Thèses sur le sujet « Asymptomatic infection »

Acquired Immunodeficiency Syndrome (AIDS) was identified more than 30 years ago. The challenges for the clinicians and Human Immunodeficiency Virus (HIV)-infected individuals have changed over the years. Nowadays, viral replication is suppressed with Antiretroviral Therapy (ART). ART prevents AIDS related complications and decreases morbidity and mortality in HIV-infected subjects. However, mortality rates among HIV-infected individuals remain 3-15 times higher than those observed in the general population. The excess of mortality observed among HIV-infected subjects can be partly attributed to HIV-related illnesses. However, more than half of the deaths observed among HIV-infected patients treated with ART are due to co-morbid disorders related to aging. It is nowadays considered that HIV-infected patients are aging prematurely. Multiple hypotheses have been made to explain this premature aging. Chronic systemic inflammation, reduced vascular endothelial reactivity, increased endovascular hypercoagulability and immune activation have been suggested as possible mechanisms. These processes are more prevalent in HIV-infected patients (treated and non-treated) than in the general population. Therefore, HIV-infected patients are prone to develop age-related diseases or co-morbidities. Among these co-morbidities, HIV-infected patients present increased cardiovascular risk, more prevalence of traditional cardiovascular risk factors and early onset of the atherosclerotic disease. However, the underlying mechanisms are not known yet. HIV-infection has been suggested as a potential contributor to atherosclerosis. Given the unique effects of HIV on the immune system, it is plausible to consider that HIV infection itself could be involved in atherosclerosis. The link between both may be the result of a generalized increase in the activity of the inflammatory pathways, especially the cytokine network. It is possible that these alterations in the inflammatory system may modulate the risk of atherosclerosis in HIV-infected individuals. These alterations may be caused by DNA sequence variants and/or by changes in the expression patterns of inflammatory pathway genes induced by the HIV-infection or by ART. The purpose of this study was to investigate the possible association between genetic variants and gene expression of genes involved in inflammation and cardiovascular risk measures in a cohort of HIV-infected subjects. The associations identified between genetic variants in the studied genes and CVR measures were modest. This suggests that SNPs may play a minor role and not be the underlying cause of the increased CVR observed in HIV-infected individuals. HIV-related CVD is probably influenced by non-genetic factors such as traditional CVR factors, the HIV-virus itself and by ART. The gene expression of the investigated genes is altered in HIV-related atherosclerotic disease. The findings regarding 5-LO pathway are the most relevant of this study. This part of the inflammatory pathway is important in the metabolism of lipids, which is closely related to atherosclerosis. To our knowledge this is the first study describing the implication of the 5-LO pathway in HIV-related atherosclerosis. Genetic variants in two key genes of this pathway (ALOX5 and ALOX5AP) were associated with HIV-related atherosclerosis. Although no differences were found in their gene expression, ART introduction reduced ALOX5AP gene expression levels, but not to the levels observed in uninfected controls justifying the importance of early ART initiation. Importantly, the 5-LO pathway interlinks lipid metabolism and inflammation and it is altered in HIV-infection. Thus, 5-LO pathway dysfunction may be critical in HIV-related atherosclerosis development. In summary, the findings reported in this thesis show that there is an intricate relationship among HIV-infection, antiretroviral treatment, atherosclerotic disease and the inflammatory pathway.

Objective: To report an outbreak of ZIKV infection among asymptomatic pregnant women during 2016 in the city of Jaen, Cajamarca. Results: Zika virus RNA was detected in 3.2% (n = 36) of cases by RT-PCR. The mean age of patients positive for ZIKV infection was 29.6 years. 7 patients (19.4%) infected with ZIKV were in their first-trimester of gestation, 13 (36.1%) were in their second-trimester, and 16 (44%) were in their third-trimester. All of the infected pregnant women were asymptomatic. ZIKV infection remains a major public health issue that calls for constant epidemiological surveillance. It can cause the congenital Zika virus syndrome in the newborns of infected mothers. The lack of molecular diagnostic methods in isolated localities and the similarity of symptoms to other arboviral infections, lead to an under-diagnosis of this disease in endemic areas.
Revisión por pares

Objective: To determine the general and genotype-specific prevalence of HPV and to identify potential risk factors for the infection in a population-based screening of Peruvian women. Results: A total of 524 samples were analyzed by PCR and a total of 100 HPV positive samples were found, of which 89 were high-risk, 19 were probably oncogenic, 9 were low-risk and 27 other HPV types. The 26–35 and 36–45 age groups showed the highest proportion of HPV positive samples with a total of 37% (37/100) and 30% (30/100), respectively. Moreover, high-risk HPV was found in 33.7% of both groups and probably oncogenic HPV in 52.6% and 31.6%, respectively. High-risk HPV were the most frequent types identified in the population studied, being HPV-52, HPV-31 and HPV-16 the most commonly detected with 17.6%, 15.7% y 12.9%, respectively. Demographic characteristics and habits were assessed in the studied population. A total of 62% high-risk HPV were detected in married/cohabiting women. Women with two children showed the highest proportion (33.8%) of high-risk HPV, followed by women with only one child (26.9%). Those women without history of abortion had a higher frequency of high-risk HPV (71.9%), followed by those with one abortion (25.8%).
Revisión por pares

Anaemia is common and frequent in HIV infection and Acquired Immune Deficiency Syndrome (AIDS). This study was aimed at exploring the interactions between the effects of HIV infection and other related anaemia-causing effects (reductive adaptation, reduced energy/nutrient intake and inflammatory and/or metabolic alterations), which may be responsible for most anaemia in this population. It is postulated that these interactions can heighten the risk levels for anaemia even in an asymptomatic HIV-infected population. The study is based on a secondary analysis of data from the Transition and Health during Urbanisation of South Africans (THUSA) survey, a population-based, cross-sectional study carried out in the North West Province of South Africa. Out of a sample population of 1854 ‘apparently healthy’ adults, aged ≥15 years, 216 (11.8%) were HIV sero-positive. A validated quantitative food frequency questionnaire was used to assess dietary intake and standard conditions and protocols used for anthropometric and biochemical measurements. Anaemia was defined using WHO haemoglobin (Hb) and haematocrit (Hct) definitions. Univariate ANOVA statistics showed that HIV-sero-positive subjects had lower Hb, Hct, serum iron, ferritin, total iron binding capacity (TIBC) but higher % saturation compared to their sero-negative peers. However, only the differences in Hct were significant (p<0.001). Anaemia prevalence was generally high but was higher though not statistically significant in sero-positives than sero-negatives (51.4% cf. 45.8%,p=0.123). Anaemia in the study population was mostly mild (about 65%), with a higher proportion of anaemia of chronic inflammation than iron deficiency anaemia. Vitamin a deficiency was significantly associated with anaemia (p=0.022). High serum total proteins, alanine transaminase (ALT), aspartate transaminase (AST) and low albumin were significantly associated with HIV sero-positivity. Predictors of anaemia in the study population by logistic regression modelling were settlement type (aOR,1.7;CI,1.2-2.5;p=0.004), serum albumin (0.6;0.4-0.9;p=0.016), TIBC (1.5;1.0-2.2;p=0.008), vitamin E (0.6;0.4-0.9;p=0.006), serum gamma-glutamyl transferase (0.6;0.4-0.9;p=0.007), Direct bilirubin (0.5;0.5-1.0;p=0.0446), and abdominal skinfold (1.8;1.2-2.5;p=0.004). HIV infection was not a significant predictor of anaemia in this asymptomatic population, but the virus and related inflammatory conditions may play a crucial role in the development of anaemia. Where HIV and other inflammatory stressors are prevalent, the overall burden of anaemia could also be increased

In the absence of an effective vaccine, vector control and surveillance of dengue fever (DF) and dengue hemorrhagic fever (DHF) are the most important strategies currently used to reduce the impact of these diseases in affected population. The objectives of this study were to estimate the incidence of symptomatic and asymptomatic dengue cases, the prevalence of antidengue antibodies, and to evaluate the laboratory and clinical aspects related to an active surveillance of dengue cases. In this study, active surveillance was incorporated as a part of the study design. At total of 3,255 people from four high risk neighborhoods were followed in a two years prospective study whereby the participants' houses were visited three times a week. During these visits, dengue cases were characterized by identifying patients with fever as well as other symptoms that were compatible with dengue disease. In addition, a biannual blood sample was taken for each study participants, to establish the prevalence and six month incidence of dengue infection. We found a crude incidence density (ID) of 3.24 by 100,000 person/days (p/d) which changed from 5.69 by 100,000 p/d for the first year of the study to 1.45 by 100.000 p/d in the second year. In both years, the months from July through September had the highest ID of 8.81 by 100,000 p/d. Children displayed higher ID when compared to adults, RR: 3.92 (2.38 - 6.48). The Plaque Reduction Neutralization Test was used to assay for the presence of antidengue antibody in 2,125 study participants (65.3% of total). The prevalence of anti dengue antibodies was found to be 86.6% (1,840 positives). The prevalence of anti DENV-1 was 74%, while 65.2 % of the participants had anti- DENV-1 and anti- DENV-2 simultaneously. The cumulative incidence of anti IgG dengue antibody in the negative participants (283 at the start of the study) was 30% in the first 6 months period, 29.6% in the second 6 months, and 23.8 in the third one. The difference between the numbers of participants detected in the active surveillance, (270 confirmed and non confirmed dengue cases) with the numbers of people who showed sero-conversion to anti-IgG dengue antibody within a relatively short period of time suggested that there was a high number of asymptomatic dengue infections present in the population. Transmissibility of the virus, the surveillance of dengue, and vaccine implementation in the near future would all be affected by the large number of asymptomatic people in hyperendemic countries.

Malaria /HIV co-infection is a major challenge to public health in developing countries and yet potential drug-drug interactions between antimalarial and antiviral regimens have not been adequately investigated in people with both HIV and Plasmodium falciparum infections. Earlier studies on the use of artemether-lumefantrine (AL) in Nigeria have neither addressed its use in HIV-positive subjects nor in asymptomatic-malaria infection. The present study investigated associations between drug resistant P. falciparum and the use of medication for HIV management, drug-drug interactions between artemether-lumefantrine and antiretroviral drugs (ARV) and the molecular markers of artemether-lumefantrine and other antimalarial drugs. Results of the study revealed an elevated day 7 lumefantrine concentrations in HIV subjects on nevirapine treatment compared to their HIV-negative counterparts. Associations between elevated day 7 levels of lumefantrine and the persistent parasitaemia could not be evaluated due to inadequate power. Genetic analysis by DNA sequence of P. falciparum isolates revealed strong selection for the pfmdr1codon86N allele among all treated individuals. This polymorphism is a strong indicator of AL treatment failure or slow clearance in vivo. There was a 72.6% prevalence of the pfcrt76T mutations in the population and this was observed to be higher in the HIV-positive subjects. Three new mutations F73S, S97L and G165R were detected on the pfmdr1 gene and the first case S436F mutation on the pfdhps gene to be reported in Nigeria. The dhpsK540E and dhfrI164L mutations, associated with high-level resistance to sulfadoxine-pyrimethamine (SP) were not observed in our small sample size. The study also revealed that HIV-positive subjects were more likely to harbour parasites, at a higher density, before and after treatment. Improvement of the immune status of HIV-infected patients was suggested by the increase of CD4 cell count level in about 68% of the HIV-positive patients. This is a preliminary study and first of its kind to investigate drug-drug interactions between ARVs and the antimalarial drug AL in HIV-positive patients co-infected with P. falciparum in relation to parasite clearance. The findings of the study are very important but more work is urgently needed with a larger sample size to confirm these findings.

Despite the advances made since the advent of germ theory, infectious diseases still wreak havoc on human societies, not only affecting us directly but impacting the crops and livestock upon which we rely. Infectious diseases also have dramatic effects on wildlife ecology. Therefore research into infectious diseases could not only directly lead to the improvement and saving of human lives, but aid in food security and the conservation of many wildlife species. Of vital importance in understanding the ecology of infectious diseases are the mechanisms by which they persist in host populations. One possible mechanism is vertical transmission: the transmission of a pathogen from a parent to its offspring as a result of the process of host reproduction. Another possible mechanism is inapparant infections, where an infected host does not display symptoms. Focusing on dengue fever and the Plodia interpunctella granulovirus laboratory system, this PhD thesis looks at the role these two mechanisms play on the persistence of two viral infections and their ecology. Regarding the Plodia interpunctella granulovirus (PiGV) low host food quality led to greater detection of vertically transmitted inapparant PiGV, but did not lead to its activation to an apparent form. Host inbreeding did not lead to vertically transmitted inapparant PiGV’s activation, nor had an effect on its vertical transmission. The vertical infection rate of PiGV was very low. I would therefore suggest that it may be better to use an insect virus system with a higher rate of vertical infection in future research into vertically transmitting inapparent infections. Regarding dengue virus I conclude that vertical transmission is not likely to play a role in the persistence of this virus. However modelling work found that inapparent infections could provide dengue viruses with a means of persistence and should be subject to further research.

Background: The burden of Sexually transmitted infections (STIs) is high globally. The World Health Organisation (WHO) recommends syndromic management of these STIs, based on presentation with signs and symptoms, in resource-limited countries. Due to this syndromic approach, there is little current data on STI prevalence, including asymptomatic STIs, in high risk populations. Methods: We reviewed secondary data collected as part of the screening procedures of 6 clinical trials between 2012 and 2017 in Cape Town, South Africa. These trials recruited populations of different sexual orientation and gender, mostly key populations at risk of HIV and STI acquisition. Routine screening for STI symptoms and testing for Chlamydia, Gonorrhoea, Trichomonas, Syphilis and HIV was performed for all of the studies at screening/enrollment. Results: A total of 639 participants were screened; 411 (64.3%) self-identifying as female, 198 (31%) males, 29 (4.5%) transgender women and 01 (0.2%) transvestite. Median age was 20 years (IQR: 18-24), with the 15-24-year age category contributing 77% to the cohort. Laboratory testing diagnosed 239 (37.4%) people with STI infections in this cohort; only 28 (11.7%) people were symptomatic. 119 (88.8%) of Chlamydial, 64 (82.1%) of Gonorrhoeal, 23 (92%) of Trichomonal and 31(79.5%) of Syphilis infections elicited no signs and/or symptoms. Conclusion: A vast majority of STIs in this high-risk population were asymptomatic. Laboratory testing of causal organism was more reliable in diagnosing STIs than the use of signs and/or symptoms as recommended by WHO.

Adequate nutritional status promotes optimal structure and function. In PLWH, few studies on the impact of dietary intake on nutritional and metabolic status have been undertaken. This cross-sectional secondary data analysis examined how different dietary patterns influenced nutritional and metabolic integrity in asymptomatic PLWH in the North-West Province of South Africa. Dietary data were collected using validated QFFQ. Data analysis was by SPSS version 14. Dietary and nutrient patterns were generated using Principal Component Analysis. Though asymptomatic, marked biochemical differences depicting altered metabolism and inflammation were observed in PLWH compared to the uninfected. PLWH also showed an anthropometric profile that depicted altered body composition and abnormal fat distribution. Four dietary patterns: animal-based, ‘recommended’, staple, and the Carbohydrate, Vegetable and Legumes (CVL) based were observed in both PLWH and the uninfected with slight differences. In PLWH, the animal-based similar to the CVL pattern was associated with better overall nutrient intake (r=0.5, p<0.001) and selected nutrients, including energy (r=0.3, p<0.001), protein (r=0.6, p<0.001), iron (r=0.5, p<0.001), zinc (r=0.6, p<0.001) and vitamin A (r=0.5, p<0.001), compared to the other dietary patterns. The animal based dietary pattern also predicted higher BMI (OR=2.2, 95% CI=0.9-5.0), LBM (3.6, 1.3-10.4), serum albumin (1.5, 0.9-2.4) and lower liver enzymes AST (0.5, 0.3-0.8) and ALT (0.6, 0.4-0.9). Using Graphical Chain Modelling, higher intake of the animal-based but lower staple-based dietary patterns were associated with better overall nutrient intake, serum vitamins A, E, lipid score, albumin, BMI and LBM suggesting that intake of this diet may provide better nutrient quality, enhancing nutritional status and metabolic proficiency, which may ultimately influence disease progression. The findings have implications for dietary guidelines for this population but further research is required. However, if these findings are true, then a predominantly animal-based diet may be ‘recommended’ for this population. Moreover, the longer term implications of high fat intake associated with the animal based dietary pattern on obesity and associated risks should be considered. This poses a challenge to imperatively weigh up the longer term risks of the overall population profile crucial for public health.

Introduction. La neurocysticercosis (NCC) est l'un des maladies helminthiques les plus courantes du SNC et elle cause de l'épilepsie symptomatique dans les régions pauvres. Il existe peu d'études communautaires sur cette zoonose et leurs comorbidités comme l'épilepsie et la NCC. Méthodologie. Dans la région nord du Pérou, trois études sur la communauté et une révision systématique ont été développés dont les objectifs étaient les suivants: a) évaluer la prévalence de la NCC asymptomatique, b) la prévalence de l'épilepsie associée à la cysticercose, c) la détermination de l'exposition à la cysticercose d) développer une intervention communautaire pour interrompre la transmission de la cysticercose. Résultats. 256 patients asymptomatiques qui avaient une tomodensitométrie (T) sans contraste, 48 (18%) avaient la NCC calcifiés. La prévalence de l'épilepsie trouvée était de 17.25 / 1000 habitants et la proportion de NCC en personnes atteintes d'épilepsie était de 39% (109/282). Le Western Blot (EITB-LLGP) pour la cysticercose a été positive dans le 40% des personnes atteintes d'épilepsie, et dans le 36,9% de la population générale. L'association entre la cysticercose et l'épilepsie avait un OR de 2,7 (95% CI 2.1 – 3.6, p <0,001). Le traitement massif avec niclosamide chez l'homme (n = 3), et plus la vaccination de la population porcine a été mis en oeuvre dans 107 communautés rurales de Tumbes. Aucun porc infecté avec la cysticercose n’a été trouvé en 105 des 107 communautés. Conclusions. (1) La NCC est un facteur contributeur de l'épilepsie, (2) La transmission de T. solium peut être réduite à échelle régionale
Backgrounds. Neurocysticercosis is a parasitic infection of the brain and a common cause of epilepsy in poor regions. There are scarce community-based studies about its comorbidities as epilepsy and neurocysticercosis. Methods. In the northern region of Peru, we performed three community based-studies and one systematic review a) to assess the prevalence of asymptomatic NCC, b) the prevalence of epilepsy and epileptic seizures and NCC c) seroprevalence of cysticercosis (EITB-LLGP) and d) to perform a community intervention to interrupt the Taenia solium transmission. Results. Of the 256 residents who underwent CT scan, 48 (18.8%) had brain calcifications consistent with NCC. Lifetime prevalence of epilepsy was 17.25/1000, the proportion of NCC in people with epilepsy was 39% (109/282), and the seroprevalence of EITB-LLGP in individuals with epilepsy was 40% and between 23.4 to 36.9% in the general population. The association between CC and epilepsy had a OR of 2.7 (95% CI 2.1-3.6, p <0.001). Three rounds of mass treatment with niclosamida in humans and mass treatment and vaccination in pigs was implemented in 107 rural communities (n=81,170 people). No infected pigs with cysticercosis were found in 105 of 107 communities. Conclusion. NCC is a strong contributor of epilepsy and epileptic seizures. We showed that transmission of Taenia solium infection was interrupted on a regional scale in endemic regions in Peru
Introducción. La neurocisticercosis (NCC) es una de las enfermedades helmínticas más frecuentes del SNC y causa de epilepsia sintomática en regiones pobres. Hay escasos estudios basados en comunidad sobre esta zoonosis y sus comorbilidades la epilepsia y la NCC. Metodología. Se desarrollaron en la Región Norte del Perú tres estudios basados en la comunidad, y una revisión sistemática cuyos objetivos fueron: a) evaluar la prevalencia de NCC asintomática, b) la prevalencia de epilepsia asociada a cisticercosis, c) determinación de la exposición a cisticercosis y d) desarrollar una intervención comunitaria que interrumpa la transmisión de cisticercosis. Resultados. De 256 pacientes asintomáticos que tuvieron una tomografía axial computarizada (TAC) cerebral sin contraste, 48 (18%) tuvo una NCC calcificada. La prevalencia de epilepsia encontrada fue de 17.25/1000 habitantes y la proporción de NCC en personas con epilepsia fue de 39% (109/282). El Western Blot (EITB-LLGP) para cisticercosis fue positivo en el 40% de los individuos con epilepsia, y en el 36.9% de la población general. La asociación entre cisticercosis y epilepsia tuvo un OR de 2.7 (95% CI 2.1-3.6, p <0.001). El tratamiento masivo con niclosamida en humanos (n=3), y población porcina más vacunación fue implementada en 107 comunidades rurales de Tumbes; en 105 de 107 no hubo nuevos cerdos infectados con cisticercosis. Conclusiones. (1) La NCC es un factor contribuidor de epilepsia, (2) Se puede cortar la trasmisión de T. solium a escala regional

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Visceral leishmaniasis (VL) is a disease caused by protozoa of the Leishmania donovani complex, whose infection has clinical spectrum ranging from asymptomatic infection to active disease characterized by fever, cachexia, hepatosplenomegaly, and immunosuppression. The healing or protective immunity require an antigen-specific type 1. The Montenegro skin test (DTH) has been interpreted as a marker of protective immunity. However, there is no known correlation between the DTH response to type 1 and DTH and immunity of type 1 are maintained in the long term. Thus, a longitudinal study of 8 years, nested in a cohort family held in Brazil, documented the status of DTH and cytokine production by peripheral blood mononuclear cells in response to antigen-specific stimulation. This study was the interdisciplinary approach of physicians, biochemists, nutritionists, veterinary medicine, biology and statistics. The results show that 46.2% of subjects were analyzed DTH positive at baseline. The prevalence of positive and DTH induration size increased with age (p = 0.0021). 15.7% of individuals positive DTH "retro-converted" the negative and 50.4% (64) of individuals negative DTH became positive. The size of DTH induration was correlated significantly with the antigen-induced production of IFN-γ (r = 0.6186, p = 0.0001). IL-6 was secreted at higher levels in peripheral blood mononuclear cells of individuals who "retro-converted" DTH positive to negative than individuals who remained stable DTH status (p = 0.005). Thus, IFN-γ produced by peripheral blood mononuclear cells, may be a surrogate marker for protective immunity instead of the DTH response. In addition, differences in innate immune response may determine whether individuals maintain or eliminate the infection by Leishmania infantum chagasi in asymptomatic patients
A leishmaniose visceral (LV) ? uma doen?a ocasionada por protozo?rios do complexo Leishmania donovani, cuja infec??o possui espectro cl?nico variando desde infec??o assintom?tica a doen?a ativa caracterizada por febre, caquexia, hepatoesplenomegalia e imunossupress?o. A cura ou prote??o exigem uma imunidade ant?geno espec?fica do tipo 1. O teste cut?neo de Montenegro (DTH) tem sido interpretado como um marcador de imunidade protetora. No entanto, n?o se sabe a correla??o do DTH com a resposta tipo 1 e se o DTH e a imunidade do tipo 1 s?o mantidos a longo prazo. Assim, um estudo longitudinal de 8 anos, aninhado a uma coorte familiar realizada no Brasil, documentou o status do DTH e a produ??o de citocinas por c?lulas mononucleares do sangue perif?rico em resposta a estimulo ant?geno-espec?fico. Os resultados obtidos mostram que 46,2% dos indiv?duos analisados foram DTH positivos no in?cio do estudo. A preval?ncia do DTH positivo e o tamanho da endura??o aumentaram com a idade (p = 0,0021). 15,7% dos indiv?duos DTH positivos retroconverteram a negativos e 50,4% (64) dos indiv?duos DTH negativos tornaram-se positivos. O tamanho da endura??o do DTH correlacionou-se significativamente com a produ??o ant?geno induzida de IFN-γ (r=0,6186, p=0,0001). IL-6 foi secretado em n?veis mais elevados por c?lulas mononucleares do sangue perif?rico dos indiv?duos que retroconverteram de DTH positivo para negativo do que os indiv?duos que mantiveram o status de DTH est?vel (p=0,005). Assim, o IFN-γ, produzido por c?lulas mononucleares do sangue perif?rico, pode ser um marcador substituto para a imunidade protetora em vez da resposta DTH. Al?m disso, as diferen?as na resposta imune inata podem determinar se os indiv?duos mant?m ou eliminam a infec??o por L. infantum chagasi em assintom?ticos

Orientador: Mariangela Ribeiro Resende
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: As informações que existem acerca da leishmaniose visceral humana, provêm em sua maioria das notificações realizadas nas áreas de alta endemicidade. Por isso, ainda há muitos aspectos a respeito da transmissão urbana e dos quadros de infecção assintomática que precisam ser elucidados. O dimensionamento real da prevalência da infecção por Leishmania chagasi pode contribuir para a definição e avaliação do impacto das medidas de controle. Com o objetivo de determinar a prevalência da infecção por L. chagasi em área de autoctonia recente, município de Araçatuba e, avaliar os fatores associados em relação aos casos humanos de leishmaniose visceral notificados, foi realizado um estudo transversal, com amostra estratificada de fase única, realizada em duas áreas urbanas de níveis sócio-econômicos distintos, designadas A1 (periférica, menor nível sócio-econômico) e A2 (central, melhor nível sócio-econômico). A soroprevalência foi avaliada com a utilização do teste imunocromatográfico com antígeno recombinante K39 (Ag-RK39). A prevalência observada foi de 18,4% (23/125) em A1 e 4,8% (6/125) em A2. A proporção entre indivíduos assintomáticos e casos de doença ativa nas áreas 1 e 2 foram respectivamente 1,35:1 e 2:1. Não houve diferença significativa da soropositividade na distribuição por idade, nem por sexo, entre as áreas. Contudo, foi observada diferença na proporção de casos assintomáticos entre as áreas, possivelmente associada aos níveis sócio-econômicos e intensidade de transmissão. Também houve relação com a presença canina nos últimos dois anos e a soropositividade para o Ag-rK39. As informações obtidas sugerem a associação da soroprevalência à presença canina nos dois últimos anos e reforça a estratégia de controle adotada
Abstract: Many information exist about human visceral leishmaniasis are origin to thepontificated cases, moreover, almost all data substantiating derive high levels transmission. So, there are many aspects about the urban transmission and asymptomatic infection to need to elucidated. The real comprehensive measurements about the Leishmania chagasi infection to be able to contribute to improve the assessment impact about the measures control. The objective to this study was determining the prevalence of asymptomatic visceral leishmaniasis infection in Araçatuba city, a recent autoctone area. This was a cross-sectional survey on a random sample of the population in two urban different areas, called A1 (outskirts, low social-economic condition) and A2 (central, good social-economic condition). The seroprevalence was assessing by the Immunochromatographic test with recombinant antibody K39 dipstick. The prevalence was 18.4% (23/125) in A1 and 4.8% (6/125) in A2. And the proportion between the asymptomatic and active disease in areas 1 and 2 was 1.35:1 and 2:1, respectively. There was no significant difference in age, nor gender, distribution of seropositivity between the areas. But we observed a difference in asymptomatic infection rates between the two areas, possibly associated with socioeconomic levels and transmission intensity. The data from this study suggest an associate between the human symptomatic seroprevalence and the presence of dogs in last two years old
Doutorado
Ciencias Basicas
Doutor em Clínica Médica

In November of 1984 and 1985, Euphorbia lathyris was planted into a field naturally infested with Macrophomina phaseolina located at the Campbell Avenue Farm in Tucson, Arizona. Plants without foliar symptoms and rhizosphere soil were sampled regularly from emergence until the following May or June. Soil rhizosphere populations ranged from 0.7-3.0 cfu/g soil in 1985 to 8.0-24.1 cfu/g soil in 1986, and did not change significantly over either growing season (P > 0.05). Both the incidence of disease and the number of infection sites per cm of root increased significantly (P < 0.05) over each growing season and were not related to rhizosphere soil populations of M. phaseolina (P > 0.05). The distribution of infection sites along the tap root over both growing seasons remained the same in that most were located in the top 0-7 cm of tap root. Infected E. lathyris without apparent symptoms were subjected to low-water and high-temperature stress treatments in growth chambers. Root infection was not found to be dependent upon any stress. Lesion development was significantly dependent upon the imposition of any stress treatment, and further root colonization was significantly dependent upon low-water stress (P < 0.05). M. phaseolina was consistently recovered from asymptomatic roots. A consistently lower leaf water potential was measured on infected E. lathyris than from non-infected controls when no stress treatment was applied. Polyclonal antisera made against hyphae and microsclerotia of M. phaseolina was not successful in detecting this pathogen in E. lathyris by I-ELISA. Antisera applied to fresh thin sections of infected plant tissue was effective in staining hyphae of M. phaseolina when used with a second antibody conjugated to fluorescence isothiocyanate or to an enzyme (to which a substrate was added to "stain" hyphae).

The aim of this thesis was to explore the features of asymptomatic bacteriuria (ASB) in elderly people living in the community, and to seek diagnostic tools to discriminate between ASB and symptomatic urinary tract infection (UTI). All men and women aged 80 and over living in an urban district of Falun, Sweden, were invited to participate. Urine samples were obtained together with information on symptoms and on health indicators. The same cohort was surveyed again after 6 and 18 months. Urinary cytokines were analysed in 16 patients with UTI, in 24 subjects with ASB and in 20 negative controls. ASB occurred at baseline in 19.0% of women and 9.4% of men, and was found at least once in 36.9% of women and in 20.2% of men. ASB in women was associated with reduced mobility and urge urinary incontinence. Of those with ASB at baseline, 60% still had bacteriuria at 6 and 18 months, but among those with repeated findings of ASB with E. coli, only 40% had the same bacterial strain after 18 months. In women, the risk of developing a UTI within 24 months was higher among those with ASB at baseline than in those without. Urinary levels of cytokines (CXCL1, CXCL8 and IL-6) and leukocyte esterase were higher in patients with UTI than in patients with ASB. There is convincing evidence that ASB is harmless and should not be treated with antibiotics. However, such treatment is still often given, thereby unnecessarily contributing to the increased number of bacteria resistant to common antibiotics. This study confirms the high prevalence of ASB in elderly people living in the community. In order not to be misled by a urinary test showing bacteria, it is important to restrict urinary testing for bacteria to patients where there is a suspicion of UTI. In elderly patients with diffuse symptoms or in patients who are unable to communicate their symptoms, further diagnostic help could possibly be obtained by evaluating the urinary levels of leukocyte esterase and/or IL-6.

Foi estudado o perfil nosológico da população ribeirinha do Baixo Rio Machado em Rondônia, área de Amazônia Ocidental no Brasil. Neste estudo, escolhemos abordar o perfil das seguintes doenças: malária, hepatite viral B e C, parasitose intestinal e papilomavírus humano. Estas doenças foram priorizadas devido à importância clínica e epidemiológica e também escassez de estudos referentes nas populações ribeirinhas amazônicas. Para isto, foi realizado um estudo descritivo no Baixo Rio Machado que se localiza a 250 km de Porto Velho (capital do Estado de Rondônia) pela margem direita do Rio Madeira, que é um afluente volumoso do Rio Amazonas, no Brasil. Nesta área, vivem aproximadamente 806 pessoas distribuídas em 55 comunidades ribeirinhas isoladas. Em Rondônia, encontramos locais, como o Rio Machado, que abrigam a presença de portadores assintomáticos do Plasmodium, fato que pode contribuir para a persistência desta doença na região. Para caracterizar o perfil da malária ribeirinha, focalizando aspectos da infecção assintomática e sintomática, foram realizados hemoscopia e Reação em Cadeia da Polimerase (PCR) com amplificação do DNA ribossomal do parasita para Plasmodium vivax e Plasmodium falciparum para o diagnóstico da malária. Foi considerado como assintomático o paciente com hemoscopia positiva ou PCR positivo que permaneceu sem sintomas durante pelo menos 60 dias. Foi realizado acompanhamento longitudinal de 70 dias após o primeiro corte transversal (nC1=585 pessoas) para observação dos pacientes assintomáticos diagnosticados por hemoscopia, onde 25 pacientes (4,25%) permaneceram assintomáticos durante todo esse seguimento. Após, foi realizado mais dois cortes transversais a cada 6 meses (nC2=583 pessoas, nC3=607 pessoas), com tratamento dos indivíduos assintomáticos diagnosticados por PCR no corte transversal anterior ou hemoscopia atual e também dos casos sintomáticos. Foi estudado, na população que permaneceu na área durante toda a pesquisa (n=379), o perfil e o impacto do tratamento da infecção assintomática. Houve diminuição da infecção por P. falciparum de seis vezes e aumento da prevalência de malária por P. vivax de aproximadamente três vezes. O diagnóstico por PCR foi de 2-5 vezes mais eficiente do que por hemoscopia e a prevalência de infecção assintomática foi de 16 a 22% nos cortes transversais. Assim, foi observada a importância do tratamento dos indivíduos assintomáticos para o controle da malária no local, sendo que o incremento de malária por Plasmodium vivax deve ter ocorrido devido a recaídas da doença. Com o estudo entomológico da área, foi verificado que o vetor Anopheles possui atividade hematofágica moderada e principalmente em região peridomiciliar, sendo o A. darlingi a principal espécie da região. Existem poucos dados sobre a prevalência de hepatites na população ribeirinha de Rondônia, o que dificulta a vigilância epidemiológica nestas regiões amazônicas. Foi realizado um estudo de prevalência de hepatite B e C na área, com 123 pacientes pertencentes a 5 comunidades ribeirinhas, incluindo todas as pessoas que estavam presentes na área no momento do corte transversal, de todas as faixas etárias. Foi realizada sorologia para os marcadores de hepatite B: HbsAg, Anti-Hbc (total) e Anti-Hbs e sorologia para hepatite C com o marcador anti-HCV. Foram encontrados 12 (14,7%) pacientes com hepatite B aguda, 29 (38,7%) pacientes apresentaram imunidade vacinal para hepatite B e 7 (9,3%) pacientes apresentaram hepatite C, sendo que um (1,3%) paciente tinha co-infecção para hepatite B e C. Notou-se que esta população ribeirinha está exposta às hepatites virais, sendo necessário intensificar a vigilância epidemiológica na área, assim como a cobertura vacinal e também fornecer cuidados preventivos, curativos e paliativos em relação a estas doenças. A infecção pelo papilomavírus humano (HPV) é altamente prevalente, sendo detectada em aproximadamente 10% a 20% da população sexualmente ativa entre 15 e 49 anos de idade. A introdução de testes mais acurados para a detecção do DNA do HPV em investigações epidemiológicas confirmou a importância do HPV, principalmente dos tipos de alto risco, como o principal fator de risco para o desenvolvimento de neoplasia intra-epitelial cervical e câncer do colo uterino. Não foram encontrados estudos sobre a existência do HPV em populações ribeirinhas amazônicas na literatura médica. Foi realizado, então, um estudo transversal para levantar a prevalência de HPV nesta população, com 84 participantes em idade sexualmente ativa presentes na área. Após coleta de consentimento informado e questionário clínico-epidemiológico, foi realizado exame para isolar o HPV. A tipagem do HPV foi realizada com amplificação dos DNAs por PCR empregando iniciadores genéricos seguida de hibridização em pontos, capaz de identificar mais de 40 tipos diferentes de HPVs. Foram encontradas 18 pacientes contaminadas pelo HPV, perfazendo 21,4% da amostra. Os tipos de HPV encontrados foram: 53, 58, 31, 56, 16, 83, 55, 66, 45, 51, 40, 42, 6, 68. Os tipos de HPV mais freqüentes foram 51 (23%), 58 (19%), 53 (7,7%), 83 (7,7%), sendo HPV 16 encontrado em 3,8% das pacientes HPV positivas e a prevalência do HPV de alto risco oncogênco foi de 13,1%. Desta forma, foi encontrado alta prevalência de HPV na população ribeirinha amazônica estudada, evidenciando a necessidade de vigilância epidemiológica para câncer de colo uterino na região. Por fim, foi estabelecido a prevalência de parasitoses intestinais na população, abordando a correlação das enteroparasitoses com malária assintomática e anemia, realizando um inquérito coproparasitológico na área incluindo pacientes de todas as faixas etárias, que estivessem dispostos a participar do estudo. A análise das amostras foi realizada pelo método da Sedimentação Espontânea (método de Lutz ou Hoffmann, Pons & Janer). Entre os 268 exames de fezes realizados, a prevalência de parasitose intestinal encontrada na região em estudo foi de 86,6%. Entre os helmintos, Ascaris lumbricoides (47%), Ancilostomideos (37,3%), Trichuris trichiura (3,4%), Capillaria hepatica (2,3%), foram os parasitas mais encontrados. Entre os protozoários foram encontrados: Entamoeba coli (21,4%), Entamoeba histolytica (12%), Giardia intestinalis (15,4%), Endolimax nana (10,1%) e Iodamoeba butschlii (7,5%). A alta prevalência de parasitose intestinal encontrada na pesquisa foi concordante com outros dados desenvolvidos na Região Amazônica. Com este estudo, a região da Amazônia Ocidental insere-se no cenário geográfico mundial de distribuição da Capillaria hepatica, particularmente, a região do Baixo Rio Machado.
Was studied the nosological profile of the riverside population of the Baixo Rio Machado in Rondônia, Western Amazon area of Brazil. In this study, was chosed the profile of following diseases: malaria, hepatitis B and C, intestinal parasite and human papillomavirus. These diseases have been prioritized due to clinical and epidemiological importance and scarcity of studies in the riverside Amazon population. For this, was conducted a descriptive study in the Baixo Rio Machado which is located 250 km from Porto Velho (capital of Rondônia State) in the right bank of the Rio Madeira which is a large tributary of the Amazon River in Brazil. In this area, live about 806 people distributed in 55 riversides communities isolated. In Rondônia, we find places such as the Rio Machado, which shelter to the presence of asymptomatic carriers of Plasmodium, which may contribute to the persistence of this disease in the region. To characterize the profile of malaria riverside, focusing on aspects of symptomatic and asymptomatic infections, were performed haemoscopia and Polymerase Chain Reaction (PCR) with amplification of ribosomal DNA for the parasite Plasmodium vivax and Plasmodium falciparum to the diagnosis of malaria. Was considered as asymptomatic patient with positive haemoscopia or positive or PCR that remained without symptoms for at least 60 days. Longitudinal follow-up was conducted for 70 days after the first cross section (nC1 = 585 people) for observation of asymptomatic patients diagnosed by haemoscopia where 25 patients (4.25%) remained asymptomatic throughout the follow-up. After was performed two cross cuts every 6 months (nC2 = 583 people, nC3 = 607 people), with treatment of asymptomatic individuals diagnosed by PCR in previous transverse cross-sections or haemoscopia a current and also symptomatic cases. We studied in the population that remained in the area throughout the study (no= 379), the profile and impact of treatment of asymptomatic infection. There was a decrease in infection by P. falciparum of six times and increased prevalence of malaria by P. vivax approximately three times. The diagnosis by PCR was 2-5 times more efficient than haemoscopia and the prevalence of asymptomatic infection was 16 to 22% in transverse cross-sections. Thus, was saw the importance of treatment of asymptomatic individuals for the control of malaria in the place, and the increase in malaria by Plasmodium vivax should have occurred due to relapse of the disease. With entomological study of the area, was saw that the vector Anopheles has moderate blood activity and especially in peridomiciliary region and the A. darlingi the main species in the region. There are few data on the prevalence of hepatitis in riverside population of Rondônia, which makes surveillance in Amazonian regions. Was conducted a study of prevalence of hepatitis B and C in the area, with 123 patients belonging to 5 communities, including all the people who were present in the area at the cross section of all ages. Serology was performed for markers of hepatitis B: HBsAg, anti-HBc (total) and anti-HBs and serology for hepatitis C with anti-HCV marker. Was found 12 (14.7%) patients with acute hepatitis B, 29(38.7%) patients demonstrated immunity to hepatitis B vaccine and 7(9.3%) patients had hepatitis C, with one (1.3%) patient had co-infection for hepatitis B and C. Realize that this riverside population is exposed to viral hepatitis, being necessary to intensify epidemiological surveillance in the area, as well as immunization coverage and provide preventive care, curative and palliative for these diseases. The infection by human papillomavirus (HPV) is highly prevalent, being detected in approximately 10% to 20% of the sexually active population between 15 and 49 years of age. The introduction of more accurate tests for the detection of HPV DNA in epidemiological investigations confirmed the importance of HPV, particularly types of high risk, as the main risk factor for the development of cervical intraepithelial neoplasia and cervical cancer. Was found no studies on the existence of HPV in riverside Amazonian populations in the medical literature. The transversal cross-section study was take up to raise the prevalence of HPV in this population, with 84 participants in sexually active age in the area. After collection of informed consent and clinical-epidemiological questionnaire, was conducted to isolate the HPV test. The typing of HPV was taking with the DNAs for PCR using generic primers followed by hybridization in points, able to identify over 40 different types of HPV. Was found 18 patients infected by HPV, comprising 21.4% of the sample. The HPV types found were: 53, 58, 31, 56, 16, 83, 55, 66, 45, 51, 40, 42, 6, 68. The most common HPV types were 51 (23%), 58 (19%), 53 (7.7%), 83 (7.7%) with HPV 16 found in 3.8% of HPV positive patients and prevalence the high risk HPV oncogenic was 13.1%. Thus, was find high prevalence of HPV in riverside Amazonian population studied, highlighting the need for surveillance for cancer of the cervix in the region. Finally, was established the prevalence of intestinal parasites in the population, deal the correlation of intestinal with asymptomatic malaria and anemia, taking the fecal examination conducting in the area including patients of all ages, who were willing to participate in the study. The analysis of samples was performed by the spontaneous sedimentation method (method of Lutz or Hoffmann, Pons & Janer). Among the 268 fecal examinations, the prevalence of intestinal parasite found in the region under study was 86.6%. Among helminths, Ascaris lumbricoides (47%), Ancilostomideos (37.3%), Trichuris trichiura (3.4%), Capillaria hepatica (2.3%) were found more parasites. Among the protozoa were: Entamoeba coli (21.4%), Entamoeba histolytica (12%), Giardia intestinalis (15.4%), Endolimax nana (10.1%) and Iodamoeba butschlii (7.5%).The high prevalence of intestinal parasite found in the survey was consistent with other data developed in the Amazon region. In this study, the region of the Western Amazon is part of the scenario of global geographic distribution of Capillaria hepatica, particularly the region of the Baixo Rio Machado.

Objective: The aims of this prospective clinical cohort study were to determine the prevalence of asymptomatic bacteriuria in dogs with cranial cruciate ligament disease and to determine which clinical parameters and clinicopathologic data are associated with asymptomatic bacteriuria. Another aim was to determine the incidence of surgical site infections in dogs with and without asymptomatic bacteriuria. Results: In 156 dogs with cruciate ligament disease, the prevalence of asymptomatic bacteriuria was 7.1%. Furthermore, the prevalence was 12.4% in female dogs and 0% in male dogs. The most common bacterial isolate was Escherichia coli. Patient sex, urine white blood cells/ high-powered field, and microscopic bacteriuria were significantly different between dogs with and without asymptomatic bacteriuria. Only 60% of dogs with microscopic bacteriuria had growth on urine aerobic culture. No significant difference was found in age, body weight, body condition score, duration of lameness, limb affected, or other urinalysis values between dogs with and without asymptomatic bacteriuria. Of the dogs that had 8-week repeat cultures, 2/3 dogs with asymptomatic bacteriuria had negative urine cultures and 3/43 without asymptomatic bacteriuria had positive urine cultures. Of 57 dogs that received surgery and had sufficient follow-up, 15 developed surgical site infection. All surgical site infections occurred in dogs without AB. The incidence of surgical site infection in this population was 26.3% (15/57). Conclusions: Prevalence of asymptomatic bacteriuria in dogs presenting with cranial cruciate ligament disease was similar to previously reported values in male and female dogs. This suggests that dogs with cranial cruciate ligament disease are not more prone to asymptomatic bacteriuria than dogs in previously studied populations. Preliminary data suggests that AB does not predispose dogs to SSI however further research and continued data collection is warranted.
Master of Science
Asymptomatic bacteriuria is defined as having bacteria in the urine without signs of lower urinary tract disease. The aim of this study was to determine the prevalence asymptomatic bacteriuria in dogs with cranial cruciate ligament disease. Additionally, another aim was to determine the incidence of surgical site infections after cranial cruciate ligament surgery in dogs with and without asymptomatic bacteriuria. Prevalence of asymptomatic bacteriuria in dogs presenting with cranial cruciate ligament disease was found to be similar to previously reported values in male and female dogs. This suggests that dogs with cranial cruciate ligament disease are not more prone to asymptomatic bacteriuria than dogs in previously studied populations. Preliminary data suggests that dogs with bacteria in the urine does not predispose dogs to SSI however further research and continued data collection is warranted.

Infections caused by resistant pathogens fail to respond to treatment, resulting in increased costs due to prolonged illness and hospitalization. Determining the extent of resistance in animal populations is thus of great importance to public health. In this work, we first showed that asymptomatic populations of Salmonella in pigs present greater genotypic and phenotypic diversity than disease-associated populations. Second, we identified a clonal population structure associated with asymptomatic Salmonella found in the Canadian swine industry and we confirmed that food-producing pigs are a significant reservoir of Salmonella enterica, more particularly the clinically important serotype Typhimurium DT104. Finally, we identified the possible independent evolution of multidrug-resistance in serotypes Typhimurium, Derby and Heidelberg. Our work on asymptomatic Salmonella enterica stresses the importance of linking ecology and evolutionary biology to public health in order to understand and predict the response of pathogenic bacteria to selective pressure imposed by host immunity, whether naturally or artificially induced.

theresa.j.ochoa@uth.tmc.edu
Article
BACKGROUND: Enteropathogenic Escherichia coli (EPEC) strains are pediatric pathogens commonly isolated from both healthy and sick children with diarrhea in areas of endemicity. The aim of this study was to compare the bacterial load of EPEC isolated from stool samples from children with and without diarrhea to determine whether bacterial load might be a useful tool for further study of this phenomenon. METHODS: EPEC was detected by polymerase chain reaction (PCR) of colonies isolated on MacConkey plates from 53 diarrheal and 90 healthy children aged <2 years. DNA was isolated from stool samples by cetyltrimethylammonium bromide extraction. To standardize quantification by quantitative real-time PCR (qRT-PCR), the correlation between fluorescence threshold cycle and copy number of the intimin gene of EPEC E2348/69 was determined. RESULTS: The detection limit of qRT-PCR was 5 bacteria/mg stool. The geometric mean load in diarrhea was 299 bacteria/mg (95% confidence interval [CI], 77-1164 bacteria/mg), compared with 29 bacteria/mg (95% CI, 10-87 bacteria/mg) in control subjects (P = .016). Bacterial load was significantly higher in children with diarrhea than in control subjects among children <12 months of age (178 vs 5 bacteria/mg; P = .006) and among children with EPEC as the sole pathogen (463 vs 24 bacteria/mg; P = .006). CONCLUSIONS: EPEC load measured by qRT-PCR is higher in diarrheal than in healthy children. qRT-PCR may be useful to study the relationship between disease and colonization in settings of endemicity.

This study demonstrates the first case report in which an NK Cell deficiency initially presented as an asymptomatic disseminated herpes simplex viremia (HSV). A pre-term 13- day- old patient presented with disseminated HSV after investigation because his twin brother was found to have HSV vesicular lesions. The patient remained asymptomatic throughout the entire hospital course. While 40% of neonates never exhibit vesicular lesions, most of the infants will be symptomatic with DIC and/or respiratory and/or hepatic failure. The HSV development in his twin brother prompted immediate multiple HSV PCR testing even though he was asymptomatic. The results were positive for HSV in both plasma & nasopharynx. He received intravenous acyclovir treatment for 21 days. Both CSF & brain MRI studies demonstrated no CNS involvement. He was discharged home with oral acyclovir for one year. Two months after being off acyclovir he developed herpetic vesicles which resolved with acyclovir treatment. Currently, he is on chronic acyclovir treatment. Lymphocyte enumeration tests demonstrated NK cell deficiency. Typically, HSV is a virulent symptomatic infection especially when it presents with viremia. Here we have a case of asymptomatic HSV viremia. Likewise, HSV infection does not usually recur after 1 year of acyclovir treatment. Here, we have a child presenting with what seems to be recurrent congenital HSV infection even with adequate treatment. These atypical HSV presentations may have been due to NK cell deficiency. We, therefore, propose that clinicians should consider NK cell deficiency as possible etiology when HSV presents in an atypical manner as described in our case.

La leishmaniose viscérale (LV) à Leishmania infantum est une zoonose qui sévit notamment autour du bassin méditerranéen. Elle atteint principalement le chien, qui représente le réservoir de l’infection. Chez l’homme, si la forme patente est rare, il existe de nombreux sujets porteurs asymptomatiques dans les zones d’endémies. Au cours de ce travail, nous avons abordé 3 problématiques importantes concernant la LV. La première problématique à porté sur l’importance du portage asymptotique humain à L. infantum au niveau mondial et de ses conséquences. Notre étude montre que la fréquence de porteurs asymptomatiques dépend des tests de détection utilisés et des populations étudiées et qu'elle peut atteindre jusqu'à 70% dans certaines zones d’endémies. Elle montre également que la transmission du parasite par don de sang est peu probable et que le rôle du portage asymptomatique comme réservoir n’est pas encore démontré. Elle souligne également la nécessité de détecter le portage asymptotique chez le donneur et le receveur de greffe et le risque de développement de la forme patente chez l’asymptomatique déprimé. La deuxième problématique porte sur le développement de procédés vaccinaux contre L. infantum par voie endonasale chez la souris BALB/c. Nos résultats montrent que la vaccination par voie nasale induit de manière reproductible une immunité systémique, cellulaire et humorale et que la protection dépend de paramètres tels que la nature et la dose des antigènes utilisées et la présence d’adjuvant tels que le CNF et le MPL. Enfin, la sélection d’une infection intradermique permet d’améliorer significativement la protection.La troisième partie porte sur la mise au point de modèles expérimentaux d’infection basés sur l’utilisation de parasites recombinants exprimant le gène de la luciférase. Nos travaux montrent que l’utilisation de tels outils permet de suivre l’infection à L. infantum in vitro, ex vivo et in vivo chez la souris BALB/c et de ce fait sont utiles pour le criblage de médicaments comme la miltéfosine et potentiellement pour tester des préparations vaccinales. Cet outil nous a permis en outre de révéler un nouveau site de prolifération parasitaire
Visceral leishmaniasis (VL) caused by L. infantum is a zoonotic disease present in the Mediterranean basin (LVM). Dogs represent the reservoir and the main victim of the disease. In man, besides a limited number of cases of patent VL, a great number of infection remains asymptomatic. In this report, three different aspects of VL have been studied.First, the prevalence and the consequences of asymptomatic carriers of L. infantum was evaluated worldwide. The prevalence of asymptomatic carriers depends on the selected detection tests and the studied population and can reach 70% in some endemic zones. Our study also shows that the role of asymptomatic carriers as reservoirs remains to be established. However, in immunocompromised asymptomatic carriers such as HIV positive individuals, infection can be reactivated.Second, we developed vaccine trials against L. infantum in the BALB/c mouse model using the nasal route. Nasal immunization with Leishmania antigens induces cellular and humoral systemic immunity. Protection depends on various parameters including the nature of antigens, the dose and the presence of adjuvants such as CNF or MPL. Protection was improved when mice were challenged by ID route.Third, we set up experimental models of infection based on the use of recombinant parasites expressing the luciferase gene. These tools allow us to trace the infection in vitro, ex vivo and in vivo and therefore are useful to evaluate the efficiency of drugs and potentially to assess vaccine preparations. Bioluminescence imaging was also useful to evidence a new potential site of parasite proliferation

Estudos relacionados à malária autóctone em regiões de baixa transmissão no Brasil ganham cada vez mais relevância científica e epidemiológica, pois revelam a manutenção desse cenário em regiões de Mata Atlântica remanescente. No sudeste do Estado de São Paulo, a ocorrência de surtos no município de Juquitiba tem sido foco de pesquisas sobre a prevalência de Plasmodium na população, com registros de casos assintomáticos. Relatos de ocorrência da doença ou da presença de anticorpos antiplasmodiais em gestantes nessa região não haviam sido descritos anteriormente. Embora infecções por P. falciparum em gestantes tenham sido amplamente abordadas na literatura, a interação entre P. vivax e P. malariae com esta coorte imunodeprimida foi pouco explorada até o momento. Nesse estudo nós monitoramos trimestralmente a circulação de Plasmodium em gestantes atendidas em cinco Unidades de Saúde de Juquitiba. Para isso foi empregado o diagnóstico por gota espessa e metodologias moleculares sensíveis para detecção do parasito, além de ensaios imunológicos para avaliação de parâmetros imunes humorais. Desse modo, foram detectadas infecções por P. vivax e P. malariae em gestantes, incluindo casos assintomáticos. A alta prevalência de anticorpos IgG nesta população mostrou importante exposição das gestantes ao Plasmodium. Em regiões com perfil semelhante ao apresentado neste estudo, o diagnóstico de malária poderia ser indicado no seguimento pré-natal
Studies related to autochthonous malaria in low transmission areas in Brazil have acquired scientific and epidemiological relevance, since they suggest continued transmission in remaining Atlantic Forest regions. In the Southeast of São Paulo State, outbreaks in the municipality of Juquitiba has been focus of studies on the prevalence of Plasmodium in the population, with reports of asymptomatic cases. Data on the occurrence of the disease or presence of antiplasmodial antibodies in pregnant women in this region were not described previously. Although P. falciparum infections in pregnant women have been widely addressed in the literature, the interaction of P. vivax and P. malariae with this immunocompromised cohort were poorly explored to date. In this study, we monitored quarterly the circulation of Plasmodium in pregnant women in five health facilities in Juquitiba. For this purpose, we performed diagnosis by thick blood film and sensitive molecular protocols for parasite DNA detection, as well immunological assays in order to evaluate humoral immune parameters. Through these tools, it was possible to detect infections due to P. vivax and P. malariae in pregnant women, including asymptomatic cases. The high prevalence of IgG antibodies showed a significant exposure of this population to Plasmodium. In regions with a similar profile presented in this study, the diagnosis of malaria might be indicated in prenatal care

This project suggested tha HIV people in Region A (Nelson Mandela Metropole, formerly Port Elizabeth) health districty of the Eastern Cape, seek HIV testing when they are already in stages three (late disease) and four (AIDS) of HIV infection. Data had been obtained from the AIDS Training Information and Counselling Centre in the Nelson Mandela Metropole in 2000. The consequences of diagnoses onlu in the advanced stages of HIV infection will have a devastating impact on case management. Therefore, this paper yielded important data for South African policy makers to write health and welfare policies that might improve the quality of life of those terminally infected with HIV.

Cette thèse se focalise sur l'étude du processus d'agrégation et de fragmentation des protéines. Plus particulièrement, des phénomènes cinétiques oscillatoires sont identifiés lors d’expériences sur les maladies à prions, une sous-catégorie des maladies amyloïdes. Dans un premier temps, nous remarquons que des oscillations atténuées et localisées à des endroits spécifiques sur les signaux expérimentaux sont observables. Ces oscillations mettent en avant la présence de phénomènes cinétiques complexes, sous-jacents, lors des processus cinétiques de protéines. Nous définissons une caractérisation paramétrique des oscillations dans le domaine fréquentiel. Puis, nous construisons un test statistique d'hypothèses permettant de confirmer la présence d'oscillations dans les signaux expérimentaux. Dans un second temps, nous introduisons et analysons mathématiquement un modèle cinétique capables d'engendrer des oscillations. Le modèle est considère deux espèces de monomères: un monomère pathologique qui polymérise et un monomère sain qui dépolymérise. Le modèle couple un système Lotka-Volterra pour les monomères à un système de croissance/fragmentation: Becker-Döring dans le cas discret en taille, Lifshitz-Slyozov dans le cas continu. L'étude mathématique de ces modèles conduit à de nouveaux problèmes intéressants et améliore la compréhension des phénomènes physiques sous-jacents
This thesis focuses on the study of the process of protein aggregation and fragmentation. In particular, oscillatory kinetic phenomena are identified in experiments on prion diseases, a subcategory of amyloid diseases. First, we notice that attenuated and localized oscillations at specific locations on the experimental signals are observable. These oscillations highlight the presence of complex, underlying kinetic phenomena during protein kinetic processes. We define a parametric characterization of oscillations in the frequency domain. Then, we construct a statistical hypothesis test to confirm the presence of oscillations in the experimental signals. In a second step, we introduce and mathematically analyze a kinetic model capable of generating oscillations. The model considers two species of monomers: a pathological monomer that polymerizes and a healthy monomer that depolymerizes. The model combines a Lotka-Volterra system for monomers with a growth/fragmentation system: Becker-Döring in the discrete case in size, Lifshitz-Slyozov in the continuous case. The mathematical study of these models leads to new and interesting problems and improves the understanding of the underlying physical phenomena

碩士
國立臺灣大學
流行病學研究所
97
Asymptomatic ratio, which is the relation of cases with no symptoms in proportion to cases infected with pathogens, is an important indicator in public health. However, symptoms of infected cases are not altogether caused by the pathogens. What is more, it is difficult to find out the real factor that leads to the symptoms of the case that is infected with multi-pathogen infection at the same time. As a result, we may have trouble estimating asymptomatic ratio of each pathogen in such a case. In this study, we use log-linear binomial regression model, in which independent variables are set as the situations of pathogen infection of the cases and dependent variable is set as whether the cases have symptoms that can be observed symptoms (symptom coding with 0, non-symptom coding with 1), for model fitting. We derive the regression coefficients of each independence variable from PROC GENMOD in SAS. Regression coefficient taking exponential is the probability of infected cases without symptoms caused by the pathogen. We call that probability pathogen-specific asymptomatic ratio. Intercept taking exponential is the probability of non-infected cases in asymptomatic state. We call that probability background asymptomatic ratio. We random sample 600 from Lin’s [1] study of 1104 children as an example. We find that while estimating asymptomatic ratio, log-linear binomial regression model is more direct and effective than logistic regression model, which is generally used in dealing with binary dependant variables. Moreover, log-linear binomial regression model is more clearly discriminate between the effects of background factors and those of pathogens. In terms of goodness-of-fit of two regression models to the data, they are both consistent with the observed data on the numbers of non-infected cases and infected cases in various situations. However, log-linear binomial regression model is more accurate than logistic regression model in fitting the observed numbers.

RESUMO - Introdução: As infecções associadas aos cuidados de saúde são um importante problema de saúde pública. Entre elas, as infecções urinárias são as mais frequentes associando‐se a elevados custos e morbilidade. Pretende‐se caracterizar as ITU adquiridas no Hospital (ITUaH) ocorridas num serviço de Medicina Interna de um hospital português. Métodos: Efectuou‐se um estudo de coorte (histórica) para determinação da incidência da ITUaH e da bacteriúria assintomática. Analisaram-se os dados correspondentes a uma amostra aleatória sistemática de 388 doentes, representativa dos 3492 admissões ocorridas, em 2014, nesse Serviço. Resultados: A taxa de incidência global de ITUaH foi de 6,2% (24/388; IC 95%:[3,8--‐8,6%]). Ocorreram 19,76 ITU por mil dias de cateter vesical (ITUaCV) e 4,17 ITUaCV por mil dias de internamento. A taxa de incidência de ITUaCV foi de 4% (15/388; IC 95%:[2%--‐6%]). Oitenta por cento destas infecções ocorreram em doentes sem indicação para a algaliação. Um quarto dos doentes desta coorte foram algaliados (24,7%; IC 95%: [20%--‐29%]), não se verificando indicação para o procedimento em 36,5% dos casos. Os principais factores de risco para a algaliação identificados foram a dependência total (OR: 24,47; IC 95%: [5,50--‐ 108,87]; p<0,001) a dependência grave (OR:11,43; IC 95% [2,56--‐50,93]; p=0,001) (escala de Barthel) e a carga de doença (OR: 1,19; IC 95% [1,03--‐1,38]; p=0,017) (índice de comorbilidade de Charlson). Foram utilizados CV em 759 dias dos 3591 dias de internamento quantificados neste estudo (21%). A Taxa de incidência de Bacteriúria Assintomática (BA) foi de 4,4% (IC 95%:[2--‐6%]). Cerca de 60% (10/17) desses doentes foram submetidos a tratamento contrariamente às recomendações clínicas actuais. Conclusões: Este estudo evidencia a necessidade de implementação de estratégias de prevenção, das quais se destaca a redução do número de algaliações. O tratamento da BA deve ser evitado.
ABSTRACT - Introduction: Healthcare associated infections associated are an important public health problem. Among them, the urinary tract infections are the most common, being associated to high costs and morbidity. We intend to characterize hospital-acquired urinary tract infections (HaUTI) occurred in an internal medicine department of a Portuguese hospital. Methods: An historical cohort study was carried out to determine both HaUTI and asymptomatic bacteriuria incidence. A systematic random sample of 388 patients, representative of the 3492 admissions occurred in that department in 2014, was analyzed. Results: The overall incidence rate of HaUTI was 6.2% (24/388; 95% CI:[3,8%--‐8,6%]). There were 19,76 urinary tract infections per thousand urinary catheter days (CAUTI) and 4,17 CAUTI per thousand days of hospitalization. The incidence rate of CAUTI was 4% (15/388; 95% CI:[2%--‐6%]). Eighty percent of these infections occurred in patients without indication for urinary catheterization. A quarter of the patients of this cohort had a urinary catheter (24,7%; 95% CI:[20--‐29%]), although there were no indications for the procedure in 36.5 % of cases. The main risk factors for urinary catheterization were the total dependence (OR: 24,47; 95% CI [5,50--‐108,87]; p < 0.001) and the severe dependency (OR: 11,43, 95% CI: [2,56 to 50,93]; p = 0.001) (Barthel Index) and the burden of disease (OR: 1,19; 95% CI: [1,03--‐1,38]; p=0,017) (Charlson Comorbidity Index). Urinary catheters were used in 759 days of the 3591 hospitalization days quantified in this study (21%). The incidence rate of asymptomatic bacteriuria (AB) was 4,4 % (95% CI: [2--‐6%]). Approximately 60 % (10/17) of these patients were treated contrarily to current clinical recommendations. Conclusions: This study highlights the need to implement prevention strategies, which stands to reduce the number of bladder catheterizations. The AB treatment should be avoided.

M.A. (Psychology)
The present study was undertaken in an attempt to understand and ascertain the nature and influence of psychological variables on the longevity of people who are infected withHN. The specific postulate of this study was that depression is the most important psychological variable that influences the longevity of people with my, either directly or indirectly. A number of variables were hypothesized to playa concomitant role with depression as factors that mediate longevity in people with my. These factors include learned helplessness, self-efficacy, sickness impact, sexual risk behaviors and substance use. The testing of these hypotheses involved an experimental group consisting ofHN positive, gay men who suffered from depression and a control group that consisted ofmv positive gay men who did not suffer from depression. None of the subjects had previously been diagnosed with depression. The subjects were subjected to testing of the mentioned psychological variables by means of the Hamilton-Depression Scale, the Attributional Style Questionnaire, the Coping Self-Efficacy Scale, the Biweekly Record of Sexual Behavior, the Substance Use Behavior Questionnaire and the Sickness Impact Profile. It was found that the experimental group differed significantly from the control group in terms of self-efficacy, sexual risk behavior, substance use and sickness impact. It has been speculated that the lack of significant difference between the experimental and control groups on learned helplessness could imply that equal amounts of learned helplessness was present in both groups.