Genetic heterogeneity in the Salmonella Typhi Vi capsule locus: a population genomic study from Fiji.

Typhoid fever is endemic in many parts of the world and remains a major public health concern in tropical and sub-tropical developing nations, including Fiji. To address high rates of typhoid fever, the Northern Division of Fiji implemented a mass vaccination with typhoid conjugate vaccine (Vi-polysaccharide conjugated to tetanus toxoid) as a public health control measure in 2023. In this study we define the genomic epidemiology of Salmonella Typhi in the Northern Division prior to island-wide vaccination, sequencing 85% (n=419) of the total cases from the Northern and Central Divisions of Fiji that occurred in the period 2017-2019. We found elevated rates of nucleotide polymorphisms in the tviD and tviE genes (responsible for Vi-polysaccharide synthesis) relative to core genome levels within the Fiji endemic S. Typhi genotype 4.2. Expansion of these findings within a globally representative database of 12 382 S. Typhi (86 genotyphi clusters) showed evidence of convergent evolution of the same tviE mutations across the S. Typhi population, indicating that tvi selection has occurred both independently and globally. The functional impact of tvi mutations on the Vi-capsular structure and other phenotypic characteristics are not fully elucidated, yet commonly occurring tviE polymorphisms localize adjacent to predicted active site residues when overlayed against the predicted TviE protein structure. Given the central role of the Vi-polysaccharide in S. Typhi biology and vaccination, further integrated epidemiological, genomic and phenotypic surveillance is required to determine the spread and functional implications of these mutations.

Knowledge, attitudes, and readiness about critical antimicrobial resistant organisms among healthcare workers at colonial war memorial hospital in Fiji: a pre and post intervention study.

BACKGROUND: Gram-negative bacteria resistant to carbapenems are also known as critical antimicrobial resistant organisms. Their emergence at Colonial War Memorial Hospital (CWMH), the largest hospital in Fiji, is a major clinical concern. This study was conducted to determine the knowledge, attitudes, and readiness of healthcare workers (HCW) at CWMH regarding management of patients with infections caused by critical antimicrobial resistant organisms. METHODS: A questionnaire was designed using a Likert scale to assess knowledge, attitudes, and readiness. Two cross-sectional studies were conducted, before and after the implementation of targeted educational activities which were informed by the pre-intervention study findings. RESULTS: A total of 393 and 420 HCW participated in the pre- and post-intervention studies, respectively. The majority of respondents were female (77.3%) and 18-34 years of age (67%). HCW professional roles included nurses (56.3%), doctors (31.6%), and laboratory personnel (12.2%). In the post-intervention study, significantly more HCW reported having received infection prevention and control (IPC) and antimicrobial resistance education and training (26.8% in pre to 45.5% in post intervention, p < 0.001). The majority of nurses and doctors (> 85% to ≥ 95%) were aware of how AMR organisms spread in healthcare settings and knew the IPC measures to prevent transmission of AMR infections including hand hygiene, standard and transmission-based precautions. Attitudes towards AMR were positive, with 84.2% pre intervention and 84.8% of HCW post intervention expressing their willingness to change their work environment to assist with AMR prevention. Perceived readiness to address the problem showed mixed results. Improvements in laboratory AMR surveillance data availability were noted (29.4-52.4%, p < 0001). Modest improvement in the hospital's capacity for outbreak response (44-51.9%, p = 0.01), and treatment of AMR infections (38.9-44.4%, p = 0.01) was reported. CONCLUSIONS: Our data revealed high levels of staff awareness and knowledge about AMR and IPC. However, readiness for outbreak response and treatment of critical AMR infections requires more attention. Improving AMR prevention and containment in CWMH will likely require sustained and multisectoral interventions with strong administrative commitment.

The epidemiology of enterococci in a tertiary hospital and primary healthcare facilities in Fiji (2019-2022).

OBJECTIVES: We analysed 4 y of laboratory data to characterise the species and determine the antimicrobial susceptibility profiles of enterococci as human pathogens in Fiji. The study also investigated the molecular epidemiology amongst the subset of vancomycin-resistant enterococci (VRE). METHODS: This retrospective study reviewed bacteriological data from Colonial War Memorial Hospital (CWMH) and other healthcare facilities in the Central and Eastern divisions of Fiji. Phenotypic, antimicrobial susceptibility and vanA and vanB PCR testing were performed using locally approved protocols. The first clinical isolates per patient with antimicrobial susceptibility testing results in a single year were included in the analysis. Data was analysed using WHONET software and Microsoft Excel. RESULTS: A total of 1817 enterococcal isolates were reported, 1415 from CWMH and 402 from other healthcare facilities. The majority of isolates, 75% (n = 1362) were reported as undifferentiated Enterococcus spp., 17.8% (n = 324) were specifically identified as Enterococcus faecalis and 6.7% (n = 122) as E. faecium. Overall, 10% of the enterococci isolates were from blood cultures. Among isolates from CWMH, <15% of E. faecium were susceptible to ampicillin, and 17.2% were vancomycin resistant. Overall, 874 enterococcal isolates (including the undifferentiated species) were tested against vancomycin, of which 4.8% (n = 42) were resistance. All of the VRE isolates tested (n = 15) expressed vanA genes. CONCLUSIONS: This study demonstrates the clinical importance of VRE, particularly van A E. faecium in the national referral hospital in Fiji. Enhanced phenotypic and molecular surveillance data are needed to better understand enterococci epidemiology and help guide specific infection prevention and control measures and antibiotic prescribing guidelines.

The changing epidemiology of antimicrobial resistance in Fiji: a descriptive analysis of antimicrobial susceptibility and trends of endemic and emerging pathogens, 2019-2022.

Background: There is a paucity of data on antimicrobial resistance in Fiji. The aim of this study was to determine the antimicrobial susceptibility profile of bacterial isolates from clinical samples at Colonial War Memorial Hospital in Fiji. Methods: This retrospective study reviewed four-year of data from January 1, 2019, through December 31, 2022. Laboratory testing was carried out using locally approved protocols. Selective antimicrobial susceptibility testing was performed whereby only isolates resistant to first line antimicrobials were tested against second line antimicrobials. Only the first isolate of a given species per patient in a single year were included in the analysis. WHONET software and Microsoft Excel were used for analysis. Findings: A total of 29,222 bacterial isolates were included, 62% (n = 18,084) were Gram-negative bacteria. K. pneumoniae was the most common (n = 5363), followed by E. coli (n = 4321). Extended spectrum beta lactamase (ESBL) production increased from 30% in 2019 to 43% in 2022 amongst K. pneumoniae, and 10%-23% in E coli. There were 733 carbapenem-resistant isolates identified from clinical samples, 61% (n = 445) were A. baumannii, 15% (n = 110) E. coli and 14% (n = 101) P. aeruginosa. Amongst the E. coli isolates tested, susceptibility to meropenem declined from 99% (272/274) in 2019 to 79% (255/325) in 2022. The rate of methicillin resistance amongst Staphylococcus aureus was steady, remaining between 11% and 13%. Interpretation: This study demonstrated a high rate of MDR amongst Gram-negative bacteria, especially ESBL producing K. pneumoniae and E. coli and carbapenem-resistant A. baumannii. The emergence and rapid spread of carbapenemase producing E. coli in Fiji's largest hospital is of particular concern. There is an urgent need to allocate resources to improve existing capacity and to develop effective multimodal strategies to detect, manage and control the spread of MDR organisms. Funding: This study was supported by the Medical Research Future Fund through the Australian government (grant number APP 1200970).

Assessment of Rapid Diagnostic Tests for Typhoid Diagnosis and Assessment of Febrile Illness Outbreaks in Fiji.

Typhoid is an endemic in Fiji with increases observed since the early 2000s and frequent outbreaks reported. We assessed the diagnostic accuracy of currently available typhoid rapid diagnostic tests (RDTs) (TUBEX, Typhidot Rapid, and Test-It assay) to establish their performance against blood culture in Fiji and to examine their suitability for rapid typhoid outbreak identification. The performance of RDTs was assessed in the public health reference laboratory in Suva, Fiji, according to the manufacturers' instructions. A simulation was used to examine the potential use of RDTs for attribution of a febrile illness outbreak to typhoid. For the diagnostic evaluation, 179 patients were included; 49 had blood culture-confirmed typhoid, 76 had fever as a result of non-typhoid etiologies, and 54 were age-matched community controls. The median (interquartile range) age was 29 (20-46) years. Of the participants, 92 (51.4%) were male and 131 (73.2%) were indigenous Fijians. The sensitivities of the tests were 77.6% for TUBEX, 75.5% for Typhidot Rapid, and 57.1% for Test-It assay. The Test-It assay had the highest specificity of 93.4%, followed by Typhidot Rapid 85.5% and TUBEX 60.5%. Typhidot Rapid had the best performance in the simulation for attribution of a febrile illness outbreak to typhoid. Typhoid RDTs performed suboptimally for individual patient diagnosis due to low sensitivity and variable specificity. We demonstrate that RDTs could be useful in the field for rapid attribution of febrile illness outbreaks to typhoid. Typhidot Rapid had the best combination of sensitivity, specificity, positive and negative predictive values, cost, and ease of use for this purpose.

A retrospective study of patients with blood culture-confirmed typhoid fever in Fiji during 2014-2015: epidemiology, clinical features, treatment and outcome.

BACKGROUND: Typhoid fever is endemic in Fiji. We sought to describe the epidemiology, clinical features and case fatality risk of blood culture-confirmed typhoid fever from January 2014 through December 2015. METHODS: Blood culture-positive patients were identified from a typhoid surveillance line list. A standardised case investigation form was used to record data from patients' medical records. RESULTS: Of 542 patients, 518 (95.6%) were indigenous Fijians (iTaukei) and 285 (52.6%) were male. The median (IQR) age was 25 (16-38) y. Mean (SD) time from the onset of illness to admission was 11.1 (6.9) d. Of 365 patients with clinical information, 346 (96.9%) had fever, 239 (66.9%) diarrhoea, 113 (33.5%) vomiting, and 72 (30.2%) abdominal pain. There were 40 (11.0%) patients with complications, including 17 (4.7%) with shock, and 11 (3.0%) with hepatitis. Nine patients died for a case fatality risk of 1.7%. Of the 544 Salmonella Typhi isolates tested, none were resistant to first line antimicrobials; 3(0.8%) were resistant to ciprofloxacin and 5(1.4%) to nalidixic acid. CONCLUSIONS: In Fiji, most blood culture-confirmed typhoid fever cases were in young adults. Common clinical manifestations were fever and gastrointestinal symptoms. Further studies are required to elucidate the factors associated with complications and death.