The Old Friends Hypothesis: Rethinking Hygiene and Infection Prevention Strategies

1. The hygiene hypothesis - a misnomer which is undermining hygiene and infection prevention strategies Sally F Bloomfield International Scientific Forum on Home Hygiene, London School of Hygiene and Tropical Medicine April 2019 Microbiology Annual Conference, Belfast

2. In future we are going to have to view our microbial world very differently • 1900s • Separate ourselves from our microbial world • Strict “cleanliness” – the Florence Nightingale approach • Mid 1900s • Golden age of vaccines and antibiotics • ” its is time to close the book on infectious disease ---” • 2000 -> • Protection against pathogen exposure has essential role in health • Exposure to microbial world has essential role in health

3. The Hygiene Hypothesis misnomer • 1989 Strachan proposed - rapid rise in childhood allergies due to lack of exposure to childhood infections • Insufficient “infection”exposure • Smaller families – less chance of exposure • higher standards of home and personal hygiene/cleanliness • “Hygiene Hypothesis” appropriate name? • Quickly realised - link to hygiene incorrect. • Too late – since 1998 “we have become too clean for our own good” widely publicised. • The hygiene hypothesis was limited and specific

4. Are we too clean for our own good ?

5. The Old Friends Hypothesis • 2003 Rook proposed: • During human evolution, microbes have evolved essential role in regulating immune system. • Microbes not infectionsbut friendly microbeswhich make up human microbiome - include mainly • Microbiota from other humans and animals • Microbiota acquired from natural environment

6. The Old Friends Hypothesis • Reduced exposure to OF microbes linked to a broad range of diseases: • Not just allergies • autoimmune diseases (MS, type 1 diabetes, IBD) • depression, obesity, leukaemia, cancers etc • Diversity is key - programmes immune system to distinguish between what is harmful and what needs to be tolerated

7. Rook likens immune system to a computer programme build memory of diverse mol structures present in our world. Old friends microbes, helminths The immune system Immune response Immune tolerance Attack and prevent infection Allergens, self antigens etc Harmful/pathogens Allergic reaction Suggests that diversity of exposure is key

8. What’s gone wrong?

9. Why have we lost contact with OFs? • Epidemiological studies implicate lifestyle changes: • 1. Reduced exposure to microbiota which live on or in us • C-section – reduced exposure to maternal microbiota during delivery (25% C-S in UK) • Breast feeding – microbes in breast milk • fewer siblings - reduced microbiota sharing, • 2. Reduced exposure to natural environment • Spend up to 80% of our time indoors

10. What’s gone wrong? Sustaining our microbiome • Diversity of microbiome is key – mediates interaction between OFs and immune system • 3. Antibiotics • antibiotics alter and reduce diversity of gut microbiota • excessive AB during pregnancy/neonatal – associated w. Increased inflammatory disease risk • 4. Diet • Diversity important to sustain diverse gut microbiome • dietary fibre essential to some of the key gut microbiota • “One of the most important is going to turn out to be antibiotics” Rook 2019

11. What about home and personal cleanliness? • Role of home & personal hygiene/cleanliness likely to be small relative to other factors: • Clean-looking homes are full of bacteria, viruses, fungi, etc. • Routine weekly cleaning - no sustained effect on microbe levels • Microbes constantly replaced via dust, air, body flora, pets, foods • Personal hygiene - temporal correlation with increased bathing/showering, shampooing/bathing since 1950s • But skin flora removed during bathing/showering rapidly regenerate • Epidemiological evidence • 2015 study 399 German families, Von Mutius et al • Development of allergies & asthma not related to increased cleaning activities (personal cleanliness (e.g HWWS) and home cleanliness)

12. “It really isn’t hygiene” Rook 2019 • Crowd infections that hygiene measures are designed to combat appeared much too late in evolutionary history to have evolved role in development of immune system. • Why do we keep repeating it? – why do we still believe it ?

13. Because we are STILL calling it the hygiene hypothesis? • After 16y of published data - most experts accept the hygiene hypothesis is inaccurate - but continue to use the hygiene hypothesis term to refer to the OF hypothesis • Some experts still believe the original hygiene hypothesis • Media still refer to it as the hygiene hypothesis • “too clean for our own good?” It’s too good a story? “The call to experts to abandon the original “hygiene” hypothesis term has fallen on deaf ears. Several researchers interviewed for this article said the issue was semantics - they didn’t care what name is used”

14. Survey of UK and US media coverage • Media articles 1999-2017 • 30/36 articles mentioned home or personal cleanliness as underlying cause of reduced microbe exposures. • From 2003 (i.e. OF mechanism proposed) • 15 articles featured “new” research showing “lifestyle factors” (C section, antibiotics etc) as underlying cause • 13 still mentioned “also home cleanliness” • Of concern • 17/25 cited antibacterials/hand sanitizers as factor • In 15/25 this was quoted as an expert opinion

15. What does the public say? • I encourage my children not to worry about being dirty, e.g If we are on a picnic I don’t bother to get them to wash their hands because they need plenty of exposure to germs to keep their immune system strong Its only by contact with dirt and germs that our body builds up our immune system. I remember a TV programme showing that children living on farms with animals had the highest immunity against almost everything because they were exposed from an early age Does exposure to dirt and germs, particularly early in life, bolster/strengthen our immunity? Immunity to infection is confused with developing tolerance to harmless antigens etc

16. RSPH public questionnaire – 2000 people Which of the following factors do you believe is preventing children coming into contact with enough good bacteria?

17. What do we actually understand about “hygiene” and cleanliness – do we know the difference?

18. What are germs? • Yuck!, Uurgh! • Nasty dirty germs • Poo – smelly! • Don’t touch! • Make you sick • disgusting • We are brainwashed as children with Germophobia

19. When we reach adulthood and have our own children to protect we ask “Tell me where are the germiest places in my home ?” • Where do germs lurk? • Where are the dirtiest places in my home? So the next misguided question we ask is “How do I get rid of germs so that my family is safe? • By getting rid of dirt? Assuming: • If a surface is dirt free it is also germ free • If surfaces / my hands look clean they are free of germs • If my home is clean – its hygienic – germ safe

20. Messages reinforced by media articles So you think your bathroom is clean?Daily Mail – 10th April 2017 “Bathroom is a haven for bacteria, breeding in places you believe are sparkling clean” “Here’s a map to help identify where germs love to lurk and help you to banish the bugs” But these millions are not harmful – and possible are beneficial

21. Do we understand the difference between hygiene and cleanliness? • Pilot study of 117 people asked – “What do YOU understand by terms clean and hygienic”

22. Is this an important issue? – why should we worry about it? “Continuing to call it the hygiene hypothesis is leading people to interpret this issue in a way which is quite wrong“ Undermining attitudes to hygiene at a time when hygiene is becoming more important. Could be increasing risk of spread of the spread of infections

23. Why is home and everyday life hygiene moving back up the health agenda? • Gastrointestinal infections - Campylobacter & norovirus - remain at unacceptable levels • Increasing “at risk” groups needing special care • elderly, very young • underlying disease: HIV/AIDS, diabetes • Increasing healthcare at home /in community • 2019 UK 5 year plan: hygiene in HEDL a key part of tackling AMR • Reduces antibiotic prescribing • Reduces “silent” spread of AMR strains in community • Promoting good health/preventing illness now key parts of gvt strategy to alleviate stress on NHS.

24. Addressing the issues • Fundamental question is • “How can we restore exposure to old friends microbes • whilst at the same time promoting good hygiene practice to protect from infectious disease” • Answer lies in targeted hygiene

25. IFH targeted approach to hygiene • IFH has developed an approach to hygiene in the home and community based on risk management • Known as “targeted hygiene”. • means breaking the chain of infection by targeting critical points at key times • This : • Maximises protection from pathogen exposure • Maintains exposure to Old Friends microbes

26. Hygiene means breaking the chain of Infection Main sources of Infection People, contaminated food, domestic animals, water Way in Mouth, nose, RT. cuts, grazes Shedding Food particles, faeces, saliva, cough, sneeze, Survival and spread Hands, surfaces, cloths, clothing, linen, baths, basins, toilets, air

27. What are the critical times ? Times when harmful microbes most likely to be spreading from an infected source Respiratory hygiene Food hygiene Looking after pets Using the toilet Nappy hygiene Laundering of clothing & linens Using baths, sink and, washbasins Waste disposal

28. What are the most critical points ? Hands Hand contact surfaces Food contact surfaces Cleaning cloths/ utensils Clothing and household linens Toilets, baths, sinks,washbasins Floors, walls, furniture etc Increasing risk

29. What methods are available for “hygienic cleaning” at critical points • Purpose - to reduce organisms on critical sites/surfaces to acceptable safety target level. • Can be achieved by: • removal, c. cleaning products (e.g detergents or soap) & cleaning utensils, and water • Inactivation in situ using products/processes i.e. heat, UV light, disinfectants, hand sanitizers • Combined removal and inactivation, sequentially or together e.g laundering and dishwashing.

30. Use of disinfectant/antibacterial products • Where should disinfectants be used • Situations where detergent-based cleaning or wipe- based cleaning is inadequate to reduce contamination to safe level • Situations where there is no access to running water e.g hand sanitizers, hand contact surfaces • Where are they not advised • For non targeted routine cleaning/antibacterial impregnated utensils – “to give a bit of extra hygiene”

31. Preparing a meal with a chicken contaminated with Salmonella or Campylobacter 33% contaminated sites had >1000 cfu/sample area Infectious dose 100-500 cfu Cogan, Bloomfield and Humphries, Letters in Appl.Microbiology 1999, 29,354-358

32. Inoculate c. Norovirus in faecal suspension Wipe c. clean cloth - sample surface & cloth Use cloth to wipe another clean surface Sample surface, cloth, hands Clean x 1 100% +ve 100% +ve Clean x 2 100% +ve 100% +ve Clean and disinfect c. bleach 0% +ve 0% +ve Effectiveness of hygiene procedures in eliminating norovirus from surfaces (N = 14) Surfaces sampled using RTP-PCR infectious dose 6—10 particles Barker, Vipond and Bloomfield, J. Hospital Infection 2004;58:42-9

33. Changing public perception of hygiene • Hygiene is different from cleanliness • It’s not: • getting rid of the germs that “lurk” in our homes through rigorous cleaning • Not about keeping our homes “germ free” • It is: • about breaking the chain of infection transmission • We can’t see microbes – so hygiene means cleaning in the prescribed way – not just until the hands/surfaces look clean

34. Potential consequences • Continuing to focus on whether we are “too clean” is distracting attention from 2 key health issues of 21st C - where workable solutions are urgently needed and could yield huge health benefits: • Sustaining healthy microbiome through lifestyle changes, probiotics etc, - fundamental impact on burden of a large range of chronic disease • Restoring public confidence in hygiene and promoting targeted hygiene - key to tackling antibiotic resistance and reducing the burden on the NHS

35. The urgent need • - restoring public confidence in hygiene • changing understanding • - • In future we are going to have to view our microbial world very differently

36. 1. Re-engaging with the public • We will have limited success in change hygiene behaviour through hygiene promotion unless and until we resolve public misunderstandings about “being too clean” • Reducing risks of immune disorders means changing lifestyles - not reducing hygiene and cleanliness • Preventing infection means targeted hygiene to break the chain of infection – not how clean or dirty we are • Hygiene is part of healthy living

37. 2. Engaging with other stakeholders – not just the public • Need to ensure that they • recognise importance of hygiene relative to other issues • Stop communicating messages which conflict with promotion of effective hygiene • Stakeholders include scientists, health professionals, industry, allergists, environmentalists, regulators

38. What do microbiome experts tell us? • The Times: health supplement Nov 3rd 2015 • Gut bacteria are key to fighting disease • Why is the human gut microbiome depleted? – 3 main culprits • Antibiotics • Sterility of modern life and diet • C-sections Expert opinion: “The idea that children should wash their hands before eating. I don’t think we should be washing our hands before a meal now. If you think about the number of food poisoning infections in the home- they are incredibly rare we are over-cleaning enough, our sterility is causing us problems

39. Fake News! MMR vaccine and autism • 1998 – Lancet : claimed link between MMR vaccine & autism • retracted 2010 • 1998-2003 • UK MMR vaccine coverage dropped from 91% to 80% • Measles cases increased from 56 to 1370 • 2019 - strong lobbying against MMR vaccine via social media

40. Fake News! - the hygiene hypothesis • 1998 - Hygiene hypothesis proposed • refuted c. 2003 in favour of the OF hypothesis • 2019 ongoing use of this term - many people still believe hygiene is underlying cause of allergies etc – still discussing whether we should be less clean/hygienic/more dirty • This issue has equally serious implications for public health?

41. International Scientific Forum on Home Hygiene • IFH - established 1997 – is working to develop & promote hygiene in home & everyday life based on sound scientific principles • www.ifh-homehygiene.org • White paper released October 2018 Time to abandon the hygiene hypothesis: New perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene. Bloomfield Rook et al Perspectives in Public Health 2016; 136, 213–224.