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Scholarly Works (2244 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2014)

Immunization has proven to be one of the most cost-effective public health interventions to date. Not only has immunization saved millions of lives, but it has also protected children from severe illness and life-changing disability. Measles, which had once been a significant childhood killer, is now targeted for elimination. Worldwide measles vaccination has led to a 71% decrease in measles-related deaths and an 88% reduction the World Health Organization African Region (WHO-AFRO) alone. In the Democratic Republic of Congo (DRC), measles immunization has had a profound effect on reducing childhood mortality; however, beginning in 2010 large-scale measles outbreaks threatened past successes. Suspected case counts increased dramatically. This was mainly attributed to a weak routine immunization system and missed supplementary immunization activities. This dissertation aims to inform the improvement and further development of the immunization program in DRC by assessing measles immunization effects, vaccine effectiveness, and compares the cost-effectiveness of different immunization strategies. Chapter 1 is a brief introduction to measles immunization worldwide and in DRC. Chapter 2 is based on measles surveillance data from the Integrated Disease Surveillance and Response (IDSR) and demonstrated that measles immunization, in particular mass campaigns are extremely effective in DRC. Chapter 3 utilized case-based surveillance data with laboratory confirmation to estimate measles vaccine effectiveness. Finally, chapter 4 further solidifies the importance of mass campaigns in DRC until routine immunization is further strengthened through a cost-effectiveness analysis of three different vaccination strategies.

    Cover page: Assessing trends in measles epidemiology, immunization coverage, vaccine efficacy, and cost-effectiveness to identify practical strategies for measles elimination in the Democratic Republic of Congo
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    • Peer Reviewed
    UC Davis Previously Published Works (2018)
    BACKGROUND: New methods to increase measles and rubella (MR) vaccination coverage are needed to achieve global and regional MR elimination goals. METHODS: Here, we developed microneedle (MN) patches designed to administer MR vaccine by minimally trained personnel, leave no biohazardous sharps waste, remove the need for vaccine reconstitution, and provide thermostability outside the cold chain. This study evaluated the immunogenicity of MN patches delivering MR vaccine to infant rhesus macaques. RESULTS: Protective titers of measles neutralizing antibodies (>120 mIU/mL) were detected in 100% of macaques in the MN group and 75% of macaques in the subcutaneous (SC) injection group. Rubella neutralizing antibody titers were >10 IU/mL for all groups. All macaques in the MN group were protected from challenge with wild-type measles virus, whereas 75% were protected in the SC group. However, vaccination by the MN or SC route was unable to generate protective immune responses to measles in infant macaques pretreated with measles immunoglobulin to simulate maternal antibody. CONCLUSIONS: These results show, for the first time, that MR vaccine delivered by MN patch generated protective titers of neutralizing antibodies to both measles and rubella in infant rhesus macaques and afforded complete protection from measles virus challenge.
      Cover page: A Microneedle Patch for Measles and Rubella Vaccination Is Immunogenic and Protective in Infant Rhesus Macaques.
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2020)
      Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. Although it is broadly accepted that this also applies to measles, the exact date of emergence for this disease is controversial. We sequenced the genome of a 1912 measles virus and used selection-aware molecular clock modeling to determine the divergence date of measles virus and rinderpest virus. This divergence date represents the earliest possible date for the establishment of measles in human populations. Our analyses show that the measles virus potentially arose as early as the sixth century BCE, possibly coinciding with the rise of large cities.
        Cover page: Measles virus and rinderpest virus divergence dated to the sixth century BCE
        • Thesis
        • Peer Reviewed
        UCLA Electronic Theses and Dissertations (2017)

        Measles is a highly contagious viral disease, and infection can result in severe symptoms, complications, and both acute and prolonged immunologic effects. The Democratic Republic of the Congo (DRC) is a resource poor and measles endemic country. Limited health care services, poor nutrition, and high levels of infectious disease, as found in the DRC, make host immune function of crucial public health importance. In addition to assessing vaccination coverage and seroprotective antibody levels, identifying and quantifying the immunologic impact of measles vaccination and disease on child health outcomes can provide valuable recommendations for public health policy and practice. The overall aim of this dissertation is twofold. First, this dissertation seeks to describe measles vaccination coverage and seroprotective levels of measles antibody in DRC and examine factors that may contribute to the large proportion of children with inadequate immunity. Second, it aims to assess associations of both measles vaccination and disease with markers of infectious disease (acute fever, cough, and diarrhea outcomes). Chapter 1 is a brief overview of measles vaccination and disease pathogenesis. Chapter 2 examines predictors of measles vaccination coverage in the DRC and describes characteristics of children who are least reached by routine measles immunization efforts. Chapter 3 utilizes a causal mediation model to quantify the impact of measles vaccination on acute fever, cough, and diarrhea outcomes. Chapter 4 describes measles antibody seroprevalence among vaccinated and unvaccinated children and identifies trends in inadequate immunization. Finally, Chapter 5 explores the immunologic impact of measles on child health outcomes by examining the association of previous measles infection with acute fever, cough, and diarrhea episodes.

          Cover page: Assessing immune response to measles vaccination and infection among children in the Democratic Republic of the Congo
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2016)

          Background

          When caring for measles patients, N95 respirator use by healthcare workers (HCWs) with documented immunity is not uniformly required or practiced. In the setting of increasingly common measles outbreaks and provider inexperience with measles, HCWs face increased risk for occupational exposures. Meanwhile, optimal infection prevention responses to healthcare-associated exposures are loosely defined. We describe measles acquisition among HCWs despite prior immunity and lessons from healthcare-associated exposure investigations during a countywide outbreak.

          Methods

          Primary and secondary cases, associated exposures, and risk factors were identified during a measles outbreak in Orange County, California from, 30 January 2014 to 21 April 2014. We reviewed the effect of different strategies in response to hospital exposures and resultant case capture.

          Results

          Among 22 confirmed measles cases, 5 secondary cases occurred in HCWs. Of these, 4 had direct contact with measles patients; none wore N95 respirators. Four HCWs had prior evidence of immunity and continued working after developing symptoms, resulting in 1014 exposures, but no transmissions. Overall, 13 of 15 secondary cases had face-to-face contact with measles patients, 8 with prior evidence of immunity.

          Conclusions

          HCWs with unmasked, direct contact with measles patients are at risk for developing disease despite evidence of prior immunity, resulting in potentially large numbers of exposures and necessitating time-intensive investigations. Vaccination may lower infectivity. Regardless of immunity status, HCWs should wear N-95 respirators (or equivalent) when evaluating suspected measles patients. Those with direct unprotected exposure should be monitored for symptoms and be furloughed at the earliest sign of illness.
            Cover page: Healthcare Workers and Post-Elimination Era Measles: Lessons on Acquisition and Exposure Prevention
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2019)
            BACKGROUND:Depression can impair the immunogenicity of vaccine administration in adults. Whereas many vaccinations are administered in childhood, it is not known whether adolescent or adult onset depression is associated with impairments in the maintenance of protection of childhood vaccines. This study tested the hypothesis that individuals with adolescent or adult onset mood disorders would display compromised immunity to measles, a target of childhood vaccination. METHODS:IgG antibodies to measles were quantified using a solid phase immunoassay in volunteers with bipolar disorder (BD, n = 64, mean age of onset = 16.6 ± 5.6), currently depressed individuals with major depressive disorder (cMDD, n = 85, mean age of onset = 17.9 ± 7.0), remitted individuals with a history of MDD (rMDD, n = 82, mean age of onset = 19.2 ± 8.6), and non-depressed comparison controls (HC, n = 202), all born after the introduction of the measles vaccine in the USA in 1963. RESULTS:Relative to HC, both the cMDD group (p = 0.021, adjusted odds ratios (OR) = 0.47, confidence interval (CI) = 0.24-0.90), and the rMDD group (p = 0.038, adjusted OR = 0.50, CI = 0.26-0.97) were less likely to test seropositive for measles. Compared with unmedicated MDD participants, currently medicated MDD participants had a longer lifetime duration of illness and were less likely to test seropositive for measles. CONCLUSIONS:Individuals with adolescent or adult onset MDD are less likely to test seropositive for measles. Because lower IgG titers are associated with increased risk of measles infection, MDD may increase the risk and severity of infection possibly because of impaired maintenance of vaccine-related protection from measles.
              Cover page: Reduced immunity to measles in adults with major depressive disorder
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2012)
              In 2010, an expert advisory panel convened by the World Health Organization to assess the feasibility of measles eradication concluded that (1) measles can and should be eradicated, (2) eradication by 2020 is feasible if measurable progress is made toward existing 2015 measles mortality reduction targets, (3) measles eradication activities should occur in the context of strengthening routine immunization services, and (4) measles eradication activities should be used to accelerate control and elimination of rubella and congenital rubella syndrome (CRS). The expert advisory panel also emphasized the critical role of research and innovation in any disease control or eradication program. In May 2011, a meeting was held to identify and prioritize research priorities to support measles and rubella/CRS control and potential eradication activities. This summary presents the questions identified by the meeting participants and their relative priority within the following categories: (1) measles epidemiology, (2) vaccine development and alternative vaccine delivery, (3) surveillance and laboratory methods, (4) immunization strategies, (5) mathematical modeling and economic analyses, and (6) rubella/CRS control and elimination.
                Cover page: Research priorities for global measles and rubella control and eradication
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                • Peer Reviewed
                Clinical Practice and Cases in Emergency Medicine, Volume 5, Issue 2 (2021)

                Introduction: Local outbreaks of measles infection are primarily mediated by international travel of persons from endemic areas, with subsequent spread of the virus via undervaccinated populations. Recent resurgences of measles in communities where vaccination rates are non-ideal secondary to philosophical objections require the emergency physician to more routinely consider the diagnosis. In cases of measles complicated by acute encephalitis or encephalopathy, the diagnosis can be especially difficult to make due to lack of a reliable primary historian.

                Case report: Here we present a case of altered mental status and new-onset bilateral lower extremity weakness in a fully vaccinated young woman diagnosed with measles infection caused by acute disseminated encephalomyelitis in the setting of vaccine failure.

                Conclusion: Despite a documented history of immunization, acute measles infection and its uncommon sequelae are possible. Recognizing vaccine failure and appropriately isolating patients are of paramount importance.

                  Cover page: Acute Demyelinating Encephalomyelitis Following Measles Infection Due to Vaccine Failure: A Case ReportCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2016)
                  Using a mathematical model with realistic demography, we analyze a large outbreak of measles in Muyinga sector in rural Burundi in 1988-1989. We generate simulated epidemic curves and age × time epidemic surfaces, which we qualitatively and quantitatively compare with the data. Our findings suggest that supplementary immunization activities (SIAs) should be used in places where routine vaccination cannot keep up with the increasing numbers of susceptible individuals resulting from population growth or from logistical problems such as cold chain maintenance. We use the model to characterize the relationship between SIA frequency and SIA age range necessary to suppress measles outbreaks. If SIAs are less frequent, they must expand their target age range.
                    Cover page: A post-honeymoon measles epidemic in Burundi: mathematical model-based analysis and implications for vaccination timing.Creative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2019)
                    Social media posts regarding measles vaccination were classified as pro-vaccination, expressing vaccine hesitancy, uncertain, or irrelevant. Spearman correlations with Centers for Disease Control and Prevention-reported measles cases and differenced smoothed cumulative case counts over this period were reported (using time series bootstrap confidence intervals). A total of 58,078 Facebook posts and 82,993 tweets were identified from 4 January 2009 to 27 August 2016. Pro-vaccination posts were correlated with the US weekly reported cases (Facebook: Spearman correlation 0.22 (95% confidence interval: 0.09 to 0.34), Twitter: 0.21 (95% confidence interval: 0.06 to 0.34)). Vaccine-hesitant posts, however, were uncorrelated with measles cases in the United States (Facebook: 0.01 (95% confidence interval: -0.13 to 0.14), Twitter: 0.0011 (95% confidence interval: -0.12 to 0.12)). These findings may result from more consistent social media engagement by individuals expressing vaccine hesitancy, contrasted with media- or event-driven episodic interest on the part of individuals favoring current policy.
                      Cover page: Facebook and Twitter vaccine sentiment in response to measles outbreaks
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