Spatio-temporal dynamics of dengue in Brazil: Seasonal travelling waves and determinants of regional synchrony.

Dengue continues to be the most important vector-borne viral disease globally and in Brazil, where more than 1.4 million cases and over 500 deaths were reported in 2016. Mosquito control programmes and other interventions have not stopped the alarming trend of increasingly large epidemics in the past few years. Here, we analyzed monthly dengue cases reported in Brazil between 2001 and 2016 to better characterise the key drivers of dengue epidemics. Spatio-temporal analysis revealed recurring travelling waves of disease occurrence. Using wavelet methods, we characterised the average seasonal pattern of dengue in Brazil, which starts in the western states of Acre and Rondônia, then travels eastward to the coast before reaching the northeast of the country. Only two states in the north of Brazil (Roraima and Amapá) did not follow the countrywide pattern and had inconsistent timing of dengue epidemics throughout the study period. We also explored epidemic synchrony and timing of annual dengue cycles in Brazilian regions. Using gravity style models combined with climate factors, we showed that both human mobility and vector ecology contribute to spatial patterns of dengue occurrence. This study offers a characterization of the spatial dynamics of dengue in Brazil and its drivers, which could inform intervention strategies against dengue and other arboviruses

Quantifying the localized relationship between vector containment activities and dengue incidence in a real-world setting: A spatial and time series modelling analysis based on geo-located data from Pakistan.

Increasing urbanization is having a profound effect on infectious disease risk, posing significant challenges for governments to allocate limited resources for their optimal control at a sub-city scale. With recent advances in data collection practices, empirical evidence about the efficacy of highly localized containment and intervention activities, which can lead to optimal deployment of resources, is possible. However, there are several challenges in analyzing data from such real-world observational settings. Using data on 3.9 million instances of seven dengue vector containment activities collected between 2012 and 2017, here we develop and assess two frameworks for understanding how the generation of new dengue cases changes in space and time with respect to application of different types of containment activities. Accounting for the non-random deployment of each containment activity in relation to dengue cases and other types of containment activities, as well as deployment of activities in different epidemiological contexts, results from both frameworks reinforce existing knowledge about the efficacy of containment activities aimed at the adult phase of the mosquito lifecycle. Results show a 10% (95% CI: 1-19%) and 20% reduction (95% CI: 4-34%) reduction in probability of a case occurring in 50 meters and 30 days of cases which had Indoor Residual Spraying (IRS) and fogging performed in the immediate vicinity, respectively, compared to cases of similar epidemiological context and which had no containment in their vicinity. Simultaneously, limitations due to the real-world nature of activity deployment are used to guide recommendations for future deployment of resources during outbreaks as well as data collection practices. Conclusions from this study will enable more robust and comprehensive analyses of localized containment activities in resource-scarce urban settings and lead to improved allocation of resources of government in an outbreak setting

Mapping the zoonotic niche of Marburg virus disease in Africa.

BACKGROUND: Marburg virus disease (MVD) describes a viral haemorrhagic fever responsible for a number of outbreaks across eastern and southern Africa. It is a zoonotic disease, with the Egyptian rousette (Rousettus aegyptiacus) identified as a reservoir host. Infection is suspected to result from contact between this reservoir and human populations, with occasional secondary human-to-human transmission. METHODS: Index cases of previous human outbreaks were identified and reports of infection in animals recorded. These data were modelled within a species distribution modelling framework in order to generate a probabilistic surface of zoonotic transmission potential of MVD across sub-Saharan Africa. RESULTS: Areas suitable for zoonotic transmission of MVD are predicted in 27 countries inhabited by 105 million people. Regions are suggested for exploratory surveys to better characterise the geographical distribution of the disease, as well as for directing efforts to communicate the risk of practices enhancing zoonotic contact. CONCLUSIONS: These maps can inform future contingency and preparedness strategies for MVD control, especially where secondary transmission is a risk. Coupling this risk map with patient travel histories could be used to guide the differential diagnosis of highly transmissible pathogens, enabling more rapid response to outbreaks of haemorrhagic fever

International travel between global urban centres vulnerable to yellow fever transmission.

OBJECTIVE: To examine the potential for international travel to spread yellow fever virus to cities around the world. METHODS: We obtained data on the international flight itineraries of travellers who departed yellow fever-endemic areas of the world in 2016 for cities either where yellow fever was endemic or which were suitable for viral transmission. Using a global ecological model of dengue virus transmission, we predicted the suitability of cities in non-endemic areas for yellow fever transmission. We obtained information on national entry requirements for yellow fever vaccination at travellers' destination cities. FINDINGS: In 2016, 45.2 million international air travellers departed from yellow fever-endemic areas of the world. Of 11.7 million travellers with destinations in 472 cities where yellow fever was not endemic but which were suitable for virus transmission, 7.7 million (65.7%) were not required to provide proof of vaccination upon arrival. Brazil, China, India, Mexico, Peru and the United States of America had the highest volumes of travellers arriving from yellow fever-endemic areas and the largest populations living in cities suitable for yellow fever transmission. CONCLUSION: Each year millions of travellers depart from yellow fever-endemic areas of the world for cities in non-endemic areas that appear suitable for viral transmission without having to provide proof of vaccination. Rapid global changes in human mobility and urbanization make it vital for countries to re-examine their vaccination policies and practices to prevent urban yellow fever epidemics

Potential for Zika virus introduction and transmission in resource-limited countries in Africa and the Asia-Pacific region: a modelling study.

BACKGROUND: As the epidemic of Zika virus expands in the Americas, countries across Africa and the Asia-Pacific region are becoming increasingly susceptible to the importation and possible local spread of the virus. To support public health readiness, we aim to identify regions and times where the potential health, economic, and social effects from Zika virus are greatest, focusing on resource-limited countries in Africa and the Asia-Pacific region. METHODS: Our model combined transportation network analysis, ecological modelling of mosquito occurrences, and vector competence for flavivirus transmission, using data from the International Air Transport Association, entomological observations from Zika's primary vector species, and climate conditions using WorldClim. We overlaid monthly flows of airline travellers arriving to Africa and the Asia-Pacific region from areas of the Americas suitable for year-round transmission of Zika virus with monthly maps of climatic suitability for mosquito-borne transmission of Zika virus within Africa and the Asia-Pacific region. FINDINGS: An estimated 2·6 billion people live in areas of Africa and the Asia-Pacific region where the presence of competent mosquito vectors and suitable climatic conditions could support local transmission of Zika virus. Countries with large volumes of travellers arriving from Zika virus-affected areas of the Americas and large populations at risk of mosquito-borne Zika virus infection include India (67 422 travellers arriving per year; 1·2 billion residents in potential Zika transmission areas), China (238 415 travellers; 242 million residents), Indonesia (13 865 travellers; 197 million residents), Philippines (35 635 travellers; 70 million residents), and Thailand (29 241 travellers; 59 million residents). INTERPRETATION: Many countries across Africa and the Asia-Pacific region are vulnerable to Zika virus. Strategic use of available health and human resources is essential to prevent or mitigate the health, economic, and social consequences of Zika virus, especially in resource-limited countries. FUNDING: Canadian Institutes of Health Research and the US Centers for Disease Control and Prevention

Global temperature constraints on Aedes aegypti and Ae. albopictus persistence and competence for dengue virus transmission.

BACKGROUND: Dengue is a disease that has undergone significant expansion over the past hundred years. Understanding what factors limit the distribution of transmission can be used to predict current and future limits to further dengue expansion. While not the only factor, temperature plays an important role in defining these limits. Previous attempts to analyse the effect of temperature on the geographic distribution of dengue have not considered its dynamic intra-annual and diurnal change and its cumulative effects on mosquito and virus populations. METHODS: Here we expand an existing modelling framework with new temperature-based relationships to model an index proportional to the basic reproductive number of the dengue virus. This model framework is combined with high spatial and temporal resolution global temperature data to model the effects of temperature on Aedes aegypti and Ae. albopictus persistence and competence for dengue virus transmission. RESULTS: Our model predicted areas where temperature is not expected to permit transmission and/or Aedes persistence throughout the year. By reanalysing existing experimental data our analysis indicates that Ae. albopictus, often considered a minor vector of dengue, has comparable rates of virus dissemination to its primary vector, Ae. aegypti, and when the longer lifespan of Ae. albopictus is considered its competence for dengue virus transmission far exceeds that of Ae. aegypti. CONCLUSIONS: These results can be used to analyse the effects of temperature and other contributing factors on the expansion of dengue or its Aedes vectors. Our finding that Ae. albopictus has a greater capacity for dengue transmission than Ae. aegypti is contrary to current explanations for the comparative rarity of dengue transmission in established Ae. albopictus populations. This suggests that the limited capacity of Ae. albopictus to transmit DENV is more dependent on its ecology than vector competence. The recommendations, which we explicitly outlined here, point to clear targets for entomological investigation

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

BACKGROUND: Substantial outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. The aims of this study were to estimate global yellow fever vaccination coverage from 1970 through to 2016 at high spatial resolution and to calculate the number of individuals still requiring vaccination to reach population coverage thresholds for outbreak prevention. METHODS: For this adjusted retrospective analysis, we compiled data from a range of sources (eg, WHO reports and health-service-provider registeries) reporting on yellow fever vaccination activities between May 1, 1939, and Oct 29, 2016. To account for uncertainty in how vaccine campaigns were targeted, we calculated three population coverage values to encompass alternative scenarios. We combined these data with demographic information and tracked vaccination coverage through time to estimate the proportion of the population who had ever received a yellow fever vaccine for each second level administrative division across countries at risk of yellow fever virus transmission from 1970 to 2016. FINDINGS: Overall, substantial increases in vaccine coverage have occurred since 1970, but notable gaps still exist in contemporary coverage within yellow fever risk zones. We estimate that between 393·7 million and 472·9 million people still require vaccination in areas at risk of yellow fever virus transmission to achieve the 80% population coverage threshold recommended by WHO; this represents between 43% and 52% of the population within yellow fever risk zones, compared with between 66% and 76% of the population who would have required vaccination in 1970. INTERPRETATION: Our results highlight important gaps in yellow fever vaccination coverage, can contribute to improved quantification of outbreak risk, and help to guide planning of future vaccination efforts and emergency stockpiling. FUNDING: The Rhodes Trust, Bill & Melinda Gates Foundation, the Wellcome Trust, the National Library of Medicine of the National Institutes of Health, the European Union's Horizon 2020 research and innovation programme

Spread of yellow fever virus outbreak in Angola and the Democratic Republic of the Congo 2015-16: a modelling study.

BACKGROUND: Since late 2015, an epidemic of yellow fever has caused more than 7334 suspected cases in Angola and the Democratic Republic of the Congo, including 393 deaths. We sought to understand the spatial spread of this outbreak to optimise the use of the limited available vaccine stock. METHODS: We jointly analysed datasets describing the epidemic of yellow fever, vector suitability, human demography, and mobility in central Africa to understand and predict the spread of yellow fever virus. We used a standard logistic model to infer the district-specific yellow fever virus infection risk during the course of the epidemic in the region. FINDINGS: The early spread of yellow fever virus was characterised by fast exponential growth (doubling time of 5-7 days) and fast spatial expansion (49 districts reported cases after only 3 months) from Luanda, the capital of Angola. Early invasion was positively correlated with high population density (Pearson's r 0·52, 95% CI 0·34-0·66). The further away locations were from Luanda, the later the date of invasion (Pearson's r 0·60, 95% CI 0·52-0·66). In a Cox model, we noted that districts with higher population densities also had higher risks of sustained transmission (the hazard ratio for cases ceasing was 0·74, 95% CI 0·13-0·92 per log-unit increase in the population size of a district). A model that captured human mobility and vector suitability successfully discriminated districts with high risk of invasion from others with a lower risk (area under the curve 0·94, 95% CI 0·92-0·97). If at the start of the epidemic, sufficient vaccines had been available to target 50 out of 313 districts in the area, our model would have correctly identified 27 (84%) of the 32 districts that were eventually affected. INTERPRETATION: Our findings show the contributions of ecological and demographic factors to the ongoing spread of the yellow fever outbreak and provide estimates of the areas that could be prioritised for vaccination, although other constraints such as vaccine supply and delivery need to be accounted for before such insights can be translated into policy. FUNDING: Wellcome Trust