Emerging diseases are an increasingly important public health problem. This research investigates space-time disease surveillance for emerging infectious diseases. A system was developed in Sri Lanka monitoring clinical diagnoses in cattle, poultry and buffalo. Veterinarians submitted surveys using mobile phones and GPS. This surveillance system proved to be both feasible and acceptable and provided timely information on animal health patterns in Sri Lanka. A critical review of software and methods for space-time disease surveillance provides guidance on the selection and implementation of appropriate analytic methods for surveillance data. For the data collected in this research, a hidden Markov model is developed which estimates region-specific prevalence estimates after controlling for sentinel-level factors. The use of cluster detection methods in surveillance research is demonstrated using data from an outbreak of suspected leptospirosis in Sri Lanka in 2005-2009. / Graduate

Objetivo: Evaluar la existencia de factores de riesgo de hipertensión, diabetes mellitus y edad avanzada y factores pronósticos de hipercreatininemia, hiperbilirrubinemia y leucocitosis asociados a la mortalidad en pacientes con Leptospirosis de un hospital del departamento de Loreto. Diseño: El estudio es una cohorte retrospectiva, que se desarrollará en los pacientes registrados en el Hospital de Contamana desde el mes de julio del 2015.

Leptospirosis, a zoonotic disease, is transferable through wild animals to other animals and humans directly and indirectly through contact with urine on mucous membranes. This disease can pose hazards for humans because of their increased contact with wild animals through increased urbanization and greater wildlife rehabilitation efforts and also through increased contact with domesticated animals. Furthermore, humans also have the potential of contracting this potentially fatal disease through recreational activities in contaminated waters or soils. The disease can present itself mildly, similar to symptoms of the flu, or more severely, leading to end-organ damage of multiple systems. Having been reinstated as a nationally notifiable disease by the Centers for Disease Control and Prevention in January 2013, leptospirosis has been recognized as a re-emerging zoonosis that has global public health implications. Understanding the disease is important in limiting its transmission; thus, this thesis aims to provide a review of the biology and transmission of leptospirosis to animals and humans, providing a basis in understanding the possible ways to limit the transmission and prevent future outbreaks. Furthermore, this thesis describes the manifestations, diagnostic testing, and treatment options for leptospirosis in canines and humans, as the increased prevalence of canines in households may pose a risk to humans in the future in the transmission of leptospirosis. According to current research, leptospires are extremely viable bacteria that can survive for long periods of time in a variety of environments and host species. Researchers have conducted various experiments to evaluate the factors that increase the virulence of leptospires. Experiments include the osmolarity, presence of serum, temperature chances, and the presence of iron. Results demonstrate that virulence increases with increased osmolarity, presence of serum, increased temperature, and the presence of iron. These characteristics of pathogenic leptospires allow them to avoid destruction by the immune system and colonize in the host, specifically in the renal tubules, allowing for excretion into the environment. Limiting the transmission of the disease is very important to prevent future outbreaks for animal species and humans. One method of limiting this transmission includes the use of vaccines. A major issue is the transmission of disease surround renal shedding, or excretion of the bacteria in urine. Canine polyvalent vaccines, containing multiple serovars, have been proven to be effective for a year, providing immunity and decreasing renal shedding of the bacteria. While vaccines for humans have been developed, they are not widely used due to the variation of serovars that are able to infect humans around the world and also the geographic distribution of disease, with prevalence mainly in tropical regions. Since leptospirosis is a disease that is not well-known, but can be found globally, there is necessity for greater emphasis on education, improved diagnostic testing, and treatment regimens. Emphasis on education is not only important for future veterinarians but also for those working in at-risk occupations. Furthermore, since experiments have shown that pet owners may not be aware of the prevalence and danger of zoonotic diseases, veterinarians should provide education for pet owners as well. Currently, the disease is underreported, which is accounted for due to the currently used diagnostic methods that are not efficient for early diagnosis, such as microscopic agglutination test, polymerase chain reaction, and cultures. In regards to treatment, antimicrobial treatment is considered controversial and there is not an agreed upon method of treatment. Thus, an emphasis should be placed on a developing a treatment method that is able to directly affect leptospires and usable across varying populations.

The capacity of zoonotic pathogens to infect multiple hosts creates surveillance challenges but also provides opportunities to gather data from animal species that can be used to understand risks to human health. This thesis presents a conceptual and practical assessment of the utility of domestic dog serosurveillance for the detection and surveillance of two pathogens, influenza A and Leptospira spp. The first chapter gives a theoretical framework that can be used to explore the attributes of animal sentinels and assess their utility in different contexts. In subsequent chapters, this framework is applied in a practical assessment of the utility of a domestic dog serosurveillance approach for the detection and surveillance influenza A and Leptospira spp. at two sites in Africa. Two cross-sectional surveys of the avian and mammal populations at a site in Northern Cameroon were conducted in early 2006 to determine if H5N1 influenza A viruses had circulated in this area and in which species that presence could be detected. Serological and molecular evidence of extensive H5 virus circulation in the domestic duck population was identified. 47% of domestic ducks at the Maga site were cELISA positive for anti-influenza A antibodies and 20% were HI test positive against an H5N1 antigen. There was also evidence of exposure to H5 subtype viruses in the local dog and pig populations. At the Kibera site in Nairobi, a cohort study was established to carry out surveillance of influenza A and Leptospira spp. in the domestic dog population and cross-sectional surveys of the domestic poultry and rodent populations were completed. There was no indication of influenza A circulation in any of the animal species surveyed, indicating low risk of zoonotic influenza A infection in the human population of Kibera. In contrast, there was extensive molecular and serological evidence of the presence of Leptospira spp. in both the rodent and dog populations. 18% of 236 trapped rodents were PCR positive for kidney carriage of pathogenic leptospires and the estimated seroprevalence of anti- Leptospira antibodies in the dog population ranged from 5-36% during the course of the study, indicating high potential risk of leptospirosis infection in the human population. The results indicate that dog serosurveillance can be used as useful tool for the determination of broad-scale patterns of pathogen presence and relative levels of population exposure. However, there are limitations of the data that can be gathered from animal sentinels and the complexities introduced particularly by incomplete understanding of diagnostic test performance must be recognized. Animal sentinel surveillance may be of most use for addressing fundamental questions of what pathogens are present where. In the developing world particularly where disease burden data are still lacking, dog sentinel serosurveillance can provide essential baseline data that can be used to target future research and resource allocation.

El objetivo de este trabajo fue realizar un estudio caso – control para evaluar factores de riesgo en la presentación de leptospirosis canina en pacientes de la Clínica de Animales Menores de la Facultad de Medicina Veterinaria de la Universidad Nacional Mayor de San Marcos. Se analizaron datos de las historias clínicas y resultados de análisis serológicos de los años 2002 al 2007. Se trabajó con un grupo caso (n=54) y un grupo control (n=394). Los datos se agruparon en las variables sexo, tamaño, edad, temporada del año y residencia. Fueron analizadas mediante la prueba de regresión logística. Los factores de riesgo asociados a la enfermedad fueron el sexo (el macho presenta el doble de riesgo que la hembra), el tamaño (los perros grandes presentan el doble de riesgo de presentar la enfermedad versus perros pequeños) y la edad (los animales de edades entre uno y tres años presentan cuatro veces más riesgo, los perros de tres a cinco años mostraron seis veces mayor riesgo, los animales de cinco a ocho años presentan diez veces mayor riesgo, y los caninos mayores de ocho años presentan ocho veces más riesgo que los menores de un año). / --- The aim of the present study was to describe potential risk factors for canine leptospirosis infections in The Small Animal Clinic of Veterinary School in San Marcos University, through the use of a case-control study. Data from clinical historical records and serological test results from 2002 to 2007 were reviewed. Forty four cases and 394 controls were enrolled into the study. The data collected; sex, size, age, season of the year and precedence; were analyzed by multivariable logistic regression. Risk factors related to the disease were: sex (male has double risk), size (bigger dogs have two times more risk) and age (dogs between 1-3 years old have four times more risk vs. 1 year old, dogs between 3-5 years old have six times more risk vs. 1 year old, dogs between 5-8 years old have ten times more risk vs. 1 year old and dogs older than 8 years old have eight times more risk vs. 1 year old).

Este trabalho foi realizado com o escopo de determinar a ocorrência de infecção leptospirótica em gatos, utilizando-se tanto da pesquisa de anticorpos específicos como de tentativas de isolamento e demonstração do agente a partir de fragmentos de rins destes espécimen. Visou-se, também, estudar aspectos clínico-laboratoriais, bacteriológicos e epidemiológicos da leptospirose felina, pela inoculação de gatos adultos com cepas autóctones, patogênicas, de L interrogans. Utilizando-se da reação de soroaglutinação microscópica, tendo como antígenos 18 sorotipos representativos de 17 sorogrupos de Leptospira, obteve-se, dentre as 172 amostras séricas examinadas, 22 sororeagentes (12,8 por cento ), com título >= 100. A maior frequência de soropositividade demonstrada foi para o sorotipo pomona. Não se observaram diferenças estatisticamente significantes (ao nível de = 0,05) com relação ao sexo, todavia, através da análise estatística (ao nível de = 0,05, demonstrou-se que a frequência da infecção é maior nos felinos adultos. Nas 172 amostras de pares de rins submetidas à cultura em meio de Fletcher, não se obteve êxito no isolamento do agente. Ademais, não se demonstrou a presença de leptospira em cortes de rins dos animais sororeagentes através da impregnação argêntica, segundo a técnica de Warthin-Starry. Após a inoculação, por via subcutânea, de 5 animais com cepa do sorotipo icteroharmorrhagiae (R-192) e de outros 5 com cepa do sorotipo canicola (CCZ-8), estes gatos ficaram sob observação durante um per1odo de 8 a 12 semanas. Em nenhum deles se manifestou qualquer alteração do estado de higidez, do quadro hemático e nos exames de urina realizados. Foram detectadas aglutininas antileptospira em 90 por cento dos animais inoculados, entre a 1ª e a 6ª semanas a contar da inoculação. Dos 9 animais que se soroconverteram, 8 permaneceram soropositivos durante 8 a 12 semanas. Apenas os animais inoculados com o sorotipo canicola eliminaram leptospiras pela urina, iniciando-se a leptospirúria entre a 2a e 4a semanas da inoculação e as sim persistinto por 2 a 8 semanas. Não se obteve nenhuma hemocultura ou nefrocultura positiva e nem se pôde demonstrar a presença de leptospiras no parênquina renal dos 10 anmais inoculados. / The occurrence of leptospiral infection in cats was determined through the detection of specific antibodies based on the results of microscopic agglutination test and the attempts of isolation and histological demonstration of leptospires from the kidneys of these animals. Clinical, laboratorial and epidemiological aspects of experimental feline leptospirosis were also studied; for this purpose, adult cats were inoculated with patogenic autochthonal strains of Leptospira interrogans. Of 172 serum samples examined by microscopic agglutination test, 22 (12,8 per cent ) were positive with titers >= 100. The most frequent serovar was pomona. In relation to the sex, statistical significant differences (level of ~ = O, 05) were not seen; however the age distribution showed that feline leptospirosis is more frequent in adult cats. The attempts for isolation and de monstration of L· interrogans from renal parenchyma either by culture or Warthin-Starry technics were unsuccessfull. Ten adult cats of mixed breed and both sexes were used for experimental infection. Five animals were inoculated subcutaneously, with serovar icterohaemorrhagiae (R-192) and other five with serovar canicola (CCZ-8) by the same route. The clinical and laboratorial findings presented no alterations in the inoculated animals. Antileptospiral agglutinins were detected in 90 per cent of the infected cats between 1st and 6th week after inoculation. From 9 cats with leptospiral agglutinins, 8 persisted seropositive for 8 to 12 weeks. The elimination of leptospires through urine was observed only in the animals infected with serovar canicola, begining 2 to 4 weeks after inoculation and lasting for 2 to 8 weeks. The hemoculture as well the kidney cultures from inoculated cats were also unsuccessfull.

Este trabalho foi realizado com o escopo de determinar a ocorrência de infecção leptospirótica em gatos, utilizando-se tanto da pesquisa de anticorpos específicos como de tentativas de isolamento e demonstração do agente a partir de fragmentos de rins destes espécimen. Visou-se, também, estudar aspectos clínico-laboratoriais, bacteriológicos e epidemiológicos da leptospirose felina, pela inoculação de gatos adultos com cepas autóctones, patogênicas, de L interrogans. Utilizando-se da reação de soroaglutinação microscópica, tendo como antígenos 18 sorotipos representativos de 17 sorogrupos de Leptospira, obteve-se, dentre as 172 amostras séricas examinadas, 22 sororeagentes (12,8 por cento ), com título >= 100. A maior frequência de soropositividade demonstrada foi para o sorotipo pomona. Não se observaram diferenças estatisticamente significantes (ao nível de = 0,05) com relação ao sexo, todavia, através da análise estatística (ao nível de = 0,05, demonstrou-se que a frequência da infecção é maior nos felinos adultos. Nas 172 amostras de pares de rins submetidas à cultura em meio de Fletcher, não se obteve êxito no isolamento do agente. Ademais, não se demonstrou a presença de leptospira em cortes de rins dos animais sororeagentes através da impregnação argêntica, segundo a técnica de Warthin-Starry. Após a inoculação, por via subcutânea, de 5 animais com cepa do sorotipo icteroharmorrhagiae (R-192) e de outros 5 com cepa do sorotipo canicola (CCZ-8), estes gatos ficaram sob observação durante um per1odo de 8 a 12 semanas. Em nenhum deles se manifestou qualquer alteração do estado de higidez, do quadro hemático e nos exames de urina realizados. Foram detectadas aglutininas antileptospira em 90 por cento dos animais inoculados, entre a 1ª e a 6ª semanas a contar da inoculação. Dos 9 animais que se soroconverteram, 8 permaneceram soropositivos durante 8 a 12 semanas. Apenas os animais inoculados com o sorotipo canicola eliminaram leptospiras pela urina, iniciando-se a leptospirúria entre a 2a e 4a semanas da inoculação e as sim persistinto por 2 a 8 semanas. Não se obteve nenhuma hemocultura ou nefrocultura positiva e nem se pôde demonstrar a presença de leptospiras no parênquina renal dos 10 anmais inoculados. / The occurrence of leptospiral infection in cats was determined through the detection of specific antibodies based on the results of microscopic agglutination test and the attempts of isolation and histological demonstration of leptospires from the kidneys of these animals. Clinical, laboratorial and epidemiological aspects of experimental feline leptospirosis were also studied; for this purpose, adult cats were inoculated with patogenic autochthonal strains of Leptospira interrogans. Of 172 serum samples examined by microscopic agglutination test, 22 (12,8 per cent ) were positive with titers >= 100. The most frequent serovar was pomona. In relation to the sex, statistical significant differences (level of ~ = O, 05) were not seen; however the age distribution showed that feline leptospirosis is more frequent in adult cats. The attempts for isolation and de monstration of L· interrogans from renal parenchyma either by culture or Warthin-Starry technics were unsuccessfull. Ten adult cats of mixed breed and both sexes were used for experimental infection. Five animals were inoculated subcutaneously, with serovar icterohaemorrhagiae (R-192) and other five with serovar canicola (CCZ-8) by the same route. The clinical and laboratorial findings presented no alterations in the inoculated animals. Antileptospiral agglutinins were detected in 90 per cent of the infected cats between 1st and 6th week after inoculation. From 9 cats with leptospiral agglutinins, 8 persisted seropositive for 8 to 12 weeks. The elimination of leptospires through urine was observed only in the animals infected with serovar canicola, begining 2 to 4 weeks after inoculation and lasting for 2 to 8 weeks. The hemoculture as well the kidney cultures from inoculated cats were also unsuccessfull.

El objetivo de este trabajo fue realizar un estudio caso – control para evaluar factores de riesgo en la presentación de leptospirosis canina en pacientes de la Clínica de Animales Menores de la Facultad de Medicina Veterinaria de la Universidad Nacional Mayor de San Marcos. Se analizaron datos de las historias clínicas y resultados de análisis serológicos de los años 2002 al 2007. Se trabajó con un grupo caso (n=54) y un grupo control (n=394). Los datos se agruparon en las variables sexo, tamaño, edad, temporada del año y residencia. Fueron analizadas mediante la prueba de regresión logística. Los factores de riesgo asociados a la enfermedad fueron el sexo (el macho presenta el doble de riesgo que la hembra), el tamaño (los perros grandes presentan el doble de riesgo de presentar la enfermedad versus perros pequeños) y la edad (los animales de edades entre uno y tres años presentan cuatro veces más riesgo, los perros de tres a cinco años mostraron seis veces mayor riesgo, los animales de cinco a ocho años presentan diez veces mayor riesgo, y los caninos mayores de ocho años presentan ocho veces más riesgo que los menores de un año). / The aim of the present study was to describe potential risk factors for canine leptospirosis infections in The Small Animal Clinic of Veterinary School in San Marcos University, through the use of a case-control study. Data from clinical historical records and serological test results from 2002 to 2007 were reviewed. Forty four cases and 394 controls were enrolled into the study. The data collected; sex, size, age, season of the year and precedence; were analyzed by multivariable logistic regression. Risk factors related to the disease were: sex (male has double risk), size (bigger dogs have two times more risk) and age (dogs between 1-3 years old have four times more risk vs. 1 year old, dogs between 3-5 years old have six times more risk vs. 1 year old, dogs between 5-8 years old have ten times more risk vs. 1 year old and dogs older than 8 years old have eight times more risk vs. 1 year old).

Thesis (Ph.D.)--Murdoch University, 2007. / Thesis submitted to the Division of Health Sciences. Includes bibliographical references (p. 171-192).

Thesis (MArch) -- University of Pretoria, 2001.