Pediatric Lyme disease: systematic assessment of post-treatment symptoms and quality of life.

BACKGROUND: Lyme disease is common among children and adolescents. Antibiotic treatment is effective, yet some patients report persistent symptoms following treatment, with or without functional impairment. This study characterized long-term outcome of pediatric patients with Lyme disease and evaluated the case definition of post-treatment Lyme disease (PTLD) syndrome. METHODS: The sample included 102 children with confirmed Lyme disease diagnosed 6 months-10 years prior to enrollment (M = 2.0 years). Lyme diagnosis and treatment information was extracted from the electronic health record; parent report identified presence, duration, and impact of symptoms after treatment. Participants completed validated questionnaires assessing health-related quality of life, physical mobility, fatigue, pain, and cognitive impact. RESULTS: Most parents reported their child's symptoms resolved completely, although time to full resolution varied. Twenty-two parents (22%) indicated their child had at least one persistent symptom >6 months post-treatment, 13 without functional impairment (PTLD symptoms) and 9 with functional impairment (PTLD syndrome). Children with PTLD syndrome had lower parent-reported Physical Summary scores and greater likelihood of elevated fatigue. CONCLUSIONS: In the current study, most children with Lyme disease experienced full resolution of symptoms, including those who initially met PTLD syndrome criteria. Effective communication about recovery rates and common symptoms that may persist post-treatment is needed. IMPACT: The majority of pediatric patients treated for all stages of Lyme disease reported full resolution of symptoms within 6 months. 22% of pediatric patients reported one or more symptom persisting >6 months, 9% with and 13% without accompanying functional impairment. Effective communication with families about recovery rates and common symptoms that may persist post-treatment of Lyme disease is needed.

Automatic brain segmentation in preterm infants with post-hemorrhagic hydrocephalus using 3D Bayesian U-Net.

Post-hemorrhagic hydrocephalus (PHH) is a severe complication of intraventricular hemorrhage (IVH) in very preterm infants. PHH monitoring and treatment decisions rely heavily on manual and subjective two-dimensional measurements of the ventricles. Automatic and reliable three-dimensional (3D) measurements of the ventricles may provide a more accurate assessment of PHH, and lead to improved monitoring and treatment decisions. To accurately and efficiently obtain these 3D measurements, automatic segmentation of the ventricles can be explored. However, this segmentation is challenging due to the large ventricular anatomical shape variability in preterm infants diagnosed with PHH. This study aims to (a) propose a Bayesian U-Net method using 3D spatial concrete dropout for automatic brain segmentation (with uncertainty assessment) of preterm infants with PHH; and (b) compare the Bayesian method to three reference methods: DenseNet, U-Net, and ensemble learning using DenseNets and U-Nets. A total of 41 T2 -weighted MRIs from 27 preterm infants were manually segmented into lateral ventricles, external CSF, white and cortical gray matter, brainstem, and cerebellum. These segmentations were used as ground truth for model evaluation. All methods were trained and evaluated using 4-fold cross-validation and segmentation endpoints, with additional uncertainty endpoints for the Bayesian method. In the lateral ventricles, segmentation endpoint values for the DenseNet, U-Net, ensemble learning, and Bayesian U-Net methods were mean Dice score = 0.814 ± 0.213, 0.944 ± 0.041, 0.942 ± 0.042, and 0.948 ± 0.034 respectively. Uncertainty endpoint values for the Bayesian U-Net were mean recall = 0.953 ± 0.037, mean  negative predictive value = 0.998 ± 0.005, mean accuracy = 0.906 ± 0.032, and mean AUC = 0.949 ± 0.031. To conclude, the Bayesian U-Net showed the best segmentation results across all methods and provided accurate uncertainty maps. This method may be used in clinical practice for automatic brain segmentation of preterm infants with PHH, and lead to better PHH monitoring and more informed treatment decisions.

Epizootiology of a Cryptococcus gattii outbreak in porpoises and dolphins from the Salish Sea.

Cryptococcus gattii is a fungal pathogen that primarily affects the respiratory and nervous systems of humans and other animals. C. gattii emerged in temperate North America in 1999 as a multispecies outbreak of cryptococcosis in British Columbia (Canada) and Washington State and Oregon (USA), affecting humans, domestic animals, and wildlife. Here we describe the C. gattii epizootic in odontocetes. Cases of C. gattii were identified in 42 odontocetes in Washington and British Columbia between 1997 and 2016. Species affected included harbor porpoises Phocoena phocoena (n = 26), Dall's porpoises Phocoenoides dalli (n = 14), and Pacific white-sided dolphins Lagenorhynchus obliquidens (n = 2). The probable index case was identified in an adult male Dall's porpoise in 1997, 2 yr prior to the initial terrestrial outbreak. The spatiotemporal extent of the C. gattii epizootic was defined, and cases in odontocetes were found to be clustered around terrestrial C. gattii hotspots. Case-control analyses with stranded, uninfected odontocetes revealed that risk factors for infection were species (Dall's porpoises), age class (adult animals), and season (winter). This study suggests that mycoses are an emerging source of mortality for odontocetes, and that outbreaks may be associated with anthropogenic environmental disturbance.

Association Between Earthquake Exposures and Mental Health Outcomes in Phulpingdanda Village After the 2015 Nepal Earthquakes.

In 2015, two strong earthquakes, as well as continuous, high magnitude aftershocks, struck Nepal. Phulpingdanda village was greatly impacted due to its lack of infrastructure and environmental remoteness. Adults from sampled households were surveyed 1-year later to examine the association between earthquake exposures and indicators of depression, post-traumatic stress disorder (PTSD), and resilience. Results showed 33% of surveyed residents screened positive for depression, 9% screened positive for severe PTSD, and 46% displayed moderate to high resilience. Additionally, participants experienced resource loss (100%), damaged home and goods (99%), and exposure to the grotesque (82%). Traumatic earthquake experiences related to personal harm were associated with symptoms of depression and PTSD and resource loss was associated with depressive symptoms. Earthquake experiences associated with less damage to home and goods, but greater exposure to the grotesque were associated with increased resilience. This research adds to our knowledge of the relationship between traumatic exposures and indicators of psychological distress and resilience following a disaster.

Multicentric plasmacytoma in a harbor porpoise Phocoena phocoena off the coast of Whidbey Island, Washington State, USA.

Necropsy of a female adult pregnant harbor porpoise Phocoena phocoena revealed a multicentric plasmacytoma. The plasmacytoma infiltrated the cranial lung lobes, mediastinal lymph nodes and the spleen. Diagnosis was based on gross, histopathologic and immunohistochemical studies. Histopathology revealed a diffuse proliferation of atypical pleomorphic neoplastic round cells with plasmacytic features. Positive immunohistochemistry with anti-CD79a and anti-CD20 antibody markers and anti-multiple myeloma oncogene 1 (MUM-1) for plasmacytoma confirmed this neoplasm to be of B-cell origin. This is the first recorded case of a plasmacytoma in a harbor porpoise. Routine viral screening was negative via standard PCR for herpesvirus and reverse transcriptase PCR for morbillivirus. Retroviral screening was not performed.

Online surveillance of media health event reporting in Nepal: digital disease detection from a One Health perspective.

BACKGROUND: Traditional media and the internet are crucial sources of health information. Media can significantly shape public opinion, knowledge and understanding of emerging and endemic health threats. As digital communication rapidly progresses, local access and dissemination of health information contribute significantly to global disease detection and reporting. METHODS: Health event reports in Nepal (October 2013-December 2014) were used to characterize Nepal's media environment from a One Health perspective using HealthMap - a global online disease surveillance and mapping tool. Event variables (location, media source type, disease or risk factor of interest, and affected species) were extracted from HealthMap. RESULTS: A total of 179 health reports were captured from various sources including newspapers, inter-government agency bulletins, individual reports, and trade websites, yielding 108 (60%) unique articles. Human health events were reported most often (n = 85; 79%), followed by animal health events (n = 23; 21%), with no reports focused solely on environmental health. CONCLUSIONS: By expanding event coverage across all of the health sectors, media in developing countries could play a crucial role in national risk communication efforts and could enhance early warning systems for disasters and disease outbreaks.

Persistent Organic Pollutant and Hormone Levels in Harbor Porpoise with B Cell Lymphoma.

B-cell lymphoma, a common morphologic variant of non-Hodgkin lymphoma, has been associated with persistent pollutants in humans, but this association is not well-characterized in top-level predators sharing marine resources with humans. We characterized and compared blubber contaminants and hormones of a pregnant harbor porpoise (Phocoena phocoena) with B-cell lymphoma, with those in two presumed healthy fishery by-caught porpoises with no lymphoma: a pregnant adult and female juvenile. Common historic use compounds, including polychlorinated biphenyls, polybrominated diphenyl ethers, and pesticides, were evaluated in blubber samples from three porpoises. In addition, blubber cortisol and progesterone levels (ng/g) were determined in all three animals. Total pollutant concentrations were highest in the juvenile porpoise, followed by the lymphoma porpoise and the nonlymphoma adult. Blubber cortisol concentrations were 191% greater in the pregnant with lymphoma porpoise compared with the pregnant no lymphoma porpoise, and 89% greater in the juvenile female compared with the pregnant no lymphoma porpoise. Although both adults were pregnant, progesterone levels were substantially greater (90%) in the healthy compared with the lymphoma adult. Health monitoring of top-level marine predators, such as porpoise, provides a sentinel measure of contaminants that serve as indicators of potential environmental exposure to humans.

Increased harbor porpoise mortality in the Pacific Northwest, USA: understanding when higher levels may be normal.

In 2006, a marked increase in harbor porpoise Phocoena phocoena strandings were reported in the Pacific Northwest of the USA, resulting in the declaration of an unusual mortality event (UME) for Washington and Oregon to facilitate investigation into potential causes. The UME was in place during all of 2006 and 2007, and a total of 114 porpoises stranded during this period. Responders examined 95 porpoises; of these, detailed necropsies were conducted on 75 animals. Here we review the findings related to this event and how these compared to the years immediately before and after the UME. Relatively equal numbers among sexes and age classes were represented, and mortalities were attributed to a variety of specific causes, most of which were categorized as trauma or infectious disease. Continued monitoring of strandings during 4 yr following the UME showed no decrease in occurrence. The lack of a single major cause of mortality or evidence of a significant change or event, combined with high levels of strandings over several post-UME years, demonstrated that this was not an actual mortality event but was likely the result of a combination of factors, including: (1) a growing population of harbor porpoises; (2) expansion of harbor porpoises into previously sparsely populated areas in Washington's inland waters; and (3) a more well established stranding network that resulted in better reporting and response. This finding would not have been possible without the integrated response and investigation undertaken by the stranding network.

Variation in hematologic and serum biochemical values of belugas (Delphinapterus leucas) under managed care.

Blood analytes are critical for evaluating the general health of cetacean populations, so it is important to understand the intrinsic variability of hematology and serum chemistry values. Previous studies have reported data for follow-up periods of several years in managed and wild populations, but studies over long periods of time (> 20 yr) have not been reported. The study objective was to identify the influences of partitioning characteristics on hematology and serum chemistry analytes of apparently healthy managed beluga (Delphinapterus leucas). Blood values from 31 managed belugas, at three facilities, collected over 22 yr, were assessed for seasonal variation and aging trends, and evaluated for biologic variation among and within individuals. Linear mixed effects models assessed the relationship between the analytes and sex, age, season, facility location, ambient air temperature, and photoperiod. Sex differences in analytes and associations with increasing age were observed. Seasonal variation was observed for hemoglobin, hematocrit, mean corpuscular volume, monocytes, alkaline phosphatase, total bilirubin, cholesterol, and triglycerides. Facilities were associated with larger effects on analyte values compared to other covariates, whereas age, sex, and ambient temperature had smaller effects compared to facility and season. Present findings provide important baseline information for future health monitoring efforts. Interpretation of blood analytes and animal health in managed and wild populations over time is aided by having available typical levels for the species and reference intervals for the degree to which individual animals vary from the species average and from their own baseline levels during long-term monitoring.

Vaginal calculi in a juvenile harbor porpoise (Phocoena phocoena).

A large number of vaginal calculi were observed in a juvenile harbor porpoise (Phocoena phocoena) stranded on Whidbey Island, Washington. Vaginal calculi have been reported in other species, but not in harbor porpoises. Histologic examination of the urinary tract revealed mucosal hyperplasia most likely attributable to the calculi. The calculi were numerous (>30), composed completely of struvite (magnesium ammonium phosphate), and on culture yielded Enterococcus spp., a bacterium not usually associated with struvite urolith formation in domestic animals. The only other lesion of note was severe hepatic lipidosis, and its relationship to the development of the vaginal calculi is unknown.

Surveillance for Antibiotic-Resistant E. coli in the Salish Sea Ecosystem.

E. coli was isolated from the Salish Sea (Puget Sound) ecosystem, including samples of marine and fresh water, and wildlife dependent on this environment. E. coli isolates were assessed for phenotypic and genotypic resistance to antibiotics. A total of 305 E. coli isolates was characterized from samples collected from: marine water obtained in four quadrants of the Salish Sea; select locations near beaches; fresh water from streams near marine beaches; and fecal samples from harbor porpoises (Phocoena phocoena), harbor seals (Phoca vitulina), river otters (Lontra canadensis), and English sole (Parophrys vetulus). Isolates were evaluated using antimicrobial susceptibility typing, whole-genome sequencing, fumC, and multilocus sequence typing. Resistance and virulence genes were identified from sequence data. Of the 305 isolates from Salish Sea samples, 20 (6.6%) of the E. coli were intermediate, and 31 (10.2%) were resistant to ≥1 class of antibiotics, with 26.9% of nonsusceptible (resistant and intermediate resistant) E. coli isolates from marine mammals and 70% from river otters. The proportion of nonsusceptible isolates from animals was significantly higher than samples taken from marine water (p < 0.0001). A total of 196 unique STs was identified including 37 extraintestinal pathogenic E. coli (ExPEC)-associated STs [ST10, ST38, ST58, ST69, ST73, ST117, ST131, and ST405]. The study suggests that animals may be potential sentinels for antibiotic-resistant and ExPEC E. coli in the Salish Sea ecosystem.

Health Reporting Characteristics among Journalists in Nepal Utilizing a One Health Framework.

Journalists play a crucial role in the dissemination of health-related information. In developing countries, such as Nepal, the media are integral in shaping the national agenda and informing the public of important health issues. With an increasing need for a collaborative effort to attain optimal health for people, animals, and the environment, the One Health approach was used to characterize health reporting in Nepal. A comprehensive survey was administered to health journalists regarding their public, animal, and environmental health reporting habits. Seventy-one journalists completed the survey across three study sites. Many journalists indicated a history of reporting across all three sectors but did not routinely focus on health reporting in general. The majority of journalists perceived the quality and overall coverage of health-related topics increased over the last five years. However, few journalists reported receiving specialized training in any health sector. Although the overall quality of health reporting in the Nepali media showed improvements, many journalists acknowledged a lack of understanding of common health topics and a desire to learn more skills related to accurate health reporting. One Health provides a conceptual framework for understanding and promoting health communication through mass media to benefit humans, animals, and ecosystems.

Geographical dissemination of Leptospira interrogans serovar Pomona during seasonal migration of California sea lions.

Leptospirosis is one of the most widespread bacterial zoonoses in the world and affects most mammalian species. Although leptospirosis is well documented and characterized in terrestrial species, less information is available regarding the distribution and impact of leptospirosis in marine mammals. Additionally, the role of animal migrations on the geographical spread of leptospirosis has not been reported. Periodic epizootic outbreaks of acute leptospirosis among California sea lions (Zalophus californianus) have been reported since 1971. In this study, we collected samples from California sea lions stranded along the Pacific coast of North America during the most recent epidemic in 2004, and maintained leptospirosis surveillance of the California sea lion population along the California coast through 2007. Several isolates of Leptospira interrogans serovar Pomona were obtained from kidney and urine samples collected during this study, a finding consistent with serological evidence that California sea lions are persistently exposed to this leptospiral serovar. Combined, these data support a model whereby California sea lions are maintenance hosts for L. interrogans serovar Pomona, yet periodically undergo outbreaks of acute infection. During the 2004 outbreak, the incidence of new leptospirosis cases among California sea lions coincided with the seasonal movement of male sea lions from rookeries along the coast of central and southern California north as far as British Columbia. These data show that seasonal animal movement contributes to the distribution of leptospirosis across a large geographical region.

Site-Specific Load-Induced Expansion of Sca-1+Prrx1+ and Sca-1-Prrx1+ Cells in Adult Mouse Long Bone Is Attenuated With Age.

Aging is associated with significant bone loss and increased fracture risk, which has been attributed to a diminished response to anabolic mechanical loading. In adults, skeletal progenitors proliferate and differentiate into bone-forming osteoblasts in response to increasing mechanical stimuli, though the effects of aging on this response are not well-understood. Here we show that both adult and aged mice exhibit load-induced periosteal bone formation, though the response is significantly attenuated with age. We also show that the acute response of adult bone to loading involves expansion of Sca-1+Prrx1+ and Sca-1-Prrx1+ cells in the periosteum. On the endosteal surface, loading enhances proliferation of both these cell populations, though the response is delayed by 2 days relative to the periosteal surface. In contrast to the periosteum and endosteum, the marrow does not exhibit increased proliferation of Sca-1+Prrx1+ cells, but only of Sca-1-Prrx1+ cells, underscoring fundamental differences in how the stem cell niche in distinct bone envelopes respond to mechanical stimuli. Notably, the proliferative response to loading is absent in aged bone even though there are similar baseline numbers of Prrx1 + cells in the periosteum and endosteum, suggesting that the proliferative capacity of progenitors is attenuated with age, and proliferation of the Sca-1+Prrx1+ population is critical for load-induced periosteal bone formation. These findings provide a basis for the development of novel therapeutics targeting these cell populations to enhance osteogenesis for overcoming age-related bone loss. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Detection of pathogenic Leptospira bacteria in pinniped populations via PCR and identification of a source of transmission for zoonotic leptospirosis in the marine environment.

Leptospirosis, caused by the spirochete Leptospira, is a geographically widespread disease that affects a broad range of mammals, including marine mammals. Among pinniped populations, periodic epizootics of leptospirosis are responsible for significant die-offs. Along the west coast of North America, the most recent leptospirosis epizootic occurred in 2004, during which samples were collected from cases ranging from California to British Columbia. The primary objective of this study was to use this well-defined sample set to determine the feasibility of using PCR techniques to diagnose Leptospira infection among pinniped populations in comparison with diagnostic methodologies commonly used for marine mammals. Successful amplification was achieved from a variety of samples, including freshly collected urine, urine stored at -80 degrees C for less than 6 months, and kidney (freshly collected, frozen, and decomposed), as well as feces- and urine-contaminated sand collected in the vicinity of a live-stranded animal. Pathological examination of tissue collected from Leptospira-infected animals revealed the presence of leptospiral antigen in the kidneys. The use of species-specific primer pairs revealed a pattern of host specificity for Leptospira interrogans in sea lions and Leptospira kirschneri in elephant seals. These studies indicate PCR is a sensitive and specific diagnostic tool for the detection of Leptospira infection in pinnipeds and reveal a potential source for epizootic, enzootic, and zoonotic spread of leptospirosis in a marine environment.

Risk factors for an outbreak of leptospirosis in California sea lions (Zalophus californianus) in California, 2004.

Leptospirosis has been reported in California sea lions (Zalophus californianus) since 1970; however, the source of infection and mode of transmission remain unknown. To elucidate these features, demographic and environmental risk factors for leptospirosis were evaluated. California sea lion stranding records from northern California for 2004 were used to identify cases of leptospirosis (n = 316) and controls (n = 143). Demographic characteristics (age class, sex) and environmental factors, representing surrogates for exposure to dogs, cattle, rainfall, and freshwater sources, were compared between cases and controls with the use of a geographic information system (GIS) and logistic regression. Multivariate analyses revealed that summer and autumn seasons, juvenile age class, male sex, high dog-park density, and close proximity to dog parks were significantly associated with leptospirosis in sea lions, whereas county farmland cattle density, rainfall levels 30 days prior to stranding, human density, and proximity to freshwater sources were not associated. Thus, dogs and dog parks, or factors associated with them, might be further investigated to assess their relationship to leptospirosis in sea lions.

Earthquake exposures and mental health outcomes in children and adolescents from Phulpingdanda village, Nepal: a cross-sectional study.

BACKGROUND: Mental health issues can reach epidemic proportions in developed countries after natural disasters, but research is needed to better understand the impact on children and adolescents in developing nations. METHODS: A cross-sectional study was performed to examine the relationship between earthquake exposures and depression, PTSD, and resilience among children and adolescents in Phulpingdanda village in Nepal, 1 year after the 2015 earthquakes, using the Depression Self-Rating Scale for Children, Child PTSD Symptom Scale, and the Child and Youth Resilience Measure, respectively. To quantify exposure, a basic demographic and household questionnaire, including an earthquake exposure assessment tool for children and adolescents, was created. RESULTS: Of the 62 respondents interviewed, 3.23% and 4.84% displayed symptomatology of depression and PTSD. A large number of respondents interviewed scored high for resiliency (80.65%). All 62 respondents were displaced from their household and witnessed severe damage of both their homes and village. The number of earthquake exposures had a strong, positive correlation with PTSD symptomatology. CONCLUSIONS: Although the number of respondents who showed signs of depression and PTSD symptomatology was lower than anticipated, resilience scores were considerably higher. Future research should explore which protective factors may contribute to high resiliency in Nepali children and adolescents.

Baleen whale cortisol levels reveal a physiological response to 20th century whaling.

One of the most important challenges researchers and managers confront in conservation ecology is predicting a population's response to sub-lethal stressors. Such predictions have been particularly elusive when assessing responses of large marine mammals to past anthropogenic pressures. Recently developed techniques involving baleen whale earplugs combine age estimates with cortisol measurements to assess spatial and temporal stress/stressor relationships. Here we show a relationship between baseline-corrected cortisol levels and corresponding whaling counts of fin, humpback, and blue whales in the Northern Hemisphere spanning the 20th century. We also model the impact of alternative demographic and environmental factors and determine that increased anomalies of sea surface temperature over a 46-year mean (1970-2016) were positively associated with cortisol levels. While industrial whaling can deplete populations by direct harvest, our data underscore a widespread stress response in baleen whales that is peripheral to whaling activities or associated with other anthropogenic change.

Application of real-time quantitative PCR assays for detecting marine Brucella spp. in fish.

Brucella ceti and Brucella pinnipedialis have been documented as occurring in marine mammals, and B. ceti has been identified in 3 naturally acquired human cases. Seroconversion and infection patterns in Pacific Northwest harbor seals ( Phoca vitulina richardii) and North Atlantic hooded seals ( Cystophora cristata) indicate post-weaning exposure through prey consumption or lungworm infection, suggesting fish and possibly invertebrates play an epizootiologic role in marine Brucella transmission and possible foodborne risk to humans. We determined if real-time quantitative PCR (qPCR) assays can detect marine Brucella DNA in fish DNA. Insertion sequence (IS) 711 gene and sequence type (ST)27 primer-probe sets were used to detect Brucella associated with marine mammals and human zoonotic infections, respectively. First, DNA extracts from paired-species fish (containing 2 species) samples were tested and determined to be Brucella DNA negative using both IS 711 and ST27 primer-probe sets. A representative paired-species fish DNA sample was spiked with decreasing concentrations of B. pinnipedialis DNA to verify Brucella detection by the IS 711 primer-probe within fish DNA. A standard curve, developed using isolated DNA from B. pinnipedialis, determined the limit of detection. Finally, the IS 711 primer-probe was used to test Atlantic cod ( Gadus morhua) DNA extracts experimentally infected with the B. pinnipedialis hooded seal strain. In culture-positive cod tissue, the IS 711 limit of detection was ~1 genome copy of Brucella. Agreement between culture and PCR results for the 9 positive and 9 negative cod tissues was 100%. Although a larger sample set is required for validation, our study shows that qPCR can detect marine Brucella in fish.