Background
Research Questions
-
Has the incidence of IID in England in the community declined since the mid 1990s?
-
What is the aetiology of IID in the community, and presenting to GPs, and by how much do national surveillance data in the UK underestimate the community and GP burden of IID?
-
How much IID is acquired abroad?
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How do molecular methods compare with traditional microbiological methods for IID diagnosis?
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What is the best research method for determining IID incidence in the community?
Methods/Design
Case definition used in all studies
Exclusion criteria used in all studies
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Patients with terminal illness.
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Patients whose first language was not English and for whom a suitable interpreter was not available.
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Patients with severe mental incapacity.
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Patients with non-infectious causes of diarrhoea: Crohn's disease, ulcerative colitis, cystic fibrosis, coeliac disease, surgical obstruction, excess alcohol, morning sickness, regurgitation in infants. The reason for these exclusions is because it is difficult to determine dates of onset for acute IID in the presence of chronic bowel disease.
Participant identification and recruitment
Bacteria | Methods |
---|---|
Campylobacter jejuni/coli* | Direct plating - modified cefeoperazone, charcoal deoxycholate (CCD) agar. Enrichment culture - Preston broth. |
Clostridium perfringens (enterotoxin) | Techlab™ (Blacksburg, USA) enzyme linked immunosorbent assay (ELISA), all positives to be cultured and isolates sent to the reference laboratory. |
Clostridium difficile cytotoxin | Premier™ (Meridian Bioscience Inc., Cincinnati, OH) toxins A and B enzyme immunoassay (EIA) |
Escherichia coli O157* | Direct plating on Cefixime Tellurite Sorbitol MacConkey agar. Enrichment in Modified Tryptone Soya Broth with Novobiocin. |
Listeria spp (monocytogenes)* | Direct plating - polymyxin acriflavine lithium chloride ceftazidime asculin mannitol (PALCAM) agar** |
Salmonella spp* | Direct plating - Xylose Lysine Dextrose (XLD) Agar and Desoxycholate Citrate Agar (DCA). Enrichment culture - Selenite F broth and Rappaport Vasilliades Salmonella enrichment broth. |
Shigella spp* | Direct plating - XLD and DCA. |
Yersinia spp* | Direct plating - Cefsulodin Irgasin Novobiocin (CIN) selective agar. Enrichment culture - Tris Buffer Yersinia enrichment broth. |
Protozoa
| |
Cryptosporidium parvum
| Techlab™ Giardia/Cryptosporidium check, r-biopharm™ RIDA™ Quick Cryptosporidium |
Giardia intestinalis
| Techlab™ Giardia/Cryptosporidium check, r-biopharm™ RIDA™ Quick Giardia |
Cyclospora | Modified Ziehl-Neelsen (ZN) stain |
Viruses
| |
Enteric viruses | (Premier™ Rotaclone, Premier™ Adenoclone). |
PCR (SOP) | Assay - chemistry | Target Organism | Gene encoding proteins | References |
---|---|---|---|---|
NOR1 | SINGLE-5'exonuclease | Norovirus genogroup 1 | RNA dependent RNA polyermerase/capsid | [34] |
NOR2 | DUPLEX-5'exonuclease | Norovirus genogroup 2 Mengo virus mutant vaccine strain MC | RNA dependent RNA polyermerase/capsid Not known | [35] Comite Europeen de Normalisation (CEN) |
ROTA | SINGLE-5'exonuclease | Rotavirus Group A | Viral Protein 6 | |
SAPO | DUPLEX-5'exonuclease | Sapovirus | Polymerase-capsid junction (2 probes) | [37] |
ASTR | SINGLE-SYBR Green | Astrovirus | Capsid | [38] |
ADEN | SINGLE-5'exonuclease | Adenovirus type 40 and 41 | Long fibre protein | [39] |
CAMP | DUPLEX-5'exonuclease |
C. jejuni
C. coli
| Membrane associated protein Lipoprotein of iron binding protein | [40] |
SALM | DUPLEX-5'exonuclease |
Salmonella enterica
Green Fluorescent Protein gene (gfp) inserted into a E. coli
| Glycotransferase GFP Protein | [41] |
EAGG | SINGLE-5'exonuclease | EnteroAggregative E. coli
| Anti aggregation transporter | |
LIST | SINGLE-5'exonuclease |
Listeria monocytogenes
| Haemolysin A | [43] |
VT1-VT2 | DUPLEX-5'exonuclease | Verocytotoxin 1 Verocytotoxin 2 | Verocytotoxin 1 Verocytotoxin 2 | [44] |
GIAR | SINGLE-5'exonuclease |
Giardia spp. | Elongation Factor 1 alpha | [43] |
CRYP | DUPLEX-5'exonuclease |
C. hominis, C. parvum, C. meleagridis, C. felis
|
Cryptosporidium oocyst wall protein | [43] |
CPER | DUPLEX-5'exonuclease |
C. perfringens alphatoxin and enterotoxin | Phospholipase C gene of C. perfringens
Enterotoxin gene of enterotoxigenic C. perfringens
| [45] |
CDIF | MULTIPLEX- 5'exonuclease | Toxin-producing C. difficile
| Toxin B gene (tcdB), binary toxin (cdt), and tcdC gene single-base deletion at nucleotide 117 (tcdB) |
Sample Sizes
Duration of recall period | Incidence in original IID recall Questionnaire | Widest acceptable CI limit | Number needed to survey |
---|---|---|---|
28 days | 6% | 4% | 500 |
7 days | 1.5% | 1% | 2500 |
England | Wales | |||||
---|---|---|---|---|---|---|
Organism/condition | Baseline incidence1
| Reduction to be detected | Person-years | GP practices | Person-years | GP practices |
All IID | 19.20% | 20% | 2,000 | 20 | 200 | 2 |
Severe cases* | 6.00% | 20% | 7,000 | 70 | 400 | 4 |
Campylobacter
| 0.87% | 20% | 500,000 | 5,000 | 2,400 | 24 |
Salmonella
| 0.22% | 20% | 500,000 | 5,000 | 9,500 | 95 |
Campylobacter+Salmonella
| 1.10% | 20% | 200,000 | 2,000 | 2,000 | 20 |
Campylobacter+Salmonella+ C. perfringens
| 1.34% | 20% | 100,000 | 1,000 | 1,600 | 16 |
Scotland
|
Northern Ireland
|
UK
| ||||
Organism/condition
|
Person-years
|
GP practices
|
Person-years
|
GP practices
|
Person-years
|
GP practices
|
All IID | 200 | 2 | 65 | 1 | 2,465 | 25 |
Severe cases* | 700 | 7 | 300 | 3 | 8,400 | 84 |
Campylobacter
| 4,200 | 42 | 1,400 | 14 | 508,000 | 508 |
Salmonella
| 16,400 | 164 | 5,500 | 55 | 531,400 | 532 |
Campylobacter+Salmonella
| 3,400 | 34 | 1,200 | 12 | 206,600 | 207 |
Campylobacter+Salmonella+ C. perfringens
| 2,800 | 28 | 1,000 | 10 | 106,200 | 107 |
England | Wales | |||||
---|---|---|---|---|---|---|
Organism | Baseline incidence* | Reduction to be detected | Person-years | GP practices | Person-years | GP practices |
Campylobacter | 4.10% | 20% | 115,000 | 20 | 7,000 | 2 |
Salmonella
| 0.16% | 50% | 41,000 | 7 | 3,000 | 1 |
Salmonella
| 0.16% | 40% | 67,000 | 12 | 4,000 | 1 |
Salmonella
| 0.16% | 30% | 127,000 | 22 | 8,000 | 2 |
Salmonella
| 0.16% | 20% | 302,000 | 51 | 18,000 | 3 |
C. perfringens
| 0.13% | 20% | 364,000 | 61 | 22,000 | 4 |
Scotland
|
Northern Ireland
|
UK
| ||||
Organism
|
Person-years
|
GP practices
|
Person-years
|
GP practices
|
Person-years
|
GP practices
|
Campylobacter | 12,000 | 2 | 4,000 | 1 | 138,000 | 25 |
Salmonella
| 5,000 | 1 | 2,000 | 1 | 51,000 | 10 |
Salmonella
| 7,000 | 2 | 3,500 | 1 | 81,500 | 16 |
Salmonella
| 13,000 | 3 | 4,500 | 1 | 152,500 | 28 |
Salmonella
| 31,000 | 6 | 10,500 | 2 | 361,500 | 62 |
C. perfringens
| 38,000 | 7 | 13,000 | 3 | 434,500 | 75 |
Plan of Analysis
Representativeness
Compliance
Under-ascertainment
Overall incidence of IID
Prevalence of aetiological organisms in IID cases and pathogen-specific incidence
Clustering
Comparison of incidence in the Prospective and Telephone Survey studies
Ethical approval to perform the IID2 Study
Discussion
-
the use of mobile phone numbers in such surveys has not yet become standard and reliable sampling frames for these are not easily available
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many mobile phone users are children and we cannot contact children directly for ethical reasons
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it is not easy to localise mobile phones to a geographical area.