Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.

BACKGROUND: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus. METHODS: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort. FINDINGS: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered. INTERPRETATION: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality. FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.

T Cells Engineered to Express Immunoreceptors Targeting the Frequently Expressed Medullary Thyroid Cancer Antigens Calcitonin, CEA, and RET M918T.

Background: Medullary thyroid cancer (MTC) is a rare malignancy originating from the calcitonin-producing C cells of the thyroid. Despite recent therapeutic advances, metastatic MTC remains incurable. Adoptive cell therapy (ACT) using genetically engineered T cells targeting either tissue-restricted tumor-associated antigens or mutated neoantigens has led to durable remissions in other metastatic solid tumors. The majority of MTC express the tumor-associated antigens calcitonin and carcinoembryonic antigen (CEA), and ∼40% of MTC harbor the RET M918T oncogenic driver mutation. Methods: We developed and characterized three immunoreceptors that recognize extracellular CEA, a calcitonin epitope presented by HLA-A*24:02, or an RET M918T neoepitope restricted by HLA-DPB1*04:01/02. The chimeric antigen receptor (CAR) targeting CEA was synthetically designed, while the T cell receptors (TCRs) targeting calcitonin and RET M918T were isolated from a transgenic mouse and patient with MTC, respectively. These immunoreceptors were genetically engineered into peripheral blood T cells and tested for antigen specificity and antitumor activity. Results: T cells expressing the anti-CEA CAR or the calcitonin-reactive TCR produced effector cytokines and displayed cytotoxicity against cell lines expressing their cognate antigen in vitro. In immunodeficient mice harboring a human MTC cell line, the adoptive transfer of T cells engineered to express the anti-CEA CAR or calcitonin-reactive TCR led to complete tumor regression. T cells expressing the HLA-DPB1*04:01/02-restricted TCR targeting RET M918T, which was cloned from peripheral blood CD4+ T cells of a patient with MTC, demonstrated specific reactivity against cells pulsed with the mutated peptide and MTC tumor cells that expressed HLA-DPB1*04:01 and RET M918T. Conclusion: The preclinical data presented herein demonstrate the potential of using genetically engineered T cells targeting CEA, calcitonin, and/or RET M918T to treat metastatic MTC.

Trypanosoma cruzi in Nonischemic Cardiomyopathy Patients, Houston, Texas, USA.

To investigate possible cardiac manifestations of Chagas disease, we tested 97 Latinx patients with nonischemic cardiomyopathy in Houston, Texas, USA, for Trypanosoma cruzi infection. We noted a high prevalence of underdiagnosed infection and discrepant results in clinical diagnostic assays. Latinx cardiac patients in the United States would benefit from laboratory screening for T. cruzi infection.

Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants.

Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium Paenibacillus, together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of Paenibacillus thiaminolyticus This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference Paenibacillus strain. These findings show that an unbiased pan-microbial approach enabled characterization of Paenibacillus in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections.

Retrospective Chart Analysis of Child and Adolescent Trichomonas vaginalis Infection in Houston, Texas.

BACKGROUND: Trichomonas vaginalis infection causes significant morbidity in the United States. Despite its high national disease burden, the epidemiologic characteristics of child and adolescent cases are not well understood. In this study, we aimed to describe the socioeconomic, transmission risk factors, clinical manifestations, and geospatial variables associated with cases of T vaginalis infection in the Houston, Texas, metropolitan area. METHODS: We performed a retrospective chart abstraction of all T vaginalis cases at 2 large pediatric hospitals in Houston between 2008 and 2016. RESULTS: We identified 87 patients (mean age, 16 years; range, 4-18 years); 30% of them were asymptomatic, and 39% were coinfected with another sexually transmitted infection(s). Almost all T vaginalis infections in sexually assaulted patients were diagnosed incidentally. Geospatial analysis identified clustering of cases in areas of high poverty and in minority populations. CONCLUSIONS: Our findings indicate that children and adolescents are at risk for T vaginalis infection; however, their risk factors might differ from those in adults. In addition, our geospatial analysis revealed the need for dedicated resources in neighborhoods associated with health disparities to prevent future incident cases.

Characterization of plasma-enhanced teflon AF for sensing benzene, toluene, and xylenes in water with near-IR surface plasmon resonance.

Near-IR surface plasmon resonance is used to characterize Teflon AF films for refractive index-based detection of the aromatic hydrocarbon contaminants benzene, toluene, and xylenes in water. The technique requires no sample preparation, and film sensitivity is found to be enhanced by oxygen plasma etching. A diffusion equation model is used to extract the diffusion and partition coefficients, which indicate film enrichment factors exceeding two orders of magnitude, permitting a limit of detection of 183, 105 and 55 ppb for benzene, toluene, and xylenes, respectively. The effect of other potential interfering contaminants is quantified.

Lookup-table method for imaging optical properties with structured illumination beyond the diffusion theory regime.

Sinusoidally structured illumination is used in concert with a phantom-based lookup-table (LUT) to map wide-field optical properties in turbid media with reduced albedos as low as 0.44. A key advantage of the lookup-table approach is the ability to measure the absorption (mu(a)) and reduced scattering coefficients (mu(s) (')) over a much broader range of values than permitted by current diffusion theory methods. Through calibration with a single reflectance standard, the LUT can extract mu(s) (') from 0.8 to 2.4 mm(-1) with an average root-mean-square (rms) error of 7% and extract mu(a) from 0 to 1.0 mm(-1) with an average rms error of 6%. The LUT is based solely on measurements of two parameters, reflectance R and modulation M at an illumination period of 10 mm. A single set of three phase-shifted images is sufficient to measure both M and R, which are then used to generate maps of absorption and scattering by referencing the LUT. We establish empirically that each pair (M,R) maps uniquely to only one pair of (micro(s) ('),micro(a)) and report that the phase function (i.e., size) of the scatterers can influence the accuracy of optical property extraction.

Fentanyl epidemic in Chicago, Illinois and surrounding Cook County.

INTRODUCTION: Epidemics related to illicit fentanyl abuse have been reported and the potential exists for a national epidemic associated with high mortality. This report describes emergency department visits for opioid toxicity and a recent outbreak of illicit fentanyl fatalities in Chicago, Illinois and surrounding Cook County. METHODS: Retrospective chart review of opioid-related overdoses seen in our emergency department and a retrospective review of data from the Cook County Medical Examiner's Office Fentanyl Fatality Database from April 2005 through December 2006. RESULTS: Our emergency department treated 43 patients with a total of 55 emergency department visits during this time. Paramedic transport was utilized for 83.6% of the emergency department visits and naloxone was administered during 80.4% of transports. Naloxone was administered during 47.3% of emergency department visits with total doses ranging from 0.4 mg to 12 mg. Eighty percent of cases were treated and discharged from the emergency department. During this same time frame, the Medical Examiner's office identified 342 fentanyl-related fatalities. In 2006, illicit fentanyl fatalities represented 6.9% of all Medical Examiner cases for that year. Approximately 80% of deaths occurred in Chicago. A peak in fentanyl-related deaths occurred in the spring of 2006 and again in the fall of 2006 while the number of emergency department visits peaked during May of 2006. CONCLUSION: Chicago and surrounding Cook County experienced an outbreak of 342 fentanyl-related deaths between April 2005 and December 2006. The experience demonstrated a clear need for an interdisciplinary approach to identifying, communicating, and managing an outbreak.

Diagnosing Plantar Fascia Rupture.

In brief Though not frequently reported in the literature, plantar fascia tears or ruptures can occur in running and jumping sports. Misdiagnosis as an acute flare of the much more common plantar fasciitis is possible. Though the injury is initially quite disabling, athletes can-as in this case report-return within weeks to competition with proper diagnosis, intervention, and rehabilitation.