Transmission from vaccinated individuals in a large SARS-CoV-2 Delta variant outbreak.

An outbreak of over 1,000 COVID-19 cases in Provincetown, Massachusetts (MA), in July 2021-the first large outbreak mostly in vaccinated individuals in the US-prompted a comprehensive public health response, motivating changes to national masking recommendations and raising questions about infection and transmission among vaccinated individuals. To address these questions, we combined viral genomic and epidemiological data from 467 individuals, including 40% of outbreak-associated cases. The Delta variant accounted for 99% of cases in this dataset; it was introduced from at least 40 sources, but 83% of cases derived from a single source, likely through transmission across multiple settings over a short time rather than a single event. Genomic and epidemiological data supported multiple transmissions of Delta from and between fully vaccinated individuals. However, despite its magnitude, the outbreak had limited onward impact in MA and the US overall, likely due to high vaccination rates and a robust public health response.

Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization.

Structural principles underlying the composition of protective antiviral monoclonal antibody (mAb) cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic mAb cocktail against Ebola virus. We systematically analyzed the antibody repertoire in human survivors and identified a pair of potently neutralizing mAbs that cooperatively bound to the ebolavirus glycoprotein (GP). High-resolution structures revealed that in a two-antibody cocktail, molecular mimicry was a major feature of mAb-GP interactions. Broadly neutralizing mAb rEBOV-520 targeted a conserved epitope on the GP base region. mAb rEBOV-548 bound to a glycan cap epitope, possessed neutralizing and Fc-mediated effector function activities, and potentiated neutralization by rEBOV-520. Remodeling of the glycan cap structures by the cocktail enabled enhanced GP binding and virus neutralization. The cocktail demonstrated resistance to virus escape and protected non-human primates (NHPs) against Ebola virus disease. These data illuminate structural principles of antibody cooperativity with implications for development of antiviral immunotherapeutics.

Novel paramyxovirus associated with severe acute febrile disease, South Sudan and Uganda, 2012.

In 2012, a female wildlife biologist experienced fever, malaise, headache, generalized myalgia and arthralgia, neck stiffness, and a sore throat shortly after returning to the United States from a 6-week field expedition to South Sudan and Uganda. She was hospitalized, after which a maculopapular rash developed and became confluent. When the patient was discharged from the hospital on day 14, arthralgia and myalgia had improved, oropharynx ulcerations had healed, the rash had resolved without desquamation, and blood counts and hepatic enzyme levels were returning to reference levels. After several known suspect pathogens were ruled out as the cause of her illness, deep sequencing and metagenomics analysis revealed a novel paramyxovirus related to rubula-like viruses isolated from fruit bats.

Correction: Detection of novel coronaviruses in bats in Myanmar.

[This corrects the article DOI: 10.1371/journal.pone.0230802.].

Multimodal surveillance of SARS-CoV-2 at a university enables development of a robust outbreak response framework.

BACKGROUND: Universities are vulnerable to infectious disease outbreaks, making them ideal environments to study transmission dynamics and evaluate mitigation and surveillance measures. Here, we analyze multimodal COVID-19-associated data collected during the 2020-2021 academic year at Colorado Mesa University and introduce a SARS-CoV-2 surveillance and response framework. METHODS: We analyzed epidemiological and sociobehavioral data (demographics, contact tracing, and WiFi-based co-location data) alongside pathogen surveillance data (wastewater and diagnostic testing, and viral genomic sequencing of wastewater and clinical specimens) to characterize outbreak dynamics and inform policy. We applied relative risk, multiple linear regression, and social network assortativity to identify attributes or behaviors associated with contracting SARS-CoV-2. To characterize SARS-CoV-2 transmission, we used viral sequencing, phylogenomic tools, and functional assays. FINDINGS: Athletes, particularly those on high-contact teams, had the highest risk of testing positive. On average, individuals who tested positive had more contacts and longer interaction durations than individuals who never tested positive. The distribution of contacts per individual was overdispersed, although not as overdispersed as the distribution of phylogenomic descendants. Corroboration via technical replicates was essential for identification of wastewater mutations. CONCLUSIONS: Based on our findings, we formulate a framework that combines tools into an integrated disease surveillance program that can be implemented in other congregate settings with limited resources. FUNDING: This work was supported by the National Science Foundation, the Hertz Foundation, the National Institutes of Health, the Centers for Disease Control and Prevention, the Massachusetts Consortium on Pathogen Readiness, the Howard Hughes Medical Institute, the Flu Lab, and the Audacious Project.

Movements of Indian Flying Fox in Myanmar as a Guide to Human-Bat Interface Sites.

Frugivorous bats play a vital role in tropical ecosystems as pollinators and seed dispersers but are also important vectors of zoonotic diseases. Myanmar sits at the intersection of numerous bioregions and contains habitats that are important for many endangered and endemic species. This rapidly developing country also forms a connection between hotspots of emerging human diseases. We deployed Global Positioning System collars to track the movements of 10 Indian flying fox (Pteropus giganteus) in the agricultural landscapes of central Myanmar. We used clustering analysis to identify foraging sites and high-utilization areas. As part of a larger viral surveillance study in bats of Myanmar, we also collected oral and rectal swab samples from 29 bats to test for key emerging viral diseases in this colony. There were no positive results detected for our chosen viruses. We analyzed their foraging movement behavior and evaluated selected foraging sites for their potential as human-wildlife interface sites.

Evidence of transmission from fully vaccinated individuals in a large outbreak of the SARS-CoV-2 Delta variant in Provincetown, Massachusetts.

Multiple summer events, including large indoor gatherings, in Provincetown, Massachusetts (MA), in July 2021 contributed to an outbreak of over one thousand COVID-19 cases among residents and visitors. Most cases were fully vaccinated, many of whom were also symptomatic, prompting a comprehensive public health response, motivating changes to national masking recommendations, and raising questions about infection and transmission among vaccinated individuals. To characterize the outbreak and the viral population underlying it, we combined genomic and epidemiological data from 467 individuals, including 40% of known outbreak-associated cases. The Delta variant accounted for 99% of sequenced outbreak-associated cases. Phylogenetic analysis suggests over 40 sources of Delta in the dataset, with one responsible for a single cluster containing 83% of outbreak-associated genomes. This cluster was likely not the result of extensive spread at a single site, but rather transmission from a common source across multiple settings over a short time. Genomic and epidemiological data combined provide strong support for 25 transmission events from, including many between, fully vaccinated individuals; genomic data alone provides evidence for an additional 64. Together, genomic epidemiology provides a high-resolution picture of the Provincetown outbreak, revealing multiple cases of transmission of Delta from fully vaccinated individuals. However, despite its magnitude, the outbreak was restricted in its onward impact in MA and the US, likely due to high vaccination rates and a robust public health response.

Genome-Wide Changes in Genetic Diversity in a Population of Myotis lucifugus Affected by White-Nose Syndrome.

Novel pathogens can cause massive declines in populations, and even extirpation of hosts. But disease can also act as a selective pressure on survivors, driving the evolution of resistance or tolerance. Bat white-nose syndrome (WNS) is a rapidly spreading wildlife disease in North America. The fungus causing the disease invades skin tissues of hibernating bats, resulting in disruption of hibernation behavior, premature energy depletion, and subsequent death. We used whole-genome sequencing to investigate changes in allele frequencies within a population of Myotis lucifugus in eastern North America to search for genetic resistance to WNS. Our results show low FST values within the population across time, i.e., prior to WNS (Pre-WNS) compared to the population that has survived WNS (Post-WNS). However, when dividing the population with a geographical cut-off between the states of Pennsylvania and New York, a sharp increase in values on scaffold GL429776 is evident in the Post-WNS samples. Genes present in the diverged area are associated with thermoregulation and promotion of brown fat production. Thus, although WNS may not have subjected the entire M. lucifugus population to selective pressure, it may have selected for specific alleles in Pennsylvania through decreased gene flow within the population. However, the persistence of remnant sub-populations in the aftermath of WNS is likely due to multiple factors in bat life history.

Detection of novel coronaviruses in bats in Myanmar.

The recent emergence of bat-borne zoonotic viruses warrants vigilant surveillance in their natural hosts. Of particular concern is the family of coronaviruses, which includes the causative agents of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and most recently, Coronavirus Disease 2019 (COVID-19), an epidemic of acute respiratory illness originating from Wuhan, China in December 2019. Viral detection, discovery, and surveillance activities were undertaken in Myanmar to identify viruses in animals at high risk contact interfaces with people. Free-ranging bats were captured, and rectal and oral swabs and guano samples collected for coronaviral screening using broadly reactive consensus conventional polymerase chain reaction. Sequences from positives were compared to known coronaviruses. Three novel alphacoronaviruses, three novel betacoronaviruses, and one known alphacoronavirus previously identified in other southeast Asian countries were detected for the first time in bats in Myanmar. Ongoing land use change remains a prominent driver of zoonotic disease emergence in Myanmar, bringing humans into ever closer contact with wildlife, and justifying continued surveillance and vigilance at broad scales.

Resurrection of an East African house bat species Scotophilus altilis Allen, 1914 (Chiroptera: Vespertilionidae).

Several house bat specimens superficially resembling the white-bellied house bat Scotophilus leucogaster (Cretzschmar, 1830), were recently captured in southwestern Ethiopia and southern South Sudan. These S. cf. leucogaster differed from typical S. leucogaster by their slightly smaller size and ventral coloration, conforming instead with the original description of S. altilis Allen, 1914. Scotophilus altilis is an overlooked taxon known from the Blue Nile region in Sudan that is currently considered a junior synonym of S. leucogaster. Phylogenetic analysis of mitochondrial cytochrome b gene (cytb) sequences revealed S. cf. leucogaster as a sister clade to S. leucogaster with a genetic distance of ca. 10%. Comparative specimens of questionable S. nigritellus de Winton, 1899 from northwestern Ethiopia and a wing biopsy sample of another S. cf. leucogaster from western Kenya also fell within this clade. Sequence data from two nuclear markers (zfy and fgb7) corroborated the distinction of S. cf. leucogaster from S. leucogaster. Likewise, morphometric analysis of cranial data largely supported this distinction, as well as taxonomic affiliation with S. altilis based on comparison with the only available paratype specimen. The position of this paratype specimen within the new Scotophilus clade, inferred from analysis of a short fragment of cytb, confirmed its taxonomic identity. Based on the presented evidence, the overlooked East African taxon S. altilis should be resurrected as a full species within the genus Scotophilus.

Energy conserving thermoregulatory patterns and lower disease severity in a bat resistant to the impacts of white-nose syndrome.

The devastating bat fungal disease, white-nose syndrome (WNS), does not appear to affect all species equally. To experimentally determine susceptibility differences between species, we exposed hibernating naïve little brown myotis (Myotis lucifugus) and big brown bats (Eptesicus fuscus) to the fungus that causes WNS, Pseudogymnoascus destructans (Pd). After hibernating under identical conditions, Pd lesions were significantly more prevalent and more severe in little brown myotis. This species difference in pathology correlates with susceptibility to WNS in the wild and suggests that survival is related to different host physiological responses. We observed another fungal infection, associated with neutrophilic inflammation, that was equally present in all bats. This suggests that both species are capable of generating a response to cold tolerant fungi and that Pd may have evolved mechanisms for evading host responses that are effective in at least some bat species. These host-pathogen interactions are likely mediated not just by host physiological responses, but also by host behavior. Pd-exposed big brown bats, the less affected species, spent more time in torpor than did control animals, while little brown myotis did not exhibit this change. This differential thermoregulatory response to Pd infection by big brown bat hosts may allow for a more effective (or less pathological) immune response to tissue invasion.

Epauletted fruit bats display exceptionally high infections with a Hepatocystis species complex in South Sudan.

Hepatocystis parasites are closely related to mammalian Plasmodium species, the causative agents of malaria. Despite the close phylogenetic relationship, Hepatocystis parasites lack the intermittent erythrocytic replication cycles, the signature and exclusive cause of malaria-related morbidity and mortality. Hepatocystis population expansion in the mammalian host is thought to be restricted to the pre-erythrocytic liver phase. Complete differentiation of first generation blood stages into sexual stages for subsequent vector transmission indicates alternative parasite/host co-evolution. In this study, we identified a region of exceptionally high prevalence of Hepatocystis infections in Old World fruit bats in South Sudan. Investigations over the course of five consecutive surveys revealed an average of 93 percent prevalence in four genera of African epauletted fruit bats. We observed a clear seasonal pattern and tolerance of high parasite loads in these bats. Phylogenetic analyses revealed several cryptic Hepatocystis parasite species and, in contrast to mammalian Plasmodium parasites, neither host specificity nor strong geographical patterns were evident. Together, our study provides evidence for Pan-African distribution and local high endemicity of a Hepatocystis species complex in Pteropodidae.

Nycteria parasites of Afrotropical insectivorous bats.

Parasitic protozoan parasites have evolved many co-evolutionary paths towards stable transmission to their host population. Plasmodium spp., the causative agents of malaria, and related haemosporidian parasites are dipteran-borne eukaryotic pathogens that actively invade and use vertebrate erythrocytes for gametogenesis and asexual development, often resulting in substantial morbidity and mortality of the infected hosts. Here, we present results of a survey of insectivorous bats from tropical Africa, including new isolates of species of the haemosporidian genus Nycteria. A hallmark of these parasites is their capacity to infect bat species of distinct families of the two evolutionary distant chiropteran suborders. We did detect Nycteria parasites in both rhinolophid and nycterid bat hosts in geographically separate areas of Sub-Saharan Africa, however our molecular phylogenetic analyses support the separation of the parasites into two distinct clades corresponding to their host genera, suggestive of ancient co-divergence and low levels of host switching. For one clade of these parasites, cytochrome b genes could not be amplified and cytochrome oxidase I sequences showed unusually high rates of evolution, suggesting that the mitochondrial genome of these parasites may have either been lost or substantially altered. This haemosporidian parasite-mammalian host system also highlights that sequential population expansion in the liver and gametocyte formation is a successful alternative to intermediate erythrocytic replication cycles.

Host, pathogen, and environmental characteristics predict white-nose syndrome mortality in captive little brown myotis (Myotis lucifugus).

An estimated 5.7 million or more bats died in North America between 2006 and 2012 due to infection with the fungus Pseudogymnoascus destructans (Pd) that causes white-nose syndrome (WNS) during hibernation. The behavioral and physiological changes associated with hibernation leave bats vulnerable to WNS, but the persistence of bats within the contaminated regions of North America suggests that survival might vary predictably among individuals or in relation to environmental conditions. To investigate variables influencing WNS mortality, we conducted a captive study of 147 little brown myotis (Myotis lucifugus) inoculated with 0, 500, 5000, 50,000, or 500,000 Pd conidia and hibernated for five months at either 4 or 10°C. We found that female bats were significantly more likely to survive hibernation, as were bats hibernated at 4°C, and bats with greater body condition at the start of hibernation. Although all bats inoculated with Pd exhibited shorter torpor bouts compared to controls, a characteristic of WNS, only bats inoculated with 500 conidia had significantly lower survival odds compared to controls. These data show that host and environmental characteristics are significant predictors of WNS mortality, and that exposure to up to 500 conidia is sufficient to cause a fatal infection. These results also illustrate a need to quantify dynamics of Pd exposure in free-ranging bats, as dynamics of WNS produced in captive studies inoculating bats with several hundred thousand conidia may differ from those in the wild.

A new genus for a rare African vespertilionid bat: insights from South Sudan.

A new genus is proposed for the strikingly patterned African vespertilionid "Glauconycteris" superba Hayman, 1939 on the basis of cranial and external morphological comparisons. A review of the attributes of a newly collected specimen from South Sudan (a new country record) and other museum specimens of "Glauconycteris" superba suggests that "Glauconycteris" superba is markedly distinct ecomorphologically from other species classified in Glauconycteris and is likely the sister taxon to Glauconycteris sensu stricto. The recent capture of this rarely collected but widespread bat highlights the need for continued research in tropical sub-Saharan Africa and in particular, for more work in western South Sudan, which has received very little scientific attention. New country records for Glauconycteris cf. poensis (South Sudan) and Glauconycteris curryae (Gabon) are also reported.

Frequent arousal from hibernation linked to severity of infection and mortality in bats with white-nose syndrome.

White-nose syndrome (WNS), an emerging infectious disease that has killed over 5.5 million hibernating bats, is named for the causative agent, a white fungus (Geomyces destructans (Gd)) that invades the skin of torpid bats. During hibernation, arousals to warm (euthermic) body temperatures are normal but deplete fat stores. Temperature-sensitive dataloggers were attached to the backs of 504 free-ranging little brown bats (Myotis lucifugus) in hibernacula located throughout the northeastern USA. Dataloggers were retrieved at the end of the hibernation season and complete profiles of skin temperature data were available from 83 bats, which were categorized as: (1) unaffected, (2) WNS-affected but alive at time of datalogger removal, or (3) WNS-affected but found dead at time of datalogger removal. Histological confirmation of WNS severity (as indexed by degree of fungal infection) as well as confirmation of presence/absence of DNA from Gd by PCR was determined for 26 animals. We demonstrated that WNS-affected bats aroused to euthermic body temperatures more frequently than unaffected bats, likely contributing to subsequent mortality. Within the subset of WNS-affected bats that were found dead at the time of datalogger removal, the number of arousal bouts since datalogger attachment significantly predicted date of death. Additionally, the severity of cutaneous Gd infection correlated with the number of arousal episodes from torpor during hibernation. Thus, increased frequency of arousal from torpor likely contributes to WNS-associated mortality, but the question of how Gd infection induces increased arousals remains unanswered.