Physical activity guidelines encouraging activity among healthy pregnant women have been issued by the Centers for Disease Control and Prevention, yet Latina women remain more sedentary than non-Latina white women. Latina women are also at higher risk for gestational diabetes mellitus and, among Latina women, Puerto Rican women have the highest rates of low birth weight and preterm-related infant death. This dissertation utilized data from the Latina GDM study, a prospective cohort study of 1,231 Latina women recruited early in pregnancy and followed through delivery. Participants were interviewed in early and mid pregnancy for assessment of sociodemographics, acculturation, medical, and behavioral factors, in addition to administration of the Kaiser Physical Activity Survey for assessment of physical activity and sedentary behaviors. Birth outcomes were abstracted from medical records following delivery. In the first chapter, we assessed the prevalence of three health behaviors (meeting physical activity guidelines, meeting fruit/vegetable consumption guidelines, and cigarette smoking) in early and mid pregnancy and identified multiple factors associated with meeting health behavior guidelines in pregnancy. In the second chapter, we examined participation in sedentary behaviors, such as time spent TV watching, sitting at work, and low levels of sports and exercise, in pre, early and mid pregnancy in relation to maternal glucose intolerance and gestational diabetes mellitus. In the final chapter, we analyzed four types of physical activity (sports/exercise, household/caregiving, occupational, and active transportation) as well as total activity in relation to risk of preterm birth and small-for-gestational age. Findings represent the first study of physical activity and maternal/fetal outcomes conducted exclusively among Latina women, a group largely understudied in epidemiologic research. Results will guide culturally specific intervention programs in this high risk population.

Hypertensive disorders of pregnancy affect approximately 8% of pregnancies, and can lead to serious complications for both mother and child. While Latinas are at two-fold increased risk of preeclampsia relative to non-Latina white women, little research on hypertension in pregnancy has been conducted in this population. Furthermore, there are few modifiable risk factors for hypertensive pregnancy. Therefore, we examined associations between psychosocial stress, physical activity, and pre-pregnancy BMI and gestational weight gain and hypertensive disorders of pregnancy using data from the Latina GDM Study, a prospective cohort study of 1,231 women. The first study evaluated the association between perceived stress in early pregnancy and hypertensive disorders of pregnancy. Prior studies suggest an increased risk of hypertensive pregnancy associated with high levels of work-related stress, however there is no previous research evaluating the impact of general psychosocial stress. Psychosocial stress was measured in early pregnancy through the Perceived Stress Scale and hypertensive disorders of pregnancy were confirmed through obstetrician review of medical records. Using multivariable logistic regression we found no statistically significant association between early pregnancy stress and hypertensive pregnancy. The second study focused on the association between pre- and early pregnancy physical activity and hypertensive pregnancy. While some prior literature suggests that pre- and early pregnancy physical activity may be inversely associated with hypertensive pregnancy, findings are not conclusive. Pre- and early pregnancy physical activity was quantified using the Kaiser Physical Activity Survey, administered early in pregnancy. In this study, there was no statistically significant association between pre-pregnancy physical activity and hypertensive pregnancy. However, early pregnancy physical activity (total and household/caregiving) was inversely associated with risk of gestational hypertension. Finally, we examined the associations between pre-pregnancy BMI and gestational weight gain and hypertensive pregnancy. Previous studies in this area have included few Latinas. We found an increase in risk of hypertensive disorders with increased pre-pregnancy BMI and gestational weight gain exceeding the current Institute of Medicine guidelines for weight gain in pregnancy. These findings extend prior research to a Latina population. In summary, this dissertation research adds to the limited research on modifiable risk factors for hypertensive disorders of pregnancy.

<p> Anaphylaxis is a potentially life-threatening systemic allergic reaction [1]. We aimed to determine the overall anaphylaxis incidence rate, the incidence of specific causes of anaphylaxis over time, and epinephrine auto-injector prescribing trends in Olmsted County, Minnesota. </p><p> Using the resources of the Rochester Epidemiology Project, a comprehensive records linkage system, we performed a population-based incidence study in Olmsted County, Minnesota, from 2001 through 2010. All cases with a diagnosis of anaphylactic shock and 20% of cases diagnosed with venom/bee sting, food allergy, and medication reactions were manually reviewed. Anaphylaxis incident cases were required to meet the National Institute of Allergy and Infectious Disease / Food Allergy and Anaphylaxis Network (NIAID/FAAN) diagnostic criteria. We also extracted all outpatient epinephrine prescriptions for all Olmsted County residents during 2003-2010 to further explore treatment of anaphylaxis. The sampling faction was accounted for in determining the reported number of anaphylaxis incidence cases. Incidence rates per 100,000 person-years were calculated using the adjusted number of incident cases of anaphylaxis (and likewise the number patients with a prescription) as the numerator and age- and sex-specific counts of the population of Olmsted County as the denominator. The relationships of age group, sex, and year of anaphylaxis with incidence rates were assessed by fitting Poisson regression models using the SAS procedure GENMOD. </p><p> We identified six hundred and thirty-one cases of anaphylaxis (51% male). The median age was 31 years (interquartile range 19-44). Incidence rates differed by year of diagnosis (p&lt;0.001) and by age group (p&lt;0.001). The overall age- and sex-adjusted incidence rate was 42 (95%CI 38.7 - 45.3) per 100,000 person-years. Four hundred and sixty eight cases (74%) of anaphylaxis were evaluated in the emergency department, 71 cases (11%) were admitted to the emergency department observation unit, and 92 cases (15%) were admitted to the hospital. Prescription data showed that the overall age- and sex-adjusted incidence rate of epinephrine prescriptions was 330 per 100,000 person-years (95% CI 320-340). Age-adjusted incidence rates for women and men were 369 (95% CI 354-385) and 288 (95% CI 274-302) per 100,000 person-years, respectively. Prescription incidence rates differed by year of diagnosis (p&lt;0.001), age group (p&lt;0.001), and sex (p&lt;0.001). The incidence rate of outpatient prescription decreased by year during 2003-2005 then became constant during 2005-2010. </p><p> Our master&rsquo;s degree thesis concludes that the overall anaphylaxis incidence rate was 42 per 100,000 person-years during 2001-2010 in the Olmsted County. The food, venom, and medication were the leading causes for anaphylaxis for younger age, middle age and the elderly, respectively. The majority of anaphylaxis cases were treated in the emergency department. The incidence rate of outpatient epinephrine prescriptions, which was 330 per 100, 000 person-years, decreased from 2003-2005 and reached plateau. Our study used updated diagnostic criteria for anaphylaxis and epinephrine prescription to demonstrate the flattening of the incidence. We would like to emphasize the clinicians to be aware of trend of anaphylaxis and supply of epinephrine in the community.</p>

Includes bibliographical references (p. 245-252). / The population of this study is a subset of the Tees Stroke Register population. The patients were all residents of the area, had their first ever in their lifetime stroke and were not inpatients in hospital at the time or stroke onset. I have written the protocols and documented all the t1owcharts. These underwent numerous drafts with reviews and input by all the study team members and supervisors. I have personally seen, consented and clinically assessed over 1200 patients out of the total of the 1898 recorded and confirmed stroke events. In addition, 1 have reviewed almost all the over 9000 suspected stroke notifications to the stroke register (this usually involved reviewing the patients medical records and / or assessing them). I have reviewed death certificate data, and where needed patients records, of all participants in the study. 1 managed and supervised the day-to-day activities of the research team, helped prepare regular feedback pamphlets detailing the progress of the study, presented progress reports to the study supervisors and presented interim findings at national and international meetings. I have undertaken the basic analyses (odds ratios etc) myself. I have required extensive assistance from the study database supervisor (who also checked my results) for the other and more complex analyses (multivariate regression etc). Dr Nick Steen, statistician for the Centre for Health Services Research, University of Newcastle assisted and guided the performance and interpretation of the basic and logistical regression analyses. My supervisor has reviewed this script and advised modifications and amendments.

Thesis (Ph.D.)--University of Western Australia, 2007.

Calves are born agammaglobulinemic and rely on colostrum consumption for the transfer of maternal passive immunity. Calves that fail to absorb adequate amounts of maternal antibodies from colostrum are commonly referred to as having failed transfer of passive immunity (FTPI). The overall aim of this dissertation was to explore the usefulness of FTPI testing in neonatal beef calves to predict their risk for subsequent illness or death. The objectives were to evaluate the impact of FTPI on pre-weaning disease in beef and dairy calves, quantify and compare the variance in IgG concentrations measured by radial immunodiffusion and serum total protein (STP) values measured by optical refractometry, and evaluate the correlation between herd-level prevalence of FTPI and herd-level prevalence of pre-weaning disease in beef calves. Evaluation of literature relevant to FTPI was compiled and assessed to quantify the impact of FTPI on pre-weaning disease in beef and dairy calves. A series of randomized trials were used to evaluate the variance in IgG concentrations and STP values from banked serum. Health records from multiple farms and IgG results were used to evaluate the relationship between FTPI and disease at the individual and herd-level. Failed transfer of passive immunity had a variable association with pre-weaning disease in beef and dairy calves. IgG concentrations were less precise than STP values especially when dilution was required. IgG concentrations and STP values were associated with an increased risk of disease in pre-weaned beef calves, but FTPI cut-off values poorly classified the risk for subsequent disease. The proportion of calves with FTPI was not correlated with the proportion of calves that developed pre-weaning disease. Using a single immunological factor, such as IgG concentration or STP, to predict disease results in the misclassification of disease risk and does not consider additional component causes of disease.

Plasmodium vivax malaria threatens nearly half the world’s population. This relapsing disease may be more severe than previously recognised and is proving refractory to current malaria control measures. This thesis aimed to describe the burden of anaemia and mortality attributable to vivax malaria in Southern Papua, Indonesia, an area endemic for multidrug-resistant P. vivax and P. falciparum, and to determine the potential of currently available antimalarial drugs to reduce transmission of P. vivax in co-endemic regions. Approximately 0.5 million uniquely identified clinical records from patients presenting to Mitra Masyarakat Hospital between April 2004 and May 2009 were matched with corresponding laboratory and pharmacy data in order to determine the burden of anaemia in the hospital setting and the effectiveness of primaquine prescription for preventing P. vivax relapses. Clinical information extracted from patient notes was used to clarify the contribution of P. vivax malaria to a series of deaths detected by an active hospital-based surveillance system. Additional secondary sources of data used in this thesis included a large house-to-house survey and multiple clinical trials of antimalarial therapy from both Southern Papua and Northwestern Thailand. In Southern Papua, P. vivax malaria is an important cause of haematological morbidity both in the hospital and community setting. This morbidity is most significant in the first year of life when P. vivax infection accounts for 23% of all severe anaemia (haemoglobin <5g/dL) in the hospital and approximately 28% of all moderate-to-severe anaemia (haemoglobin <7g/dL) in the community. In this region concomitant P. vivax infection accentuates haematological impairment associated with P. falciparum malaria. Plasmodium vivax in Southern Papua rarely causes death directly but rather indirectly contributes to mortality through exacerbation of comorbid conditions. In Northwestern Thailand, 53.8% of patients with falciparum malaria who were treated with a rapidly eliminated drug between 1991 and 2005 had a recurrence of vivax malaria within two months making P. vivax infection the most common cause of parasitological failure in these individuals. Slowly eliminated artemisinin combination therapies (ACT) provided the greatest protection against recurrent P. vivax parasitaemia during 63 days of follow-up. In three randomised controlled trials from Papua and Thailand, P. vivax gametocytaemia was shown to mirror asexual parasitaemia closely and to have the same characteristics in acute and recurrent infections. This emphasises that the most important chemotherapeutic means of blocking P. vivax transmission is prevention of future relapse. Primaquine is recommended for this purpose but analyses in this thesis suggest that in Southern Papua, unsupervised primaquine at a dose of 0.5mg/kg/day for 14 days, does not reduce the risk of subsequent relapse (Adjusted Hazard Ratio = 1.01 [95% confidence interval 0.95-1.07]). Plasmodium vivax malaria should not be neglected. High priority must be given to new hypnozoitocidal drug discovery. In the interim, optimising the safety and effectiveness of primaquine and adoption of a unified ACT-based blood schizontocidal treatment strategy for malaria of any parasitological cause in co-endemic regions will be crucial for controlling P. vivax malaria.

Most in-hospital deaths secondary to infections in under-five deaths within sub-Saharan Africa (SSA) occur in the initial 24 hours of admission and shock has been identified as a major risk factor for the early deaths. However, controversies exist on the appropriate clinical diagnosis of shock, choice of ideal fluid for resuscitation (crystalloid or colloid), and safety of fluid resuscitation in severe malnutrition or severe malaria. This thesis investigates these aspects and also reviews the evidence base of current paediatric fluid resuscitation guidelines for children (aged >60 days and ≤12 years) with severe febrile illnesses. Capillary refill time >2 seconds, weak pulse volume, or bradycardia, in the presence of abnormal temperature and severe disease are predictive of impaired perfusion (defined by lactic acidosis) and death. Tachycardia and temperature gradient are neither associated with increased risk of death nor predictive of hypoperfusion. Existing international definitions of shock have low sensitivities (FEAST=44%, WHO=2%, and ACCM=59%) and high specificities (FEAST=82%, WHO=100%, and ACCM=66%) for diagnosis of impaired perfusion. Clinical criteria derived (called derived shock) had a sensitivity of 30% and specificity of 93%. Shock in children with severe febrile illnesses in Kilifi has a complex presentation but mainly presents with hyperdynamic circulation (high cardiac index) and vasodilatation. Cases with low cardiac index (myocardial dysfunction) are relatively rare but increase the risk of mortality when present. Synthetic colloids (gelofusine, hydroxyethyl starch 130/0.4 (HES), and dextran 70) are safe for use in fluid resuscitation in children with severe malaria. However, HES is the most promising compared to other synthetic colloids concerns still remain about its renal safety. However, further evaluation of synthetic colloids for treatment of shock is not warranted due to the findings of FEAST trial. A Pilot trial shows that bolus isotonic fluids are safe, have better efficacy, and produce faster resolution of shock compared to low-sodium solutions at volumes and rates recommended by WHO in children with severe malnutrition. Evidence available from all ten the trials in children with sepsis show that fluid resuscitation using crystalloids and colloids result in similar survival. However, fluid bolus resuscitation results in increased mortality compared to no bolus (control) in children in SSA. This finding excludes children with gastroenteritis, trauma, burns, and malnutrition. Colloids are better than crystalloids for severe dengue shock but both have similar efficacy in moderate dengue shock.

Lyme disease (LD) is the most prevalent vector borne disease is North America with 300,000-600,000 human cases each year. Preventative strategies for LD in humans are poorly developed and largely inadequate. While preventive vaccines for LD are widely used in veterinary medicine, there are no vaccines available for use in humans. The goal of this study was to develop a human vaccine that can elicit antibody responses that kill spirochetes in both the tick and mammalian environments. The approach applied in this study centered on the development of chimeric epitope proteins, referred to as chimeritopes. Chimeritopes consist of a series of epitopes derived from one or more proteins or protein variants. Three chimeritope proteins designated as Chv1, Chv2 and Chv3 were designed. These proteins harbor the same set of 18 linear epitopes derived from 9 different OspC type proteins. They differ in epitope arrangement or by the presence or absence of linkers between specific protein segments. The immunogenicity of each protein was assessed in multiple animal models including mice, rats, and purpose bred beagles. Immunoblot, ELISA, and IFA analyses using sera from immunized animals demonstrated that the Chv proteins elicit IgG responses that recognize a diverse array of OspC type proteins. Anti-Chv and anti-OspA antisera displayed complement dependent bactericidal activity. To assess protective efficacy, purpose bred beagles were immunized with each vaccine formulation and then challenged by infestation with infected ticks. Efficacy was assessed by monitoring seroconversion, cultivation of tissue biopsies, clinical presentation and histopathological analysis of joints and tissues. All dogs vaccinated with the Chv2-OspA combination were fully protected. All dogs in this group were seronegative for LD, biopsy culture negative and did not develop LD associated symptoms including lameness or lesions in tissues or joints. In light of market concerns centered on the use of full length OspA in a human vaccine, epitope mapping was performed to identify a linear epitope that could be employed in development of a possible OspC-OspA chimeritope. A linear epitope, designated as OspA221-240was identified. Antisera to KLH-OspA221-240displayed potent and broad bactericidal activity. Interestingly, the OspA221-240epitope has homology to residues 244 to 263 of OspB suggesting that OspB may also be a potential candidate for inclusion in a human vaccine. This study establishes proof of principle for the use of OspC chimeritopes in LD subunit vaccines and highlights the need to employ a multi-valent, multi-antigen vaccine approach in development of a human LD vaccine.

Malignant catarrhal fever (MCF) is a lymphoproliferative and inflammatory syndrome affecting primarily ruminant species. The disease, which is often fatal, is most often described as affecting bovids and cervids. No vaccines are available for prevention of MCFV infection. The primary method to control spread of disease is to prevent contact between carriers and clinically susceptible species. There is no known method to control infection of malignant catarrhal fever virus-white-tailed deer variant (MCFV-WTD), as the carrier animal of this virus is unknown. To determine the prevalence of malignant catarrhal fever viruses in Tennessee ruminant populations, blood and/or lymph node samples were collected from farms, animal processing and disposal facilities, and hunter check-in stations from 2006-2008 from several species of animals including cervids, cattle, and goats. Strain-specific real time PCR was developed to detect ovine herpesvirus-2 (OvHV-2), caprine herpesvirus-2 (CpHV-2), and MCFV-WTD DNA. MCFV DNA was detected in all species of ruminants sampled. Although disease related to infection with MCFV-WTD and CpHV-2 has not been reported in Tennessee cattle or cervid populations, MCFV-WTD DNA was detected in 3 percent of cervid samples, and MCFV-WTD and CpHV-2 DNA was detected in 27 and 3 percent respectively of cattle samples from animal disposal facilities that process dead or debilitated animals. One hunter harvested deer (n=781) and 25 cattle (n=165) tested from animal disposal facilities were positive for OvHV-2 DNA. This study demonstrated that healthy cattle and cervids can be infected with OvHV-2 and MCFV-WTD without apparent disease, and dead or debilitated cattle were infected with OvHV-2, MCFV-WTD and CpHV-2 at a higher percentage than healthy herd animals. Prevalence of CpHV-2 in Tennessee goat populations (7%) was significantly lower than reported in other goat populations (73%). Low prevalence of CpHV-2 in Tennessee goat populations likely explains why no evidence of infection was found in cervids tested, and the low prevalence of CpHV-2 infection in dead or debilitated cattle compared to prevalence of infection with OvHV-2 and MCFV-WTD. The discovery of infection in cattle with CpHV-2 and MCFV-WTD opens a new avenue of investigation into the pathology and virulence of MCFV’s in domestic cattle.