Emerging and Reemerging Infectious Diseases: Biocomplexity as an Interdisciplinary Paradigm

Understanding factors responsible for reemergence of diseases believed to have been controlled and outbreaks of previously unknown infectious diseases is one of the most difficult scientific problems facing society today. Significant knowledge gaps exist for even the most studied emerging infectious diseases. Coupled with failures in the response to the resurgence of infectious diseases, this lack of information is embedded in a simplistic view of pathogens and disconnected from a social and ecological context, and assumes a linear response of pathogens to environmental change. In fact, the natural reservoirs and transmission rates of most emerging infectious diseases primarily are affected by environmental factors, such as seasonality or meteorological events, typically producing nonlinear responses that are inherently unpredictable. A more realistic view of emerging infectious diseases requires a holistic perspective that incorporates social as well as physical, chemical, and biological dimensions of our planet’s systems. The notion of biocomplexity captures this depth and richness, and most importantly, the interactions of human and natural systems. This article provides a brief review and a synthesis of interdisciplinary approaches and insights employing the biocomplexity paradigm and offers a social–ecological approach for addressing and garnering an improved understanding of emerging infectious diseases. Drawing on findings from studies of cholera and other examples of emerging waterborne, zoonotic, and vectorborne diseases, a “blueprint” for the proposed interdisciplinary research framework is offered which integrates biological processes from the molecular level to that of communities and regional systems, incorporating public health infrastructure and climate aspects.     

Examining Associations between Health Information Seeking Behavior and Adult Education Status in the U.S.: An Analysis of the 2012 PIAAC Data

This paper presents data from the Program for the International Assessment of Adult Competencies with a focus on the interrelationships among health information seeking behavior (HISB), and health status or use of preventive health measures for U.S. adults both with and without a high school diploma. Key results of ordinal and binary logistic regression analyses indicated that, after controlling for demographic factors, (1) adults with a high school diploma use more text-based health information sources while adults without a high school diploma use more oral sources, (2) using the Internet as a source of health information is more strongly related to reporting excellent/very good health status than having a high school diploma, (3) those without a high school diploma who use the Internet report the largest increase in health status over any other health information source, and (4) for those with learning disability or vision problem, a high facility in reading English is an important predictor of whether the Internet is used as a health information source. The Internet appears to play a key role in both enhancing health status and enabling use of preventive measures for those with and without a high school diploma; although, individuals without a high school diploma who use the Internet for health information derive substantial benefit in health status.     

The density and diversity of gymnamoebae associated with terrestrial moss communities (Bryophyta: Bryopsida) in a northeastern U.S. forest

Moss communities are commonly found in temperate forests and form a nearly continuous understory in some high latitude forests. However, little is known about the microbial component of these communities, especially the non-testate amoeboid protists. Fifty morphospecies of naked amoebae were identified in samples collected at eight sites in a northeastern North American forest. The mean number (+/-SE) of morphospecies found per sample site based on laboratory cultures was 17+/-2.1. The density of amoebae expressed as number/g dry weight of moss ranged from 3.5+/-0.04 x 10(3) to 4.3+/-0.2 x 10(4) and was positively correlated with the moss moisture content (r=0.9, P<0.001, df=26). Densities of gymnamoebae in the moss are generally higher than found in the surrounding soil, but this may be due in part to the greater weight of soil per unit volume compared with moss. The percentage of encysted forms was inversely related to the moisture content of the moss sample.     

Phenotypic and Phylogenetic Identification of Coliform Bacteria Obtained Using 12 Coliform Methods Approved by the U.S. Environmental Protection Agency

The current definition of coliform bacteria is method dependent, and when different culture-based methods are used, discrepancies in results can occur and affect the accuracy of identification of true coliforms. This study used an alternative approach to the identification of true coliforms by combining the phenotypic traits of the coliform isolates and the phylogenetic affiliation of 16S rRNA gene sequences with the use of lacZ and uidA genes. A collection of 1,404 isolates detected by 12 U.S. Environmental Protection Agency-approved coliform-testing methods were characterized based on their phylogenetic affiliations and responses to their original isolation media and lauryl tryptose broth, m-Endo, and MI agar media. Isolates were phylogenetically classified into 32 true-coliform, or targeted Enterobacteriaceae (TE), groups and 14 noncoliform, or nontargeted Enterobacteriaceae (NTE), groups. It was shown statistically that detecting true-positive (TP) events is more challenging than detecting true-negative (TN) events. Furthermore, most false-negative (FN) events were associated with four TE groups (i.e., Serratia group I and the Providencia, Proteus, and Morganella groups) and most false-positive (FP) events with two NTE groups, the Aeromonas and Plesiomonas groups. In Escherichia coli testing, 18 out of 145 E. coli isolates identified by enzymatic methods were validated as FN. The reasons behind the FP and FN reactions could be explained through analysis of the lacZ and uidA genes. Overall, combining the analyses of the 16S rRNA, lacZ, and uidA genes with the growth responses of TE and NTE on culture-based media is an effective way to evaluate the performance of coliform detection methods.     

An introduction to a series of U.S. Environmental Protection Agency special committee reports on testing approaches for the detection of chemically induced aneuploidy

A committee of scientists was established by the U.S. Environmental Protection Agency to appraise the current state of aneuploidy test methodology, to compile and analyze published data on the chemical induction of aneuploidy, and to provide guidance for additional test development and validation. The reports that follow in this special issue of Mutation Research, document the urgent need for test method development and validation in this important area of environmental mutagenesis, and provide directions for further research.     

An evaluation of the mouse sperm morphology test and other sperm tests in nonhuman mammals. A report of the U.S. Environmental Protection Agency Gene-Tox Program

The literature on the mouse sperm morphology test and on other sperm tests in nonhuman mammals was reviewed (a) to evaluate the relationship of these tests to chemically induced spermatogenic dysfunction, germ-cell mutagenicity, and carcinogenicity, and (b) to make an interspecies comparison to chemicals. A total of 71 papers were reviewed. The mouse sperm morphology test was used to assess the effects of 154 of the 182 chemical agents covered. 4 other murine sperm tests were also used: the induction of acrosomal abnormalities (4 agents), reduction in sperm counts, (6 agents), motility (5 agents), and F1 sperm morphology (7 agents)). In addition, sperm tests for the spermatogenic effects of 35 agents were done in 9 nonmurine mammalian species; these included analyses for sperm count, motility, and morphology, using a large variety of study designs. For the mouse sperm morphology test, 41 agents were judged by the reviewing committee to be positive inducers of sperm-head shape abnormalities, 103 were negative, and 10 were inconclusive. To evaluate the relationship between changes in sperm morphology and germ cell mutagenicity, the effects of 41 agents on mouse sperm shape were compared to available data from 3 different mammalian germ-cell mutational tests (specific locus, heritable translocation, and dominant lethal). The mouse sperm morphology test was found to be highly sensitive to germ-cell mutagens; 100% of the known mutagens were correctly identified as positives in the sperm morphology test. Data are insufficient at present to access the rate of false positives. Although it is biologically unclear why one might expect changes in sperm morphology to be related to carcinogenesis, we found that (a) a positive response in the mouse sperm morphology test is highly specific for carcinogenic potential (100% for the agents surveyed), and (b) overall, only 50% of carcinogens were positive in the test (i.e., sensitivity approximately equal to 50%). Since many carcinogens do not produce abnormally shaped sperm even at lethal doses, negative findings with the sperm test cannot be used to classify agents as noncarcinogens. We conclude that the mouse sperm morphology test has potential use for identifying chemicals that induce spermatogenic dysfunction and perhaps heritable mutations. Insufficient numbers of chemicals agents have been studied by the other sperm tests to permit similar comparisons. A comparison of 25 chemicals tested with sperm counts, motility, and morphology in at least 2 species (including man, mouse and 9 other mammals) demonstrated good agreement in response among species. With further study, interspecies comparisons of chemically induced sperm changes may be useful for predicting and evaluating human effects.     

Cell transformation by chemical agents--a review and analysis of the literature. A report of the U.S. Environmental Protection Agency Gene-Tox Program

The literature on cell transformation by chemical carcinogens has been critically reviewed. This subject is highly relevant to carcinogenesis in vivo, because the phenotypic changes that are collectively referred to as cell transformation usually involve the acquisition of tumorigenicity on inoculation into suitable rodent hosts. The systems chosen for review fall into 3 categories: cell strains (cells with a limited lifespan); cell lines (cells with an unlimited lifespan); and oncogenic viral-chemical interactions involving cells (Fischer rat embryo cells expressing an endogenous retrovirus, mouse embryo cells expressing the AKR leukemia virus, chemical enhancement of a simian adenovirus, SA7 transformation of Syrian hamster or rat embryo cells). Of the entire literature reviewed, 117 papers have been accepted for data abstraction by pre-defined criteria; these include 41 references to cell strains, 40 in cell lines, and 38 in viral-chemical interactions including cells. Because different systems have been reviewed, it would be meaningless to group all the compounds. The overall summary of the systems is as follows (many compounds have been tested in more than one system and, hence, are duplicated in these totals). (Chart: see text) In general, there is a reasonably good correlation between the results of the cell transformation systems and in vivo carcinogenesis. However, the many deficiencies of the EPA Merged Carcinogen List preclude definitive comparisons. Moreover, a number of 'false negatives' were obtained in systems that did not employ external metabolic activation. Further validation of all systems is required, but it seems very probable that several cell transformation systems will become valuable in assaying (with reasonable time and cost) the carcinogenic potential of environmental chemicals.     

An evaluation of human sperm as indicators of chemically induced alterations of spermatogenic function. A report of the U.S. Environmental Protection Agency Gene-Tox Program

To evaluate the utility of sperm tests as indicators of chemical effects on human spermatogenesis, the literature on 4 sperm tests used to assess chemically induced testicular dysfunction was reviewed. The tests surveyed included sperm count, motility, morphology (seminal cytology), and double Y-body (a fluorescence-based test thought to detect Y-chromosomal nondisjunction). There were 132 papers that provided sufficient data for evaluation. These reports encompassed 89 different chemical exposures: 53 were to single agents; 14 to complex mixtures; and 22 to combinations of 2 or more identified agents. Approximately 85% of the exposures were to experimental or therapeutic drugs, 10% were to occupational or environmental agents, and 5% were to drugs for personal use. The most common sperm parameter studied was sperm count (for 87 of the 89 exposures reviewed). Sperm motility was evaluated for 59 exposures, morphology for 44, and double Y-bodies for only 4. The 89 exposures reviewed were grouped into 4 classes: those which adversely effected spermatogenesis, as measured by one or more of the sperm tests (52); those suggestive of improving semen quality (11); those showing inconclusive evidence of adverse effects from exposure (14); and those showing no significant changes (12). Since the reviewed reports had a large variety of study designs, and since every attempt was made to include all reports with interpretable data, these classifications were based on reviewing committee decisions rather than on uniform statistical criteria. This review gives strong evidence that human sperm tests can be used to identify chemicals that affect sperm production, but because of our limited understanding of underlying mechanisms, the extent to which they can detect mutagens, carcinogens or agents that affect fertility remains uncertain. For the very few agents studied with both human and mouse sperm tests, similar test-responses were seen; thus sperm tests in mice and other laboratory mammals may have a potential role in hazard identification. An overall comparison of the 4 human sperm tests suggests that no one test is biologically more responsive than another; all of them may thus be needed when testing for chemically induced changes from agents of unknown activity. This review also gives evidence that sperm tests can be used to assess the extent and the potential reversibility of induced spermatogenic damage. The reviewing committee recommends further studies to determine (a) the dose-response characteristics of the human sperm tests, (b) details of the reversibility of induced changes with time after exposure, (c) the relative responses in the 4 sperm tests in exposed individuals, (d) the mechanism of action, (e) the biological and genetic implications of chemically induced effects, and (f) the comparison of responses among different species for risk assessment. The reviewing committee outlines specific considerations for planning new sperm studies on chemically exposed men.     

The in vivo micronucleus assay in mammalian bone marrow and peripheral blood. A report of the U.S. Environmental Protection Agency Gene-Tox Program

The protocol recommended for the micronucleus assay in mammalian bone marrow has been revised and simplified. The number of sample times has been reduced to one or two, depending upon the dosing protocol. The minimum number of cells to be scored per treatment group has been increased to 20,000 to increase the ability of the assay to detect a doubling of the control micronucleus frequency. Use of both male and female animals is recommended. Scoring of micronuclei in polychromatic erythrocytes of peripheral blood is included as a variation of the bone marrow assay. Published data on chemicals tested by the micronucleus assay have been reviewed and are summarized.     

Association between Smoking and Latent Tuberculosis in the U.S. Population: An Analysis of the National Health and Nutrition Examination Survey

Background

Evidence of an association between cigarette smoking and latent tuberculosis infection (LTBI) is based on studies in special populations and/or from high prevalence settings. We sought to evaluate the association between LTBI and smoking in a low prevalence TB setting using population-based data from the National Health and Nutrition Examination Survey (NHANES).

Methods

In 1999–2000, NHANES assessed LTBI (defined as a tuberculin skin test measurement ≥10 mm) in participants, and those ≥20 years of age were queried regarding their tobacco use and serum cotinine was measured. We evaluated the association of LTBI with self-reported smoking history and smoking intensity in multivariable logistic regression models that adjusted for known confounders (gender, age, birthplace, race/ethnicity, poverty, education, history of BCG vaccination, and history of household exposure to tuberculosis disease).

Results

Estimated LTBI prevalence was 5.3% among those ≥20 years of age. The LTBI prevalence among never smokers, current smokers, and former smokers was 4.1%, 6.6%, and 6.2%, respectively. In a multivariable model, current smoking was associated with LTBI (OR 1.8; 95% CI, 1.1–2.9). The association between smoking and LTBI was strongest for Mexican-American and black individuals. In multivariate analysis stratified by race/ethnicity, cigarette packs per day among Mexican-American smokers and cotinine levels among black smokers, were significantly associated with LTBI.

Conclusions

In the large, representative, population-based NHANES sample, smoking was independently associated with significantly increased risks of LTBI. In certain populations, a greater risk of LTBI corresponded with increased smoking exposure.     

Chemical carcinogens. A review and analysis of the literature of selected chemicals and the establishment of the Gene-Tox Carcinogen Data Base. A report of the U.S. Environmental Protection Agency Gene-Tox Program

The literature on 506 selected chemicals has been evaluated for evidence that these chemicals induce tumors in experimental animals and this assessment comprises the Gene-Tox Carcinogen Data Base. Three major sources of information were used to create this evaluated data base: all 185 chemicals determined by the International Agency for Research on Cancer to have Sufficient evidence of carcinogenic activity in experimental animals, 28 selected chemicals bioassayed for carcinogenic activity by the National Toxicology Program/National Cancer Institute and found to induce tumors in mice and rats, and 293 selected chemicals which had been evaluated in genetic toxicology and related bioassays as determined from previous Gene-Tox reports. The literature data on the 239 chemicals were analyzed by the Gene-Tox Carcinogenesis Panel in an organized, rational and consistent manner. Criteria were established to assess individual studies employing single chemicals and 4 categories of response were developed: Positive, Negative, Inconclusive (Equivocal) and Inconclusive. After evaluating each of the individual studies on the 293 chemicals, the Panel placed each of the 506 chemicals in an overall classification category based on the strength of the evidence indicating the presence or absence of carcinogenic effects. An 8-category decision scheme was established using a modified version of the International Agency for Research on Cancer approach. This scheme included two categories of Positive (Sufficient and Limited), two categories of Negative (Sufficient and Limited), a category of Equivocal (the evidence of carcinogenicity from well-conducted and well-reported lifetime studies had uncertain significance and was neither clearly positive nor negative), and three categories of Inadequate (the evidence of carcinogenicity was insufficient to make a decision, however, the data suggested a positive or negative indication). Of the 506 chemicals in the Gene-Tox Carcinogen Data Base, 252 were evaluated as Sufficient Positive, 99 as Limited Positive, 40 as Sufficient Negative, 21 as Limited Negative, 1 as Equivocal, 13 as Inadequate with the data suggesting a positive indication, 32 as Inadequate with the data suggesting a negative indication, and 48 Inadequate with the data not suggesting any indication of activity. This data base was analyzed and examined according to chemical class, using a 29 chemical class scheme.(ABSTRACT TRUNCATED AT 400 WORDS)     

Health and wealth: The late-20th century obesity epidemic in the U.S.

Obesity is a rapidly growing public health issue. This paper investigates obesity's relationship to individuals' wealth by analyzing data from a large U.S. longitudinal socio-economic survey. The results show a large negative association between BMI and White female's net worth, a smaller negative association for Black women and White males and no relationship for Black males. Weight changes and dieting also appear associated with wealth changes. Individuals who lose small amounts of weight experience little change in net worth, but those who lose large amounts of weight have a dramatically improved financial position, with Whites showing larger changes than Blacks.     

A review and analysis of the Chinese hamster ovary/hypoxanthine guanine phosphoribosyl transferase assay to determine the mutagenicity of chemical agents. A report of phase III of the U.S. Environmental Protection Agency Gene-Tox Program

Published literature on the Chinese hamster ovary cell/hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT) assay from mid-1979 through June 1986 was reviewed and evaluated. Data from the papers considered acceptable include test results on 121 chemicals belonging to 25 chemical classes. A total of 87 chemicals were evaluated positive, 3 negative, and 31 inconclusive. Mutagenicity data on 49 of the 121 chemicals evaluated could also be compared with in vivo animal carcinogenicity data. 40 of the 43 reported animal carcinogens were considered mutagenic. Caprolactam, the only definitive noncarcinogen in the group of 49, was not mutagenic. The CHO/HGPRT assay was concluded to be an appropriate assay system for use in the screening of chemicals for genotoxicity.     

Biodiversity and community structure of temperate butterfly species within a gradient of human disturbance: An analysis based on the concept of generalist vs. Specialist strategies

We monitored nine butterfly communities with varying degrees of human disturbance by conducting a census twice a month during 1980 by the line transect method in and around Tsukuba City, central Japan. We analyzed the biodiversity and community structures using the generalist/specialist concept. The site (community) order based on decreasing human disturbance was positively correlated with butterfly species diversity (H′), species richness (the total number of species), and the number of specialist species in a community, but not with the number of generalist species. The number of generalist species was rather constant, irrespective of the degree of human disturbance. Thus, both the butterfly species diversity and species richness were more dependent on the specialists than the generalists. Our analyses also showed that the generalist species were distributed widely over the communities, and they maintained high population densities, resulting in high rank status in abundance in a community, with more spatial variation in density per species. Specialist species showed the opposite trends. These results demonstrate that the generalist/specialist concept is a powerful tool applicable to analyse the biodiversity and structure of natural communities.