ABSTRACT
We developed mathematical models to analyze a large dengue virus (DENV) epidemic in Reunion Island in 2018-2019. Our models captured major drivers of uncertainty including the complex relationship between climate and DENV transmission, temperature trends, and underreporting. Early assessment correctly concluded that persistence of DENV transmission during the austral winter 2018 was likely and that the second epidemic wave would be larger than the first one. From November 2018, the detection probability was estimated at 10%-20% and, for this range of values, our projections were found to be remarkably accurate. Overall, we estimated that 8% and 18% of the population were infected during the first and second wave, respectively. Out of the 3 models considered, the best-fitting one was calibrated to laboratory entomological data, and accounted for temperature but not precipitation. This study showcases the contribution of modeling to strengthen risk assessments and planning of national and local authorities.
Subject(s)
Aedes , Dengue Virus , Dengue , Epidemics , Animals , Humans , Reunion/epidemiology , WeatherABSTRACT
Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.
Subject(s)
COVID-19 , Neglected Diseases , Tropical Medicine , Neglected Diseases/prevention & control , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Models, Theoretical , World Health Organization , SARS-CoV-2 , Decision Making , Global HealthABSTRACT
The Ross-Macdonald model has exerted enormous influence over the study of malaria transmission dynamics and control, but it lacked features to describe parasite dispersal, travel, and other important aspects of heterogeneous transmission. Here, we present a patch-based differential equation modeling framework that extends the Ross-Macdonald model with sufficient skill and complexity to support planning, monitoring and evaluation for Plasmodium falciparum malaria control. We designed a generic interface for building structured, spatial models of malaria transmission based on a new algorithm for mosquito blood feeding. We developed new algorithms to simulate adult mosquito demography, dispersal, and egg laying in response to resource availability. The core dynamical components describing mosquito ecology and malaria transmission were decomposed, redesigned and reassembled into a modular framework. Structural elements in the framework-human population strata, patches, and aquatic habitats-interact through a flexible design that facilitates construction of ensembles of models with scalable complexity to support robust analytics for malaria policy and adaptive malaria control. We propose updated definitions for the human biting rate and entomological inoculation rates. We present new formulas to describe parasite dispersal and spatial dynamics under steady state conditions, including the human biting rates, parasite dispersal, the "vectorial capacity matrix," a human transmitting capacity distribution matrix, and threshold conditions. An [Formula: see text] package that implements the framework, solves the differential equations, and computes spatial metrics for models developed in this framework has been developed. Development of the model and metrics have focused on malaria, but since the framework is modular, the same ideas and software can be applied to other mosquito-borne pathogen systems.
Subject(s)
Culicidae , Malaria, Falciparum , Malaria , Adult , Animals , Humans , Malaria/epidemiology , Culicidae/physiology , Ecology , EcosystemABSTRACT
[This corrects the article DOI: 10.1371/journal.pmed.1003793.].
ABSTRACT
BACKGROUND: Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. METHODS: We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc.). RESULTS: We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 papers published 2002-2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: (i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, (ii) regional models used to predict the spread of major epidemics between countries and (iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures. CONCLUSIONS: Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping.
Subject(s)
Aedes , Arbovirus Infections , Arboviruses , Chikungunya Fever , Dengue , Yellow Fever , Zika Virus Infection , Zika Virus , Animals , Humans , Arbovirus Infections/epidemiology , Yellow Fever/epidemiology , Mosquito Vectors , Dengue/epidemiologyABSTRACT
BACKGROUND: The COVID-19 epidemic has differentially impacted communities across England, with regional variation in rates of confirmed cases, hospitalisations and deaths. Measurement of this burden changed substantially over the first months, as surveillance was expanded to accommodate the escalating epidemic. Laboratory confirmation was initially restricted to clinical need ("pillar 1") before expanding to community-wide symptomatics ("pillar 2"). This study aimed to ascertain whether inconsistent measurement of case data resulting from varying testing coverage could be reconciled by drawing inference from COVID-19-related deaths. METHODS: We fit a Bayesian spatio-temporal model to weekly COVID-19-related deaths per local authority (LTLA) throughout the first wave (1 January 2020-30 June 2020), adjusting for the local epidemic timing and the age, deprivation and ethnic composition of its population. We combined predictions from this model with case data under community-wide, symptomatic testing and infection prevalence estimates from the ONS infection survey, to infer the likely trajectory of infections implied by the deaths in each LTLA. RESULTS: A model including temporally- and spatially-correlated random effects was found to best accommodate the observed variation in COVID-19-related deaths, after accounting for local population characteristics. Predicted case counts under community-wide symptomatic testing suggest a total of 275,000-420,000 cases over the first wave - a median of over 100,000 additional to the total confirmed in practice under varying testing coverage. This translates to a peak incidence of around 200,000 total infections per week across England. The extent to which estimated total infections are reflected in confirmed case counts was found to vary substantially across LTLAs, ranging from 7% in Leicester to 96% in Gloucester with a median of 23%. CONCLUSIONS: Limitations in testing capacity biased the observed trajectory of COVID-19 infections throughout the first wave. Basing inference on COVID-19-related mortality and higher-coverage testing later in the time period, we could explore the extent of this bias more explicitly. Evidence points towards substantial under-representation of initial growth and peak magnitude of infections nationally, to which different parts of the country contribute unequally.
Subject(s)
COVID-19 , Bayes Theorem , COVID-19/epidemiology , Cost of Illness , Humans , Information Storage and Retrieval , SARS-CoV-2ABSTRACT
BACKGROUND: With enough advanced notice, dengue outbreaks can be mitigated. As a climate-sensitive disease, environmental conditions and past patterns of dengue can be used to make predictions about future outbreak risk. These predictions improve public health planning and decision-making to ultimately reduce the burden of disease. Past approaches to dengue forecasting have used seasonal climate forecasts, but the predictive ability of a system using different lead times in a year-round prediction system has been seldom explored. Moreover, the transition from theoretical to operational systems integrated with disease control activities is rare. METHODS AND FINDINGS: We introduce an operational seasonal dengue forecasting system for Vietnam where Earth observations, seasonal climate forecasts, and lagged dengue cases are used to drive a superensemble of probabilistic dengue models to predict dengue risk up to 6 months ahead. Bayesian spatiotemporal models were fit to 19 years (2002-2020) of dengue data at the province level across Vietnam. A superensemble of these models then makes probabilistic predictions of dengue incidence at various future time points aligned with key Vietnamese decision and planning deadlines. We demonstrate that the superensemble generates more accurate predictions of dengue incidence than the individual models it incorporates across a suite of time horizons and transmission settings. Using historical data, the superensemble made slightly more accurate predictions (continuous rank probability score [CRPS] = 66.8, 95% CI 60.6-148.0) than a baseline model which forecasts the same incidence rate every month (CRPS = 79.4, 95% CI 78.5-80.5) at lead times of 1 to 3 months, albeit with larger uncertainty. The outbreak detection capability of the superensemble was considerably larger (69%) than that of the baseline model (54.5%). Predictions were most accurate in southern Vietnam, an area that experiences semi-regular seasonal dengue transmission. The system also demonstrated added value across multiple areas compared to previous practice of not using a forecast. We use the system to make a prospective prediction for dengue incidence in Vietnam for the period May to October 2020. Prospective predictions made with the superensemble were slightly more accurate (CRPS = 110, 95% CI 102-575) than those made with the baseline model (CRPS = 125, 95% CI 120-168) but had larger uncertainty. Finally, we propose a framework for the evaluation of probabilistic predictions. Despite the demonstrated value of our forecasting system, the approach is limited by the consistency of the dengue case data, as well as the lack of publicly available, continuous, and long-term data sets on mosquito control efforts and serotype-specific case data. CONCLUSIONS: This study shows that by combining detailed Earth observation data, seasonal climate forecasts, and state-of-the-art models, dengue outbreaks can be predicted across a broad range of settings, with enough lead time to meaningfully inform dengue control. While our system omits some important variables not currently available at a subnational scale, the majority of past outbreaks could be predicted up to 3 months ahead. Over the next 2 years, the system will be prospectively evaluated and, if successful, potentially extended to other areas and other climate-sensitive disease systems.
Subject(s)
Dengue/epidemiology , Disease Outbreaks , Public Health/methods , Dengue/virology , Forecasting/methods , Humans , Incidence , Models, Statistical , Seasons , Vietnam/epidemiologyABSTRACT
BACKGROUND: The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research. METHODS AND FINDINGS: We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies. CONCLUSIONS: These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.
Subject(s)
Biomedical Research/standards , COVID-19/epidemiology , Checklist/standards , Epidemics , Guidelines as Topic/standards , Research Design , Biomedical Research/methods , Checklist/methods , Communicable Diseases/epidemiology , Epidemics/statistics & numerical data , Forecasting/methods , Humans , Reproducibility of ResultsABSTRACT
BACKGROUND: Diarrheal diseases are the third leading cause of disease and death in children younger than 5 years of age in Africa and were responsible for an estimated 30 million cases of severe diarrhea (95% credible interval, 27 million to 33 million) and 330,000 deaths (95% credible interval, 270,000 to 380,000) in 2015. The development of targeted approaches to address this burden has been hampered by a paucity of comprehensive, fine-scale estimates of diarrhea-related disease and death among and within countries. METHODS: We produced annual estimates of the prevalence and incidence of diarrhea and diarrhea-related mortality with high geographic detail (5 km2) across Africa from 2000 through 2015. Estimates were created with the use of Bayesian geostatistical techniques and were calibrated to the results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016. RESULTS: The results revealed geographic inequality with regard to diarrhea risk in Africa. Of the estimated 330,000 childhood deaths that were attributable to diarrhea in 2015, more than 50% occurred in 55 of the 782 first-level administrative subdivisions (e.g., states). In 2015, mortality rates among first-level administrative subdivisions in Nigeria differed by up to a factor of 6. The case fatality rates were highly varied at the national level across Africa, with the highest values observed in Benin, Lesotho, Mali, Nigeria, and Sierra Leone. CONCLUSIONS: Our findings showed concentrated areas of diarrheal disease and diarrhea-related death in countries that had a consistently high burden as well as in countries that had considerable national-level reductions in diarrhea burden. (Funded by the Bill and Melinda Gates Foundation.).
Subject(s)
Diarrhea/epidemiology , Africa/epidemiology , Bayes Theorem , Child, Preschool , Diarrhea/mortality , Geography, Medical , Humans , Incidence , Infant , Mortality/trends , PrevalenceABSTRACT
BACKGROUND: Stratifying dengue risk within endemic countries is crucial for allocating limited control interventions. Current methods of monitoring dengue transmission intensity rely on potentially inaccurate incidence estimates. We investigated whether incidence or alternate metrics obtained from standard, or laboratory, surveillance operations represent accurate surrogate indicators of the burden of dengue and can be used to monitor the force of infection (FOI) across urban centres. METHODS: Among those who reported and resided in 13 cities across the Philippines, we collected epidemiological data from all dengue case reports between 2014 and 2017 (N 80,043) and additional laboratory data from a cross-section of sampled case reports (N 11,906) between 2014 and 2018. At the city level, we estimated the aggregated annual FOI from age-accumulated IgG among the non-dengue reporting population using catalytic modelling. We compared city-aggregated FOI estimates to aggregated incidence and the mean age of clinically and laboratory diagnosed dengue cases using Pearson's Correlation coefficient and generated predicted FOI estimates using regression modelling. RESULTS: We observed spatial heterogeneity in the dengue average annual FOI across sampled cities, ranging from 0.054 [0.036-0.081] to 0.249 [0.223-0.279]. Compared to FOI estimates, the mean age of primary dengue infections had the strongest association (ρ -0.848, p value<0.001) followed by the mean age of those reporting with warning signs (ρ -0.642, p value 0.018). Using regression modelling, we estimated the predicted annual dengue FOI across urban centres from the age of those reporting with primary infections and revealed prominent spatio-temporal heterogeneity in transmission intensity. CONCLUSIONS: We show the mean age of those reporting with their first dengue infection or those reporting with warning signs of dengue represent superior indicators of the dengue FOI compared to crude incidence across urban centres. Our work provides a framework for national dengue surveillance to routinely monitor transmission and target control interventions to populations most in need.
Subject(s)
Dengue , Cities/epidemiology , Dengue/epidemiology , Humans , Incidence , Laboratories , Philippines/epidemiologyABSTRACT
BackgroundPopulation-level mathematical models of outbreaks typically assume that disease transmission is not impacted by population density ('frequency-dependent') or that it increases linearly with density ('density-dependent').AimWe sought evidence for the role of population density in SARS-CoV-2 transmission.MethodsUsing COVID-19-associated mortality data from England, we fitted multiple functional forms linking density with transmission. We projected forwards beyond lockdown to ascertain the consequences of different functional forms on infection resurgence.ResultsCOVID-19-associated mortality data from England show evidence of increasing with population density until a saturating level, after adjusting for local age distribution, deprivation, proportion of ethnic minority population and proportion of key workers among the working population. Projections from a mathematical model that accounts for this observation deviate markedly from the current status quo for SARS-CoV-2 models which either assume linearity between density and transmission (30% of models) or no relationship at all (70%). Respectively, these classical model structures over- and underestimate the delay in infection resurgence following the release of lockdown.ConclusionIdentifying saturation points for given populations and including transmission terms that account for this feature will improve model accuracy and utility for the current and future pandemics.
Subject(s)
COVID-19 , SARS-CoV-2 , Communicable Disease Control , England/epidemiology , Ethnic and Racial Minorities , Ethnicity , Humans , Minority GroupsABSTRACT
Dengue is an emerging viral disease principally transmitted by the Aedes (Stegomyia) aegypti mosquito. It is one of the fastest-growing global infectious diseases, with 100-400 million new infections a year, and is now entrenched in a growing number of tropical megacities. Behind this rapid rise is the simple adaptation of Ae. aegypti to a new entomological niche carved out by human habitation. This review describes the expansion of dengue and explores how key changes in the ecology of Ae. aegypti allowed it to become a successful invasive species and highly efficient disease vector. We argue that characterizing geographic heterogeneity in mosquito bionomics will be a key research priority that will enable us to better understand future dengue risk and design control strategies to reverse its global spread.
Subject(s)
Aedes/virology , Animal Distribution , Dengue Virus/physiology , Dengue/transmission , Mosquito Vectors/virology , AnimalsABSTRACT
BACKGROUND: Release of virus-blocking Wolbachia-infected mosquitoes is an emerging disease control strategy that aims to control dengue and other arboviral infections. Early entomological data and modelling analyses have suggested promising outcomes, and wMel Wolbachia releases are now ongoing or planned in 12 countries. To help inform government, donor, or philanthropist decisions on scale-up beyond single city releases, we assessed this technology's cost-effectiveness under alternative programmatic options. METHODS: Using costing data from existing Wolbachia releases, previous dynamic model-based estimates of Wolbachia effectiveness, and a spatially explicit model of release and surveillance requirements, we predicted the costs and effectiveness of the ongoing programme in Yogyakarta City and three new hypothetical programmes in Yogyakarta Special Autonomous Region, Jakarta, and Bali. RESULTS: We predicted Wolbachia to be a highly cost-effective intervention when deployed in high-density urban areas with gross cost-effectiveness below $1500 per DALY averted. When offsets from the health system and societal perspective were included, such programmes even became cost saving over 10-year time horizons with favourable benefit-cost ratios of 1.35 to 3.40. Sequencing Wolbachia releases over 10 years could reduce programme costs by approximately 38% compared to simultaneous releases everywhere, but also delays the benefits. Even if unexpected challenges occurred during deployment, such as emergence of resistance in the medium-term or low effective coverage, Wolbachia would remain a cost-saving intervention. CONCLUSIONS: Wolbachia releases in high-density urban areas are expected to be highly cost-effective and could potentially be the first cost-saving intervention for dengue. Sites with strong public health infrastructure, fiscal capacity, and community support should be prioritised.
Subject(s)
Cost-Benefit Analysis/methods , Dengue/economics , Dengue/therapy , Wolbachia/pathogenicity , Animals , Dengue/epidemiology , Humans , Indonesia/epidemiologyABSTRACT
BACKGROUND: In dengue-endemic countries, targeting limited control interventions to populations at risk of severe disease could enable increased efficiency. Individuals who have had their first (primary) dengue infection are at risk of developing more severe secondary disease, thus could be targeted for disease prevention. Currently, there is no reliable algorithm for determining primary and post-primary (infection with more than one flavivirus) status from a single serum sample. In this study, we developed and validated an immune status algorithm using single acute serum samples from reporting patients and investigated dengue immuno-epidemiological patterns across the Philippines. METHODS: During 2015/2016, a cross-sectional sample of 10,137 dengue case reports provided serum for molecular (anti-DENV PCR) and serological (anti-DENV IgM/G capture ELISA) assay. Using mixture modelling, we re-assessed IgM/G seroprevalence and estimated functional, disease day-specific, IgG:IgM ratios that categorised the reporting population as negative, historical, primary and post-primary for dengue. We validated our algorithm against WHO gold standard criteria and investigated cross-reactivity with Zika by assaying a random subset for anti-ZIKV IgM and IgG. Lastly, using our algorithm, we explored immuno-epidemiological patterns of dengue across the Philippines. RESULTS: Our modelled IgM and IgG seroprevalence thresholds were lower than kit-provided thresholds. Individuals anti-DENV PCR+ or IgM+ were classified as active dengue infections (83.1%, 6998/8425). IgG- and IgG+ active dengue infections on disease days 1 and 2 were categorised as primary and post-primary, respectively, while those on disease days 3 to 5 with IgG:IgM ratios below and above 0.45 were classified as primary and post-primary, respectively. A significant proportion of post-primary dengue infections had elevated anti-ZIKV IgG inferring previous Zika exposure. Our algorithm achieved 90.5% serological agreement with WHO standard practice. Post-primary dengue infections were more likely to be older and present with severe symptoms. Finally, we identified a spatio-temporal cluster of primary dengue case reporting in northern Luzon during 2016. CONCLUSIONS: Our dengue immune status algorithm can equip surveillance operations with the means to target dengue control efforts. The algorithm accurately identified primary dengue infections who are at risk of future severe disease.
Subject(s)
Dengue Virus/pathogenicity , Dengue/epidemiology , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Philippines , Young AdultABSTRACT
BACKGROUND: In sub-Saharan Africa, women are most likely to receive skilled and adequate childbirth care in hospital settings, yet the use of hospital for childbirth is low and inequitable. The poorest and those living furthest away from a hospital are most affected. But the relative contribution of poverty and travel time is convoluted, since hospitals are often located in wealthier urban places and are scarcer in poorer remote area. This study aims to partition the variability in hospital-based childbirth by poverty and travel time in four sub-Saharan African countries. METHODS: We used data from the most recent Demographic and Health Survey in Kenya, Malawi, Nigeria and Tanzania. For each country, geographic coordinates of survey clusters, the master list of hospital locations and a high-resolution map of land surface friction were used to estimate travel time from each DHS cluster to the nearest hospital with a shortest-path algorithm. We quantified and compared the predicted probabilities of hospital-based childbirth resulting from one standard deviation (SD) change around the mean for different model predictors. RESULTS: The mean travel time to the nearest hospital, in minutes, was 27 (Kenya), 31 (Malawi), 25 (Nigeria) and 62 (Tanzania). In Kenya, a change of 1SD in wealth led to a 33.2 percentage points change in the probability of hospital birth, whereas a 1SD change in travel time led to a change of 16.6 percentage points. The marginal effect of 1SD change in wealth was weaker than that of travel time in Malawi (13.1 vs. 34.0 percentage points) and Tanzania (20.4 vs. 33.7 percentage points). In Nigeria, the two were similar (22.3 vs. 24.8 percentage points) but their additive effect was twice stronger (44.6 percentage points) than the separate effects. Random effects from survey clusters also explained substantial variability in hospital-based childbirth in all countries, indicating other unobserved local factors at play. CONCLUSIONS: Both poverty and long travel time are important determinants of hospital birth, although they vary in the extent to which they influence whether women give birth in a hospital within and across countries. This suggests that different strategies are needed to effectively enable poor women and women living in remote areas to gain access to skilled and adequate care for childbirth.
Subject(s)
Delivery, Obstetric/statistics & numerical data , Health Services Accessibility/economics , Health Services Accessibility/statistics & numerical data , Poverty/statistics & numerical data , Travel/statistics & numerical data , Demography , Female , Humans , Kenya , Malawi , Nigeria , Pregnancy , Tanzania , Time FactorsABSTRACT
BACKGROUND: In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were significantly lower, suggesting alternate causes or the involvement of arboviral cofactors in exacerbating microcephaly rates. METHODS AND FINDINGS: We merged data from multiple national reporting databases in Brazil to estimate exposure to 9 known or hypothesized causes of microcephaly for every pregnancy nationwide since the beginning of the ZIKV outbreak; this generated between 3.6 and 5.4 million cases (depending on analysis) over the time period 1 January 2015-23 May 2017. The association between ZIKV and microcephaly was statistically tested against models with alternative causes or with effect modifiers. We found no evidence for alternative non-ZIKV causes of the 2015-2017 microcephaly outbreak, nor that concurrent exposure to arbovirus infection or vaccination modified risk. We estimate an absolute risk of microcephaly of 40.8 (95% CI 34.2-49.3) per 10,000 births and a relative risk of 16.8 (95% CI 3.2-369.1) given ZIKV infection in the first or second trimester of pregnancy; however, because ZIKV infection rates were highly variable, most pregnant women in Brazil during the ZIKV outbreak will have been subject to lower risk levels. Statistically significant associations of ZIKV with other birth defects were also detected, but at lower relative risks than that of microcephaly (relative risk < 1.5). Our analysis was limited by missing data prior to the establishment of nationwide ZIKV surveillance, and its findings may be affected by unmeasured confounding causes of microcephaly not available in routinely collected surveillance data. CONCLUSIONS: This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate leads us to hypothesize that the Northeast region was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason.
Subject(s)
Disease Outbreaks , Microcephaly/epidemiology , Pregnancy Complications, Infectious/epidemiology , Zika Virus Infection/epidemiology , Brazil/epidemiology , Female , Humans , Infant, Newborn , Male , Microcephaly/diagnosis , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Risk Factors , Zika Virus Infection/diagnosis , Zika Virus Infection/transmissionABSTRACT
BACKGROUND: Wolbachia-infected mosquitoes reduce dengue virus transmission, and city-wide releases in Yogyakarta city, Indonesia, are showing promising entomological results. Accurate estimates of the burden of dengue, its spatial distribution and the potential impact of Wolbachia are critical in guiding funder and government decisions on its future wider use. METHODS: Here, we combine multiple modelling methods for burden estimation to predict national case burden disaggregated by severity and map the distribution of burden across the country using three separate data sources. An ensemble of transmission models then predicts the estimated reduction in dengue transmission following a nationwide roll-out of wMel Wolbachia. RESULTS: We estimate that 7.8 million (95% uncertainty interval [UI] 1.8-17.7 million) symptomatic dengue cases occurred in Indonesia in 2015 and were associated with 332,865 (UI 94,175-754,203) lost disability-adjusted life years (DALYs). The majority of dengue's burden was due to non-severe cases that did not seek treatment or were challenging to diagnose in outpatient settings leading to substantial underreporting. Estimated burden was highly concentrated in a small number of large cities with 90% of dengue cases occurring in 15.3% of land area. Implementing a nationwide Wolbachia population replacement programme was estimated to avert 86.2% (UI 36.2-99.9%) of cases over a long-term average. CONCLUSIONS: These results suggest interventions targeted to the highest burden cities can have a disproportionate impact on dengue burden. Area-wide interventions, such as Wolbachia, that are deployed based on the area covered could protect people more efficiently than individual-based interventions, such as vaccines, in such dense environments.
Subject(s)
Aedes/microbiology , Dengue/prevention & control , Models, Theoretical , Pest Control, Biological/methods , Wolbachia , Animals , Cost of Illness , Dengue/epidemiology , Dengue/transmission , Dengue Virus , Humans , Indonesia/epidemiologyABSTRACT
Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes. For some patients, dengue is a life-threatening illness. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread. The contemporary worldwide distribution of the risk of dengue virus infection and its public health burden are poorly known. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation.
Subject(s)
Dengue/epidemiology , Global Health/statistics & numerical data , Cohort Studies , Databases, Factual/standards , Dengue/transmission , Dengue/virology , Dengue Virus/physiology , Humans , Incidence , Public Health/statistics & numerical data , Quality Control , Rain , Risk Factors , Temperature , Tropical Climate , Urbanization , World Health OrganizationABSTRACT
BACKGROUND: Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease. METHODS: In this multistage analysis, we quantified three stages underlying the potential of widespread viral haemorrhagic fever epidemics. Environmental suitability maps were used to define stage 1, index-case potential, which assesses populations at risk of infection due to spillover from zoonotic hosts or vectors, identifying where index cases could present. Stage 2, outbreak potential, iterates upon an existing framework, the Index for Risk Management, to measure potential for secondary spread in people within specific communities. For stage 3, epidemic potential, we combined local and international scale connectivity assessments with stage 2 to evaluate possible spread of local outbreaks nationally, regionally, and internationally. FINDINGS: We found epidemic potential to vary within Africa, with regions where viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa) and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both ranking highly. Tracking transitions between stages showed how an index case can escalate into a widespread epidemic in the absence of intervention (eg, Nigeria and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly susceptible to any outbreak at subnational levels. INTERPRETATION: Our analysis provides a unified assessment of potential epidemic trajectories, with the aim of allowing national and international agencies to pre-emptively evaluate needs and target resources. Within each country, our framework identifies at-risk subnational locations in which to improve surveillance, diagnostic capabilities, and health systems in parallel with the design of policies for optimal responses at each stage. In conjunction with pandemic preparedness activities, assessments such as ours can identify regions where needs and provisions do not align, and thus should be targeted for future strengthening and support. FUNDING: Paul G Allen Family Foundation, Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development.
Subject(s)
Hemorrhagic Fevers, Viral/epidemiology , Pandemics , Africa/epidemiology , Disease Outbreaks/statistics & numerical data , Epidemics/statistics & numerical data , Humans , Pandemics/statistics & numerical data , Risk AssessmentABSTRACT
BACKGROUND: Zika virus (ZIKV) emerged in Latin America and the Caribbean (LAC) region in 2013, with serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and the lack of a comprehensive collation of data from affected countries. METHODS: Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 90 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vectorial capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories. RESULTS: There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 would present within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p < 0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases. CONCLUSIONS: The findings suggest that the ZIKV epidemic is by and large over within LAC, with incidence projected to be low in most cities in 2018. Local low levels of transmission are probable, but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.