Molecular epidemiology and evolution of HIV-1 in Portugal and portuguese speaking african countries

The aims of this thesis were to better characterize HIV-1 diversity in Portugal, Angola, Mozambique and Cape Verde and to investigate the origin and epidemiological history of HIV-1 in these countries. The impact of these issues in diagnosis, disease progression and susceptibility to ARV therapy was also investigated. Finally, the nature, dynamics and prevalence of transmitted drug resistance (TDR) was determined in untreated HIV-1 infected patients. In Angola, practically all HIV-1 genetic forms were found, including almost all subtypes, untypable (U) strains, CRFs and URFs. Recombinants (first and second generation) were present in 47.1% of the patients. HIV/AIDS epidemic in Angola probably started in 1961, the major cause being the independence war, subsequently spreading to Portugal. In Maputo, 81% of the patients were infected with subtype C viruses. Subtype G, U and recombinants such as CRF37_cpx, were also present. The results suggest that HIV-1 epidemic in Mozambique is evolving rapidly in genetic complexity. In Cape Verde, where HIV-1 and HIV-2 co-circulate, subtype G is the prevailed subtype. Subtypes B, C, F1, U, CRF02_AG and other recombinant strains were also found. HIV-2 isolates belonged to group A, some being closely related to the original ROD isolate. In all three countries numerous new polymorphisms were identified in the RT and PR of HIV-1 viruses. Mutations conferring resistance to the NRTIs or NNRTIs were found in isolates from 2 (2%) patients from Angola, 4 (6%) from Mozambique and 3 (12%) from Cape Verde. None of the isolates containing TDR mutations would be fully sensitive to the standard first-line therapeutic regimens used in these countries. Close surveillance in treated and untreated populations will be crucial to prevent further transmission of drug resistant strains and maximize the efficacy of ARV therapy. In Portugal, investigation of a seronegative case infection with rapid progression to AIDS and death revealed that the patient was infected with a CRF14_BG-like R5-tropic strain selectively transmitted by his seropositive sexual partner. The results suggest a massive infection with a highly aggressive CRF14_BG like strain and/or the presence of an unidentified immunological problem that prevented the formation of HIV-1-specific antibodies. Near full-length genomic sequences obtained from three unrelated patients enabled the first molecular and phylogenomic characterization of CRF14_BG from Portugal; all sequences were strongly related with CRF14_BG Spanish isolates. The mean date of origin of CRF14_BG was estimated to be 1992. We propose that CRF14_BG emerged in Portugal in the early 1990s, spread to Spain in late 1990s as a consequence of IDUs migration and then to the rest of Europe. Most CRF14_BG strains were predicted to use CXCR4 and were associated with rapid CD4 depletion and disease progression. Finally, we provide evidence suggesting that the X4 tropism of CRF14_BG may have resulted from convergent evolution of the V3 loop possibly driven by an effective escape from neutralizing antibody response.

O Papel das Agências de Viagens e Turismo no Desenvolvimento do Turismo Emissor e Receptor

Devido a mudanças tecnológicas e da globalização, o turismo vem passando por grandes transformações, permitindo um maior acesso às informações e uma maior aproximação entre o consumidor e o mercado turístico. O papel das agências de viagens e turismo (AVT’s) é de fundamental importância para o desenvolvimento da actividade turística de um país. Face a isto, as AVT’s devem aderir ao novo cenário, procurando acompanhar a evolução, renovando e actualizando sempre os seus serviços. O presente estudo tem por objectivo avaliar o papel das AVT’s da ilha de São Vicente, no âmbito do turismo emissor e receptor. Foi realizado um estudo de caso, incluindo os doze representantes das AVT’s da ilha de S. Vicente, com excepção das empresas exclusivamente marítimas. Foi usado um guião de entrevistas para a obtenção de dados relacionados aos responsáveis dos serviços, a empresa, aos colaboradores internos, clientes, serviços oferecidos, sazonalidade e sua problemática, parceiros, as tecnologias de informação e as perspectivas futuras. As informações foram analisadas sob um enquadramento teórico e prático. Constatou-se que sete agências dedicam-se ao turismo emissor e receptor, três ao turismo emissor, e duas ao receptor. Foi possível observar que as AVT’s apresentam semelhanças na prestação de serviços e a maioria tem a preocupação de acompanhar as exigências actuais do turismo. Pode-se concluir que o turismo emissor e receptor estão bem representados pelas AVT’s de São Vicente. Technological changes and globalization has allowed big transformations in Tourism, greater access to information and a closer relationship between the consumer and tourist market. The role of the Travel and Tourism Agencies (TTA) has fundamental importance for the tourism development in a country, and they must adhere to the new environment, trying to follow the evolution, always renewing and updating their services. The present study aims to evaluate the role of TTA’s in São Vicente Island, in the field of inbound and outbound tourism. It was conducted a case study, including 12 representatives of TTA's in São Vicente, with exception of shipping companies. It was used a scripted interview to obtain data about the service delegate, the company, internal employees, customers, offered services, seasonality and its problems, partners, information technology and future prospects. Data were analyzed from a theoretical and practical view. It was found that seven agencies dedicated to inbound and outbound tourism, three to outbound and two to inbound. The TTA’s have similarities in service delivery and most have the concern to keep up with current demands of tourism. It can be concluded that inbound and outbound tourism are well represented by TTA’s in São Vicente.