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Open Access Publications from the University of California

Scholarly Works (24 results)

  • Thesis
  • Peer Reviewed
UC Davis Electronic Theses and Dissertations (2021)

Advances in computational performance and the advent of big data have allowed the emergence of new methodologies for modeling infectious diseases as complex systems representing aspects such as non-linearity, emergence, and feedback loops, among others, with increasing spatio-temporal resolution. Agent based models have been used in many other disciplines such as social sciences, ecology, city planing, and, more recently, epidemiology. With the objective of better integration of data and theory, we used agent based modeling and global sensitivity analysis of complex models under different epidemiological scenarios and with varying degrees of data availability and quality. In the first chapter, we integrated data from publications between February 2020-February 2021 and from phone interviews in a typical nursing home in California to develop an agent based model to explore the impact of non-pharmaceutical interventions and vaccination in the prevention and control of COVID-19 in nursing homes. In the second chapter, we used information from the literature and from sow farm production records in the Midwestern United States to develop a model that evaluate the effect of herd management and vaccination in the control of porcine reproductive and respiratory syndrome (PRRS), an endemic disease in the US pork industry. In the third chapter, we used data provided by the national veterinary services (AGROCALIDAD) of Ecuador to evaluate the impact of simulated re-introductions of foot and mouth disease (FMD), which is in the last phase of disease eradication in Ecuador, and to evaluate strategies for control of FMD. The findings for each of the presented chapters can be used to support disease eradication efforts of communicable disease outbreaks through approaches centering local epidemiological dynamics under different settings.

    Cover page: Agent based modeling to explore intervention strategies for prevention and control of infectious diseases, complex systems modeling in epidemiology
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2016)

    Objective

    The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event.

    Methods

    This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30 days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported.

    Results

    The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5 days (range, 50-254 days). In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs) included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk, and central scotomas in each eye.

    Conclusion

    In our small population, linezolid was generally well tolerated and AEs were consistent with the known safety profile. Extensive ophthalmologic testing of all 24 linezolid-treated patients identified one case adjudicated as probable, linezolid-associated optic neuropathy.
      Cover page: Safety of long-term use of linezolid: results of an open-label study
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2022)

      Background

      Efforts to protect residents in nursing homes involve non-pharmaceutical interventions, testing, and vaccine. We sought to quantify the effect of testing and vaccine strategies on the attack rate, length of the epidemic, and hospitalization.

      Methods

      We developed an agent-based model to simulate the dynamics of SARS-CoV-2 transmission among resident and staff agents in a nursing home. Interactions between 172 residents and 170 staff based on data from a nursing home in Los Angeles, CA. Scenarios were simulated assuming different levels of non-pharmaceutical interventions, testing frequencies, and vaccine efficacy to reduce transmission.

      Results

      Under the hypothetical scenario of widespread SARS-CoV-2 in the community, 3-day testing frequency minimized the attack rate and the time to eradicate an outbreak. Prioritization of vaccine among staff or staff and residents minimized the cumulative number of infections and hospitalization, particularly in the scenario of high probability of an introduction. Reducing the probability of a viral introduction eased the demand on testing and vaccination rate to decrease infections and hospitalizations.

      Conclusions

      Improving frequency of testing from 7-days to 3-days minimized the number of infections and hospitalizations, despite widespread community transmission. Vaccine prioritization of staff provides the best protection strategy when the risk of viral introduction is high.
        Cover page: Testing and vaccination to reduce the impact of COVID-19 in nursing homes: an agent-based approach
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2018)
        Archaeological research has the potential to contribute to our understanding of social vulnerability to environmental change by providing examples of change in the deep and recent past. Here we argue that human activity and historical processes deeply transform tropical environments through time, and that these changes accumulate on the landscape affecting social vulnerability. These changes, however, are not always evident due to rapid vegetation growth obscuring past human impact. Our research investigates the northernmost 25 km of the Manatí Hydrological Basin in Puerto Rico, focusing on evidence of human activity and environmental characteristics including topography, sediments and vegetation cover. The data collected, which articulates archaeological and ethnographic records, covers the span of pre-Columbian occupation of the region, through the colonial periods, and into the twentieth century. Results show that human activity through time has deeply altered the forests. The accumulation of long-term histories of biotic, abiotic and cultural dynamics affects social sensitivity and exposure. Human ingenuity can widen resilience thresholds, making long-term practices particularly important components of adaptive strategies. Deep-time socioecological perspectives can contribute to current vulnerability assessments by enhancing local and historical records that can feed predictive models and inform decision-making in the present.
          Cover page: A Deep-Time Socioecosystem Framework to Understand Social Vulnerability on a Tropical Island
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2024)
          Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy approved for the treatment of hematologic malignancies. This therapy leads to a variety of immunologic deficits that could place patients at risk for invasive fungal disease (IFD). Studies assessing IFD in this setting are limited by inconsistent definitions and heterogeneity in prophylaxis use, although the incidence of IFD after CAR T-cell therapy, particularly for lymphoma and myeloma, appears to be low. This review evaluates the incidence of IFD after CAR T-cell therapy, and discusses optimal approaches to prevention, highlighting areas that require further study as well as future applications of cellular therapy that may impact IFD risk. As the use of CAR T-cell therapy continues to expand for hematologic malignancies, solid tumors, and most recently to include non-oncologic diseases, understanding the risk for IFD in this uniquely immunosuppressed population is imperative to prevent morbidity and mortality.
            Cover page: The Burden of Invasive Fungal Disease Following Chimeric Antigen Receptor T-Cell Therapy and Strategies for Prevention.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2010)
              Cover page: Reply to: The diagnostic accuracy of 18F-FDG PET in cutaneous malignant melanoma
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2023)
              BACKGROUND: Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration. METHODS: This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (<96 h of treatment start) composed the modified intent-to-treat (mITT) population. Primary efficacy endpoint was treatment success at the end of study treatment (EOST) as determined by the Data Review Committee. Success was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at the EOST. RESULTS: Treatment success was 80% (16/20, mITT; EOST) and Day 30 survival was 85% (17/20; 3 deaths unrelated to fosmanogepix). Ten of 21 (48%) were switched to oral fosmanogepix. Fosmanogepix was well tolerated with no treatment-related serious adverse events/discontinuations. Fosmanogepix had potent in vitro activity against baseline isolates of Candida spp. (MICrange: CLSI, 0.002-0.03 mg/L). CONCLUSIONS: Results from this single-arm Phase 2 trial suggest that fosmanogepix may be a safe, well-tolerated, and efficacious treatment for non-neutropenic patients with candidaemia, including those with renal impairment.
                Cover page: Clinical safety and efficacy of novel antifungal, fosmanogepix, for the treatment of candidaemia: results from a Phase 2 trial.
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2021)

                Background

                Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC).

                Methods

                Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤4 weeks. Efficacy assessments included overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14 (primary endpoint), investigator-assessed clinical response at day 14, and 30-day all-cause mortality (ACM) (secondary endpoints), and time to negative blood culture. Safety was evaluated by adverse events and ACM through follow-up.

                Results

                Of 207 patients enrolled, 183 were in the microbiological intent-to-treat population (~21% IC). Overall cure rates were 60.5% (46/76) for RZF 400 mg, 76.1% (35/46) for RZF 400/200 mg, and 67.2% (41/61) for CAS; investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. In total, 30-day ACM was 15.8% for RZF 400 mg, 4.4% for RZF 400/200 mg, and 13.1% for CAS. Candidemia was cleared in 19.5 and 22.8 hours in RZF and CAS patients, respectively. No concerning safety trends were observed; ACM through follow-up was 15.2% (21/138) for RZF and 18.8% (13/69) for CAS.

                Conclusions

                RZF was safe and efficacious in the treatment of candidemia and/or IC.

                Clinical trials registration

                NCT02734862.
                  Cover page: Rezafungin versus Caspofungin in a Phase 2, Randomized, Double-Blind Study for the Treatment of Candidemia and Invasive Candidiasis- The STRIVE Trial
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2016)

                  Background

                  Invasive fungal diseases (IFD) caused by Cryptococcus and dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISAV) is a novel, broad-spectrum, triazole antifungal agent (IV and by mouth [PO]) developed for the treatment of IFD. It displays potent activity in vitro against these pathogens and in this report we examine outcomes of patients with cryptococcosis or dimorphic fungal infections treated with ISAV.

                  Methods

                  The VITAL study was an open-label nonrandomized phase 3 trial conducted to evaluate the efficacy and safety of ISAV treatment in management of rare IFD. Patients received ISAV 200 mg 3 times daily for 2 days followed by 200 mg once-daily (IV or PO). Proven IFD and overall response at end of treatment (EOT) were determined by an independent, data-review committee. Mortality and safety were also assessed.

                  Results

                  Thirty-eight patients received ISAV for IFD caused by Cryptococcus spp. (n = 9), Paracoccidioides spp. (n = 10), Coccidioides spp. (n = 9), Histoplasma spp. (n = 7) and Blastomyces spp. (n = 3). The median length of therapy was 180 days (range 2-331 days). At EOT 24/38 (63%) patients exhibited a successful overall response. Furthermore, 8 of 38 (21%) had stable IFD at the end of therapy without progression of disease, and 6 (16%) patients had progressive IFD despite this antifungal therapy. Thirty-three (87%) patients experienced adverse events.

                  Conclusions

                  ISAV was well tolerated and demonstrated clinical activity against these endemic fungi with a safety profile similar to that observed in larger studies, validating its broad-spectrum in vitro activity and suggesting it may be a valuable alternative to currently available agents.

                  Clinical trials registration

                  NCT00634049.
                    Cover page: Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses
                    • Article
                    • Peer Reviewed
                    UC Davis Previously Published Works (2022)
                    Zika virus (ZIKV) is unique among mosquito-borne flaviviruses in that it is also vertically and sexually transmitted by humans. The male reproductive tract is thought to be a ZIKV reservoir; however, the reported magnitude and duration of viral persistence in male genital tissues vary widely in humans and non-human primate models. ZIKV tissue and cellular tropism and potential effects on male fertility also remain unclear. The objective of this study was to resolve these questions by analyzing archived genital tissues from 51 ZIKV-inoculated male macaques and correlating data on plasma viral kinetics, tissue tropism, and ZIKV-induced pathological changes in the reproductive tract. We hypothesized that ZIKV would persist in the male macaque genital tract for longer than there was detectable viremia, where it would localize to germ and epithelial cells and associate with lesions. We detected ZIKV RNA and infectious virus in testis, epididymis, seminal vesicle, and prostate gland. In contrast to prepubertal males, sexually mature macaques were significantly more likely to harbor persistent ZIKV RNA or infectious virus somewhere in the genital tract, with detection as late as 60 days post-inoculation. ZIKV RNA localized primarily to testicular stem cells/sperm precursors and epithelial cells, including Sertoli cells, epididymal duct epithelium, and glandular epithelia of the seminal vesicle and prostate gland. ZIKV infection was associated with microscopic evidence of inflammation in the epididymis and prostate gland of sexually mature males, pathologies that were absent in uninfected controls, which could have significant effects on male fertility. The findings from this study increase our understanding of persistent ZIKV infection which can inform risk of sexual transmission during assisted reproductive therapies as well as potential impacts on male fertility.
                      Cover page: Zika virus persistence in the male macaque reproductive tract
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