SNIFF AND TELL: THE FEASIBILITY OF USING BIO-DETECTION DOGS AS A MOBILE DIAGNOSTIC INTERVENTION FOR ASYMPTOMATIC MALARIA IN SUB-SAHARAN AFRICA.

Bio-Detection Dogs (BDDs) are used in some high-income countries as a diagnostic intervention, yet little is known about their potential in low/middle-income countries with limited diagnostic resources. This exploratory study investigated the opportunities and implications of deploying BDDs as a mobile diagnostic intervention to identify people with asymptomatic malaria, particularly at ports of entry, as an important step to malaria elimination in a population. A qualitative study design consisting of participant observation, five focus group discussions and informal conversations was employed in The Gambia in April-May 2017. A disciplined German Shepherd companion dog (not trained as a BDD) was introduced to research participants and their perceptions recorded. Field-notes and discussions were transcribed, translated and analysed thematically. Most research participants viewed positively the possibility of using BDDs to detect malaria, with the major advantage of being non-invasive. Some concerns, however, were raised regarding safety and efficacy, as well as cultural issues around the place of dogs within human society. The Gambia is a rabies-endemic country, and unfamiliar dogs are not usually approached, with implications for how research participants perceived BDDs. Understanding such concerns and working with local people to address such issues must be part of any successful strategy to deploy BDDs in new settings. Bio-Detection Dogs represent a potentially non-invasive diagnostic tool for the detection of asymptomatic or chronic malaria infections, particularly in areas with very low parasite rates. However, it is important to understand local concerns and work closely with communities to address those concerns. Wider deployment of BDDs will also require careful planning and sustained financial support.

Using sniffing behavior to differentiate true negative from false negative responses in trained scent-detection dogs.

False negatives are recorded in every chemical detection system, but when animals are used as a scent detector, some false negatives can arise as a result of a failure in the link between detection and the trained alert response, or a failure of the handler to identify the positive alert. A false negative response can be critical in certain scenarios, such as searching for a live person or detecting explosives. In this study, we investigated whether the nature of sniffing behavior in trained detection dogs during a controlled scent-detection task differs in response to true positives, true negatives, false positives, and false negatives. A total of 200 videos of 10 working detection dogs were pseudorandomly selected and analyzed frame by frame to quantify sniffing duration and the number of sniffing episodes recorded in a Go/No-Go single scent-detection task using an eight-choice test apparatus. We found that the sniffing duration of true negatives is significantly shorter than false negatives, true positives, and false positives. Furthermore, dogs only ever performed one sniffing episode towards true negatives, but two sniffing episodes commonly occurred in the other situations. These results demonstrate how the nature of sniffing can be used to more effectively assess odor detection by dogs used as biological detection devices.

Detection of SARS-CoV-2 by Canine Olfaction: A Pilot Study.

Background: As the number of coronavirus disease 2019 (COVID-19) cases continue to surge worldwide and new variants emerge, additional accurate, rapid, and noninvasive screening methods to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed. The number of COVID-19 cases reported globally is >455 million, and deaths have surpassed 6 million. Current diagnostic methods are expensive, invasive, and produce delayed results. While COVID-19 vaccinations are proven to help slow the spread of infection and prevent serious illness, they are not equitably available worldwide. Almost 40% of the world's population remains unvaccinated. Evidence suggests that SARS-CoV-2 virus-associated volatile organic compounds found in the breath, urine, and sweat of infected individuals can be detected by canine olfaction. Medical detection dogs may be a feasible, accurate, and affordable SARS-CoV-2 screening method. Methods: In this double-blinded, case-control, validation study, we obtained sweat samples from inpatients and outpatients tested for SARS-CoV-2 by a polymerase chain reaction test. Medical detection dogs were trained to distinguish SARS-CoV-2-positive samples from SARS-CoV-2-negative samples using reward-based reinforcement. Results: Samples were obtained from 584 individuals (6-97 years of age; 24% positive SARS-CoV-2 samples and 76% negative SARS-CoV-2 samples). In the testing phase, all dogs performed with high accuracy in detecting SARS-CoV-2. The overall diagnostic sensitivity was 98%, and specificity was 92%. In a follow-up phase, 1 dog screened 153 patients for SARS-CoV-2 in a hospital setting with 96% diagnostic sensitivity and 100% specificity. Conclusions: Canine olfaction is an accurate and feasible method for diagnosis of SARS-CoV-2, including asymptomatic and presymptomatic infected individuals.

Using trained dogs and organic semi-conducting sensors to identify asymptomatic and mild SARS-CoV-2 infections: an observational study.

BACKGROUND: A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry. METHODS: Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected individuals, with sensitivity and specificity as the primary outcome. Mathematical modelling was used to investigate the impact of bio-detection dogs for screening. RESULTS: About, 3921 adults were enrolled in the study and odour samples collected from 1097 SARS-CoV-2 infected and 2031 uninfected individuals. OSC sensors were able to distinguish between SARS-CoV-2 infected individuals and uninfected, with sensitivity from 98% (95% CI 95-100) to 100% and specificity from 99% (95% CI 97-100) to 100%. Six dogs were able to distinguish between samples with sensitivity ranging from 82% (95% CI 76-87) to 94% (95% CI 89-98) and specificity ranging from 76% (95% CI 70-82) to 92% (95% CI 88-96). Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only. CONCLUSIONS: People infected with SARS-CoV-2, with asymptomatic or mild symptoms, have a distinct odour that can be identified by sensors and trained dogs with a high degree of accuracy. Odour-based diagnostics using sensors and/or dogs may prove a rapid and effective tool for screening large numbers of people.Trial Registration NCT04509713 (clinicaltrials.gov).

Feasibility of integrating canine olfaction with chemical and microbial profiling of urine to detect lethal prostate cancer.

Prostate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs' diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70-76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples.

A Lesson in Standardization - Subtle Aspects of the Processing of Samples Can Greatly Affect Dogs' Learning.

Training new medical odors presents challenges in procuring sufficient target samples, and suitably matched controls. Organizations are often forced to choose between using fewer samples and risking dogs learning individuals or using differently sourced samples. Even when aiming to standardize all aspects of collection, processing, storage and presentation, this risks there being subtle differences which dogs use to discriminate, leading to artificially high performance, not replicable when novel samples are presented. We describe lessons learnt during early training of dogs to detect prostate cancer from urine. Initially, six dogs were trained to discriminate between hospital-sourced target and externally-sourced controls believed to be processed and stored the same way. Dogs performed well: mean sensitivity 93.5% (92.2-94.5) and specificity 87.9% (78.2-91.9). When training progressed to include hospital-sourced controls, dogs greatly decreased in specificity 67.3% (43.2-83.3). Alerted to a potential issue, we carried out a methodical, investigation. We presented new strategically chosen samples to the dogs and conducted a logistic regression analysis to ascertain which factor most affected specificity. We discovered the two sets of samples varied in a critical aspect, hospital-processed samples were tested by dipping the urinalysis stick into the sample, whilst for externally sourced samples a small amount of urine was poured onto the stick. Dogs had learnt to distinguish target aided by the odor of this stick. This highlights the importance of considering every aspect of sample processing even when using urine, often believed to be less susceptible to contamination than media like breath.

An Owner-Independent Investigation of Diabetes Alert Dog Performance.

Objective: To quantify Diabetes Alert Dog (DAD) performance by using owner-independent measures. Research Design and Methods: Eight owners of accredited DADs used a FreeStyle Libre Flash Glucose Monitoring System (FGMS). Concurrent Closed Circuit Television (CCTV) footage was collected for between 5 and 14 days in each owner's home or workplace. The footage was blind-coded for dogs' alerting behaviors. The sensitivity, False Positive Rate and Positive Predictive Values (PPV) of dogs' alerts to out-of-range (OOR) episodes were calculated. Ratings for 11 attributes describing participant's lifestyle and compliance (taken from each dog's instructor) and the percentage of DAD alerts responded to by the owner as per training protocol (taken from CCTV footage) were assessed for association with dog performance. Results: Dogs alerted more often when their owners' glucose levels were outside vs. inside target range (hypoglycaemic 2.80-fold, p = 0.001; hyperglycaemic 2.29-fold, p = 0.005). Sensitivity to hypoglycaemic episodes ranged from 33.3 to 91.7%, the mean was 55.9%. Mean PPV for OOR episodes was 69.7%. Sensitivity and PPV were associated with aspects of the dog and owner's behavior, and the owner's adherence to training protocol. Conclusions: Owner-independent methods support that some dogs alert to hypo- and hyperglycaemic events accurately, but performance varies between dogs. We find that DAD performance is affected by traits and behaviors of both the dog and owner. Combined with existing research showing the perceived psychosocial value and reduced critical health care needs of DAD users, this study supports the value of a DAD as part of a diabetes care plan. It also highlights the importance of ongoing training and continued monitoring to ensure optimal performance.

How effective are trained dogs at alerting their owners to changes in blood glycaemic levels?: Variations in performance of glycaemia alert dogs.

AIMS: Domestic dogs are trained to a wide variety of roles including an increasing number of medical assistance tasks. Glycaemia alert dogs are reported to greatly improve the quality of life of owners living with Type 1 diabetes. Research into their value is currently sparse, on small numbers of dogs and provides conflicting results. In this study we assess the reliability of a large number of trained glycaemic alert dogs at responding to hypo- and hyper-glycaemic (referred to as out-of-range, OOR) episodes, and explore factors associated with variations in their performance. METHODS: Routine owner records were used to assess the sensitivity and specificity of each of 27 dogs, trained by a single UK charity during almost 4000 out-of-range episodes. Sensitivity and positive predictive values are compared to demographic factors and instructors' ratings of the dog, owner and partnership. RESULTS: Dogs varied in their performance, with median sensitivity to out-of-range episodes at 70% (25th percentile = 50, 75th percentile = 95). To hypoglycaemic episodes the median sensitivity was 83% (66-94%) while to hyperglyaemic episodes it was 67% (17-91%). The median positive predictive value (PPV) was 81% (68-94%), i.e. on average 81% of alerts occurred when glucose levels were out of target range. For four dogs, PPV was 100%. Individual characteristics of the dog, the partnership and the household were significantly associated with performance (e.g., whether the dog was previously a pet, when it was trained, whether its partner was an adult or child). CONCLUSIONS: The large sample shows that the individual performance of dogs is variable, but overall their sensitivity and specificity to OOR episodes are better than previous studies suggest. Results show that optimal performance of glycaemic alert dogs depends not only on good initial and ongoing training, but also careful selection of dogs for the conditions in which they will be working.

Canine Olfactory Thresholds to Amyl Acetate in a Biomedical Detection Scenario.

Dogs' abilities to respond to concentrations of odorant molecules are generally deemed superior to electronic sensors. This sensitivity has been used traditionally in many areas; but is a more recent innovation within the medical field. As a bio-detection sensor for human diseases such as cancer and infections, dogs often need to detect volatile organic compounds in bodily fluids such as urine and blood. Although the limits of olfactory sensitivity in dogs have been studied since the 1960s, there is a gap in our knowledge concerning these limits in relation to the concentration of odorants presented in a fluid phase. Therefore, the aim of this study was to estimate olfactory detection thresholds to an inert substance, amyl acetate presented in a liquid phase. Ten dogs were trained in a "Go/No go" single scent-detection task using an eight-choice carousel apparatus. They were trained to respond to the presence of solutions of amyl acetate diluted to varying degrees in mineral oil by sitting in front of the positive sample, and not responding to the 7 other control samples. Training and testing took place in an indoor room with the same handler throughout using a food reward. After 30 weeks of training, using a forward chaining technique, dogs were tested for their sensitivity. The handler did not assist the dog during the search and was blind to the concentration of amyl acetate tested and the position of the target in the carousel. The global olfactory threshold trend for each dog was estimated by fitting a least-squares logistic curve to the association between the proportion of true positives and amyl acetate concentration. Results show an olfactory detection threshold for fluid mixtures ranging from 40 parts per billion to 1.5 parts per trillion. There was considerable inter-dog difference in sensitivity, even though all dogs were trained in the same way and worked without the assistance of the handler. This variation highlights factors to be considered in future work assessing olfactory detection performance by dogs.

Application of quality improvement techniques to reduce parenteral nutrition wastage in a national intestinal failure unit.

OBJECTIVES: Parenteral nutrition (PN) costs approximately £80 per day per bag. Unpredictable changes in patients' clinical condition, venous access loss or reasons related to the processes involved in administering PN can lead to PN wastage. Cost efficiencies are imperative to optimise limited resource utilisation in all current healthcare economies. We undertook a quality improvement (QI) project to reduce PN wastage in an adult acute hospital setting. The project SMART's (specific, measurable, achievable, realistic, time-based) objective was reducing in-patient PN wastage by 10% in 9 months using QI methodology on a national intestinal failure unit (IFU). METHOD: Wastage reasons were evaluated through pareto charts to target waste reduction using 'Plan, Do, Study, Act' (PDSA) cycles. Variation was mapped using c-charts. RESULTS: 12-week baseline wastage data predicted 1000 bags wasted per annum (p.a.). PDSA cycles actioned included: regular enhanced clinical team awareness of wastage; unused PN bags redistributed within expiry date; stock bag rotation; critical path analysis of PN bag journey; enhanced discharge planning/coordination; reorganisation of fridge PN storage according to weekday; changing ordering frequency and bag type (from tailored to standard) to increase flexibility around discharge date and PN weaning. Implementation of PDSA cycles led to a 34% reduction in PN wastage in 9 months. CONCLUSION: In a high-use IFU, PN wastage is common and costly. Using a QI approach with concurrent PDSA cycles and a motivated multidisciplinary team, high levels of wastage reduction are possible with associated significant cost savings and from this study a predicted cost saving of approximately £30 000 p.a.

Investigation into the value of trained glycaemia alert dogs to clients with type I diabetes.

Previous studies have suggested that some pet dogs respond to their owners' hypoglycaemic state. Here, we show that trained glycaemia alert dogs placed with clients living with diabetes afford significant improvements to owner well-being. We investigated whether trained dogs reliably respond to their owners' hypoglycaemic state, and whether owners experience facilitated tightened glycaemic control, and wider psychosocial benefits. Since obtaining their dog, all seventeen clients studied reported positive effects including reduced paramedic call outs, decreased unconscious episodes and improved independence. Owner-recorded data showed that dogs alerted their owners, with significant, though variable, accuracy at times of low and high blood sugar. Eight out of the ten dogs (for which owners provided adequate records) responded consistently more often when their owner's blood sugars were reported to be outside, than within, target range. Comparison of nine clients' routine records showed significant overall change after obtaining their dogs, with seven clients recording a significantly higher proportion of routine tests within target range after obtaining a dog. HbA1C showed a small, non significant reduction after dog allocation. Based on owner-reported data we have shown, for the first time, that trained detection dogs perform above chance level. This study points to the potential value of alert dogs, for increasing glycaemic control, client independence and consequent quality of life and even reducing the costs of long-term health care.

Volatile organic compounds as biomarkers of bladder cancer: Sensitivity and specificity using trained sniffer dogs.

In a previous canine study, we demonstrated that volatile organic compounds specific to bladder cancer are present in urine headspace, subsequently showing that up to 70% of tumours can be correctly classified using an electronic nose. This study aimed to evaluate the sensitivity and specificity which can be achieved by a group of four trained dogs. In a series of 30 double-blind test runs, each consisting of one bladder cancer urine sample placed alongside six controls, the highest sensitivity achieved by the best performing dog was 73% (95% CI 55-86%), with the group as a whole correctly identifying the cancer samples 64% (95% CI 55-73%) of the time. Specificity of the dogs individually ranged from 92% (95% CI 82-97%) for urine samples obtained from healthy, young volunteers down to 56% (95% CI 42-68%) for those taken from older patients with non-cancerous urological disease. Odds ratio comparisons confirmed a significant decrease in performance as the extent of urine dipstick abnormality and/or pathology amongst the control population increased. Importantly, however, statistical analysis indicated that covariates such as smoking, gender and age, as well as blood, protein and /or leucocytes in the urine did not significantly alter the odds of response to the cancer samples. Our results provide further evidence that volatile biomarkers for bladder cancer exist in urine headspace, and that these have the potential to be exploited for diagnosis.

Hearing dogs: a longitudinal study of social and psychological effects on deaf and hard-of-hearing recipients.

The organization Hearing Dogs for Deaf People provides assistance dogs that alert their deaf or hard-of-hearing recipients to key sounds, thus increasing their independence and also providing companionship. Fifty-one recipients took part in a longitudinal study to monitor the dogs' working performance over time and to examine the social and psychological effects of having a Hearing Dog. The Profile of Mood State (POMS) questionnaire and the General Health Questionnaire (GHQ) were used together with a Hearing Dog Questionnaire (HDQ) specifically developed for this study. There were a number of significant differences in measures of well-being between the period prior to placing the Hearing Dog and the period after placement, but there were no comparable differences during the year-long waiting period prior to placement of the dog. Recipients reported significant reductions in hearing-related problems such as response to environmental sounds; significant reductions in measures of tension, anxiety, and depression; and significant improvements in social involvement and independence. The longitudinal nature of this study supports evidence that these improvements persist for some time after the placement of a dog, with significant differences being reported, in many cases, up to 18 months after acquiring a dog.

Olfactory detection of human bladder cancer by dogs: proof of principle study.

OBJECTIVE: To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. DESIGN: Experimental, "proof of principle" study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. PARTICIPANTS: 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years--54 samples used in training; 54 used for testing). MAIN OUTCOME MEASURE: Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). RESULTS: Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. CONCLUSIONS: Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.