The Hygiene Hypothesis and Old Friends Hypothesis focus attention on the coevolutionary relationship between humans and pathogens, positing that reduced pathogen exposure in economically developed nations is responsible for immune dysregulation and associated increases in chronic inflammation, allergy, and autoimmunity. Despite progress in testing these ideas, few studies have examined these relationships among populations undergoing the transition from traditional to more market-based lifestyles. The present study tests relationships between economic development and social change, altered infectious disease exposure, and immune function among the Shuar forager-horticulturalists of Amazonian Ecuador, a population undergoing rapid economic change associated with increased market participation. Using stool samples to assess soil-transmitted helminth (STHs; parasitic intestinal worms) burden, dried blood spot measurement of the inflammatory marker C-reactive protein (CRP), and interviews to evaluate level of market integration (MI; the suite of social and cultural changes associated with rapid economic development) and disgust sensitivity, this dissertation tests the Hygiene and Old Friends Hypotheses. The first study tests relationships between STH exposure and MI, using geographic location in relation to the regional market center as a proxy for MI. This study documents lower rates of STHs in people living in more market integrated regions. The second study tests the coevolutionary role that STHs and other pathogens have played in shaping human psychology and behavior. Findings suggest that pathogen exposure has acted as a selective pressure, resulting in evolved disgust sensitivity toward pathogen related stimuli. This study provides evidence that disgust sensitivity is calibrated to local environments, acting to decrease STH exposure. The third study tests the role of STHs in immune function. CRP was positively related to age in uninfected individuals. No relationships existed for more traditionally living or infected individuals. These findings suggest that STH exposure may decrease the risk of developing chronic inflammation and associated diseases with advancing age. These studies provide support for the idea that STHs provide stimuli that decrease chronic inflammation, suggesting that altered intestinal microflora in developed nations may be partially responsible for the development of chronic inflammatory disorders like allergy and autoimmunity. This dissertation includes previously published and unpublished coauthored material.

p. 1-112 / Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-04-24T21:04:41Z No. of bitstreams: 1 11111111111.pdf: 829006 bytes, checksum: d72adf5912d3d4a5a6ab9659a04a516d (MD5) / Approved for entry into archive by Maria Creuza Silva(mariakreuza@yahoo.com.br) on 2013-05-04T17:26:41Z (GMT) No. of bitstreams: 1 11111111111.pdf: 829006 bytes, checksum: d72adf5912d3d4a5a6ab9659a04a516d (MD5) / Made available in DSpace on 2013-05-04T17:26:41Z (GMT). No. of bitstreams: 1 11111111111.pdf: 829006 bytes, checksum: d72adf5912d3d4a5a6ab9659a04a516d (MD5) Previous issue date: 2008 / Introducción: El control de las infecciones causadas por geohelmintos está basado en la administración periódica de drogas antihelmínticas a los grupos de alto riesgo, particularmente a niños en edad escolar que viven en áreas endémicas. Existen datos limitados sobre la efectividad de tratamientos antihelmínticos periódicos a largo plazo en la prevalencia de infecciones por geohelmintos particularmente desde programas operacionales. Objetivo: El presente estudio investigó el impacto de 17 años de tratamiento en masa con un antihelmíntico de amplio espectro, la ivermectina, usada para el control de la oncocercosis, en la parevalencia e intensidad de infección por geohelmintos en niños escolares. Métodos: Un estudio transversal fue conducido en comunidades que han recibido tratamientos anuales o bianuales y comunidades adyacentes que no han recibido dicho tratamiento en dos cantones de la Provincia de Esmeraldas en Ecuador. Una única muestra de heces fue colectada de cada niño y fue examinada usando las técnicas de Kato Katz y por concentración con formol-éter. Datos sobre los factores de riesgo para las infecciones por geohelmintos fueron colectadas por medio de cuestionarios aplicados a los padres. Resultados: Un total de 3563 niños en edad escolar (6-16 años) de 31 comunidades tratadas y 27 comunidades no tratadas fueron investigados. El tratamiento con ivermectina tuvo un efecto significante en la prevalencia (ORadj= 0,06; IC 95%: 0,03-0,14) y en la intensidad de la infección (RPadj=0,28; IC 95%: 0,11-0,70) por Trichuris trichiura pero no se observó dicho efecto en la infección por Ascaris lumbricoides o uncinarias. Conclusión: Tratamientos con ivermectina anuales y bianuales por un periodo de alrededor de 17 años tuvieron un efecto significante en la infección por T. trichiura pero no sobre otras infecciones por geohelmintos. La adición de una segunda droga antihelmíntica, tal como el albendazol, sería necesaria para obtener un efecto a largo plazo en la infección por A. lumbricoides en áreas altamente endémicas. / Salvador

Malaria is one of the most prevalent vector-borne infectious diseases with major morbidity and mortality in sub-Saharan Africa and Southeast Asia. Recent epidemiological studies have shown that co-occurrence of soil-transmitted helminth (STH) infections, or infection caused by parasitic worms, are associated with increased risk of malaria infection. However, studies of the association between STH and malaria, and the effect of antihelminth (deworming) treatments that are more commonly used in areas with high STH infection rates, are sparse. Therefore, we explored the relationship between STH and malaria infection in an Indonesian community (N=1997) with high prevalence of both STH and malaria while controlling for covariates and evaluating the role of deworming treatment as a covariate. Participants with STH infection and/or malaria infection were categorized as either infected or uninfected using PCR testing (cycle threshold count) at both baseline and end of study. Self-report, blood, and stool samples were used to assess overall STH and malaria infection from September 2008 to July 2010. Descriptive statistics were used to assess the impact of STH infection on malaria outcomes. To quantify these associations, robust Poisson regression models were used to assess the impact of baseline infections including STH infection on malaria while adjusting for age, sex, and the use of deworming treatment. Approximately 39.5% and 19.1% of all participants were infected with Plasmodium vivax and P. falciparum, respectively, at the start, while 18.0% and 9.96%, respectively, were infected at the end. A positive association was observed between Ascaris lumbricoides and P. vivax, and between Necator americanus and P. falciparum (PR = 1.04, 95% CI = 0.53 to 2.04; PR = 2.07, 95% CI = 1.00 to 4.29, respectively). While a negative association was observed between N. americanus and P. vivax, and between A. lumbricoides and P. falciparum (PR = 0.91, 95% CI = 0.44 to 1.89; PR = 0.66, 95% CI = 0.27 to 1.65, respectively). Overall, two of these models were significant (p = 0.062; p = 0.008; p = 0.030; p = 0.062, respectively). Similarly, there was a positive association observed between the use of albendazole treatment and STH and malaria outcomes.

The United Nations Millennium Development Goals have prioritized improving access to sanitation, but unfortunately about a third of the global population is still without an improved sanitation source and one billion still practice open defecation. Lack of access to adequate and safe sanitation means the proliferation of dangerous pathogens in the environment, especially soil-transmitted helminths (STHs). In the Bocas del Toro Province of Panama (and similar locations in the world), composting latrines have been built in many of the indigenous communities in the area. They are a form of dry or ecological sanitation and are designed to produce an end product that can be used as a soil amendment for agricultural purposes. The issue is that many of these latrines are not working as designed and do not go through the composting process. Instead, they may act as incubators for harmful pathogens, such as Ascaris lumbricoides (roundworm). This research 1) provides an extensive literature review of the health situation of Panama, focusing on indigenous populations; soil-transmitted helminths and helminthiasis; Ascaris lumbricoides and its implications for wastewater reuse and land application of biosolids/sewage sludge; and inactivation of Ascaris in composting latrines; and 2) develops and proposes an experimental plan, with field-based methods, to assess the inactivation of Ascaris, by urea and solar heat (increased temperature), in composting latrines in Panama. Various experiments have been conducted in the laboratory using urea and increased temperature to inactive Ascaris; however few have been carried out in dry toilet technologies in the field. The contribution of this thesis is the field-based experimental design developed for inactivating Ascaris in composting latrines. The methods build upon previous research carried out both in the laboratory and in the field.

MSc (Applied Mathematics) / Department of Mathematics and Applied Mathematics / In this study, we develop a multiscale model of soil transmitted helminths in humans with a special reference to hookworm infection. Firstly, we develop a single scale model that comprises of five between host scale populations namely; susceptible humans, infected humans, eggs in the physical environment, noninfective worms in the physical environment and infective worms in the physical environment. Secondly, we extend the single scale model to incorporate within-host scales namely; infective larvae within-host, immature worms in small intestine, mature worm population and within-host egg population which resulted to a multiscale model. The models are analysed both numerically and analytically. The models are epidemiologically and mathematically well posed. Numerical simulation results show that there is a bidirectional relationship between the between-host and within-host scales. This is in agreement with the sensitivity analysis results, we noted that the same parameters that reduce reproductive number R0 are the same parameters that reduce the infective worms endemic equilibrium point. From the comparative effectiveness of hookworm interventions analysis results, we notice that any intervention combination that include wearing shoes controls and reduces the spread of the infection. The modelling framework developed in this study is vigorous to be applicable to other soil transmitted helminths infections / NRF

Neglected tropical diseases are parasitic and bacterial diseases mainly prevalent in developing countries affecting people living in poverty. The World Health Organization’s human rights-based approach emphasizes the “prevention, control, elimination and eradication of neglected tropical diseases” through the use of preventative chemotherapy, such as the mass administration of deworming drugs to improve people’s health.This research paper will take a deeper look at how WHO has been communicating NTDs to make them less ‘neglected’ and how the NTD discourse has been shaping development organizations’ action. In addition, it aims to investigate how successful mass deworming has really been in terms of the recent debate.This study is using a combination of a discourse analysis and qualitative interviews in order to investigate how the NTD discourse and recent initiatives by international organizations have contributed to making NTDs less neglected. It deconstructs representations of the ‘Other’ – the superiority of the ‘West’ over the ‘Rest’ – in relation to the NTD discourse and its inherent power structures. Discourses are analyzed to identify power relations between governments, development organizations, pharmaceutical industries, and recipients of deworming drugs as part of Kenya’s 2013 deworming campaign.The results showed that the NTD discourse has helped raise awareness for NTDs. NTDs and their debilitating effect on populations have been better and more widely communicated, making them less ‘neglected’. WHO and other development organizations’ actions have contributed to making NTDs more visible and have given NTDs higher priority on the global health agenda. Findings from this research study revealed that the ongoing debate has not had a negative impact on international funding. More research and development of a vaccine against NTDs is needed to find more ways to tackle these devastating diseases.