Search

Abstract The surveillance of drug resistance in the HIV-1 naïve population remains critical to optimizing the effectiveness of antiretroviral therapy (ART), mainly in the era of integrase strand transfer inhibitor (INSTI) regimens. Currently, there is no data regarding resistance to INSTI in Angola since Dolutegravir-DTG was included in the first-line ART regimen. Herein, we investigated the HIV-1 genetic diversity and pretreatment drug resistance (PDR) profile against nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and INSTIs, using a next-generation sequencing (NGS) approach with MinION, established to track and survey DRMs in Angola. This was a cross-sectional study comprising 48 newly HIV-diagnosed patients from Luanda, Angola, screened between March 2022 and May 2023. PR, RT, and IN fragments were sequenced for drug resistance and molecular transmission cluster analysis. A total of 45 out of the 48 plasma samples were successfully sequenced. Of these, 10/45 (22.2%) presented PDR to PIs/NRTIs/NNRTIs. Major mutations for NRTIs (2.2%), NNRTIs (20%), PIs (2.2%), and accessory mutations against INSTIs (13.3%) were detected. No major mutations against INSTIs were detected. M41L (2%) and I85V (2%) mutations were detected for NRTI and PI, respectively. K103N (7%), Y181C (7%), and K101E (7%) mutations were frequently observed in NNRTI. The L74M (9%) accessory mutation was frequently observed in the INSTI class. HIV-1 pure subtypes C (33%), F1 (17%), G (15%), A1 (10%), H (6%), and D (4%), CRF01_AG (4%) were observed, while about 10% were recombinant strains. About 31% of detected HIV-1C sequences were in clusters, suggesting small-scale local transmission chains. No major mutations against integrase inhibitors were detected, supporting the continued use of INSTI in the country. Further studies assessing the HIV-1 epidemiology in the era of INSTI-based ART regimens are needed in Angola.

ABSTRACT: Objectives: Emergence of the plasmid-born mobile colistin resistance (mcr) gene is a growing concern in healthcare. Therefore, this study aimed to genomically characterise multidrug-resistant Escherichia coli and Klebsiella pneumoniae co-harbouring the mcr-1 and mcr-3 genes in young children. Methods: E. coli (n = 3) and K. pneumoniae (n = 2) were collected from abdominal secretions and blood, respectively. The isolates were screened using tryptone soy broth with 4 µL/mL polymyxin-B. Growing bacteria were identified using the VITEK-2 system, matrix-assisted laser desorption/ionisation time-of-flight, and 16s RNA sequencing, followed by antibiotic susceptibility testing. Metallo-β-lactamase (MBL) and extended-spectrum β-lactamase (ESBL) production was also detected. Afterwards, strains were subjected to molecular screening targeting mcr variants and ESBL/MBL-encoding genes. Conjugation, pulsed-field gel electrophoresis, Southern hybridisation, multilocus sequence typing, and phylogenic group detection were performed, along with plasmid-genome sequencing and bioinformatics analysis. Results: E. coli isolates (EC-19–322, 323, and 331) and K. pneumoniae isolates (KP-19–225 and 226) harboured both mcr-1 and mcr-3 genes. These strains were also found to be resistant to more than three classes of antibiotics. The conjugation experiment revealed the presence of mcr-1 and mcr-3 on a single plasmid, and the transmission frequency was 10–2 to 10–3. Both strains were found to be able to produce ESBLs and MBL. E. coli EC-19–322 and 323 were identified as ST131(O25a:H41); SP-19–331, as ST1577 (O16:H30); and K. pneumoniae, as ST231 (K2). All E. coli strains belonged to phylogenetic group B2, and the results of pulsed-field gel electrophoresis supported the multilocus sequence typing findings. Conclusion: This study reported the co-occurrence of mcr-1 and mcr-3 genes on a single plasmid in pathogenic ESBL/MBL-producing E. coli and K. pneumoniae isolated from young children.

Abstract Background and Aims The acute tropical infectious disease known as yellow fever (YF) is caused by an arbovirus and is characterized by fever, jaundice, hemorrhage, headache, muscle pain, nausea, vomiting, and fatigue. Angola experienced a yellow fever virus (YFV) outbreak that was documented in December 2015. However, little is known about the outcome of this outbreak. We aimed to demonstrate epidemic features and lessons learned during the YF epidemic in Angola. Methods A total of 4618 blood samples from suspected YF cases were sent to the Instituto Nacional de Investigação em Saúde (INIS), a national referral and public health laboratory, between December 5, 2015, and December 23, 2016. Sample analyses were conducted using enzyme‐linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT‐PCR) assays. Blood samples were sent from 16 out of the 18 provinces of Angola. Results We detected 884 (19.1%) cases that were positive for ELISA, which were confirmed by RT‐PCR assay. Considering the positive cases, the incidence among male patients was around three times higher (n = 223; 10.9%) than in female patients (n = 59; 2.6%) in the 20–29 age group, followed by the age group 10–19 with n = 211 (6.8%) in males versus n = 108 (3.3%) in females; and the age group 30–39 had n = 68 (4.8%) in males versus n = 28 (1.8%) in females. The other groups had an incidence below 3.0%. The case fatality ratio for YF was in young adults in the age group 20–29 with n = 39 cases, followed by the age group 10–19 with n = 16 cases, and finally the age group 0–9 with n = 13 cases. The other age groups had several deaths by YF below 10 cases. Conclusions This study demonstrates features of the YF epidemic that occurred in Angola. Also, it demonstrates that YF causes deaths in young people but is preventable by high vaccine coverage. Thus, public health laboratory surveillance must be strengthened to reduce the possibility of emerging and re‐emerging human infections.

Abstract Background and Aims SARS‐CoV‐2 infection is a public health concern. Several aspects related to the pattern of infection remain unclear. This study aimed to investigate the blood pressure pattern among blood donors exposed to SARS‐CoV‐2 in Luanda, Angola, a sub‐Saharan African country. Methods We performed a retrospective analysis containing 343 blood donors from December 2019 to September 2020. Parametric tests compared means while χ2 and logistic regression checked features associated with high blood pressure and were considered significant when p 0.05). A significant link was observed, between the Rhesus factor and blood pressure status (p = 0.032). Conclusion We showed important variations in blood pressure indices of the Angolan population exposed to SARS‐CoV‐2. Older age and non‐O blood groups appear to be important biological factors for SARS‐CoV‐2 infection, as well as the risk of developing cardiovascular disease after or during SARS‐CoV‐2 exposure. Further studies assessing the impact on cardiovascular functions with ongoing or long‐term SARS‐CoV‐2 exposure in individuals from resource‐limited countries should be considered.

Abstract Background and Aims Hypertension is a public health concern, mainly in resource‐limited countries. We investigated the characteristics and risk factors related to high blood pressure in healthy blood donors from, Luanda, the capital city of Angola. Methods This was a retrospective study that included 343 healthy donors from December 2019 to September 2020. Results The mean age was 32 ± 9 years. Men represented 93% of the population. Mean systolic blood pressure (SBP) was 131 ± 12.3 mmHg (ranging from 100 to 160 mmHg) and diastolic blood pressure (DBP) was 80.1 ± 9.72 mmHg (from 56.0 to 100 mmHg). DBP was related to age and gender (p 140/90 mmHg). Age between 20 and 40 years (odds ratio [OR]: 2.52, p = 0.043), women (OR: 1.87, p = 0.548), nonurbanized areas (OR: 0.39, p = 0.067), high educational level (OR: 0.76, p = 0.637), employed (OR: 0.49, p = 0.491), voluntary donors (OR: 0.87, p = 0.799), blood group B (OR: 2.06, p = 0.346), and Rh‐ (OR: 0.26, p = 0.104), were potentially related with high‐pressure. The high‐pressure cases increased from December 2019 (4%) to September 2020 (28%) (p = 0.019). Conclusion We showed high pressure among the healthy blood donors population. Demographic characteristics, ABO/Rh blood group, and year period are features that should be considered in cardiovascular disease control strategies. Biological and nonbiological features related to blood pressure changes should be considered for further studies in the Angolan population.

Abstract Background and Aims Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is a public health concern. Until 2021, more than 2 million cumulative deaths were reported worldwide. Herein, we investigated the immune profile of healthcare professionals 6 months after vaccination or exposure to SARS‐CoV‐2 in Angola. Methods This was a prospective study conducted with 1068 Angolan healthcare professionals between August and December 2021. Participants were screened for the presence of IgG and IgM against SARS‐CoV‐2. Results About 9.6% and 98.2% of the participants had prior exposure to SARS‐CoV‐2 or vaccination against it, respectively. Participants aged between 20 and 40 years (11.2%), female (12.4%), with higher educational level (12.8%), from Luanda (60.3%), and nonhealthcare professionals (8.1%) were the most affected by the SARS‐CoV‐2. Gender, education, and local residence were related to SARS‐CoV‐2 exposure (p 3 months. Individuals who received only the first dose regardless of the type of vaccine had a higher immunity duration (>3 months) than those who received two doses. For individuals who received the Sputnik and Johnson, the average immunity was lower (

Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T cell research and development. CD19 CAR-T cell is most commonly used, and other targets, including CD20, CD30, CD38 and CD138 are being studied. Although this novel therapy is promising, there are several disadvantages. In this review we discuss the applications of CAR-T cells in different hematological malignancies, and pave a way for future improvement on the effectiveness and persistence of these adoptive cell therapies. KEY WORDS: Chimeric antigen receptor T cell, Clinical applications, Immunotherapy, Malignancies

Beta-defensins 2 and 3 (BD2 and BD3) are inducible peptides present at the sites of infection, and they are well characterized for their antimicrobial activities and immune-regulatory functions. However, no study has thoroughly investigated their immunomodulatory effects on macrophage-mediated immune responses against Pseudomonas aeruginosa (PA). Here, we use THP-1 and RAW264.7 cell lines and demonstrate that BD2 and BD3 suppressed macrophage autophagy but enhanced the engulfment of PA and Zymosan bioparticles as well as the formation of phagolysosomes, using immunofluorescence staining and confocal microscopy. Plate count assay showed that macrophage-mediated phagocytosis and intracellular killing of PA were promoted by BD2 and BD3. Furthermore, microarray and real-time PCR showed that the expression of two genes, early growth response gene-1 (EGR1) and c-FOS, was attenuated by BD2 and BD3. Western blot revealed that BD2 and BD3 inhibited the expression and nuclear translocation of EGR1 and c-FOS. Knockdown of EGR1 and c-FOS by siRNA transfection suppressed macrophage autophagy before and after PA infection; while overexpression of these two transcription factors enhanced autophagy but reversed the role of BD2 and BD3 on macrophage-mediated PA eradication. Together, these results demonstrate a novel immune defense activity of BD2 and BD3, which promotes clearance of PA by inhibiting macrophage autophagy through downregulation of EGR1 and c-FOS.

BackgroundDespite the guidelines provided by the World Health Organization for the treatment of malaria, treatment failure occurs in many hospitalized patients.ObjectiveEvaluate whether blood cell count parameters may serve as predictors for malaria treatment.MethodologyA cross-sectional study with a quantitative approach.ResultsOf the 219 patients, 21.5% showed failure to antimalarial treatment, Patient with 21 and 40 years (72.6%), male (53.4%), from peri-urban area (47.5%), with high parasitemia (59.8%), treated with Arthemeter (90.9%) and the mortality were 5.9%. Significant associations were observed between occupation, level of parasitemia and outcome with resistance to antimalarial treatment (pConclusionThe importance of blood cell count parameters in monitoring malaria therapy necessitates the urgent need to re-evaluate Artemether-based therapy. Future studies involving more participants in different settings are needed to provide further evidence.