Clinical characterization and placental pathology of mpox infection in hospitalized patients in the Democratic Republic of the Congo.

We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L'Hopital General de Reference de Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Mpox study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Soeurs Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human mpox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT.

Design and Optimization of a Monkeypox virus Specific Serological Assay.

Monkeypox virus (MPXV), a member of the Orthopoxvirus (OPXV) genus, is a zoonotic virus, endemic to central and western Africa that can cause smallpox-like symptoms in humans with fatal outcomes in up to 15% of patients. The incidence of MPXV infections in the Democratic Republic of the Congo, where the majority of cases have occurred historically, has been estimated to have increased as much as 20-fold since the end of smallpox vaccination in 1980. Considering the risk global travel carries for future disease outbreaks, accurate epidemiological surveillance of MPXV is warranted as demonstrated by the recent Mpox outbreak, where the majority of cases were occurring in non-endemic areas. Serological differentiation between childhood vaccination and recent infection with MPXV or other OPXVs is difficult due to the high level of conservation within OPXV proteins. Here, a peptide-based serological assay was developed to specifically detect exposure to MPXV. A comparative analysis of immunogenic proteins across human OPXVs identified a large subset of proteins that could potentially be specifically recognized in response to a MPXV infection. Peptides were chosen based upon MPXV sequence specificity and predicted immunogenicity. Peptides individually and combined were screened in an ELISA against serum from well-characterized Mpox outbreaks, vaccinee sera, and smallpox sera collected prior to eradication. One peptide combination was successful with ~86% sensitivity and ~90% specificity. The performance of the assay was assessed against the OPXV IgG ELISA in the context of a serosurvey by retrospectively screening a set of serum specimens from the region in Ghana believed to have harbored the MPXV-infected rodents involved in the 2003 United States outbreak.

Robotic Autonomy for Magnetic Endoscope Biopsy.

Magnetically actuated endoscopes are currently transitioning in to clinical use for procedures such as colonoscopy, presenting numerous benefits over their conventional counterparts. Intelligent and easy-to-use control strategies are an essential part of their clinical effectiveness due to the un-intuitive nature of magnetic field interaction. However, work on developing intelligent control for these devices has mainly been focused on general purpose endoscope navigation. In this work, we investigate the use of autonomous robotic control for magnetic colonoscope intervention via biopsy, another major component of clinical viability. We have developed control strategies with varying levels of robotic autonomy, including semi-autonomous routines for identifying and performing targeted biopsy, as well as random quadrant biopsy. We present and compare the performance of these approaches to magnetic endoscope biopsy against the use of a standard flexible endoscope on bench-top using a colonoscopy training simulator and silicone colon model. The semi-autonomous routines for targeted and random quadrant biopsy were shown to reduce user workload with comparable times to using a standard flexible endoscope.

Enabling the future of colonoscopy with intelligent and autonomous magnetic manipulation.

Early diagnosis of colorectal cancer significantly improves survival. However, over half of cases are diagnosed late due to demand exceeding the capacity for colonoscopy - the "gold standard" for screening. Colonoscopy is limited by the outdated design of conventional endoscopes, associated with high complexity of use, cost and pain. Magnetic endoscopes represent a promising alternative, overcoming drawbacks of pain and cost, but struggle to reach the translational stage as magnetic manipulation is complex and unintuitive. In this work, we use machine vision to develop intelligent and autonomous control of a magnetic endoscope, for the first time enabling non-expert users to effectively perform magnetic colonoscopy in-vivo. We combine the use of robotics, computer vision and advanced control to offer an intuitive and effective endoscopic system. Moreover, we define the characteristics required to achieve autonomy in robotic endoscopy. The paradigm described here can be adopted in a variety of applications where navigation in unstructured environments is required, such as catheters, pancreatic endoscopy, bronchoscopy, and gastroscopy. This work brings alternative endoscopic technologies closer to the translational stage, increasing availability of early-stage cancer treatments.

Intelligent magnetic manipulation for gastrointestinal ultrasound.

Diagnostic endoscopy in the gastrointestinal tract has remained largely unchanged for decades and is limited to the visualization of the tissue surface, the collection of biopsy samples for diagnoses, and minor interventions such as clipping or tissue removal. In this work, we present the autonomous servoing of a magnetic capsule robot for in-situ, subsurface diagnostics of microanatomy. We investigated and showed the feasibility of closed-loop magnetic control using digitized microultrasound (µUS) feedback; this is crucial for obtaining robust imaging in an unknown and unconstrained environment. We demonstrated the functionality of an autonomous servoing algorithm that uses µUS feedback, both on benchtop trials as well as in-vivo in a porcine model. We have validated this magnetic-µUS servoing in instances of autonomous linear probe motion and were able to locate markers in an agar phantom with 1.0 ± 0.9 mm position accuracy using a fusion of robot localization and µUS image information. This work demonstrates the feasibility of closed-loop robotic µUS imaging in the bowel without the need for either a rigid physical link between the transducer and extracorporeal tools or complex manual manipulation.

Magnetic Levitation for Soft-Tethered Capsule Colonoscopy Actuated With a Single Permanent Magnet: A Dynamic Control Approach.

The present letter investigates a novel control approach for magnetically driven soft-tethered capsules for colonoscopy-a potentially painless approach for colon inspection. The focus of this work is on a class of devices composed of a magnetic capsule endoscope actuated by a single external permanent magnet. Actuation is achieved by manipulating the external magnet with a serial manipulator, which in turn produces forces and torques on the internal magnetic capsule. We propose a control strategy which, counteracting gravity, achieves levitation of the capsule. This technique, based on a nonlinear backstepping approach, is able to limit contact with the colon walls, reducing friction, avoiding contact with internal folds, and facilitating the inspection of nonplanar cavities. The approach is validated on an experimental setup, which embodies a general scenario faced in colonoscopy. The experiments show that we can attain 19.5% of contact with the colon wall, compared to the almost 100% of previously proposed approaches. Moreover, we show that the control can be used to navigate the capsule through a more realistic environment-a colon phantom-with reasonable completion time.

Maternal and Fetal Outcomes Among Pregnant Women With Human Monkeypox Infection in the Democratic Republic of Congo.

Human monkeypox is an endemic disease in rain-forested regions of central Democratic Republic of Congo. We report fetal outcomes for 1 of 4 pregnant women who participated in an observational study at the General Hospital of Kole (Sankuru Province), where 222 symptomatic subjects were followed between 2007 and 2011. Of the 4 pregnant women, 1 gave birth to a healthy infant, 2 had miscarriages in the first trimester, and 1 had fetal death, with the macerated stillborn showing diffuse cutaneous maculopapillary skin lesions involving the head, trunk and extremities, including palms of hands and soles of feet.

Imaging protein deposits on contact lens materials.

PURPOSE: The majority of studies investigating protein deposition on contact lens materials require that the deposit of interest be removed, potentially resulting in erroneous results if some proteins are not removed adequately. The purpose of this study was to investigate the use of in situ imaging methods to examine protein deposition on conventional poly(2-hydroxyethyl methacrylate) (polyHEMA)-based and silicone hydrogel contact lens materials. METHODS: Six silicone hydrogel and five polyHEMA-based hydrogel contact lens materials were examined by Atomic Force Microscopy (AFM) and/or Scanning Electron Microscopy (SEM) techniques, after being deposited with proteins in an in vitro model. AFM studies examined lenses deposited solely with lysozyme at approximate physiological concentrations and SEM studies were conducted on lenses exposed to a dilute mixture of lysozyme and albumin-conjugated gold spheres. RESULTS: AFM studies demonstrated that the lens materials had markedly differing surface topographies. SEM results showed that galyfilcon A and balafilcon A lenses deposited both lysozyme and albumin in relatively large aggregates, as compared with lotrafilcon A and B, in which the proteins were deposited in a more evenly spread, monolayer formation. Polymacon lenses deposited more protein than any of the silicone hydrogel materials and much of the protein was aggregated together. AFM data indicated that balafilcon A, lotrafilcon A and polymacon deposited lysozyme in a similar manner, with very little lysozyme being deposited in discrete areas. Galyfilcon A behaved very differently, with the lysozyme exhibiting both aggregates as well as string-like formations over the lens surface. CONCLUSIONS: Imaging techniques that allow proteins to be examined in situ show much promise for determining the extent and physical characterization of protein on contact lens materials. These techniques indicate that the pattern of deposition of proteins onto silicone hydrogel contact lens materials differs between materials, depending upon their bulk and surface composition.

Managing potential laboratory exposure to ebola virus by using a patient biocontainment care unit.

In 2004, a scientist from the US Army Medical Research Institute of Infectious Diseases (USAMRIID) was potentially exposed to a mouse-adapted variant of the Zaire species of Ebola virus. The circumstances surrounding the case are presented, in addition to an update on historical admissions to the medical containment suite at USAMRIID. Research facilities contemplating work with pathogens requiring Biosafety Level 4 laboratory precautions should be mindful of the occupational health issues highlighted in this article.

Designing a biocontainment unit to care for patients with serious communicable diseases: a consensus statement.

In spite of great advances in medicine, serious communicable diseases are a significant threat. Hospitals must be prepared to deal with patients who are infected with pathogens introduced by a bioterrorist act (e.g., smallpox), by a global emerging infectious disease (e.g., avian influenza, viral hemorrhagic fevers), or by a laboratory accident. One approach to hazardous infectious diseases in the hospital setting is a biocontainment patient care unit (BPCU). This article represents the consensus recommendations from a conference of civilian and military professionals involved in the various aspects of BPCUs. The role of these units in overall U.S. preparedness efforts is discussed. Technical issues, including medical care issues (e.g., diagnostic services, unit access); infection control issues (e.g., disinfection, personal protective equipment); facility design, structure, and construction features; and psychosocial and ethical issues, are summarized and addressed in detail in an appendix. The consensus recommendations are presented to standardize the planning, design, construction, and operation of BPCUs as one element of the U.S. preparedness effort.