Hand Hygiene and Disease Prevention, Part II

Oct 1st, 2020

Robert Y. Lochhead, Ph.D., and Margaret Lochhead, University of Southern Mississippi, Hattiesburg, MS

Read this article in its entirety in the October 2020 digital edition. . .

Editor’s note: This second part in our series on hand hygiene provides a brief history of its evolution, considers the nature of viruses, explores hand hygiene protocols and describes the formulation of hand sanitizer gels and foams. Future parts will cover the efficacy of hand sanitizers, regulatory aspects, IP and litigation, and more. Follow along in our upcoming November issue. (See Part I and Part III).

Do Hand Sanitizers Work?

The antimicrobial efficacy of an ethanol-based hand sanitizer is shown in Table 1. Alcohol-based treatments are preferred because they generally act more rapidly than other antiseptics. They also spread rapidly over the skin and quickly evaporate to leave no residuals that could cause the emergence of multi-drug resistant microorganisms.^{68, 69} Moreover, after the alcohol has evaporated, the resident skin flora can be restored in a relatively short time. Alcohol-based sanitizers can be placed or carried almost anywhere for easy use and availability, which is more convenient than a permanently situated wash basin.

Hand sanitizer gels appeared in the late 20th century. The now-familiar gels were enabled by stimuli-responsive polymers^a, carbomer and acrylates C10-30 alkyl acrylate crosspolymer.^70-75

These polymers are cross-linked microgels that served to thicken hydroalcoholic solutions and confer shear-thinning rheology for facile dispensing. Upon contact with the hands, salt on the skin’s surface, as previously described, causes the microgels to immediately shrink to squeeze out fluid, sanitizing alcohol to spread and permeate the wrinkles, nooks and crannies on the hands. See this mechanism in action in a Video Demo on Page 39 of your digital edition. Ideally, a hand sanitizer should remove transient flora, especially pathogens; allow the resident skin flora (the microbiome) to recover; and should not compromise the skin barrier function.⁷⁶

Comparing the performance of plain soap and water with alcohol, it has been observed that washing with the former can physically remove adherent flora but it does not always remove all the pathogens. Moreover, the skin can become irritated by alkaline soap and the resulting lesions can become colonized by microorganisms. Furthermore, Gram-negative bacteria can colonize soap.

On the other hand, alcohol rubs have a long history of successful use in Europe. The U.S. Food and Drug Administration (FDA) lists alcohol rubs as eligible for evaluation under the FDA New Rule for Antiseptic products.⁷⁷ Alcohol hand rubs have excellent germicidal activity in vitro, including activity against Gram-positive and Gram-negative bacteria, and enveloped lipophilic viruses. The CDC/Healthcare Infection Control Practices Advisory Committee also states that alcohol hand rubs represent the standard of care for hand hygiene.⁷⁸

The World Health Organization (WHO) has a comprehensive set of guidelines for Hand Hygiene.⁷⁹ It is a tome, with 1,156 references and to reduce it to a single paragraph does not do it justice. However, I refer to this document to list one relevant set of WHO recommendations; specifically that hand hygiene protocols should:

• Compare the efficacy of products;

• Update the testing protocols and make them economically justifiable;

• Use realistic in vivo test models with appropriate test organisms and choice of subjects;

• Emphasize efficacy requirements rather than limiting goals to what is commercially available; and

• Design clinical studies for equivalence to meet a standard rather than compare products.

The WHO recommends two sanitizing hand rub formulas (see Formulas 1 and 2). It is surprising to see hydrogen peroxide and ethanol and glycerin together in these formulations because the peroxide would be expected to react with the alcohol and glycerin to reduce the efficacy of the formulation. Apparently, hydrogen peroxide and glycerol are included to eliminate bacterial spores during storage and to increase acceptability, and hydrogen peroxide is not an agent for antisepsis in these formulations.

These are non-thickened formulations. The WHO requires pharmacopoeial quality reagents because they are designed for the entire world and there is a need to be wary of unsafe contaminants. It is interesting that the WHO formulations do not meet the bacterial count log reductions in the time required by the European standards; the WHO formulations require 60 sec whereas the European standard mandates no more than 30 sec for the required log reduction of colony-forming units.

The WHO and also the CDC inform that efficacy cannot be judged merely by alcohol content but varies from formula to formula.⁸⁰ It is reasonable to conclude that the variability could be related to the availability of alcohol to penetrate all the cracks and creases of the hands, and may be reliant on the ability of the formula to release alcohol upon contact with the hands.

Alcohol Hand Rubs and Virucidal Activity

Pathogenic viruses on the hands can remain viable for hours^{81, 82} and transferral from hands is recognized as a potential mode of direct and indirect spread of infectious diseases.^83-85 Frequent hand-washing with water and soap can damage the skin barrier, however, and this can lead to a route of entry for SARS-CoV-2 (COVID -19) since the cell receptor for SARS-CoV-2 entry, angiotensin-converting enzyme 2, is abundant in blood vessels/capillaries of the epidermal basal layer, hair follicles and eccrine glands. There is thus a need to use suitable skin barrier prophylactics and therapeutics to ameliorate the damage caused by frequent hand-washing.⁸⁶

Alcohol-based hand sanitizers may be less damaging than frequent hand-washing with soap and water. In fact, the CDC’s guideline on hand hygiene documents that alcohol is more effective than soap and water, and that the in vivo antimicrobial activity of alcohol antiseptics shows a fast log reduction, recovery of the microbiome and activity against enveloped viruses—recall that coronaviruses are lipid-enveloped viruses.⁸⁷ Further studies are needed to find the minimum virucidal activity that interrupts cross-infection, however; in addition, alcohol is not sporicidal.

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