Environmental DNA in human and veterinary parasitology - Current applications and future prospects for monitoring and control.

Parasites are important pathogens with significant global economic, public and animal health impacts. Successful control or elimination of many parasitic diseases, not least neglected tropical parasites, will require scalable, sensitive and cost-effective monitoring tools. Environmental DNA (eDNA) methods, used extensively in ecology for biomonitoring in natural ecosystems, offer promising advantages such reduced costs and labor requirements for species monitoring. Yet, the use of eDNA-based methods in parasitology and disease surveillance, has only recently begun to be explored. With this review, we wish to give an up-to-date overview of current uses and limitations of eDNA in human and veterinary parasitology, and how existing challenges can be overcome to fully utilize the potential of eDNA for monitoring and control of parasitic diseases. We begin by systematically searching published literature to identify studies that apply eDNA methods in parasitology and synthesize the main findings from these studies. We find that eDNA applications in parasitology only account for a small proportion (73/1960) of all eDNA publications up to now, and even fewer (27/73) studies, that apply eDNA methods specifically for parasites of human or veterinary importance. The majority of studies concern snail-borne trematodes and their intermediate host snails, while a few apply eDNA for mosquito vector species detection. A strong geographical bias, with only very few studies undertaken on the African continent, where parasites are of the biggest public health concern, is also noted. Current obstacles hindering further advances of eDNA methods in parasitology include incomplete reference databases, and challenges related to real-time monitoring in remote areas, and in certain LMIC settings. Finally, we point to future opportunities for eDNA-based research in parasitology and highlight recent innovations in eDNA research, which could further develop its application for monitoring and control of parasitic diseases and vectors in the future.

Sero-prevalence and risk factors of Toxoplasma gondii infection in wild cervids in Denmark.

Toxoplasma gondii is a zoonotic protozoan parasite capable of infecting possibly all warm-blooded animals including humans, and is one of the most widespread zoonotic pathogens known. Free-ranging wildlife can be valuable sentinels for oocyst contaminated environments, as well as a potential source for human foodborne infection with T. gondii. Here we aimed to determine the sero-prevalence of T. gondii in Danish wild deer populations and examine risk factors associated with increased exposure to the parasite. Blood samples were collected from 428 cervids (87 fallow deer (Dama dama), 272 red deer (Cervus elaphus), 55 roe deer (Capreolus capreolus) and 14 sika deer (Cervus Nippon) from 23 hunting sites in Denmark. The animals were shot during the hunting season 2017/2018, and screened for antibodies against T. gondii using a commercial ELISA kit. One hundred and five (24.5%) cervids were sero-positive. Sero-prevalence was significantly different between species (p < 0.05), with odds of sero-positivity being 4.5 times higher in roe deer than fallow deer, and 3.0 times higher in red deer than in fallow deer. A significant increase in sero-prevalence with age was observed, driven by a significant increase in risk in adult red deer compared to calves (OR: 13.22; 95% CI: 5.96-33.7). The only other significant risk factor associated with wild cervid T. gondii sero-positivity was fencing, with the highest exposure associated with deer from non-fenced hunting areas (OR: 2.21; 95% CI: 1.05-4.99). This study documented a widespread exposure to T. gondii in Danish cervids. Therefore the meat of the wild deer, in particular from roe deer and red deer, should be considered a significant risk of T. gondii infections to humans, if not properly cooked. Further, molecular studies to confirm the presence of infective parasitic stages in the muscles of deer used for consumption is recommended.

Quality of life in childhood, adolescence and adult food allergy: Patient and parent perspectives.

BACKGROUND: Studies of children with food allergy typically only include the mother and have not investigated the relationship between the amount of allergen needed to elicit a clinical reaction (threshold) and health-related quality of life (HRQL). Our aims were (i) to compare self-reported and parent-reported HRQL in different age groups, (ii) to evaluate the impact of severity of allergic reaction and threshold on HRQL, and (iii) to investigate factors associated with patient-reported and parent-reported HRQL. METHODS: Age-appropriate Food Allergy Quality of Life Questionnaires (FAQLQ) were completed by 73 children, 49 adolescents and 29 adults with peanut, hazelnut or egg allergy. Parents (197 mothers, 120 fathers) assessed their child's HRQL using the FAQLQ-Parent form. Clinical data and threshold values were obtained from a hospital database. Significant factors for HRQL were investigated using univariate and multivariate regression. RESULTS: Female patients reported greater impact of food allergy on HRQL than males did. Egg and hazelnut thresholds did not affect HRQL, but lower peanut threshold was associated with worse HRQL. Both parents scored their child's HRQL better than the child's own assessment, but whereas mother-reported HRQL was significantly affected by limitations in the child's social life, father-reported HRQL was affected by limitations in the family's social life. Severity of allergic reaction did not contribute significantly to HRQL. CONCLUSION: The risk of accidental allergen ingestion and limitations in social life are associated with worse HRQL. Fathers provide a unique perspective and should have a greater opportunity to contribute to food allergy research.

Green, Yellow, and Red risk perception in everyday life - a communication tool.

BACKGROUND: Adolescents have the highest risk for food allergy-related fatalities. Our main aim was to investigate the level of risk in everyday social situations as perceived by adolescents/young adults with peanut allergy, their families, and their friends. METHODS: The web-based 'Colours Of Risks' (COR) questionnaire was completed by 70 patients (aged 12-23 years), 103 mothers and fathers, 31 siblings (aged 12-26 years), and 42 friends (aged 12-24 years). COR deals with six main contexts (home, school/university, work, visiting/social activities, special occasions/parties, and vacations), each with 1-12 items. Response categories are green (I feel safe), yellow (I feel uncertain), or red (I feel everything is risky). RESULTS: There was a high level of agreement between participants in defining situations as safe, uncertain, or risky, but female patients and mothers rated fewer situations as safe compared to male patients and fathers. Being with close friends and family, and attending planned parties without alcohol were perceived as situations of low risk. While 94% of patients took an epinephrine auto-injector (EAI) into risky situations, only 65% took it into safe situations. In contrast to the close family, 31% of the friends did not know the patient had an EAI, and fewer knew how to administer the EAI. CONCLUSION: Young adults with peanut allergy face challenges when moving from the safe home with ready assistance if needed, to independence with unpredictable surroundings and less certain help. Perceived 'safe' situations may in fact be the riskiest, as patients often do not take the EAI with them.

Remote sensing, geographical information system and spatial analysis for schistosomiasis epidemiology and ecology in Africa.

Beginning in 1970, the potential of remote sensing (RS) techniques, coupled with geographical information systems (GIS), to improve our understanding of the epidemiology and control of schistosomiasis in Africa, has steadily grown. In our current review, working definitions of RS, GIS and spatial analysis are given, and applications made to date with RS and GIS for the epidemiology and ecology of schistosomiasis in Africa are summarised. Progress has been made in mapping the prevalence of infection in humans and the distribution of intermediate host snails. More recently, Bayesian geostatistical modelling approaches have been utilized for predicting the prevalence and intensity of infection at different scales. However, a number of challenges remain; hence new research is needed to overcome these limitations. First, greater spatial and temporal resolution seems important to improve risk mapping and understanding of transmission dynamics at the local scale. Second, more realistic risk profiling can be achieved by taking into account information on people's socio-economic status; furthermore, future efforts should incorporate data on domestic access to clean water and adequate sanitation, as well as behavioural and educational issues. Third, high-quality data on intermediate host snail distribution should facilitate validation of infection risk maps and modelling transmission dynamics. Finally, more emphasis should be placed on risk mapping and prediction of multiple species parasitic infections in an effort to integrate disease risk mapping and to enhance the cost-effectiveness of their control.

Modeling freshwater snail habitat suitability and areas of potential snail-borne disease transmission in Uganda.

Geographic information system (GIS-based modeling of an intermediate host snail species environmental requirements using known occurrence records can provide estimates of its spatial distribution. When other data are lacking, this can be used as a rough spatial prediction of potential snail-borne disease transmission areas. Furthermore, knowledge of abiotic factors affecting intra-molluscan parasitic development can be used to make "masks" based on remotely sensed climatic data, and these can in turn be used to refine these predictions. We used data from a recent freshwater snail survey from Uganda, environmental data and the genetic algorithm for rule-set prediction (GARP) to map the potential distribution of snail species known to act as intermediate hosts of several human and animal parasites. The results suggest that large areas of Uganda are suitable habitats for many of these snail species, indicating a large potential for disease transmission. The lack of parasitological data still makes it difficult to determine the magnitude of actual disease transmission, but the predicted snail distributions might be used as indicators of potential present and future risk areas. Some of the predicted snail distribution maps were furthermore combined with temperature masks delineating suitable temperature regimes of the parasites they host. This revealed the coinciding suitable areas for snail and parasite, but also areas suitable for host snails, but apparently not for the parasites. Assuming that the developed models correctly reflect areas suitable for transmission, the applied approach could prove useful for targeting control interventions.

Modeling the distribution of Schistosoma mansoni and host snails in Uganda using satellite sensor data and Geographical Information Systems.

The potential value of MODIS satellite sensor data on Normalized Difference Vegetation Index (NDVI) and land surface temperatures (LST) for describing the distribution of the Schistosoma mansoni-"Biomphalaria pfeifferi"/Biomphalaria sudanica parasite-snail system in inland Uganda, were tested by developing annual and seasonal composite models, and iteratively analysing for their relationship with parasite and snail distribution. The dry season composite model predicted an endemic area that produced the best fit with the distribution of schools with > or =5% prevalence. NDVI values of 151-174, day temperatures of 26-36 degrees C, and night temperatures of 15-20 degrees C were used as criteria for the prediction model. Using the same approach with host snail data indicated that most of Uganda is suitable "B. pfeifferi"/B. sudanica habitat, except for possibly the north-eastern region of the country. The parasite, however, appears to be restricted in its distribution in both the north-eastern and the south-western regions of Uganda. The absence of disease in the south-west can not be attributed to the absence of snail hosts. Results suggest a combination of satellite sensor data on temperature and standard climate data on precipitation, as the best ecological determinants of the S. mansoni-"B. pfeifferi"/B. sudanica system. Satellite composite models and logistic regression analysis, suggest low night time temperature as one of the significant factors inhibiting S. mansoni transmission in the south-western highland areas of Uganda. The developed models are, however, unique, representing species-specific ecologic preferences of the S. mansoni-"B. Pfeifferi"/B. sudanica system in inland Uganda. Further validation studies are needed to test the value of the model in other countries in East Africa.

Knee extensor strength, activation, and size in very elderly people following strength training.

Muscle strength, activation, and size were studied in 11 very elderly subjects (8 women and 3 men; age range, 85-97 years) who completed 12 weeks of strength training of the knee extensor muscles. Training increased the maximum amount of weight that could be lifted once (134%; P < 0.05) and maximum voluntary isometric strength, measured as both force recorded at the ankle with the knee flexed 90 degrees (17%, ns) and as torque with the knee flexed 60 degrees (37%; P < 0.05). Anatomical lean quadriceps cross-sectional area (LCSA) measured at midthigh using magnetic resonance imaging increased from 27.5 +/- 9.6 cm2 to 30.2 +/- 10.0 cm2 (9.8%; P < 0. 05) after training. Both before and after training, isometric strength was closely related to LCSA, but training resulted in no significant change in muscle force per unit area of quadriceps muscle. Using the twitch interpolation technique, muscle activation during a maximal voluntary isometric contraction was shown to be incomplete in all subjects before training (ranging from 69% to 93%) and was not significantly increased after training. An increase in skeletal muscle mass may have important functional and metabolic benefits for very elderly people.

N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia.

Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA is distributed within the ischemic area. Rats were exposed to middle cerebral artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by 1H-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reduction during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA]e) was determined by microdialysis using [3H]NAA to assess in vivo recovery. After induction of ischemia, [NAA]e increased linearly from 70 micromol/L to a peak level of 2 mmol/L after 2 to 3 hours before declining to 0.7 mmol/L at 7 hours. For comparison, [NAA]e was measured in striatum during global ischemia, revealing that [NAA]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA.

Visual activation in infants and young children studied by functional magnetic resonance imaging.

The purpose of this study was to determine whether visual stimulation in sleeping infants and young children can be examined by functional magnetic resonance imaging. We studied 17 children, aged 3 d to 48 mo, and three healthy adults. Visual stimulation was performed with 8-Hz flickering light through the sleeping childs' closed eyelids. Functional magnetic resonance imaging was performed with a gradient echoplanar sequence in a l.5-T magnetic resonance scanner. Six subjects were excluded because of movement artifacts; the youngest infant showed no response. In 10 children, we could demonstrate areas of signal decrease during visual stimulation in the occipital cortex (mean decrease 2.21%), contrary to the signal increase observed in the adult controls (mean increase 2.82%). This decrease may be due to a higher proportional increase in oxygen extraction compared with increase in cerebral blood flow during activation. The different response patterns in young children and adults can reflect developmental or behavioral differences. Localization of the activation seemed to be age-dependent. In the older children and the adults, it encompassed the whole length of the calcarine sulcus, whereas it was restricted to the anterior and medial part of the calcarine sulcus in the younger infants. This may reflect a different functional organization of the young child's visual cortex or the on-going retinal development.

A two-compartment phantom for VOI profile measurements in small-bore 31P MR spectroscopy.

A two-compartment gel phantom for VOI profile measurements in volume-selective 31P spectroscopy in small-bore units is presented. The phantom is cylindrical with two compartments divided by a very thin (30 microm) polyethene film. This thin film permits measurements with a minimum of susceptibility influences from the partition wall. The phantom was used for evaluation of the volume selection method ISIS (image-selected in vivo spectroscopy). The position of the phantom was fixed in the magnet during the measurements, while the volume of interest (VOI) was moved stepwise over the border. The signal from the two compartments was measured for each position and the data were evaluated following differentiation. We have found this phantom suitable for VOI profile measurements of ISIS in small-bore systems. The phantom forms a useful complement to recommended phantoms for small bore-spectroscopy.

Planar quadrature coil design using shielded-loop resonators.

The shielded-loop resonator is known to have a low capacitive sample loss due to a perfect balancing. In this paper, it is demonstrated that shielded-loop technology also can be used to improve design of planar quadrature coils. Both a dual-loop circuit and especially a dual-mode circuit may benefit from use of shielded-loop resonators. Observations in measurements agree with theory for both a dual-loop coil and a dual-mode coil. The coils were designed for use as transmit/receive coil for 1H imaging and spectroscopy at 4.7 T in rat brain.

Twelve-hour brain lithium concentration in lithium maintenance treatment of manic-depressive disorder: daily versus alternate-day dosing schedule.

The 12-h brain lithium concentration was measured by lithium-7 magnetic resonance spectroscopy in ten manic-depressive patients receiving daily or alternate-day lithium carbonate treatment. The median dose of lithium carbonate was 800 mg in the daily treatment group and 1200 mg in the alternate-day group. Median 12-h serum lithium concentration in the two groups was 0.86 mmol l-1 and 0.55 mmol l-1, respectively, while the corresponding concentration in brain was 0.67 mmol l-1 and 0.52 mmol l-1, respectively. The 12-h brain lithium concentration was independent of lithium dosing schedule (multiple linear regression), but correlated significantly with the 12-h serum lithium concentration (P = 0.003; B = 0.53, 95% c.l. 0.24-0.82; beta = 0.83). Thus at identical 12-h serum lithium concentrations the 12-h brain lithium concentration is similar with both treatment regimes. As the risk of manic-depressive relapse during alternate-day lithium treatment is in our experience 3-fold greater than with daily treatment (at similar mean 12-h serum lithium concentration), the findings suggest that the difference in the prophylactic efficacy of the two dosing schedules is unrelated to differences in the 12-h brain lithium concentration.

Quantitative 1D saturation profiles on chalk by NMR.

Quantitative one-dimensional saturation profiles showing the distribution of water and oil in chalk core samples are calculated from NMR measurements utilizing a 1D CSI spectroscopy pulse sequence. Saturation profiles may be acquired under conditions of fluid flow through the sample. Results reveal that strong saturation gradients exist in chalk core samples after core floods, due to capillary effects. The method is useful in analysis of corefloods, e.g., for determination of capillary pressure functions.

24-hour lithium concentration in human brain studied by Li-7 magnetic resonance spectroscopy.

Brain and serum lithium concentrations were measured every second hour during a 24-hr period following lithium intake, and again 48-hr later in two normal subjects in steady state lithium treatment receiving lithium carbonate (Priadel Synthelabo) once every evening. The brain-lithium concentration was measured by 7Li magnetic resonance spectroscopy (MRS). The brain lithium level was found to undulate in a peak-trough pattern that followed the serum lithium profile, although in an attenuated form. The brain/serum lithium concentration ratio varied considerably during the 48-hr period, ranging from 0.5 to 1.3, but the ratio was independent of the serum-lithium concentration. The median half-life for lithium was 28 hr in the brain, and 16 hr in serum. The brain lithium concentration in the morning was about 75% of the clinically relevant standard 12-hr serum lithium concentration. The finding that brain lithium undulates during the day means that MRS measurements of brain lithium can only be compared if carried out under standard conditions that include a fixed interval following lithium intake and an identical treatment regimen.

Accuracy and precision of MR velocity mapping in measurement of stenotic cross-sectional area, flow rate, and pressure gradient.

Reliability of magnetic resonance (MR) velocity mapping to assess severity of stenosis was assessed in vitro. Steady flow at different flow rates through five stenoses with a central orifice area ranging from 17 to 176 mm2 was measured with velocity mapping performed perpendicular to the stenotic jet. Besides determination of the stenotic cross-sectional area and flow rate, the pressure gradient was calculated with the modified Bernoulli equation and compared with manometer measurements. Cross-sectional areas were measured with an accuracy of > or = 76%, a precision of > or = 91%, and an error of < or = 19 mm2. Flow rates had an accuracy of > or = 72%, a precision of > or = 94%, and an error of < or = 1.4 L/min. The modification of the Bernoulli equation limited its reliability to stenoses with areas of 35-113 mm2. Pressure gradients were calculated with an accuracy of > or = 80%, a precision of > or = 88%, and an error of < or = 15 mm Hg. The method was applied in a single patient with aortic stenosis and gave estimates that agreed with those obtained by heart catheterization.

Functional MR imaging at 1.5 T. Initial results using photic and motoric stimulation.

A preliminary investigation of the effects of stimulation of the visual and the motor cortex was made on a conventional 1.5 T MR imaging scanner. Both types of activation gave a detectable change in the signal between rest and stimulation using a gradient echo sequence with an echo time of 60 ms. The observed effects were assumed to be caused by variation in the amount of paramagnetic deoxyhemoglobin between stimulation and rest due to local increase of capillary blood flow in the human brain during stimulation.