School of BioSciences - Research Publications
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ItemEstablishment of Wolbachia Strain wAlbB in Malaysian Populations of Aedes aegypti for Dengue Control(CELL PRESS, 2019-12-16)Dengue has enormous health impacts globally. A novel approach to decrease dengue incidence involves the introduction of Wolbachia endosymbionts that block dengue virus transmission into populations of the primary vector mosquito, Aedes aegypti. The wMel Wolbachia strain has previously been trialed in open releases of Ae. aegypti; however, the wAlbB strain has been shown to maintain higher density than wMel at high larval rearing temperatures. Releases of Ae. aegypti mosquitoes carrying wAlbB were carried out in 6 diverse sites in greater Kuala Lumpur, Malaysia, with high endemic dengue transmission. The strain was successfully established and maintained at very high population frequency at some sites or persisted with additional releases following fluctuations at other sites. Based on passive case monitoring, reduced human dengue incidence was observed in the release sites when compared to control sites. The wAlbB strain of Wolbachia provides a promising option as a tool for dengue control, particularly in very hot climates.
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ItemPast and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus (vol 4, pg 854, 2019)(NATURE PUBLISHING GROUP, 2019-05)This Article was mistakenly not made Open Access when originally published; this has now been amended, and information about the Creative Commons Attribution 4.0 International License has been added into the 'Additional information' section.
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ItemPast and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus (vol 4, pg 854, 2019)(NATURE PUBLISHING GROUP, 2019-05)In the version of this Article originally published, the affiliation for author Catherine Linard was incorrectly stated as '6Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK'. The correct affiliation is '9Spatial Epidemiology Lab (SpELL), Universite Libre de Bruxelles, Brussels, Belgium'. The affiliation for author Hongjie Yu was also incorrectly stated as '11Department of Statistics, Harvard University, Cambridge, MA, USA'. The correct affiliation is '15School of Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China'. This has now been amended in all versions of the Article.
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ItemMapping the spatial distribution of the Japanese encephalitis vector, Culex tritaeniorhynchus Giles, 1901 (Diptera: Culicidae) within areas of Japanese encephalitis risk(BIOMED CENTRAL LTD, 2017-03-16)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.
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ItemSpread of yellow fever virus outbreak in Angola and the Democratic Republic of the Congo 2015-16: a modelling study(ELSEVIER SCI LTD, 2017-03)BACKGROUND: Since late 2015, an epidemic of yellow fever has caused more than 7334 suspected cases in Angola and the Democratic Republic of the Congo, including 393 deaths. We sought to understand the spatial spread of this outbreak to optimise the use of the limited available vaccine stock. METHODS: We jointly analysed datasets describing the epidemic of yellow fever, vector suitability, human demography, and mobility in central Africa to understand and predict the spread of yellow fever virus. We used a standard logistic model to infer the district-specific yellow fever virus infection risk during the course of the epidemic in the region. FINDINGS: The early spread of yellow fever virus was characterised by fast exponential growth (doubling time of 5-7 days) and fast spatial expansion (49 districts reported cases after only 3 months) from Luanda, the capital of Angola. Early invasion was positively correlated with high population density (Pearson's r 0·52, 95% CI 0·34-0·66). The further away locations were from Luanda, the later the date of invasion (Pearson's r 0·60, 95% CI 0·52-0·66). In a Cox model, we noted that districts with higher population densities also had higher risks of sustained transmission (the hazard ratio for cases ceasing was 0·74, 95% CI 0·13-0·92 per log-unit increase in the population size of a district). A model that captured human mobility and vector suitability successfully discriminated districts with high risk of invasion from others with a lower risk (area under the curve 0·94, 95% CI 0·92-0·97). If at the start of the epidemic, sufficient vaccines had been available to target 50 out of 313 districts in the area, our model would have correctly identified 27 (84%) of the 32 districts that were eventually affected. INTERPRETATION: Our findings show the contributions of ecological and demographic factors to the ongoing spread of the yellow fever outbreak and provide estimates of the areas that could be prioritised for vaccination, although other constraints such as vaccine supply and delivery need to be accounted for before such insights can be translated into policy. FUNDING: Wellcome Trust.
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ItemEstimating the number of cases of podoconiosis in Ethiopia using geostatistical methods.(F1000 Research Ltd, 2017)BACKGROUND: In 2011, the World Health Organization recognized podoconiosis as one of the neglected tropical diseases. Nonetheless, the number of people with podoconiosis and the geographical distribution of the disease is poorly understood. Based on a nationwide mapping survey and geostatistical modelling, we predict the prevalence of podoconiosis and estimate the number of cases across Ethiopia. METHODS: We used nationwide data collected in Ethiopia between 2008 and 2013. Data were available for 141,238 individuals from 1,442 villages in 775 districts from all nine regional states and two city administrations. We developed a geostatistical model of podoconiosis prevalence among adults (individuals aged 15 years or above), by combining environmental factors. The number of people with podoconiosis was then estimated using a gridded map of adult population density for 2015. RESULTS: Podoconiosis is endemic in 345 districts in Ethiopia: 144 in Oromia, 128 in Southern Nations, Nationalities and People's [SNNP], 64 in Amhara, 4 in Benishangul Gumuz, 4 in Tigray and 1 in Somali Regional State. Nationally, our estimates suggest that 1,537,963 adults (95% confidence intervals, 290,923-4,577,031 adults) were living with podoconiosis in 2015. Three regions (SNNP, Oromia and Amhara) contributed 99% of the cases. The highest proportion of individuals with podoconiosis resided in the SNNP (39%), while 32% and 29% of people with podoconiosis resided in Oromia and Amhara Regional States, respectively. Tigray and Benishangul Gumuz Regional States bore lower burdens, and in the remaining regions, podoconiosis was almost non-existent. Discussion: The estimates of podoconiosis cases presented here based upon the combination of currently available epidemiological data and a robust modelling approach clearly show that podoconiosis is highly endemic in Ethiopia. Given the presence of low cost prevention, and morbidity management and disability prevention services, it is our collective responsibility to scale-up interventions rapidly.
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ItemLocal, national, and regional viral haemorrhagic fever pandemic potential in Africa: a multistage analysis(ELSEVIER SCIENCE INC, 2017-12-16)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.
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ItemHow will climate change pathways and mitigation options alter incidence of vector-borne diseases? A framework for leishmaniasis in South and Meso-America(PUBLIC LIBRARY SCIENCE, 2017-10-11)The enormous global burden of vector-borne diseases disproportionately affects poor people in tropical, developing countries. Changes in vector-borne disease impacts are often linked to human modification of ecosystems as well as climate change. For tropical ecosystems, the health impacts of future environmental and developmental policy depend on how vector-borne disease risks trade off against other ecosystem services across heterogeneous landscapes. By linking future socio-economic and climate change pathways to dynamic land use models, this study is amongst the first to analyse and project impacts of both land use and climate change on continental-scale patterns in vector-borne diseases. Models were developed for cutaneous and visceral leishmaniasis in the Americas-ecologically complex sand fly borne infections linked to tropical forests and diverse wild and domestic mammal hosts. Both diseases were hypothesised to increase with available interface habitat between forest and agricultural or domestic habitats and with mammal biodiversity. However, landscape edge metrics were not important as predictors of leishmaniasis. Models including mammal richness were similar in accuracy and predicted disease extent to models containing only climate and land use predictors. Overall, climatic factors explained 80% and land use factors only 20% of the variance in past disease patterns. Both diseases, but especially cutaneous leishmaniasis, were associated with low seasonality in temperature and precipitation. Since such seasonality increases under future climate change, particularly under strong climate forcing, both diseases were predicted to contract in geographical extent to 2050, with cutaneous leishmaniasis contracting by between 35% and 50%. Whilst visceral leishmaniasis contracted slightly more under strong than weak management for carbon, biodiversity and ecosystem services, future cutaneous leishmaniasis extent was relatively insensitive to future alternative socio-economic pathways. Models parameterised at narrower geographical scales may be more sensitive to land use pattern and project more substantial changes in disease extent under future alternative socio-economic pathways.
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ItemMapping under-5 and neonatal mortality in Africa, 2000-15: a baseline analysis for the Sustainable Development Goals(ELSEVIER SCIENCE INC, 2017-11-11)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.
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ItemGlobal yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis(ELSEVIER SCI LTD, 2017-11)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.