Investigating travellers’ diarrhoea aetiology, burden, diagnostics and the carriage of extended spectrum ß-lactamase producing Enterobacterales in contemporary military operational settings

Toriro, Romeo (2024) Investigating travellers’ diarrhoea aetiology, burden, diagnostics and the carriage of extended spectrum ß-lactamase producing Enterobacterales in contemporary military operational settings, Thesis (Doctoral), Liverpool School of Tropical Medicine.

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Abstract

Introduction
Travellers’ diarrhoea (TD) is amongst the most dominant causes of morbidity in military populations. Data on TD aetiology, impact and diagnostics in British military populations are scant. Military deployments typically involve travel to resource limited settings with inadequatediagnostic capability, and a high-risk for acquisition of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE), and carbapenem-resistant Enterobacterales (CRE). This thesis investigates TD epidemiology, prevalence and impact, including ESBL-PE and CRE baseline rates and evaluates different faecal storage media reliability for utility in point of care testing in contemporary British military settings.
Methods
(i) A Cochrane protocol was developed as the initial step towards conducting a Cochrane Review which will assess the effects of antibiotic treatment in reducing the duration and severity of TD. (ii) Self-assessed questionnaires were analysed and a descriptive comparison of TD clinical features, associated risk factors and impact on British military deployments to Kenya and Oman was performed. (iii) Faecal samples were collected during a cryptosporidiosis outbreak investigation for immediate testing using PCR BioFire® FilmArray® (FilmArray®), andoutbreak isolates were later characterised using a duplex real-time PCR. (iv) Faecal samples from the cryptosporidiosis outbreak were tested onsite using FilmArray® and preserved corresponding samples were tested 6-18 months later to determine OMNIgene® 200, DNA/RNA shield DX™ and Whatman FTA™ Elute cards reliability versus the onsite test. (v) Faecal samples collected from service personnel (SP) before, during, and post deployment to low-and-medium income countries were analysed by PCR to determine the ESBL-PE and CRE baseline prevalencerates, and to identify β-lactamase and CRE encoding genes.
Results
(i) The completed Cochrane Protocol is the first stage of the Review which will assess the effects of antibiotic treatment for TD in relation to illness duration, adverse events, and acquisition of multidrug resistant organisms. (ii) Diarrhoea incidence over 6-weeks was 14.2% (95% CI; 8.02 -22.61) in Kenya compared to 3.9% (95% CI; 1.10 - 9.91) in Oman (OR 3.56, 95% CI 2.18 – 5.8; p 17 <0.0001). (iii) 14.3% SP developed diarrhoea over 69 days. 106 primary faecal samples were tested, and 63/106 (59.4%; 95% CI, 0.49%–0.69%) were positive for Cryptosporidium spp. 38 had Cryptosporidium spp. alone, and 25 had Cryptosporidium spp. with ≥1 other enteropathogens. (iv) Test sensitivity for Campylobacter spp. and Enteroaggregative Escherichia coli was high across all three storage modalities (86.4-100%). OMNIgene®200 and DNA/RNA shield™ showed significant concordance with the onsite test for other pathogens, but FTA™ Elute card tests had low sensitivity for STEC and poor specificity for Campylobacter spp. (v) The ESBL prevalence was 40/239 (16.7%); ESBL-producing Escherichia coli were detected in 39 (16.3%) samples, and ESBL-producing Klebsiella pneumoniae in 1 (0.4%) sample.
Conclusions
(i) The Cochrane Review is ongoing. (ii) TD still impacts on military operational effectiveness, and close contact with an unwell colleague is the most significant risk factor. (iii) Multiplex PCR faecal testing was critical in managing a large cryptosporidiosis outbreak. (iv) OMNIgene® and DNA shield™ are suitable for storage of diarrhoeal samples for up to 18 months at ambient temperature without significant impact on performance characteristics. Further studies are needed to optimise the customised FTA™ cards protocol. (v) ESBL-PE prevalence in cohorts of British SP closely matches that of civilian populations in England, but ESBL genotypic distribution differs.

Item Type:	Thesis (Doctoral)
Subjects:	QW Microbiology and Immunology > Bacteria > QW 138 Enterobacteriaceae WA Public Health > WA 20.5 Research (General) WI Digestive System > WI 20 Research (General) WI Digestive System > WI 407 Diarrhea
Repository link:	Item title Item URI Antibiotic treatment to reduce the duration and severity of travellers’ diarrhoea (Protocol). https://archive.lstmed.ac.uk/23455/ Outbreak of diarrhea caused by a novel Cryptosporidium hominis subtype during British military training in Kenya https://archive.lstmed.ac.uk/23951/ Prevalence of extended-spectrum β-lactamase-producing Enterobacterales and carbapenemase-resistant Enterobacterales in British military cohorts https://archive.lstmed.ac.uk/25554/ Prospective evaluation of different faecal preservation media for travellers’ diarrhoea diagnostic application with multiplex PCR BioFire FilmArray in resource limited settings. https://archive.lstmed.ac.uk/26156/ Epidemiology and impact of travellers’ diarrhoea differs during UK military exercises in Kenya and Oman. https://archive.lstmed.ac.uk/26081/
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	26 Mar 2025 10:34
Last Modified:	26 Mar 2025 10:39
URI:	https://archive.lstmed.ac.uk/id/eprint/26448

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