Xavier Rodó

Refractory periods and climate forcing in cholera dynamics

Outbreaks of many infectious diseases, including cholera, malaria and dengue, vary over characteristic periods longer than 1 year. Evidence that climate variability drives these interannual cycles has been highly controversial, chiefly because it is difficult to isolate the contribution of environmental forcing while taking into account nonlinear epidemiological dynamics generated by mechanisms such as host immunity. Here we show that a critical interplay of environmental forcing, specifically climate variability, and temporary immunity explains the interannual disease cycles present in a four-decade cholera time series from Matlab, Bangladesh. We reconstruct the transmission rate, the key epidemiological parameter affected by extrinsic forcing, over time for the predominant strain (El Tor) with a nonlinear population model that permits a contributing effect of intrinsic immunity. Transmission shows clear interannual variability with a strong correspondence to climate patterns at long periods (over 7 years, for monsoon rains and Brahmaputra river discharge) and at shorter periods (under 7 years, for flood extent in Bangladesh, sea surface temperatures in the Bay of Bengal and the El Niño–Southern Oscillation). The importance of the interplay between extrinsic and intrinsic factors in determining disease dynamics is illustrated during refractory periods, when population susceptibility levels are low as the result of immunity and the size of cholera outbreaks only weakly reflects climate forcing.

ENSO and cholera: a nonstationary link related to climate change?

We present here quantitative evidence for an increased role of interannual climate variability on the temporal dynamics of an infectious disease. The evidence is based on time-series analyses of the relationship between El Niño/Southern Oscillation (ENSO) and cholera prevalence in Bangladesh (formerly Bengal) during two different time periods. A strong and consistent signature of ENSO is apparent in the last two decades (1980–2001), while it is weaker and eventually uncorrelated during the first parts of the last century (1893–1920 and 1920–1940, respectively). Concomitant with these changes, the Southern Oscillation Index (SOI) undergoes shifts in its frequency spectrum. These changes include an intensification of the approximately 4-yr cycle during the recent interval as a response to the well documented Pacific basin regime shift of 1976. This change in remote ENSO modulation alone can only partially serve to substantiate the differences observed in cholera. Regional or basin-wide changes possibly linked to global warming must be invoked that seem to facilitate ENSO transmission. For the recent cholera series and during specific time intervals corresponding to local maxima in ENSO, this climate phenomenon accounts for over 70% of disease variance. This strong association is discontinuous in time and can only be captured with a technique designed to isolate transient couplings.

Association of Kawasaki disease with tropospheric wind patterns.

The causal agent of Kawasaki disease (KD) remains unknown after more than 40 years of intensive research. The number of cases continues to rise in many parts of the world and KD is the most common cause of acquired heart disease in childhood in developed countries. Analyses of the three major KD epidemics in Japan, major non-epidemic interannual fluctuations of KD cases in Japan and San Diego, and the seasonal variation of KD in Japan, Hawaii, and San Diego, reveals a consistent pattern wherein KD cases are often linked to large-scale wind currents originating in central Asia and traversing the north Pacific. Results suggest that the environmental trigger for KD could be wind-borne. Efforts to isolate the causative agent of KD should focus on the microbiology of aerosols.

Chapter 3 Relations between variability in the Mediterranean region and mid-latitude variability

Publisher Summary The Mediterranean climate is under the influence of both tropical and mid-latitude climate dynamics, being directly affected by continental and maritime air masses with significant origin differences. The peak of the winter season occurs between December and February, when the mid-latitude cyclone belt has usually reached its southernmost position. However, spring and autumn also contribute to a significant amount of precipitation. Being located at the southern limit of the North Atlantic storm tracks; the Mediterranean region is particularly sensitive to interannual shifts in the trajectories of mid-latitude cyclones that can lead to the remarkable anomalies of precipitation and, to a lesser extent, of temperature. Storm-track variability impacts primarily the western Mediterranean, but it hasa signature clearly detected in the eastern Mediterranean as well. The complex orography that characterizes most regions surrounding the Mediterranean basin can modulate and even distort climate anomaly patterns that otherwise would be geographically much more homogenous. Lack of water in winter and spring reflects in the crop yield. However, too much water in winter is harmful by drowning the seeds and retarding root development. The variability of precipitation plays a crucial role in the management of regional agriculture, in environment, in water resources and ecosystems, as well as social development and behavior.

Long-term projections and acclimatization scenarios of temperature-related mortality in Europe

The steady increase in greenhouse gas concentrations is inducing a detectable rise in global temperatures. The sensitivity of human societies to warming temperatures is, however, a transcendental question not comprehensively addressed to date. Here we show the link between temperature, humidity and daily numbers of deaths in nearly 200 European regions, which are subsequently used to infer transient projections of mortality under state-of-the-art high-resolution greenhouse gas scenario simulations. Our analyses point to a change in the seasonality of mortality, with maximum monthly incidence progressively shifting from winter to summer. The results also show that the rise in heat-related mortality will start to completely compensate the reduction of deaths from cold during the second half of the century, amounting to an average drop in human lifespan of up 3-4 months in 2070-2100. Nevertheless, projections suggest that human lifespan might indeed increase if a substantial degree of adaptation to warm temperatures takes place.

Chapter 2 Relations between climate variability in the Mediterranean region and the tropics: ENSO, South Asian and African monsoons, hurricanes and Saharan dust

Publisher Summary The Mediterranean climate is affected by several tropical and subtropical systems as illustrated by some evidence presented in this chapter. These factors range from the El Nino Southern Oscillation (ENSO) and tropical hurricanes to the South Asian Monsoon and Saharan dust. This leads to complex features in the Mediterranean climate variability. It reviews some tropical and subtropical teleconnections to the Mediterranean climate. It discusses the South Asian Monsoon (SAM), which is a key factor influencing the climate of the eastern and central Mediterranean. It causes high variability in sea level pressure (SLP) over Arabia and the Middle East with high pressures in winter and low pressures in summer. The adjustment to the SAM couples the falling pressure and land temperature over the Indian subcontinent/Asia Minor with rising pressure and temperature over the Persian Gulf and Iraq. Red Sea Trough intrusions into the Eastern Mediterranean and the Saharan dust are also discussed in the chapter.

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan

Significance Kawasaki disease (KD), the leading cause of acquired heart disease in children worldwide, has remained a mystery for more than 40 y. No etiological agent has yet been identified. By using simulations with the flexible particle dispersion model from different Japanese cities from each single high (low) KD incidence day, the source region KD is retrieved in cereal croplands in northeastern China. We infer the incubation time for KD ranges from 6 h to 2 d, thus favoring an antigenic or toxic exposure as the trigger. Candida sp. is reported as the dominant fungal species collected aloft (54% of all fungal DNA clones) demonstrating the potential for human disease in aerosols transported by wind currents traveling long distances. Evidence indicates that the densely cultivated region of northeastern China acts as a source for the wind-borne agent of Kawasaki disease (KD). KD is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 y. We used residence times from simulations with the flexible particle dispersion model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. The postepidemic interval (1987–2010) and the extreme epidemics (1979, 1982, and 1986) pointed to the same source region. Results suggest a very short incubation period (<24 h) from exposure, thus making an infectious agent unlikely. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols compared with ground aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, consistent with the Candida animal model for KD, provide support for the concept and feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD, consistent with an agricultural source, a short incubation time and synchronized outbreaks. Our study suggests that the causative agent of KD is a preformed toxin or environmental agent rather than an organism requiring replication. We propose a new paradigm whereby an idiosyncratic immune response, influenced by host genetics triggered by an environmental exposure carried on winds, results in the clinical syndrome known as acute KD.

Climate change and infectious diseases: Can we meet the needs for better prediction?

The next generation of climate-driven, disease prediction models will most likely require a mechanistically based, dynamical framework that parameterizes key processes at a variety of locations. Over the next two decades, consensus climate predictions make it possible to produce forecasts for a number of important infectious diseases that are largely independent of the uncertainty of longer-term emissions scenarios. In particular, the role of climate in the modulation of seasonal disease transmission needs to be unravelled from the complex dynamics resulting from the interaction of transmission with herd immunity and intervention measures that depend upon previous burdens of infection. Progress is also needed to solve the mismatch between climate projections and disease projections at the scale of public health interventions. In the time horizon of seasons to years, early warning systems should benefit from current developments on multi-model ensemble climate prediction systems, particularly in areas where high skill levels of climate models coincide with regions where large epidemics take place. A better understanding of the role of climate extremes on infectious diseases is urgently needed.

Dengue outlook for the World Cup in Brazil: an early warning model framework driven by real-time seasonal climate forecasts

BACKGROUND With more than a million spectators expected to travel among 12 different cities in Brazil during the football World Cup, June 12-July 13, 2014, the risk of the mosquito-transmitted disease dengue fever is a concern. We addressed the potential for a dengue epidemic during the tournament, using a probabilistic forecast of dengue risk for the 553 microregions of Brazil, with risk level warnings for the 12 cities where matches will be played. METHODS We obtained real-time seasonal climate forecasts from several international sources (European Centre for Medium-Range Weather Forecasts [ECMWF], Met Office, Meteo-France and Centro de Previsão de Tempo e Estudos Climáticos [CPTEC]) and the observed dengue epidemiological situation in Brazil at the forecast issue date as provided by the Ministry of Health. Using this information we devised a spatiotemporal hierarchical Bayesian modelling framework that enabled dengue warnings to be made 3 months ahead. By assessing the past performance of the forecasting system using observed dengue incidence rates for June, 2000-2013, we identified optimum trigger alert thresholds for scenarios of medium-risk and high-risk of dengue. FINDINGS Our forecasts for June, 2014, showed that dengue risk was likely to be low in the host cities Brasília, Cuiabá, Curitiba, Porto Alegre, and São Paulo. The risk was medium in Rio de Janeiro, Belo Horizonte, Salvador, and Manaus. High-risk alerts were triggered for the northeastern cities of Recife (p(high)=19%), Fortaleza (p(high)=46%), and Natal (p(high)=48%). For these high-risk areas, particularly Natal, the forecasting system did well for previous years (in June, 2000-13). INTERPRETATION This timely dengue early warning permits the Ministry of Health and local authorities to implement appropriate, city-specific mitigation and control actions ahead of the World Cup. FUNDING European Commissions Seventh Framework Research Programme projects DENFREE, EUPORIAS, and SPECS; Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro.

Seasonality of Kawasaki Disease: A Global Perspective

Background Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. Methods Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. Results A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. Conclusion Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter months in the Northern Hemisphere extra-tropics.