Despite the World Health Organization identifying pregnant women as the highest priority group for seasonal influenza vaccination, many pregnant women remain unaware of the recommendation and have substantial concerns about the adverse effects of the vaccine on them and their unborn foetuses. Few interventions have been conducted to improve influenza vaccine uptake among pregnant women. Among these studies, the results are inconsistent and the quality is generally low. Brief education has been previously shown to improve women’s health practices during pregnancy. An open-label randomized control trial was conducted to assess the effect of providing brief education on influenza vaccine uptake among pregnant women. A total of 163 unvaccinated pregnant women in at least their second trimester were recruited from antenatal clinics of four public hospitals in Hong Kong. They were randomized to receive standard care or a one-to-one brief education session that provided an overview of the safety and benefits of the vaccine to both pregnant women and their foetuses. Participants were followed up by telephone at two to three weeks postpartum to ascertain vaccination status. The primary study outcome was the influenza vaccine uptake rate and the second study outcomes were the proportion of participants initiating discussion about influenza vaccine with their health care providers, the proportion attempting to be vaccinated, and their knowledge of influenza infection and vaccination. A total of 163 participants were recruited with 155 (95%) participants completing follow-up. The overall influenza vaccine uptake rate was 17.8%. When compared with those receiving standard care, the vaccination rate was higher among participants who received the intervention (23.5% vs. 12.2%; p=0.06). In addition, the increase in the rate of self-initiated discussion with HCPs before and after the intervention was significantly higher in intervention group (26.7% vs. 9.3%; p<0.001) but not in standard care group (13.3% vs. 8%; p=0.481). Among participants who did not receive influenza vaccine, pregnant women in intervention group were substantially more likely to have made an unsuccessful attempt to be vaccinated (39.3% vs. 9.2%; p<0.001). Almost one-third of the pregnant women who had attempted to receive the vaccine (n=13) reported they received advice against vaccination during pregnancy from HCPs. If participants had not been advised against influenza vaccine and were successfully vaccinated, the overall difference in the vaccine uptake rate between the two treatment groups would have been statistically significant (34.6% vs. 18.3%; p=0.02). Brief education can be one strategy to improve vaccination uptake rates among pregnant women. In addition, it is clear from this and other studies that recommendations from HCPs substantially influence vaccination behaviours among pregnant women, both positively and negatively. Therefore, multicomponent approaches should be considered in future vaccination programmes and the synergistic effect of both brief education and HCP recommendations should be further evaluated. / published_or_final_version / Nursing Studies / Master / Master of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Zoology / Master / Master of Philosophy

published_or_final_version / Zoology / Master / Master of Philosophy

Syfte: Syftet med denna studie var att undersöka om oral administrering av två milliliter 30 % glukos har någon smärtlindrande effekt vid vaccination mot mässling, påssjuka och röda hund [MPR]. Metod: Urvalsgruppen bestod av 18 månader gamla barn som besökte Samariterhemmet- och Eriksbergs barnavårdcentral (interventionsgrupp) eller Flogsta barnavårdcentral (kontrollgrupp) för en 18-månaderskontroll och MPR-vaccination under tiden för studien. Totalt deltog 24 barn, interventionsgruppen bestod av 14 barn och kontrollgruppen bestod av 10 barn. Studien har genomförts med en kvantitativ, kvasi-experimentell design. Vid observation av deltagarna mättes skriktid samt föräldrarnas upplevelse av barnets smärta. Resultat: Vid mätning av skriktid kunde inte två milliliter 30 % glukos ses ha någon analgetisk effekt i samband med procedurrelaterad smärta. Föräldrarna i interventionsgruppen skattade sina barns smärta högre än de i kontrollgruppen. Slutsats: Då ingen analgetisk effekt utav två milliliter 30 % glukos till 18 månader gamla barn har kunnat påvisas stödjer denna studie inte att glukos som smärtlindringsmetod implementeras vid procedurrelaterad smärta i åldersgruppen. Studien har dock sina begränsningar då studiegruppen var liten och 8 av 10 deltagare i kontrollgruppen fick ett annat typ av vaccin. Detta vaccin (Priorix) anses orsaka mindre smärta än det vaccin som gavs till de övriga deltagarna (MMR-II). / Aim: The aim of this study was to investigate whether oral administration of two milliliters of 30 % glucose have an analgesic effect during vaccination against measles, mumps and rubella in 18-month-old children. Method: The sample group consisted of 18-month-old children who had their 18-month visit at Samariterhemmet or Eriksberg’s healthcare center (intervention group) or Flogsta healthcare center (control group) during the period of the study. The total amount of participants was 24 children; 14 children in the intervention group were observed at Samariterhemmet and Erikbergs healthcare center and 10 children were observed in the control group at Flogsta healthcare center. The study was conducted as a quantitative quasi-experimental study. During the visits the duration of the child’s crying/screaming and the parents’ perception of their child’s pain were observed and noted. Results: When measuring the duration of the child’s crying/screaming, two milliliters of 30 % glucose could not be considered to have any analgesic effect on procedure-related pain. Parents in the study group perceived their children as having more pain than the parents in the control group. Conclusion: Since this study could not show any positive analgesic effect attributed to the administration of 30 % glucose in 18-month-old children this procedure cannot be recommended for this age group. However, this study has its limitations, the low amount of participants should be considered and also the fact that eight out of ten children in the control group received a different type of vaccine (Priorix) than the rest of the sample group (MMR-II). This vaccine has been found to cause less pain than MMR-II.

Background: Pertussis, also known as whooping cough, is an infectious disease of the respiratory tract caused by the bacterium bordatella pertussis. In 2008, the Centers for Disease Control and Prevention (CDC) recommended that all post-partum women not previously vaccinated receive the Tdap (tetanus, diphtheria and acellular pertussis) vaccine in the immediate post-partum period in an effort to protect their newborns from this serious infection. In response, some birthing units in the state of Georgia have introduced programs to administer the Tdap vaccination to their post-partum patients. The purpose of this study is to examine the availability, design and effectiveness of these programs. Methodology: Surveys were sent to 72 birthing units in the state of Georgia. The survey was designed to illicit insight into each birthing unit’s policies and procedures regarding the administration and dissemination of the vaccine to post-partum women. In addition, the data collection instrument provided information on which centers offer the vaccination to their post-partum patients, how successful their program has been in reaching the target population and what barriers may need to be addressed to increase vaccination compliance to this particular population. Results: The results of this study suggest that Tdap programs in Georgia birthing centers can be successful in reaching the intended population and educating patients and hospital staff members on the importance of this vaccination. The majority of birthing centers in middle and southern Georgia do not have Tdap programs. In addition, barriers to Tdap vaccination programs have been identified such as lack of funding, lack of available education resources for both patient and hospital staff and absence of available staff members to administer vaccination. Conclusion: The examination of Tdap vaccination programs in Georgia birthing units can assist policy makers and public health agencies understand how to best allocate resources in an effort to increase vaccination compliance. Further research needs to be conducted to better understand how to improve program quality and availability state-wide and to correlate birthing center Tdap programs with increased vaccination compliance in postpartum women.

Behaviour is often neglected when modelling vaccination policies. This thesis shows the importance of incorporating behaviour in vaccination models of the impact of vaccines on disease dynamics. This thesis consists of three projects pertaining to voluntary vaccination in a network setting. The first project focuses on the effectiveness of voluntary ring vaccination under the presence of imitation. The contacts of a single index case vaccinate when symptoms first appear. We assume the contacts are unable to transmit infection to one another; however, we assume they are able to share their vaccination strategies. Under the presence of strong imitation, the effectiveness of voluntary ring vaccination becomes unpredictable. The second project focuses on the impact of personal experiences on voluntary influenza vaccination in a uniform network. Vaccination behaviour is based upon past infection and vaccination experiences, which creates a feedback loop between incidence and behaviour. Long-term memory acts as a stabilizing factor; however, long-term memory also decreases perceived vaccine efficacy. Vaccines conferring slowly waning immunity decrease vaccination coverage, leading to sporadic outbreaks in the absence of non-influenzal influenza-like-illness (niILI). Our results show evidence of vaccination strategy correlations being formed in the absence of imitation through past experiences. Allowing niILI to be mistaken for true influenza breaks up the strategy correlations, while stabilizing dynamics. The final model focuses on vaccination strategies targeting superspreaders, with the option of distributing economic incentives. We take a more psychological approach to influenza vaccination behaviour, where transmission of influenza occurs on an empirically based network. On average, superspreaders view the vaccine to be less effective; however, superspreaders still find vaccination more appealing because they are at a greater risk of becoming infected. The incorporation of behaviour leads to superspreader strategies to become less effective due to policy resistance; neglecting behaviour can lead to an overestimation of reduction of incidence. Public health officials should be concerned about the policy resistance and decreased perceived vaccine efficacy among superspreaders. The effectiveness of the vaccination or control policies could be diminished by the presence of behaviour, even when pro-active preventative measures are implemented by public health. / Ontario Graduate Fellowship, Ontario Graduate Scholarship in Science and Technology

Invasive amebiasis, caused by the protozoan parasite Entamoeba histolytica, is one of the leading parasitic causes of mortality worldwide, and there are no vaccines available to control the disease. The heavy subunit of the E. histolytica Gal-lectin is regarded as a potential subunit vaccine candidate. A Th1 (cell-mediated) immune response is protective against invasive amebiasis, and DNA vaccination is a strategy to induce such a response against specific antigens. The objective of this study was to construct and test a Gal-lectin-based DNA vaccine against E. histolytica. DNA encoding as 894--1081 of the Gal-lectin heavy subunit was resynthesized using a gerbil codon frequency bias and inserted in a mammalian expression vector to generate the DNA vaccine pCISToGL6. Balb/c mice vaccinated intradermally developed a Gal-lectin-specific cellular immune response, as well as an anti-Gal-lectin humoral immune response. Serum antibodies recognized a recombinant portion of the Gal-lectin heavy subunit by immunoblot and ELISA, and bound to native Gal-lectin on the surface of live trophozoites, inhibiting adherence to target cells. The Gal-lectin-specific serum antibodies were of the IgG2a isotype, indicating that a Th1 response was stimulated by the vaccine. We were also interested in using DNA encoding IL-12, IL-18 or GM-CSF as genetic adjuvants co-injected with pCISToGL6 to potentiate the immune response. Since the DNA vaccine was destined to confer protection in the gerbil model of invasive amebiasis, we cloned gerbil IL-12 (p35 and p40), IL-18 and its convertase caspase-1, and GM-CSF. The proteins were expressed in mammalian cells and showed bioactivity in vitro. Taken together, these results have laid the foundation to optimize and test a working Gal-lectin with co-stimulatory molecules to elicit a Th1 immune response for protective immunity against invasive amebiasis.

Entamoeba histolytica, etiological agent of amebiasis, continues to be a significant threat to human health worldwide. The disease affects 10% of the world's population and leads to an estimated 100, 000 deaths a year. The parasite's surface Gal-lectin is an immunodominant protein that also mediates colonization and pathogenicity. The Gal-lectin is the most promising vaccine candidate against amebiasis. However, the immune mechanisms involved in protection against disease remain unclear. The objective of this study was to characterize the immunological basis of the host defense mechanisms using a Gal-lectin based vaccine. Exposure of the Gal-lectin with immature dendritic cells increased cell maturation and activation and upregulated co-stimulatory molecules and pro-inflammatory cytokines production. Dendritic cell activation was dependent on NF-kappaB and MAPK activation. In vaccination studies, the adjuvant effect of CpG-ODN, a synthetic oligodeoxynucleotide capable of stimulating Th1 immune responses enhanced the immune response to the Gal-lectin when administered systemically or mucosally. Protected animals had elevated anti-Gal-lectin serum and stool IgA antibodies capable of blocking parasite adherence in vitro. Analysis of cytokine responses in vaccinated and protected animals revealed increased IFN-gamma production compared to controls. Finally, E. histolytica DNA was shown to activate macrophages in a TLR9 and MYD88-dependent manner. Immunized gerbils with Gal-lectin and E. histolytica DNA induced protective immunity against a challenge infection. Taken together, these findings underscore the importance of multivalent subunit vaccines in Th1 mediated immune responses in host defense against amebiasis.

Rapid expansion of the aquaculture industry in recent decades has resulted in infectious diseases emerging as a major constraint to fish production, causing large economical losses worldwide. Therefore, prevention practices are indispensable for maintaining the industry's profitability and sustainability. Vaccination is a proven effective strategy for disease control in aquaculture; however, improvements in vaccine efficacy are still needed. Because amino acid supplementation not only enhances fish growth but also immune responses, a series of experiments were conducted to test the hypothesis that dietary supplementation of arginine and glutamine, two amino acids with immunomodulatory roles, may promote growth and increase the efficacy of vaccination against Edwardsiella ictaluri in channel catfish. An initial experiment demonstrated that dietary arginine supplementation at 2 and 4% of diet enhanced growth and feed efficiency of channel catfish. Dietary arginine deficiency diminished plasma levels of arginine, citrulline, ornithine, glutamine and glutamate, and impaired innate performance of macrophages and neutrophils. In a separate experiment, dietary glutamine supplementation failed to enhance growth responses; however, supplementation at 2% of diet had strong positive effects on intestinal histology and enterocyte migration rate. In addition, serine, asparagine, glycine and threonine were increased in plasma of fish fed the diet with glutamine at 2%. A third experiment revealed that activated macrophages utilized large quantities of glutamine in media and to a lesser extent arginine. These two amino acids also were the most utilized by proliferating lymphocytes. Supplementing media with these amino acids positively modulated phagocytosis and bactericidal capacity of macrophages, as well as increased the proliferation rate of lymphocytes. A final experiment indicated that dietary supplementation of arginine (4%) and glutamine (2%) optimized the nutritional and immunological status of channel catfish, and enhanced responses to E. ictaluri vaccination. At the same time, this supplementation ameliorated some short-term adverse effects of vaccination on growth. Higher specific antibody titers, better lymphocyte responsiveness and survival to the bacterium were seen in vaccinated fish fed arginine- and glutamine-supplemented diets. These results support an expanded role of dietary arginine and glutamine manipulation as a tool to improve growth and vaccine efficacy of channel catfish.