Simultaneous Presentation of B-Acute Lymphoblastic Leukemia and Streptococcus agalactiae Meningitis in a 3-Year-old Girl.

Infection is a major cause of treatment-related morbidity and mortality in pediatric acute lymphoblastic leukemia (ALL). Most children with ALL who develop life-threatening bacterial infections do so during induction therapy. We describe a rare case of ALL presenting simultaneously with Streptococcus agalactiae group B Streptococcus bacteremia and meningitis in a 3-year-old girl. She received appropriate antimicrobial therapy and a 2-drug early induction regimen consisting of vincristine and dexamethasone, leading to slow neurologic recovery and a favorable initial response to anti-neoplastic therapy as evidenced by minimal residual disease of 1.12% on day 15 of induction.

Surveillance for Lyme Disease After Implementation of a Revised Case Definition - United States, 2022.

Lyme disease, a tickborne zoonosis caused by certain species of Borrelia spirochetes, is the most common vectorborne disease in the United States. Approximately 90% of all cases are reported from 15 high-incidence jurisdictions in the Northeast, mid-Atlantic, and upper-Midwest regions. After the implementation of a revised surveillance case definition in 2022, high-incidence jurisdictions report cases based on laboratory evidence alone, without need for additional clinical information. In 2022, 62,551 Lyme disease cases were reported to CDC, 1.7 times the annual average of 37,118 cases reported during 2017-2019. Annual incidence increased most in older age groups, with incidence among adults aged ≥65 years approximately double that during 2017-2019. The sharp increase in reported Lyme disease cases in 2022 likely reflects changes in surveillance methods rather than change in disease risk. Although these changes improve standardization of surveillance across jurisdictions, they preclude detailed comparison with historical data.

Tularemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006-2021.

BACKGROUND: Tularemia, a potentially fatal zoonosis caused by Francisella tularensis, has been reported from nearly all US states. Information on relative effectiveness of various antimicrobials for treatment of tularemia is limited, particularly for newer classes such as fluoroquinolones. METHODS: Data on clinical manifestations, antimicrobial treatment, and illness outcome of patients with tularemia are provided voluntarily through case report forms to the US Centers for Disease Control and Prevention by state and local health departments. We summarized available demographic and clinical information submitted during 2006-2021 and evaluated survival according to antimicrobial treatment. We grouped administered antimicrobials into those considered effective for treatment of tularemia (aminoglycosides, fluoroquinolones, and tetracyclines) and those with limited efficacy. Logistic regression models with a bias-reduced estimation method were used to evaluate associations between antimicrobial treatment and survival. RESULTS: Case report forms were available for 1163 US patients with tularemia. Francisella tularensis was cultured from a clinical specimen (eg, blood, pleural fluid) in approximately half of patients (592; 50.9%). Nearly three-quarters (853; 73.3%) of patients were treated with a high-efficacy antimicrobial. A total of 27 patients (2.3%) died. After controlling for positive culture as a proxy for illness severity, use of aminoglycosides, fluoroquinolones, and tetracyclines was independently associated with increased odds of survival. CONCLUSIONS: Most US patients with tularemia received high-efficacy antimicrobials; their use was associated with improved odds of survival regardless of antimicrobial class. Our findings provide supportive evidence that fluoroquinolones are an effective option for treatment of tularemia.

Engagement with Traditional Healers for Early Detection of Plague in Uganda.

In rural Uganda, many people who are ill consult traditional healers prior to visiting the formal healthcare system. Traditional healers provide supportive care for common illnesses, but their care may delay diagnosis and management of illnesses that can increase morbidity and mortality, hinder early detection of epidemic-prone diseases, and increase occupational risk to traditional healers. We conducted open-ended, semi-structured interviews with a convenience sample of 11 traditional healers in the plague-endemic West Nile region of northwestern Uganda to assess their knowledge, practices, and attitudes regarding plague and the local healthcare system. Most were generally knowledgeable about plague transmission and its clinical presentation and expressed willingness to refer patients to the formal healthcare system. We initiated a public health outreach program to further improve engagement between traditional healers and local health centers to foster trust in the formal healthcare system and improve early identification and referral of patients with plaguelike symptoms, which can reflect numerous other infectious and noninfectious conditions. During 2010-2019, 65 traditional healers were involved in the outreach program; 52 traditional healers referred 788 patients to area health centers. The diagnosis was available for 775 patients; malaria (37%) and respiratory tract infections (23%) were the most common diagnoses. One patient had confirmed bubonic plague. Outreach to improve communication and trust between traditional healers and local healthcare settings may result in improved early case detection and intervention not only for plague but also for other serious conditions.

Laboratory Aspects of Minimal / Measurable Residual Disease Testing in B-Lymphoblastic Leukemia.

Minimal residual disease detection provides critical prognostic predictor of treatment outcome and is the standard of care for B lymphoblastic leukemia. Flow cytometry-based minimal residual disease detection is the most common test modality and has high sensitivity (0.01%) and a rapid turnaround time (24 hours). This article details the leukemia associated immunophenotype analysis approach for flow cytometry-based minimal residual disease detection used at St. Jude Children's Research Hospital and importance of using guide gates and back-gating.

The Texas A&M University Hypervelocity Impact Laboratory: A modern aeroballistic range facility.

Novel engineering materials and structures are increasingly designed for use in severe environments involving extreme transient variations in temperature and loading rates, chemically reactive flows, and other conditions. The Texas A&M University Hypervelocity Impact Laboratory (HVIL) enables unique ultrahigh-rate materials characterization, testing, and modeling capabilities by tightly integrating expertise in high-rate materials behavior, computational and polymer chemistry, and multi-physics multiscale numerical algorithm development, validation, and implementation. The HVIL provides a high-throughput test bed for development and tailoring of novel materials and structures to mitigate hypervelocity impacts (HVIs). A conventional, 12.7 mm, smooth bore, two-stage light gas gun (2SLGG) is being used as the aeroballistic range launcher to accelerate single and simultaneously launched projectiles to velocities in the range 1.5-7.0 km/s. The aeroballistic range is combined with conventional and innovative experimental, diagnostic, and modeling capabilities to create a unique HVI and hypersonic test bed. Ultrahigh-speed imaging (10M fps), ultrahigh-speed schlieren imaging, multi-angle imaging, digital particle tracking, flash x-ray radiography, nondestructive/destructive inspection, optical and scanning electron microscopy, and other techniques are being used to characterize HVIs and study interactions between hypersonic projectiles and suspended aerosolized particles. Additionally, an overview of 65 2SLGG facilities operational worldwide since 1990 is provided, which is the most comprehensive survey published to date. The HVIL aims to (i) couple recent theoretical developments in shock physics with advances in numerical methods to perform HVI risk assessments of materials and structures, (ii) characterize environmental effects (water, ice, dust, etc.) on hypersonic vehicles, and (iii) address key high-rate materials and hypersonics research problems.

Rapid COVID-19 Testing and On-site Case Investigation and Contact Tracing in an Underresourced Area of Salt Lake City, Utah, December 2020-April 2021.

This case study describes how we paired free SARS-CoV-2 rapid antigen testing with on-site case investigation and contact tracing at a drive-through site in an underresourced area of Salt Lake City. Residents of this area had lower rates of employment and health insurance and higher rates of poverty than in the Utah general population. People were given an option to remain on-site and wait until their test results were ready. If a vehicle occupant received a positive test result, the case investigation occurred on-site; contact tracing with the other vehicle occupants was also initiated. People were provided resources to support isolation and quarantine. Bilingual staff who spoke Spanish were incorporated into the workflow. From December 2020 through April 2021, public health staff administered 39 587 rapid tests; 4094 people received a positive test result and 1133 stayed for on-site case investigation. More than half (60.5%) of people with a positive test result who agreed to stay for on-site case investigation were Hispanic or self-reported belonging to a non-Hispanic racial minority group (American Indian/Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, or other racial identities). Pairing rapid antigen testing with on-site case investigation and contact tracing is feasible and improved the timeliness of case investigation by ≥1 day. On-site vaccination services were later integrated. Future emergency responses might consider assisting underresourced communities with on-site services that provide convenient and accessible public health interventions. By providing dependable and reliable services, we were able to achieve buy-in and become a consistent resource for those in the community.

Epidemiology of Lyme Disease.

Lyme disease is the most common vector-borne illness in North America and Europe. The etiologic agent, Borrelia burgdorferi sensu lato, is transmitted to humans by certain species of Ixodes ticks, which are found widely in temperate regions of the Northern hemisphere. Clinical features are diverse but death is rare. The risk of human infection is determined by the distribution and abundance of vector ticks, ecologic factors influencing tick infection rates, and human behaviors that promote tick bite. Rates of infection are highest among children aged 5 to 15 years and adults aged more than 50 years. In the northeastern United States where disease is most common, exposure occurs primarily in areas immediately around the home. Knowledge of disease epidemiology is important for patient management and proper diagnosis.

Association Between Prolonged Shedding of Zika Virus in Human Semen and Male Reproductive Tract Inflammation.

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes congenital defects. Sexual transmission of ZIKV was confirmed in a recent epidemic; however, mechanisms behind ZIKV infection and persistence in the male reproductive tract (MRT) are unknown. Previously, we found that approximately 33% of men with symptomatic ZIKV infections shed ZIKV RNA in semen, and some men shed ZIKV RNA for >3 months. Here, we evaluated the semen of 49 ZIKV-infected men to identify immune factors correlating with long-term ZIKV shedding in semen and ZIKV-infected cell types in semen. We found that prolonged ZIKV RNA shedding in semen was associated with MRT inflammation, indicated by higher leukocyte counts and inflammatory cytokine concentrations in semen of long-term versus short-term shedders. In addition, we found ZIKV RNA in seminal leukocytes and epithelial cells. This study of human semen from ZIKV-infected men provides critical insights into the effects of ZIKV on MRT health.

Effectiveness of personal protection measures against Lyme disease: A review of epidemiologic studies from the United States.

Lyme disease, the most commonly reported vector-borne disease in the United States, is caused by the bacteria Borrelia burgdorferi and is transmitted through the bite of an infected blacklegged tick. In the absence of a licensed vaccine, the prevention of Lyme disease relies heavily on limiting tick exposure. Methods for limiting tick exposure include personal protection measures such as repellent use, wearing protective clothing, avoiding areas where ticks may be present, bathing after exposure to tick habitat and performing regular tick checks. Public health officials typically recommend all these personal protection measures; however, there is limited evidence to promote one behaviour or practice over another. The focus of this article is to review available literature that examines the effectiveness of recommended personal protection measures to prevent Lyme and other Ixodes-transmitted diseases in humans. Articles included in this review were identified through Google Scholar and PubMed searches using specific search terms. We identified over 56,000 articles using Google Scholar and PubMed searches. Of those, 16 studies fit our criteria for inclusion and were reviewed in their entirety. Among the personal protection measures evaluated, no intervention was predominantly or consistently effective across studies, demonstrating that, currently, there is no single best method for primary prevention of Ixodes-transmitted diseases in the United States. Frequently recommended practices such as tick checks, repellent use and protective clothing had mixed results across studies. Study design differences limited comparability among studies, and sample sizes for these studies may have been too small to detect statistically significant results even if a prevention method was effective. Though many of the reviewed personal protection measures are frequently recommended to the public, limited evidence demonstrates their ability to prevent tick-borne disease. Additional standardized studies are needed to evaluate personal protection measures.

Abdominal tuberculosis masquerading as ovarian carcinoma in a Caucasian woman: a diagnostic challenge.

We present a case of a 37-year-old Caucasian woman with abdominal distension and loss of weight. She was initially presumed to be a case of ovarian malignancy due to an elevated serum cancer antigen 125 (CA 125) level and imaging of abdomen and pelvis that showed ascites and bulky ovaries. However, histological examination of biopsy later revealed it to be a case of abdominal tuberculosis (AbT). Ascitic fluid was also found to be positive for Mycobacterium tuberculosis by whole genome sequencing. The patient was started on antituberculosis treatment following which she showed a significant improvement in her symptoms.

Enhancer retargeting of CDX2 and UBTF::ATXN7L3 define a subtype of high-risk B-progenitor acute lymphoblastic leukemia.

Transcriptome sequencing has identified multiple subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL) of prognostic significance, but a minority of cases lack a known genetic driver. Here, we used integrated whole-genome (WGS) and -transcriptome sequencing (RNA-seq), enhancer mapping, and chromatin topology analysis to identify previously unrecognized genomic drivers in B-ALL. Newly diagnosed (n = 3221) and relapsed (n = 177) B-ALL cases with tumor RNA-seq were studied. WGS was performed to detect mutations, structural variants, and copy number alterations. Integrated analysis of histone 3 lysine 27 acetylation and chromatin looping was performed using HiChIP. We identified a subset of 17 newly diagnosed and 5 relapsed B-ALL cases with a distinct gene expression profile and 2 universal and unique genomic alterations resulting from aberrant recombination-activating gene activation: a focal deletion downstream of PAN3 at 13q12.2 resulting in CDX2 deregulation by the PAN3 enhancer and a focal deletion of exons 18-21 of UBTF at 17q21.31 resulting in a chimeric fusion, UBTF::ATXN7L3. A subset of cases also had rearrangement and increased expression of the PAX5 gene, which is otherwise uncommon in B-ALL. Patients were more commonly female and young adult with median age 35 (range,12-70 years). The immunophenotype was characterized by CD10 negativity and immunoglobulin M positivity. Among 16 patients with known clinical response, 9 (56.3%) had high-risk features including relapse (n = 4) or minimal residual disease >1% at the end of remission induction (n = 5). CDX2-deregulated, UBTF::ATXN7L3 rearranged (CDX2/UBTF) B-ALL is a high-risk subtype of leukemia in young adults for which novel therapeutic approaches are required.

Direct Anterior Approach to Total Hip Arthroplasty Improves the Likelihood of Return to Previous Recreational Activities Compared with Posterior Approach.

Total hip arthroplasty offers relief and functional improvement, with the rate of direct anterior approach (DAA) increasing compared with the posterior approach (PA). This study aimed to assess the effect of surgical approach on return to recreational activity after total hip arthroplasty. Total hip arthroplasty performed for primary or posttraumatic osteoarthritis were identified; 100 DAA patients were matched with 100 PA patients on age, sex, diagnosis, and surgical year. Patients were mailed a recreational activity survey, Harris Hip Function, and Hip disability and Osteoarthritis Outcome Score questionnaires. Two hundred surveys were mailed, 130 (65%) responded (66 DAA and 64 PA) and were included. The mean follow-up was 2.5 years for the DAA group and 2.3 years for the PA group (P = 0.256). Among DAA patients, 51% returned to activity within 6 months, compared with 44% of PA patients (P = 0.360). Among those who returned to activity, 71% in the DAA group tried their main presurgery sport, compared with 53% in the PA group (P = 0.019). Twenty-eight percent of DAA patients and 4% of PA patients reported the surgical approach influenced their return to activity (P = 0.001). Outcome scores were clinically similar between groups. Objective data did not favor one approach over the other.

Changing Trends in Age and Sex Distributions of Lyme Disease-United States, 1992-2016.

Lyme disease is the most common vector-borne disease in the United States and is characterized by a bimodal age distribution and male predominance. We examined trends in reported cases during a 25-year period to describe changes in the populations most affected by Lyme disease in the United States. We examined demographic characteristics of people with confirmed cases of Lyme disease reported to the Centers for Disease Control and Prevention during 1992-2016 through the National Notifiable Diseases Surveillance System. We grouped cases into 5-year periods (1992-1996, 1997-2001, 2002-2006, 2007-2011, 2012-2016). We calculated the average annual incidence by age and sex and used incidence rate ratios (IRRs) to describe changes in Lyme disease incidence by age and sex over time. We converted patient age at time of illness into patient birth year to ascertain disease patterns according to birth cohorts. The incidence of Lyme disease in the United States doubled from 1992-1996 to 2012-2016 (IRR = 1.74; 95% CI, 1.70-1.78) and increased disproportionately among males; IRRs were 39%-89% higher among males than among females for most age groups. During the study period, children aged 5-9 years were most frequently and consistently affected. In contrast, the average age of adults with Lyme disease increased over time; of all adults, people born during 1950-1964 were the most affected by Lyme disease. Our findings suggest that age-related behaviors and susceptibilities may drive infections among children, and the shifting peak among adults likely reflects a probability proportional to the relative size of the baby boom population. These findings can inform targeted and efficient public health education and intervention efforts.

Effects of COVID-19 Pandemic on Reported Lyme Disease, United States, 2020.

Surveys indicate US residents spent more time outdoors in 2020 than in 2019, but fewer tick bite-related emergency department visits and Lyme disease laboratory tests were reported. Despite ongoing exposure, Lyme disease case reporting for 2020 might be artificially reduced due to coronavirus disease-associated changes in healthcare-seeking behavior.

Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response.

This report provides CDC recommendations to U.S. health care providers regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of plague. Yersinia pestis, the bacterium that causes plague, leads to naturally occurring disease in the United States and other regions worldwide and is recognized as a potential bioterrorism weapon. A bioweapon attack with Y. pestis could potentially infect thousands, requiring rapid and informed decision making by clinicians and public health agencies. The U.S. government stockpiles a variety of medical countermeasures to mitigate the effects of a bioterrorism attack (e.g., antimicrobials, antitoxins, and vaccines) for which the 21st Century Cures Act mandates the development of evidence-based guidelines on appropriate use. Guidelines for treatment and postexposure prophylaxis of plague were published in 2000 by a nongovernmental work group; since then, new human clinical data, animal study data, and U.S. Food and Drug Administration approvals of additional countermeasures have become available. To develop a comprehensive set of updated guidelines, CDC conducted a series of systematic literature reviews on human treatment of plague and other relevant topics to collect a broad evidence base for the recommendations in this report. Evidence from CDC reviews and additional sources were presented to subject matter experts during a series of forums. CDC considered individual expert input while developing these guidelines, which provide recommended best practices for treatment and prophylaxis of human plague for both naturally occurring disease and following a bioterrorism attack. The guidelines do not include information on diagnostic testing, triage decisions, or logistics involved in dispensing medical countermeasures. Clinicians and public health officials can use these guidelines to prepare their organizations, hospitals, and communities to respond to a plague mass-casualty event and as a guide for treating patients affected by plague.

Laboratory Aspects of Minimal / Measurable Residual Disease Testing in B-Lymphoblastic Leukemia.

Minimal residual disease detection provides critical prognostic predictor of treatment outcome and is the standard of care for B lymphoblastic leukemia. Flow cytometry-based minimal residual disease detection is the most common test modality and has high sensitivity (0.01%) and a rapid turnaround time (24 hours). This article details the leukemia associated immunophenotype analysis approach for flow cytometry-based minimal residual disease detection used at St. Jude Children's Research Hospital and importance of using guide gates and back-gating.

Enhancer Hijacking Drives Oncogenic BCL11B Expression in Lineage-Ambiguous Stem Cell Leukemia.

Lineage-ambiguous leukemias are high-risk malignancies of poorly understood genetic basis. Here, we describe a distinct subgroup of acute leukemia with expression of myeloid, T lymphoid, and stem cell markers driven by aberrant allele-specific deregulation of BCL11B, a master transcription factor responsible for thymic T-lineage commitment and specification. Mechanistically, this deregulation was driven by chromosomal rearrangements that juxtapose BCL11B to superenhancers active in hematopoietic progenitors, or focal amplifications that generate a superenhancer from a noncoding element distal to BCL11B. Chromatin conformation analyses demonstrated long-range interactions of rearranged enhancers with the expressed BCL11B allele and association of BCL11B with activated hematopoietic progenitor cell cis-regulatory elements, suggesting BCL11B is aberrantly co-opted into a gene regulatory network that drives transformation by maintaining a progenitor state. These data support a role for ectopic BCL11B expression in primitive hematopoietic cells mediated by enhancer hijacking as an oncogenic driver of human lineage-ambiguous leukemia. SIGNIFICANCE: Lineage-ambiguous leukemias pose significant diagnostic and therapeutic challenges due to a poorly understood molecular and cellular basis. We identify oncogenic deregulation of BCL11B driven by diverse structural alterations, including de novo superenhancer generation, as the driving feature of a subset of lineage-ambiguous leukemias that transcend current diagnostic boundaries.This article is highlighted in the In This Issue feature, p. 2659.