Neglected Consequences: Role of Introduced Aquatic Species in the Spread of Infectious Diseases

Introduction of aquatic organisms to new ecosystems has led to massive alterations to the structure and function of natural ecosystems, and to extinction of native flora and fauna. The ecological impacts caused by exotic aquatic species worldwide have been widely recognized, but the past and potential human health impacts of these introductions have been largely ignored. This review identifies several modes by which introduced aquatic species negatively impact human health: a) the direct introduction of human pathogens and/or their hosts; b) the introduction of pathogens of species upon which humans depend; and c) structural and functional alterations of ecosystems that affect other aquatic species upon which humans depend. The literature review presented here focuses on the first of these modes, presenting examples of either pathogens or hosts of pathogens (or both) that are documented to have been introduced, and that either affect or have the potential to affect human health, and occur in aquatic environments. Documented or suspected cases of introduced species that have caused human health impacts include: a) introduced dinoflagellates, which cause the accumulation of human neurotoxins in shellfish; b) various species of freshwater snails hosting a variety of human disease organisms, including Schistosoma mansoni (the cause of intestinal schistosomiasis), schistosomes that cause swimmers itch (cercarial dermatitis), the liver fluke Fasciola hepatica, and others; c) Vibrio cholerae, the agent of infection of cholera disease; and d) introduced mitten crabs, which can carry a human lung fluke.     

Representative Contact Diaries for Modeling the Spread of Infectious Diseases in Taiwan

Recent studies of infectious diseases have attempted to construct more realistic parameters of interpersonal contact patterns from diary-approach surveys. To ensure that such diary-based contact patterns provide accurate baseline data for policy implementation in densely populated Taiwan, we collected contact diaries from a national sample, using 3-stage systematic probability sampling and rigorous in-person interviews. A representative sample of 1,943 contact diaries recorded a total of 24,265 wide-range, face-to-face interpersonal contacts during a 24-hour period. Nearly 70% of the contacts occurred outside of respondents'' households. The most active age group was schoolchildren (ages 5–14), who averaged around 16–18 daily contacts, about 2–3 times as many as the least active age groups. We show how such parameters of contact patterns help modify a sophisticated national simulation system that has been used for years to model the spread of pandemic diseases in Taiwan. Based on such actual and representative data that enable researchers to infer findings to the whole population, our analyses aim to facilitate implementing more appropriate and effective strategies for controlling an emerging or pandemic disease infection.     

Animal Ownership and Touching Enrich the Context of Social Contacts Relevant to the Spread of Human Infectious Diseases

Many human infectious diseases originate from animals or are transmitted through animal vectors. We aimed to identify factors that are predictive of ownership and touching of animals, assess whether animal ownership influences social contact behavior, and estimate the probability of a major zoonotic outbreak should a transmissible influenza-like pathogen be present in animals, all in the setting of a densely populated European country. A diary-based social contact survey (n = 1768) was conducted in Flanders, Belgium, from September 2010 until February 2011. Many participants touched pets (46%), poultry (2%) or livestock (2%) on a randomly assigned day, and a large proportion of participants owned such animals (51%, 15% and 5%, respectively). Logistic regression models indicated that larger households are more likely to own an animal and, unsurprisingly, that animal owners are more likely to touch animals. We observed a significant effect of age on animal ownership and touching. The total number of social contacts during a randomly assigned day was modeled using weighted-negative binomial regression. Apart from age, household size and day type (weekend versus weekday and regular versus holiday period), animal ownership was positively associated with the total number of social contacts during the weekend. Assuming that animal ownership and/or touching are at-risk events, we demonstrate a method to estimate the outbreak potential of zoonoses. We show that in Belgium animal-human interactions involving young children (0–9 years) and adults (25–54 years) have the highest potential to cause a major zoonotic outbreak.     

Contact Profiles in Eight European Countries and Implications for Modelling the Spread of Airborne Infectious Diseases

Background

For understanding the spread of infectious diseases it is crucial to have knowledge of the patterns of contacts in a population during which the infection can be transmitted. Besides contact rates and mixing between age groups, the way individuals distribute their contacts across different locations may play an important role in determining how infections spread through a population.

Methods and Findings

Representative surveys were performed in eight countries to assess the number of social contacts (talking to another person at close distance either with or without physical contact), using a diary approach in which participants recorded individual contacts. The overall sample size was 7290 respondents. We analyzed the reported numbers of contacts per respondent in six different settings (household, work, school, leisure, transportation and others) to define different contact profiles. The identification of the profiles and classification of respondents according to these profiles was conducted using a two-step cluster analysis algorithm as implemented in SPSS.We identified seven distinct contact profiles: respondents having (1) mixed: contacts predominantly at school, during transportation and leisure time, (2) contacts during leisure time, (3) contacts mainly in the household (large family), (4) contacts at work, (5) contacts solely at school, (6) contacts in other places and finally (7) respondents having a low number of contacts in any setting. Similar contact profiles can be found in all eight European countries which participated in the study. The distributions of respondents across the profiles were similar in all countries. The profiles are dominated by work, school and household contacts. But also contacts during leisure activities play an important role in the daily lives of a large fraction of individuals. A surprisingly large number of individuals has only few contacts in all locations. There was a distinct age-dependence in the distribution of the population across contact profiles.

Conclusions

In contrast with earlier studies that focussed on the contribution of different age groups to the spread of an infectious disease, our results open up the opportunity to analyze how an infection spreads between locations and how locations as work or school are interconnected via household contacts. Mathematical models that take these local contact patterns into account can be used to assess the effect of intervention measures like school closure and cancelling of leisure activities on the spread of influenza.     

Inferring the Structure of Social Contacts from Demographic Data in the Analysis of Infectious Diseases Spread

Social contact patterns among individuals encode the transmission route of infectious diseases and are a key ingredient in the realistic characterization and modeling of epidemics. Unfortunately, the gathering of high quality experimental data on contact patterns in human populations is a very difficult task even at the coarse level of mixing patterns among age groups. Here we propose an alternative route to the estimation of mixing patterns that relies on the construction of virtual populations parametrized with highly detailed census and demographic data. We present the modeling of the population of 26 European countries and the generation of the corresponding synthetic contact matrices among the population age groups. The method is validated by a detailed comparison with the matrices obtained in six European countries by the most extensive survey study on mixing patterns. The methodology presented here allows a large scale comparison of mixing patterns in Europe, highlighting general common features as well as country-specific differences. We find clear relations between epidemiologically relevant quantities (reproduction number and attack rate) and socio-demographic characteristics of the populations, such as the average age of the population and the duration of primary school cycle. This study provides a numerical approach for the generation of human mixing patterns that can be used to improve the accuracy of mathematical models in the absence of specific experimental data.     

A Household-Based Study of Contact Networks Relevant for the Spread of Infectious Diseases in the Highlands of Peru

Background

Few studies have quantified social mixing in remote rural areas of developing countries, where the burden of infectious diseases is usually the highest. Understanding social mixing patterns in those settings is crucial to inform the implementation of strategies for disease prevention and control. We characterized contact and social mixing patterns in rural communities of the Peruvian highlands.

Methods and Findings

This cross-sectional study was nested in a large prospective household-based study of respiratory infections conducted in the province of San Marcos, Cajamarca-Peru. Members of study households were interviewed using a structured questionnaire of social contacts (conversation or physical interaction) experienced during the last 24 hours. We identified 9015 reported contacts from 588 study household members. The median age of respondents was 17 years (interquartile range [IQR] 4–34 years). The median number of reported contacts was 12 (IQR 8–20) whereas the median number of physical (i.e. skin-to-skin) contacts was 8.5 (IQR 5–14). Study participants had contacts mostly with people of similar age, and with their offspring or parents. The number of reported contacts was mainly determined by the participants’ age, household size and occupation. School-aged children had more contacts than other age groups. Within-household reciprocity of contacts reporting declined with household size (range 70%-100%). Ninety percent of household contact networks were complete, and furthermore, household members'' contacts with non-household members showed significant overlap (range 33%-86%), indicating a high degree of contact clustering. A two-level mixing epidemic model was simulated to compare within-household mixing based on observed contact networks and within-household random mixing. No differences in the size or duration of the simulated epidemics were revealed.

Conclusion

This study of rural low-density communities in the highlands of Peru suggests contact patterns are highly assortative. Study findings support the use of within-household homogenous mixing assumptions for epidemic modeling in this setting.     

Modeling Spatial Spread of Infectious Diseases with a Fixed Latent Period in a Spatially Continuous Domain

In this paper, with the assumptions that an infectious disease in a population has a fixed latent period and the latent individuals of the population may diffuse, we formulate an SIR model with a simple demographic structure for the population living in a spatially continuous environment. The model is given by a system of reaction-diffusion equations with a discrete delay accounting for the latency and a spatially non-local term caused by the mobility of the individuals during the latent period. We address the existence, uniqueness, and positivity of solution to the initial-value problem for this type of system. Moreover, we investigate the traveling wave fronts of the system and obtain a critical value c ^* which is a lower bound for the wave speed of the traveling wave fronts. Although we can not prove that this value is exactly the minimal wave speed, numeric simulations seem to suggest that it is. Furthermore, the simulations on the PDE model also suggest that the spread speed of the disease indeed coincides with c ^*. We also discuss how the model parameters affect c ^*.     

Rapid Generation of Human-Like Neutralizing Monoclonal Antibodies in Urgent Preparedness for Influenza Pandemics and Virulent Infectious Diseases

Background

The outbreaks of emerging infectious diseases caused by pathogens such as SARS coronavirus, H5N1, H1N1, and recently H7N9 influenza viruses, have been associated with significant mortality and morbidity in humans. Neutralizing antibodies from individuals who have recovered from an infection confer therapeutic protection to others infected with the same pathogen. However, survivors may not always be available for providing plasma or for the cloning of monoclonal antibodies (mAbs).

Methodology/Principal Findings

The genome and the immunoglobulin genes in rhesus macaques and humans are highly homologous; therefore, we investigated whether neutralizing mAbs that are highly homologous to those of humans (human-like) could be generated. Using the H5N1 influenza virus as a model, we first immunized rhesus macaques with recombinant adenoviruses carrying a synthetic gene encoding hemagglutinin (HA). Following screening an antibody phage display library derived from the B cells of immunized monkeys, we cloned selected macaque immunoglobulin heavy chain and light chain variable regions into the human IgG constant region, which generated human-macaque chimeric mAbs exhibiting over 97% homology to human antibodies. Selected mAbs demonstrated potent neutralizing activities against three clades (0, 1, 2) of the H5N1 influenza viruses. The in vivo protection experiments demonstrated that the mAbs effectively protected the mice even when administered up to 3 days after infection with H5N1 influenza virus. In particular, mAb 4E6 demonstrated sub-picomolar binding affinity to HA and superior in vivo protection efficacy without the loss of body weight and obvious lung damage. The analysis of the 4E6 escape mutants demonstrated that the 4E6 antibody bound to a conserved epitope region containing two amino acids on the globular head of HA.

Conclusions/Significance

Our study demonstrated the generation of neutralizing mAbs for potential application in humans in urgent preparedness against outbreaks of new influenza infections or other virulent infectious diseases.     

噬菌体展示技术的理论基础及其在感染性疾病防治中的应用

噬菌体展示技术是一种高通量研究基因功能、蛋白质表达及其相互作用的有效方法,具有与生物芯片一样的大量快速检测、发现并鉴定功能基因及蛋白质-蛋白质相互作用的优点。我们着重介绍噬菌体展示技术的种类、原理,及其在感染性疾病防治中的应用。     

实时荧光定量PCR及其在传染性疾病检测中的应用

实时荧光定量PCR技术被广泛应用于实验研究、临床检测中。与普通的PCR相比,实时荧光定量PCR技术具有特异性强、灵敏度高、重复性好、定量准确、速度快、全封闭反应等优点。我们综述了实时荧光定量PCR技术的原理、定量方法,及其在传染性疾病检测研究中的应用。     

Deciphering Serology to Understand the Ecology of Infectious Diseases in Wildlife

The ecology of infectious disease in wildlife has become a pivotal theme in animal and public health. Studies of infectious disease ecology rely on robust surveillance of pathogens in reservoir hosts, often based on serology, which is the detection of specific antibodies in the blood and is used to infer infection history. However, serological data can be inaccurate for inference to infection history for a variety of reasons. Two major aspects in any serological test can substantially impact results and interpretation of antibody prevalence data: cross-reactivity and cut-off thresholds used to discriminate positive and negative reactions. Given the ubiquitous use of serology as a tool for surveillance and epidemiological modeling of wildlife diseases, it is imperative to consider the strengths and limitations of serological test methodologies and interpretation of results, particularly when using data that may affect management and policy for the prevention and control of infectious diseases in wildlife. Greater consideration of population age structure and cohort representation, serological test suitability and standardized sample collection protocols can ensure that reliable data are obtained for downstream modeling applications to characterize, and evaluate interventions for, wildlife disease systems.