Within-host dynamics of infection: from ecological insights to evolutionary predictions.

O.R. is supported by a University Research Fellowship from The Royal Society.This is the final version of the article. It first appeared from Royal Society Publishing via http://dx.doi.org/10.1098/rstb.2014.030

Malaria-filaria coinfection in mice makes malarial disease more severe unless filarial infection achieves patency

Coinfections are common in natural populations, and the literature suggests that helminth coinfection readily affects how the immune system manages malaria. For example, type 1–dependent control of malaria parasitemia might be impaired by the type 2 milieu of preexisting helminth infection. Alternatively, immunomodulatory effects of helminths might affect the likelihood of malarial immunopathology. Using rodent models of lymphatic filariasis (Litomosoides sigmodontis) and noncerebral malaria (clone AS Plasmodium chabaudi chabaudi), we quantified disease severity, parasitemia, and polyclonal splenic immune responses in BALB/c mice. We found that coinfected mice, particularly those that did not have microfilaremia (Mf), had more severe anemia and loss of body mass than did mice with malaria alone. Even when controlling for parasitemia, malaria was most severe in Mf coinfected mice, and this was associated with increased interferon-g responsiveness. Thus, in Mf mice, filariasis upset a delicate immunological balance in malaria infection and exacerbated malaria-induced immunopathology. Helminth infections are prevalent throughout tropical regions where malaria is transmitted [1–5]. Interactions among infections commonly alter disease severity [6, 7], and malaria-helminth coinfection can either exac

Universal or Specific? A Modeling-Based Comparison of Broad-Spectrum Influenza Vaccines against Conventional, Strain-Matched Vaccines

Despite the availability of vaccines, influenza remains a major public health challenge. A key reason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza, while novel influenza viruses invade the human population to cause a pandemic every few decades. Current vaccines have to be updated continually to keep up to date with this antigenic change, but emerging ‘universal’ vaccines—targeting more conserved components of the influenza virus—offer the potential to act across all influenza A strains and subtypes. Influenza vaccination programmes around the world are steadily increasing in their population coverage. In future, how might intensive, routine immunization with novel vaccines compare against similar mass programmes utilizing conventional vaccines? Specifically, how might novel and conventional vaccines compare, in terms of cumulative incidence and rates of antigenic evolution of seasonal influenza? What are their potential implications for the impact of pandemic emergence? Here we present a new mathematical model, capturing both transmission dynamics and antigenic evolution of influenza in a simple framework, to explore these questions. We find that, even when matched by per-dose efficacy, universal vaccines could dampen population-level transmission over several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunity in the population, conventional vaccines could allow the increased spread of a novel pandemic strain. Conversely, universal vaccines could mitigate both seasonal and pandemic spread. However, where it is not possible to maintain annual, intensive vaccination coverage, the duration and breadth of immunity raised by universal vaccines are critical determinants of their performance relative to conventional vaccines. In future, conventional and novel vaccines are likely to play complementary roles in vaccination strategies against influenza: in this context, our results suggest important characteristics to monitor during the clinical development of emerging vaccine technologies

Aligning Perspectives of Subjective Well-Being: Comparing Spouse and Colleague Perceptions of Social Worker Happiness

Social workers experience higher rates of burnout and attrition when compared to other health related occupational groups. Previous research on the well being of social workers has tended to focus on the social workers themselves. But the development of well-being is dynamic and is fostered through relationships and interactions with others. In the case of social workers, these relationships include workplace, professional, and personal life interactions. This research sought to better understand the level of congruence between a social worker’s perspective of well-being and perspectives held by significant people in their workplace and at home. Utilizing qualitative methods we interviewed colleagues and spouses (n=10) of social workers that were found to have high levels of work-related subjective well-being. The findings support previous conclusions on the positive subjective well-being (SWB) of practicing social workers, but also indicate a lack of a deeper understanding of the nuances that contribute to social worker SWB. These findings are particularly useful for social workers trying to enhance their SWB, and have direct applicability in education and professional development settings that seek to enhance social worker self-care

Precision test of a Fermion mass texture

Texture zeros in the quark Yukawa matrices generally lead to precise and simple expressions for CKM matrix elements in terms of ratios of quark masses. Using the new data on $b-$decays we test a particularly promising texture zero solution and show that it is at best approximate. We analyse the approximate texture zero structure and show it is consistent with experiment. We investigate the implications for the CKM unitarity triangle, measurements at $BaBar$ and $BELLE$ as well as for the theories which invoke family symmetries

Aptamer conjugated silver nanoparticles for the detection of interleukin 6

The controlled assembly of plasmonic nanoparticles by a molecular binding event has emerged as a simple yet sensitive methodology for protein detection. Metallic nanoparticles (NPs) coated with functionalized aptamers can be utilized as biosensors by monitoring changes in particle optical properties, such as the LSPR shift and enhancement of the SERS spectra, in the presence of a target protein. Herein we test this method using two modified aptamers selected for the protein biomarker interleukin 6, an indicator of the dengue fever virus and other diseases including certain types of cancers, diabetes, and even arthritis. IL6 works by inducing an immunological response within the body that can be either anti-inflammatory or pro-inflammatory. The results show that the average hydrodynamic diameter of the NPs as measured by Dynamic Light Scattering was ∼42 nm. After conjugation of the aptamers, the peak absorbance of the AgNPs shifted from 404 to 408 nm indicating a surface modification of the NPs due to the presence of the aptamer. Lastly, preliminary results were obtained showing an increase in SERS intensity occurs when the IL-6 protein was introduced to the conjugate solution but the assay will still need to be optimized in order for it to be able to monitor varying concentration changes within and across the desired range

Social Media Use and Access to Digital Technology in US Young Adults in 2016.

BACKGROUND: In 2015, 90% of US young adults with Internet access used social media. Digital and social media are highly prevalent modalities through which young adults explore identity formation, and by extension, learn and transmit norms about health and risk behaviors during this developmental life stage. OBJECTIVE: The purpose of this study was to provide updated estimates of social media use from 2014 to 2016 and correlates of social media use and access to digital technology in data collected from a national sample of US young adults in 2016. METHODS: Young adult participants aged 18-24 years in Wave 7 (October 2014, N=1259) and Wave 9 (February 2016, N=989) of the Truth Initiative Young Adult Cohort Study were asked about use frequency for 11 social media sites and access to digital devices, in addition to sociodemographic characteristics. Regular use was defined as using a given social media site at least weekly. Weighted analyses estimated the prevalence of use of each social media site, overlap between regular use of specific sites, and correlates of using a greater number of social media sites regularly. Bivariate analyses identified sociodemographic correlates of access to specific digital devices. RESULTS: In 2014, 89.42% (weighted n, 1126/1298) of young adults reported regular use of at least one social media site. This increased to 97.5% (weighted n, 965/989) of young adults in 2016. Among regular users of social media sites in 2016, the top five sites were Tumblr (85.5%), Vine (84.7%), Snapchat (81.7%), Instagram (80.7%), and LinkedIn (78.9%). Respondents reported regularly using an average of 7.6 social media sites, with 85% using 6 or more sites regularly. Overall, 87% of young adults reported access or use of a smartphone with Internet access, 74% a desktop or laptop computer with Internet access, 41% a tablet with Internet access, 29% a smart TV or video game console with Internet access, 11% a cell phone without Internet access, and 3% none of these. Access to all digital devices with Internet was lower in those reporting a lower subjective financial situation; there were also significant differences in access to specific digital devices with Internet by race, ethnicity, and education. CONCLUSIONS: The high mean number of social media sites used regularly and the substantial overlap in use of multiple social media sites reflect the rapidly changing social media environment. Mobile devices are a primary channel for social media, and our study highlights disparities in access to digital technologies with Internet access among US young adults by race/ethnicity, education, and subjective financial status. Findings from this study may guide the development and implementation of future health interventions for young adults delivered via the Internet or social media sites

Experimental manipulation of immune-mediated disease and its fitness costs for rodent malaria parasites

<p>Abstract</p> <p>Background</p> <p>Explaining parasite virulence (harm to the host) represents a major challenge for evolutionary and biomedical scientists alike. Most theoretical models of virulence evolution assume that virulence arises as a direct consequence of host exploitation, the process whereby parasites convert host resources into transmission opportunities. However, infection-induced disease can be immune-mediated (immunopathology). Little is known about how immunopathology affects parasite fitness, or how it will affect the evolution of parasite virulence. Here we studied the effects of immunopathology on infection-induced host mortality rate and lifetime transmission potential – key components of parasite fitness – using the rodent malaria model, <it>Plasmodium chabaudi chabaudi</it>.</p> <p>Results</p> <p>Neutralizing interleukin [IL]-10, an important regulator of inflammation, allowed us to experimentally increase the proportion of virulence due to immunopathology for eight parasite clones. <it>In vivo </it>blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in a shorter time to death that was independent of parasite density and was particularly marked for normally avirulent clones. This suggests that IL-10 induction may provide a pathway to avirulence for <it>P. c. chabaudi</it>. Despite the increased investment in transmission-stage parasites observed for some clones in response to IL-10R blockade, experimental enhancement of immunopathology incurred a uniform fitness cost to all parasite clones by reducing lifetime transmission potential.</p> <p>Conclusion</p> <p>This is the first experimental study to demonstrate that infection-induced immunopathology and parasite genetic variability may together have the potential to shape virulence evolution. In accord with recent theory, the data show that some forms of immunopathology may select for parasites that make hosts less sick.</p

Experimental parasite community perturbation reveals associations between Sin Nombre virus and gastrointestinal nematodes in a rodent reservoir host

Individuals are often co-infected with several parasite species, yet measuring within-host interactions remains difficult in the wild. Consequently, the impact of such interactions on host fitness and epidemiology are often unknown. We used anthelmintic drugs to experimentally reduce nematode infection and measured the effects on both nematodes and the important zoonosis Sin Nombre virus (SNV) in its primary reservoir (Peromyscus spp.). Treatment significantly reduced nematode infection, but increased SNV seroprevalence. Furthermore, mice that were co-infected with both nematodes and SNV were in better condition and survived up to four times longer than uninfected or singly-infected mice. These results highlight the importance of investigating multiple parasites for understanding interindividual variation and epidemiological dynamics in reservoir populations with zoonotic transmission potential.Funding provided by: Wellcome TrustCrossref Funder Registry ID: http://dx.doi.org/10.13039/100010269Award Number: Strategic grant 095831Funding provided by: Defense Advanced Research Projects AgencyCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000185Award Number: 68255-LS-DRPFunding provided by: Sigma XiCrossref Funder Registry ID: http://dx.doi.org/10.13039/100011084Award Number: G20101015154773Funding provided by: National Science FoundationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000001Award Number: DBI-1005104; DBI-045338