Amniotic fluid embolism: lessons for rapid recognition and intervention.

Amniotic fluid embolism is a rare, often fatal complication of labor and delivery. The classic presentation is the sudden onset of a triad of clinical manifestations: hypoxia, hypotension and coagulopathy. Understanding of the syndrome as an immunologically mediated, complicated and often catastrophic maternal response to fetal or placental antigens is coming into focus. New treatments such as extracorporeal membrane oxygenation (ECMO) and better use of old treatments such as transfusion offer hope, but the condition is often rapidly fatal, so saving the maternal and fetal lives depends on rapid recognition of the syndrome. This series of three cases illustrates the clinical features enabling the rapid recognition needed for successful treatment of amniotic fluid embolism syndrome.

Amniotic fluid embolism: lessons for rapid recognition and intervention

Amniotic fluid embolism is a rare, often fatal complication of labor and delivery. The classic presentation is the sudden onset of a triad of clinical manifestations: hypoxia, hypotension and coagulopathy. Understanding of the syndrome as an immunologically mediated, complicated and often catastrophic maternal response to fetal or placental antigens is coming into focus. New treatments such as extracorporeal membrane oxygenation (ECMO) and better use of old treatments such as transfusion offer hope, but the condition is often rapidly fatal, so saving the maternal and fetal lives depends on rapid recognition of the syndrome. This series of three cases illustrates the clinical features enabling the rapid recognition needed for successful treatment of amniotic fluid embolism syndrome.

Virulence phenotypes result from interactions between pathogen ploidy and genetic background.

Studying fungal virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. However, the role of ploidy has often been overlooked when studying virulence in eukaryotic pathogens. Since fungal pathogens, including the human opportunistic pathogen Candida albicans, can display extensive ploidy variation, assessing how ploidy impacts virulence has important clinical relevance. As an opportunistic pathogen, C. albicans causes nonlethal, superficial infections in healthy individuals, but life-threatening bloodstream infections in individuals with compromised immune function. Here, we determined how both ploidy and genetic background of C. albicans impacts virulence phenotypes in healthy and immunocompromised nematode hosts by characterizing virulence phenotypes in four near-isogenic diploid and tetraploid pairs of strains, which included both laboratory and clinical genetic backgrounds. We found that C. albicans infections decreased host survival and negatively impacted host reproduction, and we leveraged these two measures to survey both lethal and nonlethal virulence phenotypes across the multiple C. albicans strains. In this study, we found that regardless of pathogen ploidy or genetic background, immunocompromised hosts were susceptible to fungal infection compared to healthy hosts. Furthermore, for each host context, we found a significant interaction between C. albicans genetic background and ploidy on virulence phenotypes, but no global differences between diploid and tetraploid pathogens were observed.

A Novel Virulence Phenotype Rapidly Assesses Candida Fungal Pathogenesis in Healthy and Immunocompromised Caenorhabditis elegans Hosts.

The yeast Candida albicans is an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. While C. albicans is the predominant species isolated in the human gastrointestinal mycobiome and is implicated in fungal infection, infections due to non-albicans Candida species are rapidly rising. Studying the factors that contribute to virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. Here, we utilize the nematode Caenorhabditis elegans as a perspicuous and efficient model host system to study fungal infections of Candida pathogens. We find that, in addition to reducing lifetime host survival, exposure to C. albicans results in delayed reproduction, which significantly reduced lineage growth over multiple generations. Furthermore, we assessed fungal pathogen virulence in C. elegans hosts compromised for innate immune function and detected increased early mortality, reduced brood sizes, and delayed reproduction relative to infected healthy hosts. Importantly, by assessing virulence in both healthy and immunocompromised host backgrounds, we reveal the pathogen potential in non-albicans Candida species. Taken together, we present a novel lineage growth assay to measure reduction in host fitness associated with fungal infection and demonstrate significant interactions between pathogen and host immune function that contribute to virulence.IMPORTANCE Opportunistic pathogens are commensals capable of causing disease and are serious threats to human health. It is critical to understand the mechanisms and host contexts under which opportunistic pathogens become virulent. In this work, we present a novel assay to quickly and quantitatively measure pathogen virulence in healthy and immunocompromised nematode hosts. We found that Candida species, one of the most prominent fungal opportunistic pathogens of humans, decrease host fitness by reducing survival and impacting host reproduction. Most importantly, by measuring virulence in hosts that have intact or compromised immune function, we can reveal the pathogenic potential of opportunistic fungal pathogens.