Mild Epidemics Research Articles

Forcing Seasonality of Influenza-like Epidemics with Daily Solar Resonance.

SummarySeasonality of acute viral respiratory diseases is a well-known and yet not fully understood phenomenon. Several models have been proposed to explain the regularity of yearly recurring outbreaks and the phase differences observed at different latitudes on the Earth. Such models consider known internal causes, primarily the periodic emergence of new virus variants that evade the host immune response. Yet, this alone is generally unable to explain the regularity of recurrences and the observed phase differences.Here we show that seasonality of viral respiratory diseases, as well as its distribution with latitude on the Earth, can be fully explained by the virucidal properties of UV-B and UV-A solar photons through a daily, minute-scale, resonant forcing mechanism. Such an induced periodicity can last, virtually unperturbed, from tens to hundreds of cycles, and even in the presence of internal dynamics (host's loss of immunity) much slower than seasonal will, on a long period, generate seasonal oscillations.

Robust Lys63-Linked Ubiquitination of RIG-I Promotes Cytokine Eruption in Early Influenza B Virus Infection.

Influenza A and B virus infections both cause a host innate immunity response. Here, we report that the robust production of type I and III interferons (IFNs), IFN-stimulated genes, and proinflammatory factors can be induced by influenza B virus rather than influenza A virus infection in alveolar epithelial (A549) cells during early infection. This response is mainly dependent on the retinoic acid-inducible gene I (RIG-I)-mediated signaling pathway. Infection by influenza B virus promotes intense Lys63-linked ubiquitination of RIG-I, resulting in cytokine eruption. It is known that the influenza A virus NS1 protein (NS1-A) interacts with RIG-I and TRIM25 to suppress the activation of RIG-I-mediated signaling. However, the present results indicate that the influenza B virus NS1 protein (NS1-B) is unable to interact with RIG-I but engages in the formation of a RIG-I/TRIM25/NS1-B ternary complex. Furthermore, we demonstrate that the N-terminal RNA-binding domain (RBD) of NS1-B is responsible for interaction with TRIM25 and that this interaction blocks the inhibitory effect of the NS1-B C-terminal effector domain (TED) on RIG-I ubiquitination. Our findings reveal a novel mechanism for the host cytokine response to influenza B virus infection through regulatory interplay between host and viral proteins. Influenza B virus generally causes local mild epidemics but is occasionally lethal to individuals. Existing studies describe the broad characteristics of influenza B virus epidemiology and pathology. However, to develop better prevention and treatments for the disease, determining the concrete molecular mechanisms of pathogenesis becomes pivotal to understand how the host reacts to the challenge of influenza B virus. Thus, we aimed to characterize the host innate immune response to influenza B virus infection. Here, we show that vigorous Lys63-linked ubiquitination of RIG-I and cytokine eruption dependent on RIG-I-mediated signal transduction are induced by virus infection. Additionally, TRIM25 positively regulates RIG-I-mediated signaling by ablating the inhibitory function of NS1-B on RIG-I ubiquitination.

A Mechanistic Model of Botrytis cinerea on Grapevines That Includes Weather, Vine Growth Stage, and the Main Infection Pathways.

A mechanistic model for Botrytis cinerea on grapevine was developed. The model, which accounts for conidia production on various inoculum sources and for multiple infection pathways, considers two infection periods. During the first period (“inflorescences clearly visible” to “berries groat-sized”), the model calculates: i) infection severity on inflorescences and young clusters caused by conidia (SEV1). During the second period (“majority of berries touching” to “berries ripe for harvest”), the model calculates: ii) infection severity of ripening berries by conidia (SEV2); and iii) severity of berry-to-berry infection caused by mycelium (SEV3). The model was validated in 21 epidemics (vineyard × year combinations) between 2009 and 2014 in Italy and France. A discriminant function analysis (DFA) was used to: i) evaluate the ability of the model to predict mild, intermediate, and severe epidemics; and ii) assess how SEV1, SEV2, and SEV3 contribute to epidemics. The model correctly classified the severity of 17 of 21 epidemics. Results from DFA were also used to calculate the daily probabilities that an ongoing epidemic would be mild, intermediate, or severe. SEV1 was the most influential variable in discriminating between mild and intermediate epidemics, whereas SEV2 and SEV3 were relevant for discriminating between intermediate and severe epidemics. The model represents an improvement of previous B. cinerea models in viticulture and could be useful for making decisions about Botrytis bunch rot control.

Weekends as social distancing and their effect on the spread of influenza

Many published influenza models treat each simulation day as a weekday and do not distinguish weekend days. Consequently, the weekend effect on influenza transmission has not been fully explored. To assess whether distinguishing between weekday and weekend transmissions in simulation models of flu-like infectious disease models matters, this study uses an agent-based model of the Chicago, Illinois metropolitan area. Our study assesses whether including weekend effects is offset by increases in weekend contact patterns and if implementing 3-day weekends dampens disease transmission enough to warrant its use as a containment strategy. Results indicate that ignoring weekend behaviors without incorporating increases in community-based non-school contacts (i.e., compensatory behaviors) causes the peak case incidence day to occur 7 days earlier and can reduce the peak attack rate by as much as 60 %. These results are sensitive to the proportion of symptomatic cases that are assumed to remain at home until they recover. The 3-day weekend intervention has interesting possibilities, but the benefits may only be effective for mild epidemics. However, a 3-day weekend for schools would be less detrimental to the educational process than sustained permanent closing because student and teacher contact is maintained throughout the epidemic period. Also, a 4-day school and work week may be more easily accommodated by many types of schools and businesses. On the other hand, an additional day per week of school closure could result in substantial societal costs, with lost productivity and child care costs outweighing the savings of preventing influenza cases.

Statistical identifiability and sample size calculations for serial seroepidemiology

Inference on disease dynamics is typically performed using case reporting time series of symptomatic disease. The inferred dynamics will vary depending on the reporting patterns and surveillance system for the disease in question, and the inference will miss mild or underreported epidemics. To eliminate the variation introduced by differing reporting patterns and to capture asymptomatic or subclinical infection, inferential methods can be applied to serological data sets instead of case reporting data. To reconstruct complete disease dynamics, one would need to collect a serological time series. In the statistical analysis presented here, we consider a particular kind of serological time series with repeated, periodic collections of population-representative serum. We refer to this study design as a serial seroepidemiology (SSE) design, and we base the analysis on our epidemiological knowledge of influenza. We consider a study duration of three to four years, during which a single antigenic type of influenza would be circulating, and we evaluate our ability to reconstruct disease dynamics based on serological data alone. We show that the processes of reinfection, antibody generation, and antibody waning confound each other and are not always statistically identifiable, especially when dynamics resemble a non-oscillating endemic equilibrium behavior. We introduce some constraints to partially resolve this confounding, and we show that transmission rates and basic reproduction numbers can be accurately estimated in SSE study designs. Seasonal forcing is more difficult to identify as serology-based studies only detect oscillations in antibody titers of recovered individuals, and these oscillations are typically weaker than those observed for infected individuals. To accurately estimate the magnitude and timing of seasonal forcing, serum samples should be collected every two months and 200 or more samples should be included in each collection; this sample size estimate is sensitive to the antibody waning rate and the assumed level of seasonal forcing.

Modeling the Effects of Cloudy Weather on Regional Epidemics of Soybean Rust.

This study simulated daily development of soybean rust (SBR), caused by Phakopsora pachyrhizi, based on cloud cover conditions. Results from a previous study that determined the relationship between shading and apparent infection rates were applied in this study to simulate SBR progress on a regional scale using a semi-empirical logistic model parameterized according to the observed cloud cover conditions. Depending on local weather data availability, cloudy days were assumed to be either (i) the days with less than 2 h of full sun or (ii) the days with complete cloud cover as measured by three daily observations. Estimated disease progress and final estimates of epidemic intensity were verified by 30 reports of seasonal disease progress in 11 regions of Brazil and South Africa from 2002 to 2007. The model predicted final disease severity and the observed final severity fall into a linear relationship with correlation coefficient r = 0.96 and a slope close to 1. Severe SBR epidemics occurred when 19.5 or more cloudy days were recorded during the period from initial disease detection to the date of final disease assessment near the end of a growing season in Brazil and South Africa. Mild epidemics were observed with less than eight cloudy days in a season.

Effects of Temperature and Moisture Variables on Brown Rust Epidemics in Sugarcane

AbstractEpidemics of brown rust in sugarcane, caused by Puccinia melanocephala, vary in severity between seasons. Natural epidemics were studied to determine the effects of temperature and moisture variables on epidemic onset, severity and decline. Variables were monitored with disease severity in two cultivars, each grown at a different location in Louisiana. Maximum daily temperature was the variable most correlated with seasonal epidemic development and decline. Disease severity was high during 2009 and low during 2010. This contrast allowed evaluation of the effects of conducive and limiting environmental conditions on severity. Lower severity resulted from a combination of unfavourable temperature and leaf wetness conditions that delayed onset then reduced the rate of disease increase. An accumulation of 23–25 days with leaf wetness periods of at least 7 h after the daily minimum temperature exceeded 17°C preceded the onset of disease on young leaves in both severe and mild epidemics. Severe epidemics in both cultivars declined once maximum ambient daily temperature was 32°C or higher. Low and high limiting temperatures determined the initiation and decline of an epidemic, respectively, under Louisiana climatic conditions. The availability of leaf wetness was then an important determinant of disease severity during the epidemic.

Towards a Characterization of Behavior-Disease Models

The last decade saw the advent of increasingly realistic epidemic models that leverage on the availability of highly detailed census and human mobility data. Data-driven models aim at a granularity down to the level of households or single individuals. However, relatively little systematic work has been done to provide coupled behavior-disease models able to close the feedback loop between behavioral changes triggered in the population by an individual's perception of the disease spread and the actual disease spread itself. While models lacking this coupling can be extremely successful in mild epidemics, they obviously will be of limited use in situations where social disruption or behavioral alterations are induced in the population by knowledge of the disease. Here we propose a characterization of a set of prototypical mechanisms for self-initiated social distancing induced by local and non-local prevalence-based information available to individuals in the population. We characterize the effects of these mechanisms in the framework of a compartmental scheme that enlarges the basic SIR model by considering separate behavioral classes within the population. The transition of individuals in/out of behavioral classes is coupled with the spreading of the disease and provides a rich phase space with multiple epidemic peaks and tipping points. The class of models presented here can be used in the case of data-driven computational approaches to analyze scenarios of social adaptation and behavioral change.

Frequency of Sexual Recombination by Mycosphaerella graminicola in Mild and Severe Epidemics

The importance of sexual recombination in determining fungal population structure cannot be inferred solely from the relative abundance of sexual and asexual spores and reproductive structures. To complement a previously reported study of proportions of Mycosphaerella graminicola ascocarps and pycnidia, we investigated the share of sexual recombinants among isolates randomly derived from the same field at the same time. Early in three successive growing seasons (those ending in 1998, 1999, and 2000), field plots of the susceptible winter wheat cultivar Stephens were inoculated with suspensions of two M. graminicola isolates that each had rare alleles at restriction fragment length polymorphism (RFLP) loci. Near harvest time, leaves were randomly sampled from the same plots, and a population of over 100 monopycnidial isolates was created for each year of the experiment. Natural populations were also sampled from noninoculated plots in the 1999 and 2000 seasons, in order to compare allele frequencies. Based on RFLP haplotypes and DNA fingerprints, isolates from the inoculated plots were categorized by both inspection and Bayesian methods as inoculant clones, recombinants, or immigrants. Inoculation in the 2000 season was delayed, and the recovery rate of inoculant types was just 1 to 2%. In 1998, a high-disease year, and 1999, a low-disease year, inoculants comprised 36 and 22 to 23% of end-of-season samples, respectively. In those 2 years, recombinants as a percentage of inoculant descendants (both sexual and asexual) were 35 and 32%, respectively. By comparison, the study of fruiting bodies had found 93 and 32% of M. graminicola fruiting bodies were ascocarps in 1998 and 1999, respectively. These findings support the hypothesis that sexual recombination makes a relatively consistent contribution to M. graminicola population structure, despite differences in epidemic severity and ascocarp proportions.

Genetic analysis of Dengue 3 virus subtype III 5′ and 3′ non-coding regions

The emergence of dengue hemorrhagic fever in Sri Lanka in 1989 correlated with the appearance of a genetic variant of Dengue 3 virus (DENV-3) subtype III (group B), closely related to the endemic group A variant. We studied the 5′ and 3′ non-coding regions (NCRs) of 15 DENV-3 subtype III isolates from Sri Lanka, Nicaragua and Martinique and found variability in the 3′ NCRs. This included an 11-nucleotide insertion common to all isolates examined and two nucleotide differences that segregated viruses geographically into an American and a Sri Lankan group. Comparisons also identified three nucleotide differences shared by all group A Sri Lankan DENV-3 III isolates linked to mild disease epidemics but not group B Sri Lankan and group B-associated American isolates linked to severe disease epidemics. Clustering of the Latin American/Caribbean isolates with Sri Lankan group B DENV-3 in phylogenetic analyses supports the proposed common East African origin for all these strains and confirms the use of the 3′ NCR for molecular epidemiologic studies of DENV-3. The differences in the 3′ NCRs reported here, as well as potential alterations in the structural and non-structural coding genes, may contribute to the increased pathogenicity of group B DENV-3.

Influenza Control

Influenza is an uncontrolled epidemic disease that occurs every winter. Epidemics, which vary in severity, are measured by excess mortality, but influenza is always the leading cause of acute respiratory tract infections that lead to health care visits or hospitalization. Therefore, when an epidemic is classified as “mild,” this comparison is only with other flu epidemics; even mild flu epidemics result in the highest rates of health care encounters for the season. The effect on health care facilities is magnified by the usual sharp seasonality of influenza outbreaks. Many patients, particularly young children, experience a sudden onset of symptoms that . . .

Rational Management of Didymella rabiei in Chickpea by Integration of Genotype Resistance and Postinfection Application of Fungicides

ABSTRACT Various aspects of the integration of genotype resistance and chemical control of Ascochyta blight (caused by Didymella rabiei) in chickpea were examined in field experiments from 1993 to 1999 and in greenhouse experiments. Four commercially available chickpea cultivars representing a range of resistance to D. rabiei were used. The efficacy of chemical control in a highly susceptible cultivar was significantly (P < 0.01) related to the conduciveness of the environment to the pathogen. Adequate disease suppression (>80% control) was achieved when weather supported mild epidemics, but insufficient control (<20%) was achieved when weather supported severe epidemics. The contribution of genotype resistance to disease suppression in a moderately susceptible cultivar varied from <10% when weather supported severe epidemics to approximately 60% when weather supported mild epidemics. Spraying a moderately resistant cultivar resulted in 95% control when weather supported mild epidemics, but only 65% control was achieved when weather supported severe epidemics. The existing level of resistance in a moderately resistant cultivar resulted in 70% control when weather supported severe epidemics; fungicides improved control efficacy significantly to >95%. Under mild epidemics, moderate resistance alone provided >95% control. The level of genotype resistance available in a highly resistant cultivar was sufficient to suppress the disease under all weather conditions, even without application of fungicides. The possibility of relying on postinfection rather than prophylactic application of fungicides was tested in the greenhouse and in four field experiments. Activity of the systemic fungicide tebuconazole was detected when the fungicide was applied up to 3 days postinfection, and application of tebuconazole or difenoconazole in the field as a postinfection treatment (i.e., after rain or overhead irrigation) suppressed the disease as effectively as preventive applications and required fewer sprays. In two experiments, the interaction between genotype resistance and chemical control at various amounts of irrigation applied via overhead sprinklers (as a simulation of rain) was tested. The results show that both the level of genotype resistance and the quantity of water should be taken into account in deciding whether to apply a postinfection spray.

Weather and Downy Mildew Epidemics of Hop in Washington State

Relationships between weather and downy mildew epidemics of hop in the Yakima Valley of Washington State over a 38-yr period were examined with linear discriminant and logistic regression analyses. A linear discriminant function with minimum temperature in April X the total number of rainfall days in April and May, an indicator variable for the presence of an epidemic the preceding year, and the minimum temperature in May X the number of occurrences of three or more consecutive rainfall days in May correctly classified the epidemic status for 92% of the years. The percentage of years with mild epidemics correctly classified (specificity) and years with severe epidemics correctly classified (sensitivity) for a 10-yr test data set were 86 and 100%, respectively [...]

Fungicidal disease suppression and yield losses associated with sunflower rust in Israel

The effects of rust on the yield components and harvested achene yield of a non-oilseed sunflower cultivar were examined in two field trials in Israel. Head area and the number of achenes per head were decreased during severe rust epidemics, but were unaffected by moderate or mild epidemics. Individual achene weight and the frequency of fertile achenes were influenced by the disease, in relation to its intensity. The fungicide tebuconazole, applied at a rate of 0.125 kg a.i. ha −1, arrested rust development for at least 14 days. Highly significant effects were obtained by spraying when anthesis had occurred only in the outer quarter of the inflorescence radius, whereas the effects of spraying when anthesis was completed were negligible. Differences in yield (0.86–1.15 t ha −1) and in net profit (US$696–1153 ha −1) between sprayed and unsprayed plots were significant ( p<0.05).

Effects of moisture and septoria tritici blotch stresses on wheat yields under semi-arid conditions: A Simulation study

The effects of Septoria tritici blotch on spring wheat were incorporated into a crop growth simulator and the model was then used to evaluate the interrelationships between moisture and disease stresses on wheat yields under semi-arid conditions. Simulation experiments revealed that moisture availability plays a role in determining the relationship between disease and yield. In a season when precipitation was distributed evenly, a non-diseased crop yielded more than diseased crops. Yield reductions in diseased crops were related to the severity of epidemics; the relationship between disease and yield was inverse and linear. In a season when water was scarce during the stage of kernel-filling, crops with mild or moderate disease epidemics (apparent infection rate of a logistic model,r, of 0.025 or 0.05 per unit) yielded more than the non-diseased crop. The yield of the crop with a severe epidemic (r of 0.1 per unit) was reduced substantially and the relationship between disease and yield was parabolic. The parabolic relationship was linearized when additional precipitation was simulated in the model.

Spatial Pattern of Downy Mildew in Hop Yards During Severe and Mild Disease Epidemics

Hop plants in hills in three or four hop yards were assessed visually during severe and mild epidemics of downy mildew in the Yakima Valley of Washington. Several methods of analysis were used to investigate the spatial pattern of hop plants systemically infected with Pseudoperonospora humuli during the two types of epidemics. When disease incidences were low during the mild epidemics and early in the development of the severe epidemics, distributions associated with aggregation of disease provided a good representation of the frequency distribution of systemically infected shoots (...)

Selection of Barley for Slow Rusting Resistance to Leaf Rust in Epidemics in Different Severity1

Slow rusting resistance is of great potential value because it may be more stable than resistance recognized by infection types. However, the conditions necessary for most effective selection for slow rusting resistance are not well defined. The barley (Hordeum vulgare L.) cultivars Gus, Larker, Vada, Volla, Gold, and the lines MN9062, MN7572 and MN7544, known to differ in slow rusting resistance, were evaluated in the field during severe and mild epidemics of race 4 of Puccinia hordei. The area under the disease progress curve (AUDPC), used to estimate slow rusting, was larger for all cultivars and lines in a severe epidemic than in a mild one. The differences among the eight cultivars and lines for AUDPC were more distinct in the severe epidemic. The ranking of the cultivars and lines according to AUDPC was similar in both epidemics as indicated by Spearman's coefficient of rank correlation (0.86, significant at P = 0.01). It is suggested that selection for slow rusting resistance preferably be done in severe epidemics with the inclusion as controls, cultivars that are known to rust slowly or rapidly.

Enteropathogenic Escherichia coli

Sir .—The article by Rudoy and Nelson (129:668-672, 1975) and the editorial comments of Neter (129:666, 1975) regarding the diarrheas apparently produced by enteropathogenic Escherichia coli do not address themselves to the clinical observation that many cases of gastroenteritis behave like viral illnesses in that they persist for five to seven days before resolving spontaneously. Mild epidemics of these diarrheas also occur each summer with monotonous regularity. I am curious as to whether anyone has investigated the possibility of a virus inducing enterotoxin production in both typable and nontypable E coli . Such a system is well delineated in the production of toxin by the diphtheria bacillus, and viral induction of toxin by bacteria might explain why many diarrheas behave like viral diseases despite a largely unrewarding search for pathogenic enteroviruses.

EXCESS MORTALITY FROM EPIDEMIC INFLUENZA, 1957–1966

Housworth, J. (Bureau of Epidemiology. Center for Disease Control, Atlanta. Georgia 30333) and A. D. Langmuir. Excess mortality from epidemic influenza. 1957–1966. Am J Epidemiol 100: 40–48. 1974.—A study of excess mortality in the United States from 1957 through 1966 revealed seven epidemic periods associated with the prevalence of influenza A2 or B or both infections, and one period in July 1966 associated with a heat wave. More than half of the excess deaths are attributed to diseases of the heart, or the circulatory or nervous systems. The proportion ascribed to respiratory causes varies from 38% in severe epidemics of influenza A2 to as low as 22% during mild epidemics of influenza B. Severe epidemics of influenza result in small but significant excess mortality attributed to tuberculosis, asthma, chronic rheumatic heart disease, diabetes, and neoplasms. Maternal deaths showed no excess mortality during influenza epidemics. Similarly, infant mortality was not influenced to a measurable degree by influenza epidemics.

Parasitological problems in high northern latitudes, with particular reference to Canada

Disease in the Canadian Arctic has, until quite recently, been of minor concern to the world. The Eskimo and northern Indian lived in a climate which was antagonistic to contact diseases and very little attention was paid to indigenous infections. During the past decade, more and more white men have gone to the Arctic to survey and mine its abundant natural resources, and to work on such projects as the DEW Line. This influx of personnel introduced bacteria and European viruses to a native population which had no resistance or immunity to the diseases of civilization, and consequently even such mild viruses as those producing colds have caused serious illnesses and mild epidemics; the introduction of tuberculosis has had tragic results.