Ticks are vectors for many pathogens of veterinary and medical interest. In order to monitor ticks and tick-borne pathogens, the “Tekenscanner” (Dutch for Tick scanner), a citizen science project, ...was launched in The Netherlands. It is a smartphone application for pet-owners to get ticks from their dog or cat, identified and checked for pathogens for free. At the same time, information about the pet and the geographic location of tick infestation becomes available for research. The application was launched in 2018, and the results of the first 6 months after launch of the app were reported. Ticks were identified based on morphology, and DNA was extracted and amplified by a panel of tick-borne pathogen-specific primers. Next, the amplicons were subjected to reverse line blot with specific probes for important pathogens to determine their presence or absence. The present paper describes the results of 2019 and 2020. There were 2260 ticks collected from 871 dogs and 255 cats (26 ticks were from an unknown host) and all pet owners were informed about the results. Four species of ticks were collected:
Ixodes ricinus
(90.0%),
Ixodes hexagonus
(7.3%),
Dermacentor reticulatus
(2.8%) and
Rhipicephalus sanguineus
(0.1%).
Ixodes ricinus
was the tick with the most divergent pathogens:
Anaplasma
sp. (1.3%),
Babesia
sp. (0.8%),
Borrelia
spp. (4.8%),
Neoehrlichia
sp. (3.7%) and
Rickettsia helvetica
(12.6%). In
I. hexagonus, R. helvetica
(1.8%) and
Babesia
sp. (0.6%) were detected and
Rickettsia raoultii
in
D. reticulatus
(16.2%). One of the two nymphs of
R. sanguineus
was co-infected with
Borrelia
and
R. helvetica
and the other one was uninfected. The high numbers of different pathogens found in this study suggest that companion animals, by definition synanthropic animals, and their ticks can serve as sentinels for emerging tick-borne pathogens.
Studies on the prevalence of feather pecking in different commercial laying hen
systems and its welfare and economic impacts are reviewed in the following
paper. Current methods for controlling ...feather pecking include beak-trimming and
alterations to light regimes, but these methods have significant disadvantages
from the perspective of bird welfare. A substantial body of research has now
identified risk factors for feather pecking during both the rearing and laying
periods. It is argued that these findings can be translated into optimised
management practices that can prevent and control feather pecking whilst
simultaneously conferring welfare benefits. The genetic basis of feather pecking
is considered, and studies that suggest group selection techniques could produce
birds with a reduced tendency to feather peck in commercial flocks are
highlighted.
Giardia duodenalis, a single-celled intestinal parasite, is divided into eight assemblages (A-H), with differences in host specificity. Giardia duodenalis reproduces asexually and cycles between the ...binucleated trophozoite (4 N) and the infectious cyst with four nuclei (16 N). Interaction between the nuclei is limited. Therefore, genetic drift causes differences in genetic make-up between the non-daughter nuclei; the allelic sequence heterozygosity (ASH). The ASH is low (0.01%--0.0023%) for the related assemblages A and E, higher (0.43-0.53) for assemblage B and much higher (0.74% -0.89%) for the assemblage C and D at the root of the phylogenetic tree. The heterozygosity in assemblage F, in the same clade as assemblage A and E, was unknown. The heterozygosity in the sequences of the gdh and dis3 genes was used as proxy for the ASH and whole genome amplification of single cysts followed by cloning and Sanger sequencing of dis3 fragment could reveal the genetic variation within the cyst. The aim of the study was to determine the level of heterozygosity within pooled and single cysts of different assemblages. The heterozygosity in gdh and dis3 was determined in pooled cysts of the assemblages A to F. Heterozygosity in the isolates of the assemblages C (n = 2) and D (n = 1) ranged from 0.41% to 0.82% for gdh and dis3 and no heterozygosity was found in the isolates of the assemblages A (n = 4), E (n = 3) and F (n = 3). The heterozygosity in assemblage B (n = 7) was intermediate (0% to 0.62%). Next, the number of haplotypes of dis3 was determined for single cysts of assemblages C, D and E. In the assemblages C and D, two to four haplotypes were found per cyst, while in assemblage E only one haplotype was identified. Having high heterozygosity is characteristic for the assemblages C and D, while having a low heterozygosity is characteristic for the clade with the assemblages A, E and F.
Summary
Salmonellosis is a public health concern in both the developed and developing countries. Although the majority of human non‐typhoidal Salmonella enterica (NTS) cases are the result of ...foodborne infections or person‐to‐person transmission, NTS infections may also be acquired by environmental and occupational exposure to animals. While a considerable number of studies have investigated the presence of NTS in farm animals and meat/carcasses, very few studies have investigated the risk of NTS colonization in humans as a result of direct animal exposure. We investigated asymptomatic NTS colonization in 204 backyard chicken farms, 204 farmers and 306 matched individuals not exposed to chicken farming, in southern Vietnam. Pooled chicken faeces, collected using boot or handheld swabs on backyard chicken farms, and rectal swabs from human participants were tested. NTS colonization prevalence was 45.6%, 4.4% and 2.6% for chicken farms, farmers and unexposed individuals, respectively. Our study observed a higher prevalence of NTS colonization among chicken farmers (4.4%) compared with age‐, sex‐ and location‐ matched rural and urban individuals not exposed to chickens (2.9% and 2.0%). A total of 164 chicken NTS strains and 17 human NTS strains were isolated, and 28 serovars were identified. Salmonella Weltevreden was the predominant serovar in both chickens and humans. NTS isolates showed resistance (20–40%) against tetracycline, chloramphenicol, sulfamethoxazole‐trimethoprim and ampicillin. Our study reflects the epidemiology of NTS colonization in chickens and humans in the Mekong delta of Vietnam and emphasizes the need of larger, preferably longitudinal studies to study the transmission dynamics of NTS between and within animal and human host populations.
Crizotinib is an oral tyrosine kinase inhibitor approved for treating patients with non‐small cell lung cancer (NSCLC) containing an anaplastic lymphoma kinase (ALK) rearrangement. We used knockout ...mice to study the roles of P‐glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) in plasma pharmacokinetics and brain accumulation of oral crizotinib, and the feasibility of improving crizotinib kinetics using coadministration of the dual ABCB1/ABCG2 inhibitor elacridar. In vitro, crizotinib was a good transport substrate of human ABCB1, but not of human ABCG2 or murine Abcg2. With low‐dose oral crizotinib (5 mg/kg), Abcb1a/1b−/− and Abcb1a/1b;Abcg2−/− mice had an approximately twofold higher plasma AUC than wild‐type mice, and a markedly (∼40‐fold) higher brain accumulation at 24 hr. Also at 4 hr, crizotinib brain concentrations were ∼25‐fold, and brain‐to‐plasma ratios ∼14‐fold higher in Abcb1a/1b−/− and Abcb1a/1b;Abcg2−/− mice than in wild‐type mice. High‐dose oral crizotinib (50 mg/kg) resulted in comparable plasma pharmacokinetics between wild‐type and Abcb1a/1b−/− mice, suggesting saturation of intestinal Abcb1. Nonetheless, brain accumulation at 24 hr was still ∼70‐fold higher in Abcb1a/1b−/− than in wild‐type mice. Importantly, oral elacridar coadministration increased the plasma and brain concentrations and brain‐to‐plasma ratios of crizotinib in wild‐type mice, equaling the levels in Abcb1a/1b;Abcg2−/− mice. Our results indicate that crizotinib oral availability and brain accumulation were primarily restricted by Abcb1 at a non‐saturating dose, and that coadministration of elacridar with crizotinib could substantially increase crizotinib oral availability and delivery to the brain. This principle might be used to enhance therapeutic efficacy of crizotinib against brain metastases in NSCLC patients.
What's new?
Crizotinib is an oral tyrosine kinase inhibitor approved for treating non‐small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase rearrangements. While NSCLC patients are likely to develop brain metastases, brain accumulation of crizotinib is limited. This study investigates the consequences of crizotinib transport by murine Abcb1 and Abcg2 and ways to counter them. Crizotinib oral availability and brain accumulation were restricted by Abcb1 at a non‐saturating dose, and co‐administration of the dual ABCB1/ABCG2 inhibitor elacridar drastically increased oral availability and brain delivery. This principle might be used to enhance therapeutic efficacy of crizotinib against brain metastases in NSCLC patients.
Brucella canis had not been isolated in the Netherlands until November 2016, when it was isolated from a dog imported from Romania. Including this case, 16 suspected cases were notified to the ...authorities during the following 25 months. Of these 16 dogs, 10 were seropositive; tracking investigations found another 8 seropositive littermates. All seropositive animals were rescue dogs imported from Eastern Europe. B. canis was cultured from urine, blood, and other specimens collected from the dogs. Genotyping of isolates revealed clustering by litter and country. Isolating B. canis in urine indicates that shedding should be considered when assessing the risk for zoonotic transmission. This case series proves introduction of B. canis into a country to which it is not endemic through import of infected dogs from B. canis–endemic areas, posing a threat to the naive autochthonous dog population and humans.
•This study is unique in its aim to target trunk mutations of the primary tumor.•Combining tremelimumab, durvalumab and SBRT on the primary tumor is safe.•Treating patients with anti-CTLA4 followed ...by anti-PDL-1 with intercalated radiotherapy or vice versa does not seem to differ.•Targeting only a part of the primary tumor with SBRT does not seem to induce major responses.
This phase I study primarily addresses the safety and tolerability of Stereotactic radiotherapy on the primary tumor combined with double Immune Checkpoint Inhibition (SICI) in patients with non-small cell lung cancer (NSCLC). Increasing the release of neoantigens by radiotherapy might enhance response to immunotherapy. Especially, by targeting trunk mutations in the primary tumor.
In three sequential cohorts, immunotherapy regimes combined with stereotactic body radiotherapy (SBRT) on the primary tumor (1x20 Gy on 9 cc) were studied in stage IIIB/IV NSCLC patients progressing on chemotherapy. The first cohort (n = 3) received durvalumab. The second (n = 6) received a combination of tremelimumab and durvalumab followed by durvalumab monotherapy. The third cohort (n = 6) was similar except that the combination was reversed. Descriptive statistics were used to assess safety parameters and the exploratory outcomes of efficacy. Adverse events were reported using NCI CTCAE version 4.03. Exhaled breath was analyzed at baseline.
Fifteen patients were included. Median irradiated volume was 9.13 cc, on a median primary tumor volume of 79 cc. There were seven patients with grade 1–2, and two patients with grade 3 treatment related adverse events. There was 1 dose limiting toxicity (colitis) with double immunotherapy.
The combination of SBRT to the primary tumor and double immunotherapy in advanced NSCLC patients is safe and feasible.
The gauging of free surface flows in waterways provides
the foundation for monitoring and managing the water resources of built and
natural environments. A significant body of literature exists ...around the
techniques and benefits of optical surface velocimetry methods to estimate
flows in waterways without intrusive instruments or structures. However, to
date, the operational application of these surface velocimetry methods has
been limited by site configuration and inherent challenging optical
variability across different natural and constructed waterway environments.
This work demonstrates a significant advancement in the operationalisation
of non-contact stream discharge gauging applied in the computer vision
stream gauging (CVSG) system through the use of methods for remotely
estimating water levels and adaptively learning discharge ratings over time.
A cost-effective stereo camera-based stream gauging device (CVSG device) has
been developed for streamlined site deployments and automated data
collection. Evaluations between reference state-of-the-art discharge
measurement technologies using DischargeLab (using surface structure image
velocimetry), Hydro-STIV (using space–time image velocimetry),
acoustic Doppler current profilers (ADCPs), and gauging station discharge ratings
demonstrated that the optical surface velocimetry methods were capable of
estimating discharge within a 5 %–15 % range between these best available
measurement approaches. Furthermore, results indicated model machine
learning approaches leveraging data to improve performance over a period of
months at the study sites produced a marked 5 %–10 % improvement in
discharge estimates, despite underlying noise in stereophotogrammetry water
level or optical flow measurements. The operationalisation of optical
surface velocimetry technology, such as CVSG, offers substantial advantages
towards not only improving the overall density and availability of data used
in stream gauging, but also providing a safe and non-contact approach for
effectively measuring high-flow rates while providing an adaptive solution
for gauging streams with non-stationary characteristics.
Display omitted
•Shortening of ERP was found on all three farms after IVM and MOX treatment.•The Cylicocyclus L3s dominate in larval cultures obtained after MOX treatment.•The shorter the ERP, the ...more cyathostomin species shortly after MOX treatment.•Decreased MOX susceptibility is the most plausible cause of shortening of the ERP.
For the control of cyathostomins in horses, the macrocyclic lactones (MLs), moxidectin (MOX) and ivermectin (IVM) are the most commonly used anthelmintics. However, reduced activity, observed as shortening of the egg reappearance period (ERP) has been described. Shortening of the ERP may be caused by a decreased susceptibility of immature worms for MLs. Alternatively, immature worms may develop faster into egg producing adults as a result of repeated ML treatments. The species composition of the larval cultures obtained shortly after ML and pyrantel (PYR) treatment can confirm the hypothesis of decreased ML susceptibility, as this is often class-specific, whereas faster development would also occur after treatment with anthelmintics with a different mode of action. From 3 farms with a known history of shortened ERP, 8 horses per farm were selected and divided into 2 groups. The MOX-PYR-MOX group was treated twice with MOX (day 0 and 126) and once with PYR (day 84) and the IVM-PYR-IVM group was treated twice with IVM (day 0 and 98) and once with PYR (day 56). Cultured infective larvae (L3s) were counted and differentiated with the reverse line blot on pooled samples. Per cyathostomin species, the number of larvae per gram was calculated. The efficacy of all ML treatments was 100% and a shortened ERP was found on all 3 farms. The species composition of the larval cultures after ML treatment did not differ significantly from that after PYR treatment in the IVM-PYR-IVM group, but it did differ in the MOX-PYR-MOX group. The larval cultures obtained after MOX treatment consisted mostly of Cylicocyclus nassatus, while after PYR treatment Cylicostephanus longibursatus was the most abundant species. In the cultures from 42days after MOX treatment 6 cyathostomin species from 3 genera were found on the farm with the lowest activity (farm 1), while on the farm with the highest activity (farm 3) only 3 species from one genus were found in the same number of examined L3s. The high numbers of L3s of Cylicocyclus species 42days after MOX treatment and the low numbers 42days after PYR treatment can be explained by reduced susceptibility of the immature worms to MOX, but not by a faster development. In conclusion, shortening of the ERP following MOX treatment is most likely a process in which an increasing number of immature worms from an increasing number of species is becoming less susceptible to the active compound.
To accurately diagnose giardiosis in dogs, knowledge of diagnostic test characteristics and expected prevalence are required. The aim of this work was to estimate test characteristics (sensitivity ...and specificity) of four commonly used diagnostic tests for detection of Giardia duodenalis in dogs.
Fecal samples from 573 dogs originating from four populations (household dogs, shelter dogs, hunting dogs and clinical dogs) were examined with centrifugation sedimentation flotation (CSF) coproscopical analysis, direct immunofluorescence assay (DFA, Merifluor Cryptosporidium/Giardia®), a rapid enzyme immunochromatographic assay (IDEXX SNAP Giardia®) and qPCR (SSU rDNA) for presence of G. duodenalis. Bayesian latent class analysis was used to determine test performance characteristics and to estimate G. duodenalis prevalence of each of the four dog populations.
All tests were highly specific. IDEXX SNAP Giardia® showed the highest specificity (99.6%) and qPCR the lowest (85.6%). The sensitivities were much more variable, with qPCR showing the highest (97.0%) and CSF the lowest (48.2%) sensitivity. DFA was more sensitive than IDEXX SNAP Giardia®, but slightly less specific. Prevalences of G. duodenalis differed substantially between populations, with the hunting dogs showing the highest G. duodenalis prevalence (64.9%) and the household dogs the lowest (7.9%).
This study identifies qPCR as a valuable screening tool because of its high sensitivity, whereas methods using microscopy for cyst identification or cyst wall detection should be used in situations where high specificity is required. G. duodenalis is a prevalent gastro-intestinal parasite in Dutch dogs, especially in dogs living in groups (hunting and shelter dogs) and clinical dogs.
PDF
