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<p>Infectious diseases spreading in a human population can occasionally exhibit sudden transitions in their qualitative dynamics. Previous work has been very successful in predicting such transitions in New York City's measles incidence rates using the standard SIR model (susceptible, infected, recovered). This work relied on a dataset spanning 45 years, which we have extended to 93 years (1891-1984). We continue previous research in transition analysis on this larger dataset, and compare resonant and transient periods predicted to exist in NYC's measles incidence rates with those observed through a continuous wavelet transform of the data. We find good agreement between SIR predictions and observation, and in particular note the likely existence of previously unobserved hysteresis early in our new time-series.</p> / Master of Science (MSc)

Les virus Nipah (NiV) et Hendra (HeV) appartiennent au genre Henipavirus au sein de la famille des Paramyxoviridae. Cette famille comporte de nombreux pathogènes tel que le virus de la rougeole (MeV). Les paramyxovirus possèdent un génome de type ARN simple brin encapsidé par la nucléoprotéine (N) au sein d'une nucléocapside hélicoïdale. N interagit avec la phosphoprotéine (P) et cette dernière recrute la polymérase (L) qui assure la transcription et la réplication du génome viral. L'objectif de mon projet de thèse était de caractériser les protéines N et P ainsi que les interactions qui existent entre elles chez les trois virus, NiV, HeV et MeV. A la différence du MeV, qui a été intensivement étudié au cours des dernières années, les données moléculaires et structurales sur les Henipavirus étaient très limitées. A l'aide d'analyses computationnelles, nous avons pu déchiffrer l'organisation modulaire de N et de P, et nous avons montré que les régions, C-terminale de N (NTAIL) et N-terminale de P (PNT), sont prédites comme intrinsèquement désordonnées (RIDs). Les RIDs sont des régions fonctionnelles dépourvues de structures secondaires et tertiaires stables dans des conditions physiologiques. En utilisant des approches biochimiques et biophysiques, nous avons confirmé que NTAIL et PNT sont désordonnées. Elles conservent toutefois des structures secondaires transitoires qui pourraient correspondre à des éléments de reconnaissance moléculaire (ou MoREs) impliqués dans de transitions structurales en présence d'un partenaire. / The Paramyxoviridae family includes many important human and animal pathogens, such as measles virus (MeV), a morbillivirus, and the emerging Nipah (NiV) and Hendra (HeV) viruses, members of the Henipavirus genus. Paramyxoviruses possess a negative-strand RNA genome that is encapsidated by the nucleoprotein (N) into a helical nucleocapsid. N interacts with the phosphoprotein (P), and this latter recruits the polymerase that ensures genome replication and transcription. My PhD project has mainly focused on the characterization of the N and P proteins and on the interactions between these two proteins from the three cognate viruses, namely NiV, HeV and MeV. While MeV has been extensively studied through the past years, structural and molecular information on Henipavirus N and P proteins were rather scarce. Using computational analyses, we deciphered the modular organization of Henipavirus N and P. Intrinsically disordered regions (IDRs) were predicted within these proteins, notably at the C-terminus of N (referred to as NTAIL), and at the N-terminus of P (referred to as PNT). IDRs are functional despite they lack of a well-defined 3-D structure under physiological conditions. Biochemical and biophysical approaches pointed out a mostly disordered state for both NTAIL and PNT, although they were shown to contain short-order prone segments (i.e. molecular recognition elements, MoREs). These latter are involved in partner recognition and in disorder-to-order transitions. The C-terminal domains of the P proteins (referred to as PXD) were found to bind to NTAIL and to induce an &#945;-helical transition thereof.

O uso de vacinas seguras e eficazes é uma intervenção em saúde pública bem consolidada nas últimas décadas com grande impacto na queda da prevalência das doenças infecciosas. O controle sorológico do estado vacinal e de proteção de uma população é essencial, entretanto precisamos de alternativas para estes estudos. Escolares são um grupo em que o acesso para coleta de sangue é problemático. A saliva pode ser um material alternativo perfeitamente aceitável para crianças e outros grupos protegidos. Para controle de vacinação e incidência de toxoplasmose, nós promovemos uma exposição interativa sobre higiene em escolas públicas para coletar saliva de 249 estudantes do 7º a 9º anos do ensino fundamental, de onde detectamos a prevalência de resposta IgG específica e, portanto, proteção vacinal para a vacina tríplice viral ou detecção de infecção pelo T. gondii. Para evitar a variabilidade da concentração de IgG em saliva, nós desenvolvemos e validamos um ensaio de captura de IgG por proteína A de S. aureus na fase sólida, com revelação da especificidade da IgG pelo uso de antígenos recombinantes de vírus do sarampo, rubéola e caxumba, além de extrato antigênico de T. gondii. Estes antígenos biotinilados ligados a IgG foram obtidos por sistema avidina-biotina-peroxidase. Foram 249 salivas de escolares, 47 soros e salivas da graduação e, para validação, cinquenta soros positivos e quarenta soros negativos para controle, sendo eles soros de infantes, entre 8 e 12 meses de idade. Os testes tinham reprodutibilidade maior que 98% e sensibilidade e especificidade maior que 95%. Detectamos na população de estudantes uma prevalência de toxoplasmose de 8,5% (I.C. 95% 5-11,9%), uma proteção vacinal para sarampo de 96,8% (I.C. 95% 94,6-99%), para rubéola de 59,1% (I.C. 95% 53-65%) e para caxumba de 57.5% (I.C. 95% 51,3-63,6%). Nossa abordagem foi eficiente em todos os aspectos, desde a exposição itinerante, o uso de saliva e no desenvolvimento de ensaios confiáveis para a determinação da proteção vacinal de estudantes e na prevenção da toxoplasmose. Com este conhecimento, medidas adequadas de saúde pública, como revacinação, podem ser adequadamente planejadas. / The use of safe vaccines and are a well-established public health intervention in recent years with great impact on the last of the infectious diseases. Serological control of the vaccination status and protection of a population is essential, the study alternatives for these studies. Schoolchildren are a group in which access to blood collection is problematic. Saliva may be an appropriate alternative material for children and other protected groups. The disclosure of vaccination and analysis on an extinguishment is one of the projected lectures of the community lectures of the education of Equality of Equality and, therefore, vaccine a viral vaccine or detection of T. gondii infection. In order to avoid IgG variability in saliva, we developed and validated an IgA capture assay by continuous-phase S. aureus protein A with IgG specificity revealed by the use of recombinant measles, rubella and mumps, as well as the antigenic extract of T. gondii. These biotinylated antigens linked an IgG antibody to the avidin-biotin-peroxidase system. 249 saliva from schoolchildren, 47 serums and graduation salutations and, for validation, fifty positive sera and forty negative sera for the control, being sera of infants between 8 and 12 months of age. The tests had greater reproducibility than 98% and sensitivity and specificity greater than 95%. We detected a prevalence of toxoplasmosis of 8.5% (95% CI 5-11.9%), measles vaccine protection from 96.8% (95% CI: 94.6-99%), for rubella of 59.1% % (95% CI 53-65%) and for mumps 57.5% (95% CI 51.3-63.6%). The approach was effective in all aspects, from the traveling exhibition, to the use of saliva and the development of research for the identification of temporary vaccination and the prevention of toxoplasmosis. With this knowledge, public health measures such as revaccination can be planned.

O uso de vacinas seguras e eficazes é uma intervenção em saúde pública bem consolidada nas últimas décadas com grande impacto na queda da prevalência das doenças infecciosas. O controle sorológico do estado vacinal e de proteção de uma população é essencial, entretanto precisamos de alternativas para estes estudos. Escolares são um grupo em que o acesso para coleta de sangue é problemático. A saliva pode ser um material alternativo perfeitamente aceitável para crianças e outros grupos protegidos. Para controle de vacinação e incidência de toxoplasmose, nós promovemos uma exposição interativa sobre higiene em escolas públicas para coletar saliva de 249 estudantes do 7º a 9º anos do ensino fundamental, de onde detectamos a prevalência de resposta IgG específica e, portanto, proteção vacinal para a vacina tríplice viral ou detecção de infecção pelo T. gondii. Para evitar a variabilidade da concentração de IgG em saliva, nós desenvolvemos e validamos um ensaio de captura de IgG por proteína A de S. aureus na fase sólida, com revelação da especificidade da IgG pelo uso de antígenos recombinantes de vírus do sarampo, rubéola e caxumba, além de extrato antigênico de T. gondii. Estes antígenos biotinilados ligados a IgG foram obtidos por sistema avidina-biotina-peroxidase. Foram 249 salivas de escolares, 47 soros e salivas da graduação e, para validação, cinquenta soros positivos e quarenta soros negativos para controle, sendo eles soros de infantes, entre 8 e 12 meses de idade. Os testes tinham reprodutibilidade maior que 98% e sensibilidade e especificidade maior que 95%. Detectamos na população de estudantes uma prevalência de toxoplasmose de 8,5% (I.C. 95% 5-11,9%), uma proteção vacinal para sarampo de 96,8% (I.C. 95% 94,6-99%), para rubéola de 59,1% (I.C. 95% 53-65%) e para caxumba de 57.5% (I.C. 95% 51,3-63,6%). Nossa abordagem foi eficiente em todos os aspectos, desde a exposição itinerante, o uso de saliva e no desenvolvimento de ensaios confiáveis para a determinação da proteção vacinal de estudantes e na prevenção da toxoplasmose. Com este conhecimento, medidas adequadas de saúde pública, como revacinação, podem ser adequadamente planejadas. / The use of safe vaccines and are a well-established public health intervention in recent years with great impact on the last of the infectious diseases. Serological control of the vaccination status and protection of a population is essential, the study alternatives for these studies. Schoolchildren are a group in which access to blood collection is problematic. Saliva may be an appropriate alternative material for children and other protected groups. The disclosure of vaccination and analysis on an extinguishment is one of the projected lectures of the community lectures of the education of Equality of Equality and, therefore, vaccine a viral vaccine or detection of T. gondii infection. In order to avoid IgG variability in saliva, we developed and validated an IgA capture assay by continuous-phase S. aureus protein A with IgG specificity revealed by the use of recombinant measles, rubella and mumps, as well as the antigenic extract of T. gondii. These biotinylated antigens linked an IgG antibody to the avidin-biotin-peroxidase system. 249 saliva from schoolchildren, 47 serums and graduation salutations and, for validation, fifty positive sera and forty negative sera for the control, being sera of infants between 8 and 12 months of age. The tests had greater reproducibility than 98% and sensitivity and specificity greater than 95%. We detected a prevalence of toxoplasmosis of 8.5% (95% CI 5-11.9%), measles vaccine protection from 96.8% (95% CI: 94.6-99%), for rubella of 59.1% % (95% CI 53-65%) and for mumps 57.5% (95% CI 51.3-63.6%). The approach was effective in all aspects, from the traveling exhibition, to the use of saliva and the development of research for the identification of temporary vaccination and the prevention of toxoplasmosis. With this knowledge, public health measures such as revaccination can be planned.

Measles remains a major global public health problem. Attainment of high population immunity to measles through vaccination is necessary to control this disease. Children infected with HIV infection often experience secondary measles vaccine failure by 2 years of age, making them susceptible to measles. It is not clear whether HIV-infected children on Highly Active Antiretroviral Treatment (HAART), older than 2 years, have a higher risk of measles than HIV-uninfected children. This retrospective cohort study, guided by the proximate determinants framework, was conducted to compare the risk of measles between HIV-infected children on HAART (exposed) and HIV-uninfected peers (unexposed). The age group with the highest measles susceptibility in the exposed children, which could inform timing for revaccination, was investigated. The role of age at initiation of HAART, low CD4+ count, and undernutrition as predictors of the risk of measles in the exposed children was examined. Univariate, bivariate, and binomial logistic regression analytical procedures were used in data analysis. Results showed no significant difference in the risk of measles between exposed and unexposed children. The age groups 5 to 9 years and 2 to 4 years were the first and second most affected by measles among the exposed children. Undernutrition (stunting) was a significant predictor of measles in exposed children (odds ratio of 4.14, p = 0.02), while age at initiation of HAART and CD4+ count prior to measles exposure were not. The study findings provide evidence to inform vaccination policy and nutrition care for HIV-infected children on HAART in Uganda, so as to reduce their risk of measles illness and mortality, thus contributing to positive social change for the children and the country.

The dissertation deals with the infant mortality decline in Iceland during the 19th and early 20th Century. It shows that despite its low degree of urbanization, pre-transitional Iceland displayed higher infant mortality rates than most other European countries. Levels are only comparable with a few areas in Europe, all of whom were known for a tradition of artificial feeding of newborns. In the Icelandic case, infants were either not breastfed at all or were weaned at a very young age. Another characteristic of infant mortality in Iceland were huge fluctuations during epidemics. Because of the isolation of the country, several diseases that had become endemie in other societies, such as measles, became dangerous epidemics in Iceland and affected all age groups. After 1850 the effects of epidemics declined and 20 years later there was a steep decline in infant mortality. By the beginning of the 20th Century infant mortality in Iceland was lower than in most other societies. Although epidemics often had important temporary consequences upon infant mortality level in pretransitional Iceland, being breastfed or not was without doubt the most important determinant of infant survival. There were huge differences in infant mortality levels between areas where breastfeeding was common and those where newborns were artificially fed. Towards the turn of the 20th Century significant changes occurred. Even though there were still differences in infant mortality between those babies who were breastfed and those who were not, infant survival had improved greatly and survival chances of Icelandic newborns that were fed artificially became in an international perspective relatively good. Midwives played a central role in the infant mortality decline in Iceland. Growing secularization during the second part of the 19th Century improved educational opportunities for women and also changed the content of education. Improved educational opportunities were reflected in changes in the education of midwives. At the same time there was growth in the publication of books that directly dealt with the issue of infant health. The increase in the number of educated midwives was a factor of central importance. The interaction between midwives and a literate population was most likely the key to infant survival in the Nordic countries. This study shows that that the custom to breastfeed spread earlier in areas with higher literacy. Not only is it plausible that the interest in changing prevailing traditions was directly related to literaey levels of individuai mothers, it is also shown that midwives had the best education in areas where literacy rates were high. On the other hand, the remarkable improvements in infant survival obtained towards the end of the 19th Century were scarcely linked to changes in the economic structure. Those factors only started to play an important role in the 20th Century. In its initial stages, changes in infant feeding and improvements in personal hygiene were more important / digitalisering@umu

<p>The aim of the study was to describe immunization coverage for DPT, Polio and Measles among children of ages between 12 to 18 months in Kawempe Division and to investigate factors associated with immunization coverage. A cross-sectional survey was conducted in 239 households with children aged between 12-18 months in five villages that were selected through multi-stage cluster sampling. Information on demographic and socio-economic factors and immunization status was obtained from mothers and caretakers. Immunization coverage and analysis of associations between immunization coverage and demographic and socio-economic factors were done.</p>

This thesis represents the first anthropological perspective to be offered on the nature of the Klondike Gold Rush population. In order to better understand the experience of the average gold rusher, morbidity and mortality patterns are examined for the residents of the Yukon Territory following the discovery of gold in the region (1898-1904). Infectious diseases such as measles, pneumonia, smallpox and typhoid fever are the primary focus of this study, however local factors such as the severe climate and the seclusion of the gold fields from the outside world also offers an interesting opportunity to examine the consequences of leading a particularly harsh and physically demanding lifestyle in an inhospitable environment. / October 2008