Jason A. Tetro

Impact of changing societal trends on the spread of infections in American and Canadian homes

Infectious diseases continue to exert a heavy toll on human health even in industrialized countries. Recent data from the World Health Organization suggests that infectious diseases are the leading cause of death in the world. Many changing trends in our society have a known or potential impact on infectious disease spread and may have an impact on the normal routine of home hygiene. Important amongst these societal trends are increasing population and life expectancy, changes in urbanization, grouping of susceptibles, increased ambulatory and home care, increased immunosuppression, increased and faster travel, changes in technology, increasing antibiotic resistance as a result of misuse of antibiotics, changes in food and water consumption, and changes in personal cleaning, washing, and laundry practices. This review will highlight these factors and their impact on home hygiene and steps that may be needed to reduce the risk from infections.

Hygienic hand antiseptics: should they not have activity and label claims against viruses?

Abstract Enteric and respiratory viruses are among the most frequent causes of human infections, and hands play an important role in the spread of these and many other viral diseases. Regular and proper hand hygiene by caregivers and food handlers in particular is essential to decontaminate hands and potentially interrupt such spread. What would be considered a proper decontamination of hands? Handwashing with regular soap and water is often considered sufficient, but what of hygienic handwash and handrub antiseptic products? Are they more effective? The evidence suggests that some clearly are. Activity against bacteria may not reflect the ability of hygienic hand antiseptics to deal with viruses, especially those that are nonenveloped. In spite of the acknowledged importance of hands as vehicles for viruses, there is a lack of suitable regulatory mechanism for handwash or handrub products to make claims of efficacy against viruses. This is in contrast with the ability of general-purpose disinfectants to make antiviral claims, although transmission of viruses from surfaces other than those of reusable medical devices may play only a minor role in virus transmission. This review discusses the (1) recent information on the relative importance of viruses as human pathogens, particularly those causing enteric and respiratory infections; (2) the survival of relevant viruses on human hands in comparison with common gram-negative and gram-positive bacteria; (3) the potential of hands to transfer or receive such contamination on casual contact; (4) role of hands in the spread of viruses; (5) the potential of hygienic measures to eliminate viruses from contaminated hands; (6) relative merits of available protocols to assess the activity of hygienic hand antiseptics against viruses; and (7) factors considered crucial in any tests to assess the activity of hygienic hand antiseptics against viruses. In addition, this review proposes surrogate viruses in such testing and discusses issues for additional consideration by researchers, manufacturers, end-users, and regulators. (Am J Infect Control 2002;30:355-72)

Foodborne spread of hepatitis A: Recent studies on virus survival, transfer and inactivation.

Hepatitis A virus (HAV) is responsible for considerable morbidity and economic losses worldwide, and is the only reportable, foodborne viral pathogen in Canada. Outbreaks caused by it occur more frequently in settings such as hospitals, daycare centres, schools, and in association with foods and food service establishments. In recent years, the incidence of hepatitis A has increased in Canada. Many factors, including changing lifestyles and demographics, faster and more frequent travel, and enhanced importation of foods from hepatitis A-endemic regions, may be behind this increase. Despite its increasing significance as a human pathogen, not much was known until recently about the survival and inactivation of HAV, and even less was understood about the effectiveness of measures to prevent and control its foodborne spread. Studies conducted in the past decade have shown that HAV can survive for several hours on human hands and for several days on environmental surfaces indoors. The virus can also retain its infectivity for several days on fruits and vegetables which are often consumed raw, and such imported items have already been incriminated in disease outbreaks. Casual contact between contaminated hands and clean food items can readily lead to a transfer of as much as 10% of the infectious virus. HAV is also relatively resistant to inactivation by heat, gamma irradiation and chemical germicides. In view of these findings, better approaches to prevent the contamination of foods with HAV and more effective methods for its inactivation in foods, on environmental surfaces and on the hands of food handlers are needed.

In Vivo Comparison of Two Human Norovirus Surrogates for Testing Ethanol-Based Handrubs: The Mouse Chasing the Cat!

Human noroviruses (HuNoV), a major cause of acute gastroenteritis worldwide, cannot be readily cultured in the lab. Therefore, a feline calicivirus (FCV) is often used as its surrogate to, among other things, test alcohol-based handrubs (ABHR). The more recent laboratory culture of a mouse norovirus (MNV) provides an alternative. While MNV is closer to HuNoV in several respects, to date, no comparative testing of FCV and MNV survival and inactivation on human hands has been performed. This study was designed to address the knowledge gap. The rates of loss in viability during drying on hands were −1.91 and −1.65% per minute for FCV and MNV, respectively. When the contaminated skin was exposed for 20 s to either a commercial ABHR with 62% (v/v) ethanol or to 75% (v/v) ethanol in water, FCV infectivity was reduced by <1 log10 while that of MNV by nearly 2.8 log10. Extending the contact time to 30 s reduced the FCV titer by almost 2 log10 by both test substances and that of MNV by >3.5 log10 by the commercial ABHR while 75% ethanol did not show any noticeable improvement in activity as compared to the 20 s contact. An 80% (v/v) aqueous solution of ethanol gave only a 1.75 log10 reduction in MNV activity after 20 s. The results show significant differences in the ethanol susceptibility of FCV and MNV in contact times relevant to field use of ABHR and also that 62% ethanol was a more effective virucide than either 75% or 80% ethanol. These findings indicate the need for a review of the continuing use of FCV as a surrogate for HuNoV.

Ultrasensitive Norovirus Detection Using DNA Aptasensor Technology

DNA aptamers were developed against murine norovirus (MNV) using SELEX (Systematic Evolution of Ligands by EXponential enrichment). Nine rounds of SELEX led to the discovery of AG3, a promising aptamer with very high affinity for MNV as well as for lab-synthesized capsids of a common human norovirus (HuNoV) outbreak strain (GII.3). Using fluorescence anisotropy, AG3 was found to bind with MNV with affinity in the low picomolar range. The aptamer could cross-react with HuNoV though it was selected against MNV. As compared to a non-specific DNA control sequence, the norovirus-binding affinity of AG3 was about a million-fold higher. In further tests, the aptamer also showed nearly a million-fold higher affinity for the noroviruses than for the feline calicivirus (FCV), a virus similar in size and structure to noroviruses. AG3 was incorporated into a simple electrochemical sensor using a gold nanoparticle-modified screen-printed carbon electrode (GNPs-SPCE). The aptasensor could detect MNV with a limit of detection of approximately 180 virus particles, for possible on-site applications. The lead aptamer candidate and the aptasensor platform show promise for the rapid detection and identification of noroviruses in environmental and clinical samples.

Dysregulation of Cytokine Response in Canadian First Nations Communities: Is There an Association with Persistent Organic Pollutant Levels?

In vitro and animal studies report that some persistent organic pollutants (POPs) trigger the secretion of proinflammatory cytokines. Whether POP exposure is associated with a dysregulation of cytokine response remains to be investigated in humans. We studied the strength of association between plasma POP levels and circulating cytokines as immune activation markers. Plasma levels of fourteen POPs and thirteen cytokines were measured in 39 Caucasians from a comparator sample in Québec City (Canada) and 72 First Nations individuals from two northern communities of Ontario (Canada). Caucasians showed significantly higher levels of organochlorine insecticides (β-HCH, p,p′-DDE and HCB) compared to First Nations. Conversely, First Nations showed higher levels of Mirex, Aroclor 1260, PCB 153, PCB 170, PCB 180 and PCB 187 compared to Caucasians. While there was no difference in cytokine levels of IL-4, IL-6, IL-10 and IL-22 between groups, First Nations had significantly greater average levels of IFNγ, IL-1β, IL-2, IL-5, IL-8, IL-12p70, IL-17A, TNFα and TNFβ levels compared to Caucasians. Among candidate predictor variables (age, body mass index, insulin resistance and POP levels), high levels of PCBs were the only predictor accounting for a small but significant effect of observed variance (∼7%) in cytokine levels. Overall, a weak but significant association is detected between persistent organochlorine pollutant exposure and elevated cytokine levels. This finding augments the already existing information that environmental pollution is related to inflammation, a common feature of several metabolic disorders that are known to be especially prevalent in Canadas remote First Nations communities.

Experimental Evaluation of an Automated Endoscope Reprocessor With In Situ Generation of Peracetic Acid for Disinfection of Semicritical Devices

OBJECTIVE To evaluate the effectiveness of a high-level disinfection solution generated inside an endoscope processing system for decontaminating external and internal surfaces of experimentally contaminated heat-sensitive medical devices. METHODS The American Society for Testing and Materials Simulated-Use Test protocol (E1837-02), which incorporates a soil load in each inoculum, was used to evaluate the efficacy of the system when processing 4 common types of endoscopes contaminated separately with 5 types of nosocomial pathogens: Pseudomonas aeruginosa (ATCC 15442), spores of Clostridium difficile (ATCC 9689), a glutaraldehyde-resistant strain of Mycobacterium chelonae, a vancomycin-resistant strain of Enterococcus faecalis, and a methicillin-resistant strain of Staphylococcus aureus. Rinse solution samples from channels and from surfaces of the processed endoscopes were tested for any microbicidal residues. RESULTS For all organisms tested, the baseline level of contamination of the endoscopes ranged from 5 log(10) to greater than 7 log(10) at each external surface site and internal channel. All tests showed reductions in viability of the test organisms to undetectable levels. All rinse solution samples from external and internal sites of the endoscopes proved to be free of any residual microbicidal activity. CONCLUSIONS The endoscope reprocessor, with its processor-generated high-level disinfection solution, successfully reduced the numbers of selected, clinically relevant pathogens to undetectable levels both in the channels and on the outside surfaces of the 4 representative endoscopes tested in this study.

Environmental survival and microbicide inactivation of coronaviruses

Since their first isolation from chickens in 1937 [1], coronaviruses have proven to be significant pathogens of many types of wild as well as economically important domesticated animals.Though coronaviruses were first identified as human respiratory pathogens in 1965 [2], only recently, with their established link with the severe acute respiratory syndrome (SARS), has there been a sudden upsurge of interest in this group of viruses. Taxonomically, these enveloped, positive-sense RNA viruses [1] belong in the genus Coronavirus of the family Coronaviridae in the order Nidovirales [3]. To date, the genus contains some 14 members. Birds and mammals are the known hosts with a wide variety of species affected. In mammals, coronaviruses have been isolated from pigs, cattle, mice, rats, dogs, horses, cats, and humans [1], and in birds mainly from chickens [4] and turkeys [5]. Coronaviruses 229E and OC43 are recognized respiratory pathogens of humans. The causative agent of SARS (SARS-CoV), which has now been fully characterized [6], awaits its formal inclusion in the genus. Genomic studies show SARS-CoV to be unique as it contains elements of both mammalian and avian ancestry [7] and the effect of this recombination has been disastrous for humans. In the first recorded outbreak in 2003, the virus caused 8,461 clinical cases and 804 recorded deaths globally [8]. Fortunately, and in spite of its seemingly high mutation rates [9], the spread of the virus was effectively controlled, mainly through general public health measures and basic infection control practices. Nevertheless, the SARS incident has had a significant impact on human health and the global economy [10] and thus highlighted the need to better understand the modes and vehicles for its spread and proper means to interrupt its environmental transmission. Environmental survival and microbicide inactivation of coronaviruses

Epitope selection to male specific antigens for sex selection in swine

Immunological approaches to gender selection have been contemplated since the discovery of the family of male-specific H-Y antigens found only on the surface of male cells. H-Y antigens are able to elicit an immune reaction when cells or tissues from a male donor are grafted to a female recipient. We describe here the development and testing of an inexpensive approach using polyclonal antibodies against four specific H-Y outer membrane proteins male enhanced antigen 1 (MEA 1), male enhanced antigen 2 (MEA 2), sex determining region Y (SRY) and testis determining factor (TDF). Epitopes based on hydrophilic primary sequences of the proteins were synthesized, N-terminal biotin-labeled, linked to streptavidin and mixed with a Ribi adjuvant prior to immunization in rabbits. The antiserum was tested to determine affinity to swine spermatozoa using anti-motility, flow cytometry and motility and sedimentation chambers. Fluorescent microscopy and fluorescent in situ hybridization (FISH) was used to identify the percentage of motile spermatozoa that contained the Y chromosome. We found that the polyclonal antibodies had high affinity to the spermatozoa leading to a cessation of motility. Furthermore, the majority of these non-motile spermatozoa contained the Y chromosome. We conclude that the use of polyclonal antiserum against synthetic H-Y peptide antigens may be an inexpensive and simple means to inhibit the motility of swine spermatozoa bearing the Y chromosome.

Vaccines against Mycobacterium Tuberculosis: Exploring Alternate Strategies to Combat a Near-perfect Pathogen

Tuberculosis is a significant threat to human health, infecting nearly one third of the world’s population and causing over a million deaths per year. The need for an effective vaccine against tuberculosis is apparent however, the current vaccine has not been successful neither in the prevention nor recovery from infection. The pathogenesis of the causative agent, Mycobacterium tuberculosis has been extensively studied. The mechanisms of immune evasion and modulation that enable persistence of infection through subclinical latency and eventually active tuberculosis have been partially described. Many of these mechanisms are directly antagonistic to the intended benefit of vaccines, leaving a conundrum that has yet to be resolved. This review will first examine the nature of tuberculosis pathogenesis in the context of the immune response and outline the varied processes utilized by the bacterium to cause modulation. The review will also investigate other vaccination options that may overwhelm these microbial mechanisms or avert them entirely, allowing for the engagement of the immune response and clearance of the bacterium.