Benefits of Using a Transdisciplinary Approach for the Design and Operationalization of a Surveillance System

Abstract During the preparatory phase of a surveillance project in Western Kenya, it was noted that several animal health activities, including meat inspection, were recorded using paper-based forms. Through discussions with the meat inspectors and other slaughterhouse actors, an electronic meat inspection form was developed, tested, and used in two slaughterhouses in Bungoma County. The meat inspectors completed and submitted a form for every animal slaughtered at their facility over a 2.75-year period. In a feedback meeting with the meat inspectors and other stakeholders, areas for improvement were highlighted, such as the timely provision of feedback to the data providers, and the inclusion of data fields that allow for more detailed animal movement information. The meat inspectors remarked that the form made them feel appreciated and added value to their work as the data could be used to educate farmers on prevailing livestock conditions and provide economic incentives for disease control interventions. The data submitted via the electronic forms were of sufficient quality to be summarized and identify trends in the animal slaughterhouse throughput, as well as frequent reasons for meat condemnation and associated costs. These data could therefore set the foundation for a syndromic surveillance system based on slaughterhouse data. Other non-traditional data sources, such as livestock and meat transport certificates, could also be leveraged to create a post-farm animal health information system. Information © The Authors 2023 </jats:sec

Evaluation of the fluorescence polarization assay as a rapid on-spot test for ruminant brucellosis in Cote d'Ivoire

Brucellosis is a zoonosis of economic and public health concern. While most diagnostic tests for brucellosis can only be performed in the laboratory, the Fluorescence Polarization Assay (FPA) was developed as a rapid point-of-care field test. This pilot project aimed to validate the use of FPA for rapid diagnosis of ruminant brucellosis on the field, and to compare the FPA performance with that of the more commonly used Rose Bengal Test (RBT). Blood samples were first collected from ruminants in a livestock market, and later from a nearby slaughterhouse in Port Bouët, Abidjan, Côte d'Ivoire. Samples collected in the livestock market were processed and tested with the FPA in a central laboratory, while samples collected in the slaughterhouse were processed immediately and the FPA was performed on site. To assess the FPA intra-test agreement, a portion of the serum samples tested at the slaughterhouse were re-tested with the FPA in the laboratory later the same day. To assess inter-test agreement, all serum samples were retested with the RBT. A total of 232 samples were tested with the FPA, 106 and 126 from the livestock market and slaughterhouse, respectively. Of these, 26 tested positive and 39 were doubtful for brucellosis. The FPA was repeated on 28 of the samples collected at the slaughterhouse, and comparison of results indicated a moderate intra-test agreement (Kappa = 0.41). The agreement improved when the doubtful category was treated as negative (Kappa = 0.65), and when cattle were excluded (Kappa = 0.56 to 0.61). The RBT was performed on 229 samples, and of these 10 tested positive. A comparison of FPA and RBT results indicated poor agreement (Kappa = 0.00); this improved to slight when only samples taken at the livestock market and tested in the laboratory were considered (Kappa = 0.14). The FPA did not perform well in tropical field conditions, possibly due to the high ambient temperatures in the slaughterhouse. Moreover, a difference in performance was noted in relation to the species tested, whereby the FPA seemed to perform better on sheep and goat samples, compared to cattle samples. These findings highlight that further adjustments are needed before implementing the FPA on the field

Electronic data collection to enhance disease surveillance at the slaughterhouse in a smallholder production system

Globally, meat inspection provides data for animal health surveillance. However, paper-based recording of data is often not reported through to higher authorities in sufficient detail. We trialled the use of an electronic meat inspection form in Kenyan slaughterhouses, in lieu of the currently used paper-based format. Meat inspectors in two ruminant slaughterhouses completed and submitted an electronic report for each animal slaughtered at their facility. The reports, which captured information on the animal demographics and any eventual condemnations, were stored in a central database and available in real-time. A stakeholder meeting was held towards the end of the study. Over the 2.75 year study period, 16,386 reports were submitted; a downward linear trend in the monthly submissions was noted. There was a week effect, whereby more reports were submitted on the market day. Of the slaughtered animals, 23% had at least a partial condemnation. The most frequently condemned organs were the liver, lungs and intestines; the primary reasons for condemnations were parasitic conditions. Lack of feedback and difficulty capturing animal origin information were the primary challenges highlighted. The study demonstrated that electronic data capture is feasible in such challenging environments, thereby improving the timeliness and resolution of the data collected

Who let the dogs out? Exploring the spatial ecology of free‐roaming domestic dogs in western Kenya

The spatial ecology of free‐roaming dogs determines their role in the transmission of zoonoses. This study describes the geographic range of and identifies sites frequently visited by free‐roaming domestic dogs in western Kenya. Eight sites in Busia county, western Kenya, were selected. At each site, ten dog‐keeping households were recruited, a questionnaire was administered, and a GPS logger was fixed around the neck of one dog in each household. Loggers were programmed to capture the dog's position every minute, for five consecutive days. Individual summaries of GPS recordings were produced, and the daily distance traveled was calculated. 50% and 95% utilization distribution isopleths were produced, and the area within these isopleths was extracted to estimate the size of the core and extended Home Ranges (HRs), respectively. Linear regression analyses were performed to identify factors associated with the movement parameters. The centroid points of the 10, 50, and 90% isopleths were reproduced, and the corresponding sites identified on the ground. Seventy‐three dogs were included in the final analyses. The median daily distance traveled was 13.5km, while the median core and extended HRs were 0.4 and 9.3 ha, respectively. Older dogs had a larger extended HR and traveled more daily, while the effect of sex on dog movement depended on their neutering status. Dogs spent most of their time at their household; other frequently visited sites included other household compounds, fields, and rubbish dumps. One of the centroids corresponded to a field located across the international Kenya–Uganda border, emphasizing the fluidity across the border in this ecosystem. Multiple dogs visited the same location, highlighting the heterogeneous contact networks between dogs, and between dogs and people. The field data presented are of value both in understanding domestic dog ecology and resource utilization, and in contextualizing infectious and parasitic disease transmission models

System Thinking and Citizen Participation Is Still Missing in One Health Initiatives - Lessons From Fifteen Evaluations.

Tackling complex public health challenges requires integrated approaches to health, such as One Health (OH). A key element of these approaches is the integration of knowledge across sectors, disciplines and stakeholders. It is not yet clear which elements of knowledge integration need endorsement to achieve best outcomes. This paper assesses 15 OH initiatives in 16 African, Asian and European countries to identify opportunities to improve knowledge integration and to investigate geographic influences on knowledge integration capacities. Two related evaluation tools, both relying on semi-quantitative questionnaires, were applied to two sets of case studies. In one tool, the questions relate to operations and infrastructure, while the other assigns questions to the three phases of "design," "implementation," and "evaluation" of the project life cycle. In both, the question scores are aggregated using medians. For analysis, extreme values were identified to highlight strengths and weaknesses. Seven initiatives were assessed by a single evaluator external to the initiative, and the other eight initiatives were jointly assessed by several internal and external evaluators. The knowledge integration capacity was greatest during the project implementation stage, and lowest during the evaluation stage. The main weaknesses pointing towards concrete potential for improvement were identified to be a lack of consideration of systemic characteristics, missing engagement of external stakeholders and poor bridging of knowledge, amplified by the absence of opportunities to learn and evolve in a collective process. Most users were unfamiliar with the systems approach to evaluation and found the use of the tools challenging, but they appreciated the new perspective and saw benefits in the ensuing reflections. We conclude that systems thinking and associated practises for OH require not only specific education in OH core competencies, but also methodological and institutional measures to endorse broad participation. To facilitate meta-analyses and generic improvement of integrated approaches to health we suggest including knowledge integration processes as elements to report according to the COHERE guidelines

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The Genome of Caenorhabditis bovis

The free-living nematode Caenorhabditis elegans is a key laboratory model for metazoan biology. C. elegans has also become a model for parasitic nematodes despite being only distantly related to most parasitic species. All of the ∼65 Caenorhabditis species currently in culture are free-living, with most having been isolated from decaying plant or fungal matter. Caenorhabditis bovis is a particularly unusual species that has been isolated several times from the inflamed ears of Zebu cattle in Eastern Africa, where it is associated with the disease bovine parasitic otitis. C. bovis is therefore of particular interest to researchers interested in the evolution of nematode parasitism. However, as C. bovis is not in laboratory culture, it remains little studied. Here, by sampling livestock markets and slaughterhouses in Western Kenya, we successfully reisolated C. bovis from the ear of adult female Zebu. We sequenced the genome of C. bovis using the Oxford Nanopore MinION platform in a nearby field laboratory and used the data to generate a chromosome-scale draft genome sequence. We exploited this draft genome sequence to reconstruct the phylogenetic relationships of C. bovis to other Caenorhabditis species and reveal the changes in genome size and content that have occurred during its evolution. We also identified expansions in several gene families that have been implicated in parasitism in other nematode species. The high-quality draft genome and our analyses thereof represent a significant advancement in our understanding of this unusual Caenorhabditis species

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response