Antibiotic resistance, the hygiene hypothesis - and the need for targeted hygiene

1. Antibiotic resistance, the hygiene hypothesis - and the need for targeted hygiene Sally Bloomfield Chairman and Scientific Advisory Board Member, IFH Hon. Professor, London School of Hygiene and Tropical Medicine

2. In the last 10-15 years hygiene has moved up the health agenda What has brought about the change ? • Food borne disease remains at unacceptably high levels • Person-to-person tranmsission is now seen a significant cause of spread of infectious intestinal & respiratory diseases • Antibiotic resistant strains - need to prevent spread • Viral agents - not treatable with antibiotics • Ongoing emergence of new hazardous agents e.g SARS • “at risk” groups in the home and community: • elderly, very young, immune-compromised • up to 1 in 7 people in US belong to an “at risk” group Good hygiene practice is key to reducing these risks - in many cases the first line of defence

3. “Too much hygiene” is bad for you ? • Lack of exposure to germs may be correlated with increased atopic disease? • lack of exposure to germs may be “weakening “ our immune system? • Biocide use is linked to development of “superbugs”? • Disinfectants harm the environment • Soap and water is all you need; disinfectants/ antibacterials don’t work

4. The International Scientific Forum on Home Hygiene (IFH) www.ifh-homehygiene.org • A not-for-profit, non-governmental organisation comprising scientists & healthcare professionals • Primary objectives: • Raise awareness of the fundamental role of hygiene in infectious disease prevention • Promote understanding of good hygiene practice in the home, based on scientific evidence • Target Audience: • Public health scientists, opinion formers, health professionals, community workers, public society

5. The International Scientific Forum on Home Hygiene (IFH) • Activities include: • detailed review of scientific literature on home hygiene • formulations of Guidelines on home hygiene • IFH covers all aspects of hygiene • food and water hygiene, handwashing, laundry, • care of the elderly, very young, at risk groups www.ifh-homehygiene.org

6. In this presentation we will examine: Biocides and antibiotic resistance The hygiene hypothesis The “targeted approach to home hygiene”

7. Biocides and antimicrobial resistance

8. Antimicrobial resistance and biocide use The problem: • Although inappropriate prescribing of antibiotics is main cause of antibiotic resistance • concern that biocide use could be a contributory factor • Proliferation of antibacterial consumer products has “fuelled” these concerns

9. A number of factors need to be considered: • Lab studies indicate possible relationship between biocide exposure and reduced susceptibility to antimicrobial agents - but • “Reduced susceptibility” does not necessarily mean “resistance” • “Reduced susceptibility” demonstrated in the lab does not necessarily mean resistance in clinical practice • Lab studies indicate several possible physiological mechanisms which might operate to link antibiotic resistance to biocide usage

10. 1. Multidrug efflux pumps • Reduced susceptibility to antibiotics can occur through expression of efflux pumps by the bacteria: • Lab expts showed that exposure to a pine oil biocide selected mutants deficient in multidrug efflux pumps - and reduced susceptibility to tetracycline, ampicillin etc • However so-called “resistance” was low level - unlikely to cause failures in clinical practice • efflux pumps are up-regulated by a whole range of agents: • a significant number of foods and household products act as inducers of efflux pumps • But - mutants with low level resistance could be precursors to mutants c. high level resistance

11. 2. Multiresistance through shared targets • Antibiotics have single specific target sites of action • Some biocides have similar specific target sites • e.g biocide triclosan targets enoyl reductase enzyme in E.coli • antibiotic isoniazid targets same enzyme in M. smegmatis • This gives the possibility that persistent exposure to triclosan could select mutant populations which are clinically resistant to isoniazid • Unlikely to apply to the oxidising biocides, alcohol etc which have non selective action i.e non-specific target site

12. In practice • No evidence of link between biocide usage and antibiotic resistance in clinical practice • Occurrence of antibiotic resistant isolates from homes much lower than for clinical isolates from hospital ICU and outpatient settings (Rutala 2000) • Household use of antibacterial cleaning products for 1 year is not a significant risk factor for occurrence of antibiotic resistant isolates from hands (Aiello et al. 2005) • No evidence of antibacterial and antibiotic cross resistance in isolates from homes of users and non users of antibacterial products (Cole et al. 2003) • Whilst biocide usage in hospitals has declined in the last 50 years, antibiotic resistance has increased

13. However • The jury is still out ? • A number of recent studies indicate how little we no about the emergence and decline in antimicrobial resistant population in the environment

14. Consensus Recommendations of the IFH • Biocides should be used prudently not indiscriminately • Biocides should be selected as appropriate to: • Give rapid/effective inactivation of micro-organisms • Avoid build-up of residues which might encourage selection of resistant strains • If biocides contribute to preventing infectious disease: • biocide use could actually reduce the impact of antibiotic resistance by reducing need for antibiotic prescribing

15. Could hygiene undermine immunity to infectious disease or promote atopic disease

16. What is the hygiene hypothesis ? • Postulated in 1989 by Strachan: • “a lower incidence of infection in early childhood, transmitted by aunhygienic contact with older siblings could be a cause of the rapid rise in the atopic disorders over the last 30 - 40 years” • Strachan also proposed: • “the reason why this exposure no longer occurs --- is not only because of the trend towards smaller families, but also “improved household amenities and higher standards of personal cleanliness”. Infection: colonisation or clinical infection? “Hygiene” hypothesis “hygiene” or “cleanliness”? We’ve become too clean for our own good?

17. Hygiene hypothesis involves 2 separate questions: • Is there a link between reduced microbial exposure and the recent rises in atopic disease ? • Is cleaning and hygiene, as opposed to other influences on microbial exposure, a significant factor?

18. 1. The link between atopy, and microbial exposure and infection • Some studies provide striking evidence supporting a causal link between atopy and microbial exposure: • inverse relationship between atopy and family size, • inverse relationship between atopy and birth order. • Protective effect for children brought up on a farm. • But • these are proxy measures of infection • there are also numerous contradictory studies • Overall the evidence remains inconclusive

19. Is exposure to infection the key factor ? This seems unlikely because: • Decline in serious infections (cholera, typhoid, TB, measles, HAV) occurred too early to be associated with the late 20th century rise in atopic disease. • Incidence of food poisoning rose during the critical period of the rise in atopy • No evidence of a decline across the broad range of gastro-intestinal, respiratory and other common infections. • Findings of a recent study in Denmark • confirm correlation with larger family sizes, farm living etc • but data suggests ID in early life is associated with increased, rather than reduced, risk of atopic dermatitis. .

20. Is background exposure to commensals or environmental strains the key? • Rook (2004) proposes that • the causative factor is decreased exposure to harmless environmental microbes continuously present throughout mammalian evolution. • saprophytic mycobacteria, helminths and lactobacilli are recognised by the immune system as harmless, but act as adjuvants for immune regulation. • The protective effect of farm living is consistent with the possibility that ‘background exposure’ from our outdoor environment is a factor. • Clinical studies using mycobacterial vaccines developed for treatment of atopic diseases have produced some promising initial results

21. 2. Is there a link to modern trends in home cleanliness and hygiene? Evidence of link with domestic hygiene is weak. • Modern homes, however “clean”, contain a rich mix of bacteria, viruses, fungi, dust mites etc • Pathogens, commensal and environmental microbes continuously brought into the home via humans, animals, food etc. • Transfer via hands, surfaces & cloths during normal daily activities • European trends of increased use of cleaning products show no temporal correlation with atopy trends • Routine daily/weekly cleaning has little effect in reducing exposure, even using disinfectants - re-colonisation of surfaces rapidly occurs • Compliance with “hygiene” practices is poor Overall data suggest that we are regularly exposed to pathogens, commensals and environmental microbes.

22. Is there a link to personal cleanliness ? • UK study (ALSPC study) suggests a possible link to personal hygiene • study showed a relationship between “hygiene scores” and atopy in young children • parents were “scored” according to: • how often in a day they wiped the child’s face and hands • how often the child was given a bath or shower • Trends towards more frequent showering and bathing show a temporal correlation with the rise in atopy ? • This aspect requires further investigation • Sherriff A, Golding J. Hygiene levels in a contemporary population cohort are associated with wheezing and atopic eczema in preschool children. Archives Diseases of Children 2002; 87(1):26-9.

23. Consensus view - the hygiene Hypothesis • Substantial evidence of a link between microbial exposure and atopy • but we need to better understand the nature of the critical changes in microbial exposure that might have occurred • types of microbes, life stage, route of exposure etc • Evidence of a link to general cleanliness and hygiene poor • Some evidence of a link to routine personal hygiene - bathing, showering • Need to rename it as the “microbial exposure hypothesis” Also need to bear in mind: • Other medical/ public health trends could be the cause • changes in non-pathogen content of water or foods consequent on changing technologies of water purification and food production • Introduction of antibiotics and vaccines

24. It may not be related to microbial exposure at all ? • significant evidence supporting a range of ‘non-microbial’ factors, such as diet/nutrition, obesity and lack of exercise which may be causative factors in the rise in atopy.

25. Developing a rational approach to home hygiene- a risk-based approach

26. A risk assessment approach to home hygiene • In recent years the concept of HACCP (Hazard Analysis Critical Control Point) - identifying critical points and targeting hygiene at these risk points has successfully controlled microbial risks in food and other manufacturing environments • To devise a hygiene policy which has real health benefits it is accepted that a risk-based approach must also be developed for the home

27. IFH approach to home hygiene • For IFH the “risk assessment” or HACCP approach to home hygiene has come to be known as the “targeted hygiene” • “Targeted hygiene” mean identifying situations where there is a significant risk of spread of harmful microbes, and intervening at the appropriate time to prevent spread

28. Developing a risk assessment approach to home hygiene • Pathogens (or potential pathogens) are introduced continually into the home via: people, food, pets, water, insects • Also -sinks, sink and basin U-tubes, toilets, wet cleaning cloths can support growth of harmful microbes (mainly opportunist but also some primary pathogens) and become a primary source of infection.

29. Developing a risk assessment approach to home hygiene • To be effective home hygiene policy based on risk assessment must consider: • Hazard identification including dose response assessment - probability of contamination c. harmful microbes - infective dose • Exposure assessment - probability of transfer/cross contamination- such that human exposure could result

31. Good hygiene is not about “creating a germ free home” but about identifying high risk sites and situations and targeting hygiene measures appropriately (i.e as and where necessary) to reduce exposure to microbes which could be harmful

32. Hygiene procedures in the home - reducing the risks

33. What do we mean by “hygienic cleaning” • The purpose of a hygiene procedure (hygienic cleaning) is to reduce microbial contamination on a surface (hands or other surface or site) to a level which is not harmful to health

34. What do we mean by “hygienically clean” “a level of germs which is not harmful to health” But • infectious dose varies: • viruses: 1-100 particles • bacteria: may be 10 --> as high as 106 • Salmonella: amplified following transfer to food • depends on the susceptibility - may be lower for “at risk” groups • Without precise data it seems reasonable that : • where there is significant risk of germs spreading (e.g. during food preparation) • aim should be to get rid of as many germs as possible

35. What methods are available for “hygiene cleaning” • A hygienically (as opposed to visibly) clean surface is achieved either by removal of microbes or application of a disinfection process or a combination of both:

36. What methods are available for “hygiene cleaning” Detergent-based hygienic cleaning • In many situations - hands, cooking/ eating utensils, hygiene achievable using detergent-based cleaning. • To be effective it must be applied in conjunction with a thorough rinsing process - to wash germs away from the surface Disinfection • Alternatively “germ kill” can be used - chemical disinfectant products - heat (e.g boiling or >60°C) or: Combined removal and kill - laundry - removal, heat and bleach kill - dishwashing - removal, heat kill

37. In deciding whether “soap and water” is the appropriate hygiene procedure or whether a disinfectant is needed - need to consider: • Can you “wash” the germs away? • Large surface, taps, biofilms ? • Have you washed the germs away? • “In homes” studies suggest that this is sometimes not the case - in some situations e.g food hygiene the extra margin of safety from use of disinfectants is advisable • Where have the germs gone ? • Contaminated water, particularly c. a cloth is highly effective means of spreading pathogens

38. Food hygiene - risks associated with preparation of a meal using a chicken contaminated with Salmonella or Campylobacter Cogan, Bloomfield and Humphries, Letters in Appl.Microbiology 1999, 29,354-358

39. UK data indicates: • 25% and 83% of raw chickens contaminated c.Salmonella and Campylobacter(Jorgensen et al. 2002). • Every day 1 in 25 homes prepare a meal with a Salmonella and/or Campylobacter-contaminated chicken • 0.4% and 0.8% of beef & lamb products from retail butchers are +ve for E. coli O157 (Chapman et al. 2001)

40. General hygiene - effectiveness of hygiene procedures in eliminating norovirus from surfaces (N = 14) Barker, Vipond and Bloomfield, J. Hospital Infection 2004, 58, 42-49 Surfaces soiled with faeces/norovirus Contaminated cloth used to wipe a clean surface

41. Key concepts of targeted hygiene • Current concept of home hygiene: • People still largely see home hygiene as a process of "getting rid of household germs" - believing that this is the appropriate means to protect their family against infection. • we need to promote the concept of “targeted hygiene” • identifying a microbes, and intervening at the appropriate time in appropriate manner to prevent spread

42. Key concepts of targeted hygiene • In the places and at the times that matter it is important to not just clean but “hygienically clean” • can be achieved by detergent based cleaning, provided this is through and accompanied by adequate “rinsing” process • within a targeted hygiene approach - in some situations it is advisable to disinfect

43. Targeted hygiene is simpler - and healthier • “Targeted” hygiene offers the means to deliver messages which make sense to consumers • It offers the means to maximise protection against infection whilst reducing the impact on our human and natural environment to the least extent

44. Education is the key factor

45. IFH guidelines on home hygiene IFH teaching/self- learning materials on home hygiene Targeted hygiene www.ifh-homehygiene.org

46. Further Reading - IFH reviews, consensus views, Guidelines, training resources etc Biocides and resistance • Microbial resistance and biocides: a review and consensus statement http://www.ifh-homehygiene.org/2003/2public/2pub03.asp Hygiene Hypothesis • The Hygiene hypothesis and its implications for hygiene. http://www.ifh-homehygiene.org/2003/2hypothesis/hh.htm Targeted approach to home hygiene • Bloomfield, S.F. (2002) Home hygiene: a risk based approach. International Journal of Hygiene and Environmental Health, 205, 1-8 IFH guidelines and teaching materials • Guidelines for prevention of infection and cross infection the domestic environment. http://www.ifh-homehygiene.org/2public/2pubgu00.htm • Recommendations for selection of suitable hygiene procedures for use in the domestic environment. http://www.ifh-homehygiene.org/2public/2pub04.htm • Home Hygiene - prevention of infection at home: a training resource for carers and their trainers http://www.ifh-homehygiene.org/2003/2public/2pub06.asp