Mapping local variation in educational attainment across Africa.

Educational attainment for women of reproductive age is linked to reduced child and maternal mortality, lower fertility and improved reproductive health. Comparable analyses of attainment exist only at the national level, potentially obscuring patterns in subnational inequality. Evidence suggests that wide disparities between urban and rural populations exist, raising questions about where the majority of progress towards the education targets of the Sustainable Development Goals is occurring in African countries. Here we explore within-country inequalities by predicting years of schooling across five by five kilometre grids, generating estimates of average educational attainment by age and sex at subnational levels. Despite marked progress in attainment from 2000 to 2015 across Africa, substantial differences persist between locations and sexes. These differences have widened in many countries, particularly across the Sahel. These high-resolution, comparable estimates improve the ability of decision-makers to plan the precisely targeted interventions that will be necessary to deliver progress during the era of the Sustainable Development Goals.

Mapping child growth failure in Africa between 2000 and 2015.

Insufficient growth during childhood is associated with poor health outcomes and an increased risk of death. Between 2000 and 2015, nearly all African countries demonstrated improvements for children under 5 years old for stunting, wasting, and underweight, the core components of child growth failure. Here we show that striking subnational heterogeneity in levels and trends of child growth remains. If current rates of progress are sustained, many areas of Africa will meet the World Health Organization Global Targets 2025 to improve maternal, infant and young child nutrition, but high levels of growth failure will persist across the Sahel. At these rates, much, if not all of the continent will fail to meet the Sustainable Development Goal target-to end malnutrition by 2030. Geospatial estimates of child growth failure provide a baseline for measuring progress as well as a precision public health platform to target interventions to those populations with the greatest need, in order to reduce health disparities and accelerate progress.

Drug-resistant enteric fever worldwide, 1990 to 2018: a systematic review and meta-analysis.

BACKGROUND: Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention. METHODS: We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance. FINDINGS: We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified. INTERPRETATION: Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice. TRIAL REGISTRATION: PROSPERO CRD42018029432.

Vulnerability to snakebite envenoming: a global mapping of hotspots.

BACKGROUND: Snakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed. METHODS: We assembled a list of snake species using WHO guidelines. Where relevant, we obtained expert opinion range (EOR) maps from WHO or the Clinical Toxinology Resources. We also obtained occurrence data for each snake species from a variety of websites, such as VertNet and iNaturalist, using the spocc R package (version 0.7.0). We removed duplicate occurrence data and categorised snakes into three groups: group A (no available EOR map or species occurrence records), group B (EOR map but <5 species occurrence records), and group C (EOR map and ≥5 species occurrence records). For group C species, we did a multivariate environmental similarity analysis using the 2008 WHO EOR maps and newly available evidence. Using these data and the EOR maps, we produced contemporary range maps for medically important venomous snake species at a 5 × 5 km resolution. We subsequently triangulated these data with three health system metrics (antivenom availability, accessibility to urban centres, and the Healthcare Access and Quality [HAQ] Index) to identify the populations most vulnerable to snakebite morbidity and mortality. FINDINGS: We provide a map showing the ranges of 278 snake species globally. Although about 6·85 billion people worldwide live within range of areas inhabited by snakes, about 146·70 million live within remote areas lacking quality health-care provisioning. Comparing opposite ends of the HAQ Index, 272·91 million individuals (65·25%) of the population within the lowest decile are at risk of exposure to any snake for which no effective therapy exists compared with 519·46 million individuals (27·79%) within the highest HAQ Index decile, showing a disproportionate coverage in reported antivenom availability. Antivenoms were available for 119 (43%) of 278 snake species evaluated by WHO, while globally 750·19 million (10·95%) of those living within snake ranges live more than 1 h from population centres. In total, we identify about 92·66 million people living within these vulnerable geographies, including many sub-Saharan countries, Indonesia, and other parts of southeast Asia. INTERPRETATION: Identifying exact populations vulnerable to the most severe outcomes of snakebite envenoming at a subnational level is important for prioritising new data collection and collation, reinforcing envenoming treatment, existing health-care systems, and deploying currently available and future interventions. These maps can guide future research efforts on snakebite envenoming from both ecological and public health perspectives and better target future estimates of the burden of this neglected tropical disease. FUNDING: Bill & Melinda Gates Foundation.

Mapping under-5 and neonatal mortality in Africa, 2000-15: a baseline analysis for the Sustainable Development Goals.

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.

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

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.

Aedes albopictus invasion across Africa: the time is now for cross-country collaboration and control.

The distribution of Aedes albopictus across west Africa is well documented. However, little has been done to synthesise data and establish the current distribution of this invasive vector in central and east Africa. In this Viewpoint, we show that A albopictus is establishing across Africa, how this is potentially related to urbanisation, and how establishment poses risks of near-term increases in arbovirus transmission. We then use existing species distribution maps for A albopictus and Aedes aegypti to produce consensus estimates of suitability and make these estimates accessible. Although urban development and increased trade have economic and other societal gains, the resulting potential changes in Aedes-borne virus epidemiology require a discussion of how cross-country collaboration and mitigation could be facilitated. Failure to respond to species invasion could result in increased transmission of Aedes-associated pathogens, including dengue, chikungunya, and Rift Valley fever viruses.

Scaling up of tsetse control to eliminate Gambian sleeping sickness in northern Uganda.

BACKGROUND: Tsetse flies (Glossina) transmit Trypanosoma brucei gambiense which causes Gambian human African trypanosomiasis (gHAT) in Central and West Africa. Several countries use Tiny Targets, comprising insecticide-treated panels of material which attract and kill tsetse, as part of their national programmes to eliminate gHAT. We studied how the scale and arrangement of target deployment affected the efficacy of control. METHODOLOGY AND PRINCIPAL FINDINGS: Between 2012 and 2016, Tiny Targets were deployed biannually along the larger rivers of Arua, Maracha, Koboko and Yumbe districts in North West Uganda with the aim of reducing the abundance of tsetse to interrupt transmission. The extent of these deployments increased from ~250 km2 in 2012 to ~1600 km2 in 2015. The impact of Tiny Targets on tsetse populations was assessed by analysing catches of tsetse from a network of monitoring traps; sub-samples of captured tsetse were dissected to estimate their age and infection status. In addition, the condition of 780 targets (~195/district) was assessed for up to six months after deployment. In each district, mean daily catches of tsetse (G. fuscipes fuscipes) from monitoring traps declined significantly by >80% following the deployment of targets. The reduction was apparent for several kilometres on adjacent lengths of the same river but not in other rivers a kilometre or so away. Expansion of the operational area did not always produce higher levels of suppression or detectable change in the age structure or infection rates of the population, perhaps due to the failure to treat the smaller streams and/or invasion from adjacent untreated areas. The median effective life of a Tiny Target was 61 (41.8-80.2, 95% CI) days. CONCLUSIONS: Scaling-up of tsetse control reduced the population of tsetse by >80% across the intervention area. Even better control might be achievable by tackling invasion of flies from infested areas within and outside the current intervention area. This might involve deploying more targets, especially along smaller rivers, and extending the effective life of Tiny Targets.

Optimising passive surveillance of a neglected tropical disease in the era of elimination: A modelling study.

BACKGROUND: Surveillance is an essential component of global programs to eliminate infectious diseases and avert epidemics of (re-)emerging diseases. As the numbers of cases decline, costs of treatment and control diminish but those for surveillance remain high even after the 'last' case. Reducing surveillance may risk missing persistent or (re-)emerging foci of disease. Here, we use a simulation-based approach to determine the minimal number of passive surveillance sites required to ensure maximum coverage of a population at-risk (PAR) of an infectious disease. METHODOLOGY AND PRINCIPAL FINDINGS: For this study, we use Gambian human African trypanosomiasis (g-HAT) in north-western Uganda, a neglected tropical disease (NTD) which has been reduced to historically low levels (<1000 cases/year globally), as an example. To quantify travel time to diagnostic facilities, a proxy for surveillance coverage, we produced a high spatial-resolution resistance surface and performed cost-distance analyses. We simulated travel time for the PAR with different numbers (1-170) and locations (170,000 total placement combinations) of diagnostic facilities, quantifying the percentage of the PAR within 1h and 5h travel of the facilities, as per in-country targets. Our simulations indicate that a 70% reduction (51/170) in diagnostic centres still exceeded minimal targets of coverage even for remote populations, with >95% of a total PAR of ~3million individuals living ≤1h from a diagnostic centre, and we demonstrate an approach to best place these facilities, informing a minimal impact scale back. CONCLUSIONS: Our results highlight that surveillance of g-HAT in north-western Uganda can be scaled back without substantially reducing coverage of the PAR. The methodology described can contribute to cost-effective and equable strategies for the surveillance of NTDs and other infectious diseases approaching elimination or (re-)emergence.

Estimating the impact of Tiny Targets in reducing the incidence of Gambian sleeping sickness in the North-west Uganda focus.

BACKGROUND: Riverine species of tsetse (Glossina) transmit Trypanosoma brucei gambiense, which causes Gambian human African trypanosomiasis (gHAT), a neglected tropical disease. Uganda aims to eliminate gHAT as a public health problem through detection and treatment of human cases and vector control. The latter is being achieved through the deployment of 'Tiny Targets', insecticide-impregnated panels of material which attract and kill tsetse. We analysed the spatial and temporal distribution of cases of gHAT in Uganda during the period 2010-2019 to assess whether Tiny Targets have had an impact on disease incidence. METHODS: To quantify the deployment of Tiny Targets, we mapped the rivers and their associated watersheds in the intervention area. We then categorised each of these on a scale of 0-3 according to whether Tiny Targets were absent (0), present only in neighbouring watersheds (1), present in the watersheds but not all neighbours (2), or present in the watershed and all neighbours (3). We overlaid all cases that were diagnosed between 2000 and 2020 and assessed whether the probability of finding cases in a watershed changed following the deployment of targets. We also estimated the number of cases averted through tsetse control. RESULTS: We found that following the deployment of Tiny Targets in a watershed, there were fewer cases of HAT, with a sampled error probability of 0.007. We estimate that during the intervention period 2012-2019 we should have expected 48 cases (95% confidence intervals = 40-57) compared to the 36 cases observed. The results are robust to a range of sensitivity analyses. CONCLUSIONS: Tiny Targets have reduced the incidence of gHAT by 25% in north-western Uganda.

Addressing the global snakebite crisis with geo-spatial analyses - Recent advances and future direction.

Venomous snakebite is a neglected tropical disease that annually leads to hundreds of thousands of deaths or long-term physical and mental ailments across the developing world. Insufficient data on spatial variation in snakebite risk, incidence, human vulnerability, and accessibility of medical treatment contribute substantially to ineffective on-ground management. There is an urgent need to collect data, fill knowledge gaps and address on-ground management problems. The use of novel, and transdisciplinary approaches that take advantage of recent advances in spatio-temporal models, 'big data', high performance computing, and fine-scale spatial information can add value to snakebite management by strategically improving our understanding and mitigation capacity of snakebite. We review the background and recent advances on the topic of snakebite related geospatial analyses and suggest avenues for priority research that will have practical on-ground applications for snakebite management and mitigation. These include streamlined, targeted data collection on snake distributions, snakebites, envenomings, venom composition, health infrastructure, and antivenom accessibility along with fine-scale models of spatio-temporal variation in snakebite risk and incidence, intraspecific venom variation, and environmental change modifying human exposure. These measures could improve and 'future-proof' antivenom production methods, antivenom distribution and stockpiling systems, and human-wildlife conflict management practices, while simultaneously feeding into research on venom evolution, snake taxonomy, ecology, biogeography, and conservation.

Quantifying geographic accessibility to improve efficiency of entomological monitoring.

BACKGROUND: Vector-borne diseases are important causes of mortality and morbidity in humans and livestock, particularly for poorer communities and countries in the tropics. Large-scale programs against these diseases, for example malaria, dengue and African trypanosomiasis, include vector control, and assessing the impact of this intervention requires frequent and extensive monitoring of disease vector abundance. Such monitoring can be expensive, especially in the later stages of a successful program where numbers of vectors and cases are low. METHODOLOGY/PRINCIPAL FINDINGS: We developed a system that allows the identification of monitoring sites where pre-intervention densities of vectors are predicted to be high, and travel cost to sites is low, highlighting the most efficient locations for longitudinal monitoring. Using remotely sensed imagery and an image classification algorithm, we mapped landscape resistance associated with on- and off-road travel for every gridded location (3m and 0.5m grid cells) within Koboko district, Uganda. We combine the accessibility surface with pre-existing estimates of tsetse abundance and propose a stratified sampling approach to determine the most efficient locations for longitudinal data collection. Our modelled predictions were validated against empirical measurements of travel-time and existing maps of road networks. We applied this approach in northern Uganda where a large-scale vector control program is being implemented to control human African trypanosomiasis, a neglected tropical disease (NTD) caused by trypanosomes transmitted by tsetse flies. Our accessibility surfaces indicate a high performance when compared to empirical data, with remote sensing identifying a further ~70% of roads than existing networks. CONCLUSIONS/SIGNIFICANCE: By integrating such estimates with predictions of tsetse abundance, we propose a methodology to determine the optimal placement of sentinel monitoring sites for evaluating control programme efficacy, moving from a nuanced, ad-hoc approach incorporating intuition, knowledge of vector ecology and local knowledge of geographic accessibility, to a reproducible, quantifiable one.

Modelling the impact of climate change on the distribution and abundance of tsetse in Northern Zimbabwe.

BACKGROUND: Climate change is predicted to impact the transmission dynamics of vector-borne diseases. Tsetse flies (Glossina) transmit species of Trypanosoma that cause human and animal African trypanosomiasis. A previous modelling study showed that temperature increases between 1990 and 2017 can explain the observed decline in abundance of tsetse at a single site in the Mana Pools National Park of Zimbabwe. Here, we apply a mechanistic model of tsetse population dynamics to predict how increases in temperature may have changed the distribution and relative abundance of Glossina pallidipes across northern Zimbabwe. METHODS: Local weather station temperature measurements were previously used to fit the mechanistic model to longitudinal G. pallidipes catch data. To extend the use of the model, we converted MODIS land surface temperature to air temperature, compared the converted temperatures with available weather station data to confirm they aligned, and then re-fitted the mechanistic model using G. pallidipes catch data and air temperature estimates. We projected this fitted model across northern Zimbabwe, using simulations at a 1 km × 1 km spatial resolution, between 2000 to 2016. RESULTS: We produced estimates of relative changes in G. pallidipes mortality, larviposition, emergence rates and abundance, for northern Zimbabwe. Our model predicts decreasing tsetse populations within low elevation areas in response to increasing temperature trends during 2000-2016. Conversely, we show that high elevation areas (> 1000 m above sea level), previously considered too cold to sustain tsetse, may now be climatically suitable. CONCLUSIONS: To our knowledge, the results of this research represent the first regional-scale assessment of temperature related tsetse population dynamics, and the first high spatial-resolution estimates of this metric for northern Zimbabwe. Our results suggest that tsetse abundance may have declined across much of the Zambezi Valley in response to changing climatic conditions during the study period. Future research including empirical studies is planned to improve model accuracy and validate predictions for other field sites in Zimbabwe.

Malaria Data by District: An open-source web application for increasing access to malaria information.

Preventable diseases still cause huge mortality in low- and middle-income countries. Research in spatial epidemiology and earth observation is helping academics to understand and prioritise how mortality could be reduced and generates spatial data that are used at a global and national level, to inform disease control policy. These data could also inform operational decision making at a more local level, for example to help officials target efforts at a local/regional level. To be usable for local decision-making, data needs to be presented in a way that is relevant to and understandable by local decision makers. We demonstrate an approach and prototype web application to make spatial outputs from disease modelling more useful for local decision making. Key to our approach is: (1) we focus on a handful of important data layers to maintain simplicity; (2) data are summarised at scales relevant to decision making (administrative units); (3) the application has the ability to rank and compare administrative units; (4) open-source code that can be modified and re-used by others, to target specific user-needs. Our prototype application allows visualisation of a handful of key layers from the Malaria Atlas Project. Data can be summarised by administrative unit for any malaria endemic African country, ranked and compared; e.g. to answer questions such as, 'does the district with the highest malaria prevalence also have the lowest coverage of insecticide treated nets?'. The application is developed in R and the code is open-source. It would be relatively easy for others to change the source code to incorporate different data layers, administrative boundaries or other data visualisations. We suggest such open-source web application development can facilitate the use of data for public health decision making in low resource settings.

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

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.

Mapping the spatial distribution of the Japanese encephalitis vector, Culex tritaeniorhynchus Giles, 1901 (Diptera: Culicidae) within areas of Japanese encephalitis risk.

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.

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

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.

The Cytochrome P450 gene CYP6P12 confers pyrethroid resistance in kdr-free Malaysian populations of the dengue vector Aedes albopictus.

Control of Aedes albopictus, major dengue and chikungunya vector, is threatened by growing cases of insecticide resistance. The mechanisms driving this resistance remain poorly characterised. This study investigated the molecular basis of insecticide resistance in Malaysian populations of Ae. albopictus. Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance. CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations. Other detoxification genes also up-regulated in permethrin resistant mosquitoes included a glucuronosyltransferase (AAEL014279-RA) and the glutathione-S transferases GSTS1 and GSTT3. Functional analyses further supported that CYP6P12 contributes to pyrethroid resistance in Ae. albopictus as transgenic expression of CYP6P12 in Drosophila was sufficient to confer pyrethroid resistance in these flies. Furthermore, molecular docking simulations predicted CYP6P12 possessing enzymatic activity towards pyrethroids. Patterns of polymorphism suggested early sign of selection acting on CYP6P12 but not on CYP6N3. The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.

Plasmodium vivax Transmission in Africa.

Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf). Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv) transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health significance of Pv, as well as the other neglected non-Pf parasites, which are currently invisible to most public health authorities in Africa, but which can cause severe clinical illness and require specific control interventions.

Mapping the zoonotic niche of Lassa fever in Africa.

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.