Doctor of Philosophy

dissertationAcute gastroenteritis (AGE) outbreaks present a significant challenge to investigating public health officials, who need to know whether point source transmission - such as contaminated food, fomites, or highly infectious individuals - has occurred to respond effectively. However, information on the mode of transmission is frequently unavailable, especially during the early stages of an outbreak when control measures have the greatest impact. Clinical decision support systems (CDS) may be used to assist outbreak investigators when only limited data are available. This dissertation research investigated a) how the guidelines for norovirus outbreaks in healthcare settings vary between state public health agencies across the U.S., b) how mathematical modeling can be used to help outbreak investigators identify potential point source outbreaks, and c) how availability of outbreak information impacts public health decision-making. After introductory material in Chapters 1 and 2, Chapter 3 describes variation in norovirus outbreak guidelines and outcomes between states. Chapter 4 describes the development of a stochastic individual-level mathematical model for predicting whether an outbreak was likely caused by point source transmission. The model's internal and external validity were assessed, and the model was used to estimate potential misclassification in outbreaks reported to have been transmitted person-to-person. Chapter 5 describes semi-structured interviews with AGE epidemiologists about decision-making in hypothetical outbreak scenarios based on different levels of data availability, including results from a CDS based on the mathematical model. There was substantial variation in state healthcare-associated norovirus outbreak response guidelines, and there were differences between states with and without guidelines consistent with national guidance. The model performed well on measures of internal and external validity, and 73% of person-to-person norovirus outbreaks had at least some evidence of point source transmission. AGE epidemiologists drew different conclusions when presented with different levels of information, and there was evidence that CDS could help improve decision-making when only minimal data are available. These results demonstrate the need for CDS for transmission mode classification, the effectiveness of mathematical modeling for outbreak response decision support in some circumstances, and the potential for CDS to improve decision-making when data are sparse and public health action is required

Early Estimation of the Basic Reproduction Number Using Minimal Outbreak Data

The basic reproduction number is a fundamental measure used to characterize infectious disease outbreaks. A modification to a previous approach is proposed that allows estimates to be obtained earlier in an outbreak using only the current case count, number currently ill, and the size of the at-risk population. This approach was tested using a mathematical model and appears to yield valid estimates of the basic reproduction number within a reasonable margin of error

Inducing Herd Immunity against Seasonal Influenza in Long-Term Care Facilities through Employee Vaccination Coverage: A Transmission Dynamics Model

Introduction. Vaccinating healthcare workers (HCWs) in long-term care facilities (LTCFs) may effectively induce herd immunity and protect residents against influenza-related morbidity and mortality. We used influenza surveillance data from all LTCFs in New Mexico to validate a transmission dynamics model developed to investigate herd immunity induction. Material and Methods. We adjusted a previously published transmission dynamics model and used surveillance data from an active system among 76 LTCFs in New Mexico during 2006-2007 for model validation. We used a deterministic compartmental model with a stochastic component for transmission between residents and HCWs in each facility in order to simulate the random variation expected in such populations. Results. When outbreaks were defined as a dichotomous variable, our model predicted that herd immunity could be induced. When defined as an attack rate, the model demonstrated a curvilinear trend, but insufficiently strong to induce herd immunity. The model was sensitive to changes in the contact parameter β but was robust to changes in the visitor contact probability. Conclusions. These results further elucidate previous studies’ findings that herd immunity may not be induced by vaccinating HCWs in LTCFs; however, increased influenza vaccination coverage among HCWs reduces the probability of influenza infection among residents

The role of kyphoplasty in the management of osteogenesis imperfecta: risk or benefit?

Kyphoplasty is a recognized treatment option in the management of symptomatic osteoporotic compression fractures, osteolytic vertebral metastases or haemangioma. To our knowledge, kyphoplasty with polymethylmethacrylate in a patient with type I osteogenesis imperfecta (OI) and a vertebral compression fracture has not been reported so far. We report on a 58-year-old patient with type I OI and a vertebral compression fracture at L2 with undislocated posterior vertebral wall and an additional older L1 fracture. Because of severe back pain resistant to conservative therapy over 5 months the indication for percutaneous kyphoplasty was made. Preoperative adjacent endplates of L2 were nearly parallel. Radiologically a minimal loss of height of the L2 vertebra was seen without adjacent fractures at 9 months follow-up. A slight increase of the preoperative kyphotic angle of overlying vertebrae L1 (8.7°/10.3°) and T12 (10.4°/11.0°) was apparent. The visual analogue scale showed decrease of low back pain from 10 to 2 allowing mobilization with a walking frame. Kyphoplasty constitutes a minimal invasive therapeutic alternative in the treatment of vertebral fractures in type I OI and pain, resistant to conservative treatment. Similar to the results of osteoporotic fractures the immediate reduction of pain and stabilization of the fracture in undislocated fragments can be achieved. No adjacent fractures occurred 9 months postoperatively after kyphoplasty in type I OI. Preoperative parallelism of the endplates seems to protect from adjacent fractures