Can Interactions between Timing of Vaccine-Altered Influenza Pandemic Waves and Seasonality in Influenza Complications Lead to More Severe Outcomes?

Vaccination can delay the peak of a pandemic influenza wave by reducing the number of individuals initially susceptible to influenza infection. Emerging evidence indicates that susceptibility to severe secondary bacterial infections following a primary influenza infection may vary seasonally, with peak susceptibility occurring in winter. Taken together, these two observations suggest that vaccinating to prevent a fall pandemic wave might delay it long enough to inadvertently increase influenza infections in winter, when primary influenza infection is more likely to cause severe outcomes. This could potentially cause a net increase in severe outcomes. Most pandemic models implicitly assume that the probability of severe outcomes does not vary seasonally and hence cannot capture this effect. Here we show that the probability of intensive care unit (ICU) admission per influenza infection in the 2009 H1N1 pandemic followed a seasonal pattern. We combine this with an influenza transmission model to investigate conditions under which a vaccination program could inadvertently shift influenza susceptibility to months where the risk of ICU admission due to influenza is higher. We find that vaccination in advance of a fall pandemic wave can actually increase the number of ICU admissions in situations where antigenic drift is sufficiently rapid or where importation of a cross-reactive strain is possible. Moreover, this effect is stronger for vaccination programs that prevent more primary influenza infections. Sensitivity analysis indicates several mechanisms that may cause this effect. We also find that the predicted number of ICU admissions changes dramatically depending on whether the probability of ICU admission varies seasonally, or whether it is held constant. These results suggest that pandemic planning should explore the potential interactions between seasonally varying susceptibility to severe influenza outcomes and the timing of vaccine-altered pandemic influenza waves.     

Relationship between Humidity and Influenza A Viability in Droplets and Implications for Influenza’s Seasonality

Humidity has been associated with influenza’s seasonality, but the mechanisms underlying the relationship remain unclear. There is no consistent explanation for influenza’s transmission patterns that applies to both temperate and tropical regions. This study aimed to determine the relationship between ambient humidity and viability of the influenza A virus (IAV) during transmission between hosts and to explain the mechanisms underlying it. We measured the viability of IAV in droplets consisting of various model media, chosen to isolate effects of salts and proteins found in respiratory fluid, and in human mucus, at relative humidities (RH) ranging from 17% to 100%. In all media and mucus, viability was highest when RH was either close to 100% or below ∼50%. When RH decreased from 84% to 50%, the relationship between viability and RH depended on droplet composition: viability decreased in saline solutions, did not change significantly in solutions supplemented with proteins, and increased dramatically in mucus. Additionally, viral decay increased linearly with salt concentration in saline solutions but not when they were supplemented with proteins. There appear to be three regimes of IAV viability in droplets, defined by humidity: physiological conditions (∼100% RH) with high viability, concentrated conditions (50% to near 100% RH) with lower viability depending on the composition of media, and dry conditions (<50% RH) with high viability. This paradigm could help resolve conflicting findings in the literature on the relationship between IAV viability in aerosols and humidity, and results in human mucus could help explain influenza’s seasonality in different regions.     

Where are the Subtropics?

The tropics are clearly defined while ‘subtropics’ and ‘subtropical’ have been applied to a variety of zones, climates, and ecosystems. However, in the recent terrestrial biology literature, they have been used mainly for the zones between the tropics (±23.4^o C) and ±30.0^o. Adopting this standard would facilitate pan‐subtropical comparisons.     

Efficacy of Influenza Vaccination and Tamiflu? Treatment – Comparative Studies with Eurasian Swine Influenza Viruses in Pigs

Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters.In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.     

Seasonality of chlorophyll and nutrients in Lake Erken – effects of weather conditions

The effect of submerged macrophytes on interactions among epilimnetic phosphorus, phytoplankton, and heterotrophic bacterioplankton has been acknowledged, but remains poorly understood. Here, we test the hypotheses that the mean summer phytoplankton biomass (chlorophyll a): phosphorus ratios decrease with increased macrophyte cover in a series of nine lakes. Further, we test that both planktonic respiration and bacterioplankton production increase with respect to phytoplankton biomass along the same gradient of increasing macrophyte cover. Increased macrophyte cover was associated with a lower fraction of particulate phosphorus in epilimnia, with total particulate phosphorus declining from over 80% of total phosphorus in a macrophyte free lake to less than 50% in a macrophyte rich lake. Phytoplankton biomass (chlorophyll a) too was lower in macrophyte dominated lakes, despite relatively high levels of total dissolved phosphorus. Planktonic respiration and bacterioplankton production were higher in macrophyte rich lakes than would be expected from phytoplankton biomass alone, pointing to a subsidy of bacterioplankton metabolism by macrophyte beds at the whole lake scale. The results suggest that the classical view of pelagic interactions, which proposes phosphorus determines phytoplankton abundance, which in turn determines bacterial abundance through the production of organic carbon, becomes less relevant as macrophyte cover increases.     

Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination?

IntroductionDetermining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes.MethodsThis was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics.Results212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics.DiscussionOur findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate.     

Does the Establishment of Sustainable Use Reserves Affect Fire Management in the Humid Tropics?

Tropical forests are experiencing a growing fire problem driven by climatic change, agricultural expansion and forest degradation. Protected areas are an important feature of forest protection strategies, and sustainable use reserves (SURs) may be reducing fire prevalence since they promote sustainable livelihoods and resource management. However, the use of fire in swidden agriculture, and other forms of land management, may be undermining the effectiveness of SURs in meeting their conservation and sustainable development goals. We analyse MODIS derived hot pixels, TRMM rainfall data, Terra-Class land cover data, socio-ecological data from the Brazilian agro-census and the spatial extent of rivers and roads to evaluate whether the designation of SURs reduces fire occurrence in the Brazilian Amazon. Specifically, we ask (1) a. Is SUR location (i.e., de facto) or (1) b. designation (i.e. de jure) the driving factor affecting performance in terms of the spatial density of fires?, and (2), Does SUR creation affect fire management (i.e., the timing of fires in relation to previous rainfall)? We demonstrate that pre-protection baselines are crucial for understanding reserve performance. We show that reserve creation had no discernible impact on fire density, and that fires were less prevalent in SURs due to their characteristics of sparser human settlement and remoteness, rather than their status de jure. In addition, the timing of fires in relation to rainfall, indicative of local fire management and adherence to environmental law, did not improve following SUR creation. These results challenge the notion that SURs promote environmentally sensitive fire-management, and suggest that SURs in Amazonia will require special attention if they are to curtail future accidental wildfires, particularly as plans to expand the road infrastructure throughout the region are realised. Greater investment to support improved fire management by farmers living in reserves, in addition to other fire users, will be necessary to help ameliorate these threats.     

Influenza Illness and Hospitalizations Averted by Influenza Vaccination in the United States, 2005–2011

Context

The goal of influenza vaccination programs is to reduce influenza-associated disease outcomes. Therefore, estimating the reduced burden of influenza as a result of vaccination over time and by age group would allow for a clear understanding of the value of influenza vaccines in the US, and of areas where improvements could lead to greatest benefits.

Objective

To estimate the direct effect of influenza vaccination in the US in terms of averted number of cases, medically-attended cases, and hospitalizations over six recent influenza seasons.

Design

Using existing surveillance data, we present a method for assessing the impact of influenza vaccination where impact is defined as either the number of averted outcomes or as the prevented disease fraction (the number of cases estimated to have been averted relative to the number of cases that would have occurred in the absence of vaccination).

Results

We estimated that during our 6-year study period, the number of influenza illnesses averted by vaccination ranged from a low of approximately 1.1 million (95% confidence interval (CI) 0.6–1.7 million) during the 2006–2007 season to a high of 5 million (CI 2.9–8.6 million) during the 2010–2011 season while the number of averted hospitalizations ranged from a low of 7,700 (CI 3,700–14,100) in 2009–2010 to a high of 40,400 (CI 20,800–73,000) in 2010–2011. Prevented fractions varied across age groups and over time. The highest prevented fraction in the study period was observed in 2010–2011, reflecting the post-pandemic expansion of vaccination coverage.

Conclusions

Influenza vaccination programs in the US produce a substantial health benefit in terms of averted cases, clinic visits and hospitalizations. Our results underscore the potential for additional disease prevention through increased vaccination coverage, particularly among nonelderly adults, and increased vaccine effectiveness, particularly among the elderly.     

When will evolution lead to deceptive signaling in the Sir Philip Sidney game?

Sir Philip Sidney games are a widely used model of simple signaling. Johnstone and Grafen [Johnstone, R.A., Grafen, A., 1993. Dishonesty and the handicap principle. Animal Behaviour 46, 759–764] present a version in which the Evolutionarily Stable Strategy (ESS) is for most signalers to “honestly” signal, with a small minority of signalers who “cheat”. This model is among the most frequently cited papers on the topic of “dishonest” signaling and supports the view that signals may be “dishonest” as long as they are “honest on average”. Using genetic algorithms, we demonstrate that another solution exists to the game, an evolutionarily stable set of Nash equilibria in which members of the set never signal and all donors give their resource. Payoffs to players using this set of strategies is greater those when playing the “dishonest” signaling ESS. We demonstrate that a random population is far more likely to evolve to this non-communicating strategy set than the “dishonest” signaling ESS. We also discuss the dynamics of biological game theory models and the advances of genetic algorithms as a heuristic solution method for these models.     

Upper Airways Microbiota in Antibiotic-Na?ve Wheezing and Healthy Infants from the Tropics of Rural Ecuador

Background

Observations that the airway microbiome is disturbed in asthma may be confounded by the widespread use of antibiotics and inhaled steroids. We have therefore examined the oropharyngeal microbiome in early onset wheezing infants from a rural area of tropical Ecuador where antibiotic usage is minimal and glucocorticoid usage is absent.

Materials and Methods

We performed pyrosequencing of amplicons of the polymorphic bacterial 16S rRNA gene from oropharyngeal samples from 24 infants with non-infectious early onset wheezing and 24 healthy controls (average age 10.2 months). We analyzed microbial community structure and differences between cases and controls by QIIME software.

Results

We obtained 76,627 high quality sequences classified into 182 operational taxonomic units (OTUs). Firmicutes was the most common and diverse phylum (71.22% of sequences) with Streptococcus being the most common genus (49.72%). Known pathogens were found significantly more often in cases of infantile wheeze compared to controls, exemplified by Haemophilus spp. (OR = 2.12, 95% Confidence Interval (CI) 1.82–2.47; P = 5.46×10⁻²³) and Staphylococcus spp. (OR = 124.1, 95%CI 59.0–261.2; P = 1.87×10⁻²⁴¹). Other OTUs were less common in cases than controls, notably Veillonella spp. (OR = 0.59, 95%CI = 0.56–0.62; P = 8.06×10⁻⁸⁶).

Discussion

The airway microbiota appeared to contain many more Streptococci than found in Western Europe and the USA. Comparisons between healthy and wheezing infants revealed a significant difference in several bacterial phylotypes that were not confounded by antibiotics or use of inhaled steroids. The increased prevalence of pathogens such as Haemophilus and Staphylococcus spp. in cases may contribute to wheezing illnesses in this age group.     

Why Was the 2009 Influenza Pandemic in England So Small?

The "Swine flu" pandemic of 2009 caused world-wide infections and deaths. Early efforts to understand its rate of spread were used to predict the probable future number of cases, but by the end of 2009 it was clear that these predictions had substantially overestimated the pandemic's eventual impact. In England, the Health Protection Agency made announcements of the number of cases of disease, which turned out to be surprisingly low for an influenza pandemic. The agency also carried out a serological survey half-way through the English epidemic. In this study, we use a mathematical model to reconcile early estimates of the rate of spread of infection, weekly data on the number of cases in the 2009 epidemic in England and the serological status of the English population at the end of the first pandemic wave. Our results reveal that if there are around 19 infections (i.e., seroconverters) for every reported case then the three data-sets are entirely consistent with each other. We go on to discuss when in the epidemic such a high ratio of seroconverters to cases of disease might have been detected, either through patterns in the case reports or through even earlier serological surveys.     

When do parasites fail to speciate in response to host speciation?

Cospeciation generally increases the similarity between host and parasite phylogenies. Incongruence between host and parasite phylogenies has previously been explained in terms of host switching, sorting, and duplication events. Here, we describe an additional process, failure of the parasite to speciate in response to host speciation, that may be important in some host-parasite systems. Failure to speciate is likely to occur when gene flow among parasite populations is much higher than that of their hosts. We reconstructed trees from mitochondrial and nuclear DNA sequences for pigeons and doves (Aves: Columbiformes) and their feather lice in the genus Columbicola (Insecta: Phthiraptera). Although comparisons of the trees from each group revealed a significant amount of cospeciation, there was also a significant degree of incongruence. Cophylogenetic analyses generally indicated that host switching may be an important process in the history of this host-parasite association. Using terminal sister taxon comparisons, we also identified three apparent cases where the host has speciated but the associated parasite has not. In two of these cases of failure to speciate, these comparisons involve allopatric sister taxa of hosts whose lice also occur on hosts sympatric with both of the allopatric sisters. These additional hosts for generalist lice may promote gene flow with lice on the allopatric sister species. Relative rate comparisons for the mitochondrial cytochrome oxidase I gene indicate that molecular substitution occurs about 11 times faster in lice than in their avian hosts.