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- Antiretroviral drug resistance surveillance among treatment-naive human immunodeficiency virus type 1-infected individuals in Angola: Evidence for low level of transmitted drug resistancePublication . Bártolo, Inês; Rocha, Cheila; Bartolomeu, José; Gama, António; Fonseca, Marlene; Mendes, Ana; Cristina, Filipa; Thamm, Sven; Epalanga, Marta; Silva, Patrícia Cavaco; Taveira, NunoThe prevalence of transmitted human immunodeficiency virus type 1 drug resistance in Angola in 2001 in 196 untreated patients was investigated. All subtypes were detected, along with unclassifiable and complex recombinant strains. Numerous new polymorphisms were identified in the reverse transcriptase and protease. Two (1.6%) unrelated patients harbored nucleoside reverse transcriptase inhibitor- and nonnucleoside reverse transcriptase inhibitor-resistant viruses (mutations: M41L, D67N, M184V, L210W, T215Y or T215F, and K103N). Continued surveillance of drug resistance is required for maximization of ART efficacy in Angola.
- Highly divergent subtypes and new recombinant forms prevail in the HIV/AIDS epidemic in Angola: New insights into the origins of the AIDS pandemicPublication . Bártolo, Inês; Rocha, Cheila; Bartolomeu, José; Gama, António; Marcelino, Rute; Fonseca, Marlene; Mendes, Ana; Epalanga, Marta; Silva, Patrícia Cavaco; Taveira, NunoAngola, located in South-Western Africa, has a remarkably low HIV/AIDS prevalence in the adult population (3.7%). It is bordered in the North by the Democratic Republic of Congo (DRC) and Republic of Congo that are at the origin of human HIV-1 infections. It is, therefore, likely that HIV-1 strains circulating in Angola are genetically diverse and representative of the origin of the HIV/AIDS epidemic. The aim of this work was to investigate in detail the genetic diversity and molecular epidemiology of HIV-1 in Angola. Almost 400 sequences were obtained from the gag (p17), pol (PR and RT) and/or env (C2C3) genes of 159 HIV-1 infected patients living in eight provinces of Angola (Benguela, Cabinda, Cuanza Norte, Luanda, Lunda Norte, Malange, Uíge, and Zaire) and their genotype was determined by phylogenetic analyses. Gene regions representing all HIV-1 group M clades were found as well as unclassifiable sequences. In env and pol (RT), two groups of sequences forming distinct sub-clusters within the subtype A radiation were found and may define new A5 and A6 sub-subtypes. Recombinant forms were found in almost half (47.1%) of the patients of which 36.0% were second-generation recombinants. Fifty-eight different patterns of recombination were found. The A subtype, including CRF02_AG, was represented in most recombinant viruses. Epidemiological data suggests that the AIDS epidemic in Angola has probably started as early as 1961, the major cause being the independence war, and spread to Portugal soon thereafter. The extraordinary degree of HIV-1 group M genetic diversity and evolution in Angola may pose unprecedented challenges to diagnostic, treatment and prevention of HIV-1 infection.
- HIV-1 genetic diversity and transmitted drug resistance in health care settings in Maputo, MozambiquePublication . Bártolo, Inês; Casanovas, José; Bastos, Rui; Rocha, Cheila; Abecasis, Ana B.; Folgosa, Elena; Mondlane, José; Manuel, Rolanda; Taveira, NunoObjectives: To characterize HIV-1 diversity and transmitted drug resistance in persons with access to care and treatment in Maputo, Mozambique. Methods: Samples were collected in 2002-2004 from 144 drug-naive patients attending public hospitals and private clinics. Plasma viremia, CD4, and CD8 cell counts were determined for each patient. The Stanford Algorithm was used for resistance genotyping on pol sequences. Subtyping was done by phylogenetic analysis. Results: Most patients had high viral load (mean, 5.0 log copies/mL) and low CD4 cell counts (median, 260 CD4 cells/μL). Protease and/or reverse transcriptase sequences were obtained from 104 (72%) samples. Patients harbored subtypes C (80.8%), G (3.8%), CRF37_cpx (6.7%), untypable (U) (1.0%), and recombinant strains (7.7%) comprising the A, C, D, F, and U clades. There were no major protease inhibitor resistance mutations. Mutations conferring resistance to the nucleoside/nucleotide reverse transcriptase inhibitors and/or nonnucleoside reverse transcriptase inhibitors were found in 4 (4/68; 5.9%) patients. Phylogenetic analysis suggested an imported origin for 2 resistant variants. Conclusions: The HIV-1 epidemic in Maputo is evolving rapidly in genetic complexity due to the recent introduction of all major subtypes and recombinant forms. Continued surveillance of drug resistance in treated and untreated populations is needed to prevent further transmission of HIV drug-resistant variants and maximize the efficacy of antiretroviral therapy in Maputo.
- Rapid clinical progression to AIDS and death in a persistently seronegative HIV-1 infected heterosexual young manPublication . Bártolo, Inês; Camacho, Ricardo; Barroso, Helena; Bezerra, Victor; Taveira, NunoSeronegative HIV-1 infection has important implications for diagnosis and prevention. We describe a case of HIV-1 infection without seroconversion and fast progression to AIDS and death. Genetic and phylogenetic analysis indicated that the patient was infected with a CRF14_BG-like 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 deficiency that has prevented the formation of HIV-1-specific antibodies.
- High genetic diversity of human immunodeficiency virus type 1 in AngolaPublication . Bártolo, Inês; Epalanga, Marta; Bartolomeu, José; Fonseca, Marlene; Mendes, Ana; Gama, António; Taveira, NunoTo investigate which HIV-1 genetic forms are circulating in Angola, we have determined the gag and/or env genotypes of 48 isolates from patients living in Cabinda and Luanda provinces. The following subtypes were identified: A1 (18 samples, 38%), C (7, 15%), H (5, 10%), J (3, 6%), G (2, 4%), A2 (2, 4%), F1 (1, 2%), and D (1, 2%). The env gene fragment was untypable in one sample. Discordant subtype classifications in the gag and env genes were found in eight (17%) samples. There were six different recombination patterns (gag/env): A1/H (3, 6%), A1/G (1, 2%), C/A2 (1, 2%), F1/B (1, 2%), G/B (1, 2%), and G/H (1, 2%). The A1/H recombinant may represent a new circulating recombinant form. The marked genetic heterogeneity of HIV-1 in Angola has important implications for vaccine development.
- Seronegative infection and AIDS caused by an A2 subsubtype HIV-1Publication . Cardoso, Ana Rita; Gonçalves, Cristina; Pascoalinho, Dulce; Gil, Catarina; Ferreira, António Fernandes; Bártolo, Inês; Taveira, NunoThe study of true seronegative HIV-1 infections may have important implications for the diagnosis and prevention of HIV-1 infection. The case of an AIDS patient with persistently negative HIV serology is described. Genetic and phylogenetic analysis indicated that she was infected with an A2 subsubtype HIV-1 transmitted by her seropositive and asymptomatic sexual partner. The clinical and serological discordant results suggest the presence of an immunological deficiency that prevents the formation of HIV-1-specific antibodies.
- Um caso de SIDA seronegativoPublication . Cardoso, Ana Rita; Gonçalves, Cristina; Pascoalinho, Dulce; Gil, Carla; Ferreira, António Fernandes; Bártolo, Inês; Taveira, NunoOs A.A. descrevem o caso de uma jovem que se apresenta com um quadro clínico de SIDA e com testes serológicos para o VIH repetidamente negativos. O diagnóstico da infecção pelo VIH-1 foi feito por determinação do Ag p24 e da carga viral por reacção de polimerização enzimática em cadeia (PCR). O parceiro sexual da doente era seropositivo para o VIH-1 e ambos estavam infectados pelo mesmo vírus, um recombinante entre os subtipos A e D. As disparidades encontradas entre este casal sugerem a existência de um defeito imunológico específico que impossibilita o desenvolvimento de anticorpos.
- Evaluation of the clinical sensitivities of three viral load assays with plasma samples from a pediatric population predominantly infected with human immunodeficiency virus type 1 subtype G and BG recombinant formsPublication . Antunes, Rute; Figueiredo, Sofia; Bártolo, Inês; Pinheiro, Manuel; Rosado, Lino; Soares, Isabel; Lourenço, Helena; Taveira, NunoThe viral load assays AMPLICOR HIV-1 Monitor Test 1.5, Nuclisens HIV-1 QT, and Quantiplex HIV RNA 3.0 (bDNA) were evaluated for their abilities to quantify human immunodeficiency virus type 1 (HIV-1) RNA in 64 plasma samples from 21 children infected in Portugal. The children were infected with HIV-1 subtypes A1, B, F1, G, and BG recombinant virus. AMPLICOR v1.5 and Quantiplex v3.0 detected all samples, and there was a good correlation of results between the two kits. Thirty-eight specimens containing HIV-1 subtype B, G, or recombinant BG, could not be detected by Nuclisens HIV-1 QT. We also evaluated the new Retina HIV-1 assay on 21 samples that were HIV-1 positive; Retina HIV-1 failed to detect 5 of 11 subtype G specimens. AMPLICOR v1.5 and Quantiplex v3.0 assays may be used for HIV-1 RNA quantification in Portugal, whereas an improvement in sensitivity for subtype G and recombinant BG is required for Nuclisens HIV-1 QT and Retina HIV-1.
- Molecular detection of Helicobacter pylori and its genotypic antimicrobial resistance patterns in dyspeptic Mozambican patientsPublication . Ismail, Muhammad; Majaliwa, Nashon D.; Vale, Filipa F.; Cumbana, Roqueia; Sumbana, José J.; Muchongo, Arsénio; Nassone, Ema; Loforte, Michella; Mondlane, Liana; Botão, Edília; Taviani, Elisa; Carrilho, Carla; Vítor, Jorge M. B.; Sacarlal, JahitBackground Helicobacter pylori strains show a high level of genotypic diversity and express several genes that contribute to their pathogenicity and resistance. In Mozambique, there is lack of information regarding its resistance pattern to antibiotics. In this study, we aimed to investigate the prevalence of H. pylori and its genotypic resistance to clarithromycin, metronidazole, and fluoroquinolones in Mozambican dyspeptic patients. Since appropriate eradication should be based on the local resistance rate, our data will guide clinicians in choosing the best drugs for the effective treatment of H. pylori-infected patients. Methods This is a cross-sectional descriptive study conducted between June 2017 and June 2020, in which 171 dyspeptic patients were recruited, and through upper gastrointestinal endoscopy, gastric biopsies were collected from those patients. Polymerase chain reaction was performed for the detection of H. pylori and its resistance mechanisms to clarithromycin (23S rRNA), metronidazole (rdxA), and fluoroquinolones (gyrA); mutations conferring resistance to these antibiotics were investigated by sequencing 23S rRNA, rdxA, and gyrA genes. Results Of the 171 samples tested, H. pylori was detected in 56.1% (96/171). The clarithromycin resistance rate was 10.4% (the responsible mutations were A2142G and A2143G), the metronidazole resistance rate was 55.2% (4 types of mutations responsible for metronidazole resistance were identified which include, D59N, R90K, H97T, and A118T. However, in many cases, they appeared in combination, with D59N + R90K + A118T being the most frequent combination), and the fluoroquinolones resistance rate was 20% (the responsible mutations were N87I and D91G). Conclusion H. pylori infection remains common in dyspeptic Mozambican patients. High resistance to metronidazole and fluoroquinolones requires continuous monitoring of antibiotic resistance and adaptation of therapy to eradicate this infection.
- Effect of α-tocopherol on the physicochemical, antioxidant and antibacterial properties of levofloxacin loaded hybrid lipid nanocarriersPublication . Islan, Germán A.; Gonçalves, Lídia; Marto, Joana; Duarte, Aida; Alvarez, Vera A.; Castro, Guillermo R.; Almeida, António JoséIn the global context of emerging pathogens associated with respiratory diseases, novel nanostructured lipid carriers (NLCs) having both antioxidant and antimicrobial properties produced by α-tocopherol (αT) and levofloxacin (LV), respectively, were developed. The hybrid NLCs were made of solid lipid esters and liquid αT as the central core, plus chitosan (Chi) and poloxamer 188 as surface stabilizers. Three formulations were rationally designed considering lipids with different physicochemical properties: cetyl ester (SS), glyceryl dibehenate (CO) and glyceryl tristearate (DY). The properties and stability of the nanoformulations were studied by dynamic light scattering considering the effects of the homogenization time, surfactant concentration, and initial lipid amount on the mean size, polydispersity index (PDI) and zeta potential of the nanoparticles. The effect of αT on the nanostructuration of the lipid matrix was demonstrated by X-ray diffraction, differential scanning calorimetry, and thermogravimetry analysis. The potential ability of the NLCs to interact with the mucosa was studied by rheological methods, demonstrating a reduction in mucin cohesiveness and elasticity due to the mucoadhesive properties of NLCs coated with chitosan. Solid lipid nanoparticles (SLNs) of SS, CO and DY encapsulated 58.0 ± 3.2, 25.7 ± 7.1, and 27.9 ± 1.5% LV, respectively, while the NLC formulations were able to encapsulate 80–90% LV and allowed controlled release of the drug. The enhanced antimicrobial properties of the SLNs/NLCs against Pseudomonas aeruginosa and Staphylococcus aureus were confirmed. The presence of αT in the formulations provided the antioxidant properties of the NLCs. Finally, no acute toxicities of the formulations were observed in two human lung cell lines (A549 and Calu-3).