Geographical Detector-based influence factors analysis for Echinococcosis prevalence in Tibet,China

Echinococcosis, caused by genus Echinococcus, is the most pathogenic zoonotic parasitic disease in the world. In Tibet of the People’s Republic of China, echinococcosis refers principally to two types of severe zoonosis, cystic echinococcosis (CE) and alveolar echinococcosis (AE), which place a serious burden on public health and economy in the local community. However, research on the spatial epidemiology of echinococcosis remains inadequate in Tibet, China. Based on the recorded human echinococcosis data, maps of the spatial distribution of human CE and AE prevalence in Tibet were produced at city level and county level respectively, which show that the prevalence of echinococcosis in northern and western Tibet was much higher than that in other regions. We employ a geographical detector to explore the influencing factors for causing CE and AE while sorting information on the maps of disease prevalence and environment factors (e.g. terrain, population, and yak population). The results of our analysis showed that biological factors have the most impact on the prevalence of echinococcosis, of which the yak population contributes the most for CE, while the dog population contributes the most for AE. In addition, the interaction between various factors, as we found out, might further explain the disease prevalence, which indicated that the echinococcosis prevalence is not simply affected by one single factor, but by multiple factors that are correlated with each other complicatedly. Our results will provide an important reference for the evaluation of the echinococcosis risk, control projects, and prevention programs in Tibet.     

Environmental changes impacting Echinococcus transmission: research to support predictive surveillance and control

Echinococcosis, resulting from infection with tapeworms Echinococcus granulosus and E. multilocularis, has a global distribution with 2–3 million people affected and 200,000 new cases diagnosed annually. Costs of treatment for humans and economic losses to the livestock industry have been estimated to exceed $2 billion. These figures are likely to be an underestimation given the challenges with its early detection and the lack of mandatory official reporting policies in most countries. Despite this global burden, echinococcosis remains a neglected zoonosis. The importance of environmental factors in influencing the transmission intensity and distribution of Echinococcus spp. is increasingly being recognized. With the advent of climate change and the influence of global population expansion, food insecurity and land‐use changes, questions about the potential impact of changing temperature, rainfall patterns, increasing urbanization, deforestation, grassland degradation and overgrazing on zoonotic disease transmission are being raised. This study is the first to comprehensively review how climate change and anthropogenic environmental factors contribute to the transmission of echinococcosis mediated by changes in animal population dynamics, spatial overlap of competent hosts and the creation of improved conditions for egg survival. We advocate rigorous scientific research to establish the causal link between specific environmental variables and echinococcosis in humans and the incorporation of environmental, animal and human data collection within a sentinel site surveillance network that will complement satellite remote‐sensing information. Identifying the environmental determinants of transmission risk to humans will be vital for the design of more accurate predictive models to guide cost‐effective pre‐emptive public health action against echinococcosis.     

Prevalence and spatial distribution characteristics of human echinococcosis in China

BackgroundEchinococcosis is a zoonotic parasitic disease caused by larval stages of cestodes belonging to the genus Echinococcus. The infection affects people’s health and safety as well as agropastoral sector. In China, human echinococcosis is a major public health burden, especially in western China. Echinococcosis affects people health as well as agricultural and pastoral economy. Therefore, it is important to understand the prevalence status and spatial distribution of human echinococcosis in order to advance our knowledge of basic information for prevention and control measures reinforcement.MethodsReport data on echinococcosis were collected in 370 counties in China in 2018 and were used to assess prevalence and spatial distribution. SPSS 21.0 was used to obtain the prevalence rate for CE and AE. For statistical analyses and mapping, all data were processed using SPSS 21.0 and ArcGIS 10.4, respectively. Chi-square test and Exact probability method were used to assess spatial autocorrelation and spatial clustering.ResultsA total of 47,278 cases of echinococcosis were recorded in 2018 in 370 endemic counties in China. The prevalence rate of human echinococcosis was 10.57 per 10,000. Analysis of the disease prevalence showed obvious spatial positive autocorrelation in globle spatial autocorrelation with two aggregation modes in local spatial autocorrelation, namely high-high and low-high aggregation areas. The high-high gathering areas were mainly concentrated in northern Tibet, western Qinghai, and Ganzi in the Tibetan Autonomous Region and in Sichuan. The low-high clusters were concentrated in Gamba, Kangma and Yadong counties of Tibet. In addition, spatial scanning analysis revealed two spatial clusters. One type of spatial clusters included 71 counties in Tibet Autonomous Region, 22 counties in Qinghai, 11 counties in Sichuan, three counties in Xinjiang Uygur Autonomous Region, two counties in Yunnan, and one county in Gansu. In the second category, six types of spatial clusters were observed in the counties of Xinjiang Uygur Autonomous Region, and the Qinghai, Gansu, and Sichuan Provinces.ConclusionThis study showed a serious prevalence of human echinococcosis with obvious spatial aggregation of the disease prevalence in China. The Qinghai-Tibet Plateau is the "hot spot" area of human echinococcosis in China. Findings from this study indicate that there is an urgent need of joint strategies to strengthen efforts for the prevention and control of echinococcosis in China, especially in the Qinghai-Tibet Plateau.     

The Global Burden of Alveolar Echinococcosis

Background

Human alveolar echinococcosis (AE) is known to be common in certain rural communities in China whilst it is generally rare and sporadic elsewhere. The objective of this study was to provide a first estimate of the global incidence of this disease by country. The second objective was to estimate the global disease burden using age and gender stratified incidences and estimated life expectancy with the disease from previous results of survival analysis. Disability weights were suggested from previous burden studies on echinococcosis.

Methodology/Principal Findings

We undertook a detailed review of published literature and data from other sources. We were unable to make a standardised systematic review as the quality of the data was highly variable from different countries and hence if we had used uniform inclusion criteria many endemic areas lacking data would not have been included. Therefore we used evidence based stochastic techniques to model uncertainty and other modelling and estimating techniques, particularly in regions where data quality was poor. We were able to make an estimate of the annual global incidence of disease and annual disease burden using standard techniques for calculation of DALYs. Our studies suggest that there are approximately 18,235 (CIs 11,900–28,200) new cases of AE per annum globally with 16,629 (91%) occurring in China and 1,606 outside China. Most of these cases are in regions where there is little treatment available and therefore will be fatal cases. Based on using disability weights for hepatic carcinoma and estimated age and gender specific incidence we were able to calculate that AE results in a median of 666,434 DALYs per annum (CIs 331,000-1.3 million).

Conclusions/Significance

The global burden of AE is comparable to several diseases in the neglected tropical disease cluster and is likely to be one of the most important diseases in certain communities in rural China on the Tibetan plateau.     

Evaluation of fecal immunoassays for canine Echinococcus infection in China

Human echinococcosis is present worldwide but it is in China that disease prevalence is the highest. In western China, especially in the Tibetan Plateau, the burden of echinococcosis is the most important. Dogs are a major definitive host of Echinococcus and monitoring the presence of Echinococcus worms in dogs is therefore essential to efficiently control the disease. Detection kits based on three different technologies including sandwich ELISA, (indirect) ELISA, and gold immunodiffusion, are currently marketed and used in China. The objective of this work was to assess the efficacy of these kits, in particular with respect to sensitivity and specificity. Four fecal antigen detection kits for canine infection reflecting the three technologies were obtained from companies and tested in parallel on 220 fecal samples. The results indicate that the performance is lower than expected, in particular in terms of sensitivity. The best results were obtained with the sandwich ELISA technology. The gold immunofiltration yielded the poorest results. In all cases, further development is needed to improve the performance of these kits which are key components for the control of echinococcosis.     

The Burden of Parasitic Zoonoses in Nepal: A Systematic Review

Background

Parasitic zoonoses (PZs) pose a significant but often neglected threat to public health, especially in developing countries. In order to obtain a better understanding of their health impact, summary measures of population health may be calculated, such as the Disability-Adjusted Life Year (DALY). However, the data required to calculate such measures are often not readily available for these diseases, which may lead to a vicious circle of under-recognition and under-funding.

Methodology

We examined the burden of PZs in Nepal through a systematic review of online and offline data sources. PZs were classified qualitatively according to endemicity, and where possible a quantitative burden assessment was conducted in terms of the annual number of incident cases, deaths and DALYs.

Principal Findings

Between 2000 and 2012, the highest annual burden was imposed by neurocysticercosis and congenital toxoplasmosis (14,268 DALYs [95% Credibility Interval (CrI): 5450–27,694] and 9255 DALYs [95% CrI: 6135–13,292], respectively), followed by cystic echinococcosis (251 DALYs [95% CrI: 105–458]). Nepal is probably endemic for trichinellosis, toxocarosis, diphyllobothriosis, foodborne trematodosis, taeniosis, and zoonotic intestinal helminthic and protozoal infections, but insufficient data were available to quantify their health impact. Sporadic cases of alveolar echinococcosis, angiostrongylosis, capillariosis, dirofilariosis, gnathostomosis, sparganosis and cutaneous leishmaniosis may occur.

Conclusions/Significance

In settings with limited surveillance capacity, it is possible to quantify the health impact of PZs and other neglected diseases, thereby interrupting the vicious circle of neglect. In Nepal, we found that several PZs are endemic and are imposing a significant burden to public health, higher than that of malaria, and comparable to that of HIV/AIDS. However, several critical data gaps remain. Enhanced surveillance for the endemic PZs identified in this study would enable additional burden estimates, and a more complete picture of the impact of these diseases.     

Impact of Increased Economic Burden Due to Human Echinococcosis in an Underdeveloped Rural Community of the People's Republic of China

Background

Ningxia is located in western People''s Republic of China, which is hyperendemic for human cystic echinococcosis (CE) throughout the entire area with alveolar echinococcosis (AE) hyperendemic in the south. This is in part due to its underdeveloped economy. Despite the recent rapid growth in P.R. China''s economy, medical expenditure for hospitalization of echinococcosis cases has become one of the major poverty generators in rural Ningxia, resulting in a significant social problem.

Methodology/Principal Findings

We reviewed the 2000 inpatient records with liver CE in surgical departments of hospitals from north, central and south Ningxia for the period 1996–2002. We carried out an analysis of health care expenditure of inpatient treatment in public hospitals, and examined the financial inequalities relating to human echinococcosis and the variation in per capita income between various socioeconomic groups with different levels of gross domestic product for different years. Hospital charges for Yinchuan, NHAR''s capital city in the north, increased approximately 35-fold more than the annual income of rural farmers with the result that they preferred to seek health care in local county hospitals, despite higher quality and more efficient treatment and diagnosis available in the city. Household income levels thus strongly influenced the choice of health care provider and the additional expense impeded access of poor people to better quality treatment.

Conclusions/Significance

Information on socioeconomic problems arising from echinococcosis, which adds considerably to the burden on patient families and communities, needs to be collected as a prerequisite for developing policies to tackle the disease in rural Ningxia.     

LIPGENE: an EU project to tackle the metabolic syndrome

LIPGENE is a new 5-year sixth framework EU project involving researchers from 14 EU countries. It will contribute to a reduction in the economic and social burden of the metabolic syndrome through research that will optimise the health impacts of dietary fat change. LIPGENE aims to: account for variation in genotype response to fatty acid modification; enable greater availability of food products that can enhance human health; enhance consumer awareness, and motivate adoption of dietary approaches to disease prevention. A truly integrated programme, LIPGENE incorporates human nutrition, animal nutrition, plant biotechnology, and economic and social/consumer sciences. The human nutrition packages will utilise data from an existing prospective study (SUVIMAX) to identify genotype and dietary interactions as risk factors for the metabolic syndrome. A multi-centre intervention will examine the effects of dietary fat on various risk factors for the metabolic syndrome, while molecular investigations will be supported by mechanistic and functional studies. The British Nutrition Foundation, as dissemination partners for this EU programme, is initiating a wide-reaching programme to disseminate information about the project and its findings. Further details, including lists of upcoming project-related events, are available at www.lipgene.tcd.ie and www.nutrition.org.uk/lipgene.     

Recent advances in the immunology and diagnosis of echinococcosis

Echinococcosis is a cosmopolitan zoonosis caused by adult or larval stages of cestodes belonging to the genus Echinococcus (family Taeniidae). The two major species of medical and public health importance are Echinococcus granulosus and Echinococcus multilocularis, which cause cystic echinococcosis and alveolar echinococcosis, respectively. Both cystic echinococcosis and alveolar echinococcosis are serious diseases, the latter especially so, with a high fatality rate and poor prognosis if managed inappropriately. This review highlights recent advances in immunity to infection and vaccination against both parasites in their intermediate and definitive hosts and procedures for diagnosis of cystic echinococcosis and alveolar echinococcosis, including the value of immunodiagnostic and DNA approaches. There is discussion also of progress in genomics and related technologies that is providing valuable insights on the functional biology of the Echinococcus organisms. These studies will underpin future research that will reveal a better understanding of the Echinococcus-host interplay, and suggest new avenues for the identification of additional targets for diagnosis, vaccination and chemotherapy.     

The uncertain burden of Plasmodium falciparum epidemics in Africa

Although the control of malaria epidemics has been a priority for the World Health Organization and other agencies for many years, surprisingly little is known about the public health burden of these epidemics. Here, we evaluate the available evidence of the morbidity and mortality impacts of individual epidemics in Africa and examine the problems associated with using these data to estimate the average annual burden of epidemics at national and continental scales. We argue that conventional approaches that are used to assess the burden of epidemics are inadequate, and outline the future steps that are required to produce estimates that are more accurate.     

Serologic and molecular diagnosis of zoonotic larval cestode infections

Neurocysticercosis, cystic echinococcosis and alveolar echinococcosis are the three major zoonotic larval cestodiases worldwide and threatening human life. Early therapeutic treatment based on early differential diagnosis at the early stage of infection and epidemiological surveillance with the expectation for control and prevention are the keys for improvement of quality of human life. Recent advances in (1). differential serodiagnosis of these three diseases, (2). molecular identification of human taeniid species and (3). polymorphism of mitochodrial DNA highly informative for future molecular epidemiology are reviewed in this article.     

Climate Change and Health Research in the Eastern Mediterranean Region

Anthropologically induced climate change, caused by an increased concentration of greenhouse gases in the atmosphere, is an emerging threat to human health. Consequences of climate change may affect the prevalence of various diseases and environmental and social maladies that affect population health. In this article, we reviewed the literature on climate change and health in the Eastern Mediterranean Region. This region already faces numerous humanitarian crises, from conflicts to natural hazards and a high burden of disease. Climate change is likely to aggravate these emergencies, necessitating a strengthening of health systems and capacities in the region. However, the existing literature on climate change from the region is sparse and informational gaps stand in the way of regional preparedness and adaptation. Further research is needed to assess climatic changes and related health impacts in the Eastern Mediterranean Region. Such knowledge will allow countries to identify preparedness vulnerabilities, evaluate capacity to adapt to climate change, and develop adaptation strategies to allay the health impacts of climate change.     

Oceans and Human Health (OHH): a European Perspective from the Marine Board of the European Science Foundation (Marine Board-ESF)

The oceans and coastal seas provide mankind with many benefits including food for around a third of the global population, the air that we breathe and our climate system which enables habitation of much of the planet. However, the converse is that generation of natural events (such as hurricanes, severe storms and tsunamis) can have devastating impacts on coastal populations, while pollution of the seas by pathogens and toxic waste can cause illness and death in humans and animals. Harmful effects from biogenic toxins produced by algal blooms (HABs) and from the pathogens associated with microbial pollution are also a health hazard in seafood and from direct contact with water. The overall global burden of human disease caused by sewage pollution of coastal waters has been estimated at 4 million lost person-years annually. Finally, the impacts of all of these issues will be exacerbated by climate change. A holistic systems approach is needed. It must consider whole ecosystems, and their sustainability, such as integrated coastal zone management, is necessary to address the highly interconnected scientific challenges of increased human population pressure, pollution and over-exploitation of food (and other) resources as drivers of adverse ecological, social and economic impacts. There is also an urgent and critical requirement for effective and integrated public health solutions to be developed through the formulation of politically and environmentally meaningful policies. The research community required to address “Oceans & Human Health” in Europe is currently very fragmented, and recognition by policy makers of some of the problems, outlined in the list of challenges above, is limited. Nevertheless, relevant key policy issues for governments worldwide include the reduction of the burden of disease (including the early detection of emerging pathogens and other threats) and improving the quality of the global environment. Failure to effectively address these issues will impact adversely on efforts to alleviate poverty, sustain the availability of environmental goods and services and improve health and social and economic stability; and thus, will impinge on many policy decisions, both nationally and internationally. Knowledge exchange (KE) will be a key element of any ensuing research. KE will facilitate the integration of biological, medical, epidemiological, social and economic disciplines, as well as the emergence of synergies between seemingly unconnected areas of science and socio-economic issues, and will help to leverage knowledge transfer across the European Union (EU) and beyond. An integrated interdisciplinary systems approach is an effective way to bring together the appropriate groups of scientists, social scientists, economists, industry and other stakeholders with the policy formulators in order to address the complexities of interfacial problems in the area of environment and human health. The Marine Board of the European Science Foundation Working Group on “Oceans and Human Health” has been charged with developing a position paper on this topic with a view to identifying the scientific, social and economic challenges and making recommendations to the EU on policy-relevant research and development activities in this arena. This paper includes the background to health-related issues linked to the coastal environment and highlights the main arguments for an ecosystem-based whole systems approach.     

Geographic disparities and moral hazards in the predicted impacts of climate change on human populations

Aim It has been qualitatively understood for a long time that climate change will have widely varying effects on human well‐being in different regions of the world. The spatial complexities underlying our relationship to climate and the geographical disparities in human demographic change have, however, precluded the development of global indices of the predicted regional impacts of climate change on humans. Humans will be most negatively affected by climate change in regions where populations are strongly dependent on climate and favourable climatic conditions decline. Here we use the relationship between the distribution of human population density and climate as a basis to develop the first global index of predicted impacts of climate change on human populations. Location Global. Methods We use spatially explicit models of the present relationship between human population density and climate along with forecasted climate change to predict climate vulnerabilities over the coming decades. We then globally represent regional disparities in human population dynamics estimated with our ecological niche model and with a demographic forecast and contrast these disparities with CO₂ emissions data to quantitatively evaluate the notion of moral hazard in climate change policies. Results Strongly negative impacts of climate change are predicted in Central America, central South America, the Arabian Peninsula, Southeast Asia and much of Africa. Importantly, the regions of greatest vulnerability are generally distant from the high‐latitude regions where the magnitude of climate change will be greatest. Furthermore, populations contributing the most to greenhouse gas emissions on a per capita basis are unlikely to experience the worst impacts of climate change, satisfying the conditions for a moral hazard in climate change policies. Main conclusions Regionalized analysis of relationships between distribution of human population density and climate provides a novel framework for developing global indices of human vulnerability to climate change. The predicted consequences of climate change on human populations are correlated with the factors causing climate change at the regional level, providing quantitative support for many qualitative statements found in international climate change assessments.     

Spinal Cystic Echinococcosis – A Systematic Analysis and Review of the Literature: Part 2. Treatment,Follow-up and Outcome

Bone involvement in human cystic echinococcosis (CE) is rare, but affects the spine in approximately 50% of cases. Despite significant advances in diagnostic imaging techniques, surgical treatment and introduction of pharmacological therapy, spinal echinococcosis remains associated with a high degree of morbidity, disability and mortality.We systematically reviewed the published literature of the last five decades to update and summarize the currently existing data on treatment, follow-up and outcome of spinal CE.     

Consequences of Future Data Center Deployment in Canada on Electricity Generation and Environmental Impacts: A 2015–2030 Prospective Study

The environmental impacts of data centers that provide information and communication technologies (ICTs) services are strongly related to electricity generation. With the increasing use of ICT, many data centers are expected to be built, causing more absolute impacts on the environment. Given that electricity distribution networks are very complex and dynamic systems, an environmental evaluation of future data centers is uncertain. This study proposes a new approach to investigate the consequences of future data center deployment in Canada and optimize this deployment based on the Energy 2020 technoeconomic model in combination with life cycle assessment methodology. The method determines specific electricity sources that will power the future Canadian data centers and computes related environmental impacts based on several indicators. In case‐study scenarios, the largest deployment of data centers leads to the smallest impact per megawatt of data centers for all of the environmental indicators. It is found that an increase in power demand by data centers would lead to a reduction in electricity exports to the United States, driving the United States to generate more electricity to meet its energy demand. Given that electricity generation in the United States is more polluting than in Canada, the deployment of data centers in Canada is indirectly linked to an increase in overall environmental impacts. However, though an optimal solution should be found to mitigate global greenhouse gas emissions, it is not clear whether the environmental burden related to U.S. electricity generation should be attributed to the Canadian data centers.     

Basic quantitative risk assessment of light sources: Comparison of light exposure assessment and endpoint life cycle impact assessment

Human Health Area of Protection (HHAoP) has been receiving greater emphasis in recent years in the scope of Environmental Impact Assessment (EIA) of products or services with more impact categories specifically dedicated to include different dimensions of HHAoP. Human health impacts of light sources, however, have received less attention despite their prevalent use for backlighting, general lighting and architectural purposes. Currently, Environmental Product Declarations (EPDs) of lighting devices and electronic devices with backlit screens do not address endpoint impacts nor do they specify technical properties of the light that can enable such an assessment. This study investigates endpoint impacts of eleven lighting devices (1) due to light exposure during the use phase and (2) due to emissions throughout their life cycle. Impacts are quantified as disease burden in terms of disability adjusted life years (DALY). The burden of exposure was calculated using attributable fraction (AF) method. The burden due to life cycle emissions was quantified using GaBi software and built-in life cycle impact assessment (LCIA) method ReCiPe. Endpoint impact categories included were climate change human health, human toxicity, ionizing radiation, ozone depletion, particulate matter formation, and photochemical oxidant formation. The disease burden due to light exposure of all light sources is of two orders of magnitude greater than the disease burden due to life cycle emissions pointing to the need for its treatment.     

Maternal grandmothers improve nutritional status and survival of children in rural Gambia

Hypotheses for the evolution of human female life-history characteristics have often focused on the social nature of human societies, which allows women to share the burden of childcare and provisioning amongst other members of their kin group. We test the hypothesis that child health and survival probabilities will be improved by the presence of kin using a longitudinal database from rural Gambia. We find that the only kin to improve the nutritional status of children significantly (apart from mothers) are maternal grandmothers, and that this is reflected in higher survival probabilities for children with living maternal grandmothers. There is also evidence that the reproductive status of the maternal grandmother influences child nutrition, with young children being taller in the presence of non-reproductive grandmothers than grandmothers who are still reproductively active. Paternal grandmothers and male kin, including fathers, have negligible impacts on the nutritional status and survival of children.     

Bacterial resistance to antimicrobial agents used in fish farming: A critical evaluation of method and meaning

The use of antimicrobial agents in aquaculture has resulted in the increase in the frequency of strains resistant to these agents. Potentially these resistant strains can have an impact on the therapy of fish diseases, the therapy of human diseases, or the environment of the fish farms. Analysis of the extent of these impacts is hindered by the limited information available and the variation in methods that have been used. There is, for example, considerable variation in the methods used to measure the sensitivity of strains and in the criteria used to determine the clinical significance of these laboratory data. It is important that some standardisation of sensitivity testing methods is attempted. The available data on the frequency of resistance in fish pathogens suggest that the use of antimicrobial agents in aquaculture has significantly reduced the therapeutic options for treating fish diseases. The data available to assess the impact of the use of these agents in aquaculture on the therapeutic options for the treatment of human infections are incomplete. At present, no quantitative assessment of this risk can be attempted. Considerations of the data on the impact of the veterinary use of these agents on the therapy of human diseases would suggest that the extent of the risk represented by their use in aquaculture is small. The epidemiology of the human pathogens that have been associated with fish would tend to confirm this assessment. There is little data pertaining to the ecology of R plasmids in the natural environment. The significance of these plasmids in transferring resistance determinants from the aquatic compartment to the human compartment can, at present, only be assessed at a theoretical level. However, such a theoretical analysis suggests that the contribution of R plasmids, selected in the aquatic environment, to the frequency of resistance in human pathogens is probably very small. Fish farmers will have to develop methods of husbandry that limit the rate at which resistant strains emerge. Without these changes in husbandry, fish farming will rapidly enter the preantibiotic era. It is probable that these changes will also have the effect of reducing any impact of antimicrobial agents used in aquaculture on the environment outside the fish farm.     

How geographic access to care shapes disease burden: The current impact of post-exposure prophylaxis and potential for expanded access to prevent human rabies deaths in Madagascar

BackgroundPost-exposure prophylaxis (PEP) is highly effective at preventing human rabies deaths, however access to PEP is limited in many rabies endemic countries. The 2018 decision by Gavi to add human rabies vaccine to its investment portfolio should expand PEP availability and reduce rabies deaths. We explore how geographic access to PEP impacts the rabies burden in Madagascar and the potential benefits of improved provisioning.Methodology & principal findingsWe use spatially resolved data on numbers of bite patients seeking PEP across Madagascar and estimates of travel times to the closest clinic providing PEP (N = 31) in a Bayesian regression framework to estimate how geographic access predicts reported bite incidence. We find that travel times strongly predict reported bite incidence across the country. Using resulting estimates in an adapted decision tree, we extrapolate rabies deaths and reporting and find that geographic access to PEP shapes burden sub-nationally. We estimate 960 human rabies deaths annually (95% Prediction Intervals (PI): 790–1120), with PEP averting an additional 800 deaths (95% PI: 640–970) each year. Under these assumptions, we find that expanding PEP to one clinic per district (83 additional clinics) could reduce deaths by 19%, but even with all major primary clinics provisioning PEP (1733 additional clinics), we still expect substantial rabies mortality. Our quantitative estimates are most sensitive to assumptions of underlying rabies exposure incidence, but qualitative patterns of the impacts of travel times and expanded PEP access are robust.Conclusions & significancePEP is effective at preventing rabies deaths, and in the absence of strong surveillance, targeting underserved populations may be the most equitable way to provision PEP. Given the potential for countries to use Gavi funding to expand access to PEP in the coming years, this framework could be used as a first step to guide expansion and improve targeting of interventions in similar endemic settings where PEP access is geographically restricted and baseline data on rabies risk is lacking. While better PEP access should save many lives, improved outreach, surveillance, and dog vaccination will be necessary, and if rolled out with Gavi investment, could catalyze progress towards achieving zero rabies deaths.