Location and appearance of dysplastic Barrett's esophagus recurrence after endoscopic eradication therapy: no additional yield from random biopsy sampling neosquamous mucosa.

BACKGROUND AND AIMS: Surveillance after complete remission of intestinal metaplasia (CRIM) is essential. Current recommendations are to sample visible lesions first, followed by random 4-quadrant biopsy sampling of the original Barrett's esophagus (BE) length. To inform post-CRIM surveillance protocols, we aimed to identify the anatomic location, appearance, and histology of BE recurrences. METHODS: We performed an analysis of 216 patients who achieved CRIM after endoscopic eradication therapy for dysplastic BE at a Barrett's Referral Unit between 2008 and 2021. The anatomic location, recurrence histology, and endoscopic appearance of dysplastic recurrences were evaluated. RESULTS: After a median of 5.5 years (interquartile range, 2.9-7.2) of follow-up after CRIM, 57 patients (26.4%) developed nondysplastic BE (NDBE) recurrence and 18 patients (8.3%) developed dysplastic recurrence. From 8158 routine surveillance biopsy samplings of normal-appearing tubular esophageal neosquamous epithelium, the yield for recurrent NDBE or dysplasia was 0%. One hundred percent of dysplastic tubular esophageal recurrences were visible and in BE islands, whereas 77.8% of gastroesophageal junction dysplastic recurrences were nonvisible. Four distinct endoscopic features suspicious for recurrent advanced dysplasia or neoplasia were identified: buried or subsquamous BE, irregular mucosal pattern, loss of vascular pattern, and nodularity or depression. CONCLUSIONS: The yield of routine surveillance biopsy sampling of normal-appearing tubular esophageal neosquamous epithelium was zero. BE islands with indistinct mucosal or loss of vascular pattern, nodularity or depression, and/or signs of buried BE should raise clinician suspicion for advanced dysplasia or neoplasia recurrence. We suggest a new surveillance biopsy sampling protocol with a focus on meticulous inspection, followed by targeted biopsy sampling of visible lesions and random 4-quadrant biopsy sampling of the gastroesophageal junction.

Direct and indirect viral associations predict coexistence in wild plant virus communities.

Viruses are a vastly underestimated component of biodiversity that occur as diverse communities across hierarchical scales from the landscape level to individual hosts. The integration of community ecology with disease biology is a powerful, novel approach that can yield unprecedented insights into the abiotic and biotic drivers of pathogen community assembly. Here, we sampled wild plant populations to characterize and analyze the diversity and co-occurrence structure of within-host virus communities and their predictors. Our results show that these virus communities are characterized by diverse, non-random coinfections. Using a novel graphical network modeling framework, we demonstrate how environmental heterogeneity influences the network of virus taxa and how the virus co-occurrence patterns can be attributed to non-random, direct statistical virus-virus associations. Moreover, we show that environmental heterogeneity changed virus association networks, especially through their indirect effects. Our results highlight a previously underestimated mechanism of how environmental variability can influence disease risks by changing associations between viruses that are conditional on their environment.

Modelling modifiable factors associated with the probability of human rabies deaths among self-reported victims of dog bites in Abuja, Nigeria.

Canine-mediated rabies kills tens of thousands of people annually in lesser-developed communities of Asia, Africa, and the Americas, primarily through bites from infected dogs. Multiple rabies outbreaks have been associated with human deaths in Nigeria. However, the lack of quality data on human rabies hinders advocacy and resource allocation for effective prevention and control. We obtained 20 years of dog bite surveillance data across 19 major hospitals in Abuja, incorporating modifiable and environmental covariates. To overcome the challenge of missing information, we used a Bayesian approach with expert-solicited prior information to jointly model missing covariate data and the additive effects of the covariates on the predicted probability of human death after rabies virus exposure. Only 1155 cases of dog bites were recorded throughout the study period, out of which 4.2% (N = 49) died of rabies. The odds for risk of human death were predicted to decrease among individuals who were bitten by owned dogs compared to those bitten by free-roaming dogs. Similarly, there was a predicted decrease in the probability of human death among victims bitten by vaccinated dogs compared to those bitten by unvaccinated dogs. The odds for the risk of human death after bitten individuals received rabies prophylaxis were predicted to decrease compared to no prophylaxis. We demonstrate the practical application of a regularised Bayesian approach to model sparse dog bite surveillance data to uncover risk factors for human rabies, with broader applications in other endemic rabies settings with similar profiles. The low reporting observed in this study underscores the need for community engagement and investment in surveillance to increase data availability. Better data on bite cases will help to estimate the burden of rabies in Nigeria and would be important to plan effective prevention and control of this disease.

Polymicrobial Foot Infection Patterns Are Common and Associated With Treatment Failure.

Background: That foot infections are predominately polymicrobial has long been recognized, but it is not clear if the various species co-occur randomly or in patterns. We sought nonrandom species co-occurrence patterns that might help better predict prognosis or guide antimicrobial selection. Methods: We analyzed tissue (bone, skin, and other soft tissue), fluid, and swab specimens collected from initial foot infection episodes during a 10-year period using a hospital registry. Nonrandom co-occurrence of microbial species was identified using simple pairwise co-occurrence rates adjusted for multiple comparisons, Markov and conditional random fields, and factor analysis. A historical cohort was used to validate pattern occurrence and identify clinical significance. Results: In total, 156 unique species were identified among the 727 specimens obtained from initial foot infection episodes in 694 patients. Multiple analyses suggested that Staphylococcus aureus is negatively associated with other staphylococci. Another pattern noted was the co-occurrence of alpha-hemolytic Streptococcus, Enterococcus fecalis, Klebsiella, Proteus, Enterobacter, or Escherichia coli, and absence of both Bacteroides and Corynebacterium. Patients in a historical cohort with this latter pattern had significantly higher risk-adjusted rates of treatment failure. Conclusions: Several nonrandom microbial co-occurrence patterns are frequently seen in foot infection specimens. One particular pattern with many Proteobacteria species may denote a higher risk for treatment failure. Staphylococcus aureus rarely co-occurs with other staphylococci.

Profiling Risk Factors for Household and Community Spatiotemporal Clusters of Q Fever Notifications in Queensland between 2002 and 2017.

Q fever, caused by the bacterium Coxiella burnetii, is an important zoonotic disease worldwide. Australia has one of the highest reported incidences and seroprevalence of Q fever, and communities in the state of Queensland are at highest risk of exposure. Despite Australia's Q fever vaccination programs, the number of reported Q fever cases has remained stable for the last few years. The extent to which Q fever notifications cluster in circumscribed communities is not well understood. This study aimed to retrospectively explore and identify the spatiotemporal variation in Q fever household and community clusters in Queensland reported during 2002 to 2017, and quantify potential within cluster drivers. We used Q fever notification data held in the Queensland Notifiable Conditions System to explore the geographical clustering patterns of Q fever incidence, and identified and estimated community Q fever spatiotemporal clusters using SatScan, Boston, MA, USA. The association between Q fever household and community clusters, and demographic and socioeconomic characteristics was explored using the chi-squared statistical test and logistic regression analysis. From the total 2175 Q fever notifications included in our analysis, we found 356 Q fever hotspots at a mesh-block level. We identified that 8.2% of Q fever notifications belonged to a spatiotemporal cluster. Within the spatiotemporal Q fever clusters, we found 44 (61%) representing household clusters and 20 (27.8%) were statistically significant with an average cluster size of 3 km radius. Our multivariable model shows statistical differences between cases belonging to clusters in comparison with cases outside clusters based on the type of reported exposure. In conclusion, our results demonstrate that clusters of Q fever notifications are temporally stable and geographically circumscribed, indicating a persistent common exposure. Furthermore, within individuals in household and community clusters, abattoir exposure (a traditional occupational exposure) was rarely reported by individuals.

Effects of Monovalent Salt on Protein-Protein Interactions of Dilute and Concentrated Monoclonal Antibody Formulations.

In this study, we used sodium chloride (NaCl) to extensively modulate non-specific protein-protein interactions (PPI) of a humanized anti-streptavidin monoclonal antibody class 2 molecule (ASA-IgG2). The changes in PPI with varying NaCl (CNaCl) and monoclonal antibody (mAb) concentration (CmAb) were assessed using the diffusion interaction parameter kD and second virial coefficient B22 measured from solutions with low to moderate CmAb. The effective structure factor S(q)eff measured from concentrated mAb solutions using small-angle X-ray and neutron scattering (SAXS/SANS) was also used to characterize the PPI. Our results found that the nature of net PPI changed not only with CNaCl, but also with increasing CmAb. As a result, parameters measured from dilute and concentrated mAb samples could lead to different predictions on the stability of mAb formulations. We also compared experimentally determined viscosity results with those predicted from interaction parameters, including kD and S(q)eff. The lack of a clear correlation between interaction parameters and measured viscosity values indicates that the relationship between viscosity and PPI is concentration-dependent. Collectively, the behavior of flexible mAb molecules in concentrated solutions may not be correctly predicted using models where proteins are considered to be uniform colloid particles defined by parameters derived from low CmAb.

Spatiotemporal heterogeneity and determinants of canine rabies evidence at Local Government Area Level in Nigeria: Implications for rabies prevention and control.

Canine rabies poses a significant risk to humans and animals in Nigeria. However, the lack of reliable tools to evaluate the performance of existing canine rabies control programs to inform public health policy decisions poses a severe obstacle. We obtained canine rabies surveillance data from the National Veterinary Research Institute (NVRI) and supplemented these data with rabies diagnoses reported in the published studies from Nigeria. To uncover contextual factors (i.e., environmental and sociodemographic) associated with canine rabies evidence at the Local Government Area (LGA) level, we classified LGAs in Nigeria into four categories based on evidence availability (i.e., LGAs with NVRI data or published studies, both, or no evidence). We described the geographical and temporal variation in coverage. We fitted a multinomial regression model to examine the association between LGA level canine rabies evidence and potential sociodemographic and ecological determinants of canine rabies evidence. The effective annual testing during the 19 years was less than one dog/100,000 Nigerian resident-year. Our results showed that 58% of Nigerian LGAs (450/774) had not been targeted by the existing national rabies surveillance or studies on rabies, including ten states capitals with high human populations. While 16% (122/774) of Nigerian LGAs concentrated in Taraba, Adamawa, and Abia had canine rabies evidence from published studies, none of these LGAs was represented in the NVRI rabies surveillance data. We also observed an increasing trend in rabies evidence over time towards the eastern part of Nigeria. Our multinomial regression model indicated that education level, poverty, population density, land use and temperature were significantly associated with canine rabies evidence at the LGA level. This study underscores the value of combining canine rabies evidence from different sources to better understand the current disease situation for targeted intervention.

Near-term forecasting of companion animal tick paralysis incidence: An iterative ensemble model.

Tick paralysis resulting from bites from Ixodes holocyclus and I. cornuatus is one of the leading causes of emergency veterinary admissions for companion animals in Australia, often resulting in death if left untreated. Availability of timely information on periods of increased risk can help modulate behaviors that reduce exposures to ticks and improve awareness of owners for the need of lifesaving preventative ectoparasite treatment. Improved awareness of clinicians and pet owners about temporal changes in tick paralysis risk can be assisted by ecological forecasting frameworks that integrate environmental information into statistical time series models. Using an 11-year time series of tick paralysis cases from veterinary clinics in one of Australia's hotspots for the paralysis tick Ixodes holocyclus, we asked whether an ensemble model could accurately forecast clinical caseloads over near-term horizons. We fit a series of statistical time series (ARIMA, GARCH) and generative models (Prophet, Generalised Additive Model) using environmental variables as predictors, and then combined forecasts into a weighted ensemble to minimise prediction interval error. Our results indicate that variables related to temperature anomalies, levels of vegetation moisture and the Southern Oscillation Index can be useful for predicting tick paralysis admissions. Our model forecasted tick paralysis cases with exceptional accuracy while preserving epidemiological interpretability, outperforming a field-leading benchmark Exponential Smoothing model by reducing both point and prediction interval errors. Using online particle filtering to assimilate new observations and adjust forecast distributions when new data became available, our model adapted to changing temporal conditions and provided further reduced forecast errors. We expect our model pipeline to act as a platform for developing early warning systems that can notify clinicians and pet owners about heightened risks of environmentally driven veterinary conditions.

Postoperative Evolution of Sagittal Parameters Over Time Does Not Differ by Upper Instrumented Vertebra.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The aim of this study was to examine sagittal alignment over time in adult spinal deformity (ASD) and to understand whether these changes vary by choice of upper instrumented vertebra (UIV). SUMMARY OF BACKGROUND DATA: Recent ASD literature has focused on specific alignment goals. Less is known about how sagittal parameters evolve over time after surgical correction and whether these changes differ by choice of UIV. METHODS: This was a retrospective review of ASD patients from a single institution. Routine 36″ sagittal x-rays were obtained preoperatively, before hospital discharge, and at 6 months, 1 year, and 2 years and sagittal parameters were measured. Patients with UIV T6 and above were classified as upper thoracic (UT) and T7 and below as lower thoracic (LT). RESULTS: A total of 102 patients with mean age 66.0 years (±7.7) were included in the analysis (49 UT, 53 LT). All sagittal and coronal alignment parameters demonstrated significant improvement from preoperatively to any postoperative time point. Although multiple parameters maintained correction over time, others (TK, TPA, and PT) demonstrated significant increase from discharge to 2 years postoperatively, with changes occurring relatively early after surgery, whereas overall global alignment was maintained. Both UT/LT groups demonstrated significantly greater TK from preoperatively to discharge to 6 months (P  < 0.05), stabilizing at that time point out to 2 years, whereas TLK preferentially increased in the LT group. There was significant improvement in sagittal vertical axis after surgery, which was maintained out to 2years of follow-up (P > 0.05). CONCLUSIONS: Our data suggest that although several key parameters are maintained over time out to 2years postopera- tively, TK tends to worsen over time for all patients, whereas TLK preferentially increases in the LT group. Nevertheless, despite these trends, compensatory changes are seen in PT such that global alignment is relatively maintained.Level of Evidence: 3.

Does loss of spondylolisthesis reduction impact clinical and radiographic outcomes after minimally invasive transforaminal lumbar interbody fusion?

BACKGROUND CONTEXT: Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is a common operative approach to address degenerative lumbar stenosis and spondylolisthesis which has failed nonoperative care. Compared to open TLIF, MI-TLIF relies to a greater extent on indirect decompression resulting in a heightened awareness of spondylolisthesis reduction among MI surgeons. To what extent intraoperative reduction is achieved as well as the rate and clinical impact of loss or reduction and slip recurrence remain unknown. PURPOSE: To determine the rate and clinical impact of slip recurrence after MI-TLIF with expandable cage technology STUDY DESIGN/SETTING: Retrospective Cohort Study PATIENT SAMPLE: Patients undergoing MI-TLIF for degenerative spondylolisthesis using an articulating, expandable cage OUTCOME MEASURES: Patient-reported outcome measures (PROMs), including the Oswestry Disability Index (ODI), visual analog scale (VAS) for back/leg pain, Short Form-12 (SF-12), and PROMIS Physical Function (PF) METHODS: Patients undergoing MI-TLIF for degenerative spondylolisthesis using articulating, expandable cages from 2017 to 2019 were retrospectively studied. Lateral radiographs were reviewed and evaluated for the presence or absence of spondylolisthesis preoperatively, intraoperatively, and at follow-up times including 2 weeks, 6 weeks, 12 weeks, 6 months, and 1 year postoperatively. Spondylolisthesis was measured from the posterior inferior corner of the cephalad vertebra to the posterior superior corner of the caudal vertebra, with any measurement >1 mm classified as spondylolisthesis, and Meyerding grade was noted. Intraoperative reduction was measured, and loss of reduction was defined as >1 mm increase in spondylolisthesis comparing follow-up imaging to intraoperative films. PROMs were recorded at the preoperative and follow-up time points. Fusion was assessed at 1 year postoperatively via CT. RESULTS: A total of 63 patients and 70 levels were included, with mean age 59.8 years (SD,13.8). 19 levels (27.1%) had complete reduction intraoperatively, 40 (57.1%) had partial reduction, and 11 (15.7%) had no reduction. Of the 30 levels with loss of reduction (50.8%), 20 (66.7%) occurred by 2 weeks postoperatively and 28 (93.3%) occurred by 12 weeks postoperatively. At 6 months, there were significant differences between those who had loss of reduction and those who did not in VAS back pain (3.0 vs. 0.9, p = .017) and SF-12 PCS (41.5 vs. 50.0, p = .035), but no differences were found between the groups for any instruments at any other time points. The overall fusion rate was 82.1% (32/39) at 1 year postoperatively. There was no significant difference in fusion rate between the loss of reduction (16/20) and no loss of reduction (20/23) groups. Patients with loss of reduction had no difference in reoperation rate (1/28) compared to those without loss of reduction (2/24). CONCLUSIONS: While a majority of patients demonstrated reduction intraoperatively, 51% had loss of reduction, most commonly in the acute postoperative period. There were few differences in PROMs between patients who had loss of reduction and those who did not, suggesting that radiographic loss of reduction after MI-TLIF in the setting of degenerative spondylolisthesis may not be clinically meaningful.

Robotics and Spine Surgery: Lessons From the Personal Computer and Industrial Revolutions.

Over the past decade, several review articles have evaluated the techniques and outcomes of robotics vs traditional methods in spine surgery. Recently, robot-assisted pedicle screw placement has emerged, representing an important milestone in the evolution of spine surgery. In the present article, the authors aim to provide the historical context regarding the use and growth of spinal robotics through the lens of the Industrial Revolution and the personal computer revolution. While the former provides insight into the current implications of robotics in spine surgery, the latter predicts future steps in this arena.

MrIML: Multi-response interpretable machine learning to model genomic landscapes.

We introduce a new R package "MrIML" ("Mister iml"; Multi-response Interpretable Machine Learning). MrIML provides a powerful and interpretable framework that enables users to harness recent advances in machine learning to quantify multilocus genomic relationships, to identify loci of interest for future landscape genetics studies, and to gain new insights into adaptation across environmental gradients. Relationships between genetic variation and environment are often nonlinear and interactive; these characteristics have been challenging to address using traditional landscape genetic approaches. Our package helps capture this complexity and offers functions that fit and interpret a wide range of highly flexible models that are routinely used for single-locus landscape genetics studies but are rarely extended to estimate response functions for multiple loci. To demonstrate the package's broad functionality, we test its ability to recover landscape relationships from simulated genomic data. We also apply the package to two empirical case studies. In the first, we model genetic variation of North American balsam poplar (Populus balsamifera, Salicaceae) populations across environmental gradients. In the second case study, we recover the landscape and host drivers of feline immunodeficiency virus genetic variation in bobcats (Lynx rufus). The ability to model thousands of loci collectively and compare models from linear regression to extreme gradient boosting, within the same analytical framework, has the potential to be transformative. The MrIML framework is also extendable and not limited to modelling genetic variation; for example, it can quantify the environmental drivers of microbiomes and coinfection dynamics.

Primary Total Hip Arthroplasty in Patients With Ankylosing Spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory spondyloarthropathy with hip involvement in 40% of patients. With the renewed interest in the hip-spine interplay, this study aimed to define long-term outcomes of primary total hip arthroplasty (THA) in the setting of AS. METHODS: We identified 309 hips (219 patients) with AS treated with primary THA from 1969 to 2018. Mean age was 49 years, 80% were males, and mean body mass index was 28 kg/m2. Cumulative incidences of any revision, reoperation, and dislocation were calculated utilizing a competing risk analysis. Harris Hip Scores and complications were also reported. Mean follow-up was 16 years. RESULTS: The cumulative incidence of any revision after primary THA was 2.3% at 5 years and 17.5% at 20 years. The most common reasons for revision (n = 73) were aseptic loosening (41%), osteolysis/polyethylene (PE) wear (30%, all with conventional PE), and femoral component fracture (8%). The cumulative incidence of dislocation was 1.9% at 5 years and 2.9% at 20 years. Younger age was associated with increased risk of revision (hazard ratio (HR) = 1.3, P < .01) and reoperation (HR = 1.2, P < .01), but not dislocation (HR = 0.7, P = .1). Twenty-eight hips (9%) experienced a postoperative complication not requiring reoperation. The mean Harris Hip Score improved from 51 to 76 after THA (P < .001). CONCLUSION: In this series of 309 primary THAs in patients with AS, the 20-year cumulative incidence of any revision after primary THA was 17.5%. Aseptic loosening, osteolysis/PE wear, and femoral component fracture were the most common reasons for revision. Notably, the cumulative incidence of dislocation at 20 years was only 2.9%. LEVEL OF EVIDENCE: Level IV.

Early Implant Failure of a 2-Level M6-Cervical Total Disc Replacement: A Case Report.

CASE: We report a case of implant failure after primary 2-level M6-cervical disc replacement (M6-C; Spinal Kinetics) at C4-5 and C5-6. At revision surgery, a full-thickness tear was identified in the sheath of the C5-6 implant. Histology from periprosthetic tissue demonstrated polyethylene particles without acute inflammation. Tissue cultures were positive for Propionibacterium acnes, but ultrasonicate cultures were negative for both prostheses. An independent laboratory test confirmed mechanical failure of the C5-6 prosthesis. CONCLUSION: This is the first report of mechanical failure associated with wear-debris osteolysis after M6-C disc arthroplasty. Therefore, continued surveillance after CTDR is necessary.

Robust geographical determinants of infection prevalence and a contrasting latitudinal diversity gradient for haemosporidian parasites in Western Palearctic birds.

Identifying robust environmental predictors of infection probability is central to forecasting and mitigating the ongoing impacts of climate change on vector-borne disease threats. We applied phylogenetic hierarchical models to a data set of 2,171 Western Palearctic individual birds from 47 species to determine how climate and landscape variation influence infection probability for three genera of haemosporidian blood parasites (Haemoproteus, Leucocytozoon, and Plasmodium). Our comparative models found compelling evidence that birds in areas with higher vegetation density (captured by the normalized difference vegetation index [NDVI]) had higher likelihoods of carrying parasite infection. Magnitudes of this relationship were remarkably similar across parasite genera considering that these parasites use different arthropod vectors and are widely presumed to be epidemiologically distinct. However, we also uncovered key differences among genera that highlighted complexities in their climate responses. In particular, prevalences of Haemoproteus and Plasmodium showed strong but contrasting relationships with winter temperatures, supporting mounting evidence that winter warming is a key environmental filter impacting the dynamics of host-parasite interactions. Parasite phylogenetic community diversities demonstrated a clear but contrasting latitudinal gradient, with Haemoproteus diversity increasing towards the equator and Leucocytozoon diversity increasing towards the poles. Haemoproteus diversity also increased in regions with higher vegetation density, supporting our evidence that summer vegetation density is important for structuring the distributions of these parasites. Ongoing variation in winter temperatures and vegetation characteristics will probably have far-reaching consequences for the transmission and spread of vector-borne diseases.

Revision Total Hip Arthroplasty in Patients With Ankylosing Spondylitis: Long-Term Results.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory spondyloarthropathy with hip involvement in 40% of patients. With the recent interest in the hip-spine interplay, the purpose of this study was to define the long-term outcomes of revision total hip arthroplasty (THA) in the setting of AS. METHODS: 174 hips in patients with AS treated with revision THA from 1969 to 2016 were identified. Mean age at revision THA was 53 years and 76% were male. Cumulative incidences of any re-revision, reoperation, and dislocation were calculated using a competing risk analysis. Mean follow-up was 13 years. RESULTS: The cumulative incidence of any re-revision after index revision THA was 7% at 5 years and 36% at 20 years. Cumulative incidence of any reoperation was 9% at 5 years and 38% at 20 years. Cumulative incidence of dislocation was 6% at 5 years and 8% at 20 years. Revision THAs performed with contemporary implants (2000-2016) had a lower but statistically nonsignificant cumulative incidence of any re-revision when compared with historical implants (before 2000) at 5 years (5% vs 8%), 10 years (11% vs 18%), and 15 years (11% vs 38%) (hazard ratio, 0.47; 95% confidence interval, 0.17-1.33; P = .016). CONCLUSION: In this large series of 174 revision THAs in patients with AS, the cumulative incidence of dislocation was 8% at 20 years. The 20-year cumulative incidence of any re-revision was 36%, which is similar to reported rates in patients with comparable demographic features without AS. LEVEL OF EVIDENCE: Level IV.

Unravelling animal exposure profiles of human Q fever cases in Queensland, Australia, using natural language processing.

Q fever, caused by the zoonotic bacterium Coxiella burnetii, is a globally distributed emerging infectious disease. Livestock are the most important zoonotic transmission sources, yet infection in people without livestock exposure is common. Identifying potential exposure pathways is necessary to design effective interventions and aid outbreak prevention. We used natural language processing and graphical network methods to provide insights into how Q fever notifications are associated with variation in patient occupations or lifestyles. Using an 18-year time-series of Q fever notifications in Queensland, Australia, we used topic models to test whether compositions of patient answers to follow-up exposure questionnaires varied between demographic groups or across geographical areas. To determine heterogeneity in possible zoonotic exposures, we explored patterns of livestock and game animal co-exposures using Markov Random Fields models. Finally, to identify possible correlates of Q fever case severity, we modelled patient probabilities of being hospitalized as a function of particular exposures. Different demographic groups consistently reported distinct sets of exposure terms and were concentrated in different areas of the state, suggesting the presence of multiple transmission pathways. Macropod exposure was commonly reported among Q fever cases, even when exposure to cattle, sheep or goats was absent. Males, older patients and those that reported macropod exposure were more likely to be hospitalized due to Q fever infection. Our study indicates that follow-up surveillance combined with text modelling is useful for unravelling exposure pathways in the battle to reduce Q fever incidence and associated morbidity.

Parasite associations predict infection risk: incorporating co-infections in predictive models for neglected tropical diseases.

BACKGROUND: Schistosomiasis and infection by soil-transmitted helminths are some of the world's most prevalent neglected tropical diseases. Infection by more than one parasite (co-infection) is common and can contribute to clinical morbidity in children. Geostatistical analyses of parasite infection data are key for developing mass drug administration strategies, yet most methods ignore co-infections when estimating risk. Infection status for multiple parasites can act as a useful proxy for data-poor individual-level or environmental risk factors while avoiding regression dilution bias. Conditional random fields (CRF) is a multivariate graphical network method that opens new doors in parasite risk mapping by (i) predicting co-infections with high accuracy; (ii) isolating associations among parasites; and (iii) quantifying how these associations change across landscapes. METHODS: We built a spatial CRF to estimate infection risks for Ascaris lumbricoides, Trichuris trichiura, hookworms (Ancylostoma duodenale and Necator americanus) and Schistosoma mansoni using data from a national survey of Rwandan schoolchildren. We used an ensemble learning approach to generate spatial predictions by simulating from the CRF's posterior distribution with a multivariate boosted regression tree that captured non-linear relationships between predictors and covariance in infection risks. This CRF ensemble was compared against single parasite gradient boosted machines to assess each model's performance and prediction uncertainty. RESULTS: Parasite co-infections were common, with 19.57% of children infected with at least two parasites. The CRF ensemble achieved higher predictive power than single-parasite models by improving estimates of co-infection prevalence at the individual level and classifying schools into World Health Organization treatment categories with greater accuracy. The CRF uncovered important environmental and demographic predictors of parasite infection probabilities. Yet even after capturing demographic and environmental risk factors, the presences or absences of other parasites were strong predictors of individual-level infection risk. Spatial predictions delineated high-risk regions in need of anthelminthic treatment interventions, including areas with higher than expected co-infection prevalence. CONCLUSIONS: Monitoring studies routinely screen for multiple parasites, yet statistical models generally ignore this multivariate data when assessing risk factors and designing treatment guidelines. Multivariate approaches can be instrumental in the global effort to reduce and eventually eliminate neglected helminth infections in developing countries.

An inverse latitudinal gradient in infection probability and phylogenetic diversity for Leucocytozoon blood parasites in New World birds.

Geographic variation in environmental conditions as well as host traits that promote parasite transmission may impact infection rates and community assembly of vector-transmitted parasites. Identifying the ecological, environmental and historical determinants of parasite distributions and diversity is therefore necessary to understand disease outbreaks under changing environments. Here, we identified the predictors and contributions of infection probability and phylogenetic diversity of Leucocytozoon (an avian blood parasite) at site and species levels across the New World. To explore spatial patterns in infection probability and lineage diversity for Leucocytozoon parasites, we surveyed 69 bird communities from Alaska to Patagonia. Using phylogenetic Bayesian hierarchical models and high-resolution satellite remote-sensing data, we determined the relative influence of climate, landscape, geography and host phylogeny on regional parasite community assembly. Infection rates and parasite diversity exhibited considerable variation across regions in the Americas. In opposition to the latitudinal gradient hypothesis, both the diversity and prevalence of Leucocytozoon parasites decreased towards the equator. Host relatedness and traits known to promote vector exposure neither predicted infection probability nor parasite diversity. Instead, the probability of a bird being infected with Leucocytozoon increased with increasing vegetation cover (NDVI) and moisture levels (NDWI), whereas the diversity of parasite lineages decreased with increasing NDVI. Infection rates and parasite diversity also tended to be higher in cooler regions and higher latitudes. Whereas temperature partially constrains Leucocytozoon diversity and infection rates, landscape features, such as vegetation cover and water body availability, play a significant role in modulating the probability of a bird being infected. This suggests that, for Leucocytozoon, the barriers to host shifting and parasite host range expansion are jointly determined by environmental filtering and landscape, but not by host phylogeny. Our results show that integrating host traits, host ancestry, bioclimatic data and microhabitat characteristics that are important for vector reproduction are imperative to understand and predict infection prevalence and diversity of vector-transmitted parasites. Unlike other vector-transmitted diseases, our results show that Leucocytozoon diversity and prevalence will likely decrease with warming temperatures.