Closing the Water Balance with a Precision Small-Scale Field Lysimeter.

We developed a set of two precision, small-scale, water balance lysimeters to provide accurate measurements of bare soil evaporation. Each lysimeter comprises a soil tank, a balance assembly with load cell, a wicking drainage system, and a stilling well to measure drained water. Fiberglass wicks installed at the bottom of the soil tanks provide -60 cm of tension to the base of the soil column, and soil water drainage is quantified to close the water balance within the lysimeter. The calibrated lysimeters return mass changes with uncertainties ranging from 3 to 8 g, corresponding to uncertainties of 0.02-0.05 mm of water. Installed at a semi-arid site in northern Nevada, the two lysimeters are filled with uniform construction sand and silt loam. Over a six-month pilot observation period, bare soil evaporation rates of 0.19 and 0.40 mm/day were measured for the construction sand and silt loam, respectively, which is consistent with meteorological data and models of potential evapotranspiration at the site. The design of the lysimeter can be adapted to specific research goals or site restrictions, and these instruments can contribute significantly to our ability to close the soil water balance.

Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics.

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

Establishing the normal range of sperm DNA fragmentation index (% DFI) for rhesus macaques.

The Sperm Chromatin Structure Assay (SCSA) is a robust test with high repeatability and precision. It is a clinically accepted assay that defines risk for infertility in men by measuring the degree of DNA fragmentation (% DFI) in sperm. The objective of this study was to adapt and validate the SCSA for rhesus macaques (Macaca mulatta) and establish a range for % DFI in fertile males. Sperm samples from two different males were used to produce a % DFI validation curve before establishing a range using additional samples from n = 11 males. Sperm labeled with acridine orange were analyzed by flow cytometry to measure green fluorescence (native or intact DNA) and red fluorescence (fragmented DNA). Data were exported to FlowJo software to determine the % DFI for each sample. DNA fragmentation ranged from 0.1 to 2.4% DFI, with a mean ± SD = 1.1 ± 0.7% DFI (validation curve optimized to R2 > 0.95). In conclusion, we were able to successfully validate the SCSA in our institution and establish the first normal range for sperm DNA fragmentation in rhesus macaques. Our study provides a quantitative baseline for future evaluations to assess macaque fertility through the SCSA test.

Travel history among persons infected with SARS-CoV-2 variants of concern in the United States, December 2020-February 2021.

The first three SARS-CoV-2 phylogenetic lineages classified as variants of concern (VOCs) in the United States (U.S.) from December 15, 2020 to February 28, 2021, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1) lineages, were initially detected internationally. This investigation examined available travel history of coronavirus disease 2019 (COVID-19) cases reported in the U.S. in whom laboratory testing showed one of these initial VOCs. Travel history, demographics, and health outcomes for a convenience sample of persons infected with a SARS-CoV-2 VOC from December 15, 2020 through February 28, 2021 were provided by 35 state and city health departments, and proportion reporting travel was calculated. Of 1,761 confirmed VOC cases analyzed, 1,368 had available data on travel history. Of those with data on travel history, 1,168 (85%) reported no travel preceding laboratory confirmation of SARS-CoV-2 and only 105 (8%) reported international travel during the 30 days preceding a positive SARS-CoV-2 test or symptom onset. International travel was reported by 92/1,304 (7%) of persons infected with the Alpha variant, 7/55 (22%) with Beta, and 5/9 (56%) with Gamma. Of the first three SARS-CoV-2 lineages designated as VOCs in the U.S., international travel was common only among the few Gamma cases. Most persons infected with Alpha and Beta variant reported no travel history, therefore, community transmission of these VOCs was likely common in the U.S. by March 2021. These findings underscore the importance of global surveillance using whole genome sequencing to detect and inform mitigation strategies for emerging SARS-CoV-2 VOCs.

US-Mexico binational COVID-19 cases in southern California border counties, California, February-June 2020.

Background: COVID-19 has had a significant public health impact on both the United States and Mexico. Cross-border mobility between southern California and Mexico raises questions of transmission trends between these jurisdictions. The objective of this project was to describe binational cases amongst California US-Mexico border county COVID-19 cases and compare incidence trends to cross-border Mexico jurisdictions. Methods: Interview data from persons with confirmed SARS-CoV-2 infections in San Diego County, CA and Imperial County, CA from February to June 2020 were reviewed for binational cases; demographics and connection to COVID-19 outbreaks were assessed. Graphs of COVID-19 incidence in San Diego County and Imperial County were compared to incidence graphs in cross-border Mexico jurisdictions of Tijuana and Mexicali. Results: Persons with COVID-19 and a binational case were older, more likely to be Hispanic, and reside in a border ZIP code than those without. Binational cases were a small proportion and tracked with overall cases during the study period. Conclusions: Binational cases had different trends than non-binational cases of SARS-CoV-2 in San Diego and Imperial counties from February to June 2020. Findings could inform SARS-CoV-2 mitigation strategies specific to the US-Mexico land border, particularly recommendations regarding cross-border land travel.

COVID-19 Case Investigations Among Federally Quarantined Evacuees From Wuhan, China, and Exposed Personnel at a US Military Base, United States, February 5-21, 2020.

In February 2020, during the early days of the COVID-19 pandemic, 232 evacuees from Wuhan, China, were placed under federal 14-day quarantine upon arrival at a US military base in San Diego, California. We describe the monitoring of evacuees and responders for symptoms of COVID-19, case and contact investigations, infection control procedures, and lessons learned to inform future quarantine protocols for evacuated people from a hot spot resulting from a novel pathogen. Thirteen (5.6%) evacuees had COVID-19-compatible symptoms and 2 (0.9%) had laboratory-confirmed SARS-CoV-2. Two case investigations identified 43 contacts; 3 (7.0%) contacts had symptoms but tested negative for SARS-CoV-2 infection. Daily symptom and temperature screening of evacuees and enacted infection control procedures resulted in rapid case identification and isolation and no detected secondary transmission among evacuees or responders. Lessons learned highlight the challenges associated with public health response to a novel pathogen and the evolution of mitigation strategies as knowledge of the pathogen evolves.

SARS-CoV-2 infection risk among vaccinated and unvaccinated household members during the Alpha variant surge - Denver, Colorado, and San Diego, California, January-April 2021.

BACKGROUND: COVID-19 vaccination reduces SARS-CoV-2 infection and transmission. However, evidence is emerging on the degree of protection across variants and in high-transmission settings. To better understand the protection afforded by vaccination specifically in a high-transmission setting, we examined household transmission of SARS-CoV-2 during a period of high community incidence with predominant SARS-CoV-2 B.1.1.7 (Alpha) variant, among vaccinated and unvaccinated contacts. METHODS: We conducted a household transmission investigation in San Diego County, California, and Denver, Colorado, during January-April 2021. Households were enrolled if they had at least one person with documented SARS-CoV-2 infection. We collected nasopharyngeal swabs, blood, demographic information, and vaccination history from all consenting household members. We compared infection risks (IRs), RT-PCR cycle threshold values, SARS-CoV-2 culture results, and antibody statuses among vaccinated and unvaccinated household contacts. RESULTS: We enrolled 493 individuals from 138 households. The SARS-CoV-2 variant was identified from 121/138 households (88%). The most common variants were Alpha (75/121, 62%) and Epsilon (19/121, 16%). There were no households with discordant lineages among household members. One fully vaccinated secondary case was symptomatic (13%); the other 5 were asymptomatic (87%). Among unvaccinated secondary cases, 105/108 (97%) were symptomatic. Among 127 households with a single primary case, the IR for household contacts was 45% (146/322; 95% Confidence Interval [CI] 40-51%). The observed IR was higher in unvaccinated (130/257, 49%, 95% CI 45-57%) than fully vaccinated contacts (6/26, 23%, 95% CI 11-42%). A lower proportion of households with a fully vaccinated primary case had secondary cases (1/5, 20%) than households with an unvaccinated primary case (66/108, 62%). CONCLUSIONS: Although SARS-CoV-2 infections in vaccinated household contacts were reported in this high transmission setting, full vaccination protected against SARS-CoV-2 infection. These findings further support the protective effect of COVID-19 vaccination and highlight the need for ongoing vaccination among eligible persons.

Comparison of Home Antigen Testing With RT-PCR and Viral Culture During the Course of SARS-CoV-2 Infection.

Importance: As self-collected home antigen tests become widely available, a better understanding of their performance during the course of SARS-CoV-2 infection is needed. Objective: To evaluate the diagnostic performance of home antigen tests compared with reverse transcription-polymerase chain reaction (RT-PCR) and viral culture by days from illness onset, as well as user acceptability. Design, Setting, and Participants: This prospective cohort study was conducted from January to May 2021 in San Diego County, California, and metropolitan Denver, Colorado. The convenience sample included adults and children with RT-PCR-confirmed infection who used self-collected home antigen tests for 15 days and underwent at least 1 nasopharyngeal swab for RT-PCR, viral culture, and sequencing. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was the daily sensitivity of home antigen tests to detect RT-PCR-confirmed cases. Secondary outcomes included the daily percentage of antigen test, RT-PCR, and viral culture results that were positive, and antigen test sensitivity compared with same-day RT-PCR and cultures. Antigen test use errors and acceptability were assessed for a subset of participants. Results: This study enrolled 225 persons with RT-PCR-confirmed infection (median [range] age, 29 [1-83] years; 117 female participants [52%]; 10 [4%] Asian, 6 [3%] Black or African American, 50 [22%] Hispanic or Latino, 3 [1%] Native Hawaiian or Other Pacific Islander, 145 [64%] White, and 11 [5%] multiracial individuals) who completed 3044 antigen tests and 642 nasopharyngeal swabs. Antigen test sensitivity was 50% (95% CI, 45%-55%) during the infectious period, 64% (95% CI, 56%-70%) compared with same-day RT-PCR, and 84% (95% CI, 75%-90%) compared with same-day cultures. Antigen test sensitivity peaked 4 days after illness onset at 77% (95% CI, 69%-83%). Antigen test sensitivity improved with a second antigen test 1 to 2 days later, particularly early in the infection. Six days after illness onset, antigen test result positivity was 61% (95% CI, 53%-68%). Almost all (216 [96%]) surveyed individuals reported that they would be more likely to get tested for SARS-CoV-2 infection if home antigen tests were available over the counter. Conclusions and Relevance: The results of this cohort study of home antigen tests suggest that sensitivity for SARS-CoV-2 was moderate compared with RT-PCR and high compared with viral culture. The results also suggest that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1 to 2 days later because test sensitivity peaked several days after illness onset and improved with repeated testing.

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Alpha Variant-United States, 2021.

BACKGROUND: In Spring 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 (Alpha) became the predominant variant in the United States. Research suggests that Alpha has increased transmissibility compared with non-Alpha lineages. We estimated household secondary infection risk (SIR), assessed characteristics associated with transmission, and compared symptoms of persons with Alpha and non-Alpha infections. METHODS: We followed households with SARS-CoV-2 infection for 2 weeks in San Diego County and metropolitan Denver, January to April 2021. We collected epidemiologic information and biospecimens for serology, reverse transcription-polymerase chain reaction (RT-PCR), and whole-genome sequencing. We stratified SIR and symptoms by lineage and identified characteristics associated with transmission using generalized estimating equations. RESULTS: We investigated 127 households with 322 household contacts; 72 households (56.7%) had member(s) with secondary infections. SIRs were not significantly higher for Alpha (61.0% [95% confidence interval, 52.4-69.0%]) than non-Alpha (55.6% [44.7-65.9%], P = .49). In households with Alpha, persons who identified as Asian or Hispanic/Latino had significantly higher SIRs than those who identified as White (P = .01 and .03, respectively). Close contact (eg, kissing, hugging) with primary cases was associated with increased transmission for all lineages. Persons with Alpha infection were more likely to report constitutional symptoms than persons with non-Alpha (86.9% vs 76.8%, P = .05). CONCLUSIONS: Household SIRs were similar for Alpha and non-Alpha. Comparable SIRs may be due to saturation of transmission risk in households due to extensive close contact, or true lack of difference in transmission rates. Avoiding close contact within households may reduce SARS-CoV-2 transmission for all lineages among household members.

Identification and Characterization of Antigen-Specific CD8+ T Cells Using Surface-Trapped TNF-α and Single-Cell Sequencing.

CD8+ T cells are key mediators of antiviral and antitumor immunity. The isolation and study of Ag-specific CD8+ T cells, as well as mapping of their MHC restriction, has practical importance to the study of disease and the development of therapeutics. Unfortunately, most experimental approaches are cumbersome, owing to the highly variable and donor-specific nature of MHC-bound peptide/TCR interactions. Here we present a novel system for rapid identification and characterization of Ag-specific CD8+ T cells, particularly well suited for samples with limited primary cells. Cells are stimulated ex vivo with Ag of interest, followed by live cell sorting based on surface-trapped TNF-α. We take advantage of major advances in single-cell sequencing to generate full-length sequence data from the paired TCR α- and ß-chains from these Ag-specific cells. The paired TCR chains are cloned into retroviral vectors and used to transduce donor CD8+ T cells. These TCR transductants provide a virtually unlimited experimental reagent, which can be used for further characterization, such as minimal epitope mapping or identification of MHC restriction, without depleting primary cells. We validated this system using CMV-specific CD8+ T cells from rhesus macaques, characterizing an immunodominant Mamu-A1*002:01-restricted epitope. We further demonstrated the utility of this system by mapping a novel HLA-A*68:02-restricted HIV Gag epitope from an HIV-infected donor. Collectively, these data validate a new strategy to rapidly identify novel Ags and characterize Ag-specific CD8+ T cells, with applications ranging from the study of infectious disease to immunotherapeutics and precision medicine.

The estimated hepatitis C seroprevalence and key population sizes in San Diego in 2018.

BACKGROUND: The Eliminate Hepatitis C San Diego County Initiative was established to provide a roadmap to reduce new HCV infections by 80% and HCV-related deaths by 65% by 2030. An estimate of the burden of HCV infections in San Diego County is necessary to inform planning and evaluation efforts. Our analysis was designed to estimate the HCV burden in San Diego County in 2018. METHODS: We synthesized data from the American Community Survey, Centers for Disease Control and Prevention, California Department of Public Health, Public Health Branch of California Correctional Health Care Services, San Diego Blood Bank, and published literature. Burden estimates were stratified by subgroup (people who inject drugs in the community [PWID], men who have sex with men in the community [MSM], general population in the community [stratified by age and sex], and incarcerated individuals). To account for parameter uncertainty, 100,000 parameter sets were sampled from each parameter's uncertainty distribution, and used to calculate the mean and 95% confidence interval estimates of the number of HCV seropositive adults in San Diego in 2018. FINDINGS: We found there were 55,354 (95% CI: 25,411-93,329) adults with a history of HCV infection in San Diego County in 2018, corresponding to an HCV seroprevalence of 2.1% (95% CI: 1.1-3.4%). Over 40% of HCV infections were among the general population aged 55-74 and one-third were among PWID. CONCLUSION: Our study found that the largest share of infections was among adults aged 55-74, indicating the importance of surveillance, prevention, testing, and linkages to care in this group to reduce mortality. Further, programs prioritizing PWID for increased HCV testing and linkage to care are important for reducing new HCV infections.

Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Public Health Role of Academic Medical Center in Community Outbreak of Hepatitis A, San Diego County, California, USA, 2016-2018.

During 2016-2018, San Diego County, California, USA, experienced one of the largest hepatitis A outbreaks in the United States in 2 decades. In close partnership with local healthcare systems, San Diego County Public Health led a public health response to the outbreak that focused on a 3-pronged strategy to vaccinate, sanitize, and educate. Healthcare systems administered nearly half of the vaccinations delivered in San Diego County. At University of California San Diego Health, the use of informatics tools assisted with the identification of at-risk populations and with vaccine delivery across outpatient and inpatient settings. In addition, acute care facilities helped prevent further disease transmission by delaying the discharge of patients with hepatitis A who were experiencing homelessness. We assessed the public health roles that acute care hospitals can play during a large community outbreak and the critical nature of ongoing collaboration between hospitals and public health systems in controlling such outbreaks.

2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus.

2019 Novel Coronavirus (2019-nCoV) is an emerging infectious disease closely related to MERS-CoV and SARS-CoV that was first reported in Wuhan City, Hubei Province, China in December 2019. As of January 2020, cases of 2019-nCoV are continuing to be reported in other Eastern Asian countries as well as in the United States, Europe, Australia, and numerous other countries. An unusually high volume of domestic and international travel corresponding to the beginning of the 2020 Chinese New Year complicated initial identification and containment of infected persons. Due to the rapidly rising number of cases and reported deaths, all countries should be considered at risk of imported 2019-nCoV. Therefore, it is essential for prehospital, clinic, and emergency department personnel to be able to rapidly assess 2019-nCoV risk and take immediate actions if indicated. The Identify-Isolate-Inform (3I) Tool, originally conceived for the initial detection and management of Ebola virus and later adjusted for other infectious agents, can be adapted for any emerging infectious disease. This paper reports a modification of the 3I Tool for use in the initial detection and management of patients under investigation for 2019-nCoV. After initial assessment for symptoms and epidemiological risk factors, including travel to affected areas and exposure to confirmed 2019-nCoV patients within 14 days, patients are classified in a risk-stratified system. Upon confirmation of a suspected 2019-nCoV case, affected persons must immediately be placed in airborne infection isolation and the appropriate public health agencies notified. This modified 3I Tool will assist emergency and primary care clinicians, as well as out-of-hospital providers, in effectively managing persons with suspected or confirmed 2019-nCoV.

Homelessness and Hepatitis A-San Diego County, 2016-2018.

BACKGROUND: Hepatitis A is a vaccine-preventable viral disease transmitted by the fecal-oral route. During 2016-2018, the County of San Diego investigated an outbreak of hepatitis A infections primarily among people experiencing homelessness (PEH) to identify risk factors and support control measures. At the time of the outbreak, homelessness was not recognized as an independent risk factor for the disease. METHODS: We tested the association between homelessness and infection with hepatitis A virus (HAV) using a test-negative study design comparing patients with laboratory-confirmed hepatitis A with control subjects who tested negative for HAV infection. We assessed risk factors for severe hepatitis A disease outcomes, including hospitalization and death, using multivariable logistic regression. We measured the frequency of indications for hepatitis A vaccination according to Advisory Committee on Immunization Practices (ACIP) guidelines. RESULTS: Among 589 outbreak-associated cases reported, 291 (49%) occurred among PEH. Compared with those who were not homeless, PEH had 3.3 (95% confidence interval [CI], 1.5-7.9) times higher odds of HAV infection, 2.5 (95% CI, 1.7-3.9) times higher odds of hospitalization, and 3.9 (95% CI, 1.1-16.9) times higher odds of death associated with hepatitis A. Among PEH, 212 (73%) patients recorded other ACIP indications for hepatitis A vaccination. CONCLUSIONS: PEH were at higher risk of infection with HAV and of severe hepatitis A disease outcomes compared with those not experiencing homelessness. Approximately one-fourth of PEH had no other ACIP indication for hepatitis A vaccination. These findings support the recent ACIP recommendation to add homelessness as an indication for hepatitis A vaccination.

Targeted molecular imaging of TLR4 in hepatocellular carcinoma using zwitterionic near-infrared fluorophores.

BACKGROUND: Tumor-associated macrophages (TAMs) are one of the most abundant immune cell types in solid tumors and implicated in tumor progression. Toll-like receptor 4 (TLR4) is expressed in TAMs and plays a key role in immune surveillance and tumor progression. Therefore, molecular imaging of TLR4 has potential not only for detection of TAM-enriched progressing tumors, but also evaluation of TLR4 expression in tumor microenvironment. METHODS: Here, we report that near-infrared (NIR) fluorescence imaging can provide a real-time imaging of a syngeneic model of murine hepatocellular carcinoma using targeted strategy against TLR4. We conjugated a zwitterionic NIR fluorophore ZW800-1C with minimal nonspecific tissue interactions to anti-TLR4 antibody and observed its targetability. The bioconjugates showed high affinity to murine macrophages in cell culture and in vivo. RESULTS: Interestingly, we observed predominant NIR signals in the tumor site, which persisted for more than 48 h after single intravenous administration of the bioconjugate. CONCLUSIONS: This result suggests that TLR4 targeting combined with NIR fluorescence imaging is a useful tool for cancer imaging. This imaging strategy could be used to detect cancerous tissue with the increased TAM content and evaluate the status of TLR4 signaling in solid tumors, ultimately impacting on the diagnostic and prognostic imaging of human cancers.

Targeted Near-Infrared Fluorescence Imaging for Regenerative Medicine.

Background: Advances in tissue engineering and regenerative medicine over the last three decades have made great progress in the development of diagnostic and therapeutic methodologies for damaged tissues. However, regenerative medicine is still not the first line of treatment for patients due to limited understanding of the tissue regeneration process. Therefore, it is prerequisite to develop molecular imaging strategies combined with appropriate contrast agents to validate the therapeutic progress of damaged tissues. Methods: The goal of this review is to discuss the progress in the development of near-infrared (NIR) contrast agents and their biomedical applications for labeling cells and scaffolds, as well as monitoring the treatment progress of native tissue in living organisms. We also discuss the design consideration of NIR contrast agents for tissue engineering and regenerative medicine in terms of their physicochemical and optical properties. Results: The use of NIR imaging system and targeted contrast agents can provide high-resolution and high sensitivity imaging to track/monitor the in vivo fate of administered cells, the degradation rate of implanted scaffolds, and the tissue growth and integration of surrounding cells during the therapeutic period. Conclusion: NIR fluorescence imaging techniques combined with targeted contrast agents can play a significant role in regenerative medicine by monitoring the therapeutic efficacy of implanted cells and scaffolds which would enhance the development of cell therapies and promote their successful clinical translations.

Novel Treatment of a Vaccinia Virus Infection from an Occupational Needlestick - San Diego, California, 2019.

Vaccinia virus (VACV) is an orthopoxvirus used in smallpox vaccines, as a vector for novel cancer treatments, and for experimental vaccine research (1). The Advisory Committee on Immunization Practices (ACIP) recommends smallpox vaccination for laboratory workers who handle replication-competent VACV (1). For bioterrorism preparedness, the U.S. government stockpiles tecovirimat, the first Food and Drug Administration-approved antiviral for treatment of smallpox (caused by variola virus and globally eradicated in 1980*,†) (2). Tecovirimat has activity against other orthopoxviruses and can be administered under a CDC investigational new drug protocol. CDC was notified about an unvaccinated laboratory worker with a needlestick exposure to VACV, who developed a lesion on her left index finger. CDC and partners performed laboratory confirmation, contacted the study sponsor to identify the VACV strain, and provided oversight for the first case of laboratory-acquired VACV treated with tecovirimat plus intravenous vaccinia immunoglobulin (VIGIV). This investigation highlights 1) the misconception among laboratory workers about the virulence of VACV strains; 2) the importance of providing laboratorians with pathogen information and postexposure procedures; and 3) that although tecovirimat can be used to treat VACV infections, its therapeutic benefit remains unclear.