EM - Egas Moniz School of Health & Science
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A Egas Moniz School of Health & Science, entidade instituidora do Instituto Universitário Egas Moniz (anteriormente designado Instituto Superior de Ciências da Saúde Egas Moniz) e da Escola Superior de Saúde Egas Moniz (Politécnico), é uma instituição de ensino de referência dedicada à formação de profissionais de saúde, assumindo-se igualmente como um pólo de responsabilidade social fortemente inserido na comunidade local através da prestação de cuidados de saúde.
Enquanto instituição académica, desenvolve atividade pedagógica e científica, contando com um corpo docente altamente qualificado e participando em projetos de investigação científica desenvolvidos em parceria com instituições nacionais e estrangeiras.
O presente repositório visa colecionar, preservar e disponibilizar o acesso à produção científica da comunidade académica da Egas Moniz, contribuindo simultaneamente para o aumento da sua visibilidade e impacto no contexto da transferência de conhecimento.
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Browsing EM - Egas Moniz School of Health & Science by Author "Abecasis, Ana"
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- Accidental father-to-son HIV-1 transmission during the seroconversion periodPublication . Ezeonwumelu, Ifeanyi; Bártolo, Inês; Martin, Francisco; Abecasis, Ana; Campos, Teresa; Romero-Severson, Ethan O.; Leitner, Thomas; Taveira, NunoA 4-year-old child born to an HIV-1 seronegative mother was diagnosed with HIV-1, the main risk factor being transmission from the child's father who was seroconverting at the time of the child's birth. In the context of a forensic investigation, we aimed to identify the source of infection of the child and date of the transmission event. Samples were collected from the father and child at two time points about 4 years after the child's birth. Partial segments of three HIV-1 genes (gag, pol, and env) were sequenced and maximum likelihood (ML) and Bayesian methods were used to determine direction and estimate date of transmission. Neutralizing antibodies were determined using a single cycle assay. Bayesian trees displayed a paraphyletic–monophyletic topology in all three genomic regions, with the father's host label at the root, which is consistent with father-to-son transmission. ML trees found similar topologies in gag and pol and a monophyletic–monophyletic topology in env. Analysis of the time of the most recent common ancestor of each HIV-1 gene population indicated that the child was infected shortly after the father. Consistent with the infection history, both father and son developed broad and potent HIV-specific neutralizing antibody responses. In conclusion, the direction of transmission implicated the father as the source of transmission. Transmission occurred during the seroconversion period when the father was unaware of the infection and was likely accidental. This case shows how genetic, phylogenetic, and serological data can contribute for the forensic investigation of HIV transmission.
- Discordant predictions of residual activity could impact dolutegravir prescription upon raltegravir failurePublication . Theys, Kristof; Abecasis, Ana; Libina, Pieter; Gomes, Perpétua; Cabanas, Joaquim; Camacho, Ricardo J.; Van Laethem, KristelBACKGROUND: Dolutegravir is approved for the treatment of HIV-1 patients exposed to other integrase inhibitors, but the decision to use dolutegravir in this setting should be informed by drug resistance testing. OBJECTIVES: This study determined the extent of disagreement in predicted residual dolutegravir activity after raltegravir use, and identified individual mutational patterns for which uncertainty exists among HIV-1 expert systems. STUDY DESIGN: Mutation patterns were classified in raltegravir signature pathways including positions 143, 148 and 155, and interpreted into clinically informative resistance levels using genotypic drug resistance interpretation systems ANRS v24, HIVdb v7.0 and Rega v9.1.0, and instructions of dolutegravir use as approved by the Food and Drug Administration and the European Medicines Agency. RESULTS: In 216HIV-1 patients failing raltegravir-therapy, 87% patients displayed mutations associated with resistance towards integrase inhibitors. A total of 141 unique mutational patterns were observed, with N155H (25.4%), Q148H (16.2%) and Y143R (8.3%) the most prevalent signature mutations. The Q148 pathway occurred almost exclusively in HIV-1 subtype B viruses. Concordances in predicted dolutegravir susceptibility scores among 5 systems were obtained in 57.8% of patients, and concordant intermediate resistant and concordant resistant scores were only observed in 6.5% and 0.9% of patients, respectively. However, systems individually scored higher levels of dolutegravir intermediate resistance and resistance, ranging from 4.2% to 10.2% and from 14.8% to 22.7% of patients, respectively. A consensus on interpreting the extent of residual activity was lacking in 34.7% of patients and was highly resistance pathway-specific. CONCLUSIONS: Dolutegravir may potentially be effective in the majority of HIV-1 patients failing raltegravir, but concern over the uncertainty in predicted residual activity could withhold clinicians from prescribing dolutegravir during its clinical assessment.
- Donor-Recipient identification in para- and poly-phyletic trees under alternative HIV-1 transmission hypotheses using approximate Bayesian computationPublication . Romero-Severson, Ethan O.; Bulla, Ingo; Hengartner, Nick; Bártolo, Inês; Abecasis, Ana; Azevedo-Pereira, José M.; Taveira, Nuno; Leitner, ThomasDiversity of the founding population of Human Immunodeficiency Virus Type 1 (HIV-1) transmissions raises many important biological, clinical, and epidemiological issues. In up to 40% of sexual infections, there is clear evidence for multiple founding variants, which can influence the efficacy of putative prevention methods, and the reconstruction of epidemiologic histories. To infer who-infected-whom, and to compute the probability of alternative transmission scenarios while explicitly taking phylogenetic uncertainty into account, we created an approximate Bayesian computation (ABC) method based on a set of statistics measuring phylogenetic topology, branch lengths, and genetic diversity. We applied our method to a suspected heterosexual transmission case involving three individuals, showing a complex monophyletic-paraphyletic-polyphyletic phylogenetic topology. We detected that seven phylogenetic lineages had been transmitted between two of the individuals based on the available samples, implying that many more unsampled lineages had also been transmitted. Testing whether the lineages had been transmitted at one time or over some length of time suggested that an ongoing superinfection process over several years was most likely. While one individual was found unlinked to the other two, surprisingly, when evaluating two competing epidemiological priors, the donor of the two that did infect each other was not identified by the host root-label, and was also not the primary suspect in that transmission. This highlights that it is important to take epidemiological information into account when analyzing support for one transmission hypothesis over another, as results may be nonintuitive and sensitive to details about sampling dates relative to possible infection dates. Our study provides a formal inference framework to include information on infection and sampling times, and to investigate ancestral node-label states, transmission direction, transmitted genetic diversity, and frequency of transmission.
- HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimenPublication . Cavaco-Silva, Joana; Abecasis, Ana; Miranda, Ana Cláudia; Poças, José; Narciso, Jorge; Águas, Maria João; Maltez, Fernando; Almeida, Isabel; Germano, Isabel; Diniz, António; Gonçalves, Maria de Fátima; Gomes, Perpétua; Cunha, Celso; Camacho, Ricardo Jorge