Reporting of social determinants of health in randomized controlled trials conducted in the pediatric intensive care unit.

Introduction: The influence of social determinants of health (SDOH) on access to care and outcomes for critically ill children remains an understudied area with a paucity of high-quality data. Recent publications have highlighted the importance of incorporating SDOH considerations into research but the frequency with which this occurs in pediatric intensive care unit (PICU) research is unclear. Our objective was to determine the frequency and categories of SDOH variables reported and how these variables were defined in published PICU randomized controlled trials (RCTs). Methods: We searched Medline, Embase, Lilacs, and Central from inception to Dec 2022. Inclusion criteria were randomized controlled trials of any intervention on children or their families in a PICU. Data related to study demographics and nine WHO SDOH categories were extracted, and descriptive statistics and qualitative data generated. Results: 586 unique RCTs were included. Studies had a median sample size of 60 patients (IQR 40-106) with 73.0% of studies including ≤100 patients and 41.1% including ≤50 patients. A total of 181 (181/586, 30.9%) studies reported ≥1 SDOH variable of which 163 (163/586, 27.8%) reported them by randomization group. The most frequently reported categories were food insecurity (100/586, 17.1%) and social inclusion and non-discrimination (73/586, 12.5%). Twenty-five of 57 studies (43.9%) investigating feeding or nutrition and 11 of 82 (13.4%) assessing mechanical ventilation reported baseline nutritional assessments. Forty-one studies investigated interventions in children with asthma or bronchiolitis of which six reported on smoking in the home (6/41, 14.6%). Discussion: Reporting of relevant SDOH variables occurs infrequently in PICU RCTs. In addition, when available, categorizations and definitions of SDOH vary considerably between studies. Standardization of SDOH variable collection along with consistent minimal reporting requirements for PICU RCT publications is needed.

Comparison of antiviral responses in two bat species reveals conserved and divergent innate immune pathways.

Bats host a range of disease-causing viruses without displaying clinical symptoms. The mechanisms behind this are a continuous source of interest. Here, we studied the antiviral response in the Egyptian fruit bat and Kuhl's pipistrelle, representing two subordinal clades. We profiled the antiviral response in fibroblasts using RNA sequencing and compared bat with primate and rodent responses. Both bats upregulate similar genes; however, a subset of these genes is transcriptionally divergent between them. These divergent genes also evolve rapidly in sequence, have specific promoter architectures, and are associated with programs underlying tolerance and resistance. Finally, we characterized antiviral genes that expanded in bats, with duplicates diverging in sequence and expression. Our study reveals a largely conserved antiviral program across bats and points to a set of genes that rapidly evolve through multiple mechanisms. These can contribute to bat adaptation to viral infection and provide directions to understanding the mechanisms behind it.

In sickness and in health: the dynamics of the fruit bat gut microbiota under a bacterial antigen challenge and its association with the immune response.

Introduction: Interactions between the gut microbiome (GM) and the immune system influence host health and fitness. However, few studies have investigated this link and GM dynamics during disease in wild species. Bats (Mammalia: Chiroptera) have an exceptional ability to cope with intracellular pathogens and a unique GM adapted to powered flight. Yet, the contribution of the GM to bat health, especially immunity, or how it is affected by disease, remains unknown. Methods: Here, we examined the dynamics of the Egyptian fruit bats' (Rousettus aegyptiacus) GM during health and disease. We provoked an inflammatory response in bats using lipopolysaccharides (LPS), an endotoxin of Gram-negative bacteria. We then measured the inflammatory marker haptoglobin, a major acute phase protein in bats, and analyzed the GM (anal swabs) of control and challenged bats using high-throughput 16S rRNA sequencing, before the challenge, 24h and 48h post challenge. Results: We revealed that the antigen challenge causes a shift in the composition of the bat GM (e.g., Weissella, Escherichia, Streptococcus). This shift was significantly correlated with haptoglobin concentration, but more strongly with sampling time. Eleven bacterial sequences were correlated with haptoglobin concentration and nine were found to be potential predictors of the strength of the immune response, and implicit of infection severity, notably Weissella and Escherichia. The bat GM showed high resilience, regaining the colony's group GM composition rapidly, as bats resumed foraging and social activities. Conclusion: Our results demonstrate a tight link between bat immune response and changes in their GM, and emphasize the importance of integrating microbial ecology in ecoimmunological studies of wild species. The resilience of the GM may provide this species with an adaptive advantage to cope with infections and maintain colony health.

Seasonal challenges of tropical bats in temperate zones.

To examine the challenges faced by free-ranging Rousettus aegyptiacus living at the northern edge of their distribution, we performed a retrospective analysis of 2196 clinical cases reported by a bat rescue NGO over a period of 36 months, from throughout Israel. All cases of injured bats were evaluated and categorized according to date, place, sex, age, and etiology of the morbidity. The data analysis revealed an increase in all types of morbidity during the wintertime, with more than two-fold the number of cases per week compared to in the summer, over three consecutive years. Moreover, we found that the number of abandoned pups peaked during spring and summer, when adult morbidity is minimal. We characterized two prominent types of previously undescribed morbidities in R. aegyptiacus. We also employed GPS tracking to monitor the movement and foraging of dozens of bats, and to examine the potential correlates of elevated winter morbidity. Our results suggest that it is mainly harsh weather that drives the observed winter morbidity, with food limitations playing a minor-role. We hypothesize that R. aegyptiacus, of tropical origin, is facing major seasonal survival difficulties near the northern edge of its distribution, probably limiting its spread further northwards still.

Revising the paradigm: Are bats really pathogen reservoirs or do they possess an efficient immune system?

While bats are often referred to as reservoirs of viral pathogens, a meta-analysis of the literature reveals many cases in which there is not enough evidence to claim so. In many cases, bats are able to confront viruses, recover, and remain immune by developing a potent titer of antibodies, often without becoming a reservoir. In other cases, bats might have carried an ancestral virus that at some time point might have mutated into a human pathogen. Moreover, bats exhibit a balanced immune response against viruses that have evolved over millions of years. Using genomic tools, it is now possible to obtain a deeper understanding of that unique immune system and its variability across the order Chiroptera. We conclude, that with the exception of a few viruses, bats pose little zoonotic danger to humans and that they operate a highly efficient anti-inflammatory response that we should strive to understand.

Induced bacterial sickness causes inflammation but not blood oxidative stress in Egyptian fruit bats (Rousettus aegyptiacus).

Bats are particularly interesting vertebrates in their response to pathogens owing to extremes in terms of tolerance and resistance. Oxidation is often a by-product of processes involved in the acute phase response, which may result in antimicrobial or self-damaging effects. We measured the immunological and oxidative status responses of Egyptian fruit bats (Rousettus aegyptiacus) to a simulated bacterial infection using lipopolysaccharide injection. As expected, experimental bats exhibited increases in two humoral immunological markers. However, they surprisingly did not show any effects across two markers of oxidative damage and four antioxidant markers. We propose that this lack of effects on oxidative status may be due to a reduction in cell metabolism through sickness behaviours or given life history traits, such as a long lifespan and a frugivorous diet. Finally, the consistency in the pattern of elevation in haptoglobin and lysozyme between current and previous findings highlights their utility as diagnostic markers for extracellular infections in bats.

Functional daylight echolocation in highly visual bats.

Bats rely on echolocation for operating in dim light or dark conditions. Accordingly, most research on echolocation is performed under dark conditions with a few exceptions. Bat species that emerge to forage before sunset have been shown to use echolocation even in relatively high light levels1-3. It has been argued that for insectivorous bats, as light levels decrease, echolocation rapidly becomes advantageous over vision for detecting tiny insects during dusk or dawn2 and that information from the two sensory modalities is integrated4,5. Functional use of echolocation in broad daylight in insectivorous bats has been scarcely reported6,7. Here, we report functional use of echolocation in broad daylight in highly visual fruit bats.

Sick bats stay home alone: fruit bats practice social distancing when faced with an immunological challenge.

Along with its many advantages, social roosting imposes a major risk of pathogen transmission. How social animals reduce this risk is poorly documented. We used lipopolysaccharide challenge to imitate bacterial infection in both a captive and a free-living colony of an extremely social, long-lived mammal-the Egyptian fruit bat. We monitored behavioral and physiological responses using an arsenal of methods, including onboard GPS to track foraging, acceleration sensors to monitor movement, infrared video to record social behavior, and blood samples to measure immune markers. Sick-like (immune-challenged) bats exhibited an increased immune response, as well as classic illness symptoms, including fever, weight loss, anorexia, and lethargy. Notably, the bats also exhibited behaviors that would reduce pathogen transfer. They perched alone and appeared to voluntarily isolate themselves from the group by leaving the social cluster, which is extremely atypical for this species. The sick-like individuals in the open colony ceased foraging outdoors for at least two nights, thus reducing transmission to neighboring colonies. Together, these sickness behaviors demonstrate a strong, integrative immune response that promotes recovery of infected individuals while reducing pathogen transmission inside and outside the roost, including spillover events to other species, such as humans.

Coordinated change at the colony level in fruit bat fur microbiomes through time.

The host-associated microbiome affects individual health and behaviour, and may be influenced by local environmental conditions. However, little is known about microbiomes' temporal dynamics in free-living species compared with their dynamics in humans and model organisms, especially in body sites other than the gut. Here, we investigate longitudinal changes in the fur microbiome of captive and free-living Egyptian fruit bats. We find that, in contrast to patterns described in humans and other mammals, the prominent dynamics is of change over time at the level of the colony as a whole. On average, a pair of fur microbiome samples from different individuals in the same colony collected on the same date are more similar to one another than a pair of samples from the same individual collected at different time points. This pattern suggests that the whole colony may be the appropriate biological unit for understanding some of the roles of the host microbiome in social bats' ecology and evolution. This pattern of synchronized colony changes over time is also reflected in the profile of volatile compounds in the bats' fur, but differs from the more individualized pattern found in the bats' gut microbiome.

REFRACTOMETRIC URINE SPECIFIC GRAVITY OF FREE-LIVING EGYPTIAN FRUIT BATS (ROUSETTUS AEGYPTIACUS).

In both human and veterinary medicine, urine specific gravity (USG) is commonly measured by refractometry to indirectly reflect the osmolality of urine to thereby evaluate the kidney's ability to concentrate or dilute urine according to physiologic need and certain disease conditions. However, for accurate interpretation of the significance of any value, knowledge of the expected USG for the healthy species in question is required. It is generally believed that fruit bats, and Egyptian fruit bats (Rousettus aegyptiacus) in particular, are unable to highly concentrate their urine. In this study, the USG was determined using a handheld urine refractometer in 43 free-living Egyptian fruit bats of both sexes. The calculated nonparametric 90% confidence interval for Egyptian fruit bats in this study was 1.006-1.050, with no association with capture site, sex, weight, or packed cell volume and total solids. Results suggest that free-living Egyptian fruit bats are able to highly concentrate their urine.

Venipuncture in bats.

Though not as common as small rodents in laboratory settings, bats are being increasingly used in research studies. Knowledge of proper blood sampling techniques is essential for care and management of bats.