Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Assessing host extinction risk following exposure to Batrachochytrium dendrobatidis.

Wildlife diseases are increasingly recognized as a major threat to biodiversity. Chytridiomycosis is an emerging infectious disease of amphibians caused by the fungus Batrachochytrium dendrobatidis (Bd). Using a mathematical model and simulations, we study its effects on a generic riparian host population with a tadpole and adult life stage. An analytical expression for the basic reproduction quotient, Qo, of the pathogen is derived. By sampling the entire relevant parameter space, we perform a statistical assessment of the importance of all considered parameters in determining the risk of host extinction, upon exposure to Bd. We find that Qo not only gives a condition for the initial invasion of the fungus, but is in fact the best predictor for host extinction. We also show that the role of tadpoles, which in some species tolerate infections, is ambivalent. While tolerant tadpoles may provide a reservoir for the fungus, thus facilitating its persistence or even amplifying its outbreaks, they can also act as a rescue buffer for a stressed host population. Our results have important implications for amphibian conservation efforts.

Susceptibility of the endangered frog Dendropsophus meridensis to the pathogenic fungus Batrachochytrium dendrobatidis.

Chytridiomycosis is an emerging disease that has driven some amphibian species to extinction while leaving others apparently unharmed. Its causative agent, Batrachochytrium dendrobatidis (Bd), now persists endemically in many amphibian communities. Understanding host species response to Bd infection is critical for managing chytridiomycosis because the epidemiology of this disease is host-specific. Dendropsophus meridensis is an endangered hylid frog endemic to the Venezuelan Andes. This species is sympatric with the American bullfrog Lithobates catesbeianus, an introduced species known to act as a reservoir for Bd. High prevalence of infection and high zoospore burdens in wild populations of D. meridensis in the Venezuelan Andes suggested some tolerance for Bd. However, experimental exposure of post-metamorphic frogs resulted in 53% mortality, a value that represents a 14-fold increase in the odds of dying compared to control frogs. Repeated diagnostics using real-time polymerase chain reaction assays demonstrated that individuals that died accumulated a higher number of zoospores than those that survived, although this value was lower than the mean zoospore burdens observed in natural populations. Given the susceptibility of D. meridensis to a strain of Bd isolated from a nearby population of bullfrogs, we emphasize the need to limit the dispersion of this invasive species.

Living with the pathogenic chytrid fungus: Exploring mechanisms of coexistence in the harlequin toad Atelopus cruciger.

Chytridiomycosis, a disease caused by the fungus Batrachochytrium dendrobatidis (Bd), has been linked with the disappearance of amphibian populations worldwide. Harlequin toads (Atelopus) are among the most severely impacted genera. Two species are already considered extinct and most of the others are at high risk of extinction. The recent rediscovery of harlequin toad populations coexisting with Bd suggest that the pathogen can maintain enzootic cycles at some locations. The mechanisms promoting coexistence, however, are not well understood. We explore the dynamics of Bd infection in harlequin toads by modeling a two-stage host population with transmission through environmental reservoirs. Simulations showed that variations in the recruitment of adults and the persistence of zoospores in the environment were more likely to drive shifts between extinction and coexistence than changes in the vulnerability of toads to infection with Bd. These findings highlight the need to identify mechanisms for assuring adult recruitment or minimizing transmission from potential reservoirs, biotic or abiotic, in recovering populations.

Signatures of the Venezuelan Humanitarian Crisis in the First Wave of COVID-19: Fuel Shortages and Border Migration.

Testing and isolation have been crucial for controlling the COVID-19 pandemic. Venezuela has one of the weakest testing infrastructures in Latin America and the low number of reported cases in the country has been attributed to substantial underreporting. However, the Venezuelan epidemic seems to have lagged behind other countries in the region, with most cases occurring within the capital region and four border states. Here, we describe the spatial epidemiology of COVID-19 in Venezuela and its relation to the population mobility, migration patterns, non-pharmaceutical interventions and fuel availability that impact population movement. Using a metapopulation model of SARS-CoV-2 transmission dynamics, we explore how movement patterns could have driven the observed distribution of cases. Low within-country connectivity most likely delayed the onset of the epidemic in most states, except for those bordering Colombia and Brazil, where high immigration seeded outbreaks. NPIs slowed early epidemic growth and subsequent fuel shortages appeared to be responsible for limiting the spread of COVID-19 across the country.

Estimating large carnivore populations at global scale based on spatial predictions of density and distribution - Application to the jaguar (Panthera onca).

Broad scale population estimates of declining species are desired for conservation efforts. However, for many secretive species including large carnivores, such estimates are often difficult. Based on published density estimates obtained through camera trapping, presence/absence data, and globally available predictive variables derived from satellite imagery, we modelled density and occurrence of a large carnivore, the jaguar, across the species' entire range. We then combined these models in a hierarchical framework to estimate the total population. Our models indicate that potential jaguar density is best predicted by measures of primary productivity, with the highest densities in the most productive tropical habitats and a clear declining gradient with distance from the equator. Jaguar distribution, in contrast, is determined by the combined effects of human impacts and environmental factors: probability of jaguar occurrence increased with forest cover, mean temperature, and annual precipitation and declined with increases in human foot print index and human density. Probability of occurrence was also significantly higher for protected areas than outside of them. We estimated the world's jaguar population at 173,000 (95% CI: 138,000-208,000) individuals, mostly concentrated in the Amazon Basin; elsewhere, populations tend to be small and fragmented. The high number of jaguars results from the large total area still occupied (almost 9 million km2) and low human densities (< 1 person/km2) coinciding with high primary productivity in the core area of jaguar range. Our results show the importance of protected areas for jaguar persistence. We conclude that combining modelling of density and distribution can reveal ecological patterns and processes at global scales, can provide robust estimates for use in species assessments, and can guide broad-scale conservation actions.

Population dynamics of the critically endangered toad Atelopus cruciger and the fungal disease chytridiomycosis.

Harlequin toads (Atelopus) are among the most severely impacted amphibians by the emergence of chytridiomycosis, a fungal disease caused by the pathogen Batrachochytrium dendrobatidis (Bd). Many species disappeared while others suffered drastic contractions of their geographic distribution to lower altitudes. A diminished virulence of Bd in warm habitats was proposed to explain the survival of lowland populations of harlequin toads (i.e. thermal refuge hypothesis). To understand the mechanisms that allow some populations to reach an endemic equilibrium with this pathogen, we estimated demographic and epidemiological parameters at one remnant population of Atelopus cruciger in Venezuela using mark-recapture data from 2007-2013. We demonstrated that Bd is highly virulent for A. cruciger, increasing the odds of dying of infected adults four times in relation to uninfected ones and reducing the life expectancy of reproductive toads to a few weeks. Despite an estimated annual loss of 18% of the reproductive population due to Bd-induced mortality, this population has persisted in an endemic equilibrium for the last decade through the large recruitment of healthy adults every year. Given the high vulnerability of harlequin toads to Bd in lowland populations, thermal refuges need to be redefined as habitats of reduced transmission rather than attenuated virulence.

The cane or marine toad, Rhinella marina (Anura, Bufonidae): two genetically and morphologically distinct species.

Rhinella marina is a Neotropical toad that has been introduced widely worldwide. Its toxic effects to frog-eating predators threaten the native and domestic fauna of some regions where it has been introduced. Despite previous studies suggesting two genetically distinct cryptic species within R. marina, one east and one west of the Andes, its taxonomic status remained unresolved due to the absence of morphological complementary evidence. For the first time, data from two mitochondrial genes (ND3 and CR) and 23 morphometric landmarks are combined to evaluate the taxonomic status of this species. Our results support the hypothesis of two separate evolutionary lineages within R. marina and demonstrate that these lineages have significantly diverged in skull shape. We identified two distinct morphotypes, one eastern and one Andean western, with no overlapping morphospaces. The geographic pattern of genetic variation was consistent with a stable structured population with no evidence of recent demographic or geographic expansions. The concordance between the observed geographic patterns in morphometric and genic traits calls for the recognition of two species under R. marina name.

Genetic relationships among some species groups within the genus Lutzomyia (Diptera: Psychodidae).

Molecular data on Lutzomyia are very scarce, despite the fact that this genus includes all the species involved in the transmission of leishmaniasis in America. We examine the genetic relationships among eight morphologic groups within the Lutzomyia genus and two Brumptomyia species, using nine enzyme loci and the last 285 basepairs of the mitochondrial cytochrome b gene. The structure of the genetic variation among the species analyzed indicated a closer genetic relationship among members of a morphologic group than between members of different groups. The lower levels of variation recorded among these groups compared with that between Brumptomyia and Lutzomyia suggest a subgeneric status for all of these groups, including Psychodopygus. A maximum likelihood tree for the allozyme data and a neighbor-joining consensus tree for the mitochondrial DNA sequences showed a general agreement with morphologic groups, with only minor differences. Nyssomyia, Verrucarum and Micropygomyia formed separate monophyletic groups. Lutzomyia could not be separated from Psathyromyia, and both Migonei species, L. dubitans and L. migonei, grouped in different clades according to the host species they are found on.

Body size selection inAcanthoscelides alboscutellatus (Coleoptera: Bruchidae) : I. Entrapment within the fruit ofLudwigia alternifolia (Onagraceae).

Direct observations and analyses of selection occurring in natural populations are rare. The biology of the bruchid beetle,Acanthoscelides alboscutellatus, on its host plant,Ludwigia alternifolia, provides an anusual opportunity to study the process of selection on the morphology of an organism under field conditions.A. alboscutellatus larvae mature within the variably dehiscent fruit ofL. alternifolia. At eclosion, adults are confined within indehiscent fruit but are not confined within dehiscent fruit. Beetles can escape from indehiscent fruit only by forcing their bodies through the fruit's apical pore (a circular opening in the top of the fruit). Thus, during the eclosion stage of this beetle's life cycle the relationship between body size and differential fitness appears to be clearly defined.We examined entrapment ofA. alboscutellatus within indehiscentL. alternifolia fruit in a natural population. Only 8.8% of the beetles that attempted to escape were successful. Smaller beetles were trapped within a narrower range of pore diameters than were larger beetles; and trapped beetles had only limited abilities to enlarge fruit pore diameter. These data suggest (1) that escape from indehiscent fruit is regulated by the relationship between adult body diameter and fruit pore diameter and (2) that adult beetles may experience strong selection for small body diameter (size) within idehiscent fruit.

Global invasion of Lantana camara: has the climatic niche been conserved across continents?

Lantana camara, a native plant from tropical America, is considered one of the most harmful invasive species worldwide. Several studies have identified potentially invasible areas under scenarios of global change, on the assumption that niche is conserved during the invasion process. Recent studies, however, suggest that many invasive plants do not conserve their niches. Using Principal Components Analyses (PCA), we tested the hypothesis of niche conservatism for L. camara by comparing its native niche in South America with its expressed niche in Africa, Australia and India. Using MaxEnt, the estimated niche for the native region was projected onto each invaded region to generate potential distributions there. Our results demonstrate that while L. camara occupied subsets of its original native niche in Africa and Australia, in India its niche shifted significantly. There, 34% of the occurrences were detected in warmer habitats nonexistent in its native range. The estimated niche for India was also projected onto Africa and Australia to identify other vulnerable areas predicted from the observed niche shift detected in India. As a result, new potentially invasible areas were identified in central Africa and southern Australia. Our findings do not support the hypothesis of niche conservatism for the invasion of L. camara. The mechanisms that allow this species to expand its niche need to be investigated in order to improve our capacity to predict long-term geographic changes in the face of global climatic changes.

Reproductive biology and mating system estimates of two Andean melocacti, Melocactus schatzlii and M. andinus (Cactaceae).

BACKGROUND AND AIMS: The genus Melocactus comprises 36 species of globose cacti with the most derived traits in the Cereeae tribe. It is the proper study system to examine what are the most derived reproductive strategies within that tribe. This study aims to characterize the reproductive biology and to estimate the mating system parameters of two Andean melocacti, Melocactus schatzlii and M. andinus. METHODS: The reproductive attributes of the two species were described, including floral morphology, anthesis patterns, floral rewards, floral visitors and visitation patterns. Levels of self-compatibility and autonomous self-pollination were estimated by hand-pollination experiments. Mating system estimates were obtained by conducting progeny array analyses using isozymes. KEY RESULTS: The flowers of the two species present the typical hummingbird-pollination syndrome. Despite their morphological resemblance, the two species differ in flower size, pollen and ovule production and anthesis pattern. Their main pollinator agents are hummingbirds, four species in M. schatzlii and one species in M. andinus. Both cacti are self-compatible and capable of self-pollination without the aid of pollen vectors. Population-level outcrossing rate was higher for M. schatzlii (t(m)=0.9) than for M. andinus (t(m)=0.4). At the family level, outcrossing rates for most mothers of M. schatzlii were higher (t(m)>0.8) than for M. andinus (t(m)<0.5). CONCLUSIONS: Although the two cacti are capable of selfing, M. schatzlii is a predominantly outcrossing species, while M. andinus behaves as a mixed-mating cactus. Hummingbirds are the only pollinators responsible for outcrossing and gene flow events in these species. In their absence, both melocacti set seeds by selfing. Based on its low population size, restricted distribution in Venezuela, low rates of floral visits, and high levels of inbreeding, M. andinus is considered to be an endangered species deserving further study to define its conservation status.