Unrecognised Ebola virus infection in contact persons: what can we learn from it?

The epidemic of Ebola virus disease in west Africa in 2014–16 was the largest and most complex the world has ever seen. The four pillars of Ebola response include: case management, case finding and contact tracing, safe and dignified burial, and social mobilisation and community engagement. These four pillars are being implemented in the current outbreak in the Democratic Republic of the Congo (DRC), which is further complicated by its location in a conflict zone.1 Increased understanding of disease pathogenesis and the evaluation of novel therapeutics and vaccine candidates has informed current control measures, while access to survivors and their contacts in west Africa has also provided a unique opportunity to research filovirus transmission

A Search for Early Optical Emission from Short and Long Duration Gamma-ray Bursts

Gamma-ray bursts of short duration may harbor vital clues to the range of phenomena producing bursts. However, recent progress from the observation of optical counterparts has not benefitted the study of short bursts. We have searched for early optical emission from six gamma-ray bursts using the ROTSE-I telephoto array. Three of these events were of short duration, including GRB 980527 which is among the brightest short bursts yet observed. The data consist of unfiltered CCD optical images taken in response to BATSE triggers delivered via the GCN. For the first time, we have analyzed the entire 16 degree by 16 degree field covered for five of these bursts. In addition, we discuss a search for the optical counterpart to GRB 000201, a well-localized long burst. Single image sensitivities range from 13th to 14th magnitude around 10 s after the initial burst detection, and 14 - 15.8 one hour later. No new optical counterparts were discovered in this analysis suggesting short burst optical and gamma-ray fluxes are uncorrelated.Comment: 8 pages, 2 figures, subm. to ApJ Let

An Untriggered Search for Optical Bursts

We present an untriggered search for optical bursts with the ROTSE-I telephoto array. Observations were taken which monitor an effective 256 square degree field continuously over 125 hours to m_{ROTSE}=15.7. The uniquely large field, moderate limiting magnitude and fast cadence of $\sim$10 minutes permits transient searches in a new region of sensitivity. Our search reveals no candidate events. To quantify this result, we simulate potential optical bursts with peak magnitude, m_{p}, at t=10 s, which fade as f=(\frac{t}{t_{0}}) ^{\alpha_{t}}, where \alpha_t < 0. Simple estimates based on observational evidence indicate that a search of this sensitivity begins to probe the possible region occupied by GRB orphan afterglows. Our observing protocol and image sensitivity result in a broad region of high detection efficiency for light curves to the bright and slowly varying side of a boundary running from [\alpha_{t},m_{p}]=[-2.0,6.0] to [-0.3,13.2]. Within this region, the integrated rate of brief optical bursts is less than 1.1\times 10^{-8} {\rm s}^{-1} {\rm deg}^{-2}. At $\sim$22 times the observed GRB rate from BATSE, this suggests a limit on \frac{\theta_{opt}}{\theta_{\gamma}}\lesssim 5 where \theta_{opt} and \theta_{\gamma} are the optical and gamma-ray collimation angles, respectively. Several effects might explain the absence of optical bursts, and a search of the kind described here but more sensitive by about 4 magnitudes should offer a more definitive probe.Comment: 8 pages, 6 figures, 1 tabl

Personal protective equipment solution for UK military medical personnel working in an Ebola virus disease treatment unit in Sierra Leone.

The combination of personal protective equipment (PPE) together with donning and doffing protocols was designed to protect British and Canadian military medical personnel in the Kerry Town Ebola Treatment Unit (ETU) in Sierra Leone. The PPE solution was selected to protect medical staff from infectious risks, notably Ebola virus, and chemical (hypochlorite) exposure. PPE maximized dexterity, enabled personnel to work in hot temperatures for periods of up to 2h, protected mucosal membranes when doffing outer layers, and minimized potential contamination of the doffing area with infectious material by reducing the requirement to spray PPE with hypochlorite. The ETU was equipped to allow medical personnel to provide a higher level of care than witnessed in many existing ETUs. This assured personnel working as part of the international response that they would receive as close to Western treatment standards as possible if they were to contract Ebola virus disease (EVD). PPE also enabled clinical interventions that are not seen routinely in West African EVD treatment regimens, whilst providing a robust protective barrier. Competency in using PPE was developed during a nine-day pre-deployment training programme. This allowed over 60 clinical personnel per deployment to practice skills in PPE in a simulated ETU and in classrooms. Overall, the training provided: (i) an evidence base underpinning the PPE solution chosen; (ii) skills in donning and doffing of PPE; (iii) personnel confidence in the selected PPE; and (iv) quantifiable testing of each individual's capability to don PPE, perform tasks and doff PPE safely

Prompt Optical Observations of Gamma-ray Bursts

The Robotic Optical Transient Search Experiment (ROTSE) seeks to measure simultaneous and early afterglow optical emission from gamma-ray bursts (GRBs). A search for optical counterparts to six GRBs with localization errors of 1 square degree or better produced no detections. The earliest limiting sensitivity is m(ROTSE) > 13.1 at 10.85 seconds (5 second exposure) after the gamma-ray rise, and the best limit is m(ROTSE) > 16.0 at 62 minutes (897 second exposure). These are the most stringent limits obtained for GRB optical counterpart brightness in the first hour after the burst. Consideration of the gamma-ray fluence and peak flux for these bursts and for GRB990123 indicates that there is not a strong positive correlation between optical flux and gamma-ray emission.Comment: 4 pages, 3 figures, submitted to ApJ Letter

Cassini VIMS observations of H3+ emission on the nightside of Jupiter

We present the first detailed analysis of H3+ nightside emission from Jupiter, using Visual and Infrared Mapping Spectrometer (VIMS) data from the Cassini flyby in 2000–2001, producing the first Jovian maps of nightside H3+ emission, temperature, and column density. Using these, we identify and characterize regions of H3+ nightside emission, compared against past observations of H3+ emission on the dayside. We focus our investigation on the region previously described as “mid-to-low latitude emission,” the source for which has been controversial. We find that the brightest of this emission is generated at Jovigraphic latitudes similar to the most equatorward extent of the main auroral emission but concentrated at longitudes eastward of this emission. The emission is produced by enhanced H3+ density, with temperatures dropping away in this region. This emission has a loose association with the predicted location of diffuse aurora produced by pitch angle scattering in the north, but not in the south. This emission also lays in the path of subrotating winds flowing from the aurora, suggesting a transport origin. Some differences are seen between dayside and nightside subauroral emissions, with dayside emission extending more equatorward, perhaps caused by the lack of sunlight ionization on the nightside, and unmeasured changes in temperature. Ionospheric temperatures are hotter in the polar region (~1100–1500 K), dropping away toward the equator (as low as 750 K), broadly similar to values on the dayside, highlighting the dominance of auroral effects in the polar region. No equatorial emission is observed, suggesting that very little particle precipitation occurs away from the polar regions

Land, history or modernization? Explaining ethnic fractionalization

Ethnic fractionalization (EF) is frequently used as an explanatory tool in models of economic development, civil war and public goods provision. However, if EF is endogenous to political and economic change, its utility for further research diminishes. This turns out not to be the case. This paper provides the first comprehensive model of EF as a dependent variable. It contributes new data on the founding date of the largest ethnic group in each state. It builds political and international variables into the analysis alongside historical and geoclimatic parameters. It extends previous work by testing models of politically relevant EF. In addition, this research interprets model results in light of competing theories of nationalism and political change. Results show that cross-national variation in EF is largely exogenous to modern politico-economic change. However, the data are inconclusive with respect to competing geoclimatic, historical institutional and modernist theories of ethnogenesis

The 2022 monkeypox outbreak: A UK military perspective.

With the emergence of SARS-CoV-2 and now monkeypox, the UK Defence Medical Services have been required to provide rapid advice in the management of patients with airborne high consequence infectious diseases (A-HCID). The Defence Public Health Network (DPHN) cadre, consisting of closely aligned uniformed and civilian public health specialists have worked at pace to provide evidence-based recommendations on the clinical management, public health response and policy for monkeypox, with military medicine and pathology clinicians (primarily infectious disease physicians and medical microbiologists). Military environments can be complicated and nuanced requiring specialist input and advice to non-specialists as well as unit commanders both in the UK and overseas. DPHN and military infection clinicians have close links with the UK National Health Service (NHS) and the UK Health Security Agency (UKHSA), allowing for a dynamic two-way relationship that encompasses patient management, public health response, research and development of both UK military and national guidelines. This is further demonstrated with the Royal Air Force (RAF) Air Transport Isolator (ATI) capability, provided by Defence to support the UK Government and UKHSA. Military infectious disease clinicians are also embedded within NHS A-HCID units. In this manuscript we provide examples of the close interdisciplinary working of the DPHN and Defence clinicians in managing military monkeypox patients, co-ordinating the public health response, advising the Command and developing monkeypox policy for Defence through cross-government partnership. We also highlight the co-operation between civilian and military medical authorities in managing the current outbreak

Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut.

In this study, samples from the 2013-2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were analyzed that had been taken from patients when they presented at the treatment center with acute illness. High-throughput RNA sequencing (RNA-seq) and bioinformatics were used to identify the potential microorganisms. This approach confirmed Ebola virus (EBOV) in all samples from patients diagnosed as acute positive for the virus by quantitative reverse transcription-PCR in deployed field laboratories. Nucleic acid mapping to Plasmodium was also used on the patient samples, confirming results obtained with an antigen-based rapid diagnostic test (RDT) conducted in the field laboratories. The data suggested that a high Plasmodium load, as determined by sequence read depth, was associated with mortality and influenced the host response, whereas a lower parasite load did not appear to affect outcome. The identifications of selected bacteria from throat swabs via RNA-seq were confirmed by culture. The data indicated that the potential pathogens identified in the blood samples were associated with translocation from the gut, suggesting the presence of bacteremia, which transcriptome data suggested may induce or aggravate the acute-phase response observed during EVD. Transcripts mapping to different viruses were also identified, including those indicative of lytic infections. The development of high-resolution analysis of samples from patients with EVD will help inform care pathways and the most appropriate general antimicrobial therapy to be used in a resource-poor setting. IMPORTANCE Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD

Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions

BACKGROUND: Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. RESULTS: We explored how porcine pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages. Porcine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages and were productively infected by pig pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, porcine PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied either in parental stem cells or directly in the macrophages by lentiviral vector transduction. CONCLUSIONS: We show that porcine PSCdMs exhibit key macrophage characteristics, including infection by a range of commercially relevant pig pathogens. In addition, genetic engineering of PSCs and PSCdMs affords new opportunities for functional analysis of macrophage biology in an important livestock species. PSCs and differentiated derivatives should therefore represent a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in pigs, and also have wider applications in livestock. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01217-8