Improving disaggregation models of malaria incidence by ensembling non-linear models of prevalence.

Maps of disease burden are a core tool needed for the control and elimination of malaria. Reliable routine surveillance data of malaria incidence, typically aggregated to administrative units, is becoming more widely available. Disaggregation regression is an important model framework for estimating high resolution risk maps from aggregated data. However, the aggregation of incidence over large, heterogeneous areas means that these data are underpowered for estimating complex, non-linear models. In contrast, prevalence point-surveys are directly linked to local environmental conditions but are not common in many areas of the world. Here, we train multiple non-linear, machine learning models on Plasmodium falciparum prevalence point-surveys. We then ensemble the predictions from these machine learning models with a disaggregation regression model that uses aggregated malaria incidences as response data. We find that using a disaggregation regression model to combine predictions from machine learning models improves model accuracy relative to a baseline model.

A simulation study of disaggregation regression for spatial disease mapping.

Disaggregation regression has become an important tool in spatial disease mapping for making fine-scale predictions of disease risk from aggregated response data. By including high resolution covariate information and modeling the data generating process on a fine scale, it is hoped that these models can accurately learn the relationships between covariates and response at a fine spatial scale. However, validating these high resolution predictions can be a challenge, as often there is no data observed at this spatial scale. In this study, disaggregation regression was performed on simulated data in various settings and the resulting fine-scale predictions are compared to the simulated ground truth. Performance was investigated with varying numbers of data points, sizes of aggregated areas and levels of model misspecification. The effectiveness of cross validation on the aggregate level as a measure of fine-scale predictive performance was also investigated. Predictive performance improved as the number of observations increased and as the size of the aggregated areas decreased. When the model was well-specified, fine-scale predictions were accurate even with small numbers of observations and large aggregated areas. Under model misspecification predictive performance was significantly worse for large aggregated areas but remained high when response data was aggregated over smaller regions. Cross-validation correlation on the aggregate level was a moderately good predictor of fine-scale predictive performance. While these simulations are unlikely to capture the nuances of real-life response data, this study gives insight into the effectiveness of disaggregation regression in different contexts.

Predicting non-state terrorism worldwide.

Several thousand people die every year worldwide because of terrorist attacks perpetrated by non-state actors. In this context, reliable and accurate short-term predictions of non-state terrorism at the local level are key for policy makers to target preventative measures. Using only publicly available data, we show that predictive models that include structural and procedural predictors can accurately predict the occurrence of non-state terrorism locally and a week ahead in regions affected by a relatively high prevalence of terrorism. In these regions, theoretically informed models systematically outperform models using predictors built on past terrorist events only. We further identify and interpret the local effects of major global and regional terrorism drivers. Our study demonstrates the potential of theoretically informed models to predict and explain complex forms of political violence at policy-relevant scales.

Maps and metrics of insecticide-treated net access, use, and nets-per-capita in Africa from 2000-2020.

Insecticide-treated nets (ITNs) are one of the most widespread and impactful malaria interventions in Africa, yet a spatially-resolved time series of ITN coverage has never been published. Using data from multiple sources, we generate high-resolution maps of ITN access, use, and nets-per-capita annually from 2000 to 2020 across the 40 highest-burden African countries. Our findings support several existing hypotheses: that use is high among those with access, that nets are discarded more quickly than official policy presumes, and that effectively distributing nets grows more difficult as coverage increases. The primary driving factors behind these findings are most likely strong cultural and social messaging around the importance of net use, low physical net durability, and a mixture of inherent commodity distribution challenges and less-than-optimal net allocation policies, respectively. These results can inform both policy decisions and downstream malaria analyses.

Global estimation of anti-malarial drug effectiveness for the treatment of uncomplicated Plasmodium falciparum malaria 1991-2019.

BACKGROUND: Anti-malarial drugs play a critical role in reducing malaria morbidity and mortality, but their role is mediated by their effectiveness. Effectiveness is defined as the probability that an anti-malarial drug will successfully treat an individual infected with malaria parasites under routine health care delivery system. Anti-malarial drug effectiveness (AmE) is influenced by drug resistance, drug quality, health system quality, and patient adherence to drug use; its influence on malaria burden varies through space and time. METHODS: This study uses data from 232 efficacy trials comprised of 86,776 infected individuals to estimate the artemisinin-based and non-artemisinin-based AmE for treating falciparum malaria between 1991 and 2019. Bayesian spatiotemporal models were fitted and used to predict effectiveness at the pixel-level (5 km × 5 km). The median and interquartile ranges (IQR) of AmE are presented for all malaria-endemic countries. RESULTS: The global effectiveness of artemisinin-based drugs was 67.4% (IQR: 33.3-75.8), 70.1% (43.6-76.0) and 71.8% (46.9-76.4) for the 1991-2000, 2006-2010, and 2016-2019 periods, respectively. Countries in central Africa, a few in South America, and in the Asian region faced the challenge of lower effectiveness of artemisinin-based anti-malarials. However, improvements were seen after 2016, leaving only a few hotspots in Southeast Asia where resistance to artemisinin and partner drugs is currently problematic and in the central Africa where socio-demographic challenges limit effectiveness. The use of artemisinin-based combination therapy (ACT) with a competent partner drug and having multiple ACT as first-line treatment choice sustained high levels of effectiveness. High levels of access to healthcare, human resource capacity, education, and proximity to cities were associated with increased effectiveness. Effectiveness of non-artemisinin-based drugs was much lower than that of artemisinin-based with no improvement over time: 52.3% (17.9-74.9) for 1991-2000 and 55.5% (27.1-73.4) for 2011-2015. Overall, AmE for artemisinin-based and non-artemisinin-based drugs were, respectively, 29.6 and 36% below clinical efficacy as measured in anti-malarial drug trials. CONCLUSIONS: This study provides evidence that health system performance, drug quality and patient adherence influence the effectiveness of anti-malarials used in treating uncomplicated falciparum malaria. These results provide guidance to countries' treatment practises and are critical inputs for malaria prevalence and incidence models used to estimate national level malaria burden.

Improved long-term time-series predictions of total blood use data from England.

BACKGROUND: Red blood cells are essential for modern medicine but managing their collection and supply to cope with fluctuating demands represents a major challenge. As deterministic models based on predicted population changes have been problematic, there remains a need for more precise and reliable prediction of use. Here, we develop three new time-series methods to predict red cell use 4 to 52 weeks ahead. STUDY DESIGN AND METHODS: From daily aggregates of red blood cell (RBC) units issued from 2005 to 2011 from the NHS Blood and Transplant, we generated a new set of non-overlapping weekly data by summing the daily data over 7 days and derived the average blood use per week over 4-week and 52-week periods. We used three new methods for linear prediction of blood use by computing the coefficients using Minimum Mean Squared Error (MMSE) algorithm. RESULTS: We optimized the time-window size, order of the prediction, and order of the polynomial fit for our data set. By exploiting the annual periodicity of the data, we achieved significant improvements in long-term predictions, as well as modest improvements in short-term predictions. The new methods predicted mean RBC use with a standard deviation of the percentage error of 2.5% for 4 weeks ahead and 3.4% for 52 weeks ahead. CONCLUSION: This paradigm allows short- and long-term prediction of RBC use and could provide reliable and precise prediction up to 52 weeks ahead to improve the efficiency of blood services and sufficiency of blood supply with reduced costs.

Prediction paradigm involving time series applied to total blood issues data from England.

BACKGROUND: Blood products are essential for modern medicine, but managing their collection and supply in the face of fluctuating demands represents a major challenge. As deterministic models based on predicted changes in population have been problematic, there remains a need for more precise and reliable prediction of demands. Here, we propose a paradigm incorporating four different time-series methods to predict red blood cell (RBC) issues 4 to 24 weeks ahead. STUDY DESIGN AND METHODS: We used daily aggregates of RBC units issued from 2005 to 2011 from the National Health Service Blood and Transplant. We generated a new set of nonoverlapping weekly data by summing the daily data over 7 days and derived the average blood issues per week over 4-week periods. We used four methods for linear prediction of blood demand by computing the coefficients with the minimum mean squared error and weighted least squares error algorithms. RESULTS: We optimized the time-window size, order of the prediction, and order of the polynomial fit for our data set. The four time-series methods, essentially using different weightings to data points, gave very similar results and predicted mean RBC issues with a standard deviation of the percentage error of 3.0% for 4 weeks ahead and 4.0% for 24 weeks ahead. CONCLUSION: This paradigm allows prediction of demand for RBCs and could be developed to provide reliable and precise prediction up to 24 weeks ahead to improve the efficiency of blood services and sufficiency of blood supply with reduced costs.

Mapping the global endemicity and clinical burden of Plasmodium vivax, 2000-17: a spatial and temporal modelling study.

BACKGROUND: Plasmodium vivax exacts a significant toll on health worldwide, yet few efforts to date have quantified the extent and temporal trends of its global distribution. Given the challenges associated with the proper diagnosis and treatment of P vivax, national malaria programmes-particularly those pursuing malaria elimination strategies-require up to date assessments of P vivax endemicity and disease impact. This study presents the first global maps of P vivax clinical burden from 2000 to 2017. METHODS: In this spatial and temporal modelling study, we adjusted routine malariometric surveillance data for known biases and used socioeconomic indicators to generate time series of the clinical burden of P vivax. These data informed Bayesian geospatial models, which produced fine-scale predictions of P vivax clinical incidence and infection prevalence over time. Within sub-Saharan Africa, where routine surveillance for P vivax is not standard practice, we combined predicted surfaces of Plasmodium falciparum with country-specific ratios of P vivax to P falciparum. These results were combined with surveillance-based outputs outside of Africa to generate global maps. FINDINGS: We present the first high-resolution maps of P vivax burden. These results are combined with those for P falciparum (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The burden of P vivax malaria decreased by 41·6%, from 24·5 million cases (95% uncertainty interval 22·5-27·0) in 2000 to 14·3 million cases (13·7-15·0) in 2017. The Americas had a reduction of 56·8% (47·6-67·0) in total cases since 2000, while South-East Asia recorded declines of 50·5% (50·3-50·6) and the Western Pacific regions recorded declines of 51·3% (48·0-55·4). Europe achieved zero P vivax cases during the study period. Nonetheless, rates of decline have stalled in the past five years for many countries, with particular increases noted in regions affected by political and economic instability. INTERPRETATION: Our study highlights important spatial and temporal patterns in the clinical burden and prevalence of P vivax. Amid substantial progress worldwide, plateauing gains and areas of increased burden signal the potential for challenges that are greater than expected on the road to malaria elimination. These results support global monitoring systems and can inform the optimisation of diagnosis and treatment where P vivax has most impact. FUNDING: Bill & Melinda Gates Foundation and the Wellcome Trust.

Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum, 2000-17: a spatial and temporal modelling study.

BACKGROUND: Since 2000, the scale-up of malaria control interventions has substantially reduced morbidity and mortality caused by the disease globally, fuelling bold aims for disease elimination. In tandem with increased availability of geospatially resolved data, malaria control programmes increasingly use high-resolution maps to characterise spatially heterogeneous patterns of disease risk and thus efficiently target areas of high burden. METHODS: We updated and refined the Plasmodium falciparum parasite rate and clinical incidence models for sub-Saharan Africa, which rely on cross-sectional survey data for parasite rate and intervention coverage. For malaria endemic countries outside of sub-Saharan Africa, we produced estimates of parasite rate and incidence by applying an ecological downscaling approach to malaria incidence data acquired via routine surveillance. Mortality estimates were derived by linking incidence to systematically derived vital registration and verbal autopsy data. Informed by high-resolution covariate surfaces, we estimated P falciparum parasite rate, clinical incidence, and mortality at national, subnational, and 5 × 5 km pixel scales with corresponding uncertainty metrics. FINDINGS: We present the first global, high-resolution map of P falciparum malaria mortality and the first global prevalence and incidence maps since 2010. These results are combined with those for Plasmodium vivax (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The P falciparum estimates span the period 2000-17, and illustrate the rapid decline in burden between 2005 and 2017, with incidence declining by 27·9% and mortality declining by 42·5%. Despite a growing population in endemic regions, P falciparum cases declined between 2005 and 2017, from 232·3 million (95% uncertainty interval 198·8-277·7) to 193·9 million (156·6-240·2) and deaths declined from 925 800 (596 900-1 341 100) to 618 700 (368 600-952 200). Despite the declines in burden, 90·1% of people within sub-Saharan Africa continue to reside in endemic areas, and this region accounted for 79·4% of cases and 87·6% of deaths in 2017. INTERPRETATION: High-resolution maps of P falciparum provide a contemporary resource for informing global policy and malaria control planning, programme implementation, and monitoring initiatives. Amid progress in reducing global malaria burden, areas where incidence trends have plateaued or increased in the past 5 years underscore the fragility of hard-won gains against malaria. Efforts towards elimination should be strengthened in such areas, and those where burden remained high throughout the study period. FUNDING: Bill & Melinda Gates Foundation.