Background: Arboviral diseases has reemerged in the last years affecting primarily the coast of Peru. Piura is an endemic region of Dengue, where the recent appearance of Chikungunya (CHIKV) and Zika (ZIKV) has been renewed. Aim: To assess the presence of DENV, CHIKV, and ZIKV in serum samples of patients with acute febrile illness in a locality of Piura, Peru and describe associated clinical features. Methodology: Descriptive cross-sectional study, sampling was done for convenience where it was obtained a total of 496 serum samples from patients with acute febrile illness were collected from 18 primary care centers. All samples were analyzed via real-time RT-PCR to detect DENV, CHIKV, and ZIKV. In addition, positive samples for DENV were also processed for serotypes 1 to 4 classification via RT-PCR. Results: DENV was the most common arbovirus detected in 170/496 (34.3%), followed by ZIKV in 39/496 (7.9%) and CHIKV in 23/496 (4.6%). Among the 170 samples positive for DENV, serotype 2 was the most predominant type present in 97/170 (57.1%) of samples, followed by the serotype 3 in 9/170 (5.3%). Headaches, muscle pain, and joint pain were the most common symptoms associated with fever in patients with DENV and ZIKV. No symptoms predominance was observed in patients with CHIKV. Conclusions: DENV is considered the most frequent arbovirus in Peru and the number of cases has increased dramatically in the last 5 years. However, it is not the only arbovirus that circulates along the northern coast of Peru. It has also been determined the presence of ZIKV and CHIKV in our population, which may suggest the circulation of other arboviruses that have not been detected. / Tesis

No description available.

Mosquito-borne diseases remain a significant burden on global public health. Maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. Although infection of the vertebrate host is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosquito vector. It is well known that invertebrates rely on small RNA pathways as an adaptive antiviral defense. The canonical antiviral response in these organisms involves dicer enzymes that cleave viral double-stranded RNA replicative intermediates (RIs) into small interfering RNAs (siRNAs; ~21-24 nucleotides). One strand of the siRNA duplex guides the targeting and destruction of complementary viral RNAs when loaded and retained in a multi-protein complex called the RNA-induced silencing complex. Here, we show that mosquito vectors mount a redundant double defense against virus infection mediated by two different small RNA pathways. Specifically, we demonstrate that in addition to a canonical antiviral response mediated by siRNAs, virus infection of the mosquito soma also triggers an antiviral immune pathway directed by ping-pong-dependent PIWI-interacting RNAs (piRNAs; ~24-30 nucleotides). The complexity of mosquito antiviral immunity has important implications for understanding how viruses both induce and modulate RNA-silencing responses in mosquito vectors. In mammals, viral RIs induce a range of relatively nonspecific antiviral responses. However, it remains unclear if viral RIs also trigger RNA silencing in mammals. Mosquito-borne viruses represent an ideal model for addressing this question as their transmission cycles involve alternating replication in mammalian and invertebrate hosts. Although we report identifying a subset of virus-derived small RNAs that appear to be products of RNA silencing in two mammalian cell lines infected with the mosquito-borne chikungunya virus (CHIKV), our studies suggest these small RNAs have little biological relevance in combating virus infections. Thus, while the accumulation of virus-derived siRNAs is essential to the survival of mosquitoes infected with CHIKV, they appear to have little functional significance in mammalian antiviral immunity. / Ph. D.

Les virus du Chikungunya (CHIKV) et de la dengue (DENV) sont deux virus émergents qui sévissent dans les régions tropicales et subtropicales du monde entier et qui sont transmis par les moustiques du genre Aedes. Ces dernières années, leur transmission a surtout progressé dans les zones urbaines et périurbaines touchant des millions d’individus et faisant de ces deux pathogènes des sujets majeurs de préoccupation pour la santé publique. Le Chikungunya et la Dengue sont des infections dites aiguës entrainant une mise en place rapide de la réponse immunitaire innée qui joue un rôle majeur dans le contrôle et l’évolution de la maladie. Les cellules Natural Killer (NK) représentent une population cellulaire clé de la réponse innée et jouent un rôle crucial dans les mécanismes de défense mis en place. A travers une étude ex vivo et in vitro, nous nous sommes intéressées à la caractérisation des cellules NK à travers (i) une étude phénotypique et fonctionnelle des cellules NK chez des patients infectés en phase aiguë par le CHIKV, DENV-2 ou par les deux virus et (ii) à la caractérisation des interactions entre les cellules NK et les cellules cibles infectées par le virus. L’ensemble de ces données contribue à mieux identifier l’implication des cellules NK dans le contrôle des infections par le CHIKV et DENV-2 permettant ainsi de mieux comprendre les mécanismes à l’origine des dérèglements de la réponse immunitaire. Au cours des dernières épidémies, plusieurs cas de patients coinfectés par les deux virus ont été répertoriés. De plus, l’expansion géographique des moustiques Aedes pourrait amener à une augmentation du nombre de cas de coinfections sans que les mécanismes sous jacents aux coinfections ne soient étudiés. Afin de pouvoir réponse à certaines questions concernant ce phénomène, nous avons mis en place un modèle expérimental de coinfection par CHIKV et DENV-2 chez le macaque Rhésus. / Chikungunya (CHIKV) and Dengue (DENV) virus are both re-emerging viruses transmitted by Aedes mosquitoes and responsible of widespread outbreaks in tropical and subtropical country. Recently, transmission of both viruses had emerged in urban and peri-urban area infecting millions of persons. Chikungunya and Dengue are both acute infections where innate immunity rapidly takes place and play a crucial role in the control and in the evolution of the disease. Natural Killer cells (NK) represent one of the major cellular population of innate immunity and play a crucial role in defense mechanism. By way of ex vivo and in vitro studies, we characterized NK cells by (i) a phenotypic and functional study of NK cells in CHIKV, DENV-2 infected patients or CHIKV/DENV-2 co-infected patients and (ii) characterization of NK cells interactions with infected target cells. During last outbreaks, several cases of co-infected patients were reported. Moreover, geographic spread of Aedes mosquitoes could increase number of coinfection cases without underlying mechanisms being explored. In order to respond to certain questions regarding coinfections, we realized a co-infected CHIKV and DENV-2 experimental model in Rhesus macaques.Together, these data will contribute to better identify NK cells implication in the control of CHIKV and DENV-2 infections allowing a better comprehension of mechanisms that causes immune system disorder.

Chikungunya is a mosquito-transmitted disease caused by Chikungunya virus (CHIKV). Symptoms of Chikungunya include debilitating joint pain and swelling, fever and rash. CHIKV was first discovered in 1953 in Tanzania, and has since caused periodic outbreaks of disease. The virus reemerged recently in 2004 and has since spread around the world affecting more than 3 million people. The different strains of CHIKV have been grouped into three phylogenetic clades: West African, Asian and East/Central/South African (ECSA). There are no FDA approved medicines or vaccines used to treat or prevent CHIKV infection. The antiviral drug, T-705 (commercially known as Favipiravir), has recently been shown to have activity against CHIKV. T-705 has already been approved in Japan for the treatment of influenza and is currently going through clinical trials in the US. Since there may be phenotypic differences between the clades of CHIKV, it is important to first characterize distinctions between the strains and determine the susceptibility of these strains to treatment. To do this, we obtained two different CHIKV strains from each of the three phylogenetic groups. These CHIKV strains displayed differences in their ability to replicate in cell culture and exhibited only slight differences in susceptibility to T-705 treatment. However, more profound differences were observed in mouse models where differences in disease severity and response to T-705 treatment were observed.

Les virus du Chikungunya (CHIKV) et de la dengue (DENV) sont deux virus émergents qui sévissent dans les régions tropicales et subtropicales du monde entier et qui sont transmis par les moustiques du genre Aedes. Ces dernières années, leur transmission a surtout progressé dans les zones urbaines et périurbaines touchant des millions d'individus et faisant de ces deux pathogènes des sujets majeurs de préoccupation pour la santé publique. Le Chikungunya et la Dengue sont des infections dites aiguës entrainant une mise en place rapide de la réponse immunitaire innée qui joue un rôle majeur dans le contrôle et l'évolution de la maladie. Les cellules Natural Killer (NK) représentent une population cellulaire clé de la réponse innée et jouent un rôle crucial dans les mécanismes de défense mis en place. A travers une étude ex vivo et in vitro, nous nous sommes intéressées à la caractérisation des cellules NK à travers (i) une étude phénotypique et fonctionnelle des cellules NK chez des patients infectés en phase aiguë par le CHIKV, DENV-2 ou par les deux virus et (ii) à la caractérisation des interactions entre les cellules NK et les cellules cibles infectées par le virus. L'ensemble de ces données contribue à mieux identifier l'implication des cellules NK dans le contrôle des infections par le CHIKV et DENV-2 permettant ainsi de mieux comprendre les mécanismes à l'origine des dérèglements de la réponse immunitaire. Au cours des dernières épidémies, plusieurs cas de patients coinfectés par les deux virus ont été répertoriés. De plus, l'expansion géographique des moustiques Aedes pourrait amener à une augmentation du nombre de cas de coinfections sans que les mécanismes sous jacents aux coinfections ne soient étudiés. Afin de pouvoir réponse à certaines questions concernant ce phénomène, nous avons mis en place un modèle expérimental de coinfection par CHIKV et DENV-2 chez le macaque Rhésus.

Chikungunya est un alphavirus transmis par les moustiques (Aedes) et qui provoque de la fièvre, des éruptions cutanées, des myalgies et des arthralgies. La maladie (CHIKVD) est transitoire, mais des formes sévères menant à des arthrites chroniques incapacitantes ont été signalées. Nous avons dans un premier temps étudié prospectivement les paramètres cliniques et immunologiques associés à la maladie chez des patients hospitalisés et identifiés comme étant 'guéris' ou 'chronique' à M12 après l'infection. Dans la deuxième partie, nous avons observé in vitro les mécanismes et le rôle de l'apoptose dans le processus infectieux permettant au virus de persister dans les sanctuaires tissulaires. En phase aiguë, une forte réponse immune dominée par une activation des cellules NK/dendritique/cellules T, la production d'anticorps spécifiques et une faible production de cytokines Th1 > Th2 a été observée mais sans aucune différence significative entre les deux groupes. Cependant, la virémie initiale s'est révélée beaucoup plus élevée dans le groupe chronique est nous avons pu identifier du matériel viral dans les macrophages du tissu synovial d'un patient chronique post-CHIKVD (M18). Dans la deuxième partie de l'étude, nous avons constaté que CHIKV est capable d'induire l'apoptose par la voie intrinsèque et extrinsèque et également par un mécanisme 'bystander'. De plus, nous avons observé que le CHIKV présent dans des corps (blebs) apoptotiques était capable d'infecter les cellules voisines (Hela et macrophage MM6). Notre étude a permis de mettre en évidence pour la première fois que CHIKV contrôle et détourne à son profit les mécanismes de défense anti-infectieux.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-02-15T14:53:05Z No. of bitstreams: 1 EdsonMenesesDaSilvaFilho_DISSERT.pdf: 1071828 bytes, checksum: 66af333e048ec8dc3d85d5abd30c9a47 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-02-20T00:13:34Z (GMT) No. of bitstreams: 1 EdsonMenesesDaSilvaFilho_DISSERT.pdf: 1071828 bytes, checksum: 66af333e048ec8dc3d85d5abd30c9a47 (MD5) / Made available in DSpace on 2018-02-20T00:13:34Z (GMT). No. of bitstreams: 1 EdsonMenesesDaSilvaFilho_DISSERT.pdf: 1071828 bytes, checksum: 66af333e048ec8dc3d85d5abd30c9a47 (MD5) Previous issue date: 2017-12-12 / O v?rus da Chikungunya (CHIK) ? uma epidemia no Brasil com 170.000 casos no primeiro semestre de 2016. Mais de 60% dos pacientes apresentam rea??o e remiss?o de artralgia cr?nica com dor debilitante que dura anos. N?o existem agentes terap?uticos espec?ficos para tratar e reabilitar pessoas infectadas com CHIK. Dor persistente pode levar ? incapacita??o exigindo tratamento farmacol?gico de longo prazo. Os avan?os nos tratamentos n?o farmacol?gicos s?o necess?rios para promover o al?vio da dor sem efeitos colaterais e restaurar a funcionalidade. Aqui, n?s demonstramos que a Estimula??o Transcraniana com Corrente Cont?nua (ETCC) sobre o c?rtex motor prim?rio reduz significativamente a dor na fase cr?nica da CHIK. Nossos achados sugerem que a ETCC pode ser uma terapia eficaz, barata e implant?vel em ?reas que n?o possuem recursos e que apresentam um grande n?mero de pacientes com dor cr?nica persistente gerada pela CHIK. / The Chikungunya (CHIK) virus is epidemic in Brazil, with 170,000 cases in the first half of 2016. More than 60% of patients present relapsing and remitting chronic arthralgia with debilitating pain lasting years. There are no specific therapeutic agents to treat and rehabilitee infected persons with CHIK. Persistent pain can lead to incapacitation, requiring long-term pharmacological treatment. Advances in non-pharmacological treatments are necessary to promote pain relief without side effects and to restore functionality. Here, we demonstrate that the transcranial direct current stimulation (tDCS) across the primary motor cortex significantly reduces pain in the chronic phase of CHIK. Our findings suggest tDCS could be an effective, inexpensive and deployable therapy to areas lacking resources with a great number of patients with chronic CHIK persistent pain.

abstract: The role of climate change, as measured in terms of changes in the climatology of geophysical variables (such as temperature and rainfall), on the global distribution and burden of vector-borne diseases (VBDs) remains a subject of considerable debate. This dissertation attempts to contribute to this debate via the use of mathematical (compartmental) modeling and statistical data analysis. In particular, the objective is to find suitable values and/or ranges of the climate variables considered (typically temperature and rainfall) for maximum vector abundance and consequently, maximum transmission intensity of the disease(s) they cause. Motivated by the fact that understanding the dynamics of disease vector is crucial to understanding the transmission and control of the VBDs they cause, a novel weather-driven deterministic model for the population biology of the mosquito is formulated and rigorously analyzed. Numerical simulations, using relevant weather and entomological data for Anopheles mosquito (the vector for malaria), show that maximum mosquito abundance occurs when temperature and rainfall values lie in the range [20-25]C and [105-115] mm, respectively. The Anopheles mosquito ecology model is extended to incorporate human dynamics. The resulting weather-driven malaria transmission model, which includes many of the key aspects of malaria (such as disease transmission by asymptomatically-infectious humans, and enhanced malaria immunity due to repeated exposure), was rigorously analyzed. The model which also incorporates the effect of diurnal temperature range (DTR) on malaria transmission dynamics shows that increasing DTR shifts the peak temperature value for malaria transmission from 29C (when DTR is 0C) to about 25C (when DTR is 15C). Finally, the malaria model is adapted and used to study the transmission dynamics of chikungunya, dengue and Zika, three diseases co-circulating in the Americas caused by the same vector (Aedes aegypti). The resulting model, which is fitted using data from Mexico, is used to assess a few hypotheses (such as those associated with the possible impact the newly-released dengue vaccine will have on Zika) and the impact of variability in climate variables on the dynamics of the three diseases. Suitable temperature and rainfall ranges for the maximum transmission intensity of the three diseases are obtained. / Dissertation/Thesis / Doctoral Dissertation Applied Mathematics 2018

Las enfermedades metaxénicas en el Perú constituyen uno de los principales problemas de salud, teniendo gran impacto sobre la salud pública nacional; debido a esta problemática se planteó la pregunta de investigación ¿cuál es el rol de la enfermera en la prevención y control del dengue, chikungunya y zika en red de servicios de salud de Chiclayo, Perú 2017?, tuvo como objetivos describir y analizar el rol de la enfermera (o) en la prevención y control en la red de servicios de salud Chiclayo. Teniendo como bases teórico conceptuales al autor Ayuso D. en su libro enfermería familiar y comunitaria, y la norma técnica peruana de prevención y control de enfermedades metaxénicas. Esta Investigación fue de tipo cualitativa con abordaje metodológico estudio de caso. Los sujetos de estudio fueron 10 enfermeras de los centros de salud de la red de servicios de salud Chiclayo escenario II y III según riesgo entomológico. El tamaño de la muestra se determinó con técnica de saturación y redundancia, se utilizó la entrevista semiestructurada para la recolección de datos, siendo analizadas en tres fases: pre análisis, codificación, categorización. Así mismo se tuvo como base los principios éticos y los criterios de rigor científico. Del análisis realizado se obtuvo como resultado cuatro categorías: Educación para la prevención y control de enfermedades como dengue, chikungunya y zika, cuidado de enfermería en la vigilancia epidemiologia y entomológica, limitantes para la prevención y control de enfermedades antes mencionadas y concertación multisectorial en enfermería en enfermedades de vigilancia epidemiológica.