Implementation and Performance of a Point-of-Care COVID-19 Test Program in 4,000 California Schools.

OBJECTIVE: To evaluate the feasibility and accuracy of an unprecedented COVID-19 antigen testing program in schools, which required a healthcare provider order, laboratory director, a Clinical Laboratory Improvement Amendments (CLIA) certificate of waiver, as well as training of school personnel. STUDY DESIGN: Descriptive report of a point-of-care, school-based antigen testing program in California from 8/1/2021 through 5/30/2022, in which participants grades K-12 self-swabbed and school personnel performed testing. Participants included 944,009 students, personnel, and community members from 4,022 California K-12 schools. Outcomes measured include sensitivity and specificity (with polymerase chain reaction [PCR] as comparator), of the Abbott BinaxNOW™ antigen test, number of tests performed, and active infections identified. RESULTS: Of 102,022 paired PCR/antigen tests, the overall sensitivity and specificity for the antigen test was 81.2% (95%CI:80.5%-81.8%) and 99.6% (95%CI:99.5%-99.6%), respectively using cycle threshold (Ct) values <30. During January through March 2022, the highest prevalence period, the positive predictive value (PPV) of antigen testing was 94.7% and the negative predictive value was 94.2%. Overall, 4,022 school sites were enrolled and 3,987,840 million antigen tests were performed on 944,009 individuals. A total of 162,927 positive antigen tests were reported in 135,163 individuals (14.3% of persons tested). CONCLUSIONS: Rapidly implementing a school-based testing program in thousands of schools is feasible. Self-swabbing and testing by school personnel can yield accurate results. On-site COVID-19 testing is no longer necessary in schools, but this model provides a framework for future infectious disease threats.

Newly Recognized Spotted Fever Group Rickettsia as Cause of Severe Rocky Mountain Spotted Fever-Like Illness, Northern California, USA.

The incidence of spotted fever group (SFG) rickettsioses in the United States has tripled since 2010. Rocky Mountain spotted fever, the most severe SFG rickettsiosis, is caused by Rickettsia rickettsii. The lack of species-specific confirmatory testing obfuscates the relative contribution of R. rickettsii and other SFG Rickettsia to this increase. We report a newly recognized rickettsial pathogen, Rickettsia sp. CA6269, as the cause of severe Rocky Mountain spotted fever-like illness in 2 case-patients residing in northern California. Multilocus sequence typing supported the recognition of this pathogen as a novel Rickettsia genotype most closely related to R. rickettsii. Cross-reactivity observed for an established molecular diagnostic test indicated that Rickettsia sp. CA6269 might be misidentified as R. rickettsii. We developed a Rickettsia sp. CA6269-specific real-time PCR to help resolve this diagnostic challenge and better characterize the spectrum of clinical disease and ecologic epidemiology of this pathogen.

Implementation of California COVIDNet - a multi-sector collaboration for statewide SARS-CoV-2 genomic surveillance.

Introduction: The SARS-CoV-2 pandemic represented a formidable scientific and technological challenge to public health due to its rapid spread and evolution. To meet these challenges and to characterize the virus over time, the State of California established the California SARS-CoV-2 Whole Genome Sequencing (WGS) Initiative, or "California COVIDNet". This initiative constituted an unprecedented multi-sector collaborative effort to achieve large-scale genomic surveillance of SARS-CoV-2 across California to monitor the spread of variants within the state, to detect new and emerging variants, and to characterize outbreaks in congregate, workplace, and other settings. Methods: California COVIDNet consists of 50 laboratory partners that include public health laboratories, private clinical diagnostic laboratories, and academic sequencing facilities as well as expert advisors, scientists, consultants, and contractors. Data management, sample sourcing and processing, and computational infrastructure were major challenges that had to be resolved in the midst of the pandemic chaos in order to conduct SARS-CoV-2 genomic surveillance. Data management, storage, and analytics needs were addressed with both conventional database applications and newer cloud-based data solutions, which also fulfilled computational requirements. Results: Representative and randomly selected samples were sourced from state-sponsored community testing sites. Since March of 2021, California COVIDNet partners have contributed more than 450,000 SARS-CoV-2 genomes sequenced from remnant samples from both molecular and antigen tests. Combined with genomes from CDC-contracted WGS labs, there are currently nearly 800,000 genomes from all 61 local health jurisdictions (LHJs) in California in the COVIDNet sequence database. More than 5% of all reported positive tests in the state have been sequenced, with similar rates of sequencing across 5 major geographic regions in the state. Discussion: Implementation of California COVIDNet revealed challenges and limitations in the public health system. These were overcome by engaging in novel partnerships that established a successful genomic surveillance program which provided valuable data to inform the COVID-19 public health response in California. Significantly, California COVIDNet has provided a foundational data framework and computational infrastructure needed to respond to future public health crises.

Trends of Enterovirus D68 Concentrations in Wastewater, California, USA, February 2021-April 2023.

In this retrospective study, we measured enterovirus D68 (EV-D68) genomic RNA in wastewater solids longitudinally at 2 California, USA, wastewater treatment plants twice per week for 26 months. EV-D68 RNA was undetectable except when concentrations increased from mid-July to mid-December 2022, which coincided with a peak in confirmed EV-D68 cases.

State of the Art: Acute Encephalitis.

Encephalitis is a devastating neurologic disease often complicated by prolonged neurologic deficits. Best practices for the management of adult patients include universal testing for a core group of etiologies, including herpes simplex virus (HSV)-1, varicella zoster virus (VZV), enteroviruses, West Nile virus, and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody encephalitis. Empiric acyclovir therapy should be started at presentation and in selected cases continued until a second HSV-1 polymerase chain reaction test is negative. Acyclovir dose can be increased for VZV encephalitis. Supportive care is necessary for other viral etiologies. Patients in whom no cause for encephalitis is identified represent a particular challenge. Management includes repeat brain magnetic resonance imaging, imaging for occult malignancy, and empiric immunomodulatory treatment for autoimmune conditions. Next-generation sequencing (NGS) or brain biopsy should be considered. The rapid pace of discovery regarding autoimmune encephalitis and the development of advanced molecular tests such as NGS have improved diagnosis and outcomes. Research priorities include development of novel therapeutics.

Pathogen genomics in public health laboratories: successes, challenges, and lessons learned from California's SARS-CoV-2 Whole-Genome Sequencing Initiative, California COVIDNet.

The capacity for pathogen genomics in public health expanded rapidly during the coronavirus disease 2019 (COVID-19) pandemic, but many public health laboratories did not have the infrastructure in place to handle the vast amount of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequence data generated. The California Department of Public Health, in partnership with Theiagen Genomics, was an early adopter of cloud-based resources for bioinformatics and genomic epidemiology, resulting in the creation of a SARS-CoV-2 genomic surveillance system that combined the efforts of more than 40 sequencing laboratories across government, academia and industry to form California COVIDNet, California's SARS-CoV-2 Whole-Genome Sequencing Initiative. Open-source bioinformatics workflows, ongoing training sessions for the public health workforce, and automated data transfer to visualization tools all contributed to the success of California COVIDNet. While challenges remain for public health genomic surveillance worldwide, California COVIDNet serves as a framework for a scaled and successful bioinformatics infrastructure that has expanded beyond SARS-CoV-2 to other pathogens of public health importance.

Lessons Learned From a COVID-19 Dog Screening Pilot in California K-12 Schools.

This diagnostic study describes a dog screening program used to identify COVID-19 infections among schoolchildren.

Field assessment of BinaxNOW antigen tests as COVID-19 treatment entry point at a community testing site in San Francisco during evolving omicron surges.

COVID-19 oral treatments require initiation within 5 days of symptom onset. Although antigen tests are less sensitive than RT-PCR, rapid results could facilitate entry to treatment. We collected anterior nasal swabs for BinaxNOW and RT-PCR testing and clinical data at a walk-up, community site in San Francisco, California between January and June 2022. SARS-CoV-2 genomic sequences were generated from positive samples and classified according to subtype and variant. Monte Carlo simulations were conducted to estimate the expected proportion of SARS-CoV-2 infected persons who would have been diagnosed within 5 days of symptom onset using RT-PCR versus BinaxNOW testing. Among 25,309 persons tested with BinaxNOW, 2,799 had concomitant RT-PCR. 1137/2799 (40.6%) were SARS-CoV-2 RT-PCR positive. We identified waves of predominant omicron BA.1, BA.2, BA.2.12, BA.4, and BA.5 among 720 sequenced samples. Among 1,137 RT-PCR positive samples, 788/1137 (69%) were detected by BinaxNOW; 94% (669/711) of those with Ct value <30 were detected by BinaxNOW. BinaxNOW detection was consistent over lineages. In analyses to evaluate entry to treatment, BinaxNOW detected 81.7% (361/442, 95% CI: 77-85%) of persons with COVID-19 within 5 days of symptom onset. In comparison, RT-PCR (24-hour turnaround) detected 84.2% (372/442, 95% CI: 80-87%) and RT-PCR (48-hour turnaround) detected 67.0% (296/442, 95% CI: 62-71%) of persons with COVID-19 within 5 days of symptom onset. BinaxNOW detected high viral load from anterior nasal swabs consistently across omicron sublineages emerging between January and June of 2022. Simulations support BinaxNOW as an entry point for COVID-19 treatment in a community field setting.

Acute Fulminant Cerebral Edema: A Newly Recognized Phenotype in Children With Suspected Encephalitis.

BACKGROUND: Encephalitis is a severe neurological syndrome associated with significant morbidity and mortality. The California Encephalitis Project (CEP) enrolled patients for more than a decade. A subset of patients with acute and fulminant cerebral edema was noted. METHODS: All pediatric encephalitis patients with cerebral edema referred to the CEP between 1998 and 2012 were reviewed. A case definition was developed for acute fulminant cerebral edema (AFCE) that included the CEP case definition for encephalitis and progression to diffuse cerebral edema on neuroimaging and/or autopsy, and no other recognized etiology for cerebral edema (eg, organic, metabolic, toxin). Prodromic features, demographic and laboratory data, neuroimaging, and outcomes were compared with non-AFCE encephalitis cases. RESULTS: Of 1955 pediatric cases referred to the CEP, 30 (1.5%) patients met the AFCE case definition. The median age for AFCE and non-AFCE cases was similar: 8.2 years (1-18 years) and 8.0 years (0.5-18 years), respectively. Asian-Pacific Islanders comprised a larger proportion of AFCE cases (44%) compared with non-AFCE cases (14%, P < .01). AFCE cases often had a prodrome of high fever, vomiting, and profound headache. Mortality among AFCE patients was significantly higher than among non-AFCE patients (80% vs 13%, P < .01). A confirmed etiology was identified in only 2 cases (enterovirus, human herpes virus type 6), while 10 others had evidence of a respiratory pathogen.Thirty pediatric patients referred to the California Encephalitis Project with a unique, and often fatal, form of encephalitis are reported. Demographic and clinical characteristics, possible etiologies and a proposed case definition for acute fulminant cerebral edema (AFCE) are described. CONCLUSIONS: AFCE is a recently recognized phenotype of encephalitis with a high mortality. AFCE may be triggered by common pediatric infections. Here, we propose a case definition.

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM.

2019 AAFP Feline Zoonoses Guidelines.

AIM: The overarching purpose of the 2019 AAFP Feline Zoonoses Guidelines (hereafter referred to as the 'Guidelines') is to provide accurate information about feline zoonotic diseases to owners, physicians and veterinarians to allow logical decisions to be made concerning cat ownership. SCOPE AND ACCESSIBILITY: The Panelists are physicians and veterinarians who worked closely together in an attempt to make these Guidelines a document that can be used to support the International One Health movement. This version of the Guidelines builds upon the first feline zoonosis panel report, published in 2003 ( catvets.com/guidelines ), and provides an updated reference list and recommendations. Each of the recommendations received full support from every Panelist. Primary recommendations are highlighted in a series of 'Panelists' advice' boxes.

Pediatric pulmonary mucormycosis in a diabetic patient treated with extended pleurectomy and Clagett procedure.

Mucor is a ubiquitous fungus that is non-pathogenic in healthy people. In immunocompromised hosts, non-functional or absent neutrophils and macrophages result in fungal invasion and infection [1]. Invasive mucor (mucormycosis) most commonly involves the sinuses, brain, or lungs. Pulmonary mucormycosis typically presents in patients with a history of organ transplantation or hematologic malignancy [2], and is rare in patients with diabetes alone. The epidemiology and management of pediatric pulmonary mucormycosis is poorly described. We report an unusual occurrence of this disease, complicated by segmental pulmonary artery thrombus in a 15-year-old with poorly controlled diabetes. His severe, medication-resistant infection was ultimately treated successfully with antifungal medication combined with aggressive surgical debridement. The pulmonary artery segmental thrombus resolved after treatment of the underlying infection without anticoagulation.

Incidence, Risk Factors and Outcomes Among Children With Acute Flaccid Myelitis: A Population-based Cohort Study in a California Health Network Between 2011 and 2016.

BACKGROUND: Acute flaccid myelitis (AFM) is defined as an acute onset of limb weakness with longitudinal spinal gray matter lesions. Reporting bias and misdiagnosis confound epidemiologic studies of AFM. We mitigated these confounders by using a large data set to assess AFM incidence, risk factors and outcomes in a fixed population. METHODS: A retrospective cohort study was conducted within Kaiser Permanente Northern California population among children 1-18 years. Cases met radiographic and clinical criteria for AFM and were confirmed by two clinicians. Clinical and demographic data were assessed. RESULTS: A total of 28 patients met study criteria for AFM between January 1, 2011 and December 31, 2016, an overall rate of 1.46 per 100,000 person-years. Incidence increased from 0.30 to 1.43 cases/per 100,000 person-years between 2011 and 2016, respectively. Median age was 9 years. Risk factors included male sex, Asian ancestry and history of asthma, atopic dermatitis or head injury. Risk factors associated with poliomyelitis were absent. Prodromal illness was common; enterovirus was the most common pathogen detected (n = 5). Among the 27 patients with 12-month follow-up, most demonstrated some improvement, 11 (41.0%) had full recovery, but several had significant deficits with one death reported after the study period. CONCLUSIONS: We employed a closed-population study to generate AFM incidence, risk and outcome data. Our findings support previous reports of male sex and atopy as risk factors. Interval increase in incidence, predisposing Asian ancestry and history of head injury were unique findings to this study. Overall prognosis was better than prior reports, but recovery was incomplete in several patients.

The Epidemiology and Clinical Features of Balamuthia mandrillaris Disease in the United States, 1974-2016.

BACKGROUND: Balamuthia mandrillaris is a free-living ameba that causes rare, nearly always fatal disease in humans and animals worldwide. B. mandrillaris has been isolated from soil, dust, and water. Initial entry of Balamuthia into the body is likely via the skin or lungs. To date, only individual case reports and small case series have been published. METHODS: The Centers for Disease Control and Prevention (CDC) maintains a free-living ameba (FLA) registry and laboratory. To be entered into the registry, a Balamuthia case must be laboratory-confirmed. Several sources were used to complete entries in the registry, including case report forms, CDC laboratory results, published case reports, and media information. SAS© version 9.3 software was used to calculate descriptive statistics and frequencies. RESULTS: We identified 109 case reports of Balamuthia disease between 1974 and 2016. Most (99%) had encephalitis. The median age was 36 years (range 4 months to 91 years). Males accounted for 68% of the case patients. California had the highest number of case reports, followed by Texas and Arizona. Hispanics constituted 55% for those with documented ethnicity. Exposure to soil was commonly reported. Among those with a known outcome, 90% of patients died. CONCLUSIONS: Balamuthia disease in the United States is characterized by a highly fatal encephalitis that affects patients of all ages. Hispanics were disproportionately affected. The southwest region of the United States reported the most cases. Clinician awareness of Balamuthia as a cause of encephalitis might lead to earlier diagnosis and initiation of treatment, resulting in better outcomes.