaviour is needed to effectively target control measures. A database of bionomics data for the dominant vector species of malaria worldwide has been compiled from published peer-reviewed literature. The data identification and collation processes are described, together with the geo-positioning and quality control methods. This is the only such dataset in existence and provides a valuable resource to researchers and policy makers in this field.

Brady OJ, Godfray HCJ, Tatem AJ, Gething PW, Cohen JM, McKenzie FE, Perkins TA, Reiner RC, Tusting LS, Sinka ME et al. 2016. Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination. Trans R Soc Trop Med Hyg, 110 (2), pp. 107-117. | Show Abstract | Read more

BACKGROUND: Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria. METHODS AND RESULTS: Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention. CONCLUSIONS: Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions.

Limmathurotsakul D, Golding N, Dance DA, Messina JP, Pigott DM, Moyes CL, Rolim DB, Bertherat E, Day NP, Peacock SJ, Hay SI. 2016. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol, 1 (1), | Show Abstract | Read more

Burkholderia pseudomallei, a highly pathogenic bacterium that causes melioidosis, is commonly found in soil in Southeast Asia and Northern Australia1,2. Melioidosis can be difficult to diagnose due to its diverse clinical manifestations and the inadequacy of conventional bacterial identification methods3. The bacterium is intrinsically resistant to a wide range of antimicrobials, and treatment with ineffective antimicrobials may result in case fatality rates (CFRs) exceeding 70%4,5. The importation of infected animals has, in the past, spread melioidosis to non-endemic areas6,7. The global distribution of B. pseudomallei and burden of melioidosis, however, remain poorly understood. Here, we map documented human and animal cases, and the presence of environmental B. pseudomallei, and combine this in a formal modelling framework8-10 to estimate the global burden of melioidosis. We estimate there to be 165,000 (95% credible interval 68,000-412,000) human melioidosis cases per year worldwide, of which 89,000 (36,000-227,000) die. Our estimates suggest that melioidosis is severely underreported in the 45 countries in which it is known to be endemic and that melioidosis is likely endemic in a further 34 countries which have never reported the disease. The large numbers of estimated cases and fatalities emphasise that the disease warrants renewed attention from public health officials and policy makers.

Patching HMM, Hudson LM, Cooke W, Garcia AJ, Hay SI, Roberts M, Moyes CL. 2015. A Supervised Learning Process to Validate Online Disease Reports for Use in Predictive Models. Big Data, 3 (4), pp. 230-237. | Show Abstract | Read more

Pathogen distribution models that predict spatial variation in disease occurrence require data from a large number of geographic locations to generate disease risk maps. Traditionally, this process has used data from public health reporting systems; however, using online reports of new infections could speed up the process dramatically. Data from both public health systems and online sources must be validated before they can be used, but no mechanisms exist to validate data from online media reports. We have developed a supervised learning process to validate geolocated disease outbreak data in a timely manner. The process uses three input features, the data source and two metrics derived from the location of each disease occurrence. The location of disease occurrence provides information on the probability of disease occurrence at that location based on environmental and socioeconomic factors and the distance within or outside the current known disease extent. The process also uses validation scores, generated by disease experts who review a subset of the data, to build a training data set. The aim of the supervised learning process is to generate validation scores that can be used as weights going into the pathogen distribution model. After analyzing the three input features and testing the performance of alternative processes, we selected a cascade of ensembles comprising logistic regressors. Parameter values for the training data subset size, number of predictors, and number of layers in the cascade were tested before the process was deployed. The final configuration was tested using data for two contrasting diseases (dengue and cholera), and 66%-79% of data points were assigned a validation score. The remaining data points are scored by the experts, and the results inform the training data set for the next set of predictors, as well as going to the pathogen distribution model. The new supervised learning process has been implemented within our live site and is being used to validate the data that our system uses to produce updated predictive disease maps on a weekly basis.

Bhatt S, Weiss DJ, Mappin B, Dalrymple U, Cameron E, Bisanzio D, Smith DL, Moyes CL, Tatem AJ, Lynch M et al. 2015. Coverage and system efficiencies of insecticide-treated nets in Africa from 2000 to 2017. Elife, 4 (DECEMBER2015), | Show Abstract | Read more

Insecticide-treated nets (ITNs) for malaria control are widespread but coverage remains inadequate. We developed a Bayesian model using data from 102 national surveys, triangulated against delivery data and distribution reports, to generate year-by-year estimates of four ITN coverage indicators. We explored the impact of two potential 'inefficiencies': uneven net distribution among households and rapid rates of net loss from households. We estimated that, in 2013, 21% (17%-26%) of ITNs were over-allocated and this has worsened over time as overall net provision has increased. We estimated that rates of ITN loss from households are more rapid than previously thought, with 50% lost after 23 (20-28) months. We predict that the current estimate of 920 million additional ITNs required to achieve universal coverage would in reality yield a lower level of coverage (77% population access). By improving efficiency, however, the 920 million ITNs could yield population access as high as 95%.

Golding N, Wilson AL, Moyes CL, Cano J, Pigott DM, Velayudhan R, Brooker SJ, Smith DL, Hay SI, Lindsay SW. 2015. Integrating vector control across diseases. BMC Med, 13 (1), pp. 249. | Show Abstract | Read more

BACKGROUND: Vector-borne diseases cause a significant proportion of the overall burden of disease across the globe, accounting for over 10 % of the burden of infectious diseases. Despite the availability of effective interventions for many of these diseases, a lack of resources prevents their effective control. Many existing vector control interventions are known to be effective against multiple diseases, so combining vector control programmes to simultaneously tackle several diseases could offer more cost-effective and therefore sustainable disease reductions. DISCUSSION: The highly successful cross-disease integration of vaccine and mass drug administration programmes in low-resource settings acts a precedent for cross-disease vector control. Whilst deliberate implementation of vector control programmes across multiple diseases has yet to be trialled on a large scale, a number of examples of 'accidental' cross-disease vector control suggest the potential of such an approach. Combining contemporary high-resolution global maps of the major vector-borne pathogens enables us to quantify overlap in their distributions and to estimate the populations jointly at risk of multiple diseases. Such an analysis shows that over 80 % of the global population live in regions of the world at risk from one vector-borne disease, and more than half the world's population live in areas where at least two different vector-borne diseases pose a threat to health. Combining information on co-endemicity with an assessment of the overlap of vector control methods effective against these diseases allows us to highlight opportunities for such integration. Malaria, leishmaniasis, lymphatic filariasis, and dengue are prime candidates for combined vector control. All four of these diseases overlap considerably in their distributions and there is a growing body of evidence for the effectiveness of insecticide-treated nets, screens, and curtains for controlling all of their vectors. The real-world effectiveness of cross-disease vector control programmes can only be evaluated by large-scale trials, but there is clear evidence of the potential of such an approach to enable greater overall health benefit using the limited funds available.

Uyoga S, Ndila CM, Macharia AW, Nyutu G, Shah S, Peshu N, Clarke GM, Kwiatkowski DP, Rockett KA, Williams TN, MalariaGEN Consortium. 2015. Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study. Lancet Haematol, 2 (10), pp. e437-e444. | Show Abstract | Read more

BACKGROUND: The global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya. METHODS: We did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3-12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category. FINDINGS: 2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant protection from severe malaria (odds ratio [OR] 0·82, 95% CI 0·70-0·97; p=0·020) among G6PD c.202T heterozygous girls but no evidence for protection among G6PD c.202T hemizygous boys and homozygous girls (OR 1·18, 0·99-1·40; p=0·056). Median follow-up for the mild disease cohort study was 2·24 years (IQR 2·22-2·85). G6PD c.202T had no effect on other common diseases of childhood in heterozygous girls (incidence rate ratio 0·98, 95% CI 0·86-1·11; p=0·82) or homozygous girls or hemizygous boys (0·93, 0·82-1·04; p=0·25), with the sole exception of a marginally significant increase in the incidence of helminth infections among heterozygous girls. INTERPRETATION: Heterozygous girls might be the driving force for the positive selection of G6PD deficiency alleles. Further studies are needed to definitively establish the mechanisms by which G6PD deficiency confers an advantage against malaria in heterozygous individuals. Such studies could lead to the development of new treatments. FUNDING: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health (as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative).

Bhatt S, Weiss DJ, Cameron E, Bisanzio D, Mappin B, Dalrymple U, Battle K, Moyes CL, Henry A, Eckhoff PA et al. 2015. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature, 526 (7572), pp. 207-211. | Show Abstract | Read more

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

Mylne AQN, Pigott DM, Longbottom J, Shearer F, Duda KA, Messina JP, Weiss DJ, Moyes CL, Golding N, Hay SI. 2015. Mapping the zoonotic niche of Lassa fever in Africa. Trans R Soc Trop Med Hyg, 109 (8), pp. 483-492. | Show Abstract | Read more

BACKGROUND: Lassa fever is a viral haemorrhagic illness responsible for disease outbreaks across West Africa. It is a zoonosis, with the primary reservoir species identified as the Natal multimammate mouse, Mastomys natalensis. The host is distributed across sub-Saharan Africa while the virus' range appears to be restricted to West Africa. The majority of infections result from interactions between the animal reservoir and human populations, although secondary transmission between humans can occur, particularly in hospital settings. METHODS: Using a species distribution model, the locations of confirmed human and animal infections with Lassa virus (LASV) were used to generate a probabilistic surface of zoonotic transmission potential across sub-Saharan Africa. RESULTS: Our results predict that 37.7 million people in 14 countries, across much of West Africa, live in areas where conditions are suitable for zoonotic transmission of LASV. Four of these countries, where at-risk populations are predicted, have yet to report any cases of Lassa fever. CONCLUSIONS: These maps act as a spatial guide for future surveillance activities to better characterise the geographical distribution of the disease and understand the anthropological, virological and zoological interactions necessary for viral transmission. Combining this zoonotic niche map with detailed patient travel histories can aid differential diagnoses of febrile illnesses, enabling a more rapid response in providing care and reducing the risk of onward transmission.

Pigott DM, Howes RE, Wiebe A, Battle KE, Golding N, Gething PW, Dowell SF, Farag TH, Garcia AJ, Kimball AM et al. 2015. Prioritising Infectious Disease Mapping. PLoS Negl Trop Dis, 9 (6), pp. e0003756. | Show Abstract | Read more

BACKGROUND: Increasing volumes of data and computational capacity afford unprecedented opportunities to scale up infectious disease (ID) mapping for public health uses. Whilst a large number of IDs show global spatial variation, comprehensive knowledge of these geographic patterns is poor. Here we use an objective method to prioritise mapping efforts to begin to address the large deficit in global disease maps currently available. METHODOLOGY/PRINCIPAL FINDINGS: Automation of ID mapping requires bespoke methodological adjustments tailored to the epidemiological characteristics of different types of diseases. Diseases were therefore grouped into 33 clusters based upon taxonomic divisions and shared epidemiological characteristics. Disability-adjusted life years, derived from the Global Burden of Disease 2013 study, were used as a globally consistent metric of disease burden. A review of global health stakeholders, existing literature and national health priorities was undertaken to assess relative interest in the diseases. The clusters were ranked by combining both metrics, which identified 44 diseases of main concern within 15 principle clusters. Whilst malaria, HIV and tuberculosis were the highest priority due to their considerable burden, the high priority clusters were dominated by neglected tropical diseases and vector-borne parasites. CONCLUSIONS/SIGNIFICANCE: A quantitative, easily-updated and flexible framework for prioritising diseases is presented here. The study identifies a possible future strategy for those diseases where significant knowledge gaps remain, as well as recognising those where global mapping programs have already made significant progress. For many conditions, potential shared epidemiological information has yet to be exploited.

Pigott DM, Golding N, Mylne A, Huang Z, Henry AJ, Weiss DJ, Brady OJ, Kraemer MUG, Smith DL, Moyes CL et al. 2014. Mapping the zoonotic niche of Ebola virus disease in Africa. Elife, 3 pp. e04395. | Show Abstract | Read more

Ebola virus disease (EVD) is a complex zoonosis that is highly virulent in humans. The largest recorded outbreak of EVD is ongoing in West Africa, outside of its previously reported and predicted niche. We assembled location data on all recorded zoonotic transmission to humans and Ebola virus infection in bats and primates (1976-2014). Using species distribution models, these occurrence data were paired with environmental covariates to predict a zoonotic transmission niche covering 22 countries across Central and West Africa. Vegetation, elevation, temperature, evapotranspiration, and suspected reservoir bat distributions define this relationship. At-risk areas are inhabited by 22 million people; however, the rarity of human outbreaks emphasises the very low probability of transmission to humans. Increasing population sizes and international connectivity by air since the first detection of EVD in 1976 suggest that the dynamics of human-to-human secondary transmission in contemporary outbreaks will be very different to those of the past.

Pigott DM, Bhatt S, Golding N, Duda KA, Battle KE, Brady OJ, Messina JP, Balard Y, Bastien P, Pratlong F et al. 2014. Global distribution maps of the leishmaniases. Elife, 3 | Show Abstract | Read more

The leishmaniases are vector-borne diseases that have a broad global distribution throughout much of the Americas, Africa, and Asia. Despite representing a significant public health burden, our understanding of the global distribution of the leishmaniases remains vague, reliant upon expert opinion and limited to poor spatial resolution. A global assessment of the consensus of evidence for leishmaniasis was performed at a sub-national level by aggregating information from a variety of sources. A database of records of cutaneous and visceral leishmaniasis occurrence was compiled from published literature, online reports, strain archives, and GenBank accessions. These, with a suite of biologically relevant environmental covariates, were used in a boosted regression tree modelling framework to generate global environmental risk maps for the leishmaniases. These high-resolution evidence-based maps can help direct future surveillance activities, identify areas to target for disease control and inform future burden estimation efforts.

Moyes CL, Henry AJ, Golding N, Huang Z, Singh B, Baird JK, Newton PN, Huffman M, Duda KA, Drakeley CJ et al. 2014. Defining the geographical range of the Plasmodium knowlesi reservoir. PLoS Negl Trop Dis, 8 (3), pp. e2780. | Show Abstract | Read more

BACKGROUND: The simian malaria parasite, Plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. Because malaria caused by P. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. Information is required on the occurrence of human cases in different locations, on which non-human primates host this parasite and on which vectors are able to transmit it to humans. We undertook a systematic review and ranked the existing evidence, at a subnational spatial scale, to investigate the potential geographical range of the parasite reservoir capable of infecting humans. METHODOLOGY/PRINCIPAL FINDINGS: After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region. CONCLUSIONS/SIGNIFICANCE: We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment.

Piel FB, Howes RE, Nyangiri OA, Moyes CL, Williams TN, Weatherall DJ, Hay SI. 2013. Online biomedical resources for malaria-related red cell disorders. Hum Mutat, 34 (7), pp. 937-944. | Show Abstract | Read more

Warnings about the expected increase of the global public health burden of malaria-related red cell disorders are accruing. Past and present epidemiological data are necessary to track spatial and temporal changes in the frequencies of these genetic disorders. A number of open access biomedical databases including data on malaria-related red cell disorders have been launched over the last two decades. Here, we review the content of these databases, most of which focus on genetic diversity, and we describe a new epidemiological resource developed by the Malaria Atlas Project. To tackle upcoming public health challenges, the integration of epidemiological and genetic data is important. As many countries are considering implementing national screening programs, strategies to make such data more accessible are also needed.

Moyes CL, Temperley WH, Henry AJ, Burgert CR, Hay SI. 2013. Providing open access data online to advance malaria research and control. Malar J, 12 (1), pp. 161. | Show Abstract | Read more

BACKGROUND: To advance research on malaria, the outputs from existing studies and the data that fed into them need to be made freely available. This will ensure new studies can build on the work that has gone before. These data and results also need to be made available to groups who are developing public health policies based on up-to-date evidence. The Malaria Atlas Project (MAP) has collated and geopositioned over 50,000 parasite prevalence and vector occurrence survey records contributed by over 3,000 sources including research groups, government agencies and non-governmental organizations worldwide. This paper describes the results of a project set up to release data gathered, used and generated by MAP. METHODS: Requests for permission to release data online were sent to 236 groups who had contributed unpublished prevalence (parasite rate) surveys. An online explorer tool was developed so that users can visualize the spatial distribution of the vector and parasite survey data before downloading it. In addition, a consultation group was convened to provide advice on the mode and format of release for data generated by MAP's modelling work. New software was developed to produce a suite of publication-quality map images for download from the internet for use in external publications. CONCLUSION: More than 40,000 survey records can now be visualized on a set of dynamic maps and downloaded from the MAP website on a free and unrestricted basis. As new data are added and new permissions to release existing data come in, the volume of data available for download will increase. The modelled data output from MAP's own analyses are also available online in a range of formats, including image files and GIS surface data, for use in advocacy, education, further research and to help parameterize or validate other mathematical models.

Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O et al. 2013. The global distribution and burden of dengue. Nature, 496 (7446), pp. 504-507. | Show Abstract | Read more

Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes. For some patients, dengue is a life-threatening illness. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread. The contemporary worldwide distribution of the risk of dengue virus infection and its public health burden are poorly known. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation.

Hay SI, George DB, Moyes CL, Brownstein JS. 2013. Big data opportunities for global infectious disease surveillance. PLoS Med, 10 (4), pp. e1001413. | Show Abstract | Read more

Simon Hay and colleagues discuss the potential and challenges of producing continually updated infectious disease risk maps using diverse and large volume data sources such as social media.

von Seidlein L, Auburn S, Espino F, Shanks D, Cheng Q, McCarthy J, Baird K, Moyes C, Howes R, Ménard D et al. 2013. Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report. Malar J, 12 (1), pp. 112. | Show Abstract | Read more

The diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency is a crucial aspect in the current phases of malaria control and elimination, which will require the wider use of 8-aminoquinolines for both reducing Plasmodium falciparum transmission and achieving the radical cure of Plasmodium vivax. 8-aminoquinolines, such as primaquine, can induce severe haemolysis in G6PD-deficient individuals, potentially creating significant morbidity and undermining confidence in 8-aminoquinoline prescription. On the other hand, erring on the side of safety and excluding large numbers of people with unconfirmed G6PD deficiency from treatment with 8-aminoquinolines will diminish the impact of these drugs. Estimating the remaining G6PD enzyme activity is the most direct, accessible, and reliable assessment of the phenotype and remains the gold standard for the diagnosis of patients who could be harmed by the administration of primaquine. Genotyping seems an unambiguous technique, but its use is limited by cost and the large range of recognized G6PD genotypes. A number of enzyme activity assays diagnose G6PD deficiency, but they require a cold chain, specialized equipment, and laboratory skills. These assays are impractical for care delivery where most patients with malaria live. Improvements to the diagnosis of G6PD deficiency are required for the broader and safer use of 8-aminoquinolines to kill hypnozoites, while lower doses of primaquine may be safely used to kill gametocytes without testing. The discussions and conclusions of a workshop conducted in Incheon, Korea in May 2012 to review key knowledge gaps in G6PD deficiency are reported here.

Hay SI, Battle KE, Pigott DM, Smith DL, Moyes CL, Bhatt S, Brownstein JS, Collier N, Myers MF, George DB, Gething PW. 2013. Global mapping of infectious disease. Philos Trans R Soc Lond B Biol Sci, 368 (1614), pp. 20120250. | Show Abstract | Read more

The primary aim of this review was to evaluate the state of knowledge of the geographical distribution of all infectious diseases of clinical significance to humans. A systematic review was conducted to enumerate cartographic progress, with respect to the data available for mapping and the methods currently applied. The results helped define the minimum information requirements for mapping infectious disease occurrence, and a quantitative framework for assessing the mapping opportunities for all infectious diseases. This revealed that of 355 infectious diseases identified, 174 (49%) have a strong rationale for mapping and of these only 7 (4%) had been comprehensively mapped. A variety of ambitions, such as the quantification of the global burden of infectious disease, international biosurveillance, assessing the likelihood of infectious disease outbreaks and exploring the propensity for infectious disease evolution and emergence, are limited by these omissions. An overview of the factors hindering progress in disease cartography is provided. It is argued that rapid improvement in the landscape of infectious diseases mapping can be made by embracing non-conventional data sources, automation of geo-positioning and mapping procedures enabled by machine learning and information technology, respectively, in addition to harnessing labour of the volunteer 'cognitive surplus' through crowdsourcing.

Qi Q, Guerra CA, Moyes CL, Elyazar IRF, Gething PW, Hay SI, Tatem AJ. 2012. The effects of urbanization on global Plasmodium vivax malaria transmission. Malar J, 11 (1), pp. 403. | Show Abstract | Read more

BACKGROUND: Many recent studies have examined the impact of urbanization on Plasmodium falciparum malaria endemicity and found a general trend of reduced transmission in urban areas. However, none has examined the effect of urbanization on Plasmodium vivax malaria, which is the most widely distributed malaria species and can also cause severe clinical syndromes in humans. In this study, a set of 10,003 community-based P. vivax parasite rate (PvPR) surveys are used to explore the relationships between PvPR in urban and rural settings. METHODS: The PvPR surveys were overlaid onto a map of global urban extents to derive an urban/rural assignment. The differences in PvPR values between urban and rural areas were then examined. Groups of PvPR surveys inside individual city extents (urban) and surrounding areas (rural) were identified to examine the local variations in PvPR values. Finally, the relationships of PvPR between urban and rural areas within the ranges of 41 dominant Anopheles vectors were examined. RESULTS: Significantly higher PvPR values in rural areas were found globally. The relationship was consistent at continental scales when focusing on Africa and Asia only, but in the Americas, significantly lower values of PvPR in rural areas were found, though the numbers of surveys were small. Moreover, except for the countries in the Americas, the same trends were found at national scales in African and Asian countries, with significantly lower values of PvPR in urban areas. However, the patterns at city scales among 20 specific cities where sufficient data were available were less clear, with seven cities having significantly lower PvPR values in urban areas and two cities showing significantly lower PvPR in rural areas. The urban-rural PvPR differences within the ranges of the dominant Anopheles vectors were generally, in agreement with the regional patterns found. CONCLUSIONS: Except for the Americas, the patterns of significantly lower P. vivax transmission in urban areas have been found globally, regionally, nationally and by dominant vector species here, following trends observed previously for P. falciparum. To further understand these patterns, more epidemiological, entomological and parasitological analyses of the disease at smaller spatial scales are needed.

Battle KE, Gething PW, Elyazar IRF, Moyes CL, Sinka ME, Howes RE, Guerra CA, Price RN, Baird KJ, Hay SI. 2012. The global public health significance of Plasmodium vivax. Adv Parasitol, 80 pp. 1-111. | Show Abstract | Read more

Plasmodium vivax occurs globally and thrives in both temperate and tropical climates. Here, we review the evidence of the biological limits of its contemporary distribution and the global population at risk (PAR) of the disease within endemic countries. We also review the most recent evidence for the endemic level of transmission within its range and discuss the implications for burden of disease assessments. Finally, the evidence-base for defining the contemporary distribution and PAR of P. vivax are discussed alongside a description of the vectors of human malaria within the limits of risk. This information along with recent data documenting the severe morbid and fatal consequences of P. vivax infection indicates that the public health significance of P. vivax is likely to have been seriously underestimated.

Gething PW, Elyazar IRF, Moyes CL, Smith DL, Battle KE, Guerra CA, Patil AP, Tatem AJ, Howes RE, Myers MF et al. 2012. A long neglected world malaria map: Plasmodium vivax endemicity in 2010. PLoS Negl Trop Dis, 6 (9), pp. e1814. | Show Abstract | Read more

BACKGROUND: Current understanding of the spatial epidemiology and geographical distribution of Plasmodium vivax is far less developed than that for P. falciparum, representing a barrier to rational strategies for control and elimination. Here we present the first systematic effort to map the global endemicity of this hitherto neglected parasite. METHODOLOGY AND FINDINGS: We first updated to the year 2010 our earlier estimate of the geographical limits of P. vivax transmission. Within areas of stable transmission, an assembly of 9,970 geopositioned P. vivax parasite rate (PvPR) surveys collected from 1985 to 2010 were used with a spatiotemporal Bayesian model-based geostatistical approach to estimate endemicity age-standardised to the 1-99 year age range (PvPR(1-99)) within every 5×5 km resolution grid square. The model incorporated data on Duffy negative phenotype frequency to suppress endemicity predictions, particularly in Africa. Endemicity was predicted within a relatively narrow range throughout the endemic world, with the point estimate rarely exceeding 7% PvPR(1-99). The Americas contributed 22% of the global area at risk of P. vivax transmission, but high endemic areas were generally sparsely populated and the region contributed only 6% of the 2.5 billion people at risk (PAR) globally. In Africa, Duffy negativity meant stable transmission was constrained to Madagascar and parts of the Horn, contributing 3.5% of global PAR. Central Asia was home to 82% of global PAR with important high endemic areas coinciding with dense populations particularly in India and Myanmar. South East Asia contained areas of the highest endemicity in Indonesia and Papua New Guinea and contributed 9% of global PAR. CONCLUSIONS AND SIGNIFICANCE: This detailed depiction of spatially varying endemicity is intended to contribute to a much-needed paradigm shift towards geographically stratified and evidence-based planning for P. vivax control and elimination.

Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Hoen AG, Moyes CL, Farlow AW, Scott TW, Hay SI. 2012. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis, 6 (8), pp. e1760. | Show Abstract | Read more

BACKGROUND: Dengue is a growing problem both in its geographical spread and in its intensity, and yet current global distribution remains highly uncertain. Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution of this disease. As such, there is a lack of agreement on national dengue status among international health organisations. Here we bring together all available information on dengue occurrence using a novel approach to produce an evidence consensus map of the disease range that highlights nations with an uncertain dengue status. METHODS/PRINCIPAL FINDINGS: A baseline methodology was used to assess a range of evidence for each country. In regions where dengue status was uncertain, additional evidence types were included to either clarify dengue status or confirm that it is unknown at this time. An algorithm was developed that assesses evidence quality and consistency, giving each country an evidence consensus score. Using this approach, we were able to generate a contemporary global map of national-level dengue status that assigns a relative measure of certainty and identifies gaps in the available evidence. CONCLUSION: The map produced here provides a list of 128 countries for which there is good evidence of dengue occurrence, including 36 countries that have previously been classified as dengue-free by the World Health Organization and/or the US Centers for Disease Control. It also identifies disease surveillance needs, which we list in full. The disease extents and limits determined here using evidence consensus, marks the beginning of a five-year study to advance the mapping of dengue virus transmission and disease risk. Completion of this first step has allowed us to produce a preliminary estimate of population at risk with an upper bound of 3.97 billion people. This figure will be refined in future work.

Pigott DM, Atun R, Moyes CL, Hay SI, Gething PW. 2012. Funding for malaria control 2006-2010: a comprehensive global assessment. Malar J, 11 (1), pp. 246. | Show Abstract | Read more

BACKGROUND: The last decade has seen a dramatic increase in international and domestic funding for malaria control, coupled with important declines in malaria incidence and mortality in some regions of the world. As the ongoing climate of financial uncertainty places strains on investment in global health, there is an increasing need to audit the origin, recipients and geographical distribution of funding for malaria control relative to populations at risk of the disease. METHODS: A comprehensive review of malaria control funding from international donors, bilateral sources and national governments was undertaken to reconstruct total funding by country for each year 2006 to 2010. Regions at risk from Plasmodium falciparum and/or Plasmodium vivax transmission were identified using global risk maps for 2010 and funding was assessed relative to populations at risk. Those nations with unequal funding relative to a regional average were identified and potential explanations highlighted, such as differences in national policies, government inaction or donor neglect. RESULTS: US$8.9 billion was disbursed for malaria control and elimination programmes over the study period. Africa had the largest levels of funding per capita-at-risk, with most nations supported primarily by international aid. Countries of the Americas, in contrast, were supported typically through national government funding. Disbursements and government funding in Asia were far lower with a large variation in funding patterns. Nations with relatively high and low levels of funding are discussed. CONCLUSIONS: Global funding for malaria control is substantially less than required. Inequity in funding is pronounced in some regions particularly when considering the distinct goals of malaria control and malaria elimination. Efforts to sustain and increase international investment in malaria control should be informed by evidence-based assessment of funding equity.

Jallow M, Teo YY, Small KS, Rockett KA, Deloukas P, Clark TG, Kivinen K, Bojang KA, Conway DJ, Pinder M et al. 2009. Genome-wide and fine-resolution association analysis of malaria in West Africa. Nat Genet, 41 (6), pp. 657-665. | Show Abstract | Read more

We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10(-7) to P = 4 × 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.

Malaria Genomic Epidemiology Network. 2008. A global network for investigating the genomic epidemiology of malaria. Nature, 456 (7223), pp. 732-737. | Show Abstract | Read more

Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries.

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Kwiatkowski D, Epidemiology MG. 2008. A global network for investigating the genomic epidemiology of malaria NATURE, 456 (7223), pp. 732-U39. | Show Abstract | Read more

Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries. © 2008 Macmillan Publishers Limited. All rights reserved.

Bavage AD, Buck E, Dale P, Moyes C, Senior I. 2002. Analysis of a backcross population from a multi-copy transgenic Brassica napus line EUPHYTICA, 124 (3), pp. 333-340. | Show Abstract | Read more

Brassica napus is one of the crops at the forefront of biotechnological development. The procedures used to produce transgenic varieties are all prone to generating plants with multiple transgene copies. There has been considereable interest in the behaviour of such multi-copy lines because gene dosage rarely appears to correlate simply with gene expression. Here we report the analysis of a population of 107 progeny from a B. napus transformant containing multiple copies of a GUS marker gene construct. A total of 12 GUS sequence copies were identified including one that was non-functional. The expression of GUS increased with increasing copy number but this increase only made up a small proportion of the total variation between lines. There was no evidence of interaction between the various GUS copies and they appeared to segregate independently. The variation between progeny lines indicated that the number of gene copies was not a good guide to the expression of the gene product and hence that the expression of the gene in progeny from a multiple-copy parent could not be predicted. The importance of these findings in relation to plant breeding and the risk assessment process is discussed.

Senior IJ, Moyes C, Dale PJ. 2002. Herbicide sensitivity of transgenic multiple herbicide-tolerant oilseed rape. Pest Manag Sci, 58 (4), pp. 405-412. | Show Abstract | Read more

Glyphosate and glufosinate-ammonium herbicide tolerance traits were combined into both winter and spring lines of Brassica napus L. This allowed the study of possible interactions between these transgenes in two genetic backgrounds when treated with a variety of herbicides. Selective herbicides that are commonly used within Brassica crops showed no adverse effects on the transgenic plants or their null controls. Lines containing both glyphosate and glufosinate transgenes remained tolerant to their respective herbicides, regardless of the presence of the second tolerance transgene. Lines containing only a single transgene retained tolerance to the encoded trait and did not show cross-tolerance to the second. Null lines were killed by either herbicide. All plant lines, regardless of their transgene content, were found to be equally susceptible to three herbicides (paraquat, metsulfuronmethyl and mecoprop), commonly used to remove volunteer B napus from succeeding crops and set-a-side land.

Moyes CL, Lilley JM, Casais CA, Cole SG, Haeger PD, Dale PJ. 2002. Barriers to gene flow from oilseed rape (Brassica napus) into populations of Sinapis arvensis. Mol Ecol, 11 (1), pp. 103-112. | Show Abstract | Read more

One concern over growing herbicide-tolerant crops is that herbicide-tolerance genes may be transferred into the weeds they are designed to control. Brassica napus (oilseed rape) has a number of wild relatives that cause weed problems and the most widespread of these is Sinapis arvensis (charlock). Sinapis arvensis seed was collected from 102 populations across the UK, within and outside B. napus-growing areas. These populations were tested for sexual compatibility with B. napus and it was found that none of them hybridized readily in the glasshouse. In contrast to previous studies, we have found that hybrids can be formed naturally with S. arvensis as the maternal parent. Six diverse B. napus cultivars (Capricorn, Drakkar, Falcon, Galaxy, Hobson and Regent) were tested for their compatibility with S. arvensis but no cultivar hybridized readily in the glasshouse. We were unable to detect gene transfer from B. napus to S. arvensis in the field, confirming the extremely low probability of hybridization predicted from the glasshouse work.

Moyes CL, Raybould AF. 2001. The role of spatial scale and intraspecific variation in secondary chemistry in host-plant location by Ceutorhynchus assimilis (Coleoptera: Curculionidae). Proc Biol Sci, 268 (1476), pp. 1567-1573. | Show Abstract | Read more

To understand the ecological role of secondary plant compounds in host location by phytophagous insects it is important to consider attraction at different scales in natural populations. The cabbage seed weevil, Ceutorhynchus assimilis, which lays eggs in pods of crucifers where the larvae feed on seed, is attracted to purified extracts of specific glucosinolate-derived volatiles. We considered the possibility that C. assimilis adults are attracted to and preferentially attack patches of plants and/or individual plants producing these volatiles. Using discrete natural populations of Brassica oleracea and Brassica nigra, we found that oviposition was highest in populations of B. oleracea producing high amounts of 3-butenylglucosinolate. No links were found between the other glucosinolates, 2-propenylglucosinolate, 2-hydroxy-3-butenylglucosinolate, 1-indolylmethylglucosinolate or 1-methoxy-3-indolylmethylglucosinolate, and oviposition in B. oleracea. B. nigra, which contains only 2-propenylglucosinolate, was not attacked by C. assimilis. Within populations of B. oleracea, neither oviposition nor the number of seeds eaten was related to the glucosinolate profiles of individual plants. We suggest that C. assimilis adults use 3-butenylglucosinolate-derived volatiles to locate host populations, whereas other cues determine oviposition on individual plants. The consequences of these results for natural selection of glucosinolate phenotypes are discussed.

Raybould AF, Moyes CL. 2001. The ecological genetics of aliphatic glucosinolates. Heredity (Edinb), 87 (Pt 4), pp. 383-391. | Show Abstract | Read more

Glucosinolates are plant secondary metabolites composed of a thioglucose group and an amino acid side-chain. They occur in the Brassicaceae and related families. A wide variety of glucosinolates exists owing to modification of the side-chain structure. Following tissue damage, myrosinase enzymes catalyse the decomposition of glucosinolates to a variety of volatile and nonvolatile products. The genetic control of concentration and side-chain modification of aliphatic glucosinolates, which have side-chains derived from methionine, are simple and well known from work on Arabidopsis and Brassica crops. In controlled conditions in the laboratory or in field trials, many aliphatic glucosinolates, or their degradation products, affect the behaviour of herbivores. For these reasons, we suggest that polymorphism for aliphatic glucosinolates in natural populations offers an attractive system for the study of ecological genetics of plant-herbivore interactions.

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Moyes CL, Collin HA, Britton G, Raybould AE. 2000. Glucosinolates and differential herbivory in wild populations of Brassica oleracea JOURNAL OF CHEMICAL ECOLOGY, 26 (11), pp. 2625-2641. | Show Abstract | Read more

Glucosinolates are known to elicit responses from Brassica herbivores in laboratory studies. To study their importance in interactions with herbivores in the field, glucosinolate profiles and levels of herbivory were ascertained for wild cabbage plants growing in four neighboring populations in the UK. Glucosinolate profiles differed between plant populations, but not between different habitats within populations. Within habitats, there was no link between individual plant glucosinolate profiles and herbivory by Pieris spp., slugs and snails, flea beetles or aphids. Plants attacked by the micromoth. Selania leplastriana, contained higher levels of 2-hydroxy-3-butenylglucosinolate and 3-indolylmethylglucosinolate than plants within the same population that were not attacked. It is concluded that the differences in glucosinolate profiles between the plant populations are unlikely to be due to differential selection pressures from herbivores feeding on the mature plants over the two years studies.

Hancock PA, Wiebe A, Gleave KA, Bhatt S, Cameron E, Trett A, Weetman D, Smith DL, Hemingway J, Coleman M et al. 2018. Associated patterns of insecticide resistance in field populations of malaria vectors across Africa. Proc Natl Acad Sci U S A, 115 (23), pp. 5938-5943. | Show Abstract | Read more

The development of insecticide resistance in African malaria vectors threatens the continued efficacy of important vector control methods that rely on a limited set of insecticides. To understand the operational significance of resistance we require quantitative information about levels of resistance in field populations to the suite of vector control insecticides. Estimation of resistance is complicated by the sparsity of observations in field populations, variation in resistance over time and space at local and regional scales, and cross-resistance between different insecticide types. Using observations of the prevalence of resistance in mosquito species from the Anopheles gambiae complex sampled from 1,183 locations throughout Africa, we applied Bayesian geostatistical models to quantify patterns of covariation in resistance phenotypes across different insecticides. For resistance to the three pyrethroids tested, deltamethrin, permethrin, and λ-cyhalothrin, we found consistent forms of covariation across sub-Saharan Africa and covariation between resistance to these pyrethroids and resistance to DDT. We found no evidence of resistance interactions between carbamate and organophosphate insecticides or between these insecticides and those from other classes. For pyrethroids and DDT we found significant associations between predicted mean resistance and the observed frequency of kdr mutations in the Vgsc gene in field mosquito samples, with DDT showing the strongest association. These results improve our capacity to understand and predict resistance patterns throughout Africa and can guide the development of monitoring strategies.

Shearer FM, Moyes CL, Pigott DM, Brady OJ, Marinho F, Deshpande A, Longbottom J, Browne AJ, Kraemer MUG, O'Reilly KM et al. 2017. Global yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis. Lancet Infect Dis, 17 (11), pp. 1209-1217. | Show Abstract | Read more

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 Union's Horizon 2020 research and innovation programme.

Moyes CL, Vontas J, Martins AJ, Ng LC, Koou SY, Dusfour I, Raghavendra K, Pinto J, Corbel V, David J-P, Weetman D. 2017. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans. PLoS Negl Trop Dis, 11 (7), pp. e0005625. | Show Abstract | Read more

Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

Wiebe A, Longbottom J, Gleave K, Shearer FM, Sinka ME, Massey NC, Cameron E, Bhatt S, Gething PW, Hemingway J et al. 2017. Geographical distributions of African malaria vector sibling species and evidence for insecticide resistance. Malar J, 16 (1), pp. 85. | Show Abstract | Read more

BACKGROUND: Many 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. RESULTS: Within 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. CONCLUSIONS: Sibling 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.

Shearer FM, Huang Z, Weiss DJ, Wiebe A, Gibson HS, Battle KE, Pigott DM, Brady OJ, Putaporntip C, Jongwutiwes S et al. 2016. Estimating Geographical Variation in the Risk of Zoonotic Plasmodium knowlesi Infection in Countries Eliminating Malaria. PLoS Negl Trop Dis, 10 (8), pp. e0004915. | Show Abstract | Read more

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.

Moyes CL, Shearer FM, Huang Z, Wiebe A, Gibson HS, Nijman V, Mohd-Azlan J, Brodie JF, Malaivijitnond S, Linkie M et al. 2016. Predicting the geographical distributions of the macaque hosts and mosquito vectors of Plasmodium knowlesi malaria in forested and non-forested areas. Parasit Vectors, 9 (1), pp. 242. | Show Abstract | Read more

BACKGROUND: Plasmodium knowlesi is a zoonotic pathogen, transmitted among macaques and to humans by anopheline mosquitoes. Information on P. knowlesi malaria is lacking in most regions so the first step to understand the geographical distribution of disease risk is to define the distributions of the reservoir and vector species. METHODS: We used macaque and mosquito species presence data, background data that captured sampling bias in the presence data, a boosted regression tree model and environmental datasets, including annual data for land classes, to predict the distributions of each vector and host species. We then compared the predicted distribution of each species with cover of each land class. RESULTS: Fine-scale distribution maps were generated for three macaque host species (Macaca fascicularis, M. nemestrina and M. leonina) and two mosquito vector complexes (the Dirus Complex and the Leucosphyrus Complex). The Leucosphyrus Complex was predicted to occur in areas with disturbed, but not intact, forest cover (> 60% tree cover) whereas the Dirus Complex was predicted to occur in areas with 10-100% tree cover as well as vegetation mosaics and cropland. Of the macaque species, M. nemestrina was mainly predicted to occur in forested areas whereas M. fascicularis was predicted to occur in vegetation mosaics, cropland, wetland and urban areas in addition to forested areas. CONCLUSIONS: The predicted M. fascicularis distribution encompassed a wide range of habitats where humans are found. This is of most significance in the northern part of its range where members of the Dirus Complex are the main P. knowlesi vectors because these mosquitoes were also predicted to occur in a wider range of habitats. Our results support the hypothesis that conversion of intact forest into disturbed forest (for example plantations or timber concessions), or the creation of vegetation mosaics, will increase the probability that members of the Leucosphyrus Complex occur at these locations, as well as bringing humans into these areas. An explicit analysis of disease risk itself using infection data is required to explore this further. The species distributions generated here can now be included in future analyses of P. knowlesi infection risk.

Sinka ME, Golding N, Massey NC, Wiebe A, Huang Z, Hay SI, Moyes CL. 2016. Modelling the relative abundance of the primary African vectors of malaria before and after the implementation of indoor, insecticide-based vector control. Malar J, 15 (1), pp. 142. | Show Abstract | Read more

BACKGROUND: Malaria remains a heavy burden across sub-Saharan Africa where transmission is maintained by some of the world's most efficient vectors. Indoor insecticide-based control measures have significantly reduced transmission, yet elimination remains a distant target. Knowing the relative abundance of the primary vector species can provide transmission models with much needed information to guide targeted control measures. Moreover, understanding how existing interventions are impacting on these relative abundances highlights where alternative control (e.g., larval source management) is needed. METHODS: Using the habitat suitability probabilities generated by predictive species distribution models combined with data collated from the literature, a multinomial generalized additive model was applied to produce relative abundance estimates for Anopheles arabiensis, Anopheles funestus and Anopheles gambiae/Anopheles coluzzii. Using pre- and post-intervention abundance data, estimates of the effect of indoor insecticide-based interventions on these relative abundances were made and are illustrated in post-intervention maps. RESULTS: Conditional effect plots and relative abundance maps illustrate the individual species' predicted habitat suitability and how they interact when in sympatry. Anopheles arabiensis and An. funestus show an affinity in habitat preference at the expense of An. gambiae/An. coluzzii, whereas increasing habitat suitability for An. gambiae/An. coluzzii is conversely less suitable for An. arabiensis but has little effect on An. funestus. Indoor insecticide-based interventions had a negative impact on the relative abundance of An. funestus, and a lesser effect on An. arabiensis. Indoor residual spraying had the greatest impact on the relative abundance of An. funestus, and a lesser effect on An. gambiae/An. coluzzii. Insecticide-treated bed nets reduced the relative abundance of both species equally. These results do not indicate changes in the absolute abundance of these species, which may be reduced for all species overall. CONCLUSIONS: The maps presented here highlight the interactions between the primary vector species in sub-Saharan Africa and demonstrate that An. funestus is more susceptible to certain indoor-based insecticide interventions than An. gambiae/An. coluzzii, which in turn, is more susceptible than An. arabiensis. This may provide An. arabiensis with a competitive advantage where it is found in sympatry with other more endophilic vectors, and potentially increase the need for outdoor-based vector interventions to deal with any residual transmission barring the way to malaria elimination.

Massey NC, Garrod G, Wiebe A, Henry AJ, Huang Z, Moyes CL, Sinka ME. 2016. A global bionomic database for the dominant vectors of human malaria. Sci Data, 3 (1), pp. 160014. | Show Abstract | Read more

Anopheles mosquitoes were first recognised as the transmitters of human malaria in the late 19th Century and have been subject to a huge amount of research ever since. Yet there is still much that is unknown regarding the ecology, behaviour (collectively 'bionomics') and sometimes even the identity of many of the world's most prominent disease vectors, much less the within-species variation in their bionomics. Whilst malaria elimination remains an ambitious goal, it is becoming increasingly clear that knowledge of vector behaviour is needed to effectively target control measures. A database of bionomics data for the dominant vector species of malaria worldwide has been compiled from published peer-reviewed literature. The data identification and collation processes are described, together with the geo-positioning and quality control methods. This is the only such dataset in existence and provides a valuable resource to researchers and policy makers in this field.

Patching HMM, Hudson LM, Cooke W, Garcia AJ, Hay SI, Roberts M, Moyes CL. 2015. A Supervised Learning Process to Validate Online Disease Reports for Use in Predictive Models. Big Data, 3 (4), pp. 230-237. | Show Abstract | Read more

Pathogen distribution models that predict spatial variation in disease occurrence require data from a large number of geographic locations to generate disease risk maps. Traditionally, this process has used data from public health reporting systems; however, using online reports of new infections could speed up the process dramatically. Data from both public health systems and online sources must be validated before they can be used, but no mechanisms exist to validate data from online media reports. We have developed a supervised learning process to validate geolocated disease outbreak data in a timely manner. The process uses three input features, the data source and two metrics derived from the location of each disease occurrence. The location of disease occurrence provides information on the probability of disease occurrence at that location based on environmental and socioeconomic factors and the distance within or outside the current known disease extent. The process also uses validation scores, generated by disease experts who review a subset of the data, to build a training data set. The aim of the supervised learning process is to generate validation scores that can be used as weights going into the pathogen distribution model. After analyzing the three input features and testing the performance of alternative processes, we selected a cascade of ensembles comprising logistic regressors. Parameter values for the training data subset size, number of predictors, and number of layers in the cascade were tested before the process was deployed. The final configuration was tested using data for two contrasting diseases (dengue and cholera), and 66%-79% of data points were assigned a validation score. The remaining data points are scored by the experts, and the results inform the training data set for the next set of predictors, as well as going to the pathogen distribution model. The new supervised learning process has been implemented within our live site and is being used to validate the data that our system uses to produce updated predictive disease maps on a weekly basis.

Golding N, Wilson AL, Moyes CL, Cano J, Pigott DM, Velayudhan R, Brooker SJ, Smith DL, Hay SI, Lindsay SW. 2015. Integrating vector control across diseases. BMC Med, 13 (1), pp. 249. | Show Abstract | Read more

BACKGROUND: Vector-borne diseases cause a significant proportion of the overall burden of disease across the globe, accounting for over 10 % of the burden of infectious diseases. Despite the availability of effective interventions for many of these diseases, a lack of resources prevents their effective control. Many existing vector control interventions are known to be effective against multiple diseases, so combining vector control programmes to simultaneously tackle several diseases could offer more cost-effective and therefore sustainable disease reductions. DISCUSSION: The highly successful cross-disease integration of vaccine and mass drug administration programmes in low-resource settings acts a precedent for cross-disease vector control. Whilst deliberate implementation of vector control programmes across multiple diseases has yet to be trialled on a large scale, a number of examples of 'accidental' cross-disease vector control suggest the potential of such an approach. Combining contemporary high-resolution global maps of the major vector-borne pathogens enables us to quantify overlap in their distributions and to estimate the populations jointly at risk of multiple diseases. Such an analysis shows that over 80 % of the global population live in regions of the world at risk from one vector-borne disease, and more than half the world's population live in areas where at least two different vector-borne diseases pose a threat to health. Combining information on co-endemicity with an assessment of the overlap of vector control methods effective against these diseases allows us to highlight opportunities for such integration. Malaria, leishmaniasis, lymphatic filariasis, and dengue are prime candidates for combined vector control. All four of these diseases overlap considerably in their distributions and there is a growing body of evidence for the effectiveness of insecticide-treated nets, screens, and curtains for controlling all of their vectors. The real-world effectiveness of cross-disease vector control programmes can only be evaluated by large-scale trials, but there is clear evidence of the potential of such an approach to enable greater overall health benefit using the limited funds available.

Moyes CL, Henry AJ, Golding N, Huang Z, Singh B, Baird JK, Newton PN, Huffman M, Duda KA, Drakeley CJ et al. 2014. Defining the geographical range of the Plasmodium knowlesi reservoir. PLoS Negl Trop Dis, 8 (3), pp. e2780. | Show Abstract | Read more

BACKGROUND: The simian malaria parasite, Plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. Because malaria caused by P. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. Information is required on the occurrence of human cases in different locations, on which non-human primates host this parasite and on which vectors are able to transmit it to humans. We undertook a systematic review and ranked the existing evidence, at a subnational spatial scale, to investigate the potential geographical range of the parasite reservoir capable of infecting humans. METHODOLOGY/PRINCIPAL FINDINGS: After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region. CONCLUSIONS/SIGNIFICANCE: We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment.

Moyes CL, Temperley WH, Henry AJ, Burgert CR, Hay SI. 2013. Providing open access data online to advance malaria research and control. Malar J, 12 (1), pp. 161. | Show Abstract | Read more

BACKGROUND: To advance research on malaria, the outputs from existing studies and the data that fed into them need to be made freely available. This will ensure new studies can build on the work that has gone before. These data and results also need to be made available to groups who are developing public health policies based on up-to-date evidence. The Malaria Atlas Project (MAP) has collated and geopositioned over 50,000 parasite prevalence and vector occurrence survey records contributed by over 3,000 sources including research groups, government agencies and non-governmental organizations worldwide. This paper describes the results of a project set up to release data gathered, used and generated by MAP. METHODS: Requests for permission to release data online were sent to 236 groups who had contributed unpublished prevalence (parasite rate) surveys. An online explorer tool was developed so that users can visualize the spatial distribution of the vector and parasite survey data before downloading it. In addition, a consultation group was convened to provide advice on the mode and format of release for data generated by MAP's modelling work. New software was developed to produce a suite of publication-quality map images for download from the internet for use in external publications. CONCLUSION: More than 40,000 survey records can now be visualized on a set of dynamic maps and downloaded from the MAP website on a free and unrestricted basis. As new data are added and new permissions to release existing data come in, the volume of data available for download will increase. The modelled data output from MAP's own analyses are also available online in a range of formats, including image files and GIS surface data, for use in advocacy, education, further research and to help parameterize or validate other mathematical models.

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