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The eradication of infectious diseases has been of key interest for many years. While the World Health Organization (WHO) and other health organizations typically track the progress of disease eradication based on whether regions are meeting their eradication targets, being able to quantify and/or visually track the eradication of a disease could prove beneficial. This thesis creates the “canonical path” to the elimination of measles in the United States (US), using similar methods as defined by Graham et al. [1]. We build on preliminary work conducted to fulfill the requirements of an Honours Bachelor of Science in Integrated Science at McMaster University, and the analysis conducted by Graham et al. [1], through the investigation of the sensitivity of the path to changes in its definition, as well how the path changes when we change the characteristics of the disease. This thesis demonstrates the ability to use a canonical path on a smaller, country-level scale, by using United States (US) state level data to create the US canonical path. We also determine the model structures necessary to simulate the canonical path, which suggests that the canonical path method is most useful for eradicable diseases for which we have ample knowledge of the disease, including the natural history of infection and vaccination. We also predict how the path is affected by the pattern of seasonality and by the natural history of infection. Overall, the analysis suggests that the more this method is implemented for other countries that have eliminated measles or for other diseases for which we have achieved elimination, we may gain insight of the successes and failures of elimination strategies. This knowledge could help the WHO and other organizations improve their disease elimination and eradication strategies in the future. / Thesis / Master of Science (MSc)

Eradication of polio outbreaks and tetanus neonatorum mortality, as well as lowering Egyptian infant mortality to less than 50 per 1000 live births, were specific goals to be achieved by the year 2000. National television immunization campaigns were launched to persuade mothers to change their attitude and vaccinate their children against the killer diseases. This study investigates the effects of these campaigns on mothers' knowledge, attitude, and behaviour regarding immunization in Egypt. A comparative study was conducted among three groups of mothers who have a child three to twelve months of age. A total of 158 mothers were selected, by systematic random sample technique (1:2), from the part of Kolosna village, in Upper Egypt, which is supplied with electricity, to constitute the viewer group. From the other part of the same village, which is not yet supplied with electricity, all mothers (98) were selected, representing the non viewer group. Another 76 mothers were selected from two prestigious social clubs in Cairo, to represent a second control group of known social class and educational level. Through comparing mothers' knowledge, attitude, and behaviour between the viewer and the non viewer groups, the effect of television immunization messages can be illustrated. Similarly, comparing the village viewer with the Cairo viewer group determines the effects of some intervening factors such as educational level, health professionals, or experience With a structured interview, mothers in the viewer group showed a significant positive and stable attitude and behaviour towards immunization, as well as more correct knowledge when compared with the non viewer group, demonstrating the positive role of television in child health promotion. Television enhances mothers' efficiency to use the available health services and promotes their perceived control over children's health. Health professionals, experience, and social support can potentiate the television's positive role. Educational level, occupation, baby's sex, or mothers' age are insignificant factors in changing mothers' attitude and behaviour.

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The boll weevil (Anthonomus grandis grandis Boheman) is currently under eradication in the U.S. The eradication program is implemented by means of area-wide applications of malathion ULV. Frequent applications of this insecticide result in high mortality of many beneficial insects, and a greater risk of secondary pest outbreaks. Notable among the latter are the outbreaks of beet armyworm (Spodoptera exigua H?bner) and cotton aphid (Aphis gossypii Glover) in the Lower Rio Grande Valley in 1995. The present study (i) compared densities of beneficial and pest insect and spider populations between cotton fields in eradication and non-eradication areas; (ii) evaluated the use of beneficial cotton arthropod population densities as indicators of pest damage risks from cotton aphid, beet armyworm, bollworm (Helicoverpa zea Boddie), and other worms (Estigmene acrea Drury, Pseudoplusia includens Walker, and Trichoplusia ni H?bner); and (iii) evaluated the effects of malathion ULV on the red imported fire ant (Solenopsis invicta Buren) a key arthropod predator in cotton agroecosystems. Studies were conducted in central Texas, in the vicinities of College Station and Dallas, during 2002 and 2003. Results showed that a majority of cotton predators were negatively impacted by malathion ULV applications. However, convergent lady beetle (Hippodamia convergens Gu?rin-M?neville) densities were greater in active eradication fields than inactive fields. Stepwise regression analyses identified densities of lacewing (Chrysoperla carnea Stephens) larvae and lady beetle larvae (H. convergens, Coleomegilla maculata De Geer, Harmonia axyridis Pallas, and Coccinella septempunctata L.) as predictors of cotton aphid density, and density of total spiders as predictors of bollworm density. Predictors of beet armyworm or other worm densities could not be determined. This study demonstrated malathion ULV was highly toxic to fire ants, and could repel ants from treated surfaces. Malathion ULV reduced the number of foraging fire ants in the cotton canopy for three weeks and reduced fire ant predation of beet armyworm eggs. Predictors of secondary pest densities have been suggested which, if utilized, may help to prevent the occurrence of secondary pest outbreaks under boll weevil eradication. Validation of these predictors should be preformed before implementing them into an eradication program.

<p>The main body of this thesis deals with three related concepts pertaining to vaccination strategies for childhood infectious disease. Chapter 2 deals with the implications of reversion in the Oral Polio Vaccine on global polio eradication programs. Chapter 3 explores the phenomenon of contact or secondary vaccination in the use of live-attenuated virus vaccines. Chapter 4 explores the importance of demographic stochasticity in pulse vaccination campaigns. largely focusing on measles dynamics. Abstracts for each chapter are given below.</p><p>Poliomyelitis vaccination via live Oral Polio Vaccine (OPV) suffers from the inherent problem of reversion: the vaccine may, upon replication in the human gut, mutate back to virulence and transmissibility resulting in circulating vaccine derived polio viruses (cVDPVs). We formulate a general mathematical model to assess the impact of cVDPVs on prospects for polio eradication. We find that for OPV coverage levels below a certain threshold, cVDPVs have a small impact in comparison to the expected endemic level of the disease in the absence of reversion. Above this threshold, the model predicts a small but significant endemic level of the disease, even where standard models predict eradication. In light of this, we consider and analyze three alternative eradication strategies involving a transition from continuous OPV vaccination to either continuous Inactivated Polio Vaccine (IPV), pulsed OPV vaccination, or a one-time IPV pulse vaccination. Stochastic modeling shows continuous IPV vaccination is effective at achieving eradication for moderate coverage levels, while pulsed OPV is effective if higher coverage levels are maintained. The one-time pulse IPV method may also be a viable strategy, especially in terms of the number of vaccinations required and time to eradication, provided that a sufficiently large pulse is practically feasible. More investigation is needed rq?;arding the frequency of revertant virus infection resulting directly from vaccination, the ability of IPV to induce gut immunity, and the potential role of spatial transmission dynamics in eradication efforts.</p> <p>Viruses contained in live-attenuated vims vaccines (LAVV) can be transmitted between individuals, resulting in secondary or contact vaccinations. This fact has been exploited successfully in the use of the Oral Polio Vaccine (OPV) to better control wild polio viruses. In this work we analyze general LAVV vaccination models for infections that confer lifelong immunity. We consider both standard (continuous) vaccination strategies and pulse vaccination programs (where mass vaccination is carried out at regular intervals). For continuous vaccination, we provide a complete global analysis of a very general compartmental ordinary differential equation LAVV model. We find that the threshold vaccination level required for eradication of wild virus depends on the basic reproduction numbers of both the wild and vaccine viruses, but is otherwise independent of the distributions of the durations in each of the sequence of stages of disease progression (e.g., latent, infectious, etc.). Furthermore, even for vaccine viruses with reproduction numbers below one. which would naturally fade from the population upon cessation of vaccination, there can be a significant reduction in the threshold vaccination level. The dependence of the threshold vaccination level on the virus reproduction numbers largely generalizes to the pulse vaccination model. For shorter pulsing periods there is negligible difference in threshold vaccination level as compared to continuous vaccination campaigns. Thus, we conclude that current policy in many countries to employ annual pulsed OPV vaccination does not significantly diminish the benefits of contact vaccination.</p><p> In the last two decades, many countries have implemented pulse vaccination for infectious diseases (mass vaccination campaigns repeated annually or at other regular intervals). Based on deterministic mathematical models, previous work has shown that the total expected cost of control or eradication (measured by the number of vaccine doses required) is identical for pulse vaccination (with any pulse interval) and for traditional, continuous vaccination. We reconsider this problem using stochastic epidemic models (both by direct simulation and by employing a moment closure approximation). We focus on measles and show that demographic stochasticity has a large impact on the relative success of pulse and continuous vaccination programs, even for well-mixed populations as large as 10 million.</p> / Thesis / Doctor of Philosophy (PhD)

Skin infections by the ectoparasitic mite Sarcoptes scabiei are a preventable source of morbidity worldwide. While scabies affects all socioeconomic sectors, it is especially prominent in the developing world where crowding, poor hygiene, and limited access to basic health care are commonplace. Mass eradication efforts of this parasite have historically been hampered by delivery and compliance issues surrounding topical standards of care. There have been advances in eradication over the last decade due to the expanded use of oral Ivermectin for the treatment and prevention of ectoparasites such as scabies. Previous research focused on various treatment aspects of the disease, yet most identified the need for basic scabies health education to accompany future studies to improve program sustainability and the overall health literacy of target populations. The Virginia College of Osteopathic Medicine sponsors a public health clinic in Veron, Dominican Republic that reports a high prevalence of scabies infections among its general patient population. The lack of any means of direct measurement, proper intervention, or control raises concerns that long-term infection may lead to multiple other secondary disease sequelae. The Veron Scabies Eradication and Education Program was designed to address this deficiency and build on previous studies related to this problem by using a novel treatment and education protocol. The purpose of this research was to identify, treat, and prevent primary and secondary health problems due to long-term scabies infection in the community of Barrio Nuevo, Veron, Dominican Republic in order to provide long-term sustainable eradication through a researcher-designed health education program and medical service protocol. Participants continued typical daily life while interventions and education were monitored to detect change over a 9-month timeline using selected measurement intervals to test multiple scabies disease and knowledge objectives and related hypotheses. Following this basic protocol, the following scabies markers were evaluated at baseline: subject demographics, scabies diagnosis and treatment history, baseline treatments and reported side effects, and scabies education pre-test results. The following scabies markers were also assessed at baseline and reassessed at 2 weeks, 1 month, 2 months, 8 months, and 9 months: risk and prevention behaviors, symptomatology, skin exam findings, and scabies education post-test results. There was a statistically significant post-intervention improvement in scabies markers when compared to pre-intervention values (p<0.05). This study demonstrated that a community scabies program involving large-scale treatment and education can provide rapid and long lasting improvements to the health of a highly endemic population. Community-wide scabies eradication is possible with the appropriate level of structure and support using low cost medication available to the health care system that serves Veron, Dominican Republic. Given the efficacy and safety profile of Ivermectin demonstrated in this study and substantiated by others, it is recommended that the Dominican Republic Ministry of Health consider adopting Ivermectin as the standard of care for scabies treatments and enforce an existing formal ban on Lindane products. The protocol from this research should be considered for adoption to provide a sustainable, practical, self-sufficient model for improved health outcomes, health behaviors, and health literacy. Future studies should replicate this research to determine validation in other settings, cultures and situations, build on the findings by exploring additional variables related to environmental risk factors, and continue to develop interventions that promote health education and enhance clinical practices. / Ph. D.

Similar to cancer cells, HIV-infected cells differ from HIV-uninfected cells in that they have altered interferon signaling pathways, the apparent reason for the selectivity of certain oncolytic viruses (OVs). Therefore, it was hypothesized that use of an OV, such as recombinant Maraba virus (MG1), may be a potential approach to eliminate latently-infected cells constituting the HIV reservoir while sparing HIV-uninfected cells. This was studied in U1, ACH-2, OM-10 and J1.1 cells and their respective HIV-uninfected parent cell lines in addition to CD4+CD25-HLADR- cells from HIV-infected individuals on effective antiretroviral therapy. Although MG1 infected and killed latently HIV-infected U1 cells to a greater degree than the HIV-uninfected parent U937 cells, this was not observed in the other HIV-infected cell lines and their respective parent cell lines. Furthermore, results from primary cells suggest that MG1 alone does not appear to eliminate cells which comprise the major HIV reservoir. Challenges of studying the HIV reservoir and priorities for future studies examining the use of OVs as a potential strategy to eliminate the HIV reservoir are discussed.

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