Environmental Predictors of Seasonal Influenza Epidemics across Temperate and Tropical Climates

<div><p>Human influenza infections exhibit a strong seasonal cycle in temperate regions. Recent laboratory and epidemiological evidence suggests that low specific humidity conditions facilitate the airborne survival and transmission of the influenza virus in temperate regions, resulting in annual winter epidemics. However, this relationship is unlikely to account for the epidemiology of influenza in tropical and subtropical regions where epidemics often occur during the rainy season or transmit year-round without a well-defined season. We assessed the role of specific humidity and other local climatic variables on influenza virus seasonality by modeling epidemiological and climatic information from 78 study sites sampled globally. We substantiated that there are two types of environmental conditions associated with seasonal influenza epidemics: “cold-dry” and “humid-rainy”. For sites where monthly average specific humidity or temperature decreases below thresholds of approximately 11–12 g/kg and 18–21°C during the year, influenza activity peaks during the cold-dry season (i.e., winter) when specific humidity and temperature are at minimal levels. For sites where specific humidity and temperature do not decrease below these thresholds, seasonal influenza activity is more likely to peak in months when average precipitation totals are maximal and greater than 150 mm per month. These findings provide a simple climate-based model rooted in empirical data that accounts for the diversity of seasonal influenza patterns observed across temperate, subtropical and tropical climates.</p> </div

Climatic thresholds predictive of influenza seasonal characteristics.

<p>(A) density plot showing the specific humidity in absolute terms (x-axis) and relative terms (y-axis) during influenza peaks across all sites. The plot shows that a vast majority of influenza peaks occurred in “cold-dry” conditions when specific humidity was lower than 8 g/kg and ranks were less than 4, or during “humid-rainy” conditions when specific humidity was greater than 14 g/kg and ranks were greater than 9. (B) a line plot showing the average annual range of specific humidity (y-axis) for each location (x-axis). Sites are ordered based on minimum specific humidity. The black dots indicate the specific humidity during the month of the primary peak and circles indicate specific humidity during secondary peaks. Together, the plots suggest that sites with the lowest annual minimum specific humidity have influenza peaks when specific humidity is at locally-minimal levels. (C) a map displaying the predictions of a logistic regression indicating the probability of an influenza peak during the cold-dry season, versus the humid-rainy season, based on annual minimum specific humidity. The markers indicate the 78 study sites with influenza peaks classified as cold-dry (circles) and humid-rainy (squares). (D) same as (C) but the model is based on annual minimum temperature.</p

Environmental models for all influenza peaks, by latitudinal interval.

*<p>p<0.05,</p><p>** p<0.01,</p>***<p>p<0.001.</p>a<p>high latitudes are regions poleward of 25°N/S.</p>b<p>middle latitudes are regions between 12.5°N/S and 25°N/S.</p>c<p>low latitudes are regions equatorward of 12.5°N/S.</p><p>The results of selected logistic regression models, based on Aikake Information Criterion (AIC) and the proportion of peaks accurately predicted by each model using a jackknife leave-one-out method. These values can be compared against the expected values and corresponding confidence intervals under the null distribution in the bottom row. The models are in descending order based on the proportion of peaks accurately predicted. Influenza peaks were lagged by 1-month with respect to each environmental variable with the exception of precipitation.</p

Influenza peaks, specific humidity and precipitation.

<p>(A) Estimated U-shaped relationship between the likelihood of an influenza peak and average monthly specific humidity across all sites, based on logistic regression (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003194#ppat-1003194-t001" target="_blank">Table 1</a>). The left side of the curve is strongly correlated with the relationship between specific humidity and influenza survival and transmission observed in laboratory studies <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003194#ppat.1003194-Shaman3" target="_blank">[17]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003194#ppat.1003194-Shechmeister1" target="_blank">[32]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003194#ppat.1003194-Schaffer1" target="_blank">[33]</a>. However, the mechanism that causes the pattern on the right side of the curve is not readily explained. (B) The relationship between average monthly specific humidity and precipitation across all sites. Influenza peaks clustered in months associated with low specific humidity and high precipitation conditions. This suggests that precipitation may explain the occurrence of humid-rainy influenza peaks and may be responsible for the right hand side of the U-shaped curve between specific humidity and influenza (A).</p

Influenza peaks and climate by latitude.

<p>The mean monthly rank of each climate variable corresponding to the month of peak influenza for each 10° latitudinal band. Solar radiation, temperature and specific humidity are lagged by 1 month. The background interval corresponds to the 95% null distribution. (A) displays the results for both primary and secondary influenza peaks; whereas (B) shows the results for primary influenza peaks only. Influenza peaks corresponded to months characterized by low ranks of temperature, solar radiation, and specific humidity in high latitudes. Primary influenza peaks corresponded to months with high ranks of humidity (both relative and specific) and precipitation in low latitudes.</p

Influenza seasonal distribution for 9 sites selected from an independent epidemiological dataset and climate model outputs.

<p>(A,C,E,G,I,K,M,O,Q) Box plots indicate the proportion of influenza cases occurring in each month of the year for 9 countries with multiyear data selected from FluNet. <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003194#s3" target="_blank">Results</a> of the best-fit climate models for all and primary peaks (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003194#ppat-1003194-t001" target="_blank">Tables 1</a> and <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003194#ppat-1003194-t002" target="_blank">2</a>) are displayed for comparison. Specific humidity and temperature were advanced one month to account for the one month lag between influenza peaks and these variables. Although the models were designed to estimate the timing of peak influenza activity, they also provide estimates of the seasonal distribution of influenza virus circulation. (B,D,F,H,J,L,N,P,R) The right column displays the monthly precipitation, temperature and specific humidity for each location. Dotted lines indicate the climatic thresholds for each variable. In general, when temperature or specific humidity drops below their respective thresholds, or precipitation surpasses its threshold, there is an increase in influenza activity.</p

Map of 78 study sites included in this study.

<p>The site symbols indicate whether a location has annual or semi-annual influenza activity, and symbol size is proportional to the duration of the epidemiological studies used to determine the month of peak activity for each location.</p

Environmental models for primary influenza peaks.

<p>* p<0.05,</p>**<p>p<0.01,</p>***<p>p<0.001.</p>a<p>high latitudes are regions poleward of 25°N/S.</p>b<p>middle latitudes are regions between 12.5°N/S and 25°N/S.</p>c<p>low latitudes are regions equatorward of 12.5°N/S.</p><p>Same as <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003194#ppat-1003194-t002" target="_blank">Table 1</a> but these are the results for primary influenza peaks only.</p