What is stirring in the reservoir? Modelling mechanisms of henipavirus circulation in fruit bat hosts

Pathogen circulation among reservoir hosts is a precondition for zoonotic spillover. Unlike the acute, high morbidity infections typical in spillover hosts, infected reservoir hosts often exhibit low morbidity and mortality. Although it has been proposed that reservoir host infections may be persistent with recurrent episodes of shedding, direct evidence is often lacking. We construct a generalized SEIR (susceptible, exposed, infectious, recovered) framework encompassing 46 sub-models representing the full range of possible transitions among those four states of infection and immunity. We then use likelihood-based methods to fit these models to nine years of longitudinal data on henipavirus serology from a captive colony of Eidolon helvum bats in Ghana. We find that reinfection is necessary to explain observed dynamics; that acute infectious periods may be very short (hours to days); that immunity, if present, lasts about 1–2 years; and that recurring latent infection is likely. Although quantitative inference is sensitive to assumptions about serology, qualitative predictions are robust. Our novel approach helps clarify mechanisms of viral persistence and circulation in wild bats, including estimated ranges for key parameters such as the basic reproduction number and the duration of the infectious period. Our results inform how future field-based and experimental work could differentiate the processes of viral recurrence and reinfection in reservoir hosts. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’

Domesticated animals as hosts of henipaviruses and filoviruses: A systematic review

Bat-borne viruses carry undeniable risks to the health of human beings and animals, and there is growing recognition of the need for a 'One Health' approach to understand their frequently complex spill-over routes. While domesticated animals can play central roles in major spill- over events of zoonotic bat-borne viruses, for example during the pig- amplified Malaysian Nipah virus outbreak of 1998-1999, the extent of their potential to act as bridging or amplifying species for these viruses has not been characterised systematically. This review aims to compile current knowledge on the role of domesticated animals as hosts of two types of bat-borne viruses, henipaviruses and filoviruses. A systematic literature search of these virus-host interactions in domesticated animals identified 72 relevant studies, which were categorised by year, location, design and type of evidence generated. The review then focusses on Africa as a case study, comparing research efforts in domesticated animals and bats with the distributions of documented human cases. Major gaps remain in our knowledge of the potential ability of domesticated animals to contract or spread these zoonoses. Closing these gaps will be necessary to fully evaluate and mitigate spill-over risks of these viruses, especially with global agricultural intensification

LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT2A receptor

Compounds that activate the 5-HT2A receptor, such as lysergic acid diethylamide (LSD), act as hallucinogens in humans. One notable exception is the LSD congener lisuride, which does not have hallucinogenic effects in humans even though it is a potent 5-HT2A agonist. LSD and other hallucinogens have been shown to disrupt prepulse inhibition (PPI), an operational measure of sensorimotor gating, by activating 5-HT2A receptors in rats. We tested whether lisuride disrupts PPI in male Sprague–Dawley rats. Experiments were also conducted to identify the mechanism(s) responsible for the effect of lisuride on PPI and to compare the effects of lisuride to those of LSD. Confirming a previous report, LSD (0.05, 0.1, and 0.2 mg/kg, s.c.) reduced PPI, and the effect of LSD was blocked by pretreatment with the selective 5-HT2A antagonist MDL 11,939. Administration of lisuride (0.0375, 0.075, and 0.15 mg/kg, s.c.) also reduced PPI. However, the PPI disruption induced by lisuride (0.075 mg/kg) was not blocked by pretreatment with MDL 11,939 or the selective 5-HT1A antagonist WAY-100635 but was prevented by pretreatment with the selective dopamine D2/D3 receptor antagonist raclopride (0.1 mg/kg, s.c). The effect of LSD on PPI is mediated by the 5-HT2A receptor, whereas activation of the 5-HT2A receptor does not appear to contribute to the effect of lisuride on PPI. These findings demonstrate that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of lisuride as a non-hallucinogenic 5-HT2A agonist

Challenges in evaluating risks and policy options around endemic establishment or elimination of novel pathogens

When a novel pathogen emerges there may be opportunities to eliminate transmission - locally or globally - whilst case numbers are low. However, the effort required to push a disease to elimination may come at a vast cost at a time when uncertainty is high. Models currently inform policy discussions on this question, but there are a number of open challenges, particularly given unknown aspects of the pathogen biology, the effectiveness and feasibility of interventions, and the intersecting political, economic, sociological and behavioural complexities for a novel pathogen. In this overview, we detail how models might identify directions for better leveraging or expanding the scope of data available on the pathogen trajectory, for bounding the theoretical context of emergence relative to prospects for elimination, and for framing the larger economic, behavioural and social context that will influence policy decisions and the pathogen’s outcome