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CHRO-2022 China Keynote
- 1. Ben Pascoe Global differences in Campylobacter epidemiology and genetics CHRO meeting Yangzhou, China November 2022
- 2. Campylobacter is just a food poisoning bug
- 3. Campylobacter: Human infection in the UK – predominantly by eating undercooked contaminated poultry products
- 4. More often in young people, but more severe in older people Seasonal differences Nichols et al 2012: BMJ Open e001179. Highest risk in older/younger people & seasonal infections
- 5. Is Campylobacter epidemiology the same all over the world? Over 50,000 WGS in pubMLST (>98,000 MLST profiles) + thousands of isolates uploaded to NCBI > 75% genomes from UK / USA https://pubmlst.org/campylobacter/
- 6. Campylobacter is a just a food poisoning bug You’re joking, right? You’re joking, right??! Campylobacter is just a food poisoning bug
- 7. Historical evidence that epidemiology is different in LMICs o Increased exposure: high-incidence among young children (when sampled – often no surveillance measures).Very little documented in adults. o Different sources? (Food and Env) o Asymptomatic infection - isolation from children and associated with growth stunting. o human-to-human transmission? Calva et al 1988: The Lancet, 1:503-6; Coker et al 2002: Emerg Infect Dis. 8:237-44.
- 8. Key themes: local differences, global similarities
- 9. Mouftah & Pascoe et al 2022: DOI 10.1099/mgen.0.000834 Globally circulating genotypes among Egyptian Campylobacter isolates Mohamed Elhadidy Shaimaa Fekry Mouftah In collaboration with Zewail University of Science and Technology, Cairo:
- 10. Global and locally dispersed lineages Pascoe et al (unpublished) *How much is down to lack of sampling? o Differences in global genetic diversity o Some lineages (clusters) have only been seen in certain regions Martin Maiden Keith Jolley https://pubmlst.org/
- 11. Local accessory genome sharing Isolates clustered by accessory genome content More genes shared within country Specific lineages (CC21 & CC828) Mouftah & Pascoe et al 2022: DOI 10.1099/mgen.0.000834
- 12. Egyptian C. coli more often MDR Mouftah & Pascoe et al 2022: DOI 10.1099/mgen.0.000834
- 13. MDR C. coli in Viet Nam OUCRU, Ho Chi Minh Stephen Baker Pascoe & Mourkas; et al (unpublished) Ineos Oxford Institute for AMR Evangelos Mourkas
- 14. Viet Nam: local sequence types New ST Pascoe & Mourkas; et al (unpublished) No Vietnamese CC21 Many common STs not represented in VN
- 15. Gene-pool transmission of AMR genes between clinical and sewage C. coli isolates in Spain Ineos Oxford Institute for AMR, Evangelos Mourkas Universidad Complutense Madrid, Diego Florez- Cuadrado Mourkas & Florez-Cuadrado et al. (2019) doi: 10.1111/1462-2920.14760
- 16. Global similarity & local variation
- 17. Asymptomatic carriage of Campylobacter in Peruvian children Lee et al (2013) PLoS Neg Trop Diseases doi:10.1371 Francesca Schiaffino (Universidad Peruana Cayetano Heredia), Margaret Kosek (University of Virginia) Kerry Cooper (University of Arizona), Craig Parker (USDA) PRISMA lab in Iquitos, Peru
- 18. Asymptomatic carriage of Campylobacter is associated with growth stunting Lee et al (2013) PLoS Neg Trop Diseases doi:10.1371 ~5% prevalence of asymptomatic carriage (higher recent estimates as identification/culturing methods have improved)
- 19. Long term carriage / chronic infection Kosek et al., unpublished Figure 1. Epidemiologic definition of an episode of persistent carriage of Campylobacter
- 20. PeruvianAmazon paediatric isolates have a local gene pool Pascoe et al (2020) PLoS Neg Trop Diseases doi: 10.1371/journal.pntd.0008533
- 21. Extensive drug resistance in Peruvian paediatric isolates Schiaffino et al (2022) In prep *Ciprofloxacin and Azithromycin used as frontline antibiotics Resistance compromises use of oral antibiotics
- 23. High risk lineages – IBS prediction Madhu Grover Mayo Clinic, Minnesota Peters & Pascoe et al (2021) https://doi.org/10.1038/s42003-021-02554-8
- 24. “There’s an awful lot you can tell about a person by their shoes – where they going; where they been.”
- 25. More than 80% paediatric cases attributed to chicken Are chicken (backyard/farmed) chickens the source ofAMR? Cooper et al (2023) In prep Caveats: Effective source attribution relies on composition of your comparison dataset: -> rare STs/CCs poorly attributed -> missing unsampled reservoirs? Pascoe et al (2020) PLoS Neg Trop Diseases doi: 10.1371/journal.pntd.0008533 Guinea pig paper Parker et al (2021): doi.org/10.3389/fcimb.2021.607747
- 26. Attributing the source of campylobacteriosis in theUS (2009 - 2018) [Contemporaneous datasets] Pascoe et al (2023) In prep Peter Evans, FSIS
- 27. Poultry is the primary source of campylobacteriosis in theUS
- 28. MRC project in theGambia, Burkina Faso &Ghana to identify the sources of Campylobacter infection Calva et al 1988: The Lancet, 1:503-6; Coker et al 2002: Emerg Infect Dis. 8:237-44.
- 29. Summary
- 30. Swansea/Bath/Oxford: Sam Sheppard, Evangelos Mourkas, Shani Ali, Billy Monteith Guillaume Meric, Jessica Calland, Sion Bayliss, Susan Murray, Leonardos Mageiros, Georgie Futcher Peru: Margaret Kosek, Francesca Schiaffino, Kerry Cooper, Craig Parker Egypt: Mohamed Elhadidy, Shaimaa Fekry Mouftah Viet Nam: Stephen Baker Spain: Diego Florez Cuadrado Gambia: Martin Antonio, Jahangir Hossain, Abdul Sesay, Henri Badji, Jarra Mane Burkina Faso: Isidore Bonkoungou Ghana: Akosua Karikari, Courage Saba Kaisa Haukka, Jukka Corander, Julian Parkhill USA (source attribution): Peter Evans, Neal Golden, Mustafa Simmons, Beau Bruce, Glenn Tillman, Lavin joseph, Charlotte Lane, Michael Williams. USA (high-risk lineages): Madhu Grover, Stephanie Peters Thanks!
- 31. Microbial Genomics: Campylobacter collection
- 32. Campylobacter is a just a food poisoning bug You’re joking, right? You’re joking, right??! Campylobacter is just a food poisoning bug
- 33. Greater proportion of French isolates attributed to ruminant sources 60 – 80 % attributed to chicken 40 – 60 % to ruminant 4 – 10 % to wild birds & environment (Sheppard et al., 2009, Kittl et al., 2013, Boysen et al., 2014, Mossong et al., 2016) HICs: Differences between countries
- 34. Machine learning to select host segregating markers
Editor's Notes
- Ben Pascoe University of Oxford How some of the differences we see in Campylobacter epidemiology around the world are reflected in their genomes
- Campylobacter is PREDOMINANTLY thought of as a food poisoning bacteria. Most research focusses on Campy as a public health risk – surveillance studies, spread of AMR genes, source attribution (how was the person infected?), which strains cause severe disease/post-infection sequalae?
- In the UK the main risk of infection comes from eating (handling?) raw/undercooked chicken products. Widespread among UK supermarket meats. Make sure you wash your hands when preparing chicken and cook thoroughly. Efforts to produce chicken vaccine (like Salmonella in the UK) – but none have attained the kind of commercial success necessary to be taken on industry-wide.
- Much higher risk in older & younger people – immunocompromised? Seasonal variation – peak in summer months – links with BBQs & outdoor eating? – but also seasonal in the chicken…
- Overwhelmingly most research has been conducted in HICs. Public repository of MLST/genomes (pubMLST) more than 75% genomes/profiles are from UK or USA. (Also bias for human / chicken samples)
- So, Campy is JUST a food poisoning bug, right? Overwhelmingly that is where research in HICs has focused. But what is going on elsewhere in the world…?
- There is historical evidence that Campy epidemiology is different in LMICs Antibody studies in children (Mexico, Africa, SE Asia…) show that high numbers of children <1 exposed to Campy Are there different (food) sources – not everyone eats as much chicken or prepares it the same way. (Supermarket vs small holding/backyard chickens) Asymptomatic infection (carriage) and potential for human to human transmission. (Chronic infection..?)
- Through a series of studies I’ve been involved with; I’m going to talk about some of these differences we see around the world, where we see some of these key themes: Lineages that we only find in specific places. Absence of common (in the UK) infection types High (/low) risk lineages associated with severe disease or specific disease sequalae (or asymptomatic carriage) Clusters of highly AMR isolates from specific countries. …and hopefully, convince you that campy is not ALWAYS a food poisoning infection.
- Recent project with Mohamed & Shaimaa where we looked at a collection of clinical Campy isolates collected over 6-12 months period in Cairo. Compared directly with a similar collection from Oxford we identify a lot of the same STs (similar frequency) - with a couple of host-generalist lineages among our most common in both locations: CC21 (cj) & CC828 (cc) [and more broadly with all of pubMLST – dotted line] -> Globally disseminated lineages is Egypt.
- If we look in pubMLST some STs/CCs are found all over the world…while others are only found in one (or a few) places. Sampling? Bias towards Europe & North America. Acknowledge what an excellent resource pubMLST is – thanks Martin & Keith!
- BUT, in our Egyptian study - we did see differences in the accessory genome – PCA clustering by accessory genome content (summarized on the right) -> more sharing in isolates from the SAME country vs DIFFERENT countries. Some lineages shared more within country accessory genes than others – including our two most common lineages – CC21 & CC828.
- We also saw a lot more MDR in Cario than in Oxford – particularly in the CC. Drill down and specific STs / clones? / variants of concern were more likely to be MDR than others. THEME: globally disseminated lineages; but local accessory genome similarity.
- Some similarities in Viet Nam – dramatically more MDR Ccoli. Project with Stephen Baker at Cambridge (now) and OUCRU in Ho Chi Min. Campy samples from a single hospital. Over the counter purchase of antibiotics for poorly stomach.
- Unlike Egypt though – many of the Vien Nam isolates are from STs that we haven’t seen before – more than 1/3 isolates from ST that is new to pubMLST. Much fewer globally disseminated host generalist isolates – look at CC21 (which is very common in UK infections). MANY STs common in the UK not represented in VN – suggests different source of infection?
- To hammer the point: example from Spain. So, not just occurring in LMICs. Project with Diego (and his boss), lead by Evangelos where we compared Spanish clinical & agricultural & sewage samples. Sharing exact alleles of AMR genes between each niche – width of bars going from each source on the circus plots C. coli: Can see aggregation of aminoglycoside AMR genes in sewage (from clinical samples).
- Cartoon trees: Global similarity – some lineages / STs /CCs /clones /variants found all over the world. (Sometimes, the absence of one or more of these globally disseminated clones can hint at differences in epidemiology – different chicken products?) Local differences: geographically unique lineages.
- Next, we’re going to take a look at some different ‘infection’ types: Margaret Kosek & Francesca and the lab in Iquitos, Peru have done some brilliant sampling of newborn children on the edge of the Amazon in Peru. Routine sampling of newborns – every few months, with/without symptoms. Consistent level of identification of Campylobacter from these children – even in the absence of symptoms (diarrhea) We’ve looked at the genomes of these isolates with Kerry and Craig from Arizona & the USDA.
- In the original study there was significant low-level carriage of asymptomatic Campylobacter – jejuni, coli & lari. Numbers are even higher now as they have improved their identification & culturing methods. The team in Peru also identified an association between carriage of Campylobacter with weight gain in these children.
- Because the tem are routinely sampling the SAME kids over a long period of time (2-5 years) they are able to identify potential cases of persistent infection – repeated isolation of Campy from the same person over long periods of time (months). Ongoing work to see if this is the SAME isolate/strain/lineage – or whtehr this is repeated infection due to high exposure rates. Also difficult to identify whether this is chronic infection, or repeated infection from the same contaminated source (water?) or even human to human transmission (within families) .
- We know that there are a lot of unique ST/CCs in this population – as well as some of those globally disseminated lineages. However, we also see very few of those host generalist ST21s – absent in Viet Nam, but very common in the UK, Europe and the North America. Large amounts of accessory genome sharing as well (not shown, but in the paper)
- There is extensive drug resistance in this Campylobacter population as well (again, dramatically more in the Ccoli) -- resistance to Ciprofloxacin AND Azithromycin means oral antibiotics are essentially compromised. Very few options for antibiotic treatment. Buy whatever AB you want over the counter for your chickens…
- Potential for different infection types – asymptomatic, chronic and maybe even human to human (within family) transmission. Geographically unique lineages associated with asymptomatic carriage or different types of infection. Widespread AMR – concentrated in specific lineages (Ccoli).
- High risk lineages are also something we have investigated in HICs with respect to IBS. In this project with Madhu at the Mayo Clinic in Minnesota, we used genome-wide association studies to identify genetic elements associated with the onset of PI-IBS and then use them as markers to identify high risk lineages. And that can be ST/CCs –or- LOS –or- Capsule types. As we increase the number of samples with this additional data (6 month follow up data) it will allow us to make better risk prediction and improved precision medicine.
- Another way for us to improve risk prediction is to identify the sources which contribute the most to clinical infection. I saw a great slide the other day, which I thought explained source attribution quite well (thanks Lance Price) Forrest Gump scene where he comments of the nurses' shoes – which are part of her uniform and tells us something about who she is and what she does. Campylobacter are similar in that when a Campylobacter colonizes a new host it has to adapt and acquire genetic elements to help it survive. We can use genomics techniques to quantify these adaptations and predict the source of human infections.
- If we apply these source attribution techniques to our clinical samples in Peru -- > 80% of infections were predicted to come from chicken sources. Can see man buying his chicken from the chicken market (this summer) – high levels of exposure! These studies rely on good comparison datasets – we’ve increased our sampling of non-human reservoirs of Campy in Peru (including Guinea pigs!) Kerry (on the left) working on project with the aim of identifying whether farmed or “backyard” chicken are the primary source of infection (and AMR) in Peruvian kids.
- That’s what we are also trying to do in HICs. Assembling large datasets to attribute the source of clinical campylobacteriosis in the US between 2009-2018 In collaboration with various US PH bodies, including FSIS – lead by Peter Evans.
- By identifying the ”shoes” the clinical Campy are wearing we can attribute the source of infection. Like Peru – primary source is Chicken. But differences (in proportion) between states. When you allay this with identification of AMR determinates you can see that over the last ten years: along with a rise in incidence, a larger proportion of cases can be attributed to chicken sources and the numbers of MDR isolates has risen.
- Final stop – Africa – where we really don’t know very much. MRC project with collaborators in the Gambia, Burkina Faso and Ghana to identify the sources of Campylobacter infection. High burden of diarrheal disease – can see from our photos that likely different sources – and flooding/contaminated water us likely an important source of infections.
- Globally circulating disease genotypes Some genotypes are region-specific Specific-lineages associated with asymptomatic infection in Peruvian Amazon paediatric cases Regional differences in accessory genome content (AMR?) Poultry is the predominant source of infection in many countries, but differences in proportions
- Of course, we couldn’t do any science without our friends and all these projects required great teams and networks of researchers.
- Special collection of papers associated with the conference in Microbial Genomics
- As well as in Peru, we have used these source attribution-type studies to estimate the relative contribution of different sources to human disease in several countries, including the UK, US and France. Peru had a high number of campylobaceriosis cases attributed to chicken sources. But we also see differences between country – chicken is always #1 source tho. Higher contribution from cattle in France. Can also use these to (tentatively) identify geographical differences between isolates (US v UK) – although the evolutionary signal associated with host adaptation is much stronger.