Biomedical subjects

C N Haas

Publications and source records attributed to C N Haas.

At least 19 recordsLinked to original sources

PubMed1999

Interaction between phenanthrene and zinc in their toxicity to the sheepshead minnow (Cyprinodon variegatus).

Many contaminated sites contain a variety of toxicants. Risk assessment and the development of water quality criteria therefore require information on the interactive effects among toxicants in such mixtures. Interactions between metals are relatively well studied, but little is known about interactions between metals and hydrocarbons. This study investigated the interaction between phenanthrene and zinc in the sheepshead minnow Cyprinodon variegatus. Interaction studies were performed with 7-day-old minnows in 96-h bioassays with zinc and phenanthrene at a fixed ratio and with varying proportions of zinc and phenanthrene. Mixture toxicity was quantified with the toxic unit, additive index, and excess function methods. All three methods generally indicated an antagonistic interaction between phenanthrene and zinc, though the results also provide some evidence for a synergistic interaction at low toxicant levels or at specific phenanthrene-to-zinc ratios. Short-term uptake experiments were conducted to determine if the strong antagonistic interaction observed when zinc and phenanthrene were present at 50% of their LC50 values was due to effects of zinc and phenanthrene on each other's uptake. Significantly less 65Zn uptake occurred in the presence of phenanthrene than in its absence. In contrast, zinc did not appear to affect the uptake of 14C-phenanthrene.http://link. springer-ny.com/link/service/journals/00244/bibs/37n2p251.++ +html

Animals↗

PubMed1999

A risk assessment framework for the evaluation of skin infections and the potential impact of antibacterial soap washing.

Antibacterial soaps may have an important role in the control of skin infection. However, quantitative estimation of their benefit is difficult because of the problems associated with conducting epidemiologic studies. An alternative benefit estimation approach, quantitative microbial risk assessment, has application to this problem. This article sets forth the quantitative microbial risk assessment method and applies it specifically to the estimation of the reduction in risk of dermal infection from Staphylococcus aureus resulting from use of antibacterial soaps. A dose-response model was formulated by using available information on growth kinetics of the organism on the skin and dose data based on the inoculation of the forearm skin in volunteers. A predictive relationship for microbial growth on the skin was developed. These data were limited, and clearly more studies are needed on inoculation at more than one site and growth leading to infection on the skin with and without the use of germicidal soaps.However, by using relationships based on extant data sets, it was estimated that the use of germicidal soap could result in a substantial reduction in the risk of infection by S aureus. The estimated risk reduction was in general concordance with published results from epidemiologic studies conducted on military cadets. The methodology of quantitative microbial risk assessment has thus been shown to be applicable to this problem and may have broader applicability in other personal hygiene contexts.

Adult↗

PubMed1999

Use of quantitative microbial risk assessment for evaluation of the benefits of laundry sanitation.

The goal of this study was to evaluate the risk assessment process for quantifying the contribution of contamination in the home to microbial infections. Whereas risks of enteric pathogens spread through food has been assessed, the spread of fecal-oral pathogens through surfaces likely at low rates would be difficult to address through epidemiologic studies. An alternative is quantitative risk assessment. The 4-step process of hazard identification, dose-response, exposure assessment, and risk characterization can be used; however, exposure assessment may follow a complicated pathway consisting of survival and transference. Microbial hazards in the home have focused primarily on enteric bacteria. Dose-response data are available; however, the transfer from the hands to the dose is uncertain. Through day care studies, Shigella has been shown to be transferred in this manner, and a dose-response model is available. By using these data and information on the transference of bacteria between clothing and hands, risk estimates were made for contaminated laundry. Risks were calculated as high as 10 per million population to much lower levels associated with lower excretion rates of the bacteria in the feces. Approximately a 90% and 99% reduction in the probability of disease through laundering and use of a sanitizing detergent, respectively, were suggested by the models. Better data are needed on incidence of disease in the population, excretion rates over the course of an infection, amount of feces spread in the home, distribution of bacteria, survival, and the transfer of the bacteria from surfaces to the hands and to the mouth.

Clothing↗

PubMed1999

On modeling correlated random variables in risk assessment.

Monte Carlo methods in risk assessment are finding increasingly widespread application. With the recognition that inputs may be correlated, the incorporation of such correlations into the simulation has become important. Most implementations rely upon the method of Iman and Conover for generating correlated random variables. In this work, alternative methods using copulas are presented for deriving correlated random variables. It is further shown that the particular algorithm or assumption used may have a substantial effect on the output results, due to differences in higher order bivariate moments.

Algorithms↗

PubMed1999

Dose response models for infectious gastroenteritis.

When pathogenic microorganisms enter the human body via ingestion with food or drinking water, they encounter a system of barriers mounted by the host. In order to reach parts of the intestinal tract that are suitable for growth and attachment, each of the barriers must be overcome successfully. The present view on infection states that at least one of the ingested pathogens must survive to start colonization. This is the basis for dose response models, used for quantitative risk assessment. In this paper, the usefulness of the Beta Poisson model for multiple barriers is corroborated. Infection is associated with the presence of elevated numbers of reproducing pathogens in the intestinal tract. This does not necessarily imply illness symptoms: when intestinal microorganisms engage in damaging activities, this may lead to illness symptoms. At the same time, these activities probably elicit defensive measures from the host, promoting the removal of pathogens and terminating infection. The duration of the period of colonization reflects the balance between the colonization potential of pathogens and the strength of host defenses. Starting from the assumption that during infection the host has a certain hazard of becoming ill, a simple dose response relation for acute gastroenteritis is developed. With the use of literature data from volunteer experiments, we show that examples can be found for three possible alternatives: an increase in the probability of illness with increasing dose, a decrease with higher doses, and a probability of illness (given infection) independent of the ingested dose. These alternatives may reflect different modes of interaction between pathogens and host.

Animals↗

PubMed1999

Semi-quantitative characterization of electroporation-assisted disinfection processes for inactivation of Giardia and Cryptosporidium.

The effect of electroporation (very short duration pulses of high voltage electricity) on the viability of Giardia cysts and Cryptosporidium oocysts, and on the viability of these organisms in the presence of free chlorine, combined chlorine, hydrogen peroxide and potassium permanganate, was examined. While electroporation itself had only a minor effect on survival, the combination of electrical and chemical treatment produced superior inactivation, particularly with combined chlorine, hydrogen peroxide and potassium permanganate. This enhancement may provide a relatively practical way of achieving enhanced inactivation of resistant protozoa by water disinfection processes. Further study of kinetics and optimum treatment combinations is needed.

Animals↗

PubMed1998

Risk assessment of waterborne protozoa: current status and future trends.

Throughout the past decade much research has been directed towards identifying the occurrence, epidemiology, and risks associated with waterborne protozoa. While outbreaks are continually documented, sporadic cases of disease associated with exposure to low levels of waterborne protozoa are of increasing concern. Current methodologies may not be sensitive enough to define these low levels of disease. However, risk assessment methods may be utilised to address these low level contamination events. The purpose of this article is to provide an introduction to microbial risk assessment for waterborne protozoa. Risk assessment is a useful tool for evaluating relative risks and can be used for development of policies to decrease risks. Numerous studies have been published on risk assessment methods for pathogenic protozoa including Cryptosporidium and Giardia. One common notion prevails: microbial risk assessment presents interesting complications to the traditional chemical risk assessment paradigm. Single microbial exposures (non-threshold) are capable of causing symptomatic illness unlike traditional chemical exposures, which require a threshold to be reached. Due to the lack of efficient recovery and detection methods for protozoa, we may be underestimating the occurrence, concentration and distribution of these pathogenic micro-organisms. To better utilize the tool of microbial risk assessment for risk management practices, future research should focus in the area of exposure assessment.

Animals↗

PubMed1997

Risk assessment of opportunistic bacterial pathogens in drinking water.

This study was undertaken to examine quantitatively the risks to human health posed by heterotrophic plate count (HPC) bacteria found naturally in ambient and potable waters. There is no clear-cut evidence that the HPC bacteria as a whole pose a public health risk. Only certain members are opportunistic pathogens. Using the four-tiered approach for risk assessment from the National Academy of Sciences, hazard identification, dose-response modeling, and exposure through ingestion of drinking water were evaluated to develop a risk characterization, which estimates the probability of infection for individuals consuming various levels of specific HPC bacteria. HPC bacteria in drinking water often include isolates from the following genera: Pseudomonas, Acinetobacter, Moraxella, Aeromonas, and Xanthomonas. Other bacteria that are commonly found are Legionella and Mycobacterium. All these genera contain species that are opportunistic pathogens which may cause serious diseases. For example, the three nonfermentative gram-negative rods most frequently isolated in the clinical laboratory are (1) Pseudomonas aeruginosa, (2) Acinetobacter, and (3) Xanthomonas maltophilia. P. aeruginosa is a major cause of hospital-acquired infections with a high mortality rate. Aeromonas is sometimes associated with wound infections and suspected to be a causative agent of diarrhea. Legionella pneumophila causes 4%-20% of cases of community-acquired pneumonia and has been ranked as the second or third most frequent cause of pneumonia requiring hospitalization. The number of cases of pulmonary disease associated with Mycobacterium avian is rapidly increasing and is approaching the incidence of M. tuberculosis in some areas. Moraxella can cause infections of the eye and upper respiratory tract. The oral infectious doses are as follows in animal and human test subjects: P. aeruginosa, 10(8)-10(9); A, hydrophila, > 10(10); M. avium, 10(4)-10(7); and X. maltophilia, 10(6)-10(9). The infectious dose for an opportunistic pathogen is lower for immunocompromised subjects or those on antibiotic treatment. These bacteria have been found in drinking water at the following frequencies: P. aeruginosa, < 1%-24%; Acinetobacter, 5%-38%; X. maltophilia, < 1%-2%; Aeromonas, 1%-27%; Moraxella, 10%-80%; M. avium, < 1%-50%; and L. pneumophila, 3%-33%. These data suggest that drinking water could be a source of infection for some of these bacteria. The risk characterization showed that risks of infection from oral ingestion ranged from a low of 7.3 x 10(-9) (7.3/billion) for low exposures to Aeromonas to higher risks predicted at high levels of exposure to Pseudomonas of 9 x 10(-2) (98/100). This higher risk was only predicted for individuals on antibiotics. Overall, the evidence suggests that specific members of HPC bacteria found in drinking water may be causative agents of both hospital- and community-acquired infections. However, the case numbers may be very low and the risks represent levels generally less than 1/10,000 for a single exposure to the bacterial agent. Future research needs include (1) determining the seasonal concentrations of these bacteria in drinking water, (2) conducting adequate dose-response studies in animal subjects or human volunteers, (3) determining the health risks for an individual with multiple exposures to the opportunistic pathogens, and (4) evaluating the increase in host susceptibility conferred by antibiotic use or immunosuppression.

Acinetobacter↗

PubMed1997

Generalization of independent response model for toxic mixtures.

Interaction between toxic compounds has long been known to researchers. Attempts to model this interaction have been based on two basic paradigms--termed additivity and independence (1, 2). Previous models based on these assumptions focused on measuring the interaction between the compounds and then classifying the type of interaction as synergism, antagonism, additivity or independence (3, 4). The aim of this work is to present a generalization of the independent action hypothesis that is quantitatively capable of describing deviations regardless of the underlying single component dose response models. The mathematical framework of copulas is employed. This approach is then tested against data sets with both human health and ecological risk applications.

Animals↗

PubMed1996

Prevalence of shigellosis in the U.S.: consistency with dose-response information.

Every year there are estimated 300000 cases of Shigella in the United States (Bennett et al., 1987, Am. J. Prev. Med. 3, 102-114). A beta-poisson model was fit to human dose-response information on pathogenic Shigella using the Maximum Likelihood Estimation technique (Haas, 1983, Am. J. Epidemiol. 118, 573-582). Pooled and separate data sets for the Shigella species were fit to the beta-Poisson model and 95% confidence limits and regions were calculated. Shigella dysentariae and Shigella flexneri confidence regions and limits overlapped with each other and with the pooled data set, suggesting that this model can describe Shigella in general. The pooled Shigella model as well as the upper and lower confidence limits of the three data sets showed average exposures based on the estimated U.S. caseload of pathogenic Shigella of 0.01 to 0.014 organisms (confidence limits 0.001-0.05) for a 7-day per annum period of exposure and ranges from 0.07 to 0.1 organisms (confidence limits 0.006-0.4). for a 1-day per annum period of exposure. The plausibility of the pooled dose-response model was then evaluated by comparison with two known cruise ship outbreaks. The pooled model estimated that the two outbreaks studied could have been due to ingestion of 344 (confidence limits 72-915) Shigella cells per meal and 10.5-12 (confidence limits 1-44) Shigella cells per glass of water by passengers.

Dysentery, Bacillary↗

PubMed1996

Assessment of the dose-response relationship of Campylobacter jejuni.

Mathematical relations describing the risk of infection after exposure to enteropathogens are important tools for the evaluation of the potential health risk from exposure via food and water. A quantitative description of the dose-response relation for Campylobacter jejuni with the Beta-Poisson model was fitted to experimental data of infection with Campylobacter jejuni (as determined by shedding of C. jejuni) obtained in human feeding studies performed by Black et al. (1988). The maximum likelihood estimates for the Beta-Poisson model parameters based on these data are: alpha = 0.145 and beta = 7.59. The fit of the model on the experimental data was good: the difference between the likelihood obtained with the Beta-Poisson model and the maximum possible likelihood was not significant. The occurrence of symptoms of intestinal illness did not follow a similar dose-related trend. Overall, 22% of the infected volunteers developed symptoms (diarrhea, fever). The highest illness-to-infection ratio was found at an intermediate dose (9 x 10(4)). The dose-response relation and the illness-to-infection ratio appeared to differ between different C. jejuni isolates. The dose-response relation derived from feeding studies with a single isolate should therefore be considered indicative. The absence of experimental data in the low dose range resulted in a relatively large confidence interval at low doses. However, in cases where the dose-response relation has been applied so far to estimate the health risk of exposure to C. jejuni in water, the uncertainty in the dose-response relation was insignificant compared to the uncertainty in the exposure estimate.

Campylobacter Infections↗

PubMed1996

Sensitive populations: who is at the greatest risk?

The purpose of this article was to review the existing literature to define those groups of individuals who would be at the greatest risk of serious illness and mortality from water and foodborne enteric microorganisms. This group was found to include the very young, the elderly, pregnant women, and the immunocompromised. This segment of the population currently represents almost 20% of the population in the United States and is expected to increase significantly by the beginning of the next century, because of increases in life-span and the number of immunocompromised individuals. More than half of documented deaths from gastroenteritis and hepatitis A illness occur in the elderly in developed countries. The overall case fatality ratio for foodborne bacterial gastroenteritis outbreaks in nursing homes is 10 times greater than the general population. Pregnant mothers suffer from a case fatality ratio from hepatitis E infections ten times greater than the general population during waterborne disease outbreaks. Enteric diseases are most common and devastating among the immunocompromised. Cryptosporidium is a serious problem among patients with acquired immuno-deficiency syndrome (AIDS). Cancer patients undergoing chemotherapy and transplant patients, are also at significantly greater risk of dying from enteric viral infections than the general population. This review indicates the need for consideration of enhanced protection for certain segments of the population who will suffer the most from food and waterborne pathogens.

AIDS-Related Opportunistic Infections↗

PubMed1994

Dose-response analysis using spreadsheets.

The task of fitting dose-response models to experimental data can be performed using a spreadsheet with a built-in optimization engine. This paper shows how the task of point and interval estimation can be performed using Microsoft EXCEL. A case study is presented on the carcinogenic dose-response behavior of chloroform.

Animals↗

PubMed1993

Risk assessment of virus in drinking water.

The reevaluation of drinking water treatment practices in a desire to minimize the formation of disinfection byproducts while assuring minimum levels of public health protection against infectious organisms has caused it to become necessary to consider the problem of estimation of risks posed from exposure to low levels of microorganisms, such as virus or protozoans, found in treated drinking water. This paper outlines a methodology based on risk assessment principles to approach the problem. The methodology is validated by comparison with results obtained in a prospective epidemiological study. It is feasible to produce both point and interval estimates of infection, illness and perhaps mortality by this methodology. Areas of uncertainty which require future data are indicated.

Epidemiologic Methods↗

PubMed1991

Risk assessment and control of waterborne giardiasis.

BACKGROUND: Waterborne giardiasis has been increasing in the United States with 95 outbreaks reported over the last 25 years. The Safe Drinking Water Act has mandated control of this pathogen. METHODS: A risk assessment model was developed to estimate risk of infection after exposure to treated waters containing varying levels of Giardia cysts. The model was defined by a dose-response curve developed from human feeding studies for Giardia and assumed 2L of water consumption per day. Data on concentrations and distribution of the organism in source waters were used to assess exposure after varying reductions achieved through treatment. RESULTS: In surveys reporting prevalence and levels of Giardia cyst contamination, average levels of cysts in surface waters ranged from 0.33 to 104/100L; from pristine watersheds (protected from all human activity) 0.6 to 5/100L. Yearly risks were 4.8 x 10(-3) for systems using polluted waters and 1.3 x 10(-4) for pristine waters with a 10(-3) treatment reduction. CONCLUSION: Public Health officials will need to work with the water industry to ensure a risk of less than 1/10,000 for source waters with 0.7 to 70 cysts per 100 liters through treatment achieving reduction of 10(-3) to 10(-5), respectively, of Giardia cysts.

Agriculture↗

PubMed1989

Estimation of microbial densities from dilution count experiments.

Although dilution counts have been widely used in quantitative microbiology, their interpretation has always been widely discussed both in microbiology and in applied statistics. Maximum-likelihood (most-probable-number) methods hae generally been used to estimate densities from dilution experiments. It has not been widely recognized that these methods are intrinsically and statistically biased at the sample sizes used in microbiology. This paper presents an analysis of proposed method for correction of such biases, and the method was found to be robust for moderate deviations from Poisson behavior. For analyses at greater variance with the Poisson assumptions, the use of the Spearman-Karber method is analyzed and shown to yield an estimate of density of lesser bias than that produced by the most-probable-number method. Revised methods of constructing confidence limits proposed by Loyer and Hamilton (M.W. Loyer and M.A. Hamilton, Biometrics 40:907-916, 1984) are also discussed, and charts for the three- and four-decimal dilution series with five tubes per dilution are presented.

Colony Count, Microbial↗

PubMed1988

Test of the validity of the Poisson assumption for analysis of most-probable-number results.

A test of the validity of the Poisson assumption for sample replicates in dilution series of finite length is proposed and its properties are examined by using Monte Carlo simulation. The test is based on an examination of the number of intervals between complete sterility and complete infection in a series. The test is applied to a data set of routine influent coliform samples at the Chicago water supply intake. By this test, the data set is rejected as being drawn from a Poisson replication. Tables for direct application to a 3-dilution, 5-tube decimal series are presented, and their application is illustrated.

Colony Count, Microbial↗

PubMed1988

Averaging of TNTC counts.

When plate count methods are used for microbial enumeration, if too-numerous-to-count results occur, they are commonly discarded. In this paper, a method for consideration of such results in computation of an average microbial density is developed, and its use is illustrated by example.

Bacteria↗