Thesis (Dr.P.H.)--Boston University / The recently classified neglected tropical diseases (NTD), -- onchocerciasis, lymphatic filariasis, schistosomiasis, and soil-transmitted helminthiasis -- are all coendemic in Nigeria. The World Health Organization recommended strategy for addressing these diseases is preventive chemotherapy through annual mass drug administration (MDA) with ivermectin, albendazole, and praziquantel. Integrated delivery of these medicines has become the de facto strategy advocated for in the literature as a means of reducing costs through shared resources. Little empirical evidence, however, exists to support this. This paper explores these diseases and the concept of integration in the context of the global strategies for their control. A literature review was conducted using PubMed to identify articles published containing any of the disease names and costs. Of the 2,028 articles returned, only 14 published between 1998 and 2011 met the criteria for review. All costs were adjusted for inflation. Overall, the mean cost of MDA by any means was 0.83 cents. No data comparing separate MDA to integrated MDA were found. To examine this, a model was created comparing MDA programs with similar distribution strategies and targeting similar diseases. Data from separate articles presenting stand alone MDA were combined to give a mean cost of 0.42 cents to deliver two medicines in two rounds. This was compared with articles showing integrated MDA, which gave a mean cost of 0.25 cents to deliver two medicines in a single round. This suggests a cost savings of 40 percent. To verify this, data from a NTD program in Nigeria that transitioned to integrated MDA was examined in detail. In 2008, eight districts received a single round of ivermectin with albendazole followed at least 1 week later by a single round of praziquantel to school-aged children. The following year, a single round of all three drugs was co-administered. The number of treated individuals was essentially unchanged during both years (1,301,864 in 2008 and 1,297,509 in 2009). The total programmatic costs for the MDA, not including drug and overhead costs, reduced by 41% from $123,624 to $72,870, similar to savings seen in the literature review. Cost savings were attributed largely to transportation and personnel costs. Integrated delivery of medicines is recommended for mature programs targeting these diseases.

Neglected Tropical Diseases (NTDs) are both causes and manifestations of poverty in developing countries. Recent advocacy efforts have increased the profile of NTDs, and led to bold new control and elimination targets set for 2020 by the World Health Organisation. However there are multifaceted challenges in effectively implementing NTD interventions in resource-poor contexts that need to be understood and engaged. While there is a growing call by researchers and international agencies for a science of global health delivery to understand these complexities, the exact nature of this science remains contested. This thesis contributes to these debates by advancing a critical social science perspective on the factors that mediate intervention effectiveness for NTD control. Grounded in a social constructivist approach using mixed methods, it critiques prevailing orthodoxies by unpacking the nature, processes and outcomes of three large-scale NTD prevention programmes in Eastern Africa. Focused on different diseases, these case studies represent different types of intervention approaches: top-down, participatory and public-private partnership. The thesis traces the social, technical and environmental processes that mediate the delivery, adoption and use of particular health technologies, such as pit latrines, insecticides and vaccination. Together, these case studies reveal surprisingly similar reasons for why many interventions do not perform according to expectations. Despite new approaches that claim to overcome stereotypical challenges of top-down planning, narrow technocratic perspectives continue to play a defining role in maintaining disjunctions between global aspirations, local realities and intervention outcomes. New perspectives and changes in orientation are needed that emphasise flexibility, learning and adaptability to local contexts. Towards this end, the thesis outlines a conceptual framework based on a comparative analysis of the case studies that highlights five interrelated domains where effectiveness is determined: geographical/livelihood variation, local agency, incentives, the socio-materiality of technology and planning/governance. I argue that addressing the shortcomings of contemporary interventions requires that programme planners actively engage these domains by seeking to “order complexity.” Greater integration of social science perspectives into the management of NTD programmes would provide significant benefit. In these ways, the thesis contributes to wider debates about the nature of global health interventions and the influence of local contexts in mediating efforts to improve the health and wellbeing of the world’s poor and marginalised.

Carrion’s disease is a neglected tropical disease caused by Bartonella bacilliformis, a vector-borne pathogen restricted to the Andean valleys of Peru, Ecuador and Colombia. Carrion’s disease is a biphasic illness; in the acute phase the case-fatality rate can be as high as 88 %, related to high parasitemia, arriving to almost all erythrocytes, and secondary bacterial infections close related with the development of transient immunosuppression in the earlier illness phases. In addition, there are an undefined number of asymptomatic carriers that are reservoirs of the etiological agent of Carrion’s disease in endemic areas, they make take into account due to they are the perpetuators of this disease. The actual scenario of Carrion’s disease, in which the illness is arriving to new areas, due to the expansion of the vector’s distribution, suggests that now may be a crucial time to design a strategy focusing on its elimination.

No description available.

Female genital schistosomiasis (FGS) is a chronic manifestation of schistosomiasis, a waterborne parasitic infection, and is estimated to impact 56 million women predominantly in Sub-Saharan Africa. Currently, there is scarce literature on FGS and related health-seeking behaviour (HSB) among at-risk women. The objective of this mixed-method study is to understand the socio-cultural determinants of HSB and the health information trust networks for women at-risk of FGS in Ghana. A cross-sectional survey and twelve focus group discussions (FGDs) were conducted in the North Tongu and Weija Districts of Ghana. A total of 863 cross-sectional surveys and 12 FGDs were administered in both districts. There was an overall lack of awareness of FGS among adult women (38.9%). Only 48.8% of women reported HSB from the 86 women who choose to talk about their FGS-related symptoms. HSB was significantly associated with monthly steady income (p-value: 0.036) and level of education (p-value: 0.15,0.27), when controlling for age group and source of trusted health information. Some of the determining themes for HSB included: environmental and systemic context, shared norms, and apprehensions. Active and passive health information-seeking behaviour also emerged through the FGDs. Taking a mixed-method approach allowed for the appraisal of both methodologies and provided validity to the results. The lack of awareness of FGS indicates the need for tailored health information campaigns in endemic communities. More research is required on the FGS diagnostic and treatment capabilities of health facilities to understand their impact on HSB of women. This investigation finds that social, environmental, and cultural determinants are involved in the HSB of women at-risk for FGS, in North Tongu and Weija.

Les kinétoplastidés sont des protozoaires flagellés responsables de maladies tropicales négligées mortelles telles que la leishmaniose viscérale (L. donovani et L. infantum) ou la trypanosomiase humaine africaine (T. brucei), pour lesquelles les traitements disponibles sont très limités. Depuis quelques années, on observe un regain d'intérêt pour le développement de nitrohétérocycles aromatiques anti-infectieux tels que le delamanide et le féxinidazole. De récentes études indiquent que l'activité anti-kinétoplastidés de ces dérivés repose sur leur bioactivation sélective par des nitroréductases parasitaires, conduisant à la formation de métabolites réduits électrophiles, fortement cytotoxiques. Suite à des études préliminaires réalisées dans notre équipe en série 8-nitroquinoléin-2(1H)-one, ces travaux de thèse portent sur la synthèse et l'étude in vitro de l'activité antiparasitaire de 80 dérivés notamment fonctionnalisés en positions 3 et 6 du pharmacophore par divers motifs, notamment via la mise au point de réactions d'halogénation sélective et de couplages pallado-catalysés. Ainsi, 5 nouvelles molécules hits (4 anti-kinétoplastidés et 1 sélective de T. brucei) ont été identifiées (0,01 µM ≤ CI50 ≤ 7 µM et 13 < IS < 1500), trois d'entre-elles étant des substrats sélectifs des nitroréductases parasitaires de type I. Afin de préciser les relations structure-activité, une étude des potentiels de réduction a également été menée. Des études physico-chimiques (solubilité, test de perméabilité PAMPA) et pharmacocinétiques in vitro (stabilité microsomale et fixation à l'albumine humaine) sont venues compléter ce travail. Enfin, des évaluations de la mutagénicité et de la génotoxicité de ces hits sur des cellules procaryotes et humaines ont été conduites, dans le but de statuer sur leur potentiel pharmaceutique antiparasitaire humain et vétérinaire. / Kinetoplastids are flagellated protozoan parasites responsible for lethal neglected tropical diseases, such as visceral leishmaniasis (L. donovani and L. infantum) or sleeping sickness (T. brucei brucei), for which very few drugs are available. Nowadays, nitroheterocyclic compounds present a renewed interest as anti-infective agents, as illustrated by the development of fexinidazole and delamanid. Some recent studies demonstrated that the antikinetoplastid activity of these derivatives involves their selective bioactivation by parasitic nitroreductases, leading to the formation of electrophilic reduced metabolites, highly cytotoxic. Based on preliminary studies conducted in our team in 8-nitroquinolin-2(1H)-one series, this PhD work is about the synthesis and in vitro antiparasitic study of 80 derivatives mainly functionalized at positions 3 and 6 of the pharmacophore by various substituents, especially via the optimization of selective halogenation and pallado-catalyzed cross coupling reactions. Thereby, 5 new hit compounds (4 antikinetoplastid and 1 selective of T. brucei) were identified (0.01 µM ≤ IC50 ≤ 7 µM and 13 < SI < 1500), three of them being selective substrates of type I parasitic nitroreductases. In order to refine the structure-activity relationship studies, an analysis of reduction potentials was also conducted. In vitro physicochemical (solubility, PAMPA permeability assay) and pharmacokinetic (microsomal stability and human albumin binding) experiments completed this work. Finally, the mutagenicity and genotoxicity evaluations of these new hit compounds toward prokaryotic and human cells were realized, in order to assess their human and veterinary antiparasitic pharmaceutical potential.

Every year, through mass drug administration (MDA), hundreds of millions of the world’s poorest people receive a single annual dose of one or more drugs to eliminate certain parasitic worm or bacterial infections. Some of these infections, mostly prevalent in tropical areas, have traditionally been neglected from the public health and research point of view. These conditions, collectively known as the neglected tropical diseases (NTDs), still cause, at the cusp of the second decade of the 21st century, a significant amount of morbidity and mortality. The existing control measures for NTD have an enormous potential, although there are still some challenges that require further investigation. For some diseases, alternative strategies may be needed, including longer duration of MDA programmes or modified drug regimens. For other diseases, such as yaws, the work must start almost from scratch, since little has been achieved in terms of control of this disease in the past 50 years. Although eight NTDs affect the region, two diseases pose a major public health problem in the South Pacific Islands, namely yaws and lymphatic filariasis and are the basis for his thesis. These two infections were selected for a number of reasons. First, they affect the South Pacific region disproportionately. Secondly, little research has been conducted in the past years. And third, but more importantly, several epidemiological, technological and historical factors make these two diseases amenable to elimination. Safe and effective tools and interventions to achieve these targets are available and concerted efforts to scale them up are likely to lead to success. Yaws is one of the most neglected of the NTDs. Yaws was one of the first diseases to be targeted for eradication on a global scale, efforts which almost led to the disease disappearance as a result of a massive treatment program started in the 1950s. After the successful eradication campaigns the primary health care systems were supposed to give the last push towards eradication of yaws. However a combination of various factors including poor political commitment and limited funding resulted in a progressive abandonment of efforts and the resurgence of the disease. Every new case of yaws was the disappointing confirmation that the public health world had missed a great opportunity. Today yaws has resurged in many tropical areas and presents new challenges including its unknown epidemiological situation, the attenuated clinical forms of the disease, a poor awareness and knowledge among health care workers, the lack of knowledge about the effectiveness of classic treatment with penicillin and, an obvious need for research into simplified administration schemes or new antibiotic treatments, particularly oral ones. There is an enormous knowledge gap regarding current reliable epidemiological information about the disease. Certainly we know little about the burden in the three Melanesian countries where the disease is highly endemic, Papua New Guinea, Solomon Islands and, Vanuatu. In Solomon Islands and Vanuatu there are indications that Yaws is widespread and prevalent, but we know that the diagnosis is unreliable. This takes us to the next point, what does a diagnosis of yaws mean? Overall the natural history of the disease in this era, where it is often subject to inadequate antibiotic pressure, is very unclear. Some authors have suggested that yaws appears to be attenuated in both Solomon Islands and Vanuatu. They state that bone involvement in yaws is now rare and implies that yaws is a mild disease not requiring efforts for elimination. However, the first paper of this thesis describes the epidemiology of yaws in Lihir Island (Papua New Guinea, PNG) and shows a high rate of classical primary ulcers (almost 60%) and significant bone and periosteal involvement (more than 15%), suggesting that “attenuation” is not an important issue. When we look at the diagnostic criteria for yaws, signs and symptoms alone are still used often in many areas to diagnose the disease. This reliance on clinical findings was the result of the difficulty of performing serological tests in remote areas. Today, available rapid serological tests are simple, rapid, inexpensive and useful for guiding confirmation of cases, making them adequate tools for the diagnosis and monitoring of the disease. The clinical diagnosis of yaws is complicated because its clinical manifestations may be unspecific. Thus, it is possible that a significant proportion of yaws cases may in fact have been falsely diagnosed. We show, in the first article, that in our experience only 60% of the cases with a clinical suspicion of yaws were finally confirmed by serologic tests. Therefore, a proper diagnosis of yaws requires the interpretation of clinical findings with reference to laboratory results and the epidemiologic history of the patient. Serological testing in yaws is not only important for diagnostic accuracy, but also is very helpful in defining the disease’s evolution and eventual cure after treatment. Rapid plasma regain (RPR) titres should decline within 6-12 months, becoming negative in less than 2 years. The second article of this thesis combines a clinical and serological approach to assess the response after treatment with benzathine benzylpenicillin, and it identifies an overall 20% treatment failure. This could be related to resistance to the antimicrobial drug used or to re-infection caused. The distinction between re-infection and true resistance to antibiotic treatment is difficult to make but these failures are worrisome. This article also proposes a multivariate model performed to identify independent determinants of failure that affected the outcome after treatment. The risk for reinfection caused by repeated contact with infected children seems to be a pivotal predictor of failure. Low baseline titters (<1:32) of RPR are also an important and independent predictor of failure, possibly as a result of the greater difficulty in resolving chronic infections which are usually accompanied by low titters. With yaws re-emerging, the development of new strategies against this infection aimed at simplifying its treatment and potentially re-focussing strategies towards its eradication seems essential. Injectable penicillin is still effective but management with an oral drug that can be easily administered on a large scale should be the preferred method for treatment. To date, there had been no studies that directly compared the efficacy of penicillin with any of the potentially alternative agents shown to work in the treatment of the non-venereal treponematoses. The fourth paper in this thesis has shown that a single-dose of oral azithromycin is non-inferior to benzathine benzylpenicillin for the treatment of yaws in children in PNG. In an open-label randomised trial, at 6-month follow-up, 96% of patients treated with azithromycin were cured, as were 93% in the benzathine benzylpenicillin group. The prospects of eliminating and eventually eradicating yaws may now be enhanced by the use of a single-dose of oral azithromycin in mass drug administration campaigns. Community based mass administration of azithromycin has been widely used in many locations for the control of trachoma, which, like yaws, is a disease of poor rural communities in developing countries, and has been used in a more limited way to control granuloma inguinale and outbreaks of venereal syphilis. Elimination of yaws and lymphatic filariasis in the South-Pacific Islands is now considered biologically feasible and programmatically attainable. The Global Programme to Eliminate Lymphatic Filariasis (GPELF) has expanded quickly to reach the target of elimination by 2020. On the other hand the strategy to eliminate yaws is again at the centre of discussions and given that infected humans are the only source of disease, its eradication could be achieved within a very relatively short time. The fifth article of the thesis comprehensively reviews antimicrobial treatments and elimination strategies against yaws. In order to control yaws and push it towards elimination, we propose to move away from penicillin to azithromycin and use mass treatment campaigns of the entire population in endemic communities irrespective of the prevalence. Also, to make sure all cases are tracked down and treated, strict follow-up measures and selective mass treatment will be required until zero case prevalence is reached. Importantly, we suggest testing the principle of interrupting transmission in pilot implementation studies, including prevalence surveys to assess the impact of the intervention and macrolide resistance monitoring which in our opinion will be essential evaluation tools to guide us towards a sustainable elimination. Lymphatic filariasis (LF), caused by the mosquito-borne nematode Wuchereria Bancrofti, is a major public-health problem in the Melanesian countries. Annual MDA over five years is currently the WHO’s recommended strategy to eliminate lymphatic filariasis. This approach aims to suppress microfilaraemia in infected individuals and bring the infection below a threshold that leads to interruption of transmission. However theoretical work and clinical field experience has highlighted how the ecological diversity between different endemic regions can result in elimination thresholds that vary between local communities. This means that the duration required might be different for different areas. Other variables have also been previously identified as potentially having an influence on the outcome of the program, including baseline prevalence of infection, vector density or the treatment coverage. The last article of this thesis provides data about the impact of a five-year filariasis control program in Papua New Guinea. The findings reported support this strategy for areas with low-to-moderate rates of transmission in regions where anopheline mosquitoes transmit this infectious disease. Additional measures or longer periods of treatment may be necessary in areas with a high rate of transmission. The experience acquired on Lihir Island in MDA programs during the campaigns for the elimination of filariasis, will be very valuable when implementing a pilot strategy for yaws control. Also, in the near future it might be important to link yaws mass treatment with other mass programmes to increase efficiency. The plan for elimination of lymphatic filariasis in PNG was approved as a pilot project in 2005 but the program still needs to be extended to the total of 20 provinces in the country where filariasis is endemic. In this context, an integrated approach to NTD control could represent an important global public health solution in PNG and other South Pacific Islands. Little has been achieved in the past decade in NTDs. We are now in a good position to translate into policies the results of our research projects. A new elimination policy for yaws around the azithromycin pillar has been sketched a WHO consultation meeting held in Morges, Switzerland last March. In the intentions of the organization, a last global mass campaign to tackle yaws should permit to reach zero cases in 2017, and the subsequent certification of worldwide interruption of transmission by 2020. / Cada año, a través de la administración masiva de medicamentos (MDA), cientos de millones de personas, las más pobres del mundo, reciben una dosis única de uno o más medicamentos para eliminar ciertas infecciones, parasitarias o bacterianas. Algunas de estas infecciones, frecuentes sobre todo en las zonas tropicales, han sido tradicionalmente desatendidas desde el punto de vista de salud pública e investigación. Estas enfermedades, conocidas comúnmente como las enfermedades tropicales desatendidas (ETD), aún causan, en el inicio de la segunda década del siglo 21, una cantidad significativa de morbilidad y mortalidad. Las medidas de control actuales para ETDs tienen un enorme potencial, pero todavía existen algunas cuestiones que requieren investigación. Para algunas de estas infecciones, son necesarias estrategias alternativas, incluyendo una mayor duración de los programas de MDA o regímenes modificados de medicamentos. Para otras enfermedades, como la enfermedad de pián, el trabajo debe comenzar casi desde cero, ya que poco se ha logrado, en términos de control de esta enfermedad, en los últimos 50 años. Aunque ocho ETDs afectan a la región, dos enfermedades constituyen un problema importante de salud pública en las Islas del Pacífico Sur, a saber: el pián y la filariasis linfática y son la base de esta tesis. Estas dos infecciones fueron elegidas por muchas razones. En primer lugar, afectan a la región del Pacífico Sur de forma desproporcionada. En segundo lugar, pocas investigaciones se han llevado a cabo en los últimos años. Y en tercer lugar, pero lo más importante, varios factores epidemiológicos, tecnológicos e históricos hacen que estas dos enfermedades sean susceptibles de eliminación. Existen armas terapéuticas seguras y eficaces para lograr este objetivo, y esfuerzos coordinados para ejecutar los programas de control pueden conducir al éxito. El pián es una de las más olvidadas de las ETDs. Ésta fue una de las primeras enfermedades en ser objetivo de erradicación a escala global. Los esfuerzos de un programa de tratamiento masivo, que se inició en la década de 1950, casi llevaron a la desaparición de la enfermedad. Después de las exitosas campañas de erradicación, los sistemas de salud de atención primaria debían dar el último empujón hacia la erradicación del pián. Sin embargo, una combinación de varios factores, incluyendo un pobre compromiso político y una financiación limitada, dieron como resultado el abandono progresivo de los esfuerzos y el resurgimiento de la enfermedad. Cada nuevo caso de pián era la decepcionante confirmación de que el mundo de la salud pública había perdido una gran oportunidad. Hoy la enfermedad de pián ha resurgido en muchas áreas tropicales con nuevos desafíos: una situación epidemiológica desconocida, formas clínicas atípicas o atenuadas, poco conocimiento de la enfermedad entre el personal sanitario, la falta de datos acerca de la eficacia del tratamiento clásico con penicilina inyectable y la necesidad de desarrollar esquemas terapéuticos simplificados o investigar en nuevos tratamientos antibióticos, en especial de administración oral. Actualmente hay una enorme brecha de conocimiento entorno a la información epidemiológica fiable sobre la enfermedad. Ciertamente, sabemos poco acerca de la incidencia en los tres países melanesios, donde la enfermedad es altamente endémica, Papúa Nueva Guinea (PNG), Islas Salomón y Vanuatu. En las Islas Salomón y Vanuatu, las cifras de incidencia son muy altas lo que demuestra que el pián es una enfermedad frecuente y ampliamente extendida, pero sabemos que el diagnóstico no es muy fiable. Esto nos lleva al siguiente punto: ¿Cuáles son los criterios diagnósticos del pián? En general, la historia natural de la enfermedad en la época actual, donde la bacteria es objeto de presión antibiótica inadecuada, no es muy clara. Algunos autores han escrito que el pián parece presentar manifestaciones “atenuadas” en las Islas Salomón y Vanuatu. Afirman que la afectación ósea en el pián es poco frecuente, lo que implica que el pián es una enfermedad leve que no requeriría esfuerzos para su eliminación. Sin embargo, el primer trabajo de esta tesis describe la epidemiología del pián en la Isla de Lihir (Papúa Nueva Guinea) y muestra una alta tasa de úlceras primarias clásicas (casi el 60% de casos) y una afectación significativa del hueso y periostio (más del 15%) que sugiere que la "atenuación" no es un tema importante. Cuando nos fijamos en los criterios diagnósticos, únicamente signos y síntomas todavía se utilizan en muchas áreas para el diagnóstico de la enfermedad. Esta confianza en los hallazgos clínicos fue el resultado de la dificultad de realizar pruebas serológicas en las zonas remotas. Hoy en día, las pruebas serológicas rápidas son simples, rápidas, económicas y útiles para orientar la confirmación de los casos. El diagnóstico clínico del pián es complicado debido a que sus manifestaciones pueden ser inespecíficas. Así, es posible, que una proporción significativa de los casos de pián puedan haber sido falsamente diagnosticados. En el primer artículo, presentamos que, en nuestra experiencia, sólo el 60% de los casos con sospecha clínica de pián fueron finalmente confirmados por pruebas serológicas. Por lo tanto, un diagnóstico adecuado del pián requiere la interpretación de los hallazgos clínicos con referencia a los resultados de laboratorio y la historia epidemiológica de los pacientes. Las pruebas serológicas en el pián no sólo son importantes para el diagnóstico de la enfermedad, también son muy útiles en la definición de curación después del tratamiento. En la prueba de la Reagina plasmática rápida (RPR) los títulos deben descender a los 6-12 meses, llegando a ser negativa en menos de 2 años. El segundo artículo de esta tesis combina un enfoque clínico / serológico para evaluar la respuesta a bencilpenicilina benzatina, e identifica una tasa de fracaso terapéutico del 20% a los 12 meses del tratamiento. Esto podría estar relacionado con resistencia al fármaco antimicrobiano, o bien indicar una re-infección por re-exposición. La distinción entre la re-infección y la resistencia verdadera al tratamiento es difícil, pero estos fracasos terapéuticos son preocupantes. En este artículo se describe un modelo multivariante realizado para identificar los factores determinantes del fracaso terapéutico. El riesgo de re-infección causado por el contacto repetido con otros niños infectados parece ser un predictor fundamental de fracaso. También es un factor de riesgo, los títulos basales bajos (< 1:32) de RPR. Este último factor podría estar relacionado con la mayor dificultad para resolver infecciones crónicas (en estadio secundario), habitualmente acompañadas de títulos bajos. Con la enfermedad de pián re-emergiendo, el desarrollo de nuevas estrategias contra la infección para hacer más fácil los esfuerzos de erradicación es esencial. La penicilina inyectable sigue siendo eficaz, pero el tratamiento con un fármaco por vía oral que pueda ser fácilmente administrado a gran escala es el método preferido para el tratamiento, prevención y finalmente eliminación en todas las regiones endémicas del mundo. Hasta la fecha, no ha habido estudios que comparen directamente la eficacia de la penicilina con cualquiera de los agentes alternativos en el tratamiento de las treponematosis no venéreas. El cuarto artículo de esta tesis ha demostrado que una dosis única de azitromicina por vía oral no es inferior a la bencilpenicilina benzatina intramuscular, para el tratamiento del pián en niños en Papúa Nueva Guinea. En un ensayo abierto, aleatorio, el 96% de los pacientes tratados con azitromicina estaban curados a los 6 meses de seguimiento, al igual que el 93% en el grupo de bencilpenicilina benzatina. Las perspectivas de finalmente erradicar el pián son ahora mayores, mediante el uso de una dosis única de azitromicina oral en campañas masivas de tratamiento. El tratamiento masivo con azitromicina ha sido ampliamente utilizado para el control del tracoma, que, al igual que el pián es una enfermedad de comunidades rurales pobres de países en desarrollo. También se ha utilizado de una manera más limitada para controlar el granuloma inguinal y brotes de sífilis venérea. En general, el uso de azitromicina ha demostrado ser seguro, y de hecho ha habido beneficios inesperados de salud en algunos programas. La eliminación del pián y la filariasis linfática en las Islas del Pacífico Sur se considera ahora biológicamente factible y operacionalmente alcanzable. El Programa Global para Eliminar la Filariasis Linfática (GPELF) se ha expandido rápidamente para alcanzar la meta de eliminación en el año 2020. Por otro lado la estrategia para eliminar el pián es nuevamente centro de atención. Además, dado que los seres humanos infectados son la única fuente de la enfermedad, su eliminación podría lograrse en un plazo relativamente corto. El quinto artículo de la tesis revisa de forma integral el tratamiento con antimicrobianos y las estrategias de eliminación contra el pián. Con el fin de controlar el pián hasta la erradicación, se propone pasar de la penicilina a la azitromicina, y el uso de campañas de tratamiento masivo de toda la población en todas las comunidades endémicas. Además, para asegurar que todos los casos son encontrados y tratados, serán necesarias medidas estrictas de seguimiento y tratamiento masivo selectivo hasta llegar al objetivo de cero casos clínicos. Es importante destacar que el principio de interrupción de la transmisión se debe probar en estudios piloto, incluyendo estudios de prevalencia, para monitorizar el impacto de la intervención, y también la valoración de resistencia a macrolidos, que en nuestra opinión, serán herramientas fundamentales que nos guíen en el camino hacia una eliminación sostenible La filariasis linfática (FL), causada por el nematodo Wuchereria bancrofti, es otro de los grandes problemas de salud pública en los países de la Melanesia. Un curso de MDA anual, durante cinco años, es la estrategia que la OMS recomienda para eliminar la FL. Este enfoque tiene como objetivo suprimir la microfilaremia en los individuos infectados y disminuir los niveles de infección por debajo de un umbral que conduzca a la interrupción de la transmisión. Sin embargo, trabajo teórico y experiencia práctica clínica han puesto de relieve cómo la diversidad ecológica, entre diferentes regiones endémicas, puede resultar en que los umbrales de eliminación varíen en diferentes comunidades. Esto significa que la duración requerida podría ser diferente para diferentes áreas. Algunas variables que han sido previamente identificadas como potenciales determinantes en el resultado de un Programa para la eliminación de FL (PELF) son la prevalencia basal de infección por filariasis, la densidad de vectores (mosquitos) o la cobertura del tratamiento en la población. El último artículo de esta tesis, proporciona datos sobre el impacto de un PELF de cinco años en PNG. Los resultados obtenidos apoyan la estrategia descrita para las zonas con baja a moderada tasas de transmisión en regiones donde mosquitos anofelinos transmiten la infección (pe. Melanesia, África). Medidas adicionales o períodos más largos de tratamiento pueden ser necesarios en áreas con una alta tasa de transmisión. La experiencia adquirida en la Isla de Lihir en los programas de tratamiento masivo durante las campañas para la eliminación de la filariasis, será muy valiosa en la aplicación de una estrategia piloto para el control del pián. Además, en un futuro próximo podría ser importante vincular los programas para el control del pián con otros programas de tratamiento masivo (por ejemplo, filariasis) para aumentar la eficiencia y reducir los costos. El plan para la eliminación de la filariasis linfática en PNG fue aprobado como proyecto piloto en 2005 en la provincia de Milne Bay. El programa todavía tiene que ser extendido a un total de 20 provincias en el país, donde la filariasis es endémica. En este contexto, un enfoque integrado para el control de enfermedades tropicales olvidadas podría representar una importante solución global de salud pública en PNG. Poco se ha logrado en la última década en enfermedades tropicales desatendidas. Ahora estamos en una buena posición para traducir los frutos de nuestra investigación en políticas de salud. Durante una consulta celebrada en la sede de la OMS en Ginebra el pasado mes de marzo, ya se ha esbozado una nueva política de eliminación para el pián que toma como pilar el tratamiento con azitromicina. La intención de la OMS es que una última campaña global debe permitir llegar a cero casos de pián en 2017, y la posterior certificación de la interrupción de la transmisión en todo el mundo en el año 2020.

Made available in DSpace on 2015-07-22T20:49:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-09-29 / As Leishmanioses são classificadas pela OMS como uma das dez doenças negligenciadas tropicais (DNT), as quais apresentam alta incidência, atingem segmentos empobrecidos da população e não obtêm visibilidade social, portanto o investimento em diagnóstico, terapêutica e imunização é precário. As Leishmanioses fazem parte das doenças tropicais em expansão e não existem mecanismos adequados para sua prevenção e controle. Representam um problema de saúde pública mundial: 88 países apresentam pelo menos uma das trinta espécies de Leishmania e 350 milhões de indivíduos estão expostos à contaminação. Em algumas espécies, a letalidade das Leishmanioses pode alcançar 100% em pacientes sem tratamento. Diante desse quadro, realizou-se uma investigação com o objetivo de identificar o perfil da produção científica brasileira sobre o tema das Leishmanioses, no período 2004-2008, a fim de subsidiar o processo de formulação de políticas e tomada de decisões da gestão governamental, no tocante ao fomento à pesquisa em saúde nessa área do conhecimento. A pesquisa se refere a um estudo descritivo, elaborado com emprego da análise bibliométrica e da pesquisa documental. A Bibliometria consiste em um conjunto de leis e princípios empíricos que compõem os fundamentos teóricos da Ciência da Informação. A análise bibliométrica compreendeu a consulta, coleta e recuperação de informações quantitativas, em bases de dados da ciência da saúde no Brasil, seguida da organização dos dados coletados, sistematização em categorias de indexação, registro da coleta em banco de dados Excel e análise interpretativa das informações científicas e tecnológicas obtidas. A pesquisa documental constou de coleta e análise de dados em acervos institucionais de setores do órgão governamental federal de saúde. Em todas as bases consultadas, foram localizadas 749 publicações, produzidas no período 2004-2008 sobre o tema das Leishmanioses, das quais 521 atenderam aos critérios de inclusão. Foram publicados 415 artigos científicos por pesquisadores brasileiros em revistas indexadas, nacionais e internacionais. No diretório dos grupos de pesquisa da Plataforma Lattes, foi identificado o cadastro de 214 grupos dedicados ao tema. Receberam títulos nessa linha de pesquisa (Leishmanioses) 43 mestres e 44 doutores. A análise bibliométrica e documental permitiu identificar tendências de crescimento da produção científica brasileira sobre as Leishmanioses, no período 2004-2008, de grande relevância para a saúde pública, por tratar-se de doença negligenciada tropical. O Brasil detém o maior número de centros de pesquisa sobre Leishmanioses no mundo e atua em cooperação técnico-científica em âmbito nacional e internacional. Pode-se afirmar, portanto, que existe capacidade de médio porte instalada no país para a pesquisa sobre a doença. Além disso, foram identificados estudos em rede e multicêntricos, que podem favorecer a expansão e fortalecimento dos grupos voltados à pesquisa sobre Leishmaniose em âmbito nacional. Entende-se que seja oportuna a indução de ações e políticas públicas de fomento à pesquisa sobre estudos clínicos de fases I, II e III e sobre desenvolvimento tecnológico, a fim de propiciar o incremento do diagnóstico e tratamento das Leishmanioses no país. / The Leishmaniasis are classified by WHO as one of ten tropical neglected diseases (NTD), which have high incidence, affecting impoverished segments of the population and do not get social visibility, so the investment in diagnostic, therapeutic and immunization are poor. The Leishmaniasis is part of the tropical diseases in expansion process and there aren’t appropriate mechanisms for its prevention and control. They represent a public health problem worldwide: 88 countries have at least one of the thirty species of Leishmania and 350 million individuals are exposed to contamination. In some species, the lethality of Leishmaniasis may reach 100% in untreated patients. Given this situation, we carried out an investigation to identify the profile of Brazilian scientific literature on the subject of Leishmaniasis in the period 2004-2008 in order to support the process of policy formulation and decision making of government administration, with regard to development of health research in this area of knowledge. The survey refers to a descriptive study with use of bibliometric analysis and documentary research. The Bibliometrics consists of a set of empirical laws and principles that form the theoretical foundations of information science. Bibliometric analysis included query, collection and recovery of quantitative information in the databases of health science in Brazil, then organization of the data collected, systematized into categories of indexing, record collection in Excel database and interpretative analysis of scientific and technological information obtained. The collection consisted of desk research and data analysis in institutional sectors of the federal government body health. In all of the following databases were located 749 publications produced in the period 2004-2008 on the theme of Leishmaniasis, of which 521 met the inclusion criteria. 415 scientific articles were published by Brazilian researchers in indexed journals, national and international. In the directory of research groups of the Lattes Platform, were identified from the register 214 groups dedicated to the theme. Received titles in this line of research (Leishmaniasis) 43 masters and 44 doctors. Bibliometric analysis and documentation identified growth trends of the Brazilian scientific production on Leishmaniasis, in the period 2004-2008, of great relevance to public health, because it is neglected tropical disease. Brazil has the largest number of research centers on Leishmaniasis in the world and serves on scientific-technical cooperation in national and international areas, so it can be stated that there is midsize capacity for research on the disease installed in the country. Identified studies in multi-center network can promote the expansion and strengthening of the groups directed to research on Leishmaniasis nationwide. It is understood that is desirable the induction of actions and policies to encourage research on clinical trials of phases I, II and III and on technological development in order to facilitate the increase in diagnosis and treatment of Leishmaniasis in the country. / TEDE / BV UNIFESP: Teses e dissertações

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.

Dengue is a major public health problem that affects tens of millions of people annually in tropical and sub-tropical countries. This acute viral infection happens to be severe and even life threatening but there is still no available drug or vaccine. Previous studies have noted early higher viral burden in patients who develop more severe symptoms suggesting that administration of a potent and safe antiviral may prevent progression to severe dengue. To verify this hypothesis, we have conducted the first RCT directed towards reducing the viral burden in vivo by administrating chloroquine (CQ), a cheap and well-tolerated drug that inhibits DENV in vitro with concentrations achievable in vivo, to 307 Vietnamese adults with suspected dengue (257 of them were laboratory-confirmed cases). Unfortunately, we did not see an effect of CQ on the duration of infection. However in patients treated with CQ, we observed a trend towards a lower incidence of severe forms. We did not find any differences in the immune response that can explain this trend. We also found more adverse events, primarily vomiting, with CQ. In addition, we have explored the relationships between clinical features, antibody responses and virological markers in these patients. We found that the early magnitude of viremia is positively associated with disease severity and there are serotype dependent differences in infection kinetics. We found as well that DENV was cleared faster and earlier in patients with secondary infections. To complete this study, we have also evaluated 2 rapid lateral flow tests for the diagnosis of dengue in a panel of plasma samples from 245 RT-PCR confirmed dengue patients and 47 with other febrile illnesses. Our data suggest that the NS1 test component of these tests are highly specific and have similar levels of sensitivity (~60%). Both NS1 assays were significantly more sensitive for primary than secondary dengue. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. All these findings are of major importance for further anti-viral drug testing.