Collaborative Efforts for Global Sustainability

Biobanks and Biological Resources Centres (BRCs) are pivotal infrastructures in biomedical, biotechnological, and environmental research, providing resources for fostering innovation in a healthy, global, and sustainable society. Most of biobanks and BRCs are located in North America and Europe. In Africa, significant consortia have been established but none of them encompassing the Community of Portuguese Language Countries (CPLP). Furthermore, Portuguese-speaking African countries (PALOP) still lack capacity, infrastructure, regulations and trained human resources, for effectively biobank samples. Nonetheless, certain institutions have initiated the establishment of biological collections, while others have expressed a keen interest in doing so. Consequently, a significant demand emerges for the exchange of experiences related to capacity building, training, and expertise in establishing biological collections. Such collaborative efforts hold the potential to invigorate local activities, foster knowledge dissemination, and contribute to the equitable sharing of benefits. This, in turn, empowers these nations to preserve and safeguard their unique biodiversity resources. The implementation of a "Lusophone Network of Biobanks and Biological Resources Centres" is currently in progress to address this need. The inaugural meeting of this network occurred last April at IHMT NOVA in Lisbon, bringing together representatives from 15 institutions from Angola, Brazil, Cabo Verde, Mozambique, and Portugal. The diversity in terms of developmental stages, existing infrastructure, strategies, programs, funding sources, and governance policies among institutions and countries was clearly evident. Several thematic areas associated with biobanking activities and infrastructure were introduced, setting the stage for future collective reflection and discussion. This network aims to yield not only immediate advantages such as enhanced data management and standardisation of operating procedures and information systems across biobanks and BRCs, in the frame of ethical guidelines, but also the potential for future collaborative trans-biobank studies.publishe

Individual variation in Plasmodium vivax malaria risk - Are repeatedly infected people just unlucky?

Copyright: © 2023 Corder et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Extensive research has examined why some people have frequent Plasmodium falciparum malaria episodes in sub-Saharan Africa while others remain free of disease most of the time. In contrast, malaria risk heterogeneity remains little studied in regions where P. vivax is the dominant species. Are repeatedly infected people in vivax malaria settings such as the Amazon just unlucky? Here, we briefly review evidence that human genetic polymorphism and acquired immunity after repeated exposure to parasites can modulate the risk of P. vivax infection and disease in predictable ways. One-fifth of the hosts account for 80% or more of the community-wide vivax malaria burden and contribute disproportionally to onward transmission, representing a priority target of more intensive interventions to achieve malaria elimination. Importantly, high-risk individuals eventually develop clinical immunity, even in areas with very low or residual malaria transmission, and may constitute a large but silent parasite reservoir.publishersversionpublishe

Genetic Modulators of Hemolytic Anemia in Angolan Children with Sickle Cell Anemia

Sickle Cell Anemia (SCA) is a recessive genetic disease caused by the c.20A>T variant in HBB gene. It is characterised by sickled erythrocytes, chronic hemolytic anemia and vaso-occlusive events. However, these manifestations are heterogeneous due to environmental and genetic modifying factors. The aim of this study was to investigate genetic modifiers of hemolytic anemia in pediatric SCA patients living in Africa, where the disease is a severe public health problem. The study was conducted on 200 Angolan SCA 3-12 year-old children. Thirteen polymorphic regions in genes previously associated with vascular cell adhesion (VCAM1 and CD36), vascular tonus (NOS3) or erythrocyte hemoglobinisation (HBA), were genotyped using PCR, RFLP, Gap-PCR and Sanger sequencing. Hematological and biochemical phenotypes were obtained at steady state and clinical adverse events were collected from patients’ medical records. Results revealed a high level (67.5%) of α-thalassemia co-inheritance (del. 3.7kb in HBA), which improve patients’ health by delaying the onset of the disease, decreasing anemia and the number of blood transfusions. Two SNPs in CD36 (rs1984112 and rs1413661) showed impact on anemia severity. Particularly, genotypes containing the rs1413661_allele C revealed to be risk factors for severe anemia, as they were associated with lower hemoglobin levels, increased number of hospitalizations and transfusions. This is the first report associating this SNP with SCA pathology. Moreover, the rs1041163_allele C in VCAM1 was associated with lower LDH levels, inversely the rs2070744_allele C in NOS3 was associated with higher LDH levels and a higher number of hospitalizations, being a possible risk factor for increased hemolytic rate. This study contributed to the understanding of SCA complex pathophysiology. It confirmed the positive role of α-thal., both in SCA related anemia and in its clinical manifestations. In addition, it reinforced the importance of vascular cell adhesion in hemolytic anemia variability. In this context, we propose the SNP rs1413661 in CD36 as an important novel genetic modulator of SCA in Africa.Partially funding by FCT/Aga Khan Dev. Network, #330842553N/

Analysis of genetic mutations associated with anti-malarial drug resistance in Plasmodium falciparum from the Democratic Republic of East Timor

<p>Abstract</p> <p>Background</p> <p>In response to chloroquine (CQ) resistance, the policy for the first-line treatment of uncomplicated malaria in the Democratic Republic of East Timor (DRET) was changed in early 2000. The combination of sulphadoxine-pyrimethamine (SP) was then introduced for the treatment of uncomplicated falciparum malaria.</p> <p>Methods</p> <p>Blood samples were collected in two different periods (2003–2004 and 2004–2005) from individuals attending hospitals or clinics in six districts of the DRET and checked for <it>Plasmodium falciparum </it>infection. 112 PCR-positive samples were inspected for genetic polymorphisms in the <it>pfcrt</it>, <it>pfmdr1</it>, <it>pfdhfr </it>and <it>pfdhps </it>genes. Different alleles were interrogated for potential associations that could be indicative of non-random linkage.</p> <p>Results</p> <p>Overall prevalence of mutations associated with resistance to CQ and SP was extremely high. The mutant form of <it>Pfcrt </it>(76T) was found to be fixed even after five years of alleged CQ removal. There was a significant increase in the prevalence of the <it>pfdhps </it>437G mutation (X²= 31.1; p = 0.001) from the first to second survey periods. A non-random association was observed between <it>pfdhfr</it>51/<it>pfdhps</it>437 (p = 0.001) and <it>pfdhfr </it>59/<it>pfdhps </it>437 (p = 0.013) alleles.</p> <p>Conclusion</p> <p>Persistence of CQ-resistant mutants even after supposed drug withdrawal suggests one or all of the following: local <it>P. falciparum </it>may still be inadvertently exposed to the drug, that mutant parasites are being "imported" into the country, and/or reduced genetic diversity and low parasite transmission help maintain mutant haplotypes. The association between <it>pfdhfr</it>51/<it>pfdhps</it>437 and <it>pfdhfr </it>59/<it>pfdhps </it>437 alleles indicates that these are undergoing concomitant positive selection in the DRET.</p

Genetic modulation of anemia severity, hemolysis level, and hospitalization rate in Angolan children with Sickle Cell Anemia

Background Sickle Cell Anemia (SCA) is a genetic disease caused by the c.20 A > T mutation in HBB gene, generally characterized by sickle erythrocytes, chronic hemolytic anemia, and vaso-occlusive events. This study aimed to investigate genetic modulators of anemia severity, chronic hemolytic rate, and clinical manifestations in pediatric SCA patients from Angola, where the disease is a severe public health problem. Methods and Results The study was conducted on 200 SCA children living in Luanda or Caxito province. Their clinical phenotype was collected from patients’ hospital records. Hematological and biochemical phenotypes were characterized in steady state condition. Twelve polymorphic regions in VCAM1, CD36 and NOS3 genes were genotyped using PCR, RFLP, and Sanger sequencing. CD36 gene promoter variants showed a significant impact on anemia severity. Particularly, the rs1413661_C allele was associated with lower hemoglobin levels, and increased number of hospitalizations and transfusions. This is the first report associating this SNP with SCA phenotypic heterogeneity. Moreover, the rs1041163_C allele in VCAM1 was associated with lower LDH levels; inversely the rs2070744_C allele in NOS3 was related with higher LDH levels and number of hospitalizations, being a risk factor for increased hemolytic rate. Conclusion This study highlights, for the first time in the Angolan population, the importance of the genetic modifiers of vascular cell adhesion and nitric oxide metabolism in SCA pediatric phenotypic variability.publishersversionpublishe

Characterization of a cohort of Angolan children with sickle cell anemia treated with hydroxyurea

Background: Sickle Cell Anemia (SCA) is a monogenic disease, although its severity and response to treatment are very heterogeneous. Objectives: This study aims to characterize a cohort of Angolan children with SCA and evaluate their response to hydroxyurea (HU) treatment and the potential side effects and toxicity. Methods: The study enrolled 215 patients between 3 and 12 years old before and after the administration of HU, at a fix dose of 20 mg/kg/day for 12 months. Results: A total of 157 patients started HU medication and 141 of them completed the 12-month treatment. After initiating HU treatment, the frequency of clinical events decreased (transfusions 53.4 %, hospitalizations 47.1 %). The response to HU medication varied among patients, with some experiencing an increase in fetal hemoglobin (HbF) of <5 %. The mean increase in HbF was 11.9 %, ranging from 1.8 % to 31 %. Responders to HU treatment were 57 %, inadequate responders 38.7 % and non-adherent 4.2 %. No clinical side effects related to HU were reported. Hematological toxicities were transient and reversible. Children naïve to HU and with lower HbF reported higher number of hospitalizations caused by malaria infection. During HU treatment, the frequency of malaria episodes did not appear to be affected by HbF levels. Conclusions: the present study provided a valuable contribution to the understanding of the clinical and laboratory profiles of Angolan children with SCA. These findings support the evidence that the implementation of prophylactic measures and treatment with HU is associated with increased survival in children with SCA.This research was funded by Fundação para a Ciência e Tecnologia Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES) and Aga Khan Foundation (FCT/MCTES/Aga Khan, project n◦ 330842553), by FCT/MCTES funding to H&TRC (UIDB/05608/2020, UIDP/05608/2020) and to GHTM IHMT NOVA (UIBD/04413/2020) and LA-REAL –LA/P/0117/2020.info:eu-repo/semantics/publishedVersio

Sickle cell disease and gut health: the influence of intestinal parasites and the microbiome on Angolan children

This work was funded by the following grants: IPL/IDI&CA2022/ParasitSCD, FCT/Aga Khan (project no. 330842553), and FCT/MCTES (https://doi.org/10.54499/UIDB/05608/2020 and https://doi.org/10.54499/UIDP/05608/2020)-H&TRC. Author M.D. has received financial support from an FCT research fellowship UI/BD/150705/2020 (https://doi.org/10.54499/UI/BD/150705/2020).Parasitic infections are a common problem in developing countries and can intensify morbidity in patients with sickle cell disease (SCD), increasing the severity of anemia and the need for transfusions. It has been demonstrated that both helminths and protozoa can affect gut microbiome composition. On the other hand, the presence of specific bacterial communities can also influence parasite establishment. Considering this, our aim was to associate the presence of intestinal parasites with the results of hematological analyses and microbiome composition evaluations in a population of Angolan children with and without SCD. A total of 113 stool samples were collected, and gut microbiome analysis was performed using 16S sequencing and real-time PCR to detect eight different intestinal parasites. In our population, more than half of children (55%) had at least one parasitic infection, and of these, 43% were co-infected. Giardia intestinalis and Ascaris lumbricoides were more frequently found in children from the rural area of Bengo. Moreover, SCD children with ascariasis exhibited higher values of leukocytes and neutrophils, whereas the total hemoglobin levels were lower. In regards to the gut microbiome, the presence of intestinal parasites lowered the prevalence of some beneficial bacteria, namely: Lactobacillus, Bifidobacterium, Cuneatibacter, Bacteroides uniformis, Roseburia, and Shuttleworthia. This study presents the prevalence of several intestinal parasites in a high-risk transmission area with scarce information and opens new perspectives for understanding the interaction between parasites, the microbiome, and SCD.info:eu-repo/semantics/publishedVersio

Sickle cell disease: current drug treatments and functional foods with therapeutic potential

Miguel Brito gratefully acknowledges the FCT/MCTES national support through the projects H&TRC UIDB/05608/2020, UIDP/05608/2020, and IPL/IDI&CA2023/Ipasthma_ESTeSL. J.M. Oliveira acknowledges the financial support of CICECO–Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by national funds through the FCT/MCTES (PIDDAC). Ana Paula Arez would like to acknowledge Fundação para a Ciência e a Tecnologia for funds to GHTM—UID/04413/2020 and LA-REAL LA/P/0117/2020.Sickle cell anemia (SCA), the most common form of sickle cell disease (SCD), is a genetic blood disorder. Red blood cells break down prematurely, causing anemia and often blocking blood vessels, leading to chronic pain, organ damage, and increased infection risk. SCD arises from a single-nucleotide mutation in the β-globin gene, substituting glutamic acid with valine in the β-globin chain. This review examines treatments evaluated through randomized controlled trials for managing SCD, analyzes the potential of functional foods (dietary components with health benefits) as a complementary strategy, and explores the use of bioactive compounds as functional food ingredients. While randomized trials show promise for certain drugs, functional foods enriched with bioactive compounds also hold therapeutic potential. Further research is needed to confirm clinical efficacy, optimal dosages, and specific effects of these compounds on SCD, potentially offering a cost-effective and accessible approach to managing the disease.info:eu-repo/semantics/publishedVersio

Epidemiological characterization of Plasmodium falciparum in the Republic of Cabo Verde: implications for potential large-scale re-emergence of malaria

BACKGROUND: Malaria has come near eradication at archipelago of Cabo Verde in 1970. Infections are now only observed in Santiago, where outbreaks occur. In these islands, malaria is considered by the international community as being of limited risk and, therefore, no prophylaxis is recommended. Since the understanding of factors that determine malaria outbreaks are crucial for controlling the disease, the present study aimed to investigate if the malaria infections observed in Santiago Island are maintained in isolated foci and in asymptomatic individuals. METHODS: The occurrence of asymptomatic carriers in villages with history of malaria as well as the level of exposure of these populations were investigated using PCR and serological analyses. RESULTS: Results indicate that malaria is maintained as asymptomatic and sub-patent infections and that the majority of the circulating parasite populations harbour chloroquine-resistant mutations. CONCLUSION: These observations highlight the alarming prospect of malaria to become a serious public health problem and underscore the need for a tighter surveillance

Differential Gene Expression of Malaria Parasite in Response to Red Blood Cell-Specific Glycolytic Intermediate 2,3-Diphosphoglycerate (2,3-DPG)

Innovative strategies to control malaria are urgently needed. Exploring the interplay between Plasmodium sp. parasites and host red blood cells (RBCs) offers opportunities for novel antimalarial interventions. Pyruvate kinase deficiency (PKD), characterized by heightened 2,3-diphosphoglycerate (2,3-DPG) concentration, has been associated with protection against malaria. Elevated levels of 2,3-DPG, a specific mammalian metabolite, may hinder glycolysis, prompting us to hypothesize its potential contribution to PKD-mediated protection. We investigated the impact of the extracellular supplementation of 2,3-DPG on the Plasmodium falciparum intraerythrocytic developmental cycle in vitro. The results showed an inhibition of parasite growth, resulting from significantly fewer progeny from 2,3-DPG-treated parasites. We analyzed differential gene expression and the transcriptomic profile of P. falciparum trophozoites, from in vitro cultures subjected or not subjected to the action of 2,3-DPG, using Nanopore Sequencing Technology. The presence of 2,3-DPG in the culture medium was associated with the significant differential expression of 71 genes, mostly associated with the GO terms nucleic acid binding, transcription or monoatomic anion channel. Further, several genes related to cell cycle control were downregulated in treated parasites. These findings suggest that the presence of this RBC-specific glycolytic metabolite impacts the expression of genes transcribed during the parasite trophozoite stage and the number of merozoites released from individual schizonts, which supports the potential role of 2,3-DPG in the mechanism of protection against malaria by PKD.publishersversionpublishe