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Open Access Publications from the University of California

Scholarly Works (82 results)

  • Article
  • Peer Reviewed
UC Berkeley Previously Published Works (2020)
The fact that many pathogens can be carried or shed without causing symptoms complicates the interpretation of microbiological data when diagnosing certain infectious disease syndromes. Diagnostic criteria that attribute symptoms to a pathogen which is detectable, whether it is or is not the aetiological agent of disease, may lead to outcome misclassification in epidemiological studies. Case-control studies are commonly undertaken to estimate vaccine effectiveness (VE) and present an opportunity to compare pathogen detection among individuals with and without clinically relevant symptoms. Considering this study context, we present a mathematical framework yielding simple estimators for the direct effects of vaccination on various aspects of host susceptibility. These include protection against acquisition of the pathogen of interest and protection against progression of this pathogen to disease following acquisition. We assess the impact of test sensitivity on these estimators and extend our framework to identify a 'vaccine probe' estimator for pathogen-specific aetiological fractions. We also derive biases affecting VE estimates under the test-negative design, a special case enrolling only symptomatic persons. Our results provide strategies for estimating pathogen-specific VE in the absence of a diagnostic gold standard. These approaches can inform the design and analysis of studies addressing numerous pathogens and vaccines.
    Cover page: Uses of pathogen detection data to estimate vaccine direct effects in case-control studies.
    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2018)
    The imperfect effectiveness of seasonal influenza vaccines is often blamed on antigenic mismatch, but even when the match appears good, effectiveness can be surprisingly low. Seasonal influenza vaccines also stand out for their variable effectiveness by age group from year to year and by recent vaccination status. These patterns suggest a role for immune history in influenza vaccine effectiveness, but inference is complicated by uncertainty about the contributions of bias to the estimates themselves. In this review, we describe unexpected patterns in the effectiveness of seasonal influenza vaccination and explain how these patterns might arise as consequences of study design, the dynamics of immune memory, or both. Resolving this uncertainty could lead to improvements in vaccination strategy, including the use of universal vaccines in experienced populations, and the evaluation of vaccine efficacy against influenza and other antigenically variable pathogens.
      Cover page: Immune History and Influenza Vaccine Effectiveness
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2018)
      After decades of declining mumps incidence amid widespread vaccination, the United States and other developed countries have experienced a resurgence in mumps cases over the last decade. Outbreaks affecting vaccinated individuals and communities with high vaccine coverage have prompted concerns about the effectiveness of the live attenuated vaccine currently in use. It is unclear whether immune protection wanes or whether the vaccine protects inadequately against currently circulating mumps virus lineages. Synthesizing data from six studies of mumps vaccine effectiveness, we estimated that vaccine-derived immune protection against mumps wanes on average 27 years (95% confidence interval, 16 to 51 years) after vaccination. After accounting for this waning, we found no evidence that the emergence of heterologous virus genotypes contributed to changes in vaccine effectiveness over time. A mathematical model of mumps transmission confirmed the central role of waning immunity to the vaccine in the re-emergence of mumps cases. Outbreaks from 2006 to the present among young adults, and outbreaks in the late 1980s and early 1990s among adolescents, aligned with peaks in mumps susceptibility of these age groups predicted to be due to loss of vaccine-derived protection. In contrast, evolution of mumps virus strains escaping immune pressure would be expected to cause a higher proportion of cases among children, not adolescents and young adults as observed. Routine use of a third vaccine dose at 18 years of age, or booster dosing throughout adulthood, may be a strategy to prevent mumps re-emergence and should be assessed in clinical trials.
        Cover page: Vaccine waning and mumps re-emergence in the United States
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2016)
        Immune heterogeneity in wild host populations indicates that disease-mediated selection is common in nature. However, the underlying dynamic feedbacks involving the ecology of disease transmission, evolutionary processes, and their interaction with environmental drivers have proven challenging to characterize. Plague presents an optimal system for interrogating such couplings: Yersinia pestis transmission exerts intense selective pressure driving the local persistence of disease resistance among its wildlife hosts in endemic areas. Investigations undertaken in colonial India after the introduction of plague in 1896 suggest that, only a decade after plague arrived, a heritable, plague-resistant phenotype had become prevalent among commensal rats of cities undergoing severe plague epidemics. To understand the possible evolutionary basis of these observations, we developed a mathematical model coupling environmentally forced plague dynamics with evolutionary selection of rats, capitalizing on extensive archival data from Indian Plague Commission investigations. Incorporating increased plague resistance among rats as a consequence of intense natural selection permits the model to reproduce observed changes in seasonal epidemic patterns in several cities and capture experimentally observed associations between climate and flea population dynamics in India. Our model results substantiate Victorian era claims of host evolution based on experimental observations of plague resistance and reveal the buffering effect of such evolution against environmental drivers of transmission. Our analysis shows that historical datasets can yield powerful insights into the transmission dynamics of reemerging disease agents with which we have limited contemporary experience to guide quantitative modeling and inference.
          Cover page: Climatic and evolutionary drivers of phase shifts in the plague epidemics of colonial India
          • Thesis
          • Peer Reviewed
          UC Berkeley Electronic Theses and Dissertations (2022)

          Vaccination and non-pharmaceutical interventions (NPIs) have been of central importance to mitigate the ongoing COVID-19 pandemic. In collaboration with California Department of Public Health, I designed and managed a test-negative design case-control study to assess risk factors for SARS-CoV-2 infection and the effectiveness of various mitigation strategies including vaccination and the use of face masks. Throughout the study period, a team of trained interviewers placed over 40,000 telephone calls and enrolled over 4,000 total cases and controls, testing positive and negative for SARS-CoV-2, respectively. In Chapter 1, I present COVID-19 vaccine effectiveness estimates using data collected between February ¬– April 2021 when Epsilon (B.1.427 and B.1.429) and Alpha (B.1.1.7) were the dominant SARS-CoV-2 variants of concern circulating in California. I demonstrate mRNA-based vaccines (BNT-162b2 [Pfizer] and mRNA-1273 [Moderna]) conferred substantial protection against documented SARS-CoV-2 infection. However, nearly one-third of participants expressed reluctance to initiate the COVID-19 vaccination series, primarily due to concerns about vaccine side effects or safety. In Chapter 2, I evaluate predictors of SARS-CoV-2 infection amongst a subset of participants who reported history of social contact with a person confirmed or suspected to have been infected with SARS-CoV-2 within 14 days of testing. Among the unvaccinated, participants had a significantly higher odds of testing SARS-CoV-2 positive when social contact was long-lasting (>3 hours), involved a household member, or occurred indoors. Additionally, in the context of these high-risk exposures, I demonstrate mask wearing was most protective among the unvaccinated or partially unvaccinated. Last, in Chapter 3, I estimate the real-world effectiveness of face masks in reducing the risk of acquiring a SARS-CoV-2 infection in public indoors settings. Participants self-reported their frequency of mask use and the type of mask typically worn in public indoor settings. I found that any mask use in public indoor settings reduced the odds the wearer acquired a SARS-CoV-2 infection and mask use exhibited additional protection with increasing frequency of use. Upgrading face masks to masks with higher filtration capacity (N95/KN95s) conferred additional protection. This work has demonstrated the value of case-control studies to rapidly collect real-time data to address and monitor emerging issues in the COVID-19 pandemic and advance public health policy.

            Cover page: Assessment of public health interventions to mitigate SARS-CoV-2 transmission and risk factors for infection in California
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2022)
            The basic reproduction number, R 0, and its real-time analogue, Rt , are summary measures that reflect the ability of an infectious disease to spread through a population. Estimation methods for Rt  have a long history, have been widely developed and are now enhanced by application to the COVID-19 pandemic. While retrospective analyses of Rt have provided insight into epidemic dynamics and the effects of control strategies in prior outbreaks, misconceptions around the interpretation of Rt have arisen with broader recognition and near real-time monitoring of this parameter alongside reported case data during the COVID-19 pandemic. Here, we discuss some widespread misunderstandings regarding the use of Rt  as a barometer for population risk and its related use as an 'on/off' switch for policy decisions regarding relaxation of non-pharmaceutical interventions. Computation of Rt  from downstream data (e.g. hospitalizations) when infection counts are unreliable exacerbates lags between when transmission happens and when events are recorded. We also discuss analyses that have shown various relationships between Rt  and measures of mobility, vaccination coverage and a test-trace-isolation intervention in different settings.
              Cover page: On the use of the reproduction number for SARS‐CoV‐2: Estimation, misinterpretations and relationships with other ecological measures
              • Article
              • Peer Reviewed
              UC Berkeley Previously Published Works (2019)
              Much of the intellectual tradition of modern epidemiology stems from efforts to understand and combat chronic diseases persisting through the 20th century epidemiologic transition of countries such as the United States and United Kingdom. After decades of relative obscurity, infectious disease epidemiology has undergone an intellectual rebirth in recent years amid increasing recognition of the threat posed by both new and familiar pathogens. Here, we review the emerging coalescence of infectious disease epidemiology around a core set of study designs and statistical methods bearing little resemblance to the chronic disease epidemiology toolkit. We offer our outlook on challenges and opportunities facing the field, including the integration of novel molecular and digital information sources into disease surveillance, the assimilation of such data into models of pathogen spread, and the increasing contribution of models to public health practice. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. These areas represent an increasingly important component of epidemiology training programs for future generations of researchers and practitioners.
                Cover page: Emerging Challenges and Opportunities in Infectious Disease Epidemiology
                • Article
                • Peer Reviewed
                UC Berkeley Previously Published Works (2020)
                  Cover page: Scientific and ethical basis for social-distancing interventions against COVID-19
                  • Article
                  • Peer Reviewed
                  UC Berkeley Previously Published Works (2020)
                  The Institute for Health Metrics and Evaluation model for predicting the course of the coronavirus disease 2019 pandemic has attracted considerable attention, including from the U.S. government. The appearance of certainty of model estimates is seductive when the world is desperate to know what lies ahead, but caution is warranted regarding the validity and usefulness of the model projections for policymakers.
                    Cover page: Caution Warranted: Using the Institute for Health Metrics and Evaluation Model for Predicting the Course of the COVID-19 Pandemic.
                    • Article
                    • Peer Reviewed
                    UC Berkeley Previously Published Works (2020)

                    Background

                    Reduced-dose pneumococcal conjugate vaccine (PCV) schedules are under consideration in countries where children are recommended to receive 3 doses. Whereas PCV-derived protection against vaccine-serotype colonization is responsible for herd effects of vaccination, dose-specific PCV effectiveness against colonization endpoints is not known. We aimed to assess the performance of differing PCV schedules against vaccine-serotype colonization in children.

                    Methods

                    From 2009-2016, we monitored pneumococcal carriage in southern Israel, where children should receive PCV at ages 2 months, 4 months, and 12 months (2 primary [p] +1 booster [b] schedule). We analyzed nasopharyngeal swabs and vaccination histories from 5928 children aged 0-59 months without symptoms of diseases potentially attributable to pneumococci. Matching individuals on age, sex, ethnicity, visit timing, and recent antibiotic receipt, we measured schedule-specific 7-valent PCV (PCV7) and 13-valent PCV (PCV13) effectiveness against vaccine-serotype colonization in a modified case-control framework. We sampled from the distribution of all possible case-control match assignments for statistical analyses.

                    Results

                    Receiving 2 primary-series PCV13 doses conferred 53% (95% confidence interval [CI], 32-67%) protection against PCV13-serotype colonization at ages ≤12 months; 1 primary-series dose was not protective. A 2p+1b PCV13 series conferred 40% (95% CI, 4-67%) and 62% (95% CI, 33-83%) protection against PCV13-serotype colonization at ages 13-24 months and 25-59 months, respectively. Estimates suggested greater PCV13-conferred protection against PCV7-targeted serotypes than the 6 PCV13-only serotypes. As compared to children receiving 2p+1b PCV13 dosing, those receiving 1p+1b and 2p+0b schedules experienced 2.05-fold (95% CI, 1.12-5.00) and 3.33-fold (95% CI, 2.28-4.93) greater odds, respectively, of vaccine-serotype pneumococcal colonization at ages 13-24 months.

                    Conclusions

                    Our results demonstrate real-world effectiveness of 2p+1b PCV dosing against vaccine-serotype colonization. Reduced-dose schedules may confer lower protection against vaccine-serotype carriage during and beyond the first year of life.
                      Cover page: Dose-specific Effectiveness of 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-serotype Streptococcus pneumoniae Colonization in Children.
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