Objectives. Acute flaccid paralysis (AFP) has recently emerged as a major central nervous system complication associated with West Nile virus (WNV) infection. The spectrum of clinical presentations of AFP in WNV infection and its sequelae have not been well-studied. Methods. We describe three patients with AFP due to WNV infection and review the clinical presentations of 56 patients with this complication derived from published studies. Results. Patients with AFP and WNV presented with a spectrum of illness ranging from single extremity paralysis to quadriparalysis with cranial nerve involvement. Patients commonly developed respiratory failure (54%) and bladder dysfunction (22%). While fever was nearly universal (92%), signs of meningismus were less common (17%). Cerebrospinal fluid (CSF) analysis generally revealed a modest pleocytosis, and imaging studies were not diagnositic. Persistent neurologic impairment occurred in all survivors; overall mortality rate was high (22%) and was associated with both the extent of paralysis and advanced age. Conclusion. AFP in the setting of WNV is associated with significant mortality and long-term morbidity.

This diploma thesis deals with the issue of the eradication of infectious polio and its current problems. Polio is a highly infectious disease of viral origin. The most effective form of protection from the disease is vaccination. The main aim of this work was to determine the major issues in polio surveillance in the Pilsen region at present. Intermediate goals were determined in relation to the main aim: to ascertain the awareness of practicing paediatricians about the principles of poliomyelitis surveillance with an emphasis on diagnosing and reporting cases of acute palsy and further to ascertain the quality of the cooperation between the locally competent public health authority and practicing paediatricians in the field of poliomyelitis surveillance. The work is divided into two parts, theoretical and practical. The practical part was elaborated using a qualitative method based on semi-structured interviews with practicing paediatricians and with the locally competent public health authority. The research was participated in by 9 practicing paediatricians and one public health authority worker from the Pilsen region, with an average length of practice of 20 years. The resulting data was then evaluated by a coding method and divided into schemes according to Švaříček and Šeďová (2007). Three research questions were defined based on the set aims: RQ1: What do practising paediatricians see as the prime problems in polio surveillance? RQ2: How many cases of acute palsy do practising paediatricians record and subsequently report to the competent public health authority? RQ3: What is the quality of the cooperation between practising paediatricians and the locally competent public health authority? The research revealed that, according to the practising paediatricians, the problem in poliomyelitis surveillance is refusal of the vaccination and the associated decreasing immunisation coverage of the population. The next most commonly reported problem was population migration. Furthermore, it was found that not one practising paediatrician recorded or reported cases of acute palsy in their surgery. Only one respondent encountered acute palsy 10 years ago. The answer to the last research question is also apparent from the information obtained. More than half of the respondents agreed that so far there is no cooperation on this issue. Although four respondents stated that the cooperation is at a high level and is of very good quality.

Submitted by Alessandra Portugal (alessandradf@ioc.fiocruz.br) on 2013-09-17T13:17:37Z No. of bitstreams: 1 Hugo Leonardo2 OK.docx.pdf: 1727936 bytes, checksum: 9b422dec3434e2e337a66ba7ab57e26b (MD5) / Made available in DSpace on 2013-09-17T13:17:37Z (GMT). No. of bitstreams: 1 Hugo Leonardo2 OK.docx.pdf: 1727936 bytes, checksum: 9b422dec3434e2e337a66ba7ab57e26b (MD5) Previous issue date: 2012-08-30 / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / Os enterovírus humanos ( Picornaviridae ) são vírus de transmissão predominantemente ent érica, possuem distribuição cosmopolita, estando entre os agentes mais prevalentes como causadores de patogenias em humanos. Atualmente, já foram descritos mais de 100 sorotipos para os enterovírus humanos e em grande parte dos casos as infecções associada s são assintomáticas. Surtos e casos esporádicos de enteroviroses são frequentemente notificados em diversas regiões do mundo causando conjuntivite hemorrágica aguda, meningite asséptica, doença de mão pé e boca e poliomielite. A poliomielite é uma doença infecciosa de caráter agudo, que pode assumir desde formas assintomáticas até formas paralíticas (paralisia flácida aguda ou PFA), causada em geral por um dos três sorotipos de poliovírus (PV). O PV selvagem está eliminado do Brasil desde 1989, atualmente sendo restrito a apenas quatro países (Nigéria, Afeganistão, Paquistão, Índia). Entretanto surtos de PFA associados à PV de origem vacinal e a enterovírus não pólio recombinantes tem sido notificados. A caracterização de EVNP é de extrema importância para a investigação da diversidade de vírus co - circulantes, e para relacionar os sintomas clínicos com o sorotipo viral envolvido, incluindo a investigação de vias de transmissão de enterovírus, durante a ocorrência de surtos, além de contribuir para estudos ep idemiológicos e com a evolução de enterovírus. Neste estudo foram analisadas amostras relacionadas à PFAs, utilizando RT - PCR e PCR com o objetivo de identificar quais são as espécies de enterovírus humanos associadas. Os membros da espécie C foram sequenci ados para a identificação de sorotipo. De um total de 190 amostras, 79 eram da espécie C, 78 da espécie B, 32 da espécie A e 1 amostra era correspondente as espécies A e C,não sendo encontradas amostras da espécie D. Entre as amostras da espécie C,58 cor respondiam a PV.Os dados obtidos apresentam similaridades com estudos similares na Europa e Ásia, cobrindo um aspecto pouco observado na epidemiologia dos enterovírus em território brasileiro. / The human enterovirus es (Picornaviridae) are predominantly enteric virus transmission, have a cosmopolitan distribution, being among the most prevalent agents as causing pathogens in humans. Currently, have been described more than 100 serotypes for human enteroviruses and in mo st cases associated infections are asymptomatic. Outbreaks and sporadic cases of enteroviruses are frequently reported in several regions of the world causing acute hemorrhagic conjunctivitis, aseptic meningitis, hand foot and mouth disease and poliomyelit es. Poliomyelites is an infectious disease of acute character, which may take from asymptomatic to paralytic form (acute flaccid paralysis or PFA), usually caused by one of three poliovirus serotypes (PV). The PV is eliminated wild in Brazil since 1989, cu rrently restricted to only four countries (Nigeria, Afghanistan, Pakistan and India). However PFA outbreaks associated with PV source vaccine and recombinant Non - polio enteroviruses has been reported. The characterization of EVNP is extremely important to investigate the diversity of co - circulating viruses, and to correlate clinical symptoms with viral serotype involved, including the investigation of routes of transmission of enteroviruses, during outbreaks, besides contributing for epidemiological studies and the evolution of enteroviruses. We analyzed samples related to AFP, using RT - PCR and PCR in order to identify which species of human enteroviruses associated. Members of the species C were sequenced for identification of serotype. From a total of 190 samples, 79 were of type C, 78 type B, 32 type A and one sample was corresponding for A and C, were not found samples of type D. Among the samples of species C, 58 corresponded to PV.Os data show similarities with similar studies in Europe and Asia, coveri ng a little noticed aspect of the epidemiology of enteroviruses in Brazilian territory.

Magister Public Health - MPH / Poliomyelitis (polio) is an infectious disease of high public health importance. In 1988, the World Health Organization (WHO) set the goal of polio eradication worldwide through the Global Polio Eradication Initiative (GPEI). A threeyear period of zero indigenous wild poliovirus in all countries, in the presence of highquality acute flaccid paralysis (AFP) surveillance, is the basis of an independent commission’s determination of when a WHO region or a country can be certified as polio free. AFP surveillance being one of the critical elements in polio eradication campaign, aims to report and investigate all cases of acute flaccid paralysis occurring in children aged less than 15 years using clinical, epidemiological and laboratory methods. The information collected is cleaned and entered, into a database and maintained in EPI Info format at the WHO country office of each of the 46 countries, the three sub regional offices or Inter country Support Teams (IST) offices and the WHO African Regional Office. In addition, data from sixteen polio laboratories in various African countries maintain records of the laboratory findings and results of confirmed polio cases. The quality of data generated through AFP surveillance and maintained in the African regional data base has not been critically and systematically reviewed and documented. This study therefore was designed to gather information and document the quality of AFP data base, a key component of the global polio eradication effort. A cross-sectional descriptive study involving the retrospective review of clinical and laboratory databases of AFP surveillance over a five year period (2004 - 2008) was designed. In this study, databases of CIFs containing clinical and laboratory data from AFP cases reported from all 46 countries of the WHO African Region comprising of 57,619 clinical and 59,843 laboratory records were critically reviewed.

The WHO member countries undertook to eliminate poliomyelitis globally by the year 2000. Acute flaccid paralysis (AFP) surveillance finds paralytic cases of polio so that swift action can be taken and shows that wild poliovirus has been eliminated when polio cases no longer occur. Mpumalanga Province, a rural province in the north-east of South Africa, developed a rapid reporting system where infection control nurses at the public and private sector hospitals report weekly to the AFP surveillance Officer, including zero reporting, on 9 infectious disease syndromes that require rapid action on clinical presentation alone. This system was implemented in 1998 and included AFP. The non-polio AFP reporting rate increased from 0.37 in 1997 to 0.55 during 1998 with more than 80% of the units reporting weekly. The binomial exact confidence intervals however include 1. A hospital record review of all paediatric admissions revealed that only 2 AFP cases were missed by the system. The AFP reporting rate remains below the international standard of 1 per 100 000 children under 15 years of age despite an adequate reporting system. The role of chance variation, particularly in small geographical areas, has not been discussed in official polio-eradication guidelines but it is . imperative that population size be taken into account when judging the rate of AFP case detection. With the low international reference rate and play of chance variation it is possible that regions with relatively small populations, low non-polio AFP detection rates and no cases of polio detected for an extended period may have adequate surveillance systems supporting polio free certification. In these areas additional criteria for determining the adequacy of the surveillance system should also be considered. / Dissertation (MMed)--University of Pretoria, 2006. / School of Health Systems and Public Health (SHSPH) / Unrestricted

<p><i>Enterovirus</i> (EV), a genus within the <i>Picornaviridae </i>family, contains icosahedral positive-stranded RNA viruses linked to different human and mammalian diseases with a variety of symptoms ranging from the common cold to central nervous system infection. An important member within this genus is EV-D68. Unlike many enteroviruses that use the gastrointestinal tract as the transmission and propagation route, EV-D68 infects the respiratory tract and causes respiratory illness, especially in children. Severe infections of EV-D68 also lead to acute flaccid myelitis (AFM), a polio-like neurological disease. Especially in recent years, EV-D68 has been on a global upswing. However, no antiviral interventions against EV-D68 infection have been developed to date. Antibodies neutralizing EV-D68 have significant vaccine and therapeutic potentials. Here, the structures of the immune complex between EV-D68 and the Fab molecules of EV-D68 human monoclonal antibodies have been reconstructed using cryo-electron microscopy (cryo-EM). These structures show two Fab binding loci on the virion surface as well as the essential amino acids involved in binding. In addition to antibodies, a drug candidate against EV-D68 has been investigated in this work as an antiviral strategy. It is likely that this drug blocks viral entry through binding in the hydrophobic pocket underneath the viral protein 1, the largest structural protein of EV-D68. Furthermore, the morphogenesis of EV-D94, another causative virus of polio-like disease, which is closely related to EV-D68 with 85% sequence identity, has been investigated using cryo-EM. Compared to EV-D68, the shape of the canyon and the loops containing the immunogenic recognition sites are different in EV-D94. The structures of each of the three stages of EV-D94 particles (the full native virion, the uncoating intermediate, and the empty virion) were identified and delineate the viral uncoating process. These findings reveal useful knowledge and new insights to develop treatments against human EVs. </p><p></p>

本文旨在比較台灣閩南語常人、弛緩型(flaccid dysarthrics)、與痙攣型(spastic dysarthrics)神經性構音障礙病患子音絕對及相對音長之差異，並探討此病態語音在了解說話運動系統之特徵以及了解語言產製過程上可能的暗示。 結果顯示神經性構音障礙病患的子音絕對音長顯著長於常人受試者，但兩組病患延長的型態並不相同。首先，弛緩型病患子音音長顯著長於痙攣型病患；再者，以子音的帶音與否、發音位置、發音方法這三個向度來看，弛緩型病患之子音音長展現了全面性的延長，而痙攣型病患則產生了選擇性的延長，其子音之延長，大多集中在有聲子音上，這些差異乃因兩組病人病理狀況不同所致。 另一個結果則顯示，雖然神經性構音障礙病患，在子音音長呈現了延長的狀況，但在子音間相對音長次序上，仍保持到某種程度的完好，可是，子音雖保持一定的次序，但彼此間音長的差值及比值卻也發生了改變。而子音在音節中的所佔比例卻又和正常人無異。 因此，本文推斷，在常人子音的產製上，是要求精確的絕對音長，而且子音間音長亦要保持一定的相對關係；但若因病變致使說話者無法同時兼顧二者時，說話者會選擇犧牲絕對音長，而仍保持子音音長間的相互關係。這可能是語言產製與感知的一些經濟原則(principles of economy)互動所導致的結果。此外，構音障礙病患表就子音在音節中的相對時長這個向度上，和常人無異，這可能是語言文法與生理限制二項因素互動所致。 / This study aims (1) to investigate the absolute and relative timing of consonant duration in Taiwanese neurogenic dysarthric speech by means of acoustic measurements, (2) and to explore their implication on the characteristics of motor system and on the status of timing control in speech production. The results show that absolute consonant duration in flaccid and spastic dysarthric speech are significantly longer than that in normal controls. However, the "lengthening" phenomena display different patterns in flaccid and spastic groups. First, for the patients with the same degree of muscular dysfunction, the flaccid dysarthrics lengthen the consonant duration significantly greater than the spastic ones do. Second, whereas absolute consonant duration in flaccid group shows overall lengthening regardless of voicing state, stricture type, and place of articulation, that in spastic group displays selective lengthening. Besides, though the absolute consonant duration is lengthened in dysarthric speech, the durational opposition between consonants is more or less distinct. However, only the durational ranking between consonants (external timing relation) is maintained in dysarthric, but the durational distance or ratio between consonants (internal timing relation) is modified. Relative timing of consonant duration, that is, the consonant-to-syllable ratio (cs-ratio) within a syllable remains intact in dysarthric speech even though the segmental duration is lengthened. Lengthened absolute consonant duration in dysarthric speech is accounted for by the neurological deficits and compensatory effects. Longer absolute consonant duration in flaccid than in spastic speech is attributed to slowness and weakness without spasticity of speech musculature in flaccid dysarthria. Overall lengthening of consonant duration in flaccid group results from the entirely-impaired cranial nerves innervating speech musculature, whereas selective lengthening of consonant in spastic group is ascribed to spasticity and the selective pattern as well as directionality of neuromuscular impairments in spastic dysarthria. The reserved durational ranking between consonants in dysarthric speech may result from the compromise of principles of economy in speech production and perception. The normal-like CS-ratios in dysarthric speech stem from the interaction between biological constraints and the grammar of a language. Based on the data collected from dysarthric speech, this study discusses the temporal variance as well as invariance in speech motor system and the status of timing in the grammar of a language. The importance of principles of economy in speech production and perception is also indicated.